FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Avruch, J Long, XM Ortiz-Vega, S Rapley, J Papageorgiou, A Dai, N AF Avruch, Joseph Long, Xiaomeng Ortiz-Vega, Sara Rapley, Joseph Papageorgiou, Angela Dai, Ning TI Amino acid regulation of TOR complex 1 SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE mammalian target of rapamycin; Rheb; rag; FKBP38; phospholipase D; guanosine 5 '-triphosphatase ID P70 S6 KINASE; TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR PROTEINS; ISOLATED RAT HEPATOCYTES; MAMMALIAN TARGET; CELL-GROWTH; SACCHAROMYCES-CEREVISIAE; SIGNALING PATHWAYS; MTOR PATHWAY; RAPAMYCIN COMPLEX-1 AB Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N. Amino acid regulation of tor complex 1. Am J Physiol Endocrinol Metab 296: E592-E602, 2009. First published September 2, 2008; doi:10.1152/ajpendo.90645.2008.-TOR complex 1 (TORC1), an oligomer of the mTOR ( mammalian target of rapamycin) protein kinase, its substrate binding subunit raptor, and the polypeptide Lst8/G beta L, controls cell growth in all eukaryotes in response to nutrient availability and in metazoans to insulin and growth factors, energy status, and stress conditions. This review focuses on the biochemical mechanisms that regulate mTORC1 kinase activity, with special emphasis on mTORC1 regulation by amino acids. The dominant positive regulator of mTORC1 is the GTP-charged form of the ras-like GTPase Rheb. Insulin, growth factors, and a variety of cellular stressors regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein. In contrast, amino acids, especially leucine, regulate mTORC1 by controlling the ability of Rheb-GTP to activate mTORC1. Rheb binds directly to mTOR, an interaction that appears to be essential for mTORC1 activation. In addition, Rheb-GTP stimulates phospholipase D1 to generate phosphatidic acid, a positive effector of mTORC1 activation, and binds to the mTOR inhibitor FKBP38, to displace it from mTOR. The contribution of Rheb's regulation of PL-D1 and FKBP38 to mTORC1 activation, relative to Rheb's direct binding to mTOR, remains to be fully defined. The rag GTPases, functioning as obligatory heterodimers, are also required for amino acid regulation of mTORC1. As with amino acid deficiency, however, the inhibitory effect of rag depletion on mTORC1 can be overcome by Rheb overexpression, whereas Rheb depletion obviates rag's ability to activate mTORC1. The rag heterodimer interacts directly with mTORC1 and may direct mTORC1 to the Rheb-containing vesicular compartment in response to amino acid sufficiency, enabling Rheb-GTP activation of mTORC1. The type III phosphatidylinositol kinase also participates in amino acid-dependent mTORC1 activation, although the site of action of its product, 3 ' OH-phosphatidylinositol, in this process is unclear. C1 [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Simches Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu RI wang, hua/H-3345-2011 FU National Institutes of Health [DK-17776, CA-73818] FX The work of the authors cited herein was supported by National Institutes of Health Grants DK-17776 and CA-73818. NR 127 TC 198 Z9 208 U1 6 U2 41 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2009 VL 296 IS 4 BP E592 EP E602 DI 10.1152/ajpendo.90645.2008 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 423SB UT WOS:000264514900003 PM 18765678 ER PT J AU Chavez, AO Coletta, DK Kamath, S Cromack, DT Monroy, A Folli, F DeFronzo, RA Tripathy, D AF Chavez, Alberto O. Coletta, Dawn K. Kamath, Subhash Cromack, Douglas T. Monroy, Adriana Folli, Franco DeFronzo, Ralph A. Tripathy, Devjit TI Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin sensitivity; adipokines; pathogenesis; type 2 diabetes mellitus ID DEPENDENT DIABETES-MELLITUS; SERUM RETINOL-BINDING-PROTEIN-4; METABOLIC SYNDROME; NONOBESE SUBJECTS; HUMAN OBESITY; VITAMIN-A; EXPRESSION; FAT; INFLAMMATION; SENSITIVITY AB Chavez AO, Coletta DK, Kamath S, Cromack DT, Monroy A, Folli F, DeFronzo RA, Tripathy D. Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans. Am J Physiol Endocrinol Metab 296: E758-E764, 2009. First published February 3, 2009; doi:10.1152/ajpendo.90737.2008.-Retinol-binding protein-4 (RBP4), a novel protein secreted mainly by adipose tissue, has been associated with insulin resistance in obese subjects and in individuals with type 2 diabetes mellitus (T2DM). We examined the relationship between plasma RBP4 levels, expression of RBP4 in skeletal muscle and adipose tissue, and insulin sensitivity in Mexican Americans with varying degrees of obesity and glucose tolerance. Seventy-two subjects [16 lean normal-glucose-tolerant (NGT), 17 obese NGT, and 39 subjects with impaired fasting glucose/impaired glucose tolerance/T2DM] received an oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Insulin secretion was measured as insulinogenic index during OGTT. In a subset of subjects, hepatic glucose production was measured by 3-[(3)H] glucose infusion, biopsies of the vastus lateralis muscle and subcutaneous adipose tissue were obtained under basal conditions, and quantitative RT-PCR was performed to measure the RBP4 mRNA gene expression. Plasma RBP4 was significantly elevated in impaired glucose tolerance/T2DM compared with NGT lean or obese subjects. Plasma RBP4 levels correlated with 2-h glucose, triglycerides, and hemoglobin A(1c). There was no association between RBP4 levels and whole body insulin sensitivity measured with either the euglycemic insulin clamp or OGTT, basal hepatic glucose production rates, and the hepatic insulin resistance index. There was no correlation between plasma RBP4 levels and indexes of insulin secretion. RBP4 mRNA expression in skeletal muscle was similar in lean NGT subjects, obese NGT subjects, and T2DM subjects. There was no difference in RBP4 mRNA expression in adipose tissue between lean and obese NGT subjects or between NGT and T2DM individuals. Plasma RBP4 levels are elevated in T2DM and associated with impaired glucose tolerance, but not associated with obesity or insulin resistance or impaired insulin secretion in Mexican Americans. C1 [Chavez, Alberto O.; Coletta, Dawn K.; Kamath, Subhash; Cromack, Douglas T.; Monroy, Adriana; Folli, Franco; DeFronzo, Ralph A.; Tripathy, Devjit] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Cromack, Douglas T.; DeFronzo, Ralph A.; Tripathy, Devjit] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Tripathy, D (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM tripathy@UTHSCSA.EDU RI Coletta, Dawn/G-6382-2016; OI folli, franco/0000-0001-9824-5222; Coletta, Dawn/0000-0001-5819-5152; Monroy, Adriana/0000-0001-6221-3763 NR 37 TC 21 Z9 21 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2009 VL 296 IS 4 BP E758 EP E764 DI 10.1152/ajpendo.90737.2008 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 423SB UT WOS:000264514900022 PM 19190263 ER PT J AU Zhang, JL Ling, YQ Tang, LP Luo, B Pollock, DM Fallon, MB AF Zhang, Junlan Ling, Yiqun Tang, Liping Luo, Bao Pollock, David M. Fallon, Michael B. TI Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE common bile duct ligation; endothelin-1; endothelial nitric oxide synthase; intravascular monocyte ID NITRIC-OXIDE SYNTHASE; BILE-DUCT LIGATION; ETB-RECEPTOR; HYPERTENSION; MODEL; VASODILATION; EXPRESSION; CIRRHOSIS; LIVER; ET-1 AB Experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL) in rat is accompanied by increased lung vascular endothelial endothelin B (ET(B)) receptor expression and increased circulating levels of endothelin-1 (ET-1). The onset of HPS is hypothesized to be triggered by ET-1/ET(B) receptor activation of endothelial nitric oxide synthase (eNOS)-derived NO production in the pulmonary endothelium. However, whether functional pulmonary vascular ET(B) receptors are required for the development of experimental HPS is not defined. We evaluated the effects of vascular ET(B) receptor deficiency on the development of experimental HPS. The molecular and physiological alterations of HPS were compared in 2-wk CBDL wild-type and ET(B) receptor-deficient (transgenic sl/sl) rats. Relative to wild-type rats, basal hepatic and plasma ET-1 levels were elevated in sl/sl controls although, unlike wild-type animals circulating ET-1 levels, did not increase further after CBDL in sl/sl animals. In contrast to wild-type animals, ET(B) receptor-deficient rats did not develop increased Akt and eNOS expression and activation and did not develop gas exchange abnormalities of HPS after CBDL. There was a similar degree of pulmonary intravascular monocyte accumulation in both 2-wk CBDL sl/sl and wild-type animals. In conclusion, ET(B) receptor deficiency inhibits lung Akt/eNOS activation and prevents the onset of experimental HPS after CBDL. This effect is independent of inhibition of pulmonary intravascular monocyte accumulation. These results demonstrate that ET-1/ET(B) receptor signaling plays a key role in the initiation of experimental HPS. C1 [Zhang, Junlan; Ling, Yiqun; Tang, Liping; Luo, Bao; Fallon, Michael B.] Univ Alabama, Dept Internal Med, Ctr Liver, Birmingham, AL USA. [Tang, Liping; Luo, Bao; Fallon, Michael B.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. [Pollock, David M.] Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA. RP Zhang, JL (reprint author), Univ Texas Hlth Sci Ctr Houston, MSB 4-248,6431 Fannin St, Houston, TX 77030 USA. EM Junlan.Zhang@uth.tmc.edu FU AHA [0735468N]; NIH [DK0203] FX This work was supported by Grants AHA 0735468N (to J. Zhang) and NIH DK0203 (to M. B. Fallon). NR 29 TC 15 Z9 19 U1 0 U2 0 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 APR PY 2009 VL 296 IS 4 BP G704 EP G708 DI 10.1152/ajpgi.90627.2008 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 426KE UT WOS:000264706400002 PM 19196949 ER PT J AU Takewa, Y Chemaly, ER Takaki, M Liang, LF Jin, HW Karakikes, I Morel, C Taenaka, Y Tatsumi, E Hajjar, RJ AF Takewa, Yoshiaki Chemaly, Elie R. Takaki, Miyako Liang, Li Fan Jin, Hongwei Karakikes, Ioannis Morel, Charlotte Taenaka, Yoshiyuki Tatsumi, Eisuke Hajjar, Roger J. TI Mechanical work and energetic analysis of eccentric cardiac remodeling in a volume overload heart failure in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE eccentric left ventricular hypertrophy; myocardial oxygen consumption; Ca(2+) handling; sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a; cross circulation; aortocaval shunt ID GENE-EXPRESSION; OXYGEN COST; O-2 USE; PRESSURE; HYPERTROPHY; DYSFUNCTION; CONTRACTILITY; VENTRICLE; AREA AB Takewa Y, Chemaly ER, Takaki M, Liang LF, Jin H, Karakikes I, Morel C, Taenaka Y, Tatsumi E, Hajjar RJ. Mechanical work and energetic analysis of eccentric cardiac remodeling in a volume overload heart failure in rats. Am J Physiol Heart Circ Physiol 296: H1117-H1124, 2009. First published February 6, 2009; doi:10.1152/ajpheart.01120.2008.-Eccentric cardiac remodeling seen in dilated cardiomyopathy or regurgitant valvular disease is a well-known process of heart failure progression, but its mechanoenergetic profile has not been yet established. We made a volume overload (VO) heart failure model in rats and for the first time investigated left ventricular (LV) mechanical work and energetics in cross-circulated whole heart preparations. Laparotomy was performed in 14 Wistar male rats, and abdominal aortic-inferior vena caval shunt was created in seven rats (VO group). Another seven rats underwent a sham operation without functional shunt (Sham group). LV dimensions changes were followed with weekly transthoracic echocardiography. Three months after surgery, we measured LV pressure and volume and myocardial O(2) consumption in isolated heart cross circulation. LV internal dimensions in both systolic and diastolic phases were significantly increased in the VO group versus the Sham group (P < 0.05). LV pressure was markedly decreased in the VO group versus in the Sham group (P < 0.05). LV end-systolic pressure-volume relation shifted downward, and myocardial O(2) consumption related to Ca(2+) handling significantly decreased. The contractile response to Ca(2+) infusion was attenuated. Nevertheless, the increase in Ca(2+) handling-related O(2) consumption per unit change in LV contractility in the VO group was significantly higher than that in the Sham group (P < 0.05). The levels of sarco(endo) plasmic reticulum Ca(2+)-ATPase 2a protein were reduced in the VO group (P < 0.01). In conclusion, VO failing rat hearts had a character of marked contractile dysfunction accompanied with less efficient energy utilization in the Ca(2+) handling processes. These results suggest that restoring Ca(2+) handling in excitation-contraction coupling would improve the contractility of the myocardium after eccentric cardiac remodeling. C1 [Takewa, Yoshiaki; Chemaly, Elie R.; Liang, Li Fan; Jin, Hongwei; Karakikes, Ioannis; Morel, Charlotte; Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY 10029 USA. [Takewa, Yoshiaki; Takaki, Miyako] Nara Med Univ, Sch Med, Dept Physiol 2, Nara, Japan. [Takewa, Yoshiaki; Taenaka, Yoshiyuki; Tatsumi, Eisuke] Natl Cardiovasc Ctr, Res Inst, Dept Artificial Organs, Osaka, Japan. [Takewa, Yoshiaki; Chemaly, Elie R.; Liang, Li Fan; Jin, Hongwei; Hajjar, Roger J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Hajjar, RJ (reprint author), Mt Sinai Sch Med, Cardiovasc Res Ctr, 1 Gustave Levy Pl,Box 1030, New York, NY 10029 USA. EM roger.hajjar@mssm.edu FU National Heart, Lung, and Blood Institute Grants [RO1-HL-078691, HL-071763, HL-080498, HL-083156] FX This work was supported in part by National Heart, Lung, and Blood Institute Grants RO1-HL-078691, HL-071763, HL-080498, and HL-083156 ( to R. Hajjar) and a grant from Transatlantic Network. NR 24 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2009 VL 296 IS 4 BP H1117 EP H1124 DI 10.1152/ajpheart.01120.2008 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 439WP UT WOS:000265658600025 PM 19201995 ER PT J AU Kumagai, T Nangaku, M Kojima, I Nagai, R Ingelfinger, JR Miyata, T Fujita, T Inagi, R AF Kumagai, Takanori Nangaku, Masaomi Kojima, Ichiro Nagai, Ryoji Ingelfinger, Julie R. Miyata, Toshio Fujita, Toshiro Inagi, Reiko TI Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE acute renal failure; advanced glycation end products; methylglyoxal; oxidative stress; tubular cells ID GLYCATION END-PRODUCTS; MITOCHONDRIAL RESPIRATION; METHYLGLYOXAL; STRESS; INHIBITION; PROTEIN; SYSTEM; CELLS; GLYCOLYSIS; LIFE AB Kumagai T, Nangaku M, Kojima I, Nagai R, Ingelfinger JR, Miyata T, Fujita T, Inagi R. Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol 296: F912-F921, 2009. First published February 11, 2009; doi:10.1152/ajprenal.90575.2008.-Methylglyoxal (MG), a highly reactive carbonyl compound generated by carbohydrate oxidation and glycolysis, is the major precursor of protein glycation and induces cytotoxicity leading to apoptosis. Although recent studies have emphasized that MG accumulates in not only chronic oxidative stress-related diseases but also acute hypoxic conditions, the pathogenic contribution of MG in acute diseases is unclear. MG is efficiently metabolized by the glyoxalase system, namely, glyoxalase I. We investigated the pathophysiological role of glyoxalase I as an MG detoxifier in rat renal ischemia-reperfusion (I/R) injury. I/R-induced tubulointerstitial injury was associated with a deterioration in renal glyoxalase I activity independent of its cofactor, GSH, as well as an increase in renal MG level. In in vitro studies, knockdown of glyoxalase I by small interference RNA transfection in rat tubular cells exacerbated cell death by hypoxia-reoxygenation compared with control cells. We also examined whether glyoxalase I overexpression prevented renal I/R damage in rats overexpressing human glyoxalase I with enzyme activity in the kidney 17-fold higher than in wild-type. The histological and functional manifestations of I/R in these rats were significantly ameliorated in association with a decrease in intracellular MG adduct accumulation, oxidative stress, and tubular cell apoptosis. In conclusion, glyoxalase I exerts renoprotective effects in renal I/R injury via a reduction in MG accumulation in tubular cells. C1 [Inagi, Reiko] Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1138655, Japan. [Nagai, Ryoji] Kumamoto Univ, Fac Med & Pharmaceut Sci, Dept Med Biochem, Kumamoto, Japan. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. [Miyata, Toshio] Tohoku Univ, Sch Med, Ctr Translat & Adv Anim Res Human Dis, Sendai, Miyagi 980, Japan. RP Inagi, R (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM inagi-npr@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 FU Japan Society for the Promotion of Science [19590939, 19390228] FX This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (19590939 to R. Inagi and 19390228 to M. Nangaku). NR 24 TC 57 Z9 58 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2009 VL 296 IS 4 BP F912 EP F921 DI 10.1152/ajprenal.90575.2008 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 422AO UT WOS:000264399600028 PM 19211689 ER PT J AU Primack, BA Douglas, EL Fine, MJ Dalton, MA AF Primack, Brian A. Douglas, Erika L. Fine, Michael J. Dalton, Madeline A. TI Exposure to Sexual Lyrics and Sexual Experience Among Urban Adolescents SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID POPULAR-MUSIC; BEHAVIOR; MEDIA; RISK; TELEVISION; WOMEN; INTERCOURSE; CHILDREN; VIOLENT; SCALE AB Background: Two thirds of all sexual references in Music are degrading in nature, yet it remains uncertain whether these references promote earlier sexual activity. The purpose of this study was to determine if exposure to lyrics describing degrading sex in popular music is independently associated with Sexual behavior in a cohort of urban adolescents. Methods: All ninth-grade health students at three large urban high schools completed in-school surveys in 2006 and 2007. Participants' exposure to lyrics describing degrading sex was computed with overall music exposure and content analyses of their favorite artists' songs. Outcomes included sexual intercourse and progression along a noncoital sexual continuum. Multivariable regression was used to assess independent associations between exposure to lyrics describing degrading sex and outcomes. Results: The 711 participants were exposed to 14.7 hours each week of songs with lyrics describing degrading sex (SD=17.0). Almost one third of participants (n=216) had previously been sexually active. Compared to those with the least exposure to lyrics describing degrading sex, those with the most exposure were more than twice as likely to have had sexual intercourse (OR=2.07; 95% CI=1.26, 3.41), even after adjusting for all covariates. Similarly, among those who had not had Sexual intercourse, those in the highest tertile of exposure to lyrics describing degrading sex were nearly twice as likely to have progressed along a noncoital sexual continuum (OR=1.88; 95% CI = 1.23, 2.88) compared to those ill the lowest tertile. Finally, the relationships between exposure to lyrics describing nondegrading sex and sexual outcomes were not significant. Conclusions: This study supports all association between exposure to lyrics describing degrading sex in popular music and early sexual experience among adolescents. C1 [Primack, Brian A.; Douglas, Erika L.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.; Douglas, Erika L.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Div Adolescent Med, Dept Pediat, Pittsburgh, PA 15213 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dalton, Madeline A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hood Ctr Children & Families,Dept Pediat, Hanover, NH 03756 USA. [Dalton, Madeline A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hood Ctr Children & Families,Community Hlth Res P, Hanover, NH 03756 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Dept Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU Robert Wood Johnson Foundation; National Cancer Institute [K07-CA114315]; Maurice Falk Foundation FX Dr. Primack is supported in part by a Physician Faculty Scholar Award from the Robert Wood Johnson Foundation; a career development award from the National Cancer Institute (K07-CA114315); and a grant from the Maurice Falk Foundation. The authors would like to thank Steven Martino, PhD, for his editorial input and his assistance with study design. Dr. Primack had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 38 TC 12 Z9 12 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2009 VL 36 IS 4 BP 317 EP 323 DI 10.1016/j.amepre.2008.11.011 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 422DP UT WOS:000264407700006 PM 19285196 ER PT J AU Zeber, JE Copeland, LA McCarthy, JF Bauer, MS Kilbourne, AM AF Zeber, John E. Copeland, Laurel A. McCarthy, John F. Bauer, Mark S. Kilbourne, Amy M. TI Perceived Access to General Medical and Psychiatric Care Among Veterans With Bipolar Disorder SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SERIOUS MENTAL-ILLNESS; HEALTH-SERVICES UTILIZATION; NATIONAL-COMORBIDITY-SURVEY; BEHAVIORAL-MODEL; VULNERABLE POPULATIONS; 12-MONTH PREVALENCE; SOCIAL SUPPORT; UNITED-STATES; OLDER-ADULTS; UNMET NEEDS AB Objectives. We examined associations between patient characteristics and self-reported difficulties in accessing mental health and general medical care services. Methods. Patients were recruited from the Continuous Improvement for Veterans in Care-Mood Disorders study. We used multivariable logistic regression analyses to assess whether predisposing (demographic characteristics), enabling (e.g., homelessness), or need (bipolar symptoms, substance abuse) factors were associated with difficulties in obtaining care, difficulties in locating specialty providers, and forgoing care because of cost. Results. Patients reported greater difficulty in accessing general medical services than in accessing psychiatric care. Individuals experiencing bipolar symptoms more frequently avoided psychiatric care because of cost (odds ratio (OR]=2.43) and perceived greater difficulties in accessing medical specialists (OR=2.06). Homeless individuals were more likely to report hospitalization barriers, whereas older and minority patients generally encountered fewer problems accessing treatment. Conclusions. Need and enabling factors were most influential in predicting self-reported difficulties in accessing care, subsequently interfering with treatment dynamics and jeopardizing clinical outcomes. Efforts in the Department of Veterans Affairs to expand mental health care access should be coupled with efforts to ensure adequate access to general medical services among patients with chronic mental illnesses. (Am J Public Health. 2009;99:720-727. doi:10.2105/AJPH.2007.131318) C1 [Zeber, John E.] S Texas Vet Hlth Care Syst, Vet Affairs HSR&D, San Antonio, TX 78229 USA. [Zeber, John E.; Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [McCarthy, John F.; Kilbourne, Amy M.] VA Serious Mental Illness Treatment Res & Evaluat, Ann Arbor, MI USA. [McCarthy, John F.; Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Bauer, Mark S.] VA Med Ctr, Providence, RI USA. [Bauer, Mark S.] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. RP Zeber, JE (reprint author), S Texas Vet Hlth Care Syst, Vet Affairs HSR&D, 7400 Merton Minter Blvd 11c6, San Antonio, TX 78229 USA. EM zeber@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs (VA); HSRD Service [IIR 02-283-2, 05-145] FX This study was supported through funds provided by the Department of Veterans Affairs (VA), HSR&D Service (Merit Review Investigator Initiated Research IIR 02-283-2, Merit Review Entry Program [MREP] Career Development Award HSR&D 02269). Laurel A. Cope-land received funding from the HSR&D Service (MREP Career Development Award 05-145). NR 59 TC 15 Z9 16 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2009 VL 99 IS 4 BP 720 EP 727 DI 10.2105/AJPH.2007.131318 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423RA UT WOS:000264512200025 PM 19150912 ER PT J AU Gross, RD Atwood, CW Ross, SB Olszewski, JW Eichhorn, KA AF Gross, Roxann Diez Atwood, Charles W., Jr. Ross, Sheryl B. Olszewski, Joan W. Eichhorn, Kimberly A. TI The Coordination of Breathing and Swallowing in Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE exacerbation; dysphagia; swallowing; deglutition; aspiration; pneumonia ID SUBGLOTTIC AIR-PRESSURE; PASSY-MUIR VALVE; BOLUS VOLUME; NORMAL ADULTS; RESPIRATORY PATTERNS; PHASE-RELATIONSHIPS; APNEA DURATION; SOLID FOOD; PHARYNGEAL; ASPIRATION AB Rationale. During deglutition, a strongly preferred exhale-swallow-exhale pattern has been shown in healthy adults. Disruption of this pattern can provoke prandial aspiration. Impaired coordination of breathing and swallowing has been measured in patients with chronic obstructive pulmonary disease (COPD) during the exacerbated state, but no reports describe the coordination of breathing and swallowing in stable patients with COPD during oral intake. Objectives: To test the hypothesis that persons with moderate to severe COPD would show disordered coordination of breathing and swallowing during oral intake when compared with a matched, healthy control group. Methods: This study used a prospective, repeated measures design using 25 subjects with COPD and 25 control subjects. Respiratory inductance plethysmography and nasal thermistry were used simultaneously to track respiratory signals. Submental surface EMG was used to mark the presence of each swallow within the respiratory cycle. Data were recorded while participants randomly and spontaneously swallowed solids and semi-solids. Measurements and Main Results: Logistic regression showed that participants with COPD swallowed solid food during inhalation more frequently than normal subjects (P = 0.002) and had a significantly higher rate of inhaling after swallowing semi-solid material (P < 0.001). Subjects with COPD also swallowed pudding at low VT significantly more often than they did the cookie (P = 0.006). Conversely, the control subjects swallowed cookie at low VT significantly more often than pudding (P = 0.034). Significant differences in deglutitive apnea durations were also found. Conclusions: Patients with COPD exhibit disrupted coordination of the respiratory cycle with deglutition. Disrupted breathing-swallowing coordination could increase the risk of aspiration in patients with advanced COPD and may contribute to exacerbations. C1 [Gross, Roxann Diez; Ross, Sheryl B.] Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Atwood, Charles W., Jr.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Olszewski, Joan W.] Henry Ford Hosp, Detroit, MI 48202 USA. RP Gross, RD (reprint author), Univ Pittsburgh, Inst Eye & Ear, Dept Otolaryngol, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM Grossrd@upmc.edu FU VA Research and Rehabilitation Merit Review Program FX Supported by the VA Research and Rehabilitation Merit Review Program. NR 51 TC 51 Z9 58 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2009 VL 179 IS 7 BP 559 EP 565 DI 10.1164/rccm.200807-1139OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 425UU UT WOS:000264663700008 PM 19151193 ER PT J AU Boland, GWL Blake, MA Holalkere, NS Hahn, PF AF Boland, Giles W. L. Blake, Michael A. Holalkere, Nagaraj S. Hahn, Peter F. TI PET/CT for the Characterization of Adrenal Masses in Patients with Cancer: Qualitative Versus Quantitative Accuracy in 150 Consecutive Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adrenal masses; nonfunctioning adenomas; oncologic imaging; PET/CT; standardized uptake ratio; standardized uptake value ID POSITRON-EMISSION-TOMOGRAPHY; DELAYED ENHANCED CT; F-18-FDG PET/CT; STANDARD UPTAKE; LESIONS; MALIGNANCY; DIAGNOSIS; ADENOMAS; DISEASE; BENIGN AB OBJECTIVE. The objective of our study was to evaluate a large cohort of patients with PET/CT to determine whether qualitative (visual) assessment, quantitative standardized uptake value (SUV), or standardized uptake ratio (SUR) techniques should be used when attempting to characterize adrenal masses in patients with cancer. MATERIALS AND METHODS. The study group was composed of 150 consecutive patients (78 men, 72 women; mean age, 60 years; range, 24-88 years) with documented adrenal lesions. All patients were known to have an underlying primary malignancy and were referred for PET/CT to evaluate the underlying primary and metastatic tumor burden. Definitive lesion characterization was determined by evaluating all histologic adrenal specimens and all relevant prior and follow-up CT scans, including unenhanced, contrast-enhanced, and delayed contrast-enhanced washout studies. RESULTS. Of the 139 benign lesions, 109 were considered benign by CT densitometry measurements and 135 by qualitative PET data. Qualitative PET characterized 28 of 30 benign lesions that were considered indeterminate by unenhanced CT. All 26 malignant lesions were characterized by PET: All showed qualitative and quantitative signal intensity greater than the liver. By combining unenhanced and qualitative CT data with the retrospective PET data, the analysis yielded a sensitivity of 100% for the detection of malignancy, a specificity of 99%, a positive predictive value (PPV) of 93%, a negative predictive value (NPV) of 100%, and an accuracy of 99% (Table 1). Conversely, for the detection of benignity, the sensitivity, specificity, PPV, NPV, and accuracy were 99%, 100%, 100%, 93%, and 99%, respectively. CONCLUSION. PET/CT is a highly accurate method for differentiating benign from malignant adrenal masses particularly when using qualitative, rather than quantitative, PET data. The routine use of quantitative mean or maximal SUV or SUR data may be unnecessary. Occasional benign lesions do show mild to moderate increased FDG uptake compared with that of the liver and may mimic some malignant lesions. Without evidence that these lesions are benign by unenhanced CT densitometry or adrenal mass stability or growth from previous CT scans, we recommend that these lesions be characterized using contrast-enhanced washout tests and that if those tests are inconclusive, using percutaneous biopsy if early lesion characterization is mandatory. C1 [Boland, Giles W. L.; Blake, Michael A.; Holalkere, Nagaraj S.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White Bldg 270C, Boston, MA 02114 USA. EM gboland@partners.org OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 29 TC 79 Z9 83 U1 0 U2 2 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 APR PY 2009 VL 192 IS 4 BP 956 EP 962 DI 10.2214/AJR.08.1431 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 421KX UT WOS:000264358900019 PM 19304700 ER PT J AU Voos, JE Shindle, MK Pruett, A Asnis, PD Kelly, BT AF Voos, James E. Shindle, Michael K. Pruett, Arianna Asnis, Peter D. Kelly, Bryan T. TI Endoscopic Repair of Gluteus Medius Tendon Tears of the Hip SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE gluteus medius tendon tear; abductor tendon; arthroscopy; lateral hip pain ID ROTATOR-CUFF TEAR; TROCHANTERIC BURSITIS; ABDUCTOR MECHANISM; ARTHROSCOPY; PAIN AB Background: Tears of the gluteus medius tendon at the greater trochanter have been termed "rotator cuff tears of the hip." Previous reports have described the open repair of these lesions. Hypothesis: Endoscopic repair of gluteus medius tears results in successful clinical outcomes in the short term. Study Design: Case series; Level of evidence, 4. Methods: Of 482 consecutive hip arthroscopies performed by the senior author, 10 patients with gluteus medius tears repaired endoscopically were evaluated prospectively. Perioperative data were analyzed on this cohort of patients. There were 8 women and 2 men, with an average age of 50.4 years (range, 33-66 years). Patients had persistent lateral hip pain and abductor weakness despite extensive conservative measures. Diagnosis was made by physical examination and magnetic resonance imaging and was confirmed at the time of endoscopy in all cases. At the most recent follow-up, patients completed the Modified Harris Hip Score and Hip Outcomes Score surveys. Results: At an average follow-up of 25 months (range, 19-38 months), all 10 patients had complete resolution of pain; 10 of 10 regained 5 of 5 motor strength in the hip abductors. Modified Harris Hip Scores at 1 year averaged 94 points (range, 84-100), and Hip Outcomes Scores averaged 93 points (range, 85-100). There were no adverse complications after abductor repairs. Seven of 10 patients said their hip was normal, and 3 said their hip was nearly normal. Conclusion: With short-term follow-up, endoscopic repair of gluteus medius tendon tears of the hip appears to provide pain relief and return of strength in select patients who have failed conservative measures. Further long-term follow-up is warranted to confirm the clinical effectiveness of this procedure. C1 [Voos, James E.; Shindle, Michael K.; Pruett, Arianna; Kelly, Bryan T.] Hosp Special Surg, New York, NY 10021 USA. [Asnis, Peter D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Voos, JE (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM voosj@hss.edu NR 21 TC 71 Z9 75 U1 0 U2 2 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 APR PY 2009 VL 37 IS 4 BP 743 EP 747 DI 10.1177/0363546508328412 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 427BH UT WOS:000264754300013 PM 19204363 ER PT J AU Mandal, RV Forcione, DG Brugge, WR Nishioka, NS Mino-Kenudson, M Lauwers, GY AF Mandal, Rajni V. Forcione, David G. Brugge, William R. Nishioka, Norman S. Mino-Kenudson, Mari Lauwers, Gregory Y. TI Effect of Tumor Characteristics and Duplication of the Muscularis Mucosae on the Endoscopic Staging of Superficial Barrett Esophagus-related Neoplasia SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Barrett esophagus; dysplasia; carcinoma; muscularis mucosal; duplication; endoscopic ultrasound ID HIGH-GRADE DYSPLASIA; INTRAMUCOSAL ADENOCARCINOMA; RESECTION; CANCER; ULTRASONOGRAPHY; EUS; ACCURACY; THERAPY; ENDOSONOGRAPHY; MANAGEMENT AB Endoscopic mucosal resection (EMR) is being advocated its a diagnostic, staging, and therapeutic technique for the management of Barrett esophagus (BE)-related neoplasia. With the emergence of new endoluminal therapy including EMR for the treatment of BE-related superficial adenocarcinomas, accurate staging has become crucial to select patients for different treatment arms. Intramucosal adenocarcinomas can be successfully treated by endoluminal techniques, whereas submucosal invasive tumors with a greater risk of lymph node metastasis are likely candidates for esophagectomy. Endoscopic ultrasound (EUS) is used to stage superficial BE-related neoplasms, vet endoscopic staging can be incongruent to that obtained after pathologic examination. In this Study, we Sought to determine morphologic factors, which may influence EUS staging in 35 cases with intramucosal adenocarcinoma diagnosed by subsequent EMR, focusing on tumor characteristics and structural changes associated with BE. Among the latter duplication of the muscularis mucosae, either fragmented or well-organized, was seen in 64% of 11 cases that were overstaged as having submucosal invasion by EUS, compared with 38% of those accurately staged. A greater vertical thickness of the tumor was also associated with overstaging by EUS (1.61 +/- 0.75 mm in the discordant vs. 1.16 +/- 0.67 mm in the concordant groups, P = 0.028). The results illustrate how morphologic factors may affect EUS staging of superficial esophageal adencearcinomas. EUS alone is not sufficient for staging these neoplasms precisely, and to accurately stratify patients into different treatment arms. EMR should play a role as a complementary staging modality. C1 [Mandal, Rajni V.; Mino-Kenudson, Mari; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Pathol Serv,Dept Pathol, Boston, MA 02114 USA. [Forcione, David G.; Brugge, William R.; Nishioka, Norman S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Gastroenterol, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Pathol Serv,Dept Pathol, 55 Fruit St,WRN 122, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 36 TC 13 Z9 13 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 APR PY 2009 VL 33 IS 4 BP 620 EP 625 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 427ZY UT WOS:000264818800017 PM 19047893 ER PT J AU Benichou, G Thomson, AW AF Benichou, G. Thomson, A. W. TI Direct versus Indirect Allorecognition Pathways: On the Right Track SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID ALLOGRAFT-REJECTION; INDIRECT RECOGNITION; T-CELLS; ALLOPEPTIDES C1 [Benichou, G.] Massachusetts Gen Hosp, Dept Surg, Transplant Res Ctr, Boston, MA 02114 USA. [Benichou, G.] Harvard Univ, Sch Med, Boston, MA USA. [Thomson, A. W.] Univ Pittsburgh, Sch Med, Starzl Transplantat Inst, Pittsburgh, PA USA. [Thomson, A. W.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Thomson, A. W.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplant Res Ctr, Boston, MA 02114 USA. EM gbenichou@partners.org FU NIAID NIH HHS [R01 AI054976, R03 AI094235] NR 8 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2009 VL 9 IS 4 BP 655 EP 656 DI 10.1111/j.1600-6143.2009.02572.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 424ZX UT WOS:000264607900002 PM 19344457 ER PT J AU Gasser, O Bihl, F Sanghavi, S Rinaldo, C Rowe, D Hess, C Stablein, D Roland, M Stock, P Brander, C AF Gasser, O. Bihl, F. Sanghavi, S. Rinaldo, C. Rowe, D. Hess, C. Stablein, D. Roland, M. Stock, P. Brander, C. TI Treatment-dependent Loss of Polyfunctional CD8+T-cell Responses in HIV-infected Kidney Transplant Recipients Is Associated with Herpesvirus Reactivation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE HIV; immunological monitoring; kidney transplantation; T cell ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CD8(+) T-CELLS; SARCOMA-ASSOCIATED HERPESVIRUS; SOLID-ORGAN TRANSPLANTATION; LYMPHOPROLIFERATIVE DISORDERS; FUNCTIONAL PROFILE; POSITIVE PATIENTS; PERIPHERAL-BLOOD; COMPETITIVE PCR AB Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases. C1 [Gasser, O.; Brander, C.] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. [Sanghavi, S.; Rinaldo, C.; Rowe, D.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Bihl, F.] Univ Hosp Geneva, Geneva, Switzerland. [Gasser, O.; Hess, C.] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Stablein, D.] Emmes Corp, Rockville, MD USA. [Roland, M.; Stock, P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brander, C.] Hosp Badalona Germans Trias & Pujol, Irsicaixa Fdn, Barcelona, Spain. [Brander, C.] ICREA, Barcelona, Spain. RP Gasser, O (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. EM ogasser@partners.org RI Gasser, Olivier/I-3663-2013; OI Brander, Christian/0000-0002-0548-5778 FU Swiss Foundation for Medical and Biological Grants; National Institute of Allergy and infectious Diseases [AI052748, R01 067077] FX This work was supported by a grant from the Swiss Foundation for Medical and Biological Grants (to O.G.) and the solid-organ transplantation in HIV: Multi-Site Study (AI052748) grant funded by the National Institute of Allergy and infectious Diseases as well as R01 067077 to CB. We thank Dr. Jose Miro at Hospital Clinic in Barcelona for helpful discussions. NR 49 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2009 VL 9 IS 4 BP 794 EP 803 DI 10.1111/j.1600-6143.2008.02539.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 424ZX UT WOS:000264607900018 PM 19298451 ER PT J AU Falqueto, A Ferreira, AL dos Santos, CB Porrozzi, R da Costa, MVS Teva, A Cupolillo, E Campos-Neto, A Grimaldi, G AF Falqueto, Aloisio Ferreira, Adelson L. dos Santos, Claudiney B. Porrozzi, Renato Santos da Costa, Marcos V. Teva, Antonio Cupolillo, Elisa Campos-Neto, Antonio Grimaldi, Gabriel, Jr. TI Cross-sectional and Longitudinal Epidemiologic Surveys of Human and Canine Leishmania infantum Visceral Infections in an Endemic Rural Area of Southeast Brazil (Pancas, Espirito Santo) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID IMMUNOFLUORESCENT-ANTIBODY-TEST; LINKED IMMUNOSORBENT ASSAYS; SKIN-TEST; IMMUNOCHROMATOGRAPHIC-DIPSTICK; VIANNIA BRAZILIENSIS; CHAGASI INFECTION; AMAZONIAN BRAZIL; NATURAL-HISTORY; FOLLOW-UP; DOGS AB In an endemic rural area of southeast Brazil, surveys confirmed that dogs serve as peridomestic reservoirs of Leishmania infantum. It is likely that the lack of efficient control is because presently used diagnostic tests miss positive dogs. Overall, 57% of the dogs had specific antibodies, but the canine infection was not uniformly fatal and many seropositive. dogs remained asymptomatic or even spontaneously recovered. Furthermore, 42% of the human residents became leishmanin-positive reactors and 47% had positive serology at the initial survey, but our estimates also point at a high recovery rate among the infected population with time. The delayed-type hypersensitivity (DTH) reaction to Leishmania was a good indicator of resistance to infection in this particular epidemiologic situation. The lack of any significant differences in infection rates by gender or age indicate that all of the population was at an equal risk of infection and most people were infected in the peridomestic setting. C1 [Falqueto, Aloisio; Ferreira, Adelson L.; dos Santos, Claudiney B.] Univ Fed Espirito Santo, Unidade Med Trop, BR-29040090 Vitoria, ES, Brazil. [Porrozzi, Renato; Santos da Costa, Marcos V.; Teva, Antonio; Cupolillo, Elisa; Grimaldi, Gabriel, Jr.] Fiocruz MS, IOC, Lab Pesquisa Leishmaniose, BR-21045090 Rio De Janeiro, Brazil. [Campos-Neto, Antonio] Forsyth Inst, Boston, MA 02115 USA. RP Grimaldi, G (reprint author), Fiocruz MS, IOC, Lab Pesquisa Leishmaniose, Pavilhao Leonidas Deane,Sala 509,Av Brasil 4365, BR-21045090 Rio De Janeiro, Brazil. EM falqueto@npd.ufes.br; adelsonlf@hotmail.com; claudincy@ppgcf.ufes.br; porrozzi@ioc.fiocruz.br; mavicos2004@yahoo.com.br; teva@ioc.fiocruz.br; ecupoli@ioc.fiocruz.br; Acampos@forsyth.org; grimaldi@ioc.fiocruz.br FU FIOCRUZ; PRONEX 3/CNPq (National Council for Scientific and Technological Development of the Ministry of Science and Technology, Brazil) FX This work was supported in part by FIOCRUZ and the PRONEX 3/CNPq (National Council for Scientific and Technological Development of the Ministry of Science and Technology, Brazil). Gabriel Grimaldi Jr. and Elisa Cupolillo are CNPq Fellow researchers, Marcos V Santos da Costa is a Master student in the Program in Parasite Biology/FIOCRUZ and sponsored by CNPq. NR 39 TC 20 Z9 20 U1 0 U2 1 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 APR PY 2009 VL 80 IS 4 BP 559 EP 565 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 432CK UT WOS:000265110900012 PM 19346375 ER PT J AU Avery, EG Hilgenberg, AD Cambria, RP Beckerly, R Donnelly, AM Laposata, M AF Avery, Edwin G. Hilgenberg, Alan D. Cambria, Richard P. Beckerly, Rena Donnelly, Anne M. Laposata, Michael TI Successful Use of Bivalirudin for Combined Carotid Endarterectomy and Coronary Revascularization with the Use of Cardiopulmonary Bypass in a Patient with an Elevated Heparin-Platelet Factor 4 Antibody Titer SO ANESTHESIA AND ANALGESIA LA English DT Article ID INDUCED THROMBOCYTOPENIA; CARDIAC-SURGERY; PROTAMINE AB We report a combined carotid endarterectomy and coronary revascularization surgery with cardiopulmonary bypass using bivalirudin for systemic anticoagulation in a patient with a positive titer for the heparin-platelet factor 4 antibody. The patient experienced procedural success for both the carotid and coronary surgeries. Increased blood and blood product transfusion was required postoperatively. C1 [Avery, Edwin G.; Beckerly, Rena; Donnelly, Anne M.] Massachusetts Gen Hosp, Ctr Heart, Dept Anesthesia & Crit Care, Div Cardiac Anesthesia, Boston, MA 02114 USA. [Hilgenberg, Alan D.] Massachusetts Gen Hosp, Ctr Heart, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc Surg, Dept Surg, Vasc Ctr, Boston, MA 02114 USA. [Laposata, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Cambridge, MA 02138 USA. RP Avery, EG (reprint author), Massachusetts Gen Hosp, Ctr Heart, Dept Anesthesia & Crit Care, Div Cardiac Anesthesia, 55 Fruit St, Boston, MA 02114 USA. EM eavery@partners.org FU Medicines Company [212867] FX Supported by The Medicines Company in association with Protocol no. TMC-BIV-02-03 from grant no. 212867. NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2009 VL 108 IS 4 BP 1113 EP 1115 DI 10.1213/ane.0b013e318196cd51 PG 3 WC Anesthesiology SC Anesthesiology GA 423ZG UT WOS:000264534700013 PM 19299772 ER PT J AU Khawaja, OM Reed, JT Shaefi, S Chitilian, HV Sandberg, WS AF Khawaja, Omar M. Reed, J. Taylor Shaefi, Shahzad Chitilian, Hovig V. Sandberg, Warren S. TI Crisis Resource Management of the Airway in a Patient with Klippel-Feil Syndrome, Congenital Deafness, and Aortic Dissection SO ANESTHESIA AND ANALGESIA LA English DT Article ID DIFFICULT TRACHEAL INTUBATION; CERVICAL-SPINE; CLINICAL SIGN; ANESTHESIA AB Klippel-Feil syndrome is a visually arresting deformity wherein severe restriction of cervical motion predicts a difficult airway. Even minor distraction of the neck risks cervical spine or neurologic injury, so regional techniques, awake fiberoptic intubation, or awake tracheostomy are recommended anesthetic approaches. We present a case of aortic dissection in a Klippel-Feil syndrome patient for whom congenital bilateral deafness, coupled with the urgency of the surgery, mitigated against the recommended first-choice techniques. Using anesthesia crisis resource management methods, a multi-member team rehearsed predefined roles and then managed the airway via inhaled induction of anesthesia, followed by flexible fiberoptic intubation. C1 [Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM wsandberg@partners.org OI Sandberg, Warren/0000-0002-9246-777X FU Department Funds of the Department of Anesthesia and Critical Care, Massachusetts General Hospital FX Supported by Department Funds of the Department of Anesthesia and Critical Care, Massachusetts General Hospital. NR 18 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2009 VL 108 IS 4 BP 1220 EP 1225 DI 10.1213/ane.0b013e3181957d9b PG 6 WC Anesthesiology SC Anesthesiology GA 423ZG UT WOS:000264534700032 PM 19299791 ER PT J AU Pa, J Boxer, A Chao, LL Gazzaley, A Freeman, K Kramer, J Miller, BL Weiner, MW Neuhaus, J Johnson, JK AF Pa, Judy Boxer, Adam Chao, Linda L. Gazzaley, Adam Freeman, Katie Kramer, Joel Miller, Bruce L. Weiner, Michael W. Neuhaus, John Johnson, Julene K. TI Clinical-Neuroimaging Characteristics of Dysexecutive Mild Cognitive Impairment SO ANNALS OF NEUROLOGY LA English DT Article ID VOXEL-BASED MORPHOMETRY; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; PREFRONTAL CORTEX; VERBAL FLUENCY; DEMENTIA; ATROPHY; LESIONS; SUBTYPES AB Objective: Subgroups of mild cognitive impairment (MCI) have been proposed, but few studies have investigated the nonamnestic, single-domain subgroup of MCI. The goal of the study was to compare clinical and neuroimaging characteristics of two single-domain MCI subgroups: amnestic MCI and dysexecutive MCI. Methods: We compared the cognitive, functional, behavioral, and brain imaging characteristics of patients with amnestic MCI (n = 26), patients with dysexecutive MCI (n = 32), and age- and education-matched control subjects (n = 36) using analysis of variance and X 2 tests. We used voxel-based morphometry to examine group differences in brain magnetic resonance imaging atrophy patterns. Results: Patients with dysexecutive MCI had significantly lower scores on the majority of executive function tests, increased behavioral symptoms, and left prefrontal cortex atrophy on magnetic resonance imaging when compared with control subjects. In contrast, patients with amnestic MCI had significantly lower scores on tests of memory and a pattern of atrophy including bilateral hippocampi and entorhinal cortex, right inferior parietal cortex, and posterior cingulate gyrus when compared with control subjects. Interpretation: Overall, the clinical and neuroimaging findings provide support for two distinct single-domain subgroups of MCI., one involving executive function and the other involving memory. The brain imaging differences suggest that the two MCI subgroups have distinct patterns of brain atrophy. Ann Neurol 2009;65:414-423 C1 [Pa, Judy; Boxer, Adam; Chao, Linda L.; Gazzaley, Adam; Freeman, Katie; Kramer, Joel; Miller, Bruce L.; Weiner, Michael W.; Johnson, Julene K.] Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, San Francisco, CA 94117 USA. [Chao, Linda L.; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Neuhaus, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA. RP Johnson, JK (reprint author), Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, 350 Parnassus,Suite 905, San Francisco, CA 94117 USA. EM jjohnson@memory.ucsf.edu FU NIH [R01-AG022538, R01-AG010897, P50-AG0300601, K23-NS408855]; John D. French Foundation FX This work was supported by the NIH (National Institute on Aging, R01-AG022538 (JKJ), R01-AG010897 (MWW), P50-AG0300601 (BLM), K23-NS408855 (AB)) and John D. French Foundation (AB). NR 47 TC 47 Z9 48 U1 2 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 APR PY 2009 VL 65 IS 4 BP 414 EP 423 DI 10.1002/ana.21591 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 439VT UT WOS:000265656200010 PM 19399879 ER PT J AU Cohen, ME Bilimoria, KY Ko, CY Richards, K Hall, BL AF Cohen, Mark E. Bilimoria, Karl Y. Ko, Clifford Y. Richards, Karen Hall, Bruce Lee TI Effect of Subjective Preoperative Variables on Risk-Adjusted Assessment of Hospital Morbidity and Mortality SO ANNALS OF SURGERY LA English DT Article ID PHYSICAL STATUS CLASSIFICATION; SURGICAL QUALITY IMPROVEMENT; ANAL ANASTOMOSIS SURGERY; LOGISTIC-REGRESSION; VASCULAR-SURGERY; PATIENT SAFETY; POUCH FAILURE; ANESTHESIOLOGISTS; CARE; QUANTIFICATION AB Objective: To examine the influence of American Society of Anesthesiologists Physical Status Classification (ASA) and preoperative Functional Health Status (FHS) variables on risk-adjusted estimates of surgical quality and to assess whether classifications are inflated at some hospitals. Background: ASA and FHS are influential in risk-adjusted comparisons of surgical quality. However, because ASA and FHS are subjective they can be inflated, making patients appear more ill than they actually are, and crediting hospitals for a sicker patient population. Methods: We identified 28,75 1 colorectal surgery patients at 170 hospitals participating in the American College of Surgeon's National Surgical Quality Improvement Program (ACS NSQIP) during 2006 to 2007. Logistic regression models were developed for morbidity and mortality with and without inclusion of ASA and FHS. Hospital quality rankings from the different models were compared. Results: Morbidity and mortality rates were 24.3% and 3.9%. respectively. Percents of patients in ASA classes I through V were 3.3%, 46.4%, 41.5%. 8.3%, and 0.7% and that were independent or partially or totally dependent were 89.2%, 7.2% and 3.6%, respectively. Models that included ASA and FHS exhibited slightly better fit (Hosmer-Lemshow statistic) and discrimination (c-statistic) than models without both these variables, though magnitudes of differences were consistent with chance. There was inconsistent evidence for improper assignment of ASA and FHS. Conclusions: The small improvements in model quality when both ASA and FHS are present versus absent, suggest that they make a unique contribution to assessing severity of preoperative risk. With little indication that these subjective variables are subject to an important level of institutional bias, it is appropriate that they be used to assess risk-adjusted surgical quality. Periodic monitoring for inappropriate inflation of ASA status is warranted. C1 [Cohen, Mark E.; Bilimoria, Karl Y.; Ko, Clifford Y.; Richards, Karen] Assoc Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Hall, Bruce Lee] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. [Hall, Bruce Lee] Univ Missouri, Ctr Hlth Policy, Columbia, MO USA. RP Cohen, ME (reprint author), Assoc Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St, Chicago, IL USA. EM markcohen@facs.org FU American College of Surgeons Clinical Scholars in Residence program FX KYB was supported by the American College of Surgeons Clinical Scholars in Residence program. NR 32 TC 29 Z9 29 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 2009 VL 249 IS 4 BP 682 EP 689 DI 10.1097/SLA.0b013e31819eda21 PG 8 WC Surgery SC Surgery GA 429CT UT WOS:000264899100024 PM 19300217 ER PT J AU Ge, L Ratcliffe, M AF Ge, Liang Ratcliffe, Mark TI The Use of Computational Flow Modeling (CFD) to Determine the Effect of Left Ventricular Shape on Blood Flow in the Left Ventricle SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID MAGNETIC-RESONANCE; ACTIVE CONTRACTION; CARDIAC-MUSCLE; MECHANICS; HEART C1 [Ge, Liang; Ratcliffe, Mark] San Francisco VA Med Ctr, VAMC Surg 112D, San Francisco, CA 94121 USA. RP Ratcliffe, M (reprint author), San Francisco VA Med Ctr, VAMC Surg 112D, 4150 Clement St, San Francisco, CA 94121 USA. EM mratcliffe@hotmail.com FU NHLBI NIH HHS [R01 HL063348] NR 11 TC 9 Z9 13 U1 0 U2 2 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 APR PY 2009 VL 87 IS 4 BP 993 EP 994 DI 10.1016/j.athoracsur.2009.02.045 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 423OQ UT WOS:000264506000001 PM 19324118 ER PT J AU Bakaeen, FG Dhaliwal, AS Chu, D Bozkurt, B Tsai, P LeMaire, SA Wall, MJ Coselli, JS Huh, J AF Bakaeen, Faisal G. Dhaliwal, Amandeep S. Chu, Danny Bozkurt, Biykem Tsai, Peter LeMaire, Scott A. Wall, Matthew J., Jr. Coselli, Joseph S. Huh, Joseph TI Does the Level of Experience of Residents Affect Outcomes of Coronary Artery Bypass Surgery? SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 05-08, 2008 CL Austin, TX SP SE Thorac Surg Assoc ID CARDIAC-SURGERY; TRAIN RESIDENTS; OPERATING-ROOM; IMPACT; SAFETY; SUPERVISION; PERFORMANCE; SENIORITY; RISK AB Background. At our institution, coronary artery bypass grafting (CABG) operations are performed by staff surgeons or by first- or second-year cardiothoracic residents under the direct supervision of attending surgeons. We evaluated the influence of surgical seniority on outcomes. Methods. Using prospectively collected data from our departmental database, we identified all primary, isolated CABG operations (n = 1,042) performed between July 1997 and April 2007. Operations were then stratified according to the seniority of the primary surgeon: first-year cardiothoracic resident (CT1), second-year cardiothoracic resident (CT2), or staff surgeon. Data were examined for any association between seniority and surgical outcomes. Results. Staff, CT2, and CT1 surgeons performed 47 (4%), 610 (59%), and 385 (37%) cases, respectively. Efficiency was correlated with experience: for CT1, CT2, and staff surgeons, respectively, operative times averaged 345, 313, and 302 minutes; perfusion times averaged 118, 106, and 96 minutes; and cross-clamp times averaged 68, 58, and 57 minutes (p < 0.05 for all comparisons). The incidences of major morbidity (10.1%, 12.3%, 12.8%) and operative mortality (0.8%, 1.5%, 2.1%) were similar after operations performed by CT1, CT2, and staff surgeons, respectively (p > 0.15 for all). In univariate and multivariate analyses, the seniority of the primary surgeon did not independently predict morbidity or perioperative mortality. On follow-up (mean, 1,485 +/- 1,015 days), there was no significant difference in patient survival (log-rank, p = 0.64). Conclusions. Lower academic seniority was associated with longer CABG operative times but did not affect outcomes. Thus, training residents to perform CABG is safe and is characterized by progressive improvement in their technical efficiency. C1 [Bakaeen, Faisal G.] Ben Taub Gen Hosp, Dept Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr,Baylor Coll, Div Cardiothorac Surg,Dept Surg,Div Cardiol,Dept, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77030 USA. RP Bakaeen, FG (reprint author), Ben Taub Gen Hosp, Dept Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr,Baylor Coll, Div Cardiothorac Surg,Dept Surg,Div Cardiol,Dept, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 23 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2009 VL 87 IS 4 BP 1127 EP 1134 DI 10.1016/j.athoracsur.2008.12.080 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 423OQ UT WOS:000264506000019 PM 19324138 ER PT J AU Jacoby, GA Gacharna, N Black, TA Miller, GH Hooper, DC AF Jacoby, George A. Gacharna, Nancy Black, Todd A. Miller, George H. Hooper, David C. TI Temporal Appearance of Plasmid-Mediated Quinolone Resistance Genes SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; AMIKACIN RESISTANCE; ESCHERICHIA-COLI; AAC(6')-IB-CR VARIANT; ANTIBIOTIC-RESISTANCE; DNA HYBRIDIZATION; MODIFYING ENZYME; DETERMINANTS; PREVALENCE; EMERGENCE AB One hundred fifty AAC(6')-Ib-positive gram-negative isolates collected between 1981 and 1991 were examined by PCR for the presence of the aac(6')-Ib-cr variant and other plasmid-mediated quinolone resistance (PMQR) genes. None had the aac(6')-Ib-cr variant, qnrA, qnrS, qnrC, or qepA, but two strains collected in 1988 had qnrB alleles, making these the earliest known PMQR genes. C1 [Jacoby, George A.; Gacharna, Nancy] Lahey Clin Fdn, Burlington, MA USA. [Black, Todd A.] Schering Plough Res Inst, Kenilworth, NJ USA. [Miller, George H.] Blanca Pharmaceut, Menlo Pk, CA USA. [Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), 41 Mall Rd, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU National Institutes of Health [AI43312, AI57576]; U.S. Public Health Service FX This study was supported in part by grants AI43312 (to G. A. J.) and AI57576 (to D. C. H.) from the National Institutes of Health, U.S. Public Health Service. NR 24 TC 38 Z9 40 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2009 VL 53 IS 4 BP 1665 EP 1666 DI 10.1128/AAC.01447-08 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 421JU UT WOS:000264356000056 PM 19164145 ER PT J AU Huppert, TJ Diamond, SG Franceschini, MA Boas, DA AF Huppert, Theodore J. Diamond, Solomon G. Franceschini, Maria A. Boas, David A. TI HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY MAR 16-20, 2008 CL St Petersburg, FL SP Opt Soc Amer ID DIFFUSE OPTICAL TOMOGRAPHY; CEREBRAL BLOOD-VOLUME; HIGHLY SCATTERING TISSUES; FMRI DATA-ANALYSIS; ADULT HEAD MODEL; OXYGENATION CHANGES; LIGHT-PROPAGATION; HEMOGLOBIN OXYGENATION; HEMODYNAMIC-RESPONSE; NEWBORN-INFANTS AB Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data. (C) 2009 Optical Society of America C1 [Huppert, Theodore J.] Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. [Huppert, Theodore J.] Univ Pittsburgh, Med Ctr, Dept Bioengn, Pittsburgh, PA 15213 USA. [Huppert, Theodore J.; Diamond, Solomon G.; Franceschini, Maria A.; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Diamond, Solomon G.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Huppert, TJ (reprint author), Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. EM huppertt@upmc.edu OI Diamond, Solomon/0000-0002-7589-2942 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-106001, P41-RR14075]; NIA NIH HHS [P30 AG024827]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-06, R01 EB001954-07] NR 138 TC 212 Z9 213 U1 6 U2 27 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2009 VL 48 IS 10 BP D280 EP D298 DI 10.1364/AO.48.00D280 PG 19 WC Optics SC Optics GA 436VH UT WOS:000265443700033 PM 19340120 ER PT J AU Sakadzic, S Yuan, S Dilekoz, E Ruvinskaya, S Vinogradov, SA Ayata, C Boas, DA AF Sakadzic, Sava Yuan, Shuai Dilekoz, Ergin Ruvinskaya, Svetlana Vinogradov, Sergei A. Ayata, Cenk Boas, David A. TI Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY MAR 16-20, 2008 CL St Petersburg, FL SP Opt Soc Amer ID POSITRON-EMISSION-TOMOGRAPHY; RAT SOMATOSENSORY CORTEX; EXTRACELLULAR PH CHANGES; LASER-SPECKLE FLOWMETRY; NEURONAL-ACTIVITY; OXIDATIVE-METABOLISM; HEMOGLOBIN CONCENTRATION; FOREPAW STIMULATION; SENSORY STIMULATION; ARTERY OCCLUSION AB We developed a novel imaging technique that provides real-time two-dimensional maps of the absolute partial pressure of oxygen and relative cerebral blood flow in rats by combining phosphorescence lifetime imaging with laser speckle contrast imaging. Direct measurement of blood oxygenation based on phosphorescence lifetime is not significantly affected by changes in the optical parameters of the tissue during the experiment. The potential of the system as a novel tool for quantitative analysis of the dynamic delivery of oxygen to support brain metabolism was demonstrated in rats by imaging cortical responses to forepaw stimulation and the propagation of cortical spreading depression waves. This new instrument will enable further study of neurovascular coupling in normal and diseased brain. 0 2009 Optical Society of America C1 [Sakadzic, Sava; Yuan, Shuai; Ruvinskaya, Svetlana; Boas, David A.] Harvard Univ, Sch Med,Massachusetts Gen Hosp, Photon Migrat Imaging Lab,Dept Radiol, MGH MIT HMS Athinuola A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Dilekoz, Ergin; Ayata, Cenk] Harvard Univ, Sch Med, Stroke & Neurovasc Regulat Lab, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Stroke Serv & Neurosci Intens Care Unit, Massachusetts Gen Hosp,Dept Neurol, Charlestown, MA 02129 USA. [Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Boas, DA (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Photon Migrat Imaging Lab,Dept Radiol, MGH MIT HMS Athinuola A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM dboas@nmr.mgh.harvard.edu RI Yuan, Shuai/A-5783-2011 FU NIA NIH HHS [P50 AG005134]; NINDS NIH HHS [P50 NS010828, 5P50-NS010828, P01 NS055104, P01 NS055104-029001, P01-NS055104, P50 NS010828-329002, R01 NS057476, R01 NS057476-02, R01 NS061505, R01 NS061505-02, R01-NS057476, R01-NS061505] NR 79 TC 31 Z9 31 U1 3 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2009 VL 48 IS 10 BP D169 EP D177 DI 10.1364/AO.48.00D169 PG 9 WC Optics SC Optics GA 436VH UT WOS:000265443700021 PM 19340106 ER PT J AU Viswanathan, A AF Viswanathan, Anand TI High-Dose B Vitamin Supplementation as a Disease-Modifying Therapy in Alzheimer Disease SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID ELEVATED PLASMA HOMOCYSTEINE; FOLIC-ACID SUPPLEMENTATION; WHITE-MATTER LESIONS; CONTROLLED-TRIAL; COGNITIVE FUNCTION; DOUBLE-BLIND; MYOCARDIAL-INFARCTION; ROTTERDAM SCAN; ASSOCIATION; STROKE C1 Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, Boston, MA 02114 USA. RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org NR 37 TC 0 Z9 0 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2009 VL 66 IS 4 BP 520 EP 522 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 431ZX UT WOS:000265104400015 PM 19364938 ER PT J AU Dastjerdi, MH Al-Arfaj, KM Nallasamy, N Hamrah, P Jurkunas, UV Pineda, R Pavan-Langston, D Dana, R AF Dastjerdi, Mohammad H. Al-Arfaj, Khalid M. Nallasamy, Nambi Hamrah, Pedram Jurkunas, Ula V. Pineda, Roberto, II Pavan-Langston, Deborah Dana, Reza TI Topical Bevacizumab in the Treatment of Corneal Neovascularization SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR, 2008 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; WEAR CONTACT-LENSES; GRAFT-SURVIVAL; INHIBITION; VEGF; ANGIOGENESIS; THERAPY; AVASTIN; TRANSPLANTATION; EXPRESSION AB Objective: To study the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV). Design: In a prospective, open-label, noncomparative study, 10 eyes from 10 patients with stable corneal NV were treated with topical bevacizumab, 1.0%, for 3 weeks and followed up for up to 24 weeks. Main Outcome Measures: The primary safety variables were the occurrence of ocular and systemic adverse events throughout the course of the study. The primary efficacy variables were neovascular area, the area of the corneal vessels themselves; vessel caliber, the mean diameter of the corneal vessels; and invasion area, the fraction of the total corneal area covered by the vessels. Results: From baseline visit to the last follow-up visit, mean reductions were 47.1% (standard deviation [SD], 36.7%) for neovascular area, 54.1% (SD, 28.1%) for vessel caliber, and 12.2% (SD, 42.0%) for invasion area. The decreases in neovascular area and vessel caliber were statistically significant (P=.001 and P <.001, respectively). However, changes in invasion area did not achieve statistical significance (P=.19). Visual acuity and central corneal thickness showed no significant changes. Topical bevacizumab was well tolerated with no adverse events. Conclusions: Short-term topical bevacizumab therapy reduces the severity of corneal NV without local or systemic adverse effects. Application to Clinical Practice: Topical bevacizumab provides an alternative therapy in the treatment of stable corneal NV. C1 [Dastjerdi, Mohammad H.; Al-Arfaj, Khalid M.; Nallasamy, Nambi; Hamrah, Pedram; Jurkunas, Ula V.; Pineda, Roberto, II; Pavan-Langston, Deborah; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Sch Med,Cornea & Refract Surg Serv,Dept Ophthalmo, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU NEI NIH HHS [K12 EY016335, K24 EY019098, K24 EY019098-01] NR 37 TC 94 Z9 98 U1 0 U2 0 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 APR PY 2009 VL 127 IS 4 BP 381 EP 389 PG 9 WC Ophthalmology SC Ophthalmology GA 431ZN UT WOS:000265103400003 PM 19365012 ER PT J AU El-Deiry, MW Futran, ND McDowell, JA Weymuller, EA Yueh, B AF El-Deiry, Mark W. Futran, Neal D. McDowell, Jennifer A. Weymuller, Ernest A., Jr. Yueh, Bevan TI Influences and Predictors of Long-term Quality of Life in Head and Neck Cancer Survivors SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 7th International Conference on Head and Neck Cancer CY JUL 19-23, 2008 CL San Francisco, CA SP Amer Head & Neck Soc ID SQUAMOUS-CELL CARCINOMA; TOTAL LARYNGECTOMY; HEALTH-STATUS; CHEMORADIATION; COMORBIDITY; VALIDATION; SURGERY AB Objective: To examine the impact of clinical predictors (pretreatment variables) and other influences (treatment and posttreatment variables) on long-term quality of life (QOL) in patients treated for squamous cell carcinoma of the upper aerodigestive tract. We hypothesized that baseline QOL and comorbidity would be predictors of QOL 1 year after treatment. Design: Retrospective cohort study. Setting: Academic Medical Center in Seattle, Washington. Patients: Patients (N=173) with baseline (pretreatment) and 1-year posttreatment QOL data. Main Outcome Measure: Head and neck-specific QOL scores at 1 year after treatment (as measured by the University of Washington Quality of Life [UW-QOL] scale). Results: We identified strong relationships between 1-year UW-QOL scores and baseline UW-QOL scores (correlation coefficient [Pearson r]=0.58; P<.001) and pretreatment comorbidity (as measured by the Adult Comorbidity Evaluation scale) (Spearman rho=0.23; P<.001). T stage and N stage were also predictive. Although not a predictive variable, the presence of a gastrostomy tube at 1 year also strongly influenced 1-year UW-QOL scores. Patients with gastrostomy tubes had UW-QOL scores 11.5 points worse than those without (P<.001), when a 7-point difference is considered clinically significant. In predictive multivariate regression models, pretreatment QOL scores, comorbidity, and T stage had the strongest prognostic impact on 1-year UW-QOL scores. Conclusions: In bivariate analyses, the presence of a gastrostomy tube worsens UW-QOL scores at 1 year and requires further investigation. When considering predictive variables only, baseline QOL and comorbidity appear to have strong influences on posttreatment QOL and have greater impact than treatment modality. Greater attention to these baseline predictors should be given when counseling patients about long-term function after treatment. C1 [El-Deiry, Mark W.] Univ S Florida, Dept Otolaryngol Head & Neck Surg, Tampa, FL 33612 USA. [Futran, Neal D.; Weymuller, Ernest A., Jr.] Univ Washington, Seattle, WA 98195 USA. [Yueh, Bevan] Univ Minnesota, Minneapolis, MN USA. [McDowell, Jennifer A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. RP El-Deiry, MW (reprint author), Univ S Florida, Dept Otolaryngol Head & Neck Surg, 12901 Magnolia Ave, Tampa, FL 33612 USA. EM mark.eldeiry@moffitt.org OI Yueh, Bevan/0000-0003-1380-1053 NR 31 TC 38 Z9 38 U1 1 U2 7 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 APR PY 2009 VL 135 IS 4 BP 380 EP 384 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 435ZD UT WOS:000265381100010 PM 19380361 ER PT J AU Hirsh, AT Turner, AP Ehde, DM Haselkorn, JK AF Hirsh, Adam T. Turner, Aaron P. Ehde, Dawn M. Haselkorn, Jodie K. TI Prevalence and Impact of Pain in Multiple Sclerosis: Physical and Psychologic Contributors SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Mental health; Multiple sclerosis; Pain; Rehabilitation ID DISABILITY; VETERANS; INTERFERENCE; SEVERITY; SAMPLE; SEX AB Hirsh AT, Turner AP, Elide DM, Haselkorn JK. Prevalence and impact of pain in multiple sclerosis: physical and psychologic contributors. Arch Phys Med Rehabil 2009;90: 646-51. Objective: To characterize the prevalence and impact of pain in veterans with multiple sclerosis (MS) and to assess their association with demographic, biologic, and psychologic variables. Design: Cross-sectional cohort study linking computerized medical record information to mailed survey data. Setting: Veterans Health Administration (VHA). Participants: Sixty-four percent (2994/4685) of veterans with MS who received services in VRA and also returned Survey questionnaires. Interventions: Not applicable. Main Outcome Measures: Items assessing pain intensity, pain interference, and physical and mental health functioning. Results: Ninety-two percent of participants reported bodily pain within the prior 4 weeks, with 69% of the total sample indicating pain of moderate or higher intensity. Eighty-five percent indicated that pain caused functional interference during the past 4 weeks, with 71% of the total sample reporting pain-related interference that was moderate or greater. No significant sex or race differences emerged for the pain indices. A significant but modest relationship between increasing age and pain interference emerged (r=.05, P<.01); however, age was not significantly related to pain intensity. Multivariate regression analyses identified pain intensity (beta=.73), physical health functioning (beta=-07), and mental health functioning (beta=-.13) variables as significant, unique contributors to the prediction of pain interference. The interaction of pain intensity and physical functioning was also significant but of minimal effect size (beta=-.03). Conclusions: Pain is highly prevalent and causes substantial interference in the lives of veterans with MS. The functional impact of pain in veterans with MS is influenced by pain intensity, physical health, and emotional functioning. Clinical practice should take each of these domains into consideration and reflect a biopsychosocial conceptualization. C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Vet Affairs Multiple Sclerosis Ctr Excellence W, Seattle, WA USA. [Hirsh, Adam T.; Turner, Aaron P.; Ehde, Dawn M.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU Veterans Affairs Rehabilitation Research and Development Service Career Development Award [B4972W]; Veterans Affairs Center of Excellence in Substance Abuse Treatment and Education; Veterans Affairs Multiple Sclerosis Center of Excellence West; Veterans Affairs Office of Quality and Performance; National Institutes of Health [F31NS049675, IR011HD057916-01]; National Institute of Disability Research and Rehabilitation [H133B9031129]; Centers for Disease Control and Prevention [R01/DD000153-01]; National Multiple Sclerosis Society [PP1465] FX Supported by a Veterans Affairs Rehabilitation Research and Development Service Career Development Award (grant no. B4972W), Veterans Affairs Center of Excellence in Substance Abuse Treatment and Education, Veterans Affairs Multiple Sclerosis Center of Excellence West, Veterans Affairs Office of Quality and Performance; National Institutes of Health (grant nos. F31NS049675, IR011HD057916-01). National Institute of Disability Research and Rehabilitation (grant no. H133B9031129), Centers for Disease Control and Prevention (grant no. R01/DD000153-01). and National Multiple Sclerosis Society (grant no. PP1465). NR 31 TC 24 Z9 24 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2009 VL 90 IS 4 BP 646 EP 651 DI 10.1016/j.apmr.2008.10.019 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 432TD UT WOS:000265156200016 PM 19345781 ER PT J AU Damrauer, SM Bordeianou, L Berger, D AF Damrauer, Scott M. Bordeianou, Liliana Berger, David TI Contained Anastomotic Leaks After Colorectal Surgery Are We Too Slow to Act? SO ARCHIVES OF SURGERY LA English DT Article ID GASTROINTESTINAL ANASTOMOSIS; CURATIVE RESECTION; CANCER; SURVIVAL AB Hypothesis: Contained and free anastomotic leaks, which occur in a small percentage of patients after colorectal surgery, are different clinical entities and consequently should be managed differently. Design: Retrospective medical record review. Setting: Academic medical center. Patients: Patients who underwent colectomy with primary anastomosis (N = 4019) between January 1, 1992, and December 13, 2004, were eligible for participation in the study. Fifty-eight patients (1.5%) with an anastomotic leak demonstrated by communication between the collection and the gastrointestinal tract were identified. Twenty-eight of the patients had free leaks and 30 had contained leaks. Main Outcome Measures: Time to presentation, symptoms at presentation, rates of reexploration, and in-hospital mortality. Results: Baseline characteristics, presenting symptoms, physical examination findings, and laboratory values were similar between patients with contained and free leaks. Almost all patients with free leaks were taken directly to the operating room, whereas those with contained leaks were initially more likely to be treated nonoperatively. However, 24 of the 28 patients with contained leaks (86%) ultimately required surgical intervention. Inhospital mortality was the same in both groups (18% in the contained leak group and 17% in the free leak group). Conclusions: In patients with contained leaks who have documented communication between the abscess cavity and the bowel, there is no difference in the rate of operative management or morbidity and mortality when compared with those with free leaks. This finding suggests that the categorization of leaks as free or contained may not be justified and argues for early operative intervention even in patients with contained leaks. C1 [Bordeianou, Liliana] Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Dept Surg, Wang Ambulatory Care Ctr, Room 460,15 Parkman St, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 13 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2009 VL 144 IS 4 BP 333 EP 338 PG 6 WC Surgery SC Surgery GA 435ZE UT WOS:000265381200010 PM 19380646 ER PT J AU Namjou, B Sestak, AL Armstrong, DL Zidovetzki, R Kelly, JA Jacob, N Ciobanu, V Kaufman, KM Ojwang, JO Ziegler, J Quismorio, FP Reiff, A Myones, BL Guthridge, JM Nath, SK Bruner, GR Mehrian-Shai, R Silverman, E Klein-Gitelman, M McCurdy, D Wagner-Weiner, L Nocton, JJ Putterman, C Bae, SC Kim, YJ Petri, M Reveille, JD Vyse, TJ Gilkeson, GS Kamen, DL Alarcon-Riquelme, ME Gaffney, PM Moser, KL Merrill, JT Scofield, RH James, JA Langefeld, CD Harley, JB Jacob, CO AF Namjou, Bahram Sestak, Andrea L. Armstrong, Don L. Zidovetzki, Raphael Kelly, Jennifer A. Jacob, Noam Ciobanu, Voicu Kaufman, Kenneth M. Ojwang, Joshua O. Ziegler, Julie Quismorio, Francesco P., Jr. Reiff, Andreas Myones, Barry L. Guthridge, Joel M. Nath, Swapan K. Bruner, Gall R. Mehrian-Shai, Ruth Silverman, Earl Klein-Gitelman, Marisa McCurdy, Deborah Wagner-Weiner, Linda Nocton, James J. Putterman, Chaim Bae, Sang-Cheol Kim, Yun Jung Petri, Michelle Reveille, John D. Vyse, Timothy J. Gilkeson, Gary S. Kamen, Diane L. Alarcon-Riquelme, Marta E. Gaffney, Patrick M. Moser, Kathy L. Merrill, Joan T. Scofield, R. Hal James, Judith A. Langefeld, Carl D. Harley, John B. Jacob, Chaim O. TI High-Density Genotyping of STAT4 Reveals Multiple Haplotypic Associations With Systemic Lupus Erythematosus in Different Racial Groups SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; STAT4-DEFICIENT MICE; TARGETED DISRUPTION; SIGNALING PATHWAY; INTERFERON-ALPHA; RISK; INDUCTION; CELLS; IRF5 AB Objective. Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. Methods. Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. Results. We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. Conclusion. Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets. C1 [Jacob, Chaim O.] Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Kaufman, Kenneth M.; Harley, John B.] Oklahoma Med Res Fdn, US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. [Armstrong, Don L.; Zidovetzki, Raphael] Univ Calif Riverside, Riverside, CA 92521 USA. [Kaufman, Kenneth M.; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Ziegler, Julie; Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Reiff, Andreas] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Myones, Barry L.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Silverman, Earl] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Klein-Gitelman, Marisa] Childrens Mem Hosp, Chicago, IL 60614 USA. [Klein-Gitelman, Marisa] Northwestern Univ, Chicago, IL 60611 USA. [McCurdy, Deborah] Univ Calif Los Angeles, Los Angeles, CA USA. [Wagner-Weiner, Linda] LaRabida Hosp, Chicago, IL USA. [Wagner-Weiner, Linda] Univ Chicago, Chicago, IL 60637 USA. [Nocton, James J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Putterman, Chaim] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Bae, Sang-Cheol; Kim, Yun Jung] Hanyang Univ, Hosp Rheumat Dis, Seoul 133791, South Korea. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Reveille, John D.] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA. [Vyse, Timothy J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Kamen, Diane L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Alarcon-Riquelme, Marta E.] Uppsala Univ, Uppsala, Sweden. RP Jacob, CO (reprint author), Univ So Calif, Sch Med, Dept Med, 2011 Zonal Ave,HMT 705, Los Angeles, CA 90033 USA. EM Jacob@usc.edu OI Armstrong, Don/0000-0002-4904-638X; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154 FU NIH [R01-AR-445650, AR-42460, RR-015577, AI-31584, AR-12253, AR-48940, DE-015223, RR-020143, AI-062629, AI-24717, AI-07633, AR-62277, P01-AR-49084, P60-AR-48095, T32-AR-07450, M01-RR00032]; Alliance for Lupus Research [52104]; Lupus Foundation of America; Alliance for Lupus Research; US Department of Veterans Affairs FX Supported in part by NIH grant R01-AR-445650 and the Alliance for Lupus Research (grant 52104) to Dr. Jacob. The Oklahoma Medical Research Foundation receives funding Support from the NIH (grants AR-42460, RR-015577, AI-31584, AR-12253, AR-48940, DE-015223, RR-020143, AI-062629, AI-24717, AI-07633, and AR-62277), the Lupus Foundation of America, the Alliance for Lupus Research, and the US Department of Veterans Affairs. The University of Alabama at Birmingham receives funding support from the NIH (grants P01-AR-49084, P60-AR-48095, T32-AR-07450, and M01-RR00032). NR 51 TC 53 Z9 55 U1 0 U2 0 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 APR PY 2009 VL 60 IS 4 BP 1085 EP 1095 DI 10.1002/art.24387 PG 11 WC Rheumatology SC Rheumatology GA 432RW UT WOS:000265152800022 PM 19333953 ER PT J AU Rivera, JJ Nasir, K Choi, EK Yoon, YE Chun, EJ Choi, SI Choi, DJ Brancati, FL Blumenthal, RS Chang, HJ AF Rivera, Juan J. Nasir, Khurram Choi, Eue-Keun Yoon, Yeonyee E. Chun, Eun-Ju Choi, Sang-il Choi, Dong-Joo Brancati, Frederick L. Blumenthal, Roger S. Chang, Hyuk-Jae TI Detection of occult coronary artery disease in asymptomatic individuals with diabetes mellitus using non-invasive cardiac angiography SO ATHEROSCLEROSIS LA English DT Article DE Diabetes; Coronary artery disease; Computed tomography angiography ID MULTISLICE COMPUTED-TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; NONDIABETIC PATIENTS; MYOCARDIAL-ISCHEMIA; DIAGNOSTIC-ACCURACY; ANGINA; QUANTIFICATION; PREVALENCE; PLAQUES; TRIAL AB Introduction/objectives: Cardiovascular disease is the leading cause of death for individuals with diabetes mellitus. Controversy exists regarding the screening of asymptomatic diabetics for occult coronary artery disease (CAD). The purpose of this study is to describe the prevalence of occult CAD in a group of asymptomatic subjects with diabetes using non-invasive coronary angiography, as well as to investigate the predictive accuracy of current guidelines with regards to their recommended criteria for further cardiac diagnostic testing in this patient population. Methods: We prospectively enrolled 217 asymptomatic Korean outpatients with type 2 diabetes who had no prior history of CAD. All underwent non-invasive coronary angiography using a 64-slice multi-detector computed tomography scanner. Results: The mean age of the study participants was 59 +/- 8 years; 66% were men. Diabetes duration was 7 +/- 7 years, mean Framingham risk score was 13%, and mean hemoglobin A1C level was 7%. Of the 217 outpatients, 138 (64%) had occult CAD based on cardiac computed tomography angiography (CCTA) findings. Thirty-six (36/138; 26%) had a significant stenosis on CCTA. Nearly half of the individuals (62/138; 45%) had a combination of non-calcifled and calcified plaques. Only 5 out of 217 (2%) individuals with significant stenosis would have been missed using the American Diabetes Association (ADA) criteria for further cardiac testing. Conclusion: Almost two thirds of asymptomatic diabetics have occult CAD, including obstructive disease. Based on CCTA findings, the ADA criteria for further cardiac diagnostic testing would identify most individuals who have a significant coronary stenosis. C1 [Chang, Hyuk-Jae] Seoul Natl Univ, Div Cardiol, Ctr Cardiovasc, Bundang Hosp, Songnam 463707, Gyeonggi Do, South Korea. [Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Nasir, Khurram] Harvard Univ, Sch Med, Boston, MA USA. [Chun, Eun-Ju; Choi, Sang-il] Seoul Natl Univ, Div Radiol, Ctr Cardiovasc, Bundang Hosp, Songnam 463707, Gyeonggi Do, South Korea. [Brancati, Frederick L.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Brancati, Frederick L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Chang, HJ (reprint author), Seoul Natl Univ, Div Cardiol, Ctr Cardiovasc, Bundang Hosp, 300 Gumi Dong, Songnam 463707, Gyeonggi Do, South Korea. EM hjchang@snu.ac.kr FU NIDDK NIH HHS [P30 DK079637] NR 29 TC 32 Z9 34 U1 0 U2 0 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 APR PY 2009 VL 203 IS 2 BP 442 EP 448 DI 10.1016/j.atherosclerosis.2008.07.030 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 437CW UT WOS:000265464800017 PM 18822414 ER PT J AU Bliss-Moreau, E Barrett, LF AF Bliss-Moreau, Eliza Barrett, Lisa Feldman TI What's reason got to do with it? Affect as the foundation of learning SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID STIMULUS; PREDICTIONS; COGNITION; BRAIN; FEAR AB We propose that learning has a top-down component, but not in the propositional terms described by Mitchell et al. Specifically, we propose that a host of learning processes, including associative learning, serve to imbue the representation of the conditioned stimulus (CS) with affective meaning. C1 [Bliss-Moreau, Eliza] Univ Calif Davis, Dept Psychiat & Behav Sci, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Bliss-Moreau, E (reprint author), Univ Calif Davis, Dept Psychiat & Behav Sci, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. EM eblissmoreau@ucdavis.edu; barretli@bc.edu NR 12 TC 6 Z9 6 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2009 VL 32 IS 2 BP 201 EP + DI 10.1017/S0140525X09000892 PG 11 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 492UD UT WOS:000269684500035 ER PT J AU Feldman, G Harley, R Kerrigan, M Jacobo, M Fava, M AF Feldman, Greg Harley, Rebecca Kerrigan, Molly Jacobo, Michelle Fava, Maurizio TI Change in emotional processing during a dialectical behavior therapy-based skills group for major depressive disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Depression; Emotional processing; Rumination; Emotion regulation; Mindfulness; Dialectical behavior therapy ID RESPONSE STYLES THEORY; METHODOLOGICAL ISSUES; THOUGHT SUPPRESSION; SELF-REPORT; LIFE EVENT; RUMINATION; MINDFULNESS; SCALE; VALIDATION; SYMPTOMS AB Across studies, paying attention to and analyzing one's emotions has been found to be both positively and negatively correlated with depression symptoms. One way of reconciling these seemingly contradictory findings is the possibility that attending to emotions in a skillful manner may help to reduce depression whereas attending to emotions with limited skill may be counterproductive. Dialectical behavior therapy (DBT) is a clinical intervention designed to foster adaptive awareness, expression, regulation, tolerance, and acceptance of emotions. Results of the present report come from a pilot study of a 16-week DBT-based skills training group for treatment-resistant major depressive disorder (MDD) as an adjunctive treatment to pharmacotherapy. Patients were randomized to treatment or a waitlist control group. A significant interaction revealed that increases in emotional processing were associated with decreases in depression symptoms in the DBT-based skills group; however, increases in emotional processing in the waitlist condition were associated with increases in depression. Results offer preliminary support for the idea that participating in DBT-based skills training may help individuals with treatment-resistant MDD to develop skills that facilitate processing emotions in a way that helps to reduce rather than exacerbate depression symptoms. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Feldman, Greg] Simmons Coll, Dept Psychol, Pk Sci Ctr, Boston, MA 02114 USA. [Feldman, Greg; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Harley, Rebecca; Jacobo, Michelle] Massachusetts Gen Hosp, Dept Psychiat, Dialect Behav Therapy Program, Boston, MA 02114 USA. RP Feldman, G (reprint author), Simmons Coll, Dept Psychol, Pk Sci Ctr, 300 Fenway, Boston, MA 02114 USA. EM greg.feldman@simmons.edu NR 40 TC 26 Z9 26 U1 1 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2009 VL 47 IS 4 BP 316 EP 321 DI 10.1016/j.brat.2009.01.005 PG 6 WC Psychology, Clinical SC Psychology GA 437GY UT WOS:000265476100007 PM 19232571 ER PT J AU Grover, S Syngal, S AF Grover, Shilpa Syngal, Sapna TI Genetic testing in gastroenterology: Lynch syndrome SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE Lynch syndrome; Hereditary non-polyposis colorectal cancer; HNPCC; mismatch repair genes ID NONPOLYPOSIS COLORECTAL-CANCER; DNA-MISMATCH-REPAIR; REVISED BETHESDA GUIDELINES; POPULATION-BASED COHORT; MSH2 MUTATION CARRIERS; MICROSATELLITE INSTABILITY; ENDOMETRIAL CANCER; CLINICAL-CRITERIA; COLON-CANCER; EXTRACOLONIC CANCER AB Lynch syndrome/Hereditary non-polyposis colorectal cancer is caused by inherited germline mutations in mismatch repair (MMR) genes, and accounts for 2-5% of colorectal cancers (CRC). It is characterized by Young onset CRC and an increased risk for gynaecologic, Urinary tract and gastrointestinal cancers. Family history evaluation is crucial in the early identification of individuals at risk for Lynch syndrome. Individuals whose family history includes multiple relatives with cancer, two or more primary cancers, or component tumours diagnosed at a young age, should undergo genetic evaluation for Lynch syndrome. Guidelines recommend initial evaluation of the tumour with immunohistochemistry or microsatellite instability testing followed by germline testing for mutations in MMR genes in those with abnormal results. Genetic test results can guide screening recommendations for patients and their families. However, results are not always conclusive and in such cases recommendations for cancer screening Should be individualized on the basis of personal and family history. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Syngal, Sapna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Syngal, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org NR 76 TC 8 Z9 8 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD APR PY 2009 VL 23 IS 2 BP 185 EP 196 DI 10.1016/j.bpg.2009.02.006 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457AI UT WOS:000266896400006 PM 19414145 ER PT J AU Li, J Makrigiorgos, GM AF Li, Jin Makrigiorgos, G. Mike TI COLD-PCR: a new platform for highly improved mutation detection in cancer and genetic testing SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE co-amplification at lower denaturation temperature-PCR (COLD-PCR); DNA amplification; genetic testing; PCR-based mutation detection; real-time PCR; sequencing ID CELL LUNG-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; PROGNOSTIC-FACTORS; DNA; RESISTANCE; GEFITINIB; P53 AB PCR is widely employed as the initial DNA amplification step for genetic testing and cancer biomarker detection. However, a key limitation of PCR-based methods, including real-time PCR, is the inability to selectively amplify low levels of variant alleles in a wild-type allele background. As a result, downstream assays are limited in their ability to identify subtle genetic changes that can have a profound impact on clinical decision-making and outcome or that can serve as cancer biomarkers. We developed COLD-PCR (co-amplification at lower denaturation temperature-PCR) [Li, Wang, Mamon, Kulke, Berbeco and Makrigiorgos (2008) Nat. Med. 14, 579-584], a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence. Consequently, COLD-PCR amplification from genomic DNA yields PCR products containing high-prevalence variant alleles that can be detected. Since PCR constitutes a ubiquitous initial step for almost all genetic analysis, COLD-PCR provides a general platform to improve the sensitivity of essentially all DNA-variation detection technologies including Sanger sequencing, pyrosequencing, single molecule sequencing, mutation scanning, mutation genotyping or methylation assays. COLD-PCR combined with real-time PCR provides a new approach to boost the capabilities of existing real-time mutation detection methods. we replaced regular PCR with COLD-PCR before sequencing or real-time mutation detection assays to improve mutation detection-sensitivity by up to 100-fold and identified novel p53/Kras/EGFR (epidermal growth factor receptor) mutations in heterogeneous cancer samples that were missed by all existing methods. For clinically relevant micro-deletions, COLD-PCR enabled exclusive amplification and isolation of the mutants. COLD-PCR is expected to have diverse applications in the fields of biomarker identification and tracing, genomic instability, infectious diseases, DNA methylation testing and prenatal identification of fetal alleles in maternal blood. C1 [Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Div DNA Repair & Med Phys & Biophys, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Level L2,Radiat Therapy,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU National Institutes of Health [CA111994-01, CA115439-01]; [5 T32 CA09078] FX This work was supported by training [grant number 5 T32 CA09078] (to J.L.) and by the National Institutes of Health [grant numbers CA111994-01 and CA115439-01]. NR 15 TC 36 Z9 38 U1 2 U2 13 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD APR PY 2009 VL 37 BP 427 EP 432 DI 10.1042/BST0370427 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429FD UT WOS:000264905400019 PM 19290875 ER PT J AU Nucera, C Goldfarb, M Hodin, R Parangi, S AF Nucera, Carmelo Goldfarb, Melanie Hodin, Richard Parangi, Sareh TI Role of B-Raf(V600E) in differentiated thyroid cancer and preclinical validation of compounds against B-Raf(V600E) SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Differentiated thyroid cancer; Papillary thyroid cancer; Papillary thyroid microcarcinoma; Extrathyroidal extension; Wild-type B-Raf; B-Raf(V600E); MAP kinases; Compounds; Preclinical validations ID BRAF V600E MUTATION; B-RAF KINASE; PAPILLARY CARCINOMAS; BRAF(V600E) MUTATION; CLINICAL-IMPLICATIONS; FUNCTIONAL-ANALYSIS; THERAPEUTIC TARGET; HOT-SPOT; ACTIVATION; TUMORS AB B-Raf(V600E), an oncogenic protein kinase, is the most frequent genetic alteration in papillary thyroid carcinomas (PTC). PTC represents 80-90% of all thyroid cancers and over the past five years, more than 200 manuscripts have been published about the relationship between "B-Raf(V600E) and thyroid cancer". B-Raf(V600E) genetically arises from a transversion point mutation (valine-to-glutamate substitution at amino acid residue-600, V600E) and leads to over activation of the mitogen-activated protein kinases (MAPK) signaling pathway. The MAPK pathway is essential for transmitting proliferation signals generated by cell surface receptors and cytoplasmic signaling elements to the nucleus. In many cancers, including thyroid cancer, B-Raf(V600E) appears to play a crucial role in cell proliferation, survival and de-differentiation. In thyroid cancer, the V600E mutation occurs with greater frequently in aggressive subtypes of PTC, and in individuals that present at advanced stages of disease with extra-thyroidal extension and/or lymph node metastases. B-Raf(V600E) is considered a marker of aggressive disease in both PTC (> 1 cm) and micro-PTC (<= 1 cm), and interestingly, is associated with both loss of I-131 avidity and PTC recurrence. Though treatment of patients with thyroid cancer is usually successful and most patients are rendered disease-free, to date there are no effective therapies for patients with invasive, non-radioiodine sensitive tumors or metastatic disease. In this article we will review the relation between B-Raf(V600E) and PTC, as well as both non-selective and selective pharmacological agents currently under investigation for treatment of B-Raf(V600E) positive PTC. (C) 2009 Elsevier B.V. All rights reserved. C1 [Nucera, Carmelo; Hodin, Richard; Parangi, Sareh] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Endocrine Surg,Thyroid Canc Res Lab,Div Gen, Boston, MA 02115 USA. [Goldfarb, Melanie] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Parangi, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Endocrine Surg,Thyroid Canc Res Lab,Div Gen, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA. EM sparangi@partners.org FU NCI NIH HHS [R01 CA149738] NR 71 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR PY 2009 VL 1795 IS 2 BP 152 EP 161 DI 10.1016/j.bbcan.2009.01.003 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 435UV UT WOS:000265369700008 PM 19356676 ER PT J AU Fernandez, A Quintero, J Hornero, R Zuluaga, P Navas, M Gomez, C Escudero, J Garcia-Campos, N Biederman, J Ortiz, T AF Fernandez, Alberto Quintero, Javier Hornero, Roberto Zuluaga, Pilar Navas, Marta Gomez, Carlos Escudero, Javier Garcia-Campos, Natalia Biederman, Joseph Ortiz, Tomas TI Complexity Analysis of Spontaneous Brain Activity in Attention-Deficit/Hyperactivity Disorder: Diagnostic Implications SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Attention-deficit/hyperactivity disorder; brain maturation; complexity; maturational delay; MEG; nonlinear analysis ID DEFICIT-HYPERACTIVITY DISORDER; NONLINEAR DYNAMICAL ANALYSIS; ALZHEIMERS-DISEASE PATIENTS; LEMPEL-ZIV COMPLEXITY; TIME-SERIES; BACKGROUND ACTIVITY; FRONTAL-CORTEX; EEG; CHILDREN; MEG AB Background: Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. Methods: Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity(LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. Results: Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. Conclusions: Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal cortex. C1 [Fernandez, Alberto; Ortiz, Tomas] Univ Complutense Madrid, Ctr Magnetoencefalog Dr Perez Modrego, E-28040 Madrid, Spain. [Fernandez, Alberto; Ortiz, Tomas] Univ Complutense Madrid, Dept Psiquiatria, E-28040 Madrid, Spain. [Zuluaga, Pilar] Univ Complutense Madrid, Dept Estadist & Invest Operat, E-28040 Madrid, Spain. [Quintero, Javier; Navas, Marta] Hosp Infanta Leonor, Serv Psiquiatria, Madrid, Spain. [Hornero, Roberto; Gomez, Carlos; Escudero, Javier] Univ Valladolid, Grp Ingn Biomed, Valladolid, Spain. [Garcia-Campos, Natalia] Inst Neuroconductual Madrid, Madrid, Spain. [Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Fernandez, A (reprint author), Univ Complutense Madrid, Ctr Magnetoencefalog Dr Perez Modrego, Avda Complutense S-N, E-28040 Madrid, Spain. EM aferlucas@med.ucm.es RI Gomez, Carlos/B-4659-2008; Escudero, Javier/B-4185-2008; Fernandez, Alberto/H-1927-2015; Hornero, Roberto/B-5398-2008; OI Gomez, Carlos/0000-0002-9488-0605; Escudero, Javier/0000-0002-2105-8725; Fernandez, Alberto/0000-0001-9998-8343; Hornero, Roberto/0000-0001-9915-2570; Quintero, Javier/0000-0002-2491-8647 NR 48 TC 43 Z9 44 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2009 VL 65 IS 7 BP 571 EP 577 DI 10.1016/j.biopsych.2008.10.046 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 420SN UT WOS:000264309600005 PM 19103438 ER PT J AU Pru, JK AF Pru, James K. TI Progesterone Signaling Outside the TATA Box SO BIOLOGY OF REPRODUCTION LA English DT Editorial Material ID EXPRESSION; BINDING; ENDOMETRIUM; INHIBITION; RECEPTORS; TISSUES; UTERINE; UTERUS; MOUSE C1 Massachusetts Gen Hosp, Ctr Reprod Biol, Boston, MA 02114 USA. RP Pru, JK (reprint author), Massachusetts Gen Hosp, Ctr Reprod Biol, Boston, MA 02114 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 2009 VL 80 IS 4 BP 842 EP 842 DI 10.1095/biolreprod.108.074948 PG 1 WC Reproductive Biology SC Reproductive Biology GA 422OG UT WOS:000264437000027 PM 19307301 ER PT J AU Oral, E Beckos, CAG Lozynsky, AJ Malhi, AS Muratoglu, OK AF Oral, Ebru Beckos, Christine A. Godleski Lozynsky, Andrew J. Malhi, Arnaz S. Muratoglu, Orhun K. TI Improved resistance to wear and fatigue fracture in high pressure crystallized vitamin E-containing ultra-high molecular weight polyethylene SO BIOMATERIALS LA English DT Article DE Semi-crystalline; Plasticity; Cross-linking; Oxidation resistance; Fatigue resistance; Biomaterials ID MECHANICAL-PROPERTIES; IRRADIATED UHMWPE; ALPHA-TOCOPHEROL; CROSS-LINKING AB Higher crystallinity and extended chain morphology are induced in ultra-high molecular weight polyethylene (UHMWPE) in the hexagonal phase at temperatures and pressures above the triple point, resulting in improved mechanical properties. In this study, we report the effects of the presence of a plasticizing agent, namely vitamin E (alpha-tocopherol), in UHMWPE during high pressure crystallization. We found that this new vitamin E-blended and high pressure crystallized UHMWPE (VEHPE) has improved fatigue strength and wear resistance compared to virgin high pressure crystallized (HP) UHMWPE. This suggested different mechanisms of wear reduction and fatigue crack propagation resistance in UHMWPE. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM orhun@alum.mit.edu FU NIH [R01 AR051142] FX This work was funded by NIH R01 AR051142 and departmental funds. NR 18 TC 33 Z9 35 U1 1 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2009 VL 30 IS 10 BP 1870 EP 1880 DI 10.1016/j.biomaterials.2008.12.029 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 418JZ UT WOS:000264145800002 PM 19135247 ER PT J AU Wang, M Hanfelt, JJ AF Wang, Molin Hanfelt, John J. TI A robust method for finely stratified familial studies with proband-based sampling SO BIOSTATISTICS LA English DT Article DE 2-Index asymptotics; Adjusted profile estimating function; Ascertainment bias; Bias reduction; Familial aggregation; Nuisance parameter; Proband; Sparse data; Stratified study ID PROFILE ESTIMATING FUNCTION; MATCHED CASE-CONTROL; AGGREGATION AB This paper presents a robust method to conduct inference in finely stratified familial studies under proband-based sampling. We assume that the interest is in both the marginal effects of subject-specific covariates on a binary response and the familial aggregation of the response, as quantified by intrafamilial pairwise odds ratios. We adopt an estimating function for proband-based family studies originally developed by Zhao and others (1998) in the context of an unstratified design and treat the stratification effects as fixed nuisance parameters. Our method requires modeling only the first 2 joint moments of the observations and reduces by 2 orders of magnitude the bias induced by fitting the stratum-specific nuisance parameters. An analytical standard error estimator for the proposed estimator is also provided. The proposed approach is applied to a matched case-control familial study of sleep apnea. A simulation study confirms the usefulness of the approach. C1 [Wang, Molin] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. [Hanfelt, John J.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. [Wang, Molin] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, M (reprint author), Harvard Univ, Dept Biostat, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. EM mwang@jimmy.harvard.edu FU U. S. National Institutes of Health [R01 MH060628] FX U. S. National Institutes of Health (R01 MH060628) to J.J.H. NR 15 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2009 VL 10 IS 2 BP 364 EP 373 DI 10.1093/biostatistics/kxn043 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 413ZX UT WOS:000263834800014 PM 19202153 ER PT J AU Janorkar, AV King, KR Megeed, Z Yarmush, ML AF Janorkar, Amol V. King, Kevin R. Megeed, Zaki Yarmush, Martin L. TI Development of an In Vitro Cell Culture Model of Hepatic Steatosis Using Hapatocyte-Derived Reporter Cells SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE steatosis; reporter cells; in vitro disease model ID NF-KAPPA-B; FATTY LIVER-DISEASE; GENE-EXPRESSION; ENDOTHELIAL-CELLS; ARACHIDONIC-ACID; LINOLEIC-ACID; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE STRESS; RAT HEPATOCYTES; ALPHA AB Fatty liver disease is a problem of growing clinical importance due to its association with the increasingly prevalent conditions of obesity and diabetes. While steatosis represents a reversible state of excess intrahepatic lipid, it is also associated with increased susceptibility to oxidative and cytokine stresses and progression to irreversible hepatic injury characterized by steatohepatitis, cirrhosis, and malignancy. Currently, the molecular mechanisms underlying progression of this dynamic disease remain poorly understood, particularly at the level of transcriptional regulation. We recently constructed a library of stable monoclonal green fluorescent protein (GFP) reporter cells that enable transcriptional regulation to be studied dynamically in living cells. Here, we adapt the reporter cells to create a model of steatosis that will allow investigation of transcriptional dynamics associated with the development of steatosis and the response to subsequent "second hit" stresses. The reporter model recapitulates many cellular features of the human disease, including fatty acid uptake, intracellular triglyceride accumulation, increased reactive oxygen species accumulation, decreased mitochondrial membrane potential, increased susceptibility to apoptotic cytokine stresses, and decreased proliferation. Finally, to demonstrate the utility of the reporter cells for studying transcriptional regulation, we compared the transcriptional dynamics of nuclear factor kappa B (NF kappa B), heat shock response element (HSE), and glucocorticoid response element (GRE) in response to their classical inducers under lean and fatty conditions and found that intracellular lipid accumulation was associated with dose-dependent impairment of NF kappa B and HSE but not GRE activation. Thus, steatotic reporter cells represent an efficient model for studying transcriptional responses and have the potential to provide important insights into the progression of fatty liver disease. C1 [Janorkar, Amol V.; King, Kevin R.; Megeed, Zaki; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Burns Inst, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Shriners Burns Inst, Massachusetts Gen Hosp,Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU National Institutes of Health [5R01AI063795, EB002503] FX Contract grant numbers: 5R01AI063795; EB002503 NR 55 TC 21 Z9 21 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD APR 1 PY 2009 VL 102 IS 5 BP 1466 EP 1474 DI 10.1002/bit.22191 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 418DE UT WOS:000264126600020 PM 19061238 ER PT J AU Potts, JT Wimalawansa, S Martin, TJ AF Potts, John T. Wimalawansa, Sunil Martin, T. John TI Iain MacIntyre FRS (1924-2008) In Memoriam SO BONE LA English DT Biographical-Item C1 [Martin, T. John] St Vincents Inst Med Res, Melbourne, Vic, Australia. [Martin, T. John] Univ Melbourne, Dept Med, Melbourne, Vic, Australia. [Potts, John T.] Massachusetts Gen Hosp East, Endocrine Unit, Boston, MA 02129 USA. [Wimalawansa, Sunil] Univ Med & Dent New Jersey, Dept Med, Div Metab Endocrinol & Nutr, New Brunswick, NJ 08903 USA. RP Martin, TJ (reprint author), St Vincents Inst Med Res, Melbourne, Vic, Australia. EM jmartin@svi.edu.au NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2009 VL 44 IS 4 BP 520 EP 521 DI 10.1016/j.bone.2008.12.001 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 425CK UT WOS:000264614400001 ER PT J AU Taghian, AG Bourgier, C AF Taghian, Alphonse G. Bourgier, Celine TI Counterpoint: Conformal external beam for accelerated partial breast irradiation SO BRACHYTHERAPY LA English DT Editorial Material ID INITIAL CLINICAL-EXPERIENCE; INTRAOPERATIVE RADIATION-THERAPY; INTENSITY-MODULATED RADIOTHERAPY; LOW-DOSE-RATE; INTERSTITIAL BRACHYTHERAPY; CONSERVING SURGERY; LUMPECTOMY CAVITY; RANDOMIZED-TRIAL; ELECTRONS ELIOT; CANCER C1 [Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Bourgier, Celine] Inst Gustave Roussy, Dept Radiat Oncol, Villejuif, France. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org NR 47 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD APR-JUN PY 2009 VL 8 IS 2 BP 184 EP 188 DI 10.1016/j.brachy.2009.02.002 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 448OT UT WOS:000266272600003 PM 19433317 ER PT J AU Taghian, AG Bourgier, C AF Taghian, Alphonse G. Bourgier, Celine TI Point: Brachytherapy for accelerated partial breast irradiation Rebuttal to Dr. Wazer SO BRACHYTHERAPY LA English DT Editorial Material C1 [Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Bourgier, Celine] Inst Gustave Roussy, Villejuif, France. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD APR-JUN PY 2009 VL 8 IS 2 BP 189 EP 189 DI 10.1016/j.brachy.2009.03.004 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 448OT UT WOS:000266272600004 ER PT J AU Dussor, G Koerber, HR Oaklander, AL Rice, FL Molliver, DC AF Dussor, G. Koerber, H. R. Oaklander, A. L. Rice, F. L. Molliver, D. C. TI Nucleotide signaling and cutaneous mechanisms of pain transduction SO BRAIN RESEARCH REVIEWS LA English DT Review DE Purinergic; Nociceptive; Inflammation; Neuropathic; Cutaneous ID DORSAL-ROOT GANGLION; GENE-RELATED PEPTIDE; HUMAN EPIDERMAL-KERATINOCYTES; PRIMARY AFFERENT NEURONS; SENSORY NEURONS; HUMAN-SKIN; P2X RECEPTORS; NERVE-FIBERS; PURINERGIC RECEPTORS; NEUROTROPHIC FACTOR AB Sensory neurons that innervate the skin provide critical information about physical contact between the organism and the environment, including information about potentially-damaging stimuli that give rise to the sensation of pain. These afferents also contribute to the maintenance of tissue homeostasis, inflammation and wound healing, while sensitization of sensory afferents after injury results in painful hypersensitivity and protective behavior. In contrast to the traditional view of primary afferent terminals as the sole site of sensory transduction, recent reports have lead to the intriguing idea that cells of the skin play an active role in the transduction of sensory stimuli. The search for molecules that transduce different types of sensory stimuli (mechanical, heat, chemical) at the axon terminal has yielded a wide range of potential effectors, many of which are expressed by keratinocytes as well as neurons. Emerging evidence underscores the importance of nucleotide signaling through P2X ionotropic and P2Y metabotropic receptors in pain processing, and implicates nucleotide signaling as a critical form of communication between cells of the skin, immune cells and sensory neurons. it is of great interest to determine whether pathological changes in these mechanisms contribute to chronic pain in human disease states such as complex regional pain syndrome (CRPS). This review discusses recent advances in our understanding of communication mechanisms between cells of the skin and sensory axons in the transduction of sensory input leading to pain. (C) 2009 Elsevier B.V. All rights reserved. C1 [Molliver, D. C.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Rice, F. L.] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Dussor, G.] Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. [Koerber, H. R.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15261 USA. RP Molliver, DC (reprint author), Univ Pittsburgh, Dept Med, S 843 Scaifie Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM dcm12@pitt.edu FU ALO [R01NS42866, K24NS059892]; Reflex Sympathetic Dystrophy Syndrome Association; National Organization for Rare Disorders [NS056122] FX Supported by: ALO: the Public Health Service (R01NS42866, K24NS059892), the Reflex Sympathetic Dystrophy Syndrome Association and the National Organization for Rare Disorders. DCM: NIH NS056122. NR 117 TC 43 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD APR PY 2009 VL 60 IS 1 BP 24 EP 35 DI 10.1016/j.brainresrev.2008.12.013 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 441LC UT WOS:000265769600003 PM 19171165 ER PT J AU Sun, ZX Goldhirsch, A Price, KN Colleoni, M Ravaioli, A Simoncini, E Campbelli, I Gelber, RD Towler, M AF Sun, Zhuoxin Goldhirsch, Aron Price, Karen N. Colleoni, Marco Ravaioli, Alberto Simoncini, Edda Campbelli, Ian Gelber, Richard D. Towler, Mark TI Bone Quality Test (BQT) scores of fingernails in postmenopausal patients treated with adjuvant letrozole or tamoxifen for early breast cancer SO BREAST LA English DT Article DE Fingernail; Bone quality test; Breast cancer; Hormonal therapy; Letrozole ID AROMATASE INHIBITOR; WOMEN; HEALTH; NAIL AB Background: The relationship between nail and bone may be measurable, thus making the fingernail a potentially Valuable too] for assessing bone health for women receiving treatment for breast cancer. In the BIG 1-98 Fingernail Pilot Substudy, Bone Quality Test (BQT) scores of fingernails were measured at two assessment timepoints. Methods: Thirteen eligible patients were enrolled into the substudy during their treatment with tamoxifen (four patients) or letrozole (nine patients). Two fingernails were tested and BQT Scores averaged for two assessments six months apart. Results: BQT scores collected six months later (second assessment) significantly decreased compared with those at first collection (p = 0.007) regardless of treatment and prior fracture. Conclusion: The reduction of BQT scores observed in the patients of our small exploratory study during exposure to bone-altering breast cancer treatments is an incentive for larger studies using this technique. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Goldhirsch, Aron; Colleoni, Marco] European Inst Oncol, Dept Med, Res Unit Med Senol, I-20141 Milan, Italy. [Sun, Zhuoxin; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Sun, Zhuoxin; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Ravaioli, Alberto] Osped Infermi Rimini, Dept Oncol, Rimini, Italy. [Ravaioli, Alberto] Ist Sci Romagnolo Studio & Cura Tumori, Meldolo, FC, Italy. [Simoncini, Edda] Oncol Med Spedali Civili, Brescia, Italy. [Campbelli, Ian] Waikato Hosp, Hamilton, New Zealand. [Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Towler, Mark] Univ Limerick, Mat & Surface Sci Inst, Limerick, Ireland. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Res Unit Med Senol, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org FU Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX Sources of support: the International Breast Cancer Study Group is supported by the Swedish Cancer Society, the Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), National Cancer Institute Grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). These groups had no role in writing this paper. NR 15 TC 0 Z9 0 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD APR PY 2009 VL 18 IS 2 BP 84 EP 88 DI 10.1016/j.breast.2009.01.003 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 446VG UT WOS:000266148900004 PM 19243946 ER PT J AU Leleu, X Hunter, ZR Xu, L Roccaro, AM Moreau, AS Santos, DD Hatjiharissi, E Bakthavachalam, V Adamia, S Ho, AW Soumerai, J Patterson, CJ Manning, RJ Hamilton, S Verselis, S Fox, E Carrasco, R Ghobrial, IM Treon, SP AF Leleu, Xavier Hunter, Zachary R. Xu, Lian Roccaro, Aldo M. Moreau, Anne-Sophie Santos, Daniel D. Hatjiharissi, Evdoxia Bakthavachalam, Vinod Adamia, Sophia Ho, Allen W. Soumerai, Jacob Patterson, Christopher J. Manning, Robert J. Hamilton, Susanna Verselis, Sigitas Fox, Edward Carrasco, Ruben Ghobrial, Irene M. Treon, Steven P. TI Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom Macroglobulinemia; XBP1; ERN1 ID UNFOLDED PROTEIN RESPONSE; INTERNATIONAL WORKSHOP; TRANSCRIPTION FACTOR; MESSENGER-RNA; ER STRESS; RECOMMENDATIONS; ATF6; MICE; XBP1 AB Waldenstrom Macroglobulinemia (WM) is a B-cell malignancy characterized by excess bone marrow (BM) lymphoplasmacytic cells (LPC). The accumulation of LPC in WM may represent a failure of B-cells to properly differentiate into plasma cells. The present study investigated transcriptional expression of genes involved in late B-cell differentiation, including PRDM1, PAX5, XBP1 transcripts and ERN1, in BM B-cells from 31 patients with WM and six healthy donors. Real time reverse transcription polymerase chain reaction (RT-PCR) determined that approximately 80% of the patients had high XBP1 spliced mRNA expression, 80% of whom had high mRNA ERN1 alpha expression. XBP1, PRDM1 and PAX5 mRNA was present in all patients studied. Using relative quantitative RT-PCR we isolated two groups with low and high expression of XBP1, XBP1 spliced and ERN1 alpha. Sequence analysis showed germline polymorphisms in all genes studied. These data depict for the first time a heterogeneous expression pattern of the genes involved in late differentiation process of plasma cells in patients with WM and propose a role of XBP1-ERN1 alpha in WM pathogenesis. C1 [Leleu, Xavier; Hunter, Zachary R.; Xu, Lian; Moreau, Anne-Sophie; Santos, Daniel D.; Hatjiharissi, Evdoxia; Bakthavachalam, Vinod; Adamia, Sophia; Ho, Allen W.; Soumerai, Jacob; Patterson, Christopher J.; Manning, Robert J.; Carrasco, Ruben; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Leleu, Xavier; Hunter, Zachary R.; Xu, Lian; Moreau, Anne-Sophie; Santos, Daniel D.; Hatjiharissi, Evdoxia; Bakthavachalam, Vinod; Adamia, Sophia; Ho, Allen W.; Soumerai, Jacob; Patterson, Christopher J.; Manning, Robert J.; Carrasco, Ruben; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Immunol Lab, Lille, France. [Roccaro, Aldo M.; Ghobrial, Irene M.] Kirsch Lab Waldenstroms Macroglobulinemia, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Ho, Allen/B-3017-2011; Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Roccaro, Aldo/0000-0002-1872-5128 NR 20 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2009 VL 145 IS 1 BP 59 EP 63 DI 10.1111/j.1365-2141.2009.07592.x PG 5 WC Hematology SC Hematology GA 417OH UT WOS:000264085100007 PM 19220283 ER PT J AU Kuhn, LT Grynpas, MD Rey, CC Wu, YT Ackerman, JL Glimcher, MJ AF Kuhn, Liisa T. Grynpas, Marc D. Rey, Christian C. Wu, Yaotang Ackerman, Jerome L. Glimcher, Melvin J. TI A Comparison of the Physical and Chemical Differences Between Cancellous and Cortical Bovine Bone Mineral at Two Ages (vol 83, pg 146, 2008) SO CALCIFIED TISSUE INTERNATIONAL LA English DT Correction C1 [Kuhn, Liisa T.] Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Farmington, CT 06107 USA. [Kuhn, Liisa T.; Wu, Yaotang; Ackerman, Jerome L.; Glimcher, Melvin J.] Harvard Univ, Childrens Hosp, Sch Med, Lab Study Skeletal Disorders & Rehabil,Dept Ortho, Boston, MA 02115 USA. [Grynpas, Marc D.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Rey, Christian C.] CNRS, Lab Phys Chim Solides, Toulouse, France. [Wu, Yaotang; Ackerman, Jerome L.] Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, Martinos Ctr, Charlestown, MA USA. RP Kuhn, LT (reprint author), Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, MC1615, Farmington, CT 06107 USA. EM lkuhn@uchc.edu RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 NR 1 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 2009 VL 84 IS 4 BP 335 EP 335 DI 10.1007/s00223-009-9234-x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 427WL UT WOS:000264809700011 ER PT J AU Yared, K Baggish, AL Wood, MJ AF Yared, Kibar Baggish, Aaron L. Wood, Malissa J. TI High-output heart failure resulting from a remote traumatic arteriovenous fistula SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 [Yared, Kibar; Baggish, Aaron L.; Wood, Malissa J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. RP Yared, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St, Boston, MA USA. EM kyared@partners.org NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD APR PY 2009 VL 25 IS 4 BP E143 EP E144 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 430YL UT WOS:000265028400024 PM 19340363 ER PT J AU Gray, SW Armstrong, K DeMichele, A Schwartz, JS Hornik, RC AF Gray, Stacy W. Armstrong, Katrina DeMichele, Angela Schwartz, J. Sanford Hornik, Robert C. TI Colon Cancer Patient Information Seeking and the Adoption of Targeted Therapy for On-Label and Off-Label Indications SO CANCER LA English DT Article DE cancer survivor; communication; information seeking; diffusion and adoption; targeted therapy; off-label drug use ID METASTATIC COLORECTAL-CANCER; NATIONAL TRENDS SURVEY; HEALTH INFORMATION; PHYSICIAN RELATIONSHIP; TECHNOLOGY DIFFUSION; DECISION-MAKING; PLUS IRINOTECAN; DRUG-USE; ONCOLOGY; INTERNET AB BACKGROUND: Despite the rise in publicly available cancer information, little is known about the association between patient information seeking and the adoption of cancer technologies. The authors of this report investigated the relation between patient information seeking and awareness about and receipt of novel targeted therapy (TT) for colon cancer among patients for whom therapy is approved by the US Food and Drug Administration (FDA) and among patients for whom therapy is not FDA approved. METHODS: A retrospective, population-based survey of 633 colon cancer patients were identified through the Pennsylvania Cancer Registry. Outcome measures were self-reported awareness about and receipt of TT (bevacizumab and cetuximab). RESULTS: After adjusting for sociodemographic characteristics, high levels of treatment information seeking were associated strongly with hearing about TT (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.49-5.38) and receiving TT (OR, 3.22; 95% Cl, 1.36-7.62). These associations were present for patients with metastatic disease, for whom the use of TT is FDA approved, and for patients with localized disease, for whom the use of TT is not FDA approved (P for interactions = .29). Internet use (OR, 2.88; 95% CI, 1.40-5,94) and newspaper/magazine use (OR, 3.44; 95% CI, 1.34-8.84) were associated with hearing about TT. Seeking information from nontreating physicians was associated with hearing about TT (OR, 1.95; 95% CI, 1.03-3.68) and receiving TT (OR, 2.64; 95% Cl, 1.16-5.97). CONCLUSIONS: Patient information seeking was related to the adoption of TT for colon cancer in both appropriate and inappropriate clinical settings. These findings emphasize the importance of exploring patient influence on physician prescribing patterns and understanding the impact of information seeking on cancer outcomes. Cancer 2009;115:1424-34. (C) 2009 American Cancer Society. C1 [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Armstrong, Katrina; DeMichele, Angela; Schwartz, J. Sanford] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Armstrong, Katrina; DeMichele, Angela; Schwartz, J. Sanford] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Armstrong, Katrina; DeMichele, Angela; Schwartz, J. Sanford; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St,SM 224, Boston, MA 02115 USA. OI Hornik, Robert/0000-0002-2148-8805 FU National Cancer Institute [5P50CA095856-05] FX Supported by Grant 5P50CA095856-05 from the National Cancer Institute. NR 56 TC 12 Z9 12 U1 4 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2009 VL 115 IS 7 BP 1424 EP 1434 DI 10.1002/cncr.24186 PG 11 WC Oncology SC Oncology GA 422ME UT WOS:000264431600008 PM 19235785 ER PT J AU Stone, RM Donohue, KA Stock, W Hars, V Linker, CA Shea, T DeAngelo, DJ Marcucci, G Bloomfield, CD Larson, RA AF Stone, Richard M. Donohue, Kathleen A. Stock, Wendy Hars, Vera Linker, Charles A. Shea, Thomas DeAngelo, Daniel J. Marcucci, Guido Bloomfield, Clara D. Larson, Richard A. CA Canc Leukemia Grp B TI A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804 SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Chronic myeloid leukemia; Cytarabine; Homoharringtonine ID CHRONIC MYELOGENOUS LEUKEMIA; LOW-DOSE CYTARABINE; BCR-ABL; CYTOGENETIC IMPROVEMENT; HEMATOLOGIC REMISSION; INTERFERON-ALPHA; FOLLOW-UP; IMATINIB; THERAPY; RESISTANCE AB Both homoharringtonine (HHT), an alkaloid derivative from the Chinese yew tree that inhibits protein synthesis, and low-dose cytarabine have independent activity in CML and have been used in combination after failure of interferon therapy. The CALGB performed a phase II trial of HHT (2.5 mg/m(2) per day) plus cytarabine (7.5 mg/m(2) per day), given together via continuous intravenous infusion for 7 days in previously untreated patients with Ph chromosome positive chronic phase CML. HHT/cytarabine cycles were repeated every 28 days if the blood counts were adequate. The primary endpoint was the major cytogenetic response rate after 9 months. Forty of the 44 enrolled patients required reduction in the infusion duration during at least one cycle. Myelosuppression was common; 66% developed neutrophil count < 500/mu l, but grade 3 infections occurred in only 7%. Thirty-six of 44 patients (82%) achieved a complete hematologic remission; the median duration has not been reached. Only 4 of the 23 patients (17%) having adequate cytogenetic response assessment achieved a major response within nine cycles. Although HHT/cytarabine was generally well tolerated, the cytogenetic response rate did not exceed the level previously seen in patients with interferon-refractory CML and was not nearly as high as associated with imatinib in newly diagnosed patients. C1 [Stone, Richard M.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Donohue, Kathleen A.; Hars, Vera] Duke Univ, Ctr Stat, CALGB, Durham, NC USA. [Stock, Wendy; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Linker, Charles A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shea, Thomas] Univ N Carolina, Chapel Hill, NC USA. [Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Columbus, OH 43210 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Room M1B-17,44 Binney St, Boston, MA 02115 USA. EM rstone@partners.org OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute [CA 33601, CA31946] FX This research was supported in part by grant CA 33601 from the National Cancer Institute. The research for CALGB 19804 was supported, in part, by 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 ( Steven George, PhD, CA33601). NR 21 TC 22 Z9 23 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2009 VL 63 IS 5 BP 859 EP 864 DI 10.1007/s00280-008-0805-8 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 413IU UT WOS:000263787600012 PM 18670778 ER PT J AU Kurian, AW Gong, GD John, EM Miron, A Felberg, A Phipps, AI West, DW Whittemore, AS AF Kurian, Allison W. Gong, Gail D. John, Esther M. Miron, Alexander Felberg, Anna Phipps, Amanda I. West, Dee W. Whittemore, Alice S. TI Performance of Prediction Models for BRCA Mutation Carriage in Three Racial/Ethnic Groups: Findings from the Northern California Breast Cancer Family Registry SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; OVARIAN-CANCER; GENETIC SUSCEPTIBILITY; GERMLINE MUTATIONS; RISK-ASSESSMENT; SCORING SYSTEM; BOADICEA MODEL; PREVALENCE; VALIDATION; EPIDEMIOLOGY AB Purpose: Patients with early-onset breast and/or ovarian cancer frequently wish to know if they inherited a mutation in one of the cancer susceptibility genes, BRCA1 or BRCA2. Accurate carrier prediction models are needed to target costly testing. Two widely used models, BRCAPRO and BOADICEA, were developed using data from non-Hispanic Whites (NHW), but their accuracies have not been evaluated in other racial/ethnic populations. Methods: We evaluated the BRCAPRO and BOADICEA models in a population-based series of African American, Hispanic, and NHW breast cancer patients tested for BRCA1 and BRCA2 mutations. We assessed model calibration by evaluating observed versus predicted mutations and attribute diagrams, and model discrimination using areas under the receiver operating characteristic curves. Results: Both models were well-calibrated within each racial/ethnic group, with some exceptions. BOADICEA overpredicted mutations in African Americans and older NHWs, and BRCAPRO underpredicted in Hispanics. In all racial/ethnic groups, the models overpredicted in cases whose personal and family histories indicated >80% probability of carriage. The two models showed similar discrimination in each racial/ethnic group, discriminating least well in Hispanics. For example, BRCAPRO's areas under the receiver operating characteristic curves were 83% (95% confidence interval, 63-93%) for NHWs, compared with 74% (59-85%) for African Americans and 58% (45-70%) for Hispanics. Conclusions: The poor performance of the model for Hispanics may be due to model misspecification in this racial/ethnic group. However, it may also reflect racial/ ethnic differences in the distributions of personal and family histories among breast cancer cases in the Northern California population. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1084-91) C1 [Kurian, Allison W.; Gong, Gail D.; John, Esther M.; Felberg, Anna; West, Dee W.; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Kurian, Allison W.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.; Phipps, Amanda I.; West, Dee W.] No Calif Canc Ctr, Fremont, CA USA. RP Whittemore, AS (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, HRP Redwood Bldg,Room T204,259 Campus Dr, Stanford, CA 94305 USA. EM alicesw@stanford.edu RI Vinnicombe, Sarah/C-2606-2012 FU National Cancer Institute, NIH [CA-95-003]; Northern California Cancer Center [U01 CA69417]; NIH [CA69417, CA94069] FX National Cancer Institute, NIH, under RFA no. CA-95-003 through a cooperative agreement with the Northern California Cancer Center (U01 CA69417), as well as NIH grants CA69417 and CA94069. NR 43 TC 25 Z9 25 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2009 VL 18 IS 4 BP 1084 EP 1091 DI 10.1158/1055-9965.EPI-08-1090 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 432HV UT WOS:000265125000009 PM 19336551 ER PT J AU Slatore, CG Au, DH Littman, AJ Satia, JA White, E AF Slatore, Christopher G. Au, David H. Littman, Alyson J. Satia, Jessie A. White, Emily TI Associaton of Nonsteroidal Anti-Inflammatory Drugs with Lung Cancer: Results from a Large Cohort Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYCLOOXYGENASE-2 EXPRESSION; RISK; CHEMOPREVENTION; DECREASES; AROMATASE; ASPIRIN; SMOKERS; KI-67; GENE AB Background: Lung cancer is the most common cause of cancer-related mortality. Smoking cessation is crucial to decrease risk, but additional prevention modalities are needed. The use of nonsteroidal anti-inflammatory drugs (NSAID) may be promising. Methods: The study was a prospective cohort of 77,125 men and women, ages 50 to 76 years, from Washington state recruited in 2000 to 2002 (the VITamin And Lifestyle study). Lung cancer cases were identified through the Seattle-Puget Sound Surveillance, Epidemiology and End Results cancer registry during 5 years of follow-up. Hazard ratios (HR) associated with 10-year average use of total NSAIDs (excluding low-dose aspirin) and specific categories of NSAIDs were calculated for total incident lung cancer and specific morphologies. Results: A total of 665 lung cancer cases were identified. After adjusting for smoking, age, gender, and acetaminophen use, there was a borderline-significant inverse trend with total NSAID use [>4.2 d/wk for >10 years versus none: HR, 0.82; 95% confidence interval (95% CI), 0.64-1.04; P for trend = 0.051. The association was strongest for adenocarcinoma (HR, 0.59; 95% CI, 0.37-0.94; P for trend = 0.01) and seemed to be limited to men (HR, 0.66; 95% CI, 0.47-0.92; P for trend = 0.01) and to long-term (>= 10 years) former smokers (HR, 0.65; 95% CI, 0.44-0.96; P for trend = 0.04). There were no appreciable differences by NSAID type. Conclusions: Total NSAID use was associated with a small reduced risk of lung cancer, which was strongest for adenocarcinoma, men, and long-term former smokers. These findings are supported by known lung carcinogenesis mechanisms and suggest that NSAIDS may be useful for chemoprevention. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1203-7) C1 [Slatore, Christopher G.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Littman, Alyson J.; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Slatore, Christopher G.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Littman, Alyson J.] VA Puget Sound Hlth Care Syst, Epidemiol Res Informat Ctr, Seattle, WA USA. [White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Slatore, CG (reprint author), Univ Washington, Div Pulm & Crit Care Med, 1959 NE Pacific St, Seattle, WA 98195 USA. EM cslatore@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 FU NIH [CA130328, CA74846, CA96556, CA119633] FX NIH grants CA130328 (C.G. Slatore), CA74846 (E. White), and CA96556 and CA119633 (J.A. Satia). NR 21 TC 36 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2009 VL 18 IS 4 BP 1203 EP 1207 DI 10.1158/1055-9965.EPI-08-1110 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 432HV UT WOS:000265125000024 PM 19293309 ER PT J AU Banez, LL Terris, MK Aronson, WJ Presti, JC Kane, CJ Amling, CL Freedland, SJ AF Banez, Lionel L. Terris, Martha K. Aronson, William J. Presti, Joseph C., Jr. Kane, Christopher J. Amling, Christopher L. Freedland, Stephen J. TI Race and Time from Diagnosis to Radical Prostatectomy: Does Equal Access Mean Equal Timely Access to the Operating Room?-Results from the SEARCH Database SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYP3A4 GENETIC VARIANT; AFRICAN-AMERICAN MEN; RACIAL-DIFFERENCES; UNITED-STATES; HEALTH-CARE; CANCER; IMPACT; DELAY; RISK; EPIDEMIOLOGY AB Background: African American men with prostate cancer are at higher risk for cancer-specific death than Caucasian men. We determine whether significant delays in management contribute to this disparity. We hypothesize that in an equal-access health care system, time interval from diagnosis to treatment would not differ by race. Methods: We identified 1,532 African American and Caucasian men who underwent radical prostatectomy (RP) from 1.988 to 2007 at one of four Veterans Affairs Medical Centers that comprise the Shared Equal-Access Regional Cancer Hospital (SEARCH) database with known biopsy date. We compared time from biopsy to RP between racial groups using linear regression adjusting for demographic and clinical variables. We analyzed risk of potential clinically relevant delays by determining odds of delays >90 and >180 days. Results: Median time interval from diagnosis to RP was 76 and 68 days for African Americans and Caucasian men, respectively (P = 0.004). After controlling for demographic and clinical variables, race was not associated with the time interval between diagnosis and RP (P = 0.09). Furthermore, race was not associated with increased risk of delays >90 (P = 0.45) or >180 days (P = 0.31). Conclusions: In a cohort of men undergoing RP in an equal-access setting, there was no significant difference between racial groups with regard to time interval from diagnosis to RP. Thus, equal-access includes equal timely access to the operating room. Given our previous finding of poorer outcomes among African Americans, treatment delays do not seem to explain these observations. Our findings need to be confirmed in patients electing other treatment modalities and in other practice settings. (Cancer Epiderniol Biomarkers Prev 2009;18(4):1208-12) C1 [Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC 27710 USA. [Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Surg, Duke Prostate Ctr, Durham, NC 27710 USA. [Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Med Ctr, Urol Sect, Vet Affairs Med Ctr, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, 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. [Kane, Christopher J.] Vet Affairs Med Ctr, Urol Sect, San Diego, CA 92161 USA. [Kane, Christopher J.] Univ Calif San Diego, Dept Urol, San Diego, CA 92103 USA. [Amling, Christopher L.] Univ Alabama, Dept Urol, Birmingham, AL USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu FU Department of Veterans Affairs, the Duke University Department of Surgery; Division of Urology, Department of Defense Prostate Cancer Research Program, the American Urological Association Foundation/Astellas Rising Star in Urology Award; NIH Specialized Programs of Research Excellence [P50 CA58236]; the Georgia Cancer Coalition, NIH [R01CA100938, P50 CA92131-01A1] FX Department of Veterans Affairs, the Duke University Department of Surgery and Division of Urology, Department of Defense Prostate Cancer Research Program, the American Urological Association Foundation/Astellas Rising Star in Urology Award, NIH Specialized Programs of Research Excellence Grant P50 CA58236, the Georgia Cancer Coalition, NIH R01CA100938, and NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1. NR 25 TC 13 Z9 13 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2009 VL 18 IS 4 BP 1208 EP 1212 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 432HV UT WOS:000265125000025 PM 19336564 ER PT J AU Gray, SW O'Grady, C Karp, L Smith, D Schwartz, JS Hornik, RC Armstrong, K AF Gray, Stacy W. O'Grady, Cristin Karp, Lauren Smith, Daniel Schwartz, J. Sanford Hornik, Robert C. Armstrong, Katrina TI Risk Information Exposure and Direct-to-Consumer Genetic Testing for BRCA Mutations among Women with a Personal or Family History of Breast or Ovarian Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PATIENT-PHYSICIAN RELATIONSHIP; SELF-RATED HEALTH; OF-THE-LITERATURE; PRIMARY-CARE; DECISION-MAKING; UNITED-STATES; PROPHYLACTIC OOPHORECTOMY; HEREDITARY BREAST; US PHYSICIANS; SUSCEPTIBILITY AB Background: Direct-to-consumer (DTC) BRCA testing may expand access to genetic testing and enhance cancer prevention efforts. It is not known, however, if current DTC websites provide adequate risk information for informed medical decision making. Methods: A total of 284 women with a personal or family history of breast/ovarian cancer were randomly assigned to view a "mock" DTC commercial website [control condition (CC); n = 93] or the same "mock" website that included information on the potential risks of obtaining genetic testing online. Risk information was framed two ways: risk information attributed to expert sources (ES; n = 98) and unattributed risk information (URI; it = 93). Participants completed an online survey. End points were intentions to get BRCA testing, testing site preference, and beliefs about DTC BRCA testing. Results: The sample was 82% white, had a mean age of 39 years (range, 18-70 years) and had a mean education of 3 years of college. Women exposed to risk information had lower intentions to get BRCA testing than women in the CC [adjusted odds ratio (OR), 0.48; 95% confidence interval (95% CI) 0.26-0.87; P = 0.016], and less positive beliefs about online BRCA testing (adjusted OR, 0.48; 95% CI, 0.27-0.86; P = 0.014). Women in the ES condition were more likely to prefer clinic-based testing than were women in the CC (adjusted OR, 2.05; 95% CI, 1.07-3.90; P = 0.030). Conclusion: Exposing women to information on the potential risks of online BRCA testing altered their intentions, beliefs, and preferences for BRCA testing. Policy makers may want to consider the content and framing of risk information on DTC websites as they formulate regulation for this rapidly growing industry. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1303-11) C1 [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [O'Grady, Cristin] Tufts Univ, Boston, MA 02111 USA. [Karp, Lauren; Smith, Daniel; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA USA. [Schwartz, J. Sanford; Armstrong, Katrina] Univ Penn, Gen Internal Med Sect, Philadelphia, PA USA. [Schwartz, J. Sanford] Univ Penn, Wharton Sch, Philadelphia, PA USA. [Armstrong, Katrina] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St,SM 224, Boston, MA 02115 USA. EM stacyw_gray@dfci.harvard.edu OI Hornik, Robert/0000-0002-2148-8805 FU NCI [5P50CA095856-05]; Robert Wood Johnson Foundation; American Society for Clinical Oncology FX NCI 5P50CA095856-05., Robert Wood Johnson Foundation and the American Society for Clinical Oncology. NR 67 TC 18 Z9 18 U1 3 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2009 VL 18 IS 4 BP 1303 EP 1311 DI 10.1158/1055-9965.EPI-08-0825 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 432HV UT WOS:000265125000039 PM 19318436 ER PT J AU Kulu, Y Dorfman, JD Kuruppu, D Fuchs, BC Goodwin, JM Fujii, T Kuroda, T Lanuti, M Tanabe, KK AF Kulu, Y. Dorfman, J. D. Kuruppu, D. Fuchs, B. C. Goodwin, J. M. Fujii, T. Kuroda, T. Lanuti, M. Tanabe, K. K. TI Comparison of intravenous versus intraperitoneal administration of oncolytic herpes simplex virus 1 for peritoneal carcinomatosis in mice SO CANCER GENE THERAPY LA English DT Article DE Herpes simplex virus; viral oncolysis; peritoneal metastases; biodistribution; hrR3 ID DIFFUSE LIVER METASTASES; RIBONUCLEOTIDE REDUCTASE; COLORECTAL-CANCER; COLON-CARCINOMA; RANDOMIZED-TRIAL; DELETION MUTANT; GASTRIC-CANCER; OVARIAN-CANCER; TUMOR-CELLS; THERAPY AB hrR3 is an oncolytic herpes simplex virus 1 (HSV-1) mutant that replicates preferentially in tumors compared with normal tissues. Portal venous administration of hrR3 in mice bearing diffuse colorectal carcinoma liver metastases significantly reduces tumor burden and prolongs animal survival. In this study, we compared survival benefit and biodistribution of hrR3 following intravenous (i.v.) administration versus intraperitoneal (i.p.) administration in immunocompetent mice bearing colon carcinoma peritoneal metastases. Mice bearing peritoneal metastases received 1 x 10(8) plaque-forming units hrR3 or mock-infected media every other day for three doses and were randomized to have the viruses administered by either an i.p. or i.v. route. Biodistribution was assessed by PCR amplification of HSV-1-specific sequences from tumor and normal tissues including the small bowel, liver, spleen, kidney, lung, heart and brain. LD(50) for i.p. administration was compared with the LD(50) for i.v. administration. In subsequent experiments, animals were monitored for survival. The frequency of HSV-1 detection in peritoneal tumors was similar in mice randomized to either i.p. or i.v. administration. However, i.p. administration resulted in a more restricted systemic biodistribution, with a reduced frequency of virus detected in the kidney, lung and heart. The LD(50) associated with i.p. administration was higher than that with i.v. administration. Tumor burden was more effectively reduced with i.p. compared with i.v. administration. Median survival following i.p. administration was approximately twice that observed with i.v. administration. I. p. administration of an HSV-1 oncolytic mutant is associated with a more restricted biodistribution, less toxicity and greater efficacy against peritoneal metastases compared with i.v. administration. C1 [Tanabe, K. K.] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. EM KTanabe@partners.org RI Fujii, Tsutomu/M-4838-2014; OI Kuroda, Toshihiko/0000-0001-6660-8930 FU Massachusetts General Hospital Tucker Gosnell Gastrointestinal Cancer Center; Fund for Medical Discovery Fellowship; Deutsche Forschungsgemeinschaft; [2R01CA76183]; [5T32CA009535] FX This study was supported by the grants 2R01CA76183 (KKT); 5T32CA009535 (JDD); Massachusetts General Hospital Tucker Gosnell Gastrointestinal Cancer Center (KKT, BCF) and Fund for Medical Discovery Fellowship (BCF); and Deutsche Forschungsgemeinschaft (YK). NR 36 TC 13 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2009 VL 16 IS 4 BP 291 EP 297 DI 10.1038/cgt.2008.83 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 420IW UT WOS:000264283900001 PM 18989355 ER PT J AU Mauceri, HJ Beckett, MA Liang, H Sutton, HG Pitroda, S Galka, E Efimova, E Darga, T Khodarev, NN King, CR Posner, MC Hellman, S Kufe, DW Weichselbaum, RR AF Mauceri, H. J. Beckett, M. A. Liang, H. Sutton, H. G. Pitroda, S. Galka, E. Efimova, E. Darga, T. Khodarev, N. N. King, C. R. Posner, M. C. Hellman, S. Kufe, D. W. Weichselbaum, R. R. TI Translational strategies exploiting TNF-alpha that sensitize tumors to radiation therapy SO CANCER GENE THERAPY LA English DT Article DE TNF-alpha signaling; tumor stroma; TNF/radiation interaction ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; PHASE-I; DEPENDENT APOPTOSIS; CANCER; CELL; GROWTH; TRIAL; BEVACIZUMAB; ANTITUMOR AB TNFerade is a radioinducible adenoviral vector expressing tumor necrosis factor-alpha (TNF-alpha) (Ad.Egr-TNF) currently in a phase III trial for inoperable pancreatic cancer. We studied B16-F1 melanoma tumors in TNF receptor wild-type (C57BL/6) and deficient (TNFR1,2-/- and TNFR1-/-) mice. Ad.Egr-TNF+IR inhibited tumor growth compared with IR in C57BL/6 but not in receptor-deficient mice. Tumors resistant to TNF-alpha were also sensitive to Ad.Egr-TNF+IR in C57BL/6 mice. Ad.Egr-TNF+IR produced an increase in tumor-associated endothelial cell apoptosis not observed in receptor-deficient animals. Also, B16-F1 tumors in mice with germline deletions of TNFR1,2, TNFR1 or TNF-alpha, or in mice receiving anti-TNF-alpha exhibited radiosensitivity. These results show that tumor-associated endothelium is the principal target for Ad.Egr-TNF radiosensitization and implicate TNF-alpha signaling in tumor radiosensitivity. C1 [Weichselbaum, R. R.] Univ Chicago, Dept Radiat & Cellular Oncol, Duchossois Ctr Adv Med, Chicago, IL 60637 USA. [Galka, E.; Posner, M. C.] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [King, C. R.] GenVec Inc, Gaithersburg, MD USA. [Kufe, D. W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kufe, D. W.] Harvard Univ, Sch Med, Boston, MA USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Duchossois Ctr Adv Med, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM rrw@radonc.uchicago.edu OI Darga, Thomas/0000-0002-8968-6701 FU NCI NIH HHS [CA111423] NR 48 TC 19 Z9 21 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2009 VL 16 IS 4 BP 373 EP 381 DI 10.1038/cgt.2008.86 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 420IW UT WOS:000264283900009 PM 18974777 ER PT J AU Bertagnolli, MM Eagle, CJ Zauber, AG Redston, M Breazna, A Kim, K Tang, J Rosenstein, RB Umar, A Bagheri, D Collins, NT Burn, J Chung, DC Dewar, T Foley, TR Hoffman, N Macrae, F Pruitt, RE Saltzman, JR Salzberg, B Sylwestrowicz, T Hawk, ET AF Bertagnolli, Monica M. Eagle, Craig J. Zauber, Ann G. Redston, Mark Breazna, Aurora Kim, KyungMann Tang, Jie Rosenstein, Rebecca B. Umar, Asad Bagheri, Donya Collins, Neal T. Burn, John Chung, Daniel C. Dewar, Thomas Foley, T. Raymond Hoffman, Neville Macrae, Finlay Pruitt, Ronald E. Saltzman, John R. Salzberg, Bruce Sylwestrowicz, Thomas Hawk, Ernest T. CA Adenoma Prevention Celecoxib Study TI Five-Year Efficacy and Safety Analysis of the Adenoma Prevention with Celecoxib Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL ADENOMAS; GASTROINTESTINAL TOXICITY; RANDOMIZED-TRIAL; ROFECOXIB; NAPROXEN; ASPIRIN; CANCER; RISK; CHEMOPREVENTION; COMPLICATIONS AB The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease. C1 [Bertagnolli, Monica M.; Redston, Mark; Saltzman, John R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Eagle, Craig J.; Breazna, Aurora; Tang, Jie; Rosenstein, Rebecca B.; Collins, Neal T.] Pfizer Inc, New York, NY USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kim, KyungMann] Univ Wisconsin, Madison, WI USA. [Bagheri, Donya] CCS Associates Inc, Mountain View, CA USA. [Burn, John] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Dewar, Thomas] Harris Methodist Hosp, Ft Worth, TX USA. [Foley, T. Raymond] Reg Gastroenterol Associates Lancaster, Lancaster, PA USA. [Hoffman, Neville] Sir Charles Gairdner Hosp, Perth, WA, Australia. [Macrae, Finlay] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Pruitt, Ronald E.] Nashville Med Res Inst, Nashville, TN USA. [Salzberg, Bruce] Atlanta Gastroenterol Associates, Atlanta, GA USA. [Sylwestrowicz, Thomas] Univ Saskatchewan, St Pauls Hosp, Saskatoon, SK, Canada. [Umar, Asad] NCI, Bethesda, MD 20892 USA. [Hawk, Ernest T.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org RI Leggett, Barbara/D-3579-2011; OI Burn, John/0000-0002-9823-2322 FU National Cancer Institute and Pfizer [N01-CN-95015] FX National Cancer Institute (N01-CN-95015) and Pfizer. NR 23 TC 107 Z9 108 U1 0 U2 1 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 APR PY 2009 VL 2 IS 4 BP 310 EP 321 DI 10.1158/1940-6207.CAPR-08-0206 PG 12 WC Oncology SC Oncology GA 429CI UT WOS:000264898000007 PM 19336730 ER PT J AU Gandhi, L McNamara, KL Li, DA Borgman, CL McDermott, U Brandstetter, KA Padera, RF Chirieac, LR Settleman, JE Wong, KK AF Gandhi, Leena McNamara, Kate L. Li, Danan Borgman, Christa L. McDermott, Ultan Brandstetter, Kathleyn A. Padera, Robert F. Chirieac, Lucian R. Settleman, Jeffrey E. Wong, Kwok-Kin TI Sunitinib Prolongs Survival in Genetically Engineered Mouse Models of Multistep Lung Carcinogenesis SO CANCER PREVENTION RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; VINORELBINE PLUS CISPLATIN; IN-VIVO; COLLABORATIVE GROUP; FACTOR RECEPTOR; PHASE-II; STAGE-I; K-RAS; CANCER AB Non-small cell lung cancer (NSCLC) has a poor prognosis, with substantial mortality rates even among patients diagnosed with early-stage disease. There are few effective measures to block the development or progression of NSCLC. Antiangiogenic drugs represent a new class of agents targeting multiple aspects of tumor progression, including cell proliferation, invasion, migration, and outgrowth of metastatic deposits. We tested the multitargeted angiogenesis inhibitor sunitinib in a novel endogenous mouse model of NSCLC, which expresses a conditional activating mutation in Kras with or without conditional deletion of Lkb1; both alterations are frequent in human NSCLC. We showed that daily treatment with sunitinib reduced tumor size, caused tumor necrosis, blocked tumor progression, and prolonged median survival in both the metastatic (Lkb1/Kras) and nonmetastatic (Kras) mouse models; median survival was not reached in the nonmetastatic model after 1 year. However, the incidence of local and distant metastases was similar in sunitinib-treated and untreated Lkb1/Kras mice, suggesting that prolonged survival with sunitinib in these mice was due to direct effects on primary tumor growth rather than to inhibition of metastatic progression. These collective results suggest that the use of angiogenesis inhibitors in early-stage disease for prevention of tumor development and growth may have major survival benefits in the setting of NSCLC. C1 [Gandhi, Leena; McNamara, Kate L.; Li, Danan; Borgman, Christa L.; Brandstetter, Kathleyn A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gandhi, Leena; Wong, Kwok-Kin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Padera, Robert F.; Chirieac, Lucian R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [McNamara, Kate L.; Li, Danan; Brandstetter, Kathleyn A.; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [McDermott, Ultan; Settleman, Jeffrey E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana Bldg 810B, Boston, MA 02115 USA. EM kwong1@partners.org OI Gandhi, Leena/0000-0002-2398-9179; McDermott, Ultan/0000-0001-9032-4700; wong, kwok kin/0000-0001-6323-235X FU NIH [R01 CA122794, R01 AG2400401]; Dana-Farber/ Harvard Cancer Center Lung Cancer Specialized Program of Research Excellence [P50 CA090578]; Joan Scarangello Foundation; Cecily and Robert Harris Foundation; Flight Attendant Medical Research Institute; Steve and Alice Cutler fund FX K-K. Wong was supported by NIH grants R01 CA122794 and R01 AG2400401, Dana-Farber/ Harvard Cancer Center Lung Cancer Specialized Program of Research Excellence grant P50 CA090578, Joan Scarangello Foundation to Conquer Lung Cancer, Cecily and Robert Harris Foundation, and Flight Attendant Medical Research Institute. L. Gandhi is supported in part by the Steve and Alice Cutler fund for Young Investigators. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/). NR 38 TC 25 Z9 25 U1 0 U2 2 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 APR PY 2009 VL 2 IS 4 BP 330 EP 337 DI 10.1158/1940-6207.CAPR-08-0213 PG 8 WC Oncology SC Oncology GA 429CI UT WOS:000264898000009 PM 19336729 ER PT J AU Lahdenranta, J Hagendoorn, J Padera, TP Hoshida, T Nelson, G Kashiwagi, S Jain, RK Fukumura, D AF Lahdenranta, Johanna Hagendoorn, Jeroen Padera, Timothy P. Hoshida, Tohru Nelson, Gregory Kashiwagi, Satoshi Jain, Rakesh K. Fukumura, Dai TI Endothelial Nitric Oxide Synthase Mediates Lymphangiogenesis and Lymphatic Metastasis SO CANCER RESEARCH LA English DT Article ID GROWTH FACTOR-C; VASCULAR-PERMEABILITY; TUMOR PROGRESSION; ACTIVATION; DISEASE; VEGFR-3; CELLS; FLOW; HYPERTENSION; INHIBITION AB Lymphatic metastasis is a critical determinant of cancer prognosis. Recently, several lymphangiogenic molecules such as vascular endothelial growth factor (VEGF)-C and VEGF-D were identified. However, the mechanistic understanding of lymphatic metastasis is still in infancy. Nitric oxide (NO) plays a crucial role in regulating blood vessel growth and function as well as lymphatic vessel function. NO synthase (NOS) expression correlates with lymphatic metastasis. However, causal relationship between NOS and lymphatic metastasis has not been documented. To this end, we first show that both VEGF receptor-2 and VEGF receptor-3 stimulation activate eNOS in lymphatic endothelial cells and that NO donors induce proliferation and/or survival of cultured lymphatic endothelial cells in a dose-dependent manner. We find that an NOS inhibitor, L-NMMA, blocked regeneration of lymphatic vessels. Using intravital microscopy that allows us to visualize the steps of lymphatic metastasis, we show that genetic deletion of eNOS as well as NOS blockade attenuates peritumor lymphatic hyperplasia of VEGF-C-overexpressing T241 fibrosarcomas and decreases the delivery of metastatic tumor cells to the draining lymph nodes. Genetic deletion of eNOS in the host also leads to a decrease in T241 tumor cell dissemination to the lymph nodes and macroscopic lymph node metastasis of B16F10 melanoma. These findings indicate that eNOS mediates VEGF-C-induced lymphangiogenesis and, consequently, plays a critical role in lymphatic metastasis. Our findings explain the correlation between NOS and lymphatic metastasis seen in a number of human tumors and open the door for potential therapies exploiting NO signaling to treat diseases of the lymphatic system. [Cancer Res 2009;69(7):2801-8] C1 [Fukumura, Dai] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; dai@steele.mgh.harvard.edu RI Nelson, Gregory/H-6315-2011; OI Nelson, Gregory/0000-0002-8382-910X; Padera, Timothy/0000-0002-3453-9384 FU National Cancer Institute [R01-CA85140, R01-CA126642, p01-CA80124, R01-CA96915]; Damon Runyon Cancer Research Foundation [DRG-1904-06] FX Grant support: National Cancer Institute grants R01-CA85140 and R01-CA126642 (R.K. Jain); p01-CA80124 (R.K. Jain and D. Fukumura); and R01-CA96915 (D. Fukumura). J Lahdenranta is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation (DRG-1904-06). NR 32 TC 51 Z9 55 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2009 VL 69 IS 7 BP 2801 EP 2808 DI 10.1158/0008-5472.CAN-08-4051 PG 8 WC Oncology SC Oncology GA 429GE UT WOS:000264908100017 PM 19318557 ER PT J AU Khodarev, NN Pitroda, SP Beckett, MA MacDermed, DM Huang, L Kufe, DW Weichselbaum, RR AF Khodarev, Nikolai N. Pitroda, Sean P. Beckett, Michael A. MacDermed, Dhara M. Huang, Lei Kufe, Donald W. Weichselbaum, Ralph R. TI MUC1-Induced Transcriptional Programs Associated with Tumorigenesis Predict Outcome in Breast and Lung Cancer SO CANCER RESEARCH LA English DT Article ID HUMAN MUC1 ONCOPROTEIN; IONIZING-RADIATION; ENDOTHELIAL-CELLS; GENE; ADENOCARCINOMA; ANTIGEN; DF3; SURVIVAL; STRESS; TUMORS AB The Mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis, and extracellular matrix remodeling. A set of experimentally derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature predicts significant decreases in both disease-free and overall survival in patients Kith breast (n = 295) and lung (n = 442) cancers. The data show that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients. [Cancer Res 2009;69(7):2833-7] C1 [Khodarev, Nikolai N.; Pitroda, Sean P.; Beckett, Michael A.; MacDermed, Dhara M.; Weichselbaum, Ralph R.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. [Huang, Lei; Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM rrw@radone.bsd.uchicago.edu FU Lung Cancer Foundation; NIH [R01 CA1114231, R01 CA97098] FX Grant support: Lung Cancer Foundation and the NIH grants R01 CA1114231 and R01 CA97098. NR 26 TC 56 Z9 59 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2009 VL 69 IS 7 BP 2833 EP 2837 DI 10.1158/0008-5472.CAN-08-4513 PG 5 WC Oncology SC Oncology GA 429GE UT WOS:000264908100021 PM 19318547 ER PT J AU Puustinen, P Junttila, MR Vanhatupa, S Sablina, AA Hector, ME Teittinen, K Raheem, O Ketola, K Lin, SJ Kast, J Haapasalo, H Hahn, WC Westermarck, J AF Puustinen, Pietri Junttila, Melissa R. Vanhatupa, Sari Sablina, Anna A. Hector, Melissa E. Teittinen, Kaisa Raheem, Olayinka Ketola, Kirsi Lin, Shujun Kast, Juergen Haapasalo, Hannu Hahn, William C. Westermarck, Jukka TI PME-1 Protects Extracellular Signal-Regulated Kinase Pathway Activity from Protein Phosphatase 2A-Mediated Inactivation in Human Malignant Glioma SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR PP2A; 2A; CANCER; ACTIVATION; METHYLESTERASE; TRANSFORMATION; PROLIFERATION; GLIOBLASTOMA; SUBUNITS; ERK/MAPK AB Extracellular signal-regulated kinase (ERR)/mitogen-activated protein kinase pathway activity is regulated by the antagonist function of activating kinases and inactivating protein phosphatases. Sustained ERK pathway activity is commonly observed in human malignancies; however, the mechanisms by which the pathway is protected from phosphatase-mediated inactivation in the tumor tissue remain obscure. Here, we show that methylesterase PME-1-mediated inhibition of the protein phosphatase 2A promotes basal ERK pathway activity and is required for efficient growth factor response. Mechanistically, PME-1 is shown to support ERK pathway signaling upstream of Raf, but downstream of growth factor receptors and protein kinase C. In malignant gliomas, PME-1 expression levels correlate with both ERR activity and cell proliferation in vivo. Moreover, PME-1 expression significantly correlates with disease progression in human astrocytic gliomas (n = 222). Together, these observations identify PME-1 expression as one mechanism by which ERK pathway activity is maintained in cancer cells and suggest an important functional role for PME-1 in the disease progression of human astrocytic gliomas. [Cancer Res 2009;69(7):2870-7] C1 [Vanhatupa, Sari; Teittinen, Kaisa; Ketola, Kirsi; Westermarck, Jukka] Univ Tampere, Inst Med Technol, Tampere 33200, Finland. [Puustinen, Pietri; Junttila, Melissa R.; Westermarck, Jukka] Univ Turku, Ctr Biotechnol, Turku, Finland. [Puustinen, Pietri; Junttila, Melissa R.; Westermarck, Jukka] Abo Akad Univ, Turku, Finland. [Raheem, Olayinka] Univ Tampere, Dept Pathol, Tampere 33200, Finland. [Vanhatupa, Sari; Teittinen, Kaisa; Ketola, Kirsi; Westermarck, Jukka] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland. [Raheem, Olayinka; Haapasalo, Hannu] Tampere Univ Hosp, Dept Pathol, Tampere, Finland. [Sablina, Anna A.; Hector, Melissa E.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lin, Shujun; Kast, Juergen] Univ British Columbia, Biomed Res Ctr, Vancouver, BC, Canada. RP Westermarck, J (reprint author), Univ Tampere, Inst Med Technol, Biokatu 6-8, Tampere 33200, Finland. EM jukwes@utu.fi RI Ketola, Kirsi/O-1071-2016; OI Hector-Greene, Melissa/0000-0001-7263-1440; Ketola, Kirsi/0000-0001-6484-9861 FU Academy of Finland [1121413]; Pirkanmaa Hospital District [9J151]; Emil Aaltonen Foundation; Helsinki University Central Hospital Research Funds; Sigrid Juselius Foundation; Finnish Cancer Society; Damon Runyon Cancer Research Foundation FX Academy of Finland (project 1121413), Competitive Research Funding of Pirkanmaa Hospital District (project 9J151), Emil Aaltonen Foundation, Helsinki University Central Hospital Research Funds, Sigrid Juselius Foundation, and Finnish Cancer Society. M.R. Juruttila is Enrique Cepero Fellow of the Damon Runyon Cancer Research Foundation. 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.; We thank Dr. Nina Nupponen for glioblastoma cell lines; Paula Kosonen, Merja Lehtinen, Taina Kalevo-Mattila, and Raisa Vuorinen for their excellent technical assistance; and Minna Niemela for participation on experiments. NR 32 TC 44 Z9 45 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2009 VL 69 IS 7 BP 2870 EP 2877 DI 10.1158/0008-5472.CAN-08-2760 PG 8 WC Oncology SC Oncology GA 429GE UT WOS:000264908100026 PM 19293187 ER PT J AU Rao, SS O'Neil, J Liberator, CD Hardwick, JS Dai, XD Zhang, T Tyminski, E Yuan, J Kohl, NE Richon, VM Van der Ploeg, LHT Carroll, PM Draetta, GF Look, AT Strack, PR Winter, CG AF Rao, Sudhir S. O'Neil, Jennifer Liberator, Cole D. Hardwick, James S. Dai, Xudong Zhang, Theresa Tyminski, Edyta Yuan, Jing Kohl, Nancy E. Richon, Victoria M. Van der Ploeg, Lex H. T. Carroll, Pamela M. Draetta, Giulio F. Look, A. Thomas Strack, Peter R. Winter, Christopher G. TI Inhibition of NOTCH Signaling by Gamma Secretase Inhibitor Engages the RB Pathway and Elicits Cell Cycle Exit in T-Cell Acute Lymphoblastic Leukemia Cells SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; C-MYC; CHROMOSOMAL TRANSLOCATIONS; HOMOZYGOUS DELETIONS; UBIQUITIN LIGASE; MTS1 P16(INK4A); S-PHASE; GENE; MUTATIONS; EXPRESSION AB NOTCH signaling is deregulated in the majority of T-cell acute lymphoblastic leukemias (T-ALL) as a result of activating mutations in NOTCH1. Gamma secretase inhibitors (GSI) block proteolytic activation of NOTCH receptors and may provide a targeted therapy for T-ALL. We have investigated the mechanisms of GSI sensitivity across a panel of T-ALL cell lines, yielding an approach for patient stratification based on pathway activity and also providing a rational combination strategy for enhanced response to GSI. Whereas the NOTCH1 mutation status does not serve as a predictor of GSI sensitivity, a gene expression signature of NOTCH pathway activity does correlate with response, and may be useful in the selection of patients more likely to respond to GSI. Furthermore, inhibition of the NOTCH pathway activity signature correlates with the induction of the cyclin-dependent kinase inhibitors CDKN2D (p19(INK4d)) and CDKN1B (p27(Kip1)), leading to derepression of RB and subsequent exit from the cell cycle. Consistent with this evidence of cell cycle exit, short-term exposure of GSI resulted in sustained molecular and phenotypic effects after withdrawal of the compound. Combination treatment with GSI and a small molecule inhibitor of CDK4 produced synergistic growth inhibition, providing evidence that GSI engagement of the CDK4/RB pathway is an important mechanism of GSI action and supports further investigation of this combination for improved efficacy in treating T-ALL. [Cancer Res 2009;69(7):3060-8] C1 [Rao, Sudhir S.; Liberator, Cole D.; Zhang, Theresa; Tyminski, Edyta; Yuan, Jing; Kohl, Nancy E.; Richon, Victoria M.; Van der Ploeg, Lex H. T.; Carroll, Pamela M.; Draetta, Giulio F.; Strack, Peter R.; Winter, Christopher G.] Merck Res Labs, Boston, MA 02115 USA. [Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [O'Neil, Jennifer; Look, A. Thomas] Childrens Hosp, Div Hematol, Boston, MA 02115 USA. [Hardwick, James S.] Merck Res Labs, West Point, PA USA. [Dai, Xudong] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA USA. RP Winter, CG (reprint author), Merck Res Labs, 33 Ave Louis Pasteur, Boston, MA 02115 USA. EM christopher_winter@merck.com FU Merck Research Laboratories (A.T. Look); Harvard Medical School Hematology Training FX Merck Research Laboratories (A.T. Look) and a Harvard Medical School Hematology Training Grant (J. O'Neil).; 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 IS U.S.C. Section 1734 solely to indicate this fact.; We acknowledge the Rosetta GELS group for microarray profiling and Jon Aster for MigR1 and MigR1 NICD vectors; we also thank Jennifer Tammam, Clay Efferson, Takaomi Sanda, Pradip Majumder, and Raphael Kopan for their guidance and support; and Lynn Winter for assistance with graphics. NR 38 TC 75 Z9 77 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2009 VL 69 IS 7 BP 3060 EP 3068 DI 10.1158/0008-5472.CAN-08-4295 PG 9 WC Oncology SC Oncology GA 429GE UT WOS:000264908100049 PM 19318552 ER PT J AU Nwachukwu, JC Mita, P Ruoff, R Ha, S Wang, Q Huang, SJ Taneja, SS Brown, M Gerald, WL Garabedian, MJ Logan, SK AF Nwachukwu, Jerome C. Mita, Paolo Ruoff, Rachel Ha, Susan Wang, Qianben Huang, S. Joseph Taneja, Samir S. Brown, Myles Gerald, William L. Garabedian, Michael J. Logan, Susan K. TI Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells SO CANCER RESEARCH LA English DT Article ID GENE ONTOLOGY; COACTIVATOR; PROTEIN; ART-27; TOOL; PROLIFERATION; COREPRESSORS; THERAPIES; APOPTOSIS; COMPLEX AB The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sites by chromatin immunoprecipitation analysis. In addition, the effect of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are up-regulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Consistent with this idea, stable reduction of ART-27 by short-hairpin RNA enhances LNCaP cell proliferation compared with control cells. The effect of ART-27 loss was also examined in response to the antiandrogen bicalutamide. Unexpectedly, cells treated with ART-27 siRNA no longer exhibited gene repression in response to bicalutamide. To examine ART-27 loss in prostate cancer progression, immunohistochemistry was conducted on a tissue array containing samples from primary tumors of individuals who were clinically followed and later shown to have either recurrent or nonrecurrent disease. Comparison of ART-27 and AR staining indicated that nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. Our studies show that reduction of ART-27 protein levels in prostate cancer may facilitate antiandrogen-resistant disease. [Cancer Res 2009;69(7):3140-7] C1 [Mita, Paolo; Ruoff, Rachel; Ha, Susan; Taneja, Samir S.; Garabedian, Michael J.; Logan, Susan K.] NYU, Sch Med, Dept Urol, New York, NY 10016 USA. [Nwachukwu, Jerome C.; Mita, Paolo; Ruoff, Rachel; Ha, Susan; Logan, Susan K.] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. [Nwachukwu, Jerome C.; Garabedian, Michael J.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. [Gerald, William L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Wang, Qianben; Brown, Myles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, S. Joseph] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. RP Logan, SK (reprint author), NYU, Sch Med, Dept Urol, 550 1St Ave,MSB424, New York, NY 10016 USA. EM susan.logan@nyumc.org RI Wang, Qianben/E-4267-2011; Ruoff, Rodney/B-7605-2009; Huang, Se-Te/F-6881-2013; OI Brown, Myles/0000-0002-8213-1658; Nwachukwu, Jerome/0000-0003-4313-9187 FU NIH [F31CA113285, R01 DK058024, R01CA112226]; ACS, DOD [W81XWH-04-1-0914]; National Cancer Institute's Dana-Farber/Harvard Cancer Center Prostate Cancer Specialized Programs of Research Excellence [K99CA126160] FX Grant support: NIH F31CA113285 (J.C. Nwachukwu); NIH R01 DK058024 (M.J. Garabedian); ACS, DOD W81XWH-04-1-0914, and NIH R01CA112226 (S.K. Logan); and National Cancer Institute's Dana-Farber/Harvard Cancer Center Prostate Cancer Specialized Programs of Research Excellence (M. Brown) and grant K99CA126160 (Q. Wang). NR 36 TC 10 Z9 11 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2009 VL 69 IS 7 BP 3140 EP 3147 DI 10.1158/0008-5472.CAN-08-3738 PG 8 WC Oncology SC Oncology GA 429GE UT WOS:000264908100058 PM 19318562 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Takashi Tsuruo Obituary SO CANCER SCIENCE LA English DT Biographical-Item C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 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 1347-9032 J9 CANCER SCI JI Cancer Sci. PD APR PY 2009 VL 100 IS 4 BP 565 EP 566 DI 10.1111/j.1349-7006.2009.01124.x PG 2 WC Oncology SC Oncology GA 438TK UT WOS:000265578100001 PM 19453545 ER PT J AU Vasudevan, A AF Vasudevan, Anju TI Angiogenesis in the central nervous system SO CELL ADHESION & MIGRATION LA English DT Editorial Material C1 [Vasudevan, Anju] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Vasudevan, Anju] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Vasudevan, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM anju.vasudevan@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6918 J9 CELL ADHES MIGR JI Celll Adhes. Migr. PD APR-JUN PY 2009 VL 3 IS 2 BP 198 EP 198 DI 10.4161/cam.3.2.8513 PG 1 WC Cell Biology SC Cell Biology GA V21VE UT WOS:000208234300017 PM 19398894 ER PT J AU Navaratna, D Guo, SZ Arai, K Lo, EH AF Navaratna, Deepti Guo, Shuzhen Arai, Ken Lo, Eng H. TI Mechanisms and targets for angiogenic therapy after stroke SO CELL ADHESION & MIGRATION LA English DT Article DE angiogenic therapy; stroke; neuroprotection; neurogenesis; angiogenesis; neurovascular unit; cerebral ischemia; stroke recovery AB Stroke remains a major health problem worldwide, and is the leading cause of serious long-term disability. Recent findings now suggest that strategies to enhance angiogenesis after focal cerebral ischemia may provide unique opportunities to improve clinical outcomes during stroke recovery. In this mini-review, we survey emerging mechanisms and potential targets for angiogenic therapies in brain after stroke. Multiple elements may be involved, including growth factors, adhesion molecules and progenitor cells. Furthermore, cross talk between angiogenesis and neurogenesis may also provide additional substrates for plasticity and remodeling in the recovering brain. A better understanding of the molecular interplay between all these complex pathways may lead to novel therapeutic avenues for tackling this difficult disease. C1 [Navaratna, Deepti] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. RP Navaratna, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, MGH E Bldg 149,Room 2401, Charlestown, MA 02129 USA. EM navaratna.deepti@mgh.harvard.edu FU NIH [P50-NS10828, P01-NS55104, R01-NS48422, R37-NS37074] FX Supported by NIH grants P50-NS10828, P01-NS55104, R01-NS48422 and R37-NS37074. NR 112 TC 40 Z9 47 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6918 J9 CELL ADHES MIGR JI Celll Adhes. Migr. PD APR-JUN PY 2009 VL 3 IS 2 BP 216 EP 223 DI 10.4161/cam.3.2.8396 PG 8 WC Cell Biology SC Cell Biology GA V21VE UT WOS:000208234300021 PM 19363301 ER PT J AU Wurdinger, T Tannous, BA AF Wuerdinger, Thomas Tannous, Bakhos A. TI Glioma angiogenesis Towards novel RNA therapeutics SO CELL ADHESION & MIGRATION LA English DT Article DE glioma; angiogenesis; anti-angiogenesis therapy; siRNA; miRNA; endothelial cells; blood vessels AB Brain tumors exhibit marked and aberrant blood vessel formation indicating angiogenic endothelial cells as a potential target for brain tumor treatment. The brain tumor blood vessels are used for nutrient delivery, and possibly for cancer cell migration. The process of angiogenesis is complex and involves multiple players. The current angiogenesis inhibitors used in clinical trials mostly target single angiogenic proteins and so far show limited effects on tumor growth. Besides the conventional angiogenesis inhibitors, RNA-based inhibitors such as small-interfering RNAs (siRNAs) are being analyzed for their capacity to silence the message of proteins involved in neovascularization. More recently, a new family of non-coding RNAs, named angiomirs [microRNAs (miRNAs) involved in angiogenesis] has emerged. These small RNAs have the advantage over siRNAs in that they have the potential of silencing multiple messages at the same time and therefore they might become therapeutically relevant in a "one-hit multiple-target" context against brain tumor angiogenesis. In this review we will discuss the emerging technologies in anti-angiogenesis emphasizing on RNA-based therapeutics. C1 [Wuerdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02115 USA. [Wuerdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02115 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wuerdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Wuerdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Dept Neurosurg, Canc Ctr Amsterdam, Neurooncol Res Grp, Amsterdam, Netherlands. RP Wurdinger, T (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM twurdinger@mgh.harvard.edu; btannous@hms.harvard.edu FU American Brain Tumor Association FX We would like to acknowledge the Steve Kaplan Fellowship from the American Brain Tumor Association and we would like to thank Dr. David P. Noske for critical reading of the manuscript, Mrs. Suzanne McDavitt and Mrs. Lee-Ann Tjon for skilled editorial assistance. NR 78 TC 16 Z9 16 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6918 J9 CELL ADHES MIGR JI Celll Adhes. Migr. PD APR-JUN PY 2009 VL 3 IS 2 BP 230 EP 235 DI 10.4161/cam.3.2.7910 PG 6 WC Cell Biology SC Cell Biology GA V21VE UT WOS:000208234300023 PM 19262177 ER PT J AU Gan, B DePinho, RA AF Gan, Boyi DePinho, Ronald A. TI mTORC1 signaling governs hematopoietic stem cell quiescence SO CELL CYCLE LA English DT Article DE hematopoietic stem cell; quiescence; cell growth; mTORC1; TSC ID LEUKEMIA-INITIATING CELLS; TUMOR SUPPRESSION; SELF-RENEWAL; RAG GTPASES; GROWTH; PTEN; DIFFERENTIATION; MAINTENANCE; STRESS; NICHES AB The stringent regulation of hematopoietic stem cell (HSC) quiescence versus cell cycle progression is essential for the preservation of a pool of long-term self-renewing cells and vital for sustaining an adequate supply of all blood lineages throughout life. Cell growth, the process that is mass increase, serves as a trigger for cell cycle progression and is regulated predominantly by mammalian target of rapamycin complex 1 (mTORC1) signaling. Emerging data from various mice models show deletion of several mTORC1 negative regulators, including PTEN, TSC1, PML and Fbxw7 result in similar HSC phenotypes characterized as HSC hyper-proliferation and subsequent exhaustion, and defective repopulating potential. Further pharmacological approaches show that PTEN, TSC1 and PML regulate HSC maintenance through mTORC1. mTORC1-mediated cell growth regulatory circuits thus play a critical role in the regulation of HSC quiescence. C1 [Gan, Boyi; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 413, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu FU National Cancer Institute [R21CA135057] FX This research was supported by National Cancer Institute grant R21CA135057 to R. A. D. and B. G. B. G. is the Research Fellow of the Leukemia & Lymphoma Society. R. A. D. is the American Cancer Society Research Professor and is supported by the Robert A. and Renee E. Belfer Institute for Applied Cancer Science. NR 28 TC 53 Z9 54 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2009 VL 8 IS 7 BP 1003 EP 1006 DI 10.4161/cc.8.7.8045 PG 4 WC Cell Biology SC Cell Biology GA 438YW UT WOS:000265593900013 PM 19270523 ER PT J AU Shen, L Zhi, L Hu, W Wu, MX AF Shen, L. Zhi, L. Hu, W. Wu, M. X. TI IEX-1 targets mitochondrial F1Fo-ATPase inhibitor for degradation SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE IEX-1; F1Fo-ATPase inhibitor; mitochondrial ROS homeostasis; protein degradation ID IMMEDIATE-EARLY GENE; PROTEIN IF1; ATPASE INHIBITOR; SYNTHASE; CELL; APOPTOSIS; HEART; PROLIFERATION; F1-ATPASE; MEMBRANE AB IEX-1 (Immediate Early response gene X-1) is a stress-inducible gene. It suppresses production of reactive oxygen species (ROS) and protects cells from apoptosis induced by a wide range of stimuli, but the underlying mechanism is not known. This study reveals that IEX-1 targets the mitochondrial F1Fo-ATPase Inhibitor (IF1) for degradation, resulting in acceleration of ATP hydrolysis, concomitant with reduction in ROS production. A prominent role for IF1 degradation in the function of IEX-1 was corroborated by siRNA- mediated gene silencing of IF1 that recapitulated the effects of IEX-1 on ATP hydrolysis and ROS production. Moreover, progressive C-terminal truncation studies demonstrated that IEX-1 interacted with the C terminus of IF1 and the interaction might render IF1 prone to degradation by an as yet unidentified mitochondrial protease. In support of a physiological importance of IEX-1 in the modulation of IF1 expression, gene-targeted deletion of IEX-1 stabilized IF1 and reduced mitochondrial F1Fo-ATPase activity in vivo. The altered activity of the F1Fo enzyme may account for a metabolic switch from oxidative phosphorylation toward glycolysis in IEX-1 deficient cells. Thus, IEX-1 deficient cells were more susceptible to glucose deprivation than wild type counterparts and displayed increased glucose uptake and lactate production in hypoxic conditions. The cells were also relatively refractory to oligomycin-mediated inhibition of ATP production. The studies offer novel insights into the primary role of IEX-1 in regulating a balance between energy provision and ROS production. C1 [Shen, L.; Zhi, L.; Hu, W.; Wu, M. X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Shen, L.; Zhi, L.; Hu, W.; Wu, M. X.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Wu, M. X.] Harvard Univ, Div Hlth Sci & Technol, MIT, Boston, MA 02115 USA. RP Wu, MX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org RI Zhi, Liang/C-7765-2009 FU National Institutes of Health [AI050822, AI070785]; American Cancer Society [RSG-01-178-01-MGO]; Crohn's and Colitis Foundation of America; American Heart Association FX We thank members in Dr Wu's group for their stimulating discussion and Drs Kenneth D Bloch and Robert E Edwards for critical reading and reviewing of the paper. This work is supported by the National Institutes of Health Grants AI050822 and AI070785, a Research Scholar Grant RSG-01-178-01-MGO from the American Cancer Society, a Senior Research Award from the Crohn's and Colitis Foundation of America, and a Grant-in-Aid award from the American Heart Association (to MXW). NR 40 TC 39 Z9 41 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2009 VL 16 IS 4 BP 603 EP 612 DI 10.1038/cdd.2008.184 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 418UX UT WOS:000264176000010 PM 19096392 ER PT J AU Myre, MA Washicosky, K Moir, RD Tesco, G Tanzi, RE Wasco, W AF Myre, Michael A. Washicosky, Kevin Moir, Robert D. Tesco, Giuseppina Tanzi, Rudolph E. Wasco, Wilma TI Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1 SO CELLULAR SIGNALLING LA English DT Article DE Amyloid beta-protein precursor; Alzheimer's disease; Phosphorylation; Differentiation inducing factor; Cell cycle; Proteolysis ID CELL-CYCLE ACTIVATION; ALZHEIMERS-DISEASE; INCREASED EXPRESSION; PHOSPHORYLATION; DICTYOSTELIUM; PROLIFERATION; METABOLISM; CANCER; BRAIN; GENE AB The detection of cell cycle proteins in Alzheimer's disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-A beta properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique. small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid beta-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of A beta 40 and A beta 42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of A beta 42 to A beta 40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of A beta. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1 -associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668. (C) 2008 Elsevier Inc. All rights reserved. C1 [Myre, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA. [Washicosky, Kevin; Moir, Robert D.; Tesco, Giuseppina; Tanzi, Rudolph E.; Wasco, Wilma] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Neurobiol Dis Lab, Boston, MA 02129 USA. RP Myre, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA. EM myre@chgr.mgh.harvard.edu FU Edward R. and Anne G. Lefler Center; National Institutes of Health [AG015379] FX We thank D.M. Kovacs for providing the anti-APP C-terminal antibody (C66): anti-APP N-term (595-611) R1736 was kindly provided by Jack Rogers; Dominic Walsh for providing us with CHO-A1 and CHO-A2 cells stably expressing either human APLP1 or APLP2. We thank Eugene Kang for technical work on the site-directed mutagenesis. The work is supported by an Edward R. and Anne G. Lefler Center Postdoctoral Fellowship for the Study of Neurological Disorders to M.A. Myre and a National Institutes of Health Grant AG015379 to W. Wasco. NR 46 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2009 VL 21 IS 4 BP 567 EP 576 DI 10.1016/j.cellsig.2008.12.008 PG 10 WC Cell Biology SC Cell Biology GA 419NL UT WOS:000264226200013 PM 19154786 ER PT J AU Makris, N Papadimitriou, GM Kaiser, JR Sorg, S Kennedy, DN Pandya, DN AF Makris, Nikos Papadimitriou, George M. Kaiser, Jonathan R. Sorg, Scott Kennedy, David N. Pandya, Deepak N. TI Delineation of the Middle Longitudinal Fascicle in Humans: A Quantitative, In Vivo, DT-MRI Study SO CEREBRAL CORTEX LA English DT Article DE DT-MRI; middle longitudinal fascicle; segmentation; tractography ID PARIETAL ASSOCIATION CORTEX; RIGHT-HEMISPHERE DOMINANCE; LIGHT-SENSITIVE NEURONS; WHITE-MATTER; HUMAN BRAIN; TOPOGRAPHIC PARCELLATION; DISCONNEXION SYNDROMES; VISUAL RESPONSES; ATTENTION; LANGUAGE AB Experimental and imaging studies in monkeys have outlined various long association fiber bundles within the temporoparietal region. In the present study the trajectory of the middle longitudinal fascicle (MdLF) has been delineated in 4 human subjects using diffusion tensor magnetic resonance imaging segmentation and tractography. The MdLF seems to extend from the inferior parietal lobule (IPL), specifically the angular gyrus, to the temporal pole remaining within the white matter of the superior temporal gyrus (STG). Comparison of the superior longitudinal fascicle II-arcuate fascicle (SLF II-AF) with the MdLF in the same subjects revealed that MdLF is located in a medial and caudal position relative to SLF II-AF and that it extends more rostrally. Given the location of MdLF between the IPL (angular gyrus) and the STG, it is suggested that MdLF could have a role in language and attention functions. C1 [Makris, Nikos; Papadimitriou, George M.; Kaiser, Jonathan R.; Sorg, Scott; Kennedy, David N.] Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Gen Hosp, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02129 USA. [Makris, Nikos; Papadimitriou, George M.; Kaiser, Jonathan R.; Sorg, Scott; Kennedy, David N.] Harvard Univ, Sch Med, Dept Neurol,Massachusetts Gen Hosp, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02129 USA. [Makris, Nikos; Papadimitriou, George M.; Kaiser, Jonathan R.; Sorg, Scott; Kennedy, David N.] Harvard Univ, Sch Med, Dept Radiol Serv,Massachusetts Gen Hosp, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02129 USA. [Makris, Nikos; Pandya, Deepak N.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal, Bldg 149,13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NCCIH NIH HHS [P01AT002048-05] NR 67 TC 64 Z9 64 U1 1 U2 5 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 APR PY 2009 VL 19 IS 4 BP 777 EP 785 DI 10.1093/cercor/bhn124 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 415PC UT WOS:000263945100003 PM 18669591 ER PT J AU Joshi, G Wilens, T AF Joshi, Gagan Wilens, Timothy TI Comorbidity in Pediatric Bipolar Disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review DE Bipolar disorder; Comorbidity; Children and adolescents; Clinical presentation; Treatment ID POSTTRAUMATIC-STRESS-DISORDER; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; SUBSTANCE USE DISORDERS; DISRUPTIVE BEHAVIOR DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; FAMILIAL RISK ANALYSIS; PROSPECTIVE FOLLOW-UP; SCHOOL-AGE-CHILDREN AB The growing literature shows the pervasiveness and importance of comorbidity in youth with bipolar disorder (BPD). For instance, up to 90% of youth with BPD have been described to manifest comorbidity with attention-deficit hyperactivity disorder. Multiple anxiety, substance use, and disruptive behavior disorders are the other most commonly reported comorbidities with BPD. Moreover, important recent data highlight the importance of obsessive-compulsive and pervasive developmental illness in the context of BPD. Data suggest that not only special developmental relationships are operant in the context of comorbidity but also that the presence of comorbid disorders with BPD results in a more severe clinical condition. Moreover, the presence of comorbidity has therapeutic implications for the treatment response for both BPD and the associated comorbid disorder. Future longitudinal studies to address the relationship and the impact of comorbid disorders on course and therapeutic response over time are required in youth with BPD. C1 [Joshi, Gagan] Harvard Univ, Massachusetts Gen Hosp, Pervas Dev Disorders Program, Clin & Res Programs Pediat Psychopharmacol,Sch Me, Boston, MA 02114 USA. [Wilens, Timothy] Harvard Univ, Substance Abuse Serv, Pediat Psychopharmacol Clin, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Joshi, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pervas Dev Disorders Program, Clin & Res Programs Pediat Psychopharmacol,Sch Me, 32 Fruit St,YAW 6A, Boston, MA 02114 USA. EM joshi.gagan@mgh.harvard.edu FU NIDA NIH HHS [R01 DA012945, K24 DA016264, R01 DA 12945, K24 DA 016264] NR 186 TC 22 Z9 23 U1 9 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2009 VL 18 IS 2 BP 291 EP + DI 10.1016/j.chc.2008.12.005 PG 31 WC Psychiatry SC Psychiatry GA 426MZ UT WOS:000264713700005 PM 19264265 ER PT J AU Mick, E Faraone, SV AF Mick, Eric Faraone, Stephen V. TI Family and Genetic Association Studies of Bipolar Disorder in Children SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Bipolar disorder; Childhood; Genetics; Comorbidity; Age at onset ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; GENOME-WIDE ASSOCIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EARLY ADOLESCENT BIPOLARITY; MANIC-DEPRESSIVE ILLNESS; PROSPECTIVE FOLLOW-UP; ONSET MOOD DISORDER; NEUROTROPHIC FACTOR; LINKAGE DISEQUILIBRIUM AB The risk of bipolar disorder (BPD) (15-42%) in first-degree relatives of children with BPD are consistently larger than the 8.7% estimate of recurrence risk of BPD in first-degree relatives of adult BPD cases. There have been no family linkage studies of pediatric BPD, but secondary analyses of adult linkage samples suggest that early-onset BPD both increases the strength of associations in linkage studies. Positive associations with pediatric BPD and the BDNF gene (VaII66), the GAD1 gene (4s2241165), and the dopamine transporter gene (rs41084) have been reported but none of these associations have been replicated in independent samples. The number of informative families examined so far is quite small and studies were vastly underpowered to detect small effects. An adequately powered sample will likely require collaborative ascertainment of cases and families from multiple sites using valid and accepted measures of pediatric BPD. C1 [Mick, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mick, Eric] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Warren 705, Boston, MA 02114 USA. EM mick@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K01 MH 065523] NR 81 TC 16 Z9 16 U1 5 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 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2009 VL 18 IS 2 BP 441 EP + DI 10.1016/j.chc.2008.11.008 PG 14 WC Psychiatry SC Psychiatry GA 426MZ UT WOS:000264713700012 PM 19264272 ER PT J AU Potter, M Moses, A Wozniak, J AF Potter, Mona Moses, Alana Wozniak, Janet TI Alternative Treatments in Pediatric Bipolar Disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review DE Complementary and alternative treatments; Pediatric bipolar disorder; Omega-3-fatty acid; Inositol; St. John's wort; SAMe; Melatonin; Acupuncture ID ST-JOHNS-WORT; ADENOSYL-L-METHIONINE; PURIFIED EICOSAPENTAENOIC ACID; MANIC-DEPRESSIVE ILLNESS; MAGNETIC-RESONANCE-SPECTROSCOPY; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; BLOOD-CELL MEMBRANES; DOUBLE-BLIND AB There has been growing interest in the use of complementary and alternative treatments in pediatric bipolar disorder (BPD). There are limited data, however, regarding the safety and efficacy of these treatments. This article discusses select complementary and alternative treatments that have been considered for use in pediatric BPD and/or depression, including omega-3-fatty acids, inositol, St. John's wort, SAMe, melatonin, lecithin, and acupuncture. Background information, reference to available adult and pediatric data, proposed mechanisms of action, dosing, side effects, and precautions of these treatments are included. Across the board, more research is necessary and warranted regarding the long-term safety and efficacy of available complementary and alternative treatments for the management of pediatric BPD. C1 [Potter, Mona; Wozniak, Janet] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Potter, Mona; Wozniak, Janet] McLean Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Moses, Alana] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Cambridge, MA 02138 USA. RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Yawkey Ctr Outpatient Care, Yawkey 6A,55 Fruit St, Boston, MA 02114 USA. EM jwozniak@partners.org NR 174 TC 6 Z9 6 U1 8 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 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2009 VL 18 IS 2 BP 483 EP + DI 10.1016/j.chc.2008.11.001 PG 33 WC Psychiatry SC Psychiatry GA 426MZ UT WOS:000264713700015 PM 19264275 ER PT J AU Di Biase, L Elayi, CS Fahmy, TS Martin, DO Ching, CK Barrett, C Bai, R Patel, D Khaykin, Y Hongo, R Hao, S Beheiry, S Pelargonio, G Dello Russo, A Casella, M Santarelli, P Potenza, D Fanelli, R Massaro, R Wang, P Al-Ahmad, A Arruda, M Themistoclakis, S Bonso, A Rossillo, A Raviele, A Schweikert, RA Burkhardt, DJ Natale, A AF Di Biase, Luigi Elayi, Claude S. Fahmy, Tamer S. Martin, David O. Ching, Chi Keong Barrett, Conor Bai, Rong Patel, Dimpi Khaykin, Yaariv Hongo, Richard Hao, Steven Beheiry, Salwa Pelargonio, Gemma Dello Russo, Antonio Casella, Michela Santarelli, Pietro Potenza, Domenico Fanelli, Raffaele Massaro, Raimondo Wang, Paul Al-Ahmad, Amin Arruda, Mauricio Themistoclakis, Sakis Bonso, Aldo Rossillo, Antonio Raviele, Antonio Schweikert, Robert A. Burkhardt, David J. Natale, Andrea TI Atrial Fibrillation Ablation Strategies for Paroxysmal Patients Randomized Comparison Between Different Techniques SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; paroxysmal atrial fibrillation; pulmonary vein antrum isolation; radiofrequency; randomized study; complex fractionated atrial electrograms or defragmentation ID VEIN ANTRUM ISOLATION; PULMONARY VEINS; CATHETER ABLATION; INSIGHTS AB Background-Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF Methods and Results-One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At I year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs. Conclusion-No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF. (Circ Arrhythmia Electrophysiol. 2009;2:113-119.) C1 [Di Biase, Luigi; Patel, Dimpi; Burkhardt, David J.; Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX 78705 USA. [Di Biase, Luigi] Univ Foggia, Dept Cardiol, Foggia, Italy. [Elayi, Claude S.] Univ Kentucky, Gill Heart Inst, Div Cardiovasc Med, Lexington, KY USA. [Martin, David O.] Cleveland Clin, Cleveland, OH 44106 USA. [Hongo, Richard; Hao, Steven; Beheiry, Salwa] Sutter Pacific Heart Ctr, San Francisco, CA USA. [Khaykin, Yaariv] Southlake Reg Hlth Ctr, New Market, ON, Canada. [Pelargonio, Gemma; Dello Russo, Antonio; Casella, Michela; Santarelli, Pietro] Catholic Univ, Rome, Italy. [Potenza, Domenico; Fanelli, Raffaele; Massaro, Raimondo] Casa Sollievo Sofferenza, Foggia, Italy. [Wang, Paul; Al-Ahmad, Amin; Natale, Andrea] Stanford Univ, Palo Alto, CA 94304 USA. [Ching, Chi Keong] Natl Heart Ctr Singapore Mistri Wing, Dept Cardiol, Singapore, Singapore. [Arruda, Mauricio; Natale, Andrea] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Fahmy, Tamer S.] Cairo Univ, Dept Crit Care Med, Cairo, Egypt. [Barrett, Conor] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Huazhong Univ Sci & Technol, Tong Ji Hosp, Tong Ji Med Coll, Dept Internal Med, Wuhan 430074, Peoples R China. [Schweikert, Robert A.] Akron Gen Hosp, Akron, OH USA. RP Natale, A (reprint author), St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, 1015 E 32nd St, Austin, TX 78705 USA. EM dr.natale@gmail.com RI Fahmy, Tamer/K-3642-2016; OI Fahmy, Tamer/0000-0001-5536-1135; Di Biase, Luigi/0000-0001-6508-4047 NR 21 TC 64 Z9 65 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2009 VL 2 IS 2 BP 113 EP 119 DI 10.1161/CIRCEP.108.798447 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446ND UT WOS:000266127400005 PM 19808455 ER PT J AU Ho, CY MacRae, CA AF Ho, Carolyn Y. MacRae, Calum A. TI Defining the Pathogenicity of DNA Sequence Variation SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE genetics; pathogenicity; genetic testing ID MUTATIONS; ASSOCIATION; PROJECT; ELEGANS; DISEASE; PHENOME; GENOME C1 [MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [MacRae, Calum A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ho, Carolyn Y.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM macrae@cvrc.mgh.harvard.edu OI Ho, Carolyn/0000-0002-7334-7924 FU NHLBI NIH HHS [R21 HL098938-02, R21 HL098938-01, R21 HL098938] NR 21 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2009 VL 2 IS 2 BP 95 EP 97 DI 10.1161/CIRCGENETICS.109.864793 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HE UT WOS:000275979200001 PM 20031572 ER PT J AU Dehghan, A Yang, Q Peters, A Basu, S Bis, JC Rudnicka, AR Kavousi, M Chen, MH Baumert, J Lowe, GDO McKnight, B Tang, WH de Maat, M Larson, MG Eyhermendy, S McArdle, WL Lumley, T Pankow, JS Hofman, A Massaro, JM Rivadeneira, F Kolz, M Taylor, KD van Duijn, CM Kathiresan, S Illig, T Aulchenko, YS Volcik, KA Johnson, AD Uitterlinden, AG Tofler, GH Gieger, C Psaty, BM Couper, DJ Boerwinkle, E Koenig, W O'Donnell, CJ Witteman, JC Strachan, DP Smith, NL Folsom, AR AF Dehghan, Abbas Yang, Qiong Peters, Annette Basu, Saonli Bis, Joshua C. Rudnicka, Alicja R. Kavousi, Maryam Chen, Ming-Huei Baumert, Jens Lowe, Gordon D. O. McKnight, Barbara Tang, Weihong de Maat, Moniek Larson, Martin G. Eyhermendy, Susana McArdle, Wendy L. Lumley, Thomas Pankow, James S. Hofman, Albert Massaro, Joseph M. Rivadeneira, Fernando Kolz, Melanie Taylor, Kent D. van Duijn, Cornelia M. Kathiresan, Sekar Illig, Thomas Aulchenko, Yurii S. Volcik, Kelly A. Johnson, Andrew D. Uitterlinden, Andre G. Tofler, Geoffrey H. Gieger, Christian Psaty, Bruce M. Couper, David J. Boerwinkle, Eric Koenig, Wolfgang O'Donnell, Christopher J. Witteman, Jacqueline C. Strachan, David P. Smith, Nicholas L. Folsom, Aaron R. CA Wellcome Trust Case Control Consor TI Association of Novel Genetic Loci With Circulating Fibrinogen Levels A Genome-Wide Association Study in 6 Population-Based Cohorts SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genome-wide association study; fibrinogen; genes; meta-analysis ID INFLAMMATORY-BOWEL-DISEASE; CARDIOVASCULAR-DISEASE; VENOUS THROMBOSIS; PLASMA-FIBRINOGEN; FRAMINGHAM; DESIGN; RISK; EXPRESSION; HEART; OBJECTIVES C1 [Dehghan, Abbas; Kavousi, Maryam; Hofman, Albert; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Yang, Qiong; Larson, Martin G.; Massaro, Joseph M.; Kathiresan, Sekar; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Dehghan, Abbas; Yang, Qiong; Chen, Ming-Huei] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Chen, Ming-Huei] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Chen, Ming-Huei] Boston Univ, Framingham Heart Study, Boston, MA 02215 USA. [Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [de Maat, Moniek] Erasmus MC, Dept Hematol, NL-3000 CA Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Larson, Martin G.; Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Tang, Weihong; Pankow, James S.; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Volcik, Kelly A.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Volcik, Kelly A.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Rudnicka, Alicja R.; Strachan, David P.] Univ London, Div Community Hlth Sci, London, England. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Bristol, Avon, England. [Lowe, Gordon D. O.] Univ Glasgow, Royal Infirm, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Wellcome Trust Case Control Consor] Wellcome Trust Res Labs, Cambridge, England. [Peters, Annette; Baumert, Jens; Kolz, Melanie; Illig, Thomas; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol 2, Ulm, Germany. [Eyhermendy, Susana] Pontificia Univ Catolica Chile, Dept Stat, Santiago, Chile. [Smith, Nicholas L.] Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [McKnight, Barbara; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. RP Witteman, JC (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM odonnellc@nhlbi.nih.gov; j.witteman@erasmusmc.nl RI Johnson, Andrew/G-6520-2013; Aulchenko, Yurii/M-8270-2013; Waldenberger, Melanie/B-5355-2014; Yang, Qiong/G-5438-2014; Peters, Annette/A-6117-2011; Rivadeneira, Fernando/O-5385-2015; Breen, Gerome/A-5540-2010; OI Gieger, Christian/0000-0001-6986-9554; Wallace, Chris/0000-0001-9755-1703; Eyre, Stephen/0000-0002-1251-6974; Pankow, James/0000-0001-7076-483X; Dehghan, Abbas/0000-0001-6403-016X; Larson, Martin/0000-0002-9631-1254; Aulchenko, Yurii/0000-0002-7899-1575; Waldenberger, Melanie/0000-0003-0583-5093; Rivadeneira, Fernando/0000-0001-9435-9441; Breen, Gerome/0000-0003-2053-1792; Massaro, Joseph/0000-0002-2682-4812; Lango Allen, Hana/0000-0002-7803-8688; Zeggini, Eleftheria/0000-0003-4238-659X; Dunger, Professor David/0000-0002-2566-9304 FU Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for Scientific Research [175.010.2005.011, 911.03.012]; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly [94800022]; Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-060-810]; National Heart, Lung, and Blood Institute [N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652]; Affymetrix Inc [N02-HL-6-4278]; National Human Genome Research Institute [U01-HG-004402]; National Institutes of Health [HHSN268200625226C]; NIH Roadmap for Medical Research; National Center for Research Rosources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Helmholtz Zentrum Munchen; German Research Center for Environmental Health (Neuherberg, Germany); German Federal Ministry of Education and Research; German National Genome Research Network; [UL1-RR-025005] FX The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organization for Scientific Research (175.010.2005.011, 911.03.012) and the Research Institute for Diseases in the Elderly. This study was further supported by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research project 050-060-810. Dr Dehghan is supported by the Netherlands Organization for Scientific Research and the Research Institute for Diseases in the Elderly (94800022).; The FHS was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195) and its contract with Affymetrix Inc for genotyping services (contract N02-HL-6-4278).; The ARIC is supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 and grants R01-HL-087641, R01-HL-59367, and R01-HL-086694; National Human Genome Research Institute contract U01-HG-004402; and National Institutes of Health contract HHSN268200625226C. The infrastructure was partly supported by grant UL1-RR-025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; The Cardiovascular Health Study is supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL 087652 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. Support was also provided by NHLBI grant HL073410 and the Leducq Foundation, Paris, France for the development of Transatlantic Networks of Excellence in Cardiovascular Research. DNA handling and genotyping was supported in part by National Center for Research Rosources grant M01RR00069 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; The MONICA/KORA studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health (Neuherberg, Germany) and supported by grants from the German Federal Ministry of Education and Research. Part of this work was financed by the German National Genome Research Network and through additional funds from the University of Ulm. NR 32 TC 56 Z9 59 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD APR PY 2009 VL 2 IS 2 BP 125 EP U91 DI 10.1161/CIRCGENETICS.108.825224 PG 17 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HE UT WOS:000275979200005 PM 20031576 ER PT J AU Mok, W Stylianopoulos, T Boucher, Y Jain, RK AF Mok, Wilson Stylianopoulos, Triantafyllos Boucher, Yves Jain, Rakesh K. TI Mathematical Modeling of Herpes Simplex Virus Distribution in Solid Tumors: Implications for Cancer Gene Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID TO-CELL SPREAD; HEPARAN-SULFATE; GLYCOPROTEIN-C; MICROVASCULAR PERMEABILITY; BIOSENSOR TECHNOLOGY; NEOPLASTIC TISSUES; ANTIBODY FRAGMENT; ONCOLYTIC VIRUS; IN-VIVO; BINDING AB Purpose: Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design: The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results: This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more, An increase in the effective diffusion coefficient can result in similar gains. Conclusions: This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. C1 [Mok, Wilson; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, EL Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. [Mok, Wilson] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, EL Steele Lab,Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU National Cancer Institute [PO1CA80124, RO1CA85140] FX National Cancer Institute (PO1CA80124 and RO1CA85140 R.K. Jain). NR 50 TC 34 Z9 34 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2009 VL 15 IS 7 BP 2352 EP 2360 DI 10.1158/1078-0432.CCR-08-2082 PG 9 WC Oncology SC Oncology GA 429YK UT WOS:000264955800018 PM 19318482 ER PT J AU Wong, KK Fracasso, PM Bukowski, RM Lynch, TJ Munster, PN Shapiro, GI Jaenne, PA Eder, JP Naughton, MJ Ellis, MJ Jones, SF Mekhail, T Zacharchuk, C Vermette, J Abbas, R Quinn, S Powell, C Burris, HA AF Wong, Kwok-K. Fracasso, Paula M. Bukowski, Ronald M. Lynch, Thomas J. Munster, Pamela N. Shapiro, Geoffrey I. Jaenne, Pasi A. Eder, Joseph P. Naughton, Michael J. Ellis, Matthew J. Jones, Suzanne F. Mekhail, Tarek Zacharchuk, Charles Vermette, Jennifer Abbas, Richat Quinn, Susan Powell, Christine Burris, Howard A. TI A Phase I Study with Neratinib (HKI-272), an Irreversible Pan ErbB Receptor Tyrosine Kinase Inhibitor, in Patients with Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; PREVIOUSLY TREATED PATIENTS; MONOCLONAL-ANTIBODY; GEFITINIB; CHEMOTHERAPY; ERLOTINIB; TUMORIGENESIS; MULTICENTER AB Purpose: The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Experimental Design: Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80,120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Results: Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >= 24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. Conclusion:The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation. C1 [Wong, Kwok-K.; Shapiro, Geoffrey I.; Jaenne, Pasi A.; Eder, Joseph P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, Kwok-K.; Shapiro, Geoffrey I.; Jaenne, Pasi A.; Eder, Joseph P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Fracasso, Paula M.; Naughton, Michael J.; Ellis, Matthew J.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Bukowski, Ronald M.; Mekhail, Tarek] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Munster, Pamela N.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine] Wyeth Res, Cambridge, MA USA. [Jones, Suzanne F.; Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana Bldg 810B, Boston, MA 02115 USA. EM kwong1@partners.org FU Wyeth Research, Collegeville. PA; Genzyme, (J Eder) FX Wyeth Research, Collegeville. PA, and royaliles from Genzyme, (J Eder). NR 23 TC 143 Z9 145 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2009 VL 15 IS 7 BP 2552 EP 2558 DI 10.1158/1078-0432.CCR-08-1978 PG 7 WC Oncology SC Oncology GA 429YK UT WOS:000264955800041 PM 19318484 ER PT J AU Milbury, CA Li, J Makrigiorgos, GM AF Milbury, Coren A. Li, Jin Makrigiorgos, G. Mike TI PCR-Based Methods for the Enrichment of Minority Alleles and Mutations SO CLINICAL CHEMISTRY LA English DT Review ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; POINT MUTATIONS; NONRADIOACTIVE DETECTION; GEL-ELECTROPHORESIS; RAS MUTATIONS; GENOMIC DNA; AMPLIFICATION; ASSAY; SAMPLES AB BACKGROUND: The ability to identify low-level somatic DNA mutations and minority alleles within an excess wild-type sample is becoming essential for characterizing early and posttreatment tumor status in cancer patients. Over the past 2 decades, much research has focused on improving the selectivity of PCR-based technologies for enhancing the detection of minority (mutant) alleles in clinical samples. Routine application in clinical and diagnostic settings requires that these techniques be accurate and cost-effective and require little effort to optimize, perform, and analyze. CONTENT: Enrichment methods typically segregate by their ability to enrich for, and detect, either known or unknown mutations. Although there are several robust approaches for detecting known mutations within a high background of wild-type DNA, there are few techniques capable of enriching and detecting low-level unknown mutations. One promising development is COLD-PCR (coamplification at lower denaturation temperature), which enables enrichment of PCR amplicons containing unknown mutations at any position, such that they can be subsequently sequenced to identify the exact nucleotide change. SUMMARY: This review summarizes technologies available for detecting minority DNA mutations, placing an emphasis on newer methods that facilitate the enrichment of unknown low-level DNA variants such that the mutation can subsequently be sequenced. The enrichment of minority alleles is imperative in clinical and diagnostic applications, especially in those related to cancer detection, and continued technology development is warranted. (C) 2009 American Association for Clinical Chemistry C1 [Milbury, Coren A.; Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dept Radiat Oncol, Div Med Phys & Biophys, Boston, MA USA. [Milbury, Coren A.; Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div DNA Repair & Genome Stabil, Boston, MA USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2 Radiat Therapy,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NIH [CA-115439, CA-111994, 5 T32 CA09078] FX NIH grants CA-115439 and CA-111994 and NIH training grant 5 T32 CA09078 (the training grant was to C.A. Milbury and J. Li). NR 41 TC 75 Z9 76 U1 5 U2 22 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2009 VL 55 IS 4 BP 632 EP 640 DI 10.1373/clinchem.2008.113035 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 427IY UT WOS:000264774200008 PM 19201784 ER PT J AU Shen, YP Wui, BL AF Shen, Yiping Wui, Bai-Lin TI Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics SO CLINICAL CHEMISTRY LA English DT Review ID COPY NUMBER VARIATION; AUTISM SPECTRUM DISORDERS; OLIGONUCLEOTIDE ARRAY-CGH; HIGH-RESOLUTION ANALYSIS; MENTAL-RETARDATION; CHROMOSOMAL REARRANGEMENTS; HYBRIDIZATION ANALYSIS; STRUCTURAL VARIATION; DEVELOPMENTAL DELAY; ENHANCED DETECTION AB BACKGROUND: Microarray-based genomic DNA profiling (MGDP) technologies are rapidly moving from translational research to clinical diagnostics and have revolutionized medical practices. Such technologies have shown great advantages in detecting genomic imbalances associated with genomic disorders and single-gene diseases. CONTENT: We discuss the development and applications of the major array platforms that are being used in both academic and commercial laboratories. Although no standardized platform is expected to emerge soon, comprehensive oligonucleotide microarray platforms-both comparative genomic hybridization arrays and genotyping hybrid arrays-are rapidly becoming the methods of choice for their demonstrated analytical validity in detecting genomic imbalances, for their flexibility in incorporating customized designs and updates, and for the advantage of being easily manufactured. Copy number variants (CNVs), the form of genomic deletions/duplications detected through MGDP, are a common etiology for a variety of clinical phenotypes. The widespread distribution of CNVs poses great challenges in interpretation. A broad survey of CNVs in the healthy population, combined with the data accumulated from the patient population in clinical laboratories, will provide a better understanding of the nature of CNVs and enhance the power of identifying genetic risk factors for medical conditions. SUMMARY: MGDP technologies for molecular diagnostics are still at an early stage but are rapidly evolving. We are in the process of extensive clinical validation and utility evaluation of different array designs and technical platforms. CNVs of currently unknown importance will be a rich source of novel discoveries. (C) 2009 American Association for Clinical Chemistry C1 [Wui, Bai-Lin] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Shen, Yiping] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shen, Yiping; Wui, Bai-Lin] Harvard Univ, Sch Med, Boston, MA USA. [Wui, Bai-Lin] Fudan Univ, Shanghai 200433, Peoples R China. RP Wui, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bai-lin.wu@childrens.harvard.edu NR 75 TC 26 Z9 26 U1 2 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2009 VL 55 IS 4 BP 659 EP 669 DI 10.1373/clinchem.2008.112821 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 427IY UT WOS:000264774200010 PM 19233918 ER PT J AU Li, J Wang, LL Janne, PA Makrigiorgos, GM AF Li, Jin Wang, Lilin Jaenne, Pasi A. Makrigiorgos, G. Mike TI Coamplification at Lower Denaturation Temperature-PCR Increases Mutation-Detection Selectivity of TaqMan-Based Real-Time PCR SO CLINICAL CHEMISTRY LA English DT Article ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISMS; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; SENSITIVE DETECTION; DNA; EGFR; GEFITINIB; AMPLICONS AB BACKGROUND: DNA genotyping with mutation-specific TaqMan (R) probes (Applied Biosystems) is broadly used in detection of single-nucleotide polymorphisms but is less so for somatic mutations because of its limited selectivity for low-level mutations. We recently described coamplification at lower denaturation temperature-PCR (COLD-PCR), a method that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences during the PCR. We demonstrate that combining COLD-PCR with TaqMan technology provides TaqMan genotyping with the selectivity needed to detect low-level somatic mutations. METHODS: Minor-groove binder-based or common TaqMan probes were designed to contain a nucleotide that matches the desired mutation approximately in the middle of the probe. The critical denaturation temperature (T(c)) of each amplicon was then experimentally determined. COLD-PCR/TaqMan genotyping was performed in 2 steps: denaturation at the T, followed by annealing and extension at a single temperature (fast COLD-PCR). The threshold cycle was used to identify mutations on the basis of serial dilutions of mutant DNA into wild-type DNA and to identify TP53 (tumor protein p53) and EGFR [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)] mutations in tumors. RESULTS: COLD-PCR/TaqMan genotyping identified G>A mutations within TP53 exon 8 (codon 273 mutation hot spot) and C>1 mutations within the EGFR gene (drug-resistance mutation T790M) with a selectivity improvement of 15- to 30-fold over regular PCR/TaqMan genotyping. A second round of COLD-PCR/TaqMan genotyping improved the selectivity by another 15- to 30-fold and enabled detection of I mutant in 2000 wild-type alleles. Use of COLD-PCR/TaqMan genotyping allowed quantitative identification of low-level TP53 and T790 mutations in colon tumor samples and in non-small-cell lung cancer cell lines treated with kinase inhibitors. CONCLUSIONS: The major improvement in selectivity provided by COLD-PCR enables the popular TaqMan genotyping method to become a powerful tool for detecting low-level mutations in clinical samples. (C) 2008 American Association for Clinical Chemistry C1 [Li, Jin; Wang, Lilin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA USA. [Li, Jin; Wang, Lilin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dept Radiat Oncol, Div Med Phys, Boston, MA USA. [Jaenne, Pasi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Level L2 Radiat Therapy,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NIH [CA-115439, CA-111994, 5 T32 CA09078] FX P.A. Janne, Pfizer; G.M. Makrigiorgos, NIH grants CA-115439 and CA-111994; J. Li, NIH training grant 5 T32 CA09078. NR 35 TC 37 Z9 42 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2009 VL 55 IS 4 BP 748 EP 756 DI 10.1373/clinchem.2008.113381 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 427IY UT WOS:000264774200020 PM 19233916 ER PT J AU Mempel, TR Bauer, CA AF Mempel, Thorsten R. Bauer, Christian A. TI Intravital imaging of CD8(+) T cell function in cancer SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Review DE Tumor immunity; Cytotoxic T lymphocytes; CTL; Multiphoton intravital microscopy; In vivo imaging; Cancer; Immune response; Cell migration; Cell trafficking; Cellular interaction; Lytic granules; Cytotoxicity; Tumor stroma ID TUMOR-NECROSIS-FACTOR; ADHESION MOLECULE-1 EXPRESSION; TIME-LAPSE MICROCINEMATOGRAPHY; GRANULE-MEDIATED CYTOTOXICITY; PERFORIN-DEFICIENT MICE; ANTIGEN-LOSS VARIANTS; NATURAL-KILLER-CELLS; IN-VIVO; DENDRITIC CELLS; LYMPH-NODES AB Recent technological advances in photonics are making intravital microscopy (IVM) an increasingly powerful approach for the mechanistic exploration of biological processes in the physiological context of complex native tissue environments. Direct, dynamic and multiparametric visualization of immune cell behavior in living animals at cellular and subcellular resolution has already proved its utility in auditing basic immunological concepts established through conventional approaches and has also generated new hypotheses that can conversely be complemented and refined by traditional experimental methods. The insight that outgrowing tumors must not necessarily have evaded recognition by the adaptive immune system, but can escape rejection by actively inducing a state of immunological tolerance calls for a detailed investigation of the cellular and molecular mechanisms by which the anti-cancer response is subverted. Along with molecular imaging techniques that provide dynamic information at the population level, IVM can be expected to make a critical contribution to this effort by allowing the observation of immune cell behavior in vivo at single cell-resolution. We review here how IVM-based investigation can help to clarify the role of cytotoxic T lymphocytes (CTL) in the immune response against cancer and identify the ways by which their function might be impaired through tolerogenic mechanisms. C1 [Mempel, Thorsten R.; Bauer, Christian A.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Mempel, Thorsten R.; Bauer, Christian A.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA. [Mempel, Thorsten R.; Bauer, Christian A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Mempel, TR (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. EM tmempel@mgh.harvard.edu FU NIH [4 R00 AI073457-02]; Deutsche Forschungsgemeinschaft FX We would like to thank Drs. Mikael Pittet and Cathryn Nagler for helpful discussions and critical reading of the manuscript. T. R. M. is supported by NIH grant 4 R00 AI073457-02 and C. A. B. is supported by a grant from the Deutsche Forschungsgemeinschaft. NR 170 TC 9 Z9 9 U1 2 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD APR PY 2009 VL 26 IS 4 BP 311 EP 327 DI 10.1007/s10585-008-9196-9 PG 17 WC Oncology SC Oncology GA 418UI UT WOS:000264174500005 PM 18665448 ER PT J AU Shire, NJ Rao, MB Succop, P Buncher, CR Andersen, JA Butt, AA Chung, RT Sherman, KE AF Shire, Norah J. Rao, Marepalli B. Succop, Paul Buncher, C. Ralph Andersen, Janet A. Butt, Adeel A. Chung, Raymond T. Sherman, Kenneth E. CA AIDS Clinical Trials Grp 5178 TI Improving Noninvasive Methods of Assessing Liver Fibrosis in Patients With Hepatitis C Virus/Human Immunodeficiency Virus Co-infection SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INFECTED PATIENTS; MARKERS; CIRRHOSIS; INDEX; PREDICTION; VALIDATION; FIBROTEST; RATIO; SCORE; HIV AB Background & Aims: Liver fibrosis is a significant concern for patients with hepatitis C virus/human immunodeficiency virus co-infection. Fibrosis staging by biopsy is accurate, but costly and invasive. Several fibrosis prediction models using noninvasive biomarkers have been developed but are suboptimal in co-infected patients. We compared results from different staging models and ordinal regression with biopsy data. Methods: Data from the Adult Acquired Immune Deficiency Syndrome Clinical Trials Group protocol A5178 were used to evaluate 5 models of fibrosis staging; areas under receiver-operator characteristic curves (AUROC) were assessed. Individual covariates were assessed with univariable regression and then entered into an ordinal logistic regression model from which a stage-wise index was developed. Results: Data from 173 patients were evaluated; 85% were on antiretroviral therapy, 31.2% had severe fibrosis (F3/F4), and 14% had cirrhosis (F4). Differences in CD4+ cell and platelets counts and international normalized ratio values were observed between those with and without F3/F4. Among existing models, the FIB-4 index ([age X AST])/[platelet count x (ALT)(1/2)]) performed best, with 88% specificity for F4 and greater than 86% negative predictive values for F3/F4, although AUROC values were low (0.56 +/- 0.03 for F3/F4). By using patients' demographic, clinical, and laboratory data, the ordinal regression model outperformed others, with an AUROC of 0.85 (standard error, 0.03) for predicting stage F3/F4 and 0.89 (standard error, 0.05) for stage 3 alone. Conclusion : Current noninvasive methods of fibrosis assessment have poor discriminatory capacity in hepatitis C virus/human immunodeficiency virus co-infected patients. Ordinal regression analysis outperformed other noninvasive fibrosis prediction models. Longitudinal studies with paired biopsies will assist in refining the Ordinal Regression Index. C1 [Shire, Norah J.] Merck & Co Inc, Infect Dis Epidemiol, N Wales, PA 19545 USA. [Shire, Norah J.; Rao, Marepalli B.; Succop, Paul; Buncher, C. Ralph] Univ Cincinnati, Coll Med, Div Epidemiol & Biostat, Cincinnati, OH USA. [Andersen, Janet A.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Div Digest Dis, Pittsburgh, PA USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, Boston, MA 02114 USA. [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH USA. RP Shire, NJ (reprint author), Merck & Co Inc, Infect Dis Epidemiol, POB 1000,UG1D-60, N Wales, PA 19545 USA. EM Norah_shire@merck.com FU NIAID NIH HHS [U01 AI068634, U01 AI068636-01, U01 AI068636, U01 AI068634-01] NR 25 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2009 VL 7 IS 4 BP 471 EP 480 DI 10.1016/j.cgh.2008.12.016 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430RQ UT WOS:000265006600018 PM 19268724 ER PT J AU Warnick, E Auger, D AF Warnick, Elizabeth Auger, Danielle TI Management of Patients With Primary Central Nervous System Lymphoma Treated With High-Dose Methotrexate SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID PRIMARY CNS LYMPHOMA AB Primary central nervous system lymphoma (PCNSL) is a rare, extranodal form of non-Hodgkin lymphoma that most commonly presents with neurologic changes. Comprehensive workup to diagnose PCNSL and rule out nodal non-Hodgkin lymphoma is critical to the development of an appropriate plan for therapy. Past PCNSL treatments have included whole-brain radiation or steroids, but high-dose methotrexate (MTX) has emerged as initial therapy. Although high-dose MTX is well tolerated, special considerations must be taken to administer the drug safely. Specific interventions include aggressive IV hydration with sodium bicarbonate fluids, monitoring blood chemistries, and the administration of leucovorin rescue. Nurses should evaluate and monitor patients closely during treatment to ensure safety and decrease drug toxicity. C1 [Warnick, Elizabeth] W Penn Allegheny Oncol Network, Med Ctr Clin, Kittanning, PA USA. [Auger, Danielle] Dana Farber Canc Inst, Boston, MA 02115 USA. [Auger, Danielle] Tufts Med Ctr, Boston, MA USA. RP Warnick, E (reprint author), W Penn Allegheny Oncol Network, Med Ctr Clin, Kittanning, PA USA. EM ewarnick@wpaon.org NR 15 TC 1 Z9 1 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2009 VL 13 IS 2 BP 177 EP 180 DI 10.1188/09.CJON.177-180 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 432DZ UT WOS:000265115000007 PM 19349264 ER PT J AU Abdel-Kader, K Myaskovsky, L Karpov, I Shah, J Hess, R Dew, MA Unruh, M AF Abdel-Kader, Khaled Myaskovsky, Larissa Karpov, Irina Shah, Jay Hess, Rachel Dew, Mary Amanda Unruh, Mark TI Individual Quality of Life in Chronic Kidney Disease: Influence of Age and Dialysis Modality SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC-HEMODIALYSIS PATIENTS; RESPONSE SHIFT; SEIQOL-DW; RELATIVE IMPORTANCE; ADVANCED CANCER; ELDERLY-PEOPLE; UNITED-STATES; HEALTH; PATIENT; COHORT AB Background and objectives: Novel individualized quality-of-life (IQOL) measures permit patients with chronic kidney disease (CKD) to nominate unique areas of their lives that contribute to their well-being. This study assessed for differences in domains nominated by patients with CKD. We also examined the strength of association between (1) multidimensional health-related quality-of-life measures and IQOL and (2) psychosocial factors and IQOL. Design, setting, participants, & measurements: We performed a cross-sectional study of 151 patients who were undergoing peritoneal dialysis or hemodialysis or had stages 4 through 5 CKD. Patients completed the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQOL-DW), an instrument that assesses IQOL on the basis of patient-identified domains. Patients also completed health-related quality-of-life and psychosocial health measures. Results: Patients with CKD nominated many domains on the SEIQOL-DW, but family and health were the most common for all groups. Kidney disease was listed more frequently by peritoneal dialysis compared with hemodialysis patients or patients with CKD (31 versus 14 versus 5%, respectively). There were no significant differences in SEIQOL-DW scores between subgroups. SEIQOL-DW scores correlated with mental well-being and inversely correlated with chronic stress and depression. Conclusions: Patients with advanced CKD demonstrate compromised quality-of-life scores comparable to dialysis patients. IQOL measures provide unique information that may help guide interventions that are better tailored to address patients' concerns about their well-being. These findings also suggest that renal clinics should have staff available to address psychosocial aspects of patient well-being. C1 [Abdel-Kader, Khaled; Shah, Jay; Unruh, Mark] Univ Pittsburgh, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. [Myaskovsky, Larissa; Hess, Rachel] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Karpov, Irina; Dew, Mary Amanda] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [Myaskovsky, Larissa] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Abdel-Kader, K (reprint author), Univ Pittsburgh, Renal Electrolyte Div, 355C Terrace St,A909 Scaife Hall, Pittsburgh, PA 15261 USA. EM abdelkaderk@upmc.edu OI Abdel-Kader, Khaled/0000-0002-6412-8498 FU Fresenius National Kidney Foundation Young Investigator; Paul Teschan Research; National Institutes of Health [DK66006, DK77785]; Ruth L. Kirschstein National Research Service Award Institutional Research Training [T32-DK061296] FX This work was supported by Fresenius National Kidney Foundation Young Investigator Grant, Paul Teschan Research Grant, National Institutes of Health grants DK66006 and DK77785 (M.U.), and Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant T32-DK061296 (K.A.). NR 50 TC 29 Z9 29 U1 2 U2 13 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 APR PY 2009 VL 4 IS 4 BP 711 EP 718 DI 10.2215/CJN.05191008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 429RN UT WOS:000264937900009 PM 19339411 ER PT J AU Desai, AA Bolus, R Nissenson, A Chertow, GM Bolus, S Solomon, MD Khawar, OS Talley, J Spiegel, BMR AF Desai, Amar A. Bolus, Roger Nissenson, Allen Chertow, Glenn M. Bolus, Sally Solomon, Matthew D. Khawar, Osman S. Talley, Jennifer Spiegel, Brennan M. R. TI Is there "Cherry Picking" in the ESRD Program? Perceptions from a Dialysis Provider Survey SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol ID STAGE RENAL-DISEASE; PAY-FOR-PERFORMANCE; STANDARDIZED PATIENTS; CHART ABSTRACTION; NATIONAL-SURVEY; UNITED-STATES; QUALITY; CARE; PAYMENT; VIGNETTES AB Background and objectives: Changes in ESRD reimbursement policy, including proposed bundled payment, have raised concern that dialysis facilities may use "cherry picking" practices to attract a healthier, better insured, or more adherent patient population. Design, setting, participants, & measurements: As part of a national survey to measure beliefs about drivers of quality in dialysis, respondents were asked about their perceptions of cherry picking, including the frequency and effect of various cherry picking strategies on dialysis outcomes. We surveyed a random sample of 250 nurse members of the American Nephrology Nurses Association, 250 nephrologist members of the American Medical Association, 50 key opinion leaders, and 2000 physician members of the Renal Physicians Association. We tested hypothesized predictors of perception, including provider group, region, age, experience, and the main practice facility features. Results: Three-quarters of respondents reported that cherry picking occurred "sometimes" or "frequently." There were no differences in perceptions by provider or facility characteristics, insurance status, or health status. In multivariable regression, perceived cherry picking was 2.8- and 3.5-fold higher in the northeast and Midwest, respectively, versus the west. Among various cherry picking strategies, having a "low threshold to 'fire' chronic no-shows/late arrivers," and having a "low threshold to 'fire' for noncompliance with diet and meds" had the largest perceived association with outcomes. Conclusions: Under current reimbursement practices, dialysis caregivers perceive that cherry picking is common and important. An improved understanding of cherry picking practices, if evident, may help to protect vulnerable patients if reimbursement practices were to change. C1 [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Dept Med, Los Angeles, CA 90073 USA. [Desai, Amar A.; Chertow, Glenn M.; Solomon, Matthew D.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA 90073 USA. [Desai, Amar A.] Stanford Univ, Ctr Hlth Policy & Primary Care Outcomes Res, Stanford, CA 94305 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Dept Med, 11301 Wilshire Blvd,Bldg 115 Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU NIDDK NIH HHS [P30 DK041301-17, 2P30 DK 041301-17, P30 DK041301] NR 22 TC 14 Z9 14 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD APR PY 2009 VL 4 IS 4 BP 772 EP 777 DI 10.2215/CJN.05661108 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 429RN UT WOS:000264937900017 PM 19339407 ER PT J AU Costello, DJ Shields, DC Cash, SS Eskandar, EN Cosgrove, GR Cole, AJ AF Costello, D. J. Shields, D. C. Cash, S. S. Eskandar, E. N. Cosgrove, G. R. Cole, A. J. TI Consideration of epilepsy surgery in adults should be independent of age SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Refractory epilepsy; Epilepsy surgery; Older adult ID TEMPORAL-LOBE EPILEPSY; QUALITY-OF-LIFE; INTRACTABLE EPILEPSY; OLDER; LOBECTOMY; YOUNGER AB Objectives: Epilepsy surgery is performed less frequently in persons over 45 years of age than in younger individuals, probably reflecting biases among patients, referring physicians and neurologists. Methods: We report on a clinically heterogenous cohort of patients aged 45 years or older who underwent epilepsy surgery for medically intractable epilepsy. Results: Over a 15-year period, 42 patients with a mean duration of epilepsy of 27.3 years underwent elective surgery. The mean follow-up period was 48 months. Thirty-two patients had an Engel class I outcome, of which 23 were totally seizure-free (Ia). Six patients had a class II outcome (rare disabling seizures), one had a class III outcome (worthwhile improvement), and three had a class IV outcome (no worthwhile improvement). The majority of patients reported an improved quality of life and satisfaction with the epilepsy surgery. A subjective improvement in cognition was reported in 7 patients while a decline was reported in 10 patients. New neuro psychiatric difficulties were reported in three patients while three patients reported improved anxiety after surgery. Only one patient became newly employed after surgery while 23 returned to driving. Permanent complications occurred in four patients (thalamic infarct during a Wada test (n = 1) and asymptomatic visual field defect (n = 3)). Conclusions: We report a favorable outcome from epilepsy surgery in a large series of older adults and conclude that age per se is not a contraindication to epilepsy surgery. We emphasize the lack of correlation between outcome from surgery and pre-operative duration of epilepsy. (C) 2008 Elsevier B.V. All rights reserved. C1 [Costello, D. J.; Cash, S. S.; Cole, A. J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Epilepsy Serv, Boston, MA 02114 USA. [Shields, D. C.; Eskandar, E. N.] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cosgrove, G. R.] Tufts Univ, Sch Med, Lahey Clin Med Ctr, Dept Neurosurg, Burlington, MA 01805 USA. RP Costello, DJ (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Epilepsy Serv, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM djcostello@partners.org NR 22 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD APR PY 2009 VL 111 IS 3 BP 240 EP 245 DI 10.1016/j.clineuro.2008.10.005 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 424QY UT WOS:000264582800005 PM 19028008 ER PT J AU Tanev, KS Yilma, M AF Tanev, Kaloyan S. Yilma, Mimi TI An unusually presenting case of sCJD-The VV1 subtype SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Creutzfeldt-Jakob disease; Dementia; Neuroimaging; Magnetic resonance imaging; Electroencephalography; Biomarkers; Prion diseases ID CREUTZFELDT-JAKOB-DISEASE; 14-3-3 PROTEIN; CEREBROSPINAL-FLUID; CLINICAL-DIAGNOSIS; CJD; CLASSIFICATION; PROTOCOL; UTILITY AB Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease caused by prions. Typically CJD presents with a triad of rapidly progressive dementia, abnormal movements (e.g., myoclonus) and electroencephalographic (EEG) changes. Recently, CJD has been subdivided into subtypes based on host genetic polymorphisms and the characteristics of the pathological prion protein. Different subtypes likely have different clinical and laboratory presentations. We describe a case of sporadic CJD of the VV1 subtype. We describe our patient's clinical symptoms, time course, laboratory workup, structural and functional neuroimaging data, EEG data and CJD biomarkers. Our patient presented with clinical symptoms atypical for CJD. Because of that, her clinical symptoms were initially attributed to psychiatric reasons. After extensive clinical and laboratory investigation, we concluded that the patient probably had CJD. Postmortem neuropathological results confirmed this clinical hypothesis. We compare our patient's clinical, laboratory and neuroimaging data to the data on typical CJD as well as the data on the few CJD VV1 cases described in the literature. We discuss our case's relevance to the diagnosis of CJD. (C) 2008 Elsevier B.V. All rights reserved. C1 [Tanev, Kaloyan S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Yilma, Mimi] Univ Connecticut, Ctr Hlth, Farmington, CT USA. RP Tanev, KS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 1220 Blake 11, Boston, MA 02114 USA. EM ktanev@partners.org NR 32 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD APR PY 2009 VL 111 IS 3 BP 282 EP 291 DI 10.1016/j.clineuro.2008.09.017 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 424QY UT WOS:000264582800013 PM 18995952 ER PT J AU Zietman, A AF Zietman, A. TI Beams, Dreams, and Proton Schemes: How a Rampant Market Distorted Prostate Cancer Care in the US and What the UK Can Learn from it SO CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Zietman, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD APR PY 2009 VL 21 IS 3 BP 240 EP 240 PG 1 WC Oncology SC Oncology GA 429IJ UT WOS:000264913800012 ER PT J AU Kaufman, AM Abraham, JA Kattapuram, SV Hornicek, FJ AF Kaufman, Adam M. Abraham, John A. Kattapuram, Susan V. Hornicek, Francis J. TI Orthopaedic center dot Radiology center dot Pathology Conference: Chronic Multifocal Chest and Leg pain in a 34-year-old Woman SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ANTACID-INDUCED OSTEOMALACIA; PRIMARY HYPERPARATHYROIDISM; PHOSPHATE DEPLETION; ALUMINUM; BONE; METABOLISM; HYPOPHOSPHATEMIA; DIAGNOSIS; INGESTION; DIALYSIS C1 [Kaufman, Adam M.] Duke Univ Hosp, Dept Orthopaed, Durham, NC 27710 USA. [Kaufman, Adam M.] Harvard Univ, Sch Med, Boston, MA USA. [Abraham, John A.] Brigham & Womens Hosp, Dept Orthopaed, Boston, MA 02115 USA. [Kattapuram, Susan V.; Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaufman, AM (reprint author), Duke Univ Hosp, Dept Orthopaed, 200 Trent Dr,5313 Duke Clin Bldg,Box 3000, Durham, NC 27710 USA. EM Adam.Kaufman@duke.edu NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2009 VL 467 IS 4 BP 1112 EP 1117 DI 10.1007/s11999-008-0516-9 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 414MU UT WOS:000263869000036 PM 18810567 ER PT J AU Berman, RM Fava, M Thase, ME Trivedi, MH Swanink, R McQuade, RD Carson, WH Adson, D Taylor, L Hazel, J Marcus, RN AF Berman, Robert M. Fava, Maurizio Thase, Michael E. Trivedi, Madhukar H. Swanink, Rene McQuade, Robert D. Carson, William H. Adson, David Taylor, Leslie Hazel, James Marcus, Ronald N. TI Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants SO CNS SPECTRUMS LA English DT Article ID STAR-ASTERISK-D; MEASUREMENT-BASED CARE; ADJUNCTIVE THERAPY; CLINICAL-PRACTICE; SELF-REPORT; OUTPATIENTS; MEDICATION; EFFICACY; OUTCOMES; TRIALS AB Introduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials., Methods: Patients (N=1,147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day). Primary outcome was the mean change in Montgomery-angstrom sberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14). Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the (MADRS) Total score were greater with adjunctive aripiprazole (-10.1) than placebo (-6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%). Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve. depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination, were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy C1 [Berman, Robert M.; Hazel, James; Marcus, Ronald N.] Bristol Myers Squibb Co, Neurosci Global Clin Res, Wallingford, CT 06492 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Thase, Michael E.] Univ Penn, Philadelphia, PA 19104 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Sch Dallas, Mood Disorders Res Program, Dallas, TX USA. [Trivedi, Madhukar H.] Univ Texas SW Med Sch Dallas, NIMH, Depress Trials Network, Dallas, TX USA. [Adson, David] Univ Minnesota, Ambulatory Res Ctr, Minneapolis, MN USA. [Adson, David] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Taylor, Leslie] Univ Wisconsin, Sch Med, Madison, WI 53706 USA. RP Berman, RM (reprint author), Bristol Myers Squibb Co, Neurosci Global Clin Res, 5 Res Pkwy, Wallingford, CT 06492 USA. EM Robert.Berman@bms.com NR 31 TC 142 Z9 147 U1 6 U2 16 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2009 VL 14 IS 4 BP 197 EP 206 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 439YB UT WOS:000265662600007 PM 19407731 ER PT J AU Helstrom, AW Bell, ME Pineles, SL AF Helstrom, Amy W. Bell, Margret E. Pineles, Suzanne L. TI Feeling Better and Smoking Less: The Relationship Between Trauma Symptoms and Smoking Over Time SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Smoking; Trauma; PTSD; Veteran; Women ID POSTTRAUMATIC-STRESS-DISORDER; NICOTINE DEPENDENCE; ANXIETY SENSITIVITY; SUBSTANCE USE; ALCOHOL; SMOKERS AB Although it is well documented that individuals who have experienced traumatic events smoke cigarettes at significantly higher rates than individuals without exposure to trauma, the longitudinal relationship between smoking and trauma-related symptoms remains unclear. The present study examined this issue among 288 female veterans receiving treatment for trauma-related disorders over a period of up to 3 years. Consistent with previous cross-sectional research, across time points more symptomatology was associated with higher rates of smoking. Longitudinally, decreases in symptoms of negative affect over time were associated with decreases in smoking. C1 [Helstrom, Amy W.; Bell, Margret E.; Pineles, Suzanne L.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Helstrom, Amy W.; Pineles, Suzanne L.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bell, Margret E.] Off Mental Hlth Serv, Mil Sexual Trauma Support Team, Dept Vet Affairs, Boston, MA USA. RP Helstrom, AW (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B, Boston, MA 02130 USA. EM amy.helstrom@va.gov NR 21 TC 2 Z9 3 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2009 VL 33 IS 2 BP 235 EP 240 DI 10.1007/s10608-008-9183-0 PG 6 WC Psychology, Clinical SC Psychology GA 417TD UT WOS:000264100500009 ER PT J AU Chandra, D Tsai, CL Camargo, CA AF Chandra, Divay Tsai, Chu-Lin Camargo, Carlos A., Jr. TI Acute Exacerbations of COPD: Delay in Presentation and the Risk of Hospitalization SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE admission; chronic obstructive pulmonary disease; emergency department; exacerbation; late presentation; time to presentation ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; SYSTEMIC GLUCOCORTICOIDS; CONTROLLED-TRIAL; ORAL PREDNISONE; LUNG-FUNCTION; BRONCHODILATOR; PREVALENCE; OUTCOMES AB To determine if a delay in presentation to the emergency department (ED) after the onset of symptoms of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of hospital admission. A prospective cohort study utilizing data from 396 patient visits to 29 North American EDs. Inclusion criteria were age >= 55 years; a diagnosis of COPD; and presentation for treatment of AECOPD, as defined by increasing shortness of breath, worsening cough, or change in sputum production at presentation. The median age was 69 years and 54% were female. Most patients (70%) presented to the ED >24 hours after symptom onset, and most (61%) were hospitalized. On multivariate logistic regression analysis, after adjusting for 12 potential confounders (including demographics, clinical features, other diagnoses, and bronchodilator use before arrival), a delay in presentation >= 24 hours was associated with a over two-fold increase in the odds of admission (odds ratio = 2.2, 95% confidence interval 1.1-4.8). This increase in risk persisted for delay in presentation >= 12 hours in place of 24 hours, after restricting the analysis to patients admitted outside the intensive care unit, and to those reporting the ED as their usual site of care. A majority of patients delay presentation to the ED for >= 24 hours after symptom onset, and are at higher risk of hospitalization. Early presentation should be emphasized to patients and caregivers to advance efforts to decrease the morbidity, mortality, and costs of AECOPD treatment. C1 Harvard Sch Publ Hlth, Dept Epidemiol, DC C LT CAC, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, C LT CAC,Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM dchandra@hsph.harvard.edu; ctsai2@partners.org; ccamargo@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 29 TC 9 Z9 11 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD APR PY 2009 VL 6 IS 2 BP 95 EP 103 DI 10.1080/15412550902751746 PG 9 WC Respiratory System SC Respiratory System GA 447TO UT WOS:000266214900005 PM 19378222 ER PT J AU Kumar, MA Rost, NS Snider, RW Chanderraj, R Greenberg, SM Smith, EE Rosand, J AF Kumar, Monisha A. Rost, Natalia S. Snider, Ryan W. Chanderraj, Rishi Greenberg, Steven M. Smith, Eric E. Rosand, Jonathan TI Anemia and hematoma volume in acute intracerebral hemorrhage SO CRITICAL CARE MEDICINE LA English DT Article DE anemia; inflammation; blood pressure; cerebral hemorrhage; intensive care unit ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; RED-CELL TRANSFUSIONS; UREMIC PATIENTS; BLOOD-TRANSFUSION; PLATELET-FUNCTION; CRITICALLY-ILL; HEART-FAILURE; PREDICTOR AB Objective: Anemia increases risk of bleeding complications in the critically ill. In primary intracerebral hemorrhage (ICH), the most fatal type of stroke, outcome is largely dependent on the volume of hemorrhage into the brain. We investigated the relationship between anemia and clinical course of acute ICH. Methods. Six hundred ninety-four consecutive subjects were identified from an ongoing single-center prospective cohort study of nontraumatic ICH during a 6-year period. Anemia was defined according to World Health Organization criteria. Study end points were ICH volume, as measured on the baseline computed tomography scan, and 30-day mortality. Results: Anemia was present in 177 (25.8%) patients on admission. Patients with anemia were older (p = 0.005) and more likely to have coronary artery disease (p < 0.0001). In multivariable analysis, anemia (p = 0.009), lobar location of ICH (p < 0.001), white blood cell count (p < 0.001), and admission diastolic blood pressure (p < 0.001) were associated with larger ICH volume. Although after accounting for ICH volume, none of these variables was a significant predictor of 30-day mortality in multivariable analysis, the size of the marginal reduction in the odds ratio for anemia suggests that it may have a small effect on mortality through mechanisms in addition to ICH volume. Conclusions. Anemia is common in acute ICH and its presence at admission is an independent predictor of larger volume of ICH. Given the central role of ICH volume in outcome, clarification of the mechanisms underlying this relationship may offer novel therapeutic targets for reducing ICH morbidity and mortality. (Crit Care Med 2009; 37:1442-1447) C1 [Kumar, Monisha A.] Thomas Jefferson Univ, Dept Neurol, Stroke & Neurocrit Care Div, Philadelphia, PA 19107 USA. [Rost, Natalia S.; Greenberg, Steven M.; Smith, Eric E.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rost, Natalia S.; Snider, Ryan W.; Chanderraj, Rishi; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Rosand, J (reprint author), Thomas Jefferson Univ, Dept Neurol, Stroke & Neurocrit Care Div, Philadelphia, PA 19107 USA. EM jrosand@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NIH [K23 NS42695, R01 NS04217]; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX Supported, in part, by The National Institute of Neurological Disorders and Stroke (NIH K23 NS42695, R01 NS04217); Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. NR 32 TC 24 Z9 26 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 APR PY 2009 VL 37 IS 4 BP 1442 EP 1447 DI 10.1097/CCM.0b013e31819ced3a PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 426HQ UT WOS:000264699000037 PM 19242340 ER PT J AU Greer, DM AF Greer, David M. TI Multimodal magnetic resonance imaging for determining prognosis in patients with traumatic brain injury-Promising but not ready for primetime SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE diffusion tensor imaging; magnetic resonance spectroscopy; traumatic brain injury; prognosis ID PREDICTION C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Greer, DM (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2009 VL 37 IS 4 BP 1523 EP 1524 DI 10.1097/CCM.0b013e31819d2df2 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 426HQ UT WOS:000264699000067 PM 19318851 ER PT J AU Wagner, JM AF Wagner, Julia M. TI Impact of a Dedicated IV Team SO CRITICAL CARE NURSE LA English DT Meeting Abstract C1 [Wagner, Julia M.] Denver VA Med Ctr, Eastern Colorado Hlth Care Syst, Denver, CO USA. EM julia.wagner@va.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD APR PY 2009 VL 29 IS 2 MA CS83 BP E12 EP E13 PG 2 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 427JB UT WOS:000264774500033 ER PT J AU Mattagajasingh, SN Huang, SC Benz, EJ AF Mattagajasingh, Subhendra N. Huang, Shu-Ching Benz, Edward J., Jr. TI Inhibition of Protein 4.1R and NuMA Interaction by Mutagenization of Their Binding-Sites Abrogates Nuclear Localization of 4.1R SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE Protein 4.1R; NuMA; mitotic spindle; nuclear localization; mutagenesis ID MEMBRANE SKELETAL PROTEIN-4.1; IN-VITRO; CONSTITUTIVE REGION; MULTIPLE ISOFORMS; MITOTIC SPINDLE; MESSENGER-RNA; EXPRESSION; CELLS; ACTIN; SPECTRIN AB Protein 4.1R (4.1R) is a multifunctional structural protein recently implicated in nuclear assembly and cell division. We earlier demonstrated that 4.1R forms a multiprotein complex with mitotic spindle and spindle pole organizing proteins, such as NuMA, dynein, and dynactin, by binding to residues 1788-1810 of NuMA through amino acids encoded by exons 20 and 21 in 24 kD domain. Employing randomand site-directed mutagenesis combined with glycine-and alanine-scanning, we have identified amino acids of 4.1R and NuMA that sustain their interaction, and have analyzed the effect of mutating the binding sites on their intracellular colocalization. We found that V762, V765, and V767 of 4.1R, and I1800, I1801, I1803, T1804, and M1805 of NuMA are necessary for their interaction. GST-fusion peptides of the 4.1R 24 kD domain bound to residues 1785-2115 of NuMA in in vitro binding assays, but the binding was inhibited by alanine substitutions of V762, V765, and V767 of 4.1R, or residues 1800-1805 of NuMA. Additionally, expression of variants of 4.1R or NuMA that inhibit their in vitro binding also abrogated nuclear localization of 4.1R and colocalization with NuMA. Our findings suggest a crucial role of 4.1R/NuMA interaction in localization and function of 4.1R in the nucleus. C1 [Huang, Shu-Ching; Benz, Edward J., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Huang, Shu-Ching; Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mattagajasingh, Subhendra N.] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. [Benz, Edward J., Jr.] Childrens Hosp, Dept Pediat, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Benz, Edward J., Jr.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Benz, EJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Edward_benz@dfci.harvard.edu FU National Institute of Health [HL- 44985] FX We thank M. Delannoy of the Johns Hopkins University, Baltimore, MD for assistance with confocal microscopy. Th is work was supported by grant HL- 44985 from the National Institute of Health to E. J. Benz, Jr. NR 52 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD APR PY 2009 VL 2 IS 2 BP 102 EP 111 DI 10.1111/j.1752-8062.2008.00087.x PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 533RR UT WOS:000272842800008 PM 20443879 ER PT J AU Weir, GC Koulamnda, M AF Weir, Gordon C. Koulamnda, Maria TI Control of inflammation with alpha1-antitrypsin: A potential treatment for islet transplantation and new-onset type 1 diabetes SO CURRENT DIABETES REPORTS LA English DT Editorial Material ID NOD MICE; ALPHA-1-ANTITRYPSIN DEFICIENCY; THERAPY; APOPTOSIS; TOLERANCE; CURE C1 [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Koulamnda, Maria] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu NR 17 TC 8 Z9 10 U1 0 U2 0 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2009 VL 9 IS 2 BP 100 EP 102 DI 10.1007/s11892-009-0018-5 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 423DW UT WOS:000264477600001 PM 19323953 ER PT J AU Goebel-Fabbri, A AF Goebel-Fabbri, Ann E. TI Disturbed eating behaviors and eating disorders in type 1 diabetes: Clinical significance and treatment recommendations SO CURRENT DIABETES REPORTS LA English DT Article ID ADOLESCENT GIRLS; YOUNG-WOMEN; BODY-WEIGHT; COMPLICATIONS; MELLITUS; DEPRESSION; PREVALENCE; OUTCOMES; FEMALES; HABITS AB Girls and women with type 1 diabetes have increased rates of disturbed eating behaviors and clinically significant eating disorders than their nondiabetic peers. Type 1 diabetes is strongly associated with several empirically supported eating disorder risk factors (eg, higher body mass index, increased body weight and shape dissatisfaction, low self-esteem and depression, and dietary restraint). It may be that specific aspects of diabetes treatment increase the risk for developing disordered eating. Disturbed eating behaviors and clinical eating disorders predispose women with diabetes to many complex medical risks and increase risk of morbidity and mortality. For this reason, it is critical that diabetes clinicians understand more about eating disorders to improve the likelihood of early risk detection and access to appropriate treatment. This article presents a review of the current scientific literature on eating disturbances in type 1 diabetes and synthesizes the existent findings into recommendations for screening and treatment. C1 Joslin Diabet Ctr, Behav & Mental Hlth Unit, Boston, MA 02215 USA. RP Goebel-Fabbri, A (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM ann.goebel-fabbri@joslin.harvard.edu NR 30 TC 29 Z9 29 U1 3 U2 11 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2009 VL 9 IS 2 BP 133 EP 139 DI 10.1007/s11892-009-0023-8 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 423DW UT WOS:000264477600006 PM 19323958 ER PT J AU Iwata, I Munshi, M AF Iwata, Isao Munshi, Medha N. TI Cognitive and psychosocial aspects of caring for elderly patients with diabetes SO CURRENT DIABETES REPORTS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DEPRESSIVE SYMPTOMS; GLYCEMIC CONTROL; BLOOD-PRESSURE; OLDER-ADULTS; COMORBID DEPRESSION; ALZHEIMER-DISEASE; DOUBLE-BLIND; SELF-CARE; MELLITUS AB The population is aging in the United States as well as worldwide. The prevalence of diabetes increases with increasing age. To provide optimal care to older adults with diabetes, unique psychosocial barriers need to be considered by medical providers. Unlike in younger adults, cognitive dysfunction/dementia and depressive mood disorders are common coexisting conditions in older adults with diabetes. This article reviews recent literature on epidemiology and clinical implications of cognitive and psychosocial dysfunctions in older patients with diabetes. This article focuses on cognitive dysfunctions, dementia, depression, and other psychosocial stresses, and their implications in the care of older adults with diabetes. C1 [Munshi, Medha N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Geriatr Diabet Programs, Boston, MA 02215 USA. RP Munshi, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Geriatr Diabet Programs, 110 Francis St,LMOB 1B, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu FU American Diabetes Association [1-07-CR-40]; Department of Defense Peer Reviewed Medical Research Program of the Office of the Congressionally Directed Medical Research Programs [W81XWH-07-1-0282] FX The work was partly supported by a clinical research award from the American Diabetes Association, 1-07-CR-40 (for Medha Munshi), and a grant from the Department of Defense Peer Reviewed Medical Research Program of the Office of the Congressionally Directed Medical Research Programs, W81XWH-07-1-0282 (for Medha Munshi). NR 49 TC 6 Z9 6 U1 3 U2 3 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2009 VL 9 IS 2 BP 140 EP 146 DI 10.1007/s11892-009-0024-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 423DW UT WOS:000264477600007 PM 19323959 ER PT J AU Frei, CR Jaso, TC Mortensen, EM Restrepo, MI Raut, MK Oramasionwu, CU Ruiz, AD Makos, BR Ruiz, JL Attridge, RT Mody, SH Fisher, A Schein, JR AF Frei, C. R. Jaso, T. C. Mortensen, E. M. Restrepo, M. I. Raut, M. K. Oramasionwu, C. U. Ruiz, A. D. Makos, B. R. Ruiz, J. L. Attridge, R. T. Mody, S. H. Fisher, A. Schein, J. R. TI Medical resource utilization among community-acquired pneumonia patients initially treated with levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily: A US-based study SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article; Proceedings Paper CT 43rd Midyear Clinical Meeting of the American-Society-of-Health-System-Pharmacists CY DEC 07-11, 2008 CL Orlando, FL SP Amer Soc Hlth Syst Pharmacists DE Beta-lactam; Clinical practice guidelines; Community-acquired pneumonia; Fluoroquinolone; Length of stay; Macrolide ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; COMBINATION ANTIBIOTIC-THERAPY; LENGTH-OF-STAY; IN-HOSPITAL MORTALITY; ANTIMICROBIAL THERAPY; STREPTOCOCCUS-PNEUMONIAE; PROPENSITY SCORE; CONTROLLED-TRIAL; BETA-LACTAM; CARE AB Objective: The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend that community-acquired pneumonia (CAP) patients admitted to hospital wards initially receive respiratory fluoroquinolone monotherapy or beta-lactam plus macrolide combination therapy. There is little evidence as to which regimen is preferred, or if differences in medical resource utilization exist between therapies. Thus, the authors compared length of hospital stay (LOS) and length of intravenous antibiotic therapy (LOIV) for patients who received initial levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily ('combination therapy'). Research design and methods: Adult hospital CAP cases from January 2005 to December 2007 were identified by principal discharge diagnosis code. Patients with a chest infiltrate and medical notes indicative of CAP were included. Direct intensive care unit admits and healthcare-associated cases were excluded. A propensity score technique was used to balance characteristics associated with initial antimicrobial therapy using multivariable regression to derive the scores. Propensity score categories, defined as propensity score quintiles, rather than propensity scores themselves, were used in the least squares regression model to assess the impact of LOS and LOIV. Results: A total of 495 patients from six hospitals met study criteria. Of these, 313 (63%) received levofloxacin and 182 (37%) received combination therapy. Groups were similar with respect to age, sex, most comorbidities, presenting signs and symptoms, and Pneumonia Severity Index (PSI) risk class. Patients on combination therapy were more likely to have heart failure and receive pre-admission antibiotics. Adjusted least squares mean (+/- SE) LOS and LOIV were shorter with levofloxacin versus combination therapy: LOS, 4.6 +/- 0.17 vs. 5.4 +/- 0.22 days, p<0.01; and LOIV, 3.6 +/- 0.17 vs. 4.8 +/- 0.21 days, p<0.01. Results for PSI risk class III or IV patients were: LOS, 5.0 +/- 0.30 vs. 5.9 +/- 0.37 days, p=0.07; and LOIV, 3.7 +/- 0.33 vs. 5.2 +/- 0.39 days, p<0.01. Due to the retrospective study design, limited sample size, and scope (single health-network), the authors encourage replication of this study in other data sources. Conclusions: Given the LOS and LOIV reductions of 0.8 and 1.2 days, respectively, utilization of levofloxacin 750 mg daily for CAP patients admitted to the medical floor has the potential to result in substantial cost savings for US hospitals. C1 [Frei, C. R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Frei, C. R.; Oramasionwu, C. U.; Ruiz, A. D.; Makos, B. R.; Ruiz, J. L.; Attridge, R. T.] Univ Texas Austin, Austin, TX 78712 USA. [Jaso, T. C.] Seton Family Hosp, Austin, TX USA. [Mortensen, E. M.; Restrepo, M. I.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Raut, M. K.; Mody, S. H.; Fisher, A.; Schein, J. R.] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Pharmacotherapy Educ & Res Ctr, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM freic@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 NR 54 TC 10 Z9 13 U1 0 U2 5 PU LIBRAPHARM/INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4 LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD APR PY 2009 VL 25 IS 4 BP 859 EP 868 DI 10.1185/03007990902779749 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 444HC UT WOS:000265970300006 PM 19231913 ER PT J AU Jia, SD Roberts, TM Zhao, JJ AF Jia, Shidong Roberts, Thomas M. Zhao, Jean J. TI Should individual PI3 kinase isoforms be targeted in cancer? SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID 3-KINASE CATALYTIC SUBUNIT; MAMMARY EPITHELIAL-CELLS; TUMOR-SUPPRESSOR GENE; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; BREAST-CANCER; P110-ALPHA ISOFORM; ONCOGENIC TRANSFORMATION; PIK3CA MUTATIONS; MEDIATED TRANSFORMATION AB Activation of the phosphoinositide-3-kinase (PI3K) signaling pathway is frequently found in common human cancers, brought about by oncogenic receptor tyrosine kinases (RTKs) acting upstream, PTEN loss, or activating mutations of PI3K itself. Recent studies have delineated distinct but overlapping functions in cell signaling and tumorigenesis for p110 alpha and p110 beta, the two major catalytic subunits of PI3K expressed in the tissues of origin for the common tumor types. In most cell types studied, p110 alpha carries the majority of the PI3K signal in classic RTK signal transcluction, while p110 beta responds to GPCRs. Both p11 alpha and p110 beta function in cellular transformation induced by alterations in components of PI3K pathway. Specifically, p110 alpha is essential for the signaling and growth of tumors driven by PIK3CA mutations and/or oncogenic RTKs/Ras, whereas p110 beta is the major isoform in mediating PTEN-deficient tumorigenesis. While pan-PI3K inhibitors are currently being tested in the clinic, p110 isoform-specific inhibition holds promise as a therapeutic strategy. C1 [Jia, Shidong; Roberts, Thomas M.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jia, Shidong; Roberts, Thomas M.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zhao, Jean J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU NCI NIH HHS [P01 CA089021-07, CA050661, CA089021, P01 CA050661, P01 CA050661-20, P01 CA089021, R01 CA030002, R01 CA030002-28, R01 CA134502, R01 CA134502-01] NR 78 TC 78 Z9 81 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2009 VL 21 IS 2 BP 199 EP 208 DI 10.1016/j.ceb.2008.12.007 PG 10 WC Cell Biology SC Cell Biology GA 441MK UT WOS:000265773000009 PM 19200708 ER PT J AU Eck, MJ Manley, PW AF Eck, Michael J. Manley, Paul W. TI The interplay of structural information and functional studies in kinase drug design: insights from BCR-Abl SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURES; PROTEIN-KINASES; HUMAN CANCER; MAP KINASE; INHIBITORS; IMATINIB AB As an inhibitor of the tyrosine kinase activity of the BCR-Abl oncoprotein, imatinib sets a new paradigm for the treatment of cancer with molecularly targeted therapies. Subsequent structural studies have provided in depth knowledge of how this antileukaemia drug interacts with the catalytic site of the enzyme and allowed the rationalisation of mechanisms of drug-resistance which can lead to patient relapse. This understanding has facilitated the design of new inhibitors of BCR-Abl, as well as the discovery of inhibitors of many other kinases. As structural information accumulates for more of the 518 kinases encoded within the human genome, the design of many more highly selective, well-tolerated kinase inhibitors should be possible. C1 [Manley, Paul W.] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. [Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Manley, PW (reprint author), Novartis Inst Biomed Res, WKL-136-4-86, CH-4002 Basel, Switzerland. EM paul.manley@novartis.com NR 49 TC 28 Z9 30 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 2009 VL 21 IS 2 BP 288 EP 295 DI 10.1016/j.ceb.2009.01.014 PG 8 WC Cell Biology SC Cell Biology GA 441MK UT WOS:000265773000019 PM 19217274 ER PT J AU Majithia, AR Florez, JC AF Majithia, Amit R. Florez, Jose C. TI Clinical translation of genetic predictors for type 2 diabetes SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE genome-wide association; pharmacogenetics; risk prediction; type 2 diabetes ID GENOME-WIDE ASSOCIATION; PLASMA-GLUCOSE LEVELS; SULFONYLUREA RECEPTOR; INCREASED RISK; E23K VARIANT; PRO12ALA POLYMORPHISM; INSULIN SENSITIVITY; COMMON VARIANTS; LOCI; SUSCEPTIBILITY AB Purpose of review To highlight recent type 2 diabetes (T2D)-associated genetic discoveries and their potential for clinical application. Recent findings The advent of genome-wide association screening has uncovered many loci newly associated with T2D. This review describes the techniques applied to discover novel T2D genes and compares their relative strengths, biases, and findings to date. The results of large-scale genome-wide association studies carried out since 2007 are summarized, and limitations of interpreting this preliminary data are offered. Recent studies exploring the clinical potential of these discoveries are reviewed, focusing on insights into T2D pathogenesis, risk prediction of future diabetes, and utility in guiding pharmacotherapy. The new T2D-associated loci have been implicated in beta-cell development and function, highlighting insulin secretion in the disease process. Preliminary risk prediction studies show that more loci are needed to improve T2D risk indices. Studies have also revealed that genes may play a role in the pharmacologic response to antidiabetic medications. Summary Since 2007, genome-wide association studies have rapidly increased the number of T2D-associated loci. This review summarizes the history of genetic association studies, the results from the new genome-wide association studies, and the clinical application of these findings. C1 [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Majithia, Amit R.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Majithia, Amit R.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Majithia, Amit R.; Florez, Jose C.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Simches Res Bldg,CPZN 5-250,185 Cambridge St, Boston, MA 02114 USA. EM jcflorez@partners.org FU National Institutes of Health [K23 DK65978-05]; Massachusetts General Hospital; Doris Duke Charitable Foundation FX Dr Florez is supported by National Institutes of Health Research Career Award K23 DK65978-05, a Physician Scientist Development Award, by the Massachusetts General Hospital, and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. Dr Florez has received consulting honoraria from Merck, bioStrategies, XOMA, and Publicis Healthcare Communications Group, a global advertising agency engaged by Amylin Pharmaceuticals. NR 50 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD APR PY 2009 VL 16 IS 2 BP 100 EP 106 DI 10.1097/MED.0b013e3283292354 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691BP UT WOS:000285055600002 PM 19306524 ER PT J AU Frachetti, KJ Goldfine, AB AF Frachetti, Katherine J. Goldfine, Allison B. TI Bariatric surgery for diabetes management SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE bariatric surgery; obesity; type 2 diabetes mellitus ID GASTRIC-BYPASS-SURGERY; MORBIDLY OBESE SUBJECTS; GLUCAGON-LIKE PEPTIDE-1; LONG-TERM MORTALITY; WEIGHT-LOSS; SURGICAL-PROCEDURES; PLASMA GHRELIN; LIFE-STYLE; HYPOGLYCEMIA; OVERWEIGHT AB Purpose of review To review the role of bariatric surgery in the treatment of patients with type 2 diabetes. Recent findings Multiple studies demonstrate that bariatric surgical approaches to obesity lead to substantial and sustained weight loss. Patients with diabetes have remission of hyperglycemia or require reduced medications. Surgical intervention for patients with more recent diabetes onset may have higher rates of resolution than patients with longer duration disease. In addition, dyslipidemia and hypertension improve. A short-term randomized clinical trial comparing laproscopic banding with optimal medical management suggests surgery leads to more improvement in multiple metabolic measures. Perioperative risk is low and observational studies suggest long-term survival is favorable for obese patients following bariatric surgery. Metabolic risks of bariatric procedures are reviewed. Summary Although there are several surgical approaches for weight management, improvements in diabetes, including achievement of near normal glycemia without medication or reduced medications, are realized in many patients. Early surgical intervention for overweight type 2 diabetes may be clinically appropriate in patients for in whom operative risks are acceptable. C1 [Frachetti, Katherine J.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Frachetti, Katherine J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu NR 42 TC 12 Z9 12 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD APR PY 2009 VL 16 IS 2 BP 119 EP 124 DI 10.1097/MED.0b013e32832912e7 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691BP UT WOS:000285055600005 PM 19276974 ER PT J AU Nyendak, MR Lewinsohn, DA Lewinsohn, DM AF Nyendak, Melissa R. Lewinsohn, Deborah A. Lewinsohn, David M. TI New diagnostic methods for tuberculosis SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE diagnosis; immunological tests; molecular probes; tuberculosis ID ACID AMPLIFICATION TESTS; BLOOD INTERFERON-GAMMA; MEDIATED ISOTHERMAL AMPLIFICATION; DRUG-SUSCEPTIBILITY ASSAY; MULTIDRUG-RESISTANT TUBERCULOSIS; POLYMERASE-CHAIN-REACTION; ENZYME-LINKED IMMUNOSPOT; HIV-INFECTED PATIENTS; LINE PROBE ASSAY; CELL-BASED ASSAY AB Purpose of review During the last decade. laboratory tests for the detection of Mycobacterium tuberculosis (Mtb) have improved dramatically. Improvements in the ability to detect latent infection with Mtb. disease associated with Mtb, and strains resistant to commonly used antibiotics are reviewed. Recent findings Advances in the detection of Mtb include light-emitting diode fluorescence microscopy, nucleic acid amplification of Mtb and drug-resistant strains, and more rapid liquid culture with adjunct drug susceptibility testing. In the detection of latent tuberculosis infection, gamma release assays offer improved accuracy over the tuberculin skin test. interferon Summary The past 10 years have seen the most rapid growth in new diagnostics for Mtb in over a century. Although these tests offer improvements in the ability to detect Mtb, drug-resistant isolates. and those with latent tuberculosis infection, these improvements are counter-balanced by the need to deploy these tests in areas where Mtb burden is highest. C1 [Lewinsohn, David M.] Portland VA Med Ctr, Div Pulm & Crit Care Med, Pulmonary & CCM, Portland, OR 97239 USA. [Nyendak, Melissa R.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. [Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Div Pediat Infect Dis, Portland, OR 97201 USA. RP Lewinsohn, DM (reprint author), Portland VA Med Ctr, Div Pulm & Crit Care Med, Pulmonary & CCM, R&D 11,3710 SW US Vet Rd, Portland, OR 97239 USA. EM lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIH/NCRR [5 KL2 RR024141-03]; NIH [N01-A1-400081, RO1 A1054474, RO1A148090] FX This work is funded by grants NIH/NCRR 5 KL2 RR024141-03 to Melissa R. Nyendak, NIH HHSN266200400081C (N01-A1-400081), RO1 A1054474 to Deborah A. Levvinsohn, and VA Merit Review Grant, Portland VA Medical Center, NIH HHSN266200400081C (N01-A1-400081). RO1A148090 to David M. Lewinsohn. NR 100 TC 38 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD APR PY 2009 VL 22 IS 2 BP 174 EP 182 DI 10.1097/QCO.0b013e3283262fe9 PG 9 WC Infectious Diseases SC Infectious Diseases GA 429YI UT WOS:000264955600014 PM 19283913 ER PT J AU Delmonico, FL AF Delmonico, Francis L. TI The implications of Istanbul Declaration on organ trafficking and transplant tourism SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE implications Istanbul Declaration; organ trafficking; transplant tourism; transplant commercialism AB Purpose of review Organ trafficking, transplant tourism and transplant commercialism are now defined by the Declaration of Istanbul; the Declaration provides principles of practice based on those definitions. Organ trafficking and transplant tourism should be prohibited because they violate the principles of equity, justice and respect for human dignity. Recent findings This report provides a country-by-country description of current events that may effect the practice of transplantation internationally for the foreseeable future. Summary The implications of the Istanbul Declaration are profound. It calls for a legal and professional framework in each country to govern organ donation and transplantation activities. It calls for a transparent regulatory oversight system that ensures donor and recipient safety and enforces the prohibitions of unethical practices. Governments should ensure the provision of care and follow-up of living donors be no less than the care and attention provided for transplants recipients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr Boston, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr Boston, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 5 TC 28 Z9 29 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2009 VL 14 IS 2 BP 116 EP 119 DI 10.1097/MOT.0b013e32832917c9 PG 4 WC Transplantation SC Transplantation GA 436HC UT WOS:000265402300002 PM 19300258 ER PT J AU Newton, AW Vandeven, AM AF Newton, Alice W. Vandeven, Andrea M. TI Update on child maltreatment SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE child abuse; child maltreatment; child sexual abuse; neglect; pediatric condition falsification; shaken baby syndrome; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; SHAKEN-BABY-SYNDROME; NONACCIDENTAL HEAD-INJURY; OPTICAL COHERENCE TOMOGRAPHY; SEXUAL-ABUSE; SKELETAL SURVEYS; PHYSICAL ABUSE; YOUNG-CHILDREN; PREVENTION; POPULATION AB Purpose of review The authors explore the literature published in the past year addressing child maltreatment issues, including sexual abuse, physical child abuse, inflicted head trauma, and child abuse prevention. Recent findings The body of knowledge about child abuse and its mimics continues to expand. Evident in this year's literature is the challenge which the diagnosis of child abuse creates for clinicians. Although further strides are being made toward universal education of providers, it is clear that there is still a reluctance to report abuse to child welfare agencies. The legal repercussions of diagnosing abuse can be extensive, and there has been a proliferation of medical defense experts who disagree with the commonly accepted tenets of abusive injury and who are vocal in the literature. Summary It remains the responsibility of pediatric providers to consider child maltreatment in the differential diagnosis of any unexplained injury or medical problem. Several studies document the high rate of spanking, slapping or shaking children, and primary care clinicians may be the first professionals in a position to begin the evaluation for possible child maltreatment. Despite the natural hesitancy to diagnose abuse, clinicians have an ethical and moral obligation to address this issue both in their practice and in their communities. The short-term and long-term costs to individuals who experience family violence have been well demonstrated and include not only emotional repercussions, but also chronic health conditions, which result in significant cost to society. C1 [Newton, Alice W.] Harvard Univ, Massachusetts Gen Hosp, Childrens Hosp,Dept Pediat,Med Sch, Child Protect Program,Child Protect Consultat Pro, Boston, MA 02115 USA. [Vandeven, Andrea M.] Univ Missouri, Dept Pediat, Kansas City CARE Program, Childrens Mercy Hosp, Kansas City, MO 64110 USA. RP Newton, AW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Childrens Hosp,Dept Pediat,Med Sch, Child Protect Program,Child Protect Consultat Pro, 300 Longwood Ave, Boston, MA 02115 USA. EM alice.newton@childrens.harvard.edu NR 71 TC 5 Z9 5 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2009 VL 21 IS 2 BP 252 EP 261 DI 10.1097/MOP.0b013e328329263d PG 10 WC Pediatrics SC Pediatrics GA 435CL UT WOS:000265320900014 PM 19300263 ER PT J AU Petryshen, TL Pauls, DL AF Petryshen, Tracey L. Pauls, David L. TI The Genetics of Reading Disability SO CURRENT PSYCHIATRY REPORTS LA English DT Article AB Genetic factors contribute substantially to the development of reading disability (RD). Family linkage studies have implicated many chromosomal regions containing RD susceptibility genes, of which putative loci at 1p34-p36 (DYX8), 2p (DYX3), 6p21.3 (DYX2), and 15q21 (DYX1) have been frequently replicated, whereas those at 3p12-q12 (DYX5), 6q13-q16 (DYX4), 11p15 (DYX7), 18p11 (DYX6), and Xq27 (DYX9) have less evidence. Association studies of positional candidate genes have implicated DCDC2 and KIAA0319 in DYX2, as well as C2ORF3 and MRPL19 (DYX3), whereas DYX1C1/EKN1 (DYX1) and ROBO1 (DYX5) were found to be disrupted by rare translocation breakpoints in reading-disabled individuals. Four of the candidate genes (DYX1C1, KIAA0319, DCDC2, and ROBO1) appear to function in neuronal migration and guidance, suggesting the importance of early neurodevelopmental processes in RD. Future studies to help us understand the function of these and other RD candidate genes promise to yield enormous insight into the neurobiologic mechanisms underlying the pathophysiology of this disorder. C1 [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu NR 52 TC 10 Z9 11 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD APR PY 2009 VL 11 IS 2 BP 149 EP 155 PG 7 WC Psychiatry SC Psychiatry GA V16XI UT WOS:000207901900009 PM 19302769 ER PT J AU Timpano, KR Buckner, JD Richey, JA Murphy, DL Schmidt, NB AF Timpano, Kiara R. Buckner, Julia D. Richey, J. Anthony Murphy, Dennis L. Schmidt, Norman B. TI EXPLORATION OF ANXIETY SENSITIVITY AND DISTRESS TOLERANCE AS VULNERABILITY FACTORS FOR HOARDING BEHAVIORS SO DEPRESSION AND ANXIETY LA English DT Article DE compulsive hoarding; anxiety sensitivity; distress tolerance ID OBSESSIVE-COMPULSIVE DISORDER; PERSONALITY-DISORDER; PANIC DISORDER; DISCOMFORT INTOLERANCE; DIMENSIONS; DEPRESSION; VALIDATION; INVENTORY; GENETICS; THERAPY AB Background: The phenomenon of compulsive boarding, characterized by the acquisition of and failure to discard a large number of possessions, is increasingly recognized as a significant public health burden. Despite the magnitude of the impairment associated with this condition, empirical research is still in the nascent stages and many facets of the phenomenology, underlying vulnerability and risk factors for boarding, are as of yet unknown. Method: The overall aim of the current investigation was to examine the association between boarding behaviors and two potential vulnerability factors-anxiety sensitivity (AS) and distress tolerance (DT). In addition, we investigated the robustness of these associations as well as the interaction between the two hypothesized risk factors. Three studies (total N = 745) involving independent nonclinical samples assessed hoarding, AS, DT, and relevant covariates using a range of measures. Results: Findings revealed that AS and boarding are significantly and robustly associated with one another beyond general depressive, anxiety, and nonhoarding obsessive-compulsive symptoms. Hoarding was also found to be associated with low DT Consistent with prediction, AS and DT interacted such that DT may play a less important role among individuals with low AS. By contrast, low DT appears to increase vulnerability to boarding symptoms among individuals high in AS. Results are discussed with regard to future research and treatment implications. Depression and Anxiety 26:343-353, 2009. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Richey, J. Anthony; Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Timpano, Kiara R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Julia D.] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schmidt, NB (reprint author), Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. EM schmidt@psy.fsu.edu RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722 FU National Institute of Mental Health [F31 MH080467-01A1]; National Institute of Drug Abuse [F31 DA12457-01]; NIH [RO1 MH064734-04al, P50 HD052120, R21 MH62056] FX This research was partially supported in part by National Research Service Awards from the National Institute of Mental Health F31 MH080467-01A1 (Timpano) and the National Institute of Drug Abuse F31 DA12457-01 (Buckner) as well as NIH awards RO1 MH064734-04al, P50 HD052120, and R21 MH62056 (Schmidt). NR 60 TC 52 Z9 52 U1 5 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2009 VL 26 IS 4 BP 343 EP 353 DI 10.1002/da.20469 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 430QD UT WOS:000265002700007 PM 19123454 ER PT J AU Nery, FG Hatch, JP Nicoletti, MA Monkul, ES Najt, P Matsuo, K Cloninger, CR Soares, JC AF Nery, Fabiano G. Hatch, John P. Nicoletti, Mark A. Monkul, E. Serap Najt, Pablo Matsuo, Koji Cloninger, C. Robert Soares, Jair C. TI TEMPERAMENT AND CHARACTER TRAITS IN MAJOR DEPRESSIVE DISORDER: INFLUENCE OF MOOD STATE AND RECURRENCE OF EPISODES SO DEPRESSION AND ANXIETY LA English DT Article DE major depressive disorder; anxiety disorders; personality; temperament; character; psychopathology ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; BIPOLAR DISORDER; UNIPOLAR DEPRESSION; INVENTORY; DIMENSIONS; ANXIETY; OUTPATIENTS; ISSUES AB Background: The objective of this study was to compare personality traits between major depressive disorder (MDD) patients and healthy comparison subjects (HC) and examine if personality traits in patients are associated with specific clinical characteristics of the disorder. Methods: Sixty MDD patients (45 depressed, 15 remitted) were compared to 60 HC using the Temperament and Character Inventory. Analysis of covariance, with age and gender as covariates, was used to compare the mean Temperament and Character Inventory scores among the subject groups. Results: Depressed MDD patients scored significantly higher than HC on novelty seeking, harm avoidance, and self-transcendence and lower on reward dependence, self-directedness, and cooperativeness. Remitted MDD patients scored significantly lower than HC only on self-directedness. Comorbidity with anxiety disorder had a main effect only on harm avoidance. Harm avoidance was positively correlated with depression intensity and with number of episodes. Self-directedness bad an inverse correlation with depression intensity. Conclusions: MDD patients present a different personality profile from HC, and these differences are influenced by mood state and comorbid anxiety disorders. When considering patients who have been in remission for some time, the differences pertain to few personality dimensions. Cumulated number of depressive episodes may result in increased harm avoidance. Depression and Anxiety 26.382-388, 2009. (c) 2009 Wiky-Liss, Inc. C1 [Nicoletti, Mark A.; Soares, Jair C.] Univ N Carolina, Dept Psychiat, CERT BD, Sch Med, Chapel Hill, NC 27599 USA. [Nery, Fabiano G.; Hatch, John P.; Monkul, E. Serap; Najt, Pablo; Matsuo, Koji] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nery, Fabiano G.; Monkul, E. Serap; Najt, Pablo; Matsuo, Koji] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Nery, Fabiano G.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Hatch, John P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. [Cloninger, C. Robert] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Soares, JC (reprint author), Univ N Carolina, Dept Psychiat, CERT BD, Sch Med, 10616 Neurosci Hosp CB 7160, Chapel Hill, NC 27599 USA. EM jsoares@med.unc.edu RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 FU UTHSCSA GCRC [M01-RR-01346]; NARSAD; Krus Endowed Chair in Psychiatry (UTHSCSA); Veterans Administration; American Foundation for Suicide Prevention (ASFP); [MH 01736]; [MH 068662] FX This research was partly supported by grants MH 01736, MH 068662, UTHSCSA GCRC (M01-RR-01346), NARSAD, the Krus Endowed Chair in Psychiatry (UTHSCSA), the Veterans Administration (VA Merit Review), and the American Foundation for Suicide Prevention (ASFP). The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this article. NR 31 TC 37 Z9 38 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2009 VL 26 IS 4 BP 382 EP 388 DI 10.1002/da.20478 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 430QD UT WOS:000265002700011 PM 19195006 ER PT J AU Asarch, A Chiu, A Kimball, AB Dellavalle, RP AF Asarch, Adam Chiu, Annie Kimball, Alexa B. Dellavalle, Robert P. TI Survey Research in Dermatology: Guidelines for Success SO DERMATOLOGIC CLINICS LA English DT Article DE Dermatology; Survey research; Response rate; Questionnaire design; Reporting survey results ID QUALITY-OF-LIFE; BASAL-CELL CARCINOMA; CHRONIC SKIN-DISEASE; RESPONSE RATES; MAILED QUESTIONNAIRES; MONETARY INCENTIVES; ATOPIC-DERMATITIS; PSORIATIC-ARTHRITIS; CUTANEOUS MELANOMA; TREATMENT PATTERNS AB Survey research has been used to investigate a wide range of issues in dermatology. The proper use of survey design and analysis is critical for achieving reliable, accurate data and high impact in the medical literature. Here we describe the use of surveys from both a theoretical and practical standpoint. We provide recommendations for limiting error and producing interpretable results, followed by an outline for achieving publication. We conclude with a discussion of previous successful uses of survey studies in dermatologic literature. C1 [Dellavalle, Robert P.] Colorado Sch Publ Hlth, Aurora, CO 80045 USA. [Asarch, Adam] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Chiu, Annie] Cedars Sinai Med Grp, Beverly Hills, CA 90211 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, CURTIS, Boston, MA 02114 USA. [Kimball, Alexa B.] Brigham & Womens Hosp, CURTIS, Boston, MA 02114 USA. [Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Denver, CO 80045 USA. [Dellavalle, Robert P.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80045 USA. [Dellavalle, Robert P.] Dept Vet Affairs Med Ctr, Dermatol Serv, Denver, CO 80220 USA. RP Dellavalle, RP (reprint author), Colorado Sch Publ Hlth, 13001 E 17th Pl,Campus Box B119, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 59 TC 5 Z9 5 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 0733-8635 EI 1558-0520 J9 DERMATOL CLIN JI Dermatol. Clin. PD APR PY 2009 VL 27 IS 2 BP 121 EP + DI 10.1016/j.det.2008.11.001 PG 12 WC Dermatology SC Dermatology GA 429PT UT WOS:000264933300007 PM 19254655 ER PT J AU Jambusaria-Pahlajani, A Miller, CJ Quon, H Smith, N Klein, RQ Schmults, CD AF Jambusaria-Pahlajani, Anokhi Miller, Christopher J. Quon, Harry Smith, Nananamibia Klein, Rhonda Quain Schmults, Chrysalyne Delling TI Surgical Monotherapy Versus Surgery Plus Adjuvant Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma: A Systematic Review of Outcomes SO DERMATOLOGIC SURGERY LA English DT Review ID MOHS MICROGRAPHIC SURGERY; CHRONIC LYMPHOCYTIC-LEUKEMIA; LOWER LIP; PERINEURAL INVASION; RETROSPECTIVE ANALYSIS; PROGNOSTIC-FACTORS; LOCAL RECURRENCE; NECK DISSECTION; SCAR CARCINOMA; EXTERNAL EAR AB Adjuvant radiotherapy (ART) has been recommended for squamous cell carcinoma (SCC) with a high risk of recurrence, particularly perineurally invasive disease. The utility of ART is unknown. This study compares reported outcomes of high-risk SCC treated with surgical monotherapy (SM) with those of surgery plus ART (S+ART). The Medline database was searched for reports of high-risk SCC treated with SM or S+ART that reported outcomes of interest: local recurrence, regional or distant metastasis, or disease-specific death. There were no controlled trials. Of the 2,449 cases of high-risk SCC included, 91 were treated with S+ART. Tumor stage and surgical margin status before ART were generally unreported. In 74 cases of perineural invasion (PNI), outcomes were statistically similar between SM and S+ART. In 943 high-risk SCC cases in which clear surgical margins were explicitly documented, risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death were 5%, 5%, 1%, and 1%, respectively. High cure rates are achieved in high-risk cutaneous SCC when clear surgical margins are obtained. Current data are insufficient to identify high-risk features in which ART may be beneficial. In cases of PNI, the extent of nerve involvement appears to affect outcomes, with involvement of larger nerves imparting a worse prognosis. The authors have indicated no significant interest with commercial supporters. C1 [Schmults, Chrysalyne Delling] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Jambusaria-Pahlajani, Anokhi; Miller, Christopher J.] Univ Penn, Dept Dermatol, Div Dermatol Surg, Philadelphia, PA 19104 USA. [Jambusaria-Pahlajani, Anokhi; Schmults, Chrysalyne Delling] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Quon, Harry] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Quon, Harry] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Smith, Nananamibia] Univ Rochester, Dept Dermatol, Sch Med, Rochester, NY 14627 USA. [Klein, Rhonda Quain] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. RP Schmults, CD (reprint author), Dana Farber Brigham & Womens Canc Ctr, Mohs Microg Surg Ctr, 1153 Ctr St,Suite 4349, Jamaica Plain, MA 02130 USA. EM cschmults@partners.org NR 69 TC 48 Z9 48 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD APR PY 2009 VL 35 IS 4 BP 574 EP 585 DI 10.1111/j.1524-4725.2009.01095.x PG 12 WC Dermatology; Surgery SC Dermatology; Surgery GA 429YJ UT WOS:000264955700002 PM 19415791 ER PT J AU Vanderzalm, PJ Pandey, A Hurwitz, ME Bloom, L Horvitz, HR Garriga, G AF Vanderzalm, Pamela J. Pandey, Amita Hurwitz, Michael E. Bloom, Laird Horvitz, H. Robert Garriga, Gian TI C. elegans CARMIL negatively regulates UNC-73/Trio function during neuronal development SO DEVELOPMENT LA English DT Article DE Cell migration; Axon guidance; Rac GTPase; CARMIL (Lrrc16a); Trio; Robo ID NEMATODE CAENORHABDITIS-ELEGANS; GROWTH CONE MIGRATIONS; ACTIN-CAPPING PROTEIN; CONTROL AXON GUIDANCE; CELL-MIGRATION; RAC ACTIVATION; SH3 DOMAIN; MYOSIN-I; RECEPTOR; MIDLINE AB Whereas many molecules that promote cell and axonal growth cone migrations have been identified, few are known to inhibit these processes. In genetic screens designed to identify molecules that negatively regulate such migrations, we identified CRML-1, the C. elegans homolog of CARMIL. Although mammalian CARMIL acts to promote the migration of glioblastoma cells, we found that CRML-1 acts as a negative regulator of neuronal cell and axon growth cone migrations. Genetic evidence indicates that CRML-1 regulates these migrations by inhibiting the Rac GEF activity of UNC-73, a homolog of the Rac and Rho GEF Trio. The antagonistic effects of CRML-1 and UNC-73 can control the direction of growth cone migration by regulating the levels of the SAX-3 ( a Robo homolog) guidance receptor. Consistent with the hypothesis that CRML-1 negatively regulates UNC-73 activity, these two proteins form a complex in vivo. Based on these observations, we propose a role for CRML-1 as a novel regulator of cell and axon migrations that acts through inhibition of Rac signaling. C1 [Vanderzalm, Pamela J.; Pandey, Amita; Garriga, Gian] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Hurwitz, Michael E.; Bloom, Laird; Horvitz, H. Robert] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Hurwitz, Michael E.; Bloom, Laird; Horvitz, H. Robert] MIT, Dept Biol, Cambridge, MA 02139 USA. [Hurwitz, Michael E.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. [Garriga, Gian] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Garriga, G (reprint author), Univ Calif Berkeley, Berkeley, CA 94720 USA. EM garriga@berkeley.edu FU National Institutes of Health [NS32057, K08 CA-104890, GM24663]; NSF FX We thank Rob Steven and Terry Kubiseski for the anti-UNC-73 antibody and advice; Lianna Wong for C. elegans cDNAs; Chun-Liang Pan for the pCL8 plasmid; Andy Fire for expression vectors; Steve Ruzin and the UC Berkeley College of Natural Resources Biological Imaging Center for help in quantifying CAN GFP levels; Yishi Jin and the C. elegans Genetics Center for some of the strains used in this study; Matt Vanderzalm for assistance with the figures; Richard Ikegami and Hector Aldaz for constructive comments on the manuscript; and members of the Garriga, Dernburg and Meyer labs for helpful discussions. This work was supported by National Institutes of Health grants NS32057 ( G. G.), K08 CA-104890 ( M. E. H.) and GM24663 ( H. R. H.). H. R. H. is an Investigator of the Howard Hughes Medical Institute. P.J.V. was supported by an NSF predoctoral fellowship. Deposited in PMC for release after 6 months. NR 48 TC 17 Z9 20 U1 0 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD APR 1 PY 2009 VL 136 IS 7 BP 1201 EP 1210 DI 10.1242/dev.026666 PG 10 WC Developmental Biology SC Developmental Biology GA 422BN UT WOS:000264402100015 PM 19244282 ER PT J AU Wuelling, M Kaiser, FJ Buelens, LA Braunholz, D Shivdasani, RA Depping, R Vortkamp, A AF Wuelling, Manuela Kaiser, Frank J. Buelens, Laetitia A. Braunholz, Diana Shivdasani, Ramesh A. Depping, Reinhard Vortkamp, Andrea TI Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Chondrocyte differentiation; Proliferation; Endochondral ossification; Tricho-Rhino-Phalangeal-syndrome; Indian hedgehog signaling; Gli3 transcription factor ID PTH-RELATED-PROTEIN; SYNDROME TYPE-I; INDIAN-HEDGEHOG; TRANSCRIPTIONAL REPRESSION; TRICHORHINOPHALANGEAL SYNDROME; PTH/PTHRP-RECEPTOR; FINGER PROTEIN; BONE-FORMATION; GROWTH; MOUSE AB Trps1, the gene mutated in human Tricho-Rhino-Phalangeal syndrome, represents an atypical member of the GATA-family of transcription factors. Here we show that Trps1 interacts with Indian hedgehog (Ihh)/Gli3 signaling and regulates chondrocyte differentiation and proliferation. We demonstrate that Trps1 specifically binds to the transactivation domain of Gli3 in vitro and in vivo, whereas the repressor form of Gli3 does not interact with Trps1. A domain of 185aa within Trps1, containing three predicted zinc fingers, is sufficient for interaction with GIB. Using different mouse models we find that in distal chondrocytes Trps1 and the repressor activity of GIB are required to expand distal cells and locate the expression domain of Parathyroid hormone related peptide. In Columnar proliferating chondrocytes Trps1 and Ihh/Gli3 have an activating function. The differentiation of columnar and hypertrophic chondrocytes is Supported by TFPSI independent of Gli3. Trps1 seems thus to organize chondrocyte differentiation interacting with different subsets of co-factors in distinct cell types. (C) 2009 Elsevier Inc. All rights reserved. C1 [Wuelling, Manuela; Buelens, Laetitia A.; Vortkamp, Andrea] Univ Duisburg Essen, Dept Dev Biol, Ctr Med Biotechnol, D-45117 Essen, Germany. [Kaiser, Frank J.; Braunholz, Diana] Med Univ Lubeck, Inst Human Genet, D-23538 Lubeck, Germany. [Depping, Reinhard] Med Univ Lubeck, Ctr Struct & Cell Biol Med, Dept Physiol, D-23528 Lubeck, Germany. [Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vortkamp, A (reprint author), Univ Duisburg Essen, Dept Dev Biol, Ctr Med Biotechnol, D-45117 Essen, Germany. EM andrea.vortkamp@uni-due.de FU DFG [VO 620/7]; Medical Faculty of Luebeck [A12-2007] FX We Would like to thank A. Ruiz y Altaba for sharing plasmids, Sabine Schneider, Antje Kettelhake, and Melanie Albrecht for excellent technical assistance. This work was supported by a DFG grant (VO 620/7) to AV and a Grant (A12-2007) of the Medical Faculty of Luebeck to F.K. NR 50 TC 35 Z9 41 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2009 VL 328 IS 1 BP 40 EP 53 DI 10.1016/j.ydbio.2009.01.012 PG 14 WC Developmental Biology SC Developmental Biology GA 419ZW UT WOS:000264259200004 PM 19389374 ER PT J AU Macotela, Y Boucher, J Tran, TT Kahn, CR AF Macotela, Yazmin Boucher, Jeremie Tran, Thien T. Kahn, C. Ronald TI Sex and Depot Differences in Adipocyte Insulin Sensitivity and Glucose Metabolism SO DIABETES LA English DT Article ID BODY-FAT DISTRIBUTION; WHITE ADIPOSE-TISSUE; RISK-FACTORS; FEMALE RATS; RECEPTOR; OBESITY; MICE; RESISTANCE; ESTROGEN; GENDER AB OBJECTIVE-To investigate how insulin sensitivity and glucose metabolism differ in adipocytes between different fat depots of male and female mice and how sex steroids contribute to these differences. RESEARCH DESIGN AND METHODS-Adipocytes from intra-abdominal/perigonadal (PG) and subcutaneous (SC) adipose tissue from normal, castrated, or steroid-implanted animals were isolated and analyzed for differences in insulin sensitivity and glucose metabolism. RESULTS-Adipocytes from both PG and SC depots of females have increased lipogenic rates compared with those from males. In females, intra-abdominal PG adipocytes are more insulin-sensitive than SC adipocytes and more insulin-sensitive than male adipocytes from either depot. When stimulated by low physiological concentrations of insulin, female PG adipocytes show a robust increase in Akt and extracellular signal-related kinase (ERK) phosphorylation and lipogenesis, whereas male adipocytes show activation only at higher insulin concentrations. Adipocytes from females have higher mRNA/protein levels of several genes involved in glucose and lipid metabolism. After castration, adipocytes of male mice showed increased insulin sensitivity and increased lipogenic rates, whereas adipocytes of females demonstrate decreased lipid production. Increasing estrogen above physiological levels, however, also reduced lipid synthesis in females, whereas increasing dihydrotestosterone in males had no effect. CONCLUSIONS-There are major sex differences in insulin sensitivity in adipose tissue, particularly in the intra-abdominal depot, that, are regulated by physiological levels of sex steroids. The increased sensitivity to insulin and lipogenesis observed in adipocytes from females may account for their lower level of insulin resistance and diabetes risk despite similar or higher fat content than in males. Diabetes 58:803-812, 2009 C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU National Institutes of Health [DK31036, DK33201, D55545]; Pew Latin American Fellows Program; American Diabetes Association FX This research was supported by grants from the National Institutes of Health (DK31036, DK33201, and D55545 to C.R.K.). Y.M. was supported by the Pew Latin American Fellows Program in the Biomedical Sciences and by the mentor-based American Diabetes Association award. No potential conflicts of interest relevant to this article were reported. We thank S. Gesta and B. Emanuelli for technical assistance and critical discussion of the work, O. Peroni for her assistance with the Coulter Counter, M. Rourk for his expertise in animal care, and 5P30 DK 36836 Specialized Assay Core at the Joslin Diabetes Center for leptin, adiponectin, and FFA measurements. NR 34 TC 116 Z9 120 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2009 VL 58 IS 4 BP 803 EP 812 DI 10.2337/db08-1054 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428AH UT WOS:000264819700005 PM 19136652 ER PT J AU Escribano, O Guillen, C Nevado, C Gomez-Hernandez, A Kahn, CR Benito, M AF Escribano, Oscar Guillen, Carlos Nevado, Carmen Gomez-Hernandez, Almudena Kahn, C. Ronald Benito, Manuel TI beta-Cell Hyperplasia Induced by Hepatic Insulin Resistance Role of a Liver-Pancreas Endocrine Axis Through Insulin Receptor A Isoform SO DIABETES LA English DT Article ID FACTOR-BINDING PROTEIN-1; GROWTH-FACTOR; TRANSGENIC MICE; COMPENSATORY GROWTH; GLUCOSE-TOLERANCE; MOUSE MODELS; KNOCKOUT; HEPATOCYTES; GENE; HYPERGLYCEMIA AB OBJECTIVE-Type 2 diabetes results from a combination of insulin resistance and impaired insulin secretion. To directly address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO). RESEARCH DESIGN AND METHODS-Using this approach, we were able to induce variable insulin receptor (IR) deficiency in a tissue-specific manner (liver mosaicism). RESULTS-iLIRKO mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased beta-cell mass, the extent of which was proportional to the deletion of hepatic IR. Our studies of iLIRKO suggest a cause-and-effect relationship between progressive insulin resistance and the fold increase of plasma insulin levels and beta-cell mass. Ultimately, the beta-cells failed to secrete sufficient insulin, leading to uncontrolled diabetes. We observed that hepatic IGF-1 expression was enhanced in iLIRKO mice, resulting in an increase of circulating IGF-1. Concurrently, the IR-A isoform was upregulated in hyperplastic beta-cells of iLIRKO mice and IGF-1-induced proliferation was higher than in the controls. In mouse beta-cell lines, IR-A, but not IR-B, conferred a proliferative capacity in response to insulin or IGF-1, providing a potential explanation for the beta-cell hyperplasia induced by liver insulin resistance in iLIRKO mice. CONCLUSIONS-Our studies of iLIRKO mice suggest a liver-pancreas endocrine axis in which IGF-1 functions as a liver-derived growth factor to promote compensatory pancreatic islet hyperplasia through IR-A. Diabetes 58:820-828, 2009 C1 [Escribano, Oscar; Guillen, Carlos; Nevado, Carmen; Gomez-Hernandez, Almudena; Benito, Manuel] Univ Complutense Madrid, Fac Pharm, Dept Biochem & Mol Biol, Madrid, Spain. [Escribano, Oscar; Guillen, Carlos; Nevado, Carmen; Gomez-Hernandez, Almudena; Benito, Manuel] CIBER Diabet & Enfermedades Metab Asociadas CIBER, Barcelona, Spain. [Kahn, C. Ronald] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Benito, M (reprint author), Univ Complutense Madrid, Fac Pharm, Dept Biochem & Mol Biol, Madrid, Spain. EM benito@farm.ucm.es RI Guillen, Carlos/J-9728-2014; Benito, Manuel/J-5637-2014; OI Guillen, Carlos/0000-0002-9370-6314; Benito, Manuel/0000-0002-7218-406X; Escribano, Oscar/0000-0002-8249-1645 FU Ministerio de Educacion y Ciencia and Red Tematica de Investigacion Cooperativa en Diabetes [SAF2005/00014, SAF2007/60058]; Ministerio de Sanidad y Consumo, Spain [RD06/0015/0005] FX We thank Dr. Deborah Burks for the English edition of the manuscript and also Gema Garcia and Sylvia Fernandez for technical assistance. We acknowledge the technical expertise of Dr. J.A. Lopez Garcia-Asenjo, Surgery Pathology Branch, Hospital Clinico San Carlos, Madrid, Spain. NR 37 TC 27 Z9 30 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2009 VL 58 IS 4 BP 820 EP 828 DI 10.2337/db08-0551 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428AH UT WOS:000264819700007 PM 19136656 ER PT J AU Lieb, W Sullivan, LM Harris, TB Roubenoff, R Benjamin, EJ Levy, D Fox, CS Wang, TJ Wilson, PW Kannel, WB Vasan, RS AF Lieb, Wolfgang Sullivan, Lisa M. Harris, Tamara B. Roubenoff, Ronenn Benjamin, Emelia J. Levy, Daniel Fox, Caroline S. Wang, Thomas J. Wilson, Peter W. Kannel, William B. Vasan, Ramachandran S. TI Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals SO DIABETES CARE LA English DT Article ID RAT VENTRICULAR MYOCYTES; RISK-FACTOR; WEIGHT; OBESITY; MICE; HYPERTROPHY; INSULIN; MEN AB OBJECTIVE - Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated With greater risk of CHF, CVD, and mortality in elderly individuals. RESEARCH DESIGN AND METHODS - We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed. RESULTS - Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CH F) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% Cl 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the. relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels. CONCLUSIONS - In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality. C1 [Lieb, Wolfgang; Benjamin, Emelia J.; Levy, Daniel; Fox, Caroline S.; Wang, Thomas J.; Kannel, William B.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Sullivan, Lisa M.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Roubenoff, Ronenn] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. [Levy, Daniel; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Wilson, Peter W.] Emory Univ, Sch Med, Atlanta, GA USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM vasan@bu.edu RI Lieb, Wolfgang/C-1990-2012; OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC25195, N01-HV28178, K24-HL04334, R01-DK080739] FX This work was supported through National Institutes of Health/National Heart, Lung, and Blood Institute Contracts N01-HC25195, N01-HV28178, K24-HL04334, and R01-DK080739. Contract N01-HC25195 funded the performance of examinations at which leptin levels were obtained. The other grants supported the interpretation of data and preparation of the manuscript.; No potential conflicts of interest relevant to this article were reported. NR 25 TC 48 Z9 50 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2009 VL 32 IS 4 BP 612 EP 616 DI 10.2337/dc08-1596 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428AI UT WOS:000264819800018 PM 19114611 ER PT J AU Rutrove, SB Veves, A Mitsa, T Nie, R Fogerson, PM Garmirian, LP Nardin, RA AF Rutrove, Seward B. Veves, Aristidis Mitsa, Theophano Nie, Rui Fogerson, Patricia M. Garmirian, Lindsay P. Nardin, Rachel A. TI Impaired Distal Thermoregulation in Diabetes and Diabetic Polyneuropathy SO DIABETES CARE LA English DT Article ID SLEEP ONSET; NEUROPATHY; TEMPERATURE; TIME; DYSFUNCTION; DIAGNOSIS; MELLITUS; FOOT; FEET AB OBJECTIVE - To determine how thermoregulation of the feet is affected by diabetes and diabetic polyneuropathy in both wakefulness and sleep. RESEARCH DESIGN AND METHODS - Normal subjects, diabetic subjects without neuropathy, diabetic subjects with small-fiber diabetic polyneuropathy, and those with advanced diabetic polyneuropathy were categorized based on neurological examination, nerve conduction studies; and quantitative sensory testing. Subjects underwent foot temperature monitoring using an iButton device attached to the foot and a second iButton for recording of ambient temperature. Socks and footwear were standardized, and subjects maintained an activity diary. Data were collected over a 32-h period and analyzed. RESULTS - A total of 39 normal subjects, 28 patients with diabetes but without diabetic polyneuropathy, 14 patients with isolated small-fiber diabetic polyneuropathy, and 27 patients with more advanced diabetic polyneuropathy participated. No consistent differences in foot temperature regulation between the four groups were identified during wakefulness. During sleep, however, multiple metrics revealed significant abnormalities in the diabetic patients. These included reduced mean foot temperature (P < 0.001), reduced maximal temperature (P < 0.001), increased rate of cooling (P < 0.001), as well as increased frequency of variation (P = 0.005), supporting that patients with diabetic polyneuropathy and even those with out), diabetes but no diabetic polyneuropathy have impaired nocturnal thermoregulation. CONCLUSIONS - Nocturnal foot thermoregulation is impaired in patients with diabetes and diabetic polyneuropathy. Because neurons are highly temperature sensitive and because foot warming is part of the normal biology of sleep onset and maintenance, these findings suggest new potentially treatable mechanisms of diabetes-associated nocturnal pain and sleep disturbance. C1 [Rutrove, Seward B.; Nie, Rui; Fogerson, Patricia M.; Garmirian, Lindsay P.; Nardin, Rachel A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Neuromuscular Dis,Dept Neurol, Boston, MA 02215 USA. [Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. [Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. [Mitsa, Theophano] Univ Massachusetts, Dept Elect & Comp Engn, Dartmouth, MA USA. RP Rutrove, SB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Neuromuscular Dis,Dept Neurol, Boston, MA 02215 USA. EM srutkove@bidmc.harvard.edu FU National Institutes of Health [R21 DK071178] FX This study was funded by National Institutes of Health Grant R21 DK071178.; No potential conflicts of interest relevant to this article were reported.; The authors thank Catherine Stamoulis for her helpful input into the biostatistical analysis. NR 24 TC 0 Z9 0 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD APR PY 2009 VL 32 IS 4 BP 671 EP 676 DI 10.2337/dc08-1844 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428AI UT WOS:000264819800029 ER PT J AU Cengiz, E Swan, KL Tamborlane, WV Steil, GM Steffen, AT Weinzimer, SA AF Cengiz, Eda Swan, Karena L. Tamborlane, William V. Steil, Garry M. Steffen, Amy T. Weinzimer, Stuart A. TI Is an Automatic Pump Suspension Feature Safe for Children with Type 1 Diabetes? An Exploratory Analysis with a Closed-Loop System SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID INSULIN DELIVERY AB Objectives: It has been proposed that the first step towards a closed-loop artificial pancreas might be to use a continuous glucose sensor to automatically suspend the basal insulin delivery based on projected low sensor glucose values. Methods: We reviewed our recent experience with an artificial pancreas system, utilizing a proportional-integrative-derivative (PID) algorithm, in 17 adolescents with type 1 diabetes (T1D) to assess the safety and efficacy of this maneuver. Results: During 34 h of closed-loop automated insulin delivery, 18 pump suspensions >= 60 min (90 +/- 18 min) occurred in eight subjects. Sensor glucose levels fell from 159 +/- 42mg/dL to a nadir of 72 +/- 13mg/dL. Corresponding plasma glucose levels fell from 168 +/- 51 to 72 +/- 16mg/dL, with values <60mg/dL recorded in only four of the 18 events. Conclusions: These data suggest that automatic pump suspension using the PID algorithm may be an effective means to prevent hypoglycemia in youth with T1D. C1 [Cengiz, Eda; Swan, Karena L.; Tamborlane, William V.; Steffen, Amy T.; Weinzimer, Stuart A.] Yale Univ, Sch Med, Sect Pediat Endocrinol, Dept Pediat, New Haven, CT 06520 USA. [Steil, Garry M.] Joslin Diabet Ctr, Sect Islet Cell Transplantat & Cell Biol, Boston, MA 02215 USA. RP Cengiz, E (reprint author), Yale Univ, Sch Med, Dept Pediat Endocrinol, 333 Cedar St,LMP 3103E, New Haven, CT 06520 USA. EM Eda.Cengiz@yale.edu FU NIH-CTSA [RR 023423]; RR 023423), the Juvenile Diabetes Research Foundation; Stephen I. Morse Pediatric Diabetes Research Fund FX This study is supported by grants from NIH-CTSA (RR 023423), the Juvenile Diabetes Research Foundation, and the Stephen I. Morse Pediatric Diabetes Research Fund. NR 11 TC 20 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2009 VL 11 IS 4 BP 207 EP 210 DI 10.1089/dia.2008.0102 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428ZZ UT WOS:000264891900001 PM 19344194 ER PT J AU Meigs, JB AF Meigs, J. B. TI Prediction of type 2 diabetes: the dawn of polygenetic testing for complex disease SO DIABETOLOGIA LA English DT Editorial Material DE Clinical; Complex disease; Genetics; Genomics; Prediction; Public health; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; RISK-FACTORS; POLYMORPHISMS; VARIANTS; IMPACT; GENES C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org NR 14 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2009 VL 52 IS 4 BP 568 EP 570 DI 10.1007/s00125-009-1296-9 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413IR UT WOS:000263787300002 PM 19214469 ER PT J AU Stolerman, ES Manning, AK McAteer, JB Fox, CS Dupuis, J Meigs, JB Florez, JC AF Stolerman, E. S. Manning, A. K. McAteer, J. B. Fox, C. S. Dupuis, J. Meigs, J. B. Florez, J. C. TI TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study SO DIABETOLOGIA LA English DT Article DE Body mass index; Proinsulin; TCF7L2; Type 2 diabetes ID ADIPOSE-TISSUE; GENE; POLYMORPHISMS; POPULATION; RISK AB Common variants in the TCF7L2 gene are associated with type 2 diabetes via impaired insulin secretion. One hypothesis is that variation in TCF7L2 impairs insulin processing in the beta cell. In contrast, the association of related TCF7L2 polymorphisms with obesity is controversial in that it has only been shown in cohorts susceptible to ascertainment bias. We reproduced the association of diabetes-associated variants with proinsulin/insulin ratios, and also examined the association of a TCF7L2 haplotype with obesity in the Framingham Heart Study (FHS). We genotyped the TCF7L2 single nucleotide polymorphisms rs7903146 and rs12255372 (previously associated with type 2 diabetes) and rs10885406 and rs7924080 (which tag haplotype A [HapA], a haplotype reported to be associated with obesity) in 2,512 FHS participants. We used age- and sex-adjusted linear mixed-effects models to test for association with glycaemic traits, proinsulin/insulin ratios and obesity measures. As expected, the T risk allele of rs7903146 was associated with higher fasting plasma glucose (p = 0.01). T/T homozygotes had a 23.5% increase in the proinsulin/insulin ratio (p = 1 x 10(-7)) compared with C/C homozygotes. There was no association of HapA with BMI (p = 0.98), waist circumference (p = 0.89), subcutaneous adipose tissue (p = 0.32) or visceral adipose tissue (p = 0.92). We confirmed that the risk allele of rs7903146 is associated with hyperglycaemia and a higher proinsulin/insulin ratio. We did not detect any association of the TCF7L2 HapA with adiposity measures, suggesting that this may have been a spurious association from ascertainment bias, possibly induced by the evaluation of obesity in separate groups of glycaemic cases and controls. C1 [Stolerman, E. S.; McAteer, J. B.; Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA. [Stolerman, E. S.; McAteer, J. B.; Florez, J. C.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Stolerman, E. S.; McAteer, J. B.; Florez, J. C.] MIT, Cambridge, MA 02139 USA. [Stolerman, E. S.; Meigs, J. B.; Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Manning, A. K.; Dupuis, J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Fox, C. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA USA. [Fox, C. S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, J. B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Simches Res Bldg-CPZN 5-250, Boston, MA 02114 USA. EM jcflorez@partners.org OI Dupuis, Josee/0000-0003-2871-3603 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Diabetes Association Career Development Award; NIH NCRR Shared Instrumentation [1S10RR163736-01A1]; NIH [T32 GM007748, K23 DK65978-04]; NIDDK [K24 DK080140]; Glaxo-SmithKline; sanofi-aventis FX This study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study ( contract no. N01-HC-25195), an American Diabetes Association Career Development Award ( J.B. Meigs), and the Boston University Linux Cluster for Genetic Analysis ( LinGA) funded by the NIH NCRR Shared Instrumentation grant ( 1S10RR163736-01A1). E. S. Stolerman is supported by NIH Training Grant T32 GM007748 Training Grant in Genetics. J.B. Meigs is also supported by NIDDK K24 DK080140. J. C. Florez is supported by NIH Research Career Award K23 DK65978-04. J. B. Meigs currently has research grants from Glaxo-SmithKline and sanofi-aventis, and serves on consultancy boards for GlaxoSmithKline, sanofi-aventis, Interleukin Genetics, Kalypsis, and Outcomes Sciences. J. C. Florez has received consulting honoraria from Merck, bioStrategies, XOMA and Publicis Healthcare Communications Group, a global advertising agency engaged by Amylin Pharmaceuticals. NR 20 TC 38 Z9 41 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2009 VL 52 IS 4 BP 614 EP 620 DI 10.1007/s00125-009-1266-2 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413IR UT WOS:000263787300010 PM 19183934 ER PT J AU Zraika, S Hull, RL Udayasankar, J Aston-Mourney, K Subramanian, SL Kisilevsky, R Szarek, WA Kahn, SE AF Zraika, S. Hull, R. L. Udayasankar, J. Aston-Mourney, K. Subramanian, S. L. Kisilevsky, R. Szarek, W. A. Kahn, S. E. TI Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis SO DIABETOLOGIA LA English DT Article DE Beta cell apoptosis; IAPP; Insulin secretion; Islet amyloid; Oxidative stress ID FORMATION IN-VITRO; HUMAN AMYLIN; DIABETES-MELLITUS; INSULIN-SECRETION; GLUCOSE TOXICITY; MOUSE ISLETS; PROTEIN GLYCOSYLATION; TRANSGENIC MOUSE; POLYPEPTIDE IAPP; FIBRIL FORMATION AB Islet amyloid in type 2 diabetes contributes to loss of beta cell mass and function. Since islets are susceptible to oxidative stress-induced toxicity, we sought to determine whether islet amyloid formation is associated with induction of oxidative stress. Human islet amyloid polypeptide transgenic and non-transgenic mouse islets were cultured for 48 or 144 h with or without the antioxidant N-acetyl-l-cysteine (NAC) or the amyloid inhibitor Congo Red. Amyloid deposition, reactive oxygen species (ROS) production, beta cell apoptosis, and insulin secretion, content and mRNA were measured. After 48 h, amyloid deposition was associated with increased ROS levels and increased beta cell apoptosis, but no change in insulin secretion, content or mRNA levels. Antioxidant treatment prevented the rise in ROS, but did not prevent amyloid formation or beta cell apoptosis. In contrast, inhibition of amyloid formation prevented the induction of oxidative stress and beta cell apoptosis. After 144 h, amyloid deposition was further increased and was associated with increased ROS levels, increased beta cell apoptosis and decreased insulin content. At this time-point, antioxidant treatment and inhibition of amyloid formation were effective in reducing ROS levels, amyloid formation and beta cell apoptosis. Inhibition of amyloid formation also increased insulin content. Islet amyloid formation induces oxidative stress, which in the short term does not mediate beta cell apoptosis, but in the longer term may feed back to further exacerbate amyloid formation and contribute to beta cell apoptosis. C1 [Zraika, S.; Hull, R. L.; Udayasankar, J.; Aston-Mourney, K.; Subramanian, S. L.; Kahn, S. E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Zraika, S.; Hull, R. L.; Udayasankar, J.; Aston-Mourney, K.; Subramanian, S. L.; Kahn, S. E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Kisilevsky, R.] Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada. [Kisilevsky, R.] Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. [Szarek, W. A.] Queens Univ, Dept Chem, Kingston, ON K7L 3N6, Canada. RP Zraika, S (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way 151, Seattle, WA 98108 USA. EM zraikas@u.washington.edu OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU Department of Veterans Affairs; NIH [DK-75998, DK-17047, DK-74404]; Juvenile Diabetes Research Foundation; American Diabetes Association; Canadian Institutes for Health Research [MOP-3153]; Natural Sciences and Engineering Research Council of Canada; Institute for the Study of Aging FX We thank B. Barrow, R. Bhatti, T. Braddock, M. Cone, M. Peters, J. Teague, M. Watts and J. Willard for excellent technical support. This work was supported by research funding from the Department of Veterans Affairs and NIH grants DK-75998 and DK-17047. S. Zraika was supported by a Juvenile Diabetes Research Foundation Postdoctoral Fellowship and an American Diabetes Association Mentor-Based Fellowship. R. L. Hull was supported by NIH grant DK-74404. Preparation and development of WAS-406 was funded by the Canadian Institutes for Health Research grant MOP-3153, the Natural Sciences and Engineering Research Council of Canada and the Institute for the Study of Aging. NR 46 TC 87 Z9 88 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2009 VL 52 IS 4 BP 626 EP 635 DI 10.1007/s00125-008-1255-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413IR UT WOS:000263787300012 PM 19148619 ER PT J AU Kikugawa, R Katsuta, H Akashi, T Yatoh, S Weir, GC Sharma, A Bonner-Weir, S AF Kikugawa, R. Katsuta, H. Akashi, T. Yatoh, S. Weir, G. C. Sharma, A. Bonner-Weir, S. TI Differentiation of COPAS-sorted non-endocrine pancreatic cells into insulin-positive cells in the mouse SO DIABETOLOGIA LA English DT Article DE Beta cell; Duct; Neogenesis; Pancreas ID GENERATED IN-VITRO; BETA-CELLS; DUCTAL CELLS; PROGENITOR CELLS; GENE-EXPRESSION; PRECURSOR CELLS; ADULT EXOCRINE; HUMAN ISLETS; PROLIFERATION; ENDOCRINE AB The regenerative process in the pancreas is of particular interest, since insulin-producing beta cells are lost in diabetes. Differentiation of new beta cells from pancreatic non-endocrine cells has been reported in vivo and in vitro, a finding that implies the existence of pancreatic stem/progenitor cells. However, while tissue-specific stem cells are well documented in skin, intestine and testis, pancreatic stem cells have been elusive. We hypothesised that pancreatic stem/progenitor cells within the non-endocrine fraction could be a source of new islets in vitro. To test if there were such cells within the pancreas, we generated pancreatic cell aggregates from tissue remaining after islet isolation from mouse insulin promoter 1-green fluorescent protein (MIP-GFP) mice. To eliminate any contamination of insulin-positive cells, we deleted all GFP-positive aggregates using COPAS Select and cultured with Matrigel. Immunohistochemistry, quantitative real-time PCR and single-cell nested RT-PCR were performed to confirm formation of insulin-producing cells. The GFP-negative cells were expanded as monolayers and then differentiated into three-dimensional cystic structures. After 1 week of culture, GFP-positive cells were found as clusters or single cells. By quantitative real-time PCR, no insulin mRNA was detected immediately after COPAS sorting, but after differentiation insulin mRNA of the whole preparation was 1.91 +/- 0.31% that of purified MIP-GFP beta cells. All GFP-positive cells expressed insulin 1; most expressed insulin 2, pancreas duodenum homeobox-1 and cytokeratin 19 by single cell nested RT-PCR. Our data support the concept that within the exocrine (acinar and ductal) pancreas of the adult mouse there are cells that can give rise to insulin-positive cells in vitro. C1 [Kikugawa, R.; Katsuta, H.; Akashi, T.; Yatoh, S.; Weir, G. C.; Sharma, A.; Bonner-Weir, S.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Kikugawa, R.; Katsuta, H.; Akashi, T.; Yatoh, S.; Weir, G. C.; Sharma, A.; Bonner-Weir, S.] Harvard Univ, Sch Med, Dept Med, Harvard Stem Cell Inst, Boston, MA USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National Institutes of Health [DK44523, DK66056]; Joslin Diabetes and Endocrinology Research Center [P30 DK36836]; Diabetes Research and Wellness Foundation FX The authors thank J. Lock, J. LaVecchio and G. Buruzula for excellent technical assistance. We also especially thank J. Thompson ( Union Biometrica) for expertise in setting the COPAS sort. This study was supported by grants from the National Institutes of Health DK44523 ( to S. Bonner-Weir), DK66056 ( to S. Bonner-Weir) and P30 DK36836 to the Joslin Diabetes and Endocrinology Research Center ( Flow Cytometry and Advanced Microscopy Cores). Support also came from the Diabetes Research and Wellness Foundation and from private donors. NR 33 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2009 VL 52 IS 4 BP 645 EP 652 DI 10.1007/s00125-009-1260-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413IR UT WOS:000263787300014 PM 19183938 ER PT J AU Coletta, DK Sriwijitkamol, A Wajcberg, E Tantiwong, P Li, M Prentki, M Madiraju, M Jenkinson, CP Cersosimo, E Musi, N DeFronzo, RA AF Coletta, D. K. Sriwijitkamol, A. Wajcberg, E. Tantiwong, P. Li, M. Prentki, M. Madiraju, M. Jenkinson, C. P. Cersosimo, E. Musi, N. DeFronzo, R. A. TI Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial SO DIABETOLOGIA LA English DT Article DE Adiponectin; AMP kinase; Insulin sensitivity; Mitochondrial; Muscle; Pioglitazone ID TYPE-2 DIABETIC SUBJECTS; ACETYL-COA CARBOXYLASE; POLYCYSTIC-OVARY-SYNDROME; PLACEBO-CONTROLLED TRIAL; INSULIN SENSITIVITY; ADIPOSE-TISSUE; MALONYL-COA; GLOBULAR DOMAIN; GAMMA AGONISTS; RECEPTOR-GAMMA AB The molecular mechanisms by which thiazolidinediones improve insulin sensitivity in type 2 diabetes are not fully understood. We hypothesised that pioglitazone would activate the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway and increase the expression of genes involved in adiponectin signalling, NEFA oxidation and mitochondrial function in human skeletal muscle. A randomised, double-blind, parallel study was performed in 26 drug-naive type 2 diabetes patients treated with: (1) pioglitazone (n = 14) or (2) aggressive nutritional therapy (n = 12) to reduce HbA(1c) to levels observed in the pioglitazone-treated group. Participants were assigned randomly to treatment using a table of random numbers. Before and after 6 months, patients reported to the Clinical Research Center of the Texas Diabetes Institute for a vastus lateralis muscle biopsy followed by a 180 min euglycaemic-hyperinsulinaemic (80 mU m(-2) min(-1)) clamp. All patients in the pioglitazone (n = 14) or nutritional therapy (n = 12) group were included in the analysis. Pioglitazone significantly increased plasma adiponectin concentration by 79% and reduced fasting plasma NEFA by 35% (both p < 0.01). Following pioglitazone, insulin-stimulated glucose disposal increased by 30% (p < 0.01), and muscle AMPK and acetyl-CoA carboxylase (ACC) phosphorylation increased by 38% and 53%, respectively (p < 0.05). Pioglitazone increased mRNA levels for adiponectin receptor 1 and 2 genes (ADIPOR1, ADIPOR2), peroxisome proliferator-activated receptor gamma, coactivator 1 gene (PPARGC1) and multiple genes involved in mitochondrial function and fat oxidation. Despite a similar reduction in HbA(1c) and similar improvement in insulin sensitivity with nutritional therapy, there were no significant changes in muscle AMPK and ACC phosphorylation, or the expression of ADIPOR1, ADIPOR2, PPARGC1 and genes involved in mitochondrial function and fat oxidation. No adverse (or unexpected) effects or side effects were reported from the study. Pioglitazone increases plasma adiponectin levels, stimulates muscle AMPK signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation. These changes may represent an important cellular mechanism by which thiazolidinediones improve skeletal muscle insulin sensitivity. Trial registration: NCT 00816218 Funding: This trial was funded by National Institutes of Health Grant DK24092, VA Merit Award, GCRC Grant RR01346, Executive Research Committee Research Award from the University of Texas Health Science Center at San Antonio, American Diabetes Association Junior Faculty Award, American Heart Association National Scientist Development Grant, Takeda Pharmaceuticals North America Grant and Canadian Institute of Health Research Grant. C1 [Coletta, D. K.] Arizona State Univ, Coll Liberal Arts & Sci, Ctr Metab Biol, Tempe, AZ 85287 USA. [Sriwijitkamol, A.; Wajcberg, E.; Tantiwong, P.; Li, M.; Jenkinson, C. P.; Cersosimo, E.; Musi, N.; DeFronzo, R. A.] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Sriwijitkamol, A.; Wajcberg, E.; Tantiwong, P.; Li, M.; Cersosimo, E.; Musi, N.; DeFronzo, R. A.] Texas Diabet Inst, San Antonio, TX USA. [Prentki, M.; Madiraju, M.] Univ Montreal, Dept Nutr, Mol Nutr Unit, Montreal, PQ H3C 3J7, Canada. [Prentki, M.; Madiraju, M.] Univ Montreal, Dept Biochem, Mol Nutr Unit, Montreal, PQ H3C 3J7, Canada. [Prentki, M.; Madiraju, M.] Univ Montreal, Montreal Diabet Res Ctr, Montreal, PQ H3C 3J7, Canada. [Prentki, M.; Madiraju, M.] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Jenkinson, C. P.; DeFronzo, R. A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Coletta, DK (reprint author), Arizona State Univ, Coll Liberal Arts & Sci, Ctr Metab Biol, POB 873704, Tempe, AZ 85287 USA. EM Dawn.Coletta@asu.edu RI Coletta, Dawn/G-6382-2016; OI Coletta, Dawn/0000-0001-5819-5152 FU NIH [DK24092]; VA Merit Award; GCRC [RR01346]; University of Texas Health Science Center at San Antonio; American Diabetes Association Junior Faculty Award; American Heart Association National Scientist Development; Takeda Pharmaceuticals North America; Canadian Institute of Health Research FX This work was supported by NIH grant DK24092 ( R. A. DeFronzo), a VA Merit Award ( R. A. DeFronzo), GCRC grant RR01346, an Executive Research Committee Research Award from the University of Texas Health Science Center at San Antonio ( N. Musi), an American Diabetes Association Junior Faculty Award ( N. Musi), an American Heart Association National Scientist Development Grant ( D. K. Coletta), a grant from Takeda Pharmaceuticals North America and a grant from the Canadian Institute of Health Research ( M. Prentki). We thank all the patients who participated in the studies and the Texas Diabetes Institute nurses who helped to perform the studies. We thank N. Cyr for excellent technical assistance. NR 50 TC 51 Z9 55 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2009 VL 52 IS 4 BP 723 EP 732 DI 10.1007/s00125-008-1256-9 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 413IR UT WOS:000263787300023 PM 19169664 ER PT J AU Yachimski, P Hur, C AF Yachimski, Patrick Hur, Chin TI Upper Endoscopy in Patients with Acute Myocardial Infarction and Upper Gastrointestinal Bleeding: Results of a Decision Analysis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE Gastrointestinal bleeding; Acute myocardial infarction; Gastrointestinal endoscopy; Esophagogastroduodenoscopy (EGD) ID NONBLEEDING VISIBLE VESSELS; ACUTE CORONARY SYNDROMES; OCCULT BLOOD-TEST; PEPTIC-ULCERS; EPINEPHRINE INJECTION; BIDIRECTIONAL ENDOSCOPY; HEMOSTATIC EFFICACY; CARDIAC-SURGERY; MEDICAL THERAPY; OBSCURE ORIGIN AB Background The management of patients with acute myocardial infarction (AMI) and upper gastrointestinal bleeding (UGIB) can present a challenge. The utility of upper endoscopy (esophagogastroduodenoscopy, EGD) and endoscopic therapy must be weighed against safety considerations. Aim To assess the utility and safety of EGD in patients with UGIB and AMI. Methods Using decision analysis, patients with UGIB and AMI were assigned to one of two strategies: (1) EGD prior to cardiac catheterization (EGD strategy) and (2) cardiac catheterization without EGD (CATH strategy). Results In patients with overt UGIB, the EGD strategy resulted in 97 deaths per 10,000 patients, compared with 600 deaths in the CATH strategy. The EGD strategy resulted in fewer non-fatal complications (1,271 vs. 6,000 per 10,000 patients). In patients with occult blood loss, the EGD strategy resulted in more deaths (59 vs. 16 per 10,000) and more non-fatal complications (888 vs. 160 per 10,000) than the CATH strategy. Conclusions Our analysis supports EGD prior to cardiac catheterization in patients with AMI and overt UGIB. This strategy results in fewer deaths and complications compared with a strategy of proceeding directly to catheterization. Our analysis does not support routine EGD prior to cardiac catheterization in patients with fecal occult blood. C1 [Yachimski, Patrick; Hur, Chin] Massachusetts Gen Hosp, Blake Gastrointestinal Unit 4, Boston, MA 02114 USA. [Yachimski, Patrick; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. [Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Yachimski, P (reprint author), Massachusetts Gen Hosp, Blake Gastrointestinal Unit 4, 55 Fruit St, Boston, MA 02114 USA. EM pyachimski@partners.org OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [K07 CA107060, K07 CA107060-03] NR 53 TC 9 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2009 VL 54 IS 4 BP 701 EP 711 DI 10.1007/s10620-008-0403-y PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 413ZB UT WOS:000263832600002 PM 18661236 ER PT J AU Iezzoni, LI Rao, SR Kinkel, RP AF Iezzoni, Lisa I. Rao, Sowmya R. Kinkel, R. Philip TI Patterns of mobility aid use among working-age persons with multiple sclerosis living in the community in the United States SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Multiple sclerosis; Mobility; Walking; Wheelchair; Walker ID QUALITY-OF-LIFE; DISABILITY; INDIVIDUALS; PROGRESSION; MSWS-12; PEOPLE; MS AB Background: Difficulty walking is the most visible sign of disability among persons with multiple sclerosis (MS). However, little is known about mobility aid use by persons with MS living in the community. Objectives: To explore perceptions of mobility problems related to MS and patterns of mobility aid use by persons with MS residing in communities across the United States. Methods: We conducted a 30-minute telephone survey in mid-2007 with 703 community-dwelling, working-age adults who self-reported having MS. We identified potential survey respondents using membership lists of the National Multiple Sclerosis Society, over-sampling individuals living in zip codes with relatively high poverty rates. All analyses, including calculation of simple percentages, used sampling weights to produce population estimates. The overall response rate was 73.4%. Survey questions asked basic information about all mobility aids used by respondents and details about up to two different aids. We used multivariable polychotomous logistic regression to predict use of various mobility aids accounting for demographic and disease characteristics. Results: In questions about the previous 2 weeks, needing to concentrate on walking because of MS was the most common problem cited (weighted percent = 79.3%), followed by MS making standing more difficult (69.9%), increased effort needed to walk (59.0%), and needing to hold onto furniture, walls, or someone's arm when walking indoors every day (40.0%). Among the 703 respondents, 434 (weighted percent = 60.5%) reported using at least one mobility aid; the majority of these individuals reported using more than one type of aid. Manual wheelchairs were the most common mobility aid (63.4%), followed by canes (56.7%), power wheelchairs (36.7%), and scooters (32.2%). Among those using three or more different types of mobility aids, the large majority used manual wheelchairs (88.2%), followed by canes (65.4%). Persons who are married or living with partners were much less likely to use powered equipment than those who were never married (adjusted odds ratio [AOR] = 0.32; 95% CI: 0.13-0.82). Women were much less likely than men to use powered equipment (AOR = 0.40; 95% CI: 0.21-0.75). Conclusion: The vast majority of persons with MS who use at least one mobility aid own more than one type and about half own three or more different types of mobility aids. Persons with MS appear to "mix and match" different devices to suit their specific mobility needs. Given restrictive health insurance coverage policies for mobility aids, these findings raise questions about how persons acquire and pay for higher-technology mobility aids. (C) 2009 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.; Rao, Sowmya R.] DHarvard Med Sch, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Kinkel, R. Philip] Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Kinkel, R. Philip] Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), DHarvard Med Sch, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. EM liezzoni@partners.org FU National Multiple Sclerosis Society (NMSS) [HC 0079] FX Although Dr Iezzoni has occasionally spoken and assisted in educational sessions sponsored by NMSS local chapters around the country, she has never accepted payment for any of these activities. This research was supported by the National Multiple Sclerosis Society (NMSS), Contract No. HC 0079. NMSS staff provided the database of their membership; however, the investigators conducted and designed the sampling scheme. NMSS staff also commented on early drafts of the questionnaire. The Center for Survey Research sent letters to potential survey participants on NMSS letterhead, and the invitation letter provided the NMSS New York office telephone number if recipients had any questions. However, we are unaware that any calls about the study were made to that number. Otherwise, the NMSS was not involved in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 37 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 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD APR PY 2009 VL 2 IS 2 BP 67 EP 76 DI 10.1016/j.dhjo.2008.12.001 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 664ZP UT WOS:000283003100003 PM 21122745 ER PT J AU Resnik, L Allen, S Isenstadt, D Wasserman, M Iezzoni, L AF Resnik, Linda Allen, Susan Isenstadt, Deborah Wasserman, Melanie Iezzoni, Lisa TI Perspectives on use of mobility aids in a diverse population of seniors: Implications for intervention SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Mobility; Assistive technology; Hispanic; African American; Seniors ID ASSISTIVE DEVICES; DISABILITY; CARE AB Background: Many older adults who might benefit from using mobility aids do not or will not use them. Studies show that attitudes and beliefs strongly affect the decision to use mobility aids. Despite the growing diversity of the population, no prior studies have compared attitudes towards and beliefs about mobility aids by race and ethnicity. Objective: This study aimed to explore whether and how attitudes towards and beliefs about mobility aid use vary by race and ethnicity. Methods: We conducted 12 focus groups with 61 community dwelling persons age 65+ years from three groups: white, non-Hispanic black, and Hispanic. Data were coded and compared across groups. Results: For all groups, perceived benefits of mobility devices in maintaining independence and control produced positive attitudes. However, the association of mobility aid use with aging and physical decline contributed to stigmatizing attitudes. Black and Hispanic participants expressed apprehension about using unsafe or inappropriate secondhand equipment, heightened concerns about mobility aid users becoming subjects of negative biases, and a preference for fashionable aids. Hispanic participants expressed a preference for human assistance. Participants of all groups perceived physicians as influencing their decisions to use aids. Conclusion: Social pressures and perceived stigma deter mobility aid use, particularly in minority populations. Greater physician involvement, positive peer models, and affordable, safe, visually appealing devices would promote greater acceptance of mobility aids. (C) 2009 Elsevier Inc. All rights reserved. C1 [Resnik, Linda] Providence VA Med Ctr, Providence, RI 02908 USA. [Resnik, Linda; Allen, Susan] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Isenstadt, Deborah; Wasserman, Melanie] ABT Associates Inc, Cambridge, MA 02138 USA. [Iezzoni, Lisa] Harvard Univ, Boston, MA 02114 USA. [Iezzoni, Lisa] Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, Lisa] Beth Israel Univ Deaconess Med Ctr, Boston, MA 02215 USA. RP Resnik, L (reprint author), Providence VA Med Ctr, Providence, RI 02908 USA. EM Linda_Resnik@Brown.edu FU National Institute on Aging [R03 AG025094-01] FX This research was supported by R03 AG025094-01, a grant from the National Institute on Aging. NR 23 TC 12 Z9 12 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD APR PY 2009 VL 2 IS 2 BP 77 EP 85 DI 10.1016/j.dhjo.2008.12.002 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 664ZP UT WOS:000283003100004 PM 20160951 ER PT J AU Bilimoria, KY Bentrem, DJ Rock, CE Stewart, AK Ko, CY Halverson, A AF Bilimoria, Karl Y. Bentrem, David J. Rock, Colin E. Stewart, Andrew K. Ko, Clifford Y. Halverson, Amy TI Outcomes and Prognostic Factors for Squamous-Cell Carcinoma of the Anal Canal: Analysis of Patients From the National Cancer Data Base SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Anal carcinoma; Surgery; Treatment; National Cancer Data Base; Staging; Disparities; Chemotherapy; Radiation ID EPIDERMOID CARCINOMA; RANDOMIZED-TRIAL; COMBINED THERAPY; RARE CANCER; HEALTH-CARE; RADIOTHERAPY; RADIATION; MITOMYCIN; SURVIVAL; RADIOCHEMOTHERAPY AB PURPOSE: The objective of this study was to assess survival and prognostic factors for anal carcinoma in the population. METHODS: Patients with squamous-cell carcinoma of the anal canal were identified from the National Cancer Data Base (1985-2000). Univariate and multivariable methods were used to assess factors associated with survival. Concordance was calculated to assess agreement between American Joint Committee on Cancer stage and actual outcome. RESULTS: Nineteen thousand one hundred ninety-nine patients with anal carcinoma were identified (Stage I, 25.3 percent; Stage II, 51.8 percent; Stage III, 17.1 percent; Stage IV, 5.7 percent). Overall five-year survival was 58.0 percent. The American Joint Committee on Cancer (6th edition) staging system provided good survival discrimination by stage: I, 69.5 percent; II, 59.0 percent; III, 40.6 percent; and IV, 18.7 percent (concordance index, 0.663). On multivariable analysis, patients with anal carcinoma had a higher risk of death if they were male, >= 65 years old, black, living in lower median incomes areas, and had more advanced T stage tumors, nodal or distant metastases, or poorly differentiated cancers (P < 0.0001). There was not a significant difference in survival by hospital type or year of diagnosis. CONCLUSION: Although tumor characteristics and staging affect prognosis, patient factors, such as gender, race, and socioeconomic status, are also important prognostic factors for squamous-cell carcinoma of the anal canal. C1 [Bilimoria, Karl Y.; Stewart, Andrew K.; Ko, Clifford Y.] Amer Coll Surg, Canc Programs, Chicago, IL 60611 USA. [Bilimoria, Karl Y.; Bentrem, David J.; Rock, Colin E.; Halverson, Amy] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Canc Programs, 633 N St Clair St,25th Floor, Chicago, IL 60611 USA. EM k-bilimori@northwestern.edu FU American College of Surgeons Clinical Scholars in Residence FX Dr. Bilimoria is supported by the American College of Surgeons Clinical Scholars in Residence program. NR 40 TC 52 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD APR PY 2009 VL 52 IS 4 BP 624 EP 631 DI 10.1007/DCR.0b013e31819eb7f0 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 544GZ UT WOS:000273643900015 PM 19404066 ER PT J AU Cacciola, JS Koppenhaver, JM Alterman, AI Mckay, JR AF Cacciola, John S. Koppenhaver, Janelle M. Alterman, Arthur I. McKay, James R. TI Posttraumatic stress disorder and other psychopathology in substance abusing patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Posttraumatic stress disorder (PTSD); Alcohol dependence; Psychiatric comorbidity ID ADDICTION SEVERITY INDEX; STRUCTURED CLINICAL INTERVIEW; TEST-RETEST RELIABILITY; PSYCHIATRIC COMORBIDITY; COCAINE DEPENDENCE; PTSD; OUTCOMES; HISTORY; WOMEN AB Studies demonstrating greater problem severity in substance abuse patients with posttraumatic stress disorder (PTSD) versus those without have rarely considered other co-occurring psychiatric disorders. This study of 466 male veterans recently admitted to outpatient substance abuse treatment attempts to identify problems associated with PTSD versus those associated with other nonsubstance use Axis I disorders. Problem severity, particularly psychiatric. was examined across four groups of patients with substance use disorders (SUDs). Those with: 1, SUDs only (SU-Only); 2, PTSD, but no other Axis I disorders (SU + PTSID): 3, PTSD and other Axis I disorders (SU + PTSD + Axis 1): and 4, no PTSD, but other Axis I disorders (SU + other Axis 1). Results suggested a hierarchy of psychiatric, and to a lesser extent, other life problem severities associated with these diagnostic groupings. The most severe group was SU + PTSD + Axis 1, followed in decreasing severity by the SU + other Axis 1, SU + PTSD, and SU-Only groups. Additional analyses comparing the SU + PTSD + Axis I patients with a subgroup of Axis I patients with more than one Axis I disorder (SU + multiple Axis 1) revealed few group differences except for more lifetime suicide attempts and psychiatric hospitalizations in the SU + PTSD + Axis I group. The findings suggest that it is not PTSD per se, but the frequent co-occurrence of PTSD and other psychopathology that largely accounts for previously reported greater problem severity of SLID patients with PTSD. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Cacciola, John S.] Treatment Res Inst, Philadelphia, PA 19106 USA. [Cacciola, John S.; Koppenhaver, Janelle M.; Alterman, Arthur I.; McKay, James R.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Ctr Studies Addict, Philadelphia, PA 19104 USA. RP Cacciola, JS (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mail W, Philadelphia, PA 19106 USA. EM jcacciola@tresearch.org FU NIDA [P60DA005186] FX Funding for this study was provided in part by NIDA Grant P60DA005186 (Charles P. O'Brien, PI); the NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 37 TC 12 Z9 14 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2009 VL 101 IS 1-2 BP 27 EP 33 DI 10.1016/j.drugalcdep.2008.10.018 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 422KS UT WOS:000264427200005 PM 19062202 ER PT J AU Schwartz, SG Flynn, HW Aiello, LP AF Schwartz, Stephen G. Flynn, Harry W., Jr. Aiello, Lloyd Paul TI RUBOXISTAURIN MESILATE HYDRATE FOR DIABETIC RETINOPATHY SO DRUGS OF TODAY LA English DT Review ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; PKC-BETA INHIBITOR; RETINAL BARRIER PERMEABILITY; SMOOTH-MUSCLE-CELLS; MACULAR EDEMA; VITREOUS HEMORRHAGE; CLINICAL-TRIAL; UNITED-STATES; VISUAL-LOSS AB Diabetic retinopathy remains a major worldwide cause of preventable blindness. The isoform of protein kinase C (PKC) may play an important role in the pathogenesis of this disorder. Ruboxistaurin mesylate hydrate is an orally bioavailable, highly-specific inhibitor of PKC beta which has shown some efficacy in several large, multicenter, randomized clinical trials. The U.S. Food and Drug Administration issued an approvable letter for ruboxistaurin in 2006, but at this time the medication is not available for routine clinical use. C1 [Schwartz, Stephen G.; Flynn, Harry W., Jr.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Naples, FL 34102 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Schwartz, SG (reprint author), Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 311 9th St N,100, Naples, FL 34102 USA. EM sschwartz2@med.miami.edu FU National Eye Institute P30 Core Center [EY014801]; Research to Prevent Blindness to the University of Miami, Miami, FL; Genentech; Pfizer FX This research was partially supported by National Eye Institute P30 Core Center Grant EY014801 and by an unrestricted grant from Research to Prevent Blindness to the University of Miami, Miami, FL.; Dr. Schwartz has received research funding from Genentech, holds equity in Pfizer and is a co-holder of a pending patent entitled "Molecular targets for modulating intraocular pressure and differentiation of steroid responders versus non-responders." NR 51 TC 3 Z9 4 U1 0 U2 1 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 1699-3993 EI 1699-4019 J9 DRUG TODAY JI Drugs Today PD APR PY 2009 VL 45 IS 4 BP 269 EP 274 DI 10.1358/dot.2009.45.4.1354195 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 652QJ UT WOS:000282024400003 PM 19499092 ER PT J AU Adlard, PA James, SA Bush, AI Masters, CL AF Adlard, Paul A. James, Simon A. Bush, Ashley I. Masters, Colin L. TI beta-AMYLOID AS A MOLECULAR THERAPEUTIC TARGET IN ALZHEIMER'S DISEASE SO DRUGS OF TODAY LA English DT Review ID INSULIN-DEGRADING ENZYME; BRAIN A-BETA; ENDOTHELIN-CONVERTING ENZYME; GAMMA-SECRETASE CLEAVAGE; CENTRAL-NERVOUS-SYSTEM; PRECURSOR PROTEIN; PLASMINOGEN-ACTIVATOR; TRANSGENIC MICE; APOLIPOPROTEIN-J; A-BETA(42) IMMUNIZATION AB Alzheimer's disease is the most common form of dementia, primarily affecting individuals during or after their sixth decade of life. Despite decades of research, there are still no effective disease-modifying drugs available to treat this neurodegenerative disorder. Current FDA-approved medications primarily offer symptomatic relief and are based upon known neurotransmitter deficits. There are, however, many drugs in preclinical and clinical development which target other aspects of AD pathogenesis. Principal among these are drugs which modulate beta-amyloid, a protein that is believed to be central to the cascade which leads to the development of Alzheimer's disease. This article will outline the metabolism of P-amyloid and review a number of different strategies, including pitfalls and future directions of such methods that are directed towards the modulation of this protein. It will become clear that beta-amyloid represents a potent molecular target for pharmacological manipulation to perhaps prevent the onset and progression of Alzheimer's disease. C1 [Adlard, Paul A.; James, Simon A.; Bush, Ashley I.; Masters, Colin L.] Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02114 USA. [Adlard, Paul A.; Bush, Ashley I.; Masters, Colin L.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [James, Simon A.] Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia. RP Adlard, PA (reprint author), Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, 155 Oak St, Parkville, Vic 3052, Australia. EM padlard@mhri.edu.au RI Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; James, Simon/0000-0001-9369-3288 FU NHMRC; J.O. and J.R. Wicking Trust; Alzheimer's Association (U.S.) FX We gratefully acknowledge the support of the NH&MRC, the J.O. and J.R. Wicking Trust and the Alzheimer's Association (U.S.). NR 101 TC 14 Z9 18 U1 1 U2 5 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 1699-3993 J9 DRUG TODAY JI Drugs Today PD APR PY 2009 VL 45 IS 4 BP 293 EP 304 DI 10.1358/dot.2009.45.4.1353853 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 652QJ UT WOS:000282024400005 PM 19499094 ER PT J AU Taub, CC Stoler, JM Perez-Sanz, T Chu, J Isselbacher, EM Picard, MH Weyman, AE AF Taub, Cynthia C. Stoler, Joan M. Perez-Sanz, Teresa Chu, John Isselbacher, Eric M. Picard, Michael H. Weyman, Arthur E. TI Mitral Valve Prolapse in Marfan Syndrome: An Old Topic Revisited SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE Marfan syndrome; mitral valve prolapse; echocardiography ID NATURAL-HISTORY; FIBRILLIN-1 GENE; MUTATIONS; DIAGNOSIS; FBN1; PREVALENCE; PHENOTYPE; FEATURES; MANAGEMENT; CHILDHOOD AB Background: The echocardiographic features of mitral valve prolapse (MVP) in Marfan syndrome have been well described, and the incidence of MVP in Marfan syndrome is reported to be 40-80%. However, most of the original research was performed in the late 1980s and early 1990s, when the diagnostic criteria for MVP were less specific. Our goal was to investigate the characteristics of MVP associated with Marfan syndrome using currently accepted diagnostic criteria for MVP. Methods: Between January 1990 and March 2004, 90 patients with definitive diagnosis of Marfan syndrome (based on standardized criteria with or without genetic testing) were referred to Massachusetts General Hospital for transthoracic echocardiography. Patients' gender, age, weight, height, and body surface area at initial examination were recorded. Mitral valve thickness and motion, the degree of mitral regurgitation and aortic regurgitation, and aortic dimensions were quantified blinded to patients' clinical information. Results: There were 25 patients (28%) with MVP, among whom 80% had symmetrical bileaflet MVP. Patients with MVP had thicker mitral leaflets (5.0 +/- 1.0 mm vs. 1.8 +/- 0.5 mm, P < 0.001), more mitral regurgitation (using a scale of 1-4, 2.2 +/- 1.0 vs. 0.90 +/- 0.60, P < 0.0001), larger LVEDD, and larger dimensions of sinus of Valsalva, sinotubular junction, aortic arch, and descending aorta indexed to square root body surface area, when compared with those without MVP. When echocardiographic features of patients younger than 18 years of age and those of patients older than 18 were compared, adult Marfan patients had larger LA dimension (indexed to square root body surface area), larger sinotubular junction (indexed to square root body surface area), and more mitral regurgitation and aortic regurgitation. Conclusions: The prevalence of MVP in Marfan syndrome is lower than previously reported. The large majority of patients with MVP have bileaflet involvement, and those with MVP have significantly larger aortic root diameters, suggesting a diffuse disease process. (ECHOCARDIOGRAPHY, Volume 26, April 2009). C1 [Taub, Cynthia C.; Stoler, Joan M.; Perez-Sanz, Teresa; Chu, John; Isselbacher, Eric M.; Picard, Michael H.; Weyman, Arthur E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Taub, CC (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 1825 Eastchester Rd, Bronx, NY 10461 USA. EM ctaub05@yahoo.com OI Picard, Michael/0000-0002-9264-3243 NR 37 TC 18 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD APR PY 2009 VL 26 IS 4 BP 357 EP 364 DI 10.1111/j.1540-8175.2008.00825.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428VD UT WOS:000264878600001 PM 19054044 ER PT J AU Nelson, EJ Tanudra, A Chowdhury, A Kane, AV Qadri, F Calderwood, SB Coburn, J Camilli, A AF Nelson, Eric J. Tanudra, Angela Chowdhury, Ashrafuzzaman Kane, Anne V. Qadri, Firdausi Calderwood, Stephen B. Coburn, Jenifer Camilli, Andrew TI High Prevalence of Spirochetosis in Cholera Patients, Bangladesh SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HUMAN INTESTINAL SPIROCHETOSIS; PATHOGEN-FREE CHICKS; BRACHYSPIRA-PILOSICOLI; INFECTION; DIARRHEA; AALBORGI; MODEL AB The microbes that accompany the etiologic agent of cholera, Vibrio cholerae, are only now being defined. In this study, spirochetes from the genus Brachyspira were identified at high titers in more than one third of cholera patients in Bangladesh. Spirochetosis should now be tracked in the setting of cholera outbreaks. C1 [Nelson, Eric J.; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Tanudra, Angela; Coburn, Jenifer] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Tanudra, Angela; Kane, Anne V.; Coburn, Jenifer] Tufts Med Ctr, Boston, MA USA. [Chowdhury, Ashrafuzzaman] Jahangirnagar Univ, Dhaka, Bangladesh. [Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu FU National Institutes of Health (NIH) [A1055058, D43 TW005572] FX This study was Supported by National Institutes of Health (NIH) grant A1055058 to A.C. E.J.N. is a recipient of the Fogarty/Ellison Fellowship in Global Health awarded by the Fogarty International Center at NIH (D43 TW005572). A.C. is an investigator of the Howard Hughes Medical Institute. NR 15 TC 7 Z9 7 U1 0 U2 0 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR PY 2009 VL 15 IS 4 BP 571 EP 573 DI 10.3201/eid1504.081214 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 425NR UT WOS:000264644900009 PM 19331734 ER PT J AU Ma, RS Latif, R Davies, TF AF Ma, Risheng Latif, Rauf Davies, Terry F. TI Thyrotropin-Independent Induction of Thyroid Endoderm from Embryonic Stem Cells by Activin A SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR MESSENGER-RNA; DEFINITIVE ENDODERM; IN-VITRO; DIFFERENTIATION; EXPRESSION; MOUSE; TSH; CULTURE AB To model the differentiation of thyroid epithelial cells, we examined embryoid bodies derived from undifferentiated murine embryonic stem cells treated with activin A to induce endoderm differentiation, the germ layer from which thyroid cells occur. The resulting endodermal cells were then further exposed to TSH and/or IGF-I for up to 21 d. Oct-4 and REX1 expression, required to sustain stem cell self-renewal and pluripotency, were appropriately down-regulated, whereas GATA-4, and alpha-fetoprotein, both endodermal-specific markers, increased as the embryonic stem cells were exposed to activin A. By d 5 culture, TSH receptor (TSHR) and sodium iodide symporter (NIS) gene and protein expression were markedly induced. Cells isolated by the fluorescence-activated cell sorter simultaneously expressed not only TSHR and NIS proteins but also PAX8 mRNA, an expression pattern unique to thyroid cells and expected in committed thyroid progenitor cells. Such expression continued until d 21 with no influence seen by the addition of TSH or IGF-I. The sequence of gene expression changes observed in these experiments demonstrated the emergence of definitive thyroid endoderm. The activin A induction of thyroid-specific markers, NIS and TSHR, occurred in the absence of TSH stimulation, and, therefore, the emergence of thyroid endoderm in vitro paralleled the emergence of thyroid cells in TSHR-knockout mice. Activin A is clearly a major regulator of thyroid endoderm. (Endocrinology 150: 1970-1975, 2009) C1 [Ma, Risheng; Latif, Rauf; Davies, Terry F.] James J Peters Vet Affairs Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, Bronx, NY 10468 USA. RP Ma, RS (reprint author), Vet Affairs Med Ctr, Room 2F-27,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM risheng.ma@mssm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK069713]; Veteran Affairs Merit Award program; David Owen Segal Endowment [T32-DK007645-19] FX Supported in part by DK069713 from the National Institute of Diabetes and Digestive and Kidney Diseases, the Veteran Affairs Merit Award program (to T. F. D.), the David Owen Segal Endowment, and the T32-DK007645-19 Training Grant in Molecular and Cellular Endocrinology. NR 20 TC 22 Z9 23 U1 0 U2 7 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 APR PY 2009 VL 150 IS 4 BP 1970 EP 1975 DI 10.1210/en.2008-1374 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 422QN UT WOS:000264442900050 PM 19074581 ER PT J AU Grozovsky, R Ribich, S Rosene, ML Mulcahey, MA Huang, SA Patti, ME Bianco, AC Kim, BW AF Grozovsky, Renata Ribich, Scott Rosene, Matthew L. Mulcahey, Michelle A. Huang, Stephen A. Patti, Mary Elizabeth Bianco, Antonio C. Kim, Brian W. TI Type 2 Deiodinase Expression Is Induced by Peroxisomal Proliferator-Activated Receptor-gamma Agonists in Skeletal Myocytes SO ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOSE-TISSUE; II IODOTHYRONINE DEIODINASE; THYROID-HORMONE ACTIVATION; RESTING ENERGY-EXPENDITURE; SMOOTH-MUSCLE-CELLS; ADAPTIVE THERMOGENESIS; THR92ALA POLYMORPHISM; TARGETED DISRUPTION; INSULIN-RESISTANCE; BILE-ACIDS AB The thyroid hormone activating type 2 deiodinase (D2) is known to play a role in brown adipose tissue-mediated adaptive thermogenesis in rodents, but the finding of D2 in skeletal muscle raises the possibility of a broader metabolic role. In the current study, we examined the regulation of the D2 pathway in primary skeletal muscle myoblasts taken from both humans and mice. We found that pioglitazone treatment led to a 1.6- to 1.9-fold increase in primary human skeletal myocyte D2 activity; this effect was seen with other peroxisomal proliferator-activated receptor-gamma agonists. D2 activity in primary murine skeletal myotubes increased 2.8-fold in response to 5 mu M pioglitazone and 1.6- fold in response to 5 nM insulin and increased in a dose-dependent manner in response to lithocholic acid (maximum response at 25 mu M was similar to 3.8-fold). We compared Akt phosphorylation in primary myotubes derived from wild-type and D2 knockout (D2KO) mice: phospho-Akt was reduced by 50% in the D2KO muscle after 1 nM insulin exposure. Expression of T(3)-responsive muscle genes via quantitative RT-PCR suggests that D2KO cells have decreased thyroid hormone signaling, which could contribute to the abnormalities in insulin signaling. D2 activity in skeletal muscle fragments from both murine and human sources was low, on the order of about 0.01 fmol/min.mg of muscle protein. The phenotypic changes seen with D2KO cells support a metabolic role for D2 in muscle, hinting at a D2-mediated linkage between thyroid hormone and insulin signaling, but the low activity calls into question whether skeletal muscle D2 is a major source of plasma T(3). (Endocrinology 150: 1976-1983, 2009) C1 [Grozovsky, Renata; Ribich, Scott; Rosene, Matthew L.; Bianco, Antonio C.; Kim, Brian W.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. [Mulcahey, Michelle A.; Huang, Stephen A.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Patti, Mary Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kim, BW (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, HIM Bldg,Room 61,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM bwkim@partners.org RI Bianco, Antonio/A-4965-2008 OI Bianco, Antonio/0000-0001-7737-6813 FU National Institutes of Health [DK77148, K08 DK064643]; American Thyroid Association FX This work was supported by National Institutes of Health Grants DK77148 and K08 DK064643 and an American Thyroid Association research grant. NR 50 TC 39 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2009 VL 150 IS 4 BP 1976 EP 1983 DI 10.1210/en.2008-0938 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 422QN UT WOS:000264442900051 PM 19036883 ER PT J AU Calafat, AM Weuve, J Ye, XY Jia, LT Hu, H Ringer, S Huttner, K Hauser, R AF Calafat, Antonia M. Weuve, Jennifer Ye, Xiaoyun Jia, Lily T. Hu, Howard Ringer, Steven Huttner, Ken Hauser, Russ TI Exposure to Bisphenol A and Other Phenols in Neonatal Intensive Care Unit Premature Infants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE benzophenone; biomonitoring; BPA; glucuronidation; neonate; NICU; paraben; triclosan ID ESTROGENIC ENDOCRINE DISRUPTORS; DEVELOPMENTAL EXPOSURE; URINARY CONCENTRATIONS; ENVIRONMENTAL PHENOLS; US POPULATION; HUMAN-LIVER; MALE RATS; HEALTH; PARABENS; MICE AB OBJECTIVE: We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices. MEASUREMENTS: We measured the urinary concentrations of free and total (free plus conjugated) species of BPA, triclosan, benzophenone-3, methyl paraben, and propyl paraben. RESULTS: The percentage of BPA present as its conjugated species was > 90% in more than three-quarters of the premature infants. Intensity of rise of products containing DEHP was strongly associated with BPA total concentrations but not with any other phenol. Adjusting for institution and sex, BPA total concentrations among infants in the group of high use of DEHP-containing products were 8.75 times as high as among infants in the low use group (p < 0.0001). Similarly, after adjusting for sex and DEHP-containing product use category, BPA total concentrations among infants in Institution A were 16.6 times as high as those among infants in Institution B (p < 0.0001). CONCLUSION: BPA geometric mean urinary concentration (30.3 mu g/L) among premature infants undergoing intensive therapeutic medical interventions was one order of magnitude higher than that among the general population. Conjugated species were the primary urinary metabolites of BPA, suggesting that premature infants have some capacity to metabolize BPA. The differences in exposure to BPA by intensity of use of DEHP-containing medical products highlight the need for further studies to determine the specific source(s) of exposure to BPA. C1 [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. [Weuve, Jennifer] Rush Univ, Rush Inst Healthy Aging, Med Ctr, Chicago, IL 60612 USA. [Weuve, Jennifer; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hu, Howard] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Hu, Howard] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Ringer, Steven] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. [Huttner, Ken] Harvard Univ, Sch Med, Neonatol Unit, Boston, MA USA. RP Calafat, AM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, 4770 Buford Hwy,Mailstop F53, Atlanta, GA 30341 USA. EM acalafat@cdc.gov OI Hu, Howard/0000-0002-3676-2707 NR 49 TC 106 Z9 111 U1 5 U2 21 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2009 VL 117 IS 4 BP 639 EP 644 DI 10.1289/ehp.0800265 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 426JQ UT WOS:000264704500040 PM 19440505 ER PT J AU Hao, BH Clancy, CJ Cheng, SJ Raman, SB Iczkowski, KA Nguyen, MH AF Hao, Binghua Clancy, Cornelius J. Cheng, Shaoji Raman, Suresh B. Iczkowski, Kenneth A. Nguyen, M. Hong TI Candida albicans RFX2 Encodes a DNA Binding Protein Involved in DNA Damage Responses, Morphogenesis, and Virulence SO EUKARYOTIC CELL LA English DT Article ID CANDIDA-ALBICANS GENES; YEAST-HYPHA MORPHOGENESIS; HUMAN ORAL CANDIDOSIS; SACCHAROMYCES-CEREVISIAE; FILAMENTOUS GROWTH; CHECKPOINT PATHWAYS; FUNGAL PATHOGEN; REPLICATION; EXPRESSION; TRANSCRIPTION AB We previously showed that Candida albicans orf19.4590, which we have renamed RFX2, expresses a protein that is reactive with antibodies in persons with candidiasis. In this study, we demonstrate that C. albicans RFX2 shares some functional redundancy with Saccharomyces cerevisiae RFX1. Complementation of an S. cerevisiae rfx1 mutant with C. albicans RFX2 partially restored UV susceptibility and the repression of DNA damage response genes. DNA damage- and UV-induced genes RAD6 and DDR48 were derepressed in a C. albicans rfx2 null mutant strain under basal conditions, and the mutant was significantly more resistant to UV irradiation, heat shock, and ethanol than wild-type strain SC5314. The rfx2 mutant was hyperfilamentous on solid media and constitutively expressed hypha-specific genes HWP1, ALS3, HYR1, ECE1, and CEK1. The mutant also demonstrated increased invasion of solid agar and significantly increased adherence to human buccal epithelial cells. During hematogenously disseminated candidiasis, mice infected with the mutant had a significantly delayed time to death compared to the wild type. During oropharyngeal candidiasis, mice infected with the mutant had significantly lower tissue burdens in the oral cavity and esophagus at 7 days and they were less likely to develop disseminated infections because of mucosal translocation. data demonstrate that C. albicans Rfx2p regulates DNA damage responses, morphogenesis, and virulence. C1 [Hao, Binghua; Clancy, Cornelius J.; Cheng, Shaoji; Raman, Suresh B.; Nguyen, M. Hong] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15203 USA. [Clancy, Cornelius J.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Iczkowski, Kenneth A.] Univ Colorado, Dept Pathol, Denver, CO 80202 USA. RP Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, 3550 Terrace St,Suite 871, Pittsburgh, PA 15203 USA. EM MHN5+@pitt.edu FU NIH Mycology Research Unit Program [5P01AI061537- 02]; VA Medical Research Service; University of Florida FX Research was funded by an NIH Mycology Research Unit Program Project Award (5P01AI061537- 02 to C. J. C. and M. H. N.) and supported by the VA Medical Research Service and the University of Florida. NR 56 TC 18 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD APR PY 2009 VL 8 IS 4 BP 627 EP 639 DI 10.1128/EC.00246-08 PG 13 WC Microbiology; Mycology SC Microbiology; Mycology GA 431DP UT WOS:000265041800023 PM 19252121 ER PT J AU Grasso, G Bush, AI D'Agata, R Rizzarelli, E Spoto, G AF Grasso, Giuseppe Bush, Ashley I. D'Agata, Roberta Rizzarelli, Enrico Spoto, Giuseppe TI Enzyme solid-state support assays: a surface plasmon resonance and mass spectrometry coupled study of immobilized insulin degrading enzyme SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Solid-state assay; Surface plasmon resonance; Mass spectrometry; Insulin degrading enzyme; Conformational change ID CONFORMATIONAL-CHANGES; KINETIC-DATA; BINDING; PROTEIN; MS; SPECTROSCOPY; AU(111); DISEASE; TARGET; DOMAIN AB Solid-support based assays offer several advantages that are not normally available in solution. Enzymes that are anchored on gold surfaces can interact with several different molecules, opening the way to high throughput array format based assays. In this scenario, surface plasmon resonance (SPR) and mass spectrometry (MS) investigations have often been applied to analyze the interaction between immobilized enzyme and its substrate molecules in a tag-free environment. Here, we propose a SPR-MS combined experimental approach aimed at studying insulin degrading enzyme (IDE) immobilized onto gold surfaces and its ability to interact with insulin. The latter is delivered by a microfluidic system to the IDE functionalized surface and the activity of the immobilized enzyme is verified by atmospheric pressure/matrix assisted laser desorption ionization (AP/MALDI) MS analysis. The SPR experiments allow the calculation of the kinetic constants involved for the interaction between immobilized IDE and insulin molecules and evidence of IDE conformational change upon insulin binding is also obtained. C1 [Grasso, Giuseppe; D'Agata, Roberta; Rizzarelli, Enrico; Spoto, Giuseppe] Univ Catania, Dipartimento Sci Chim, I-95125 Catania, Italy. [Bush, Ashley I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestone, MA USA. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Spoto, Giuseppe] CNR, Ist Biostrutture & Bioimmagini, I-95125 Catania, Italy. RP Grasso, G (reprint author), Univ Catania, Dipartimento Sci Chim, Vle A Doria 6, I-95125 Catania, Italy. EM grassog@unict.it RI Grasso, Giuseppe/E-3893-2010; Bush, Ashley/A-1186-2007 OI Grasso, Giuseppe/0000-0002-7179-4835; Bush, Ashley/0000-0001-8259-9069 FU MIUR [FIRB RBNE03PX83, RBIN04L28Y]; "EURAMY: Systemic Amyloidoses in Europe'', 037525 [LSHM-CT-2006-037525] FX We thank MIUR ( FIRB RBNE03PX83, RBIN04L28Y) and "EURAMY: Systemic Amyloidoses in Europe'', 037525 (LSHM-CT-2006-037525) for partial financial support. NR 36 TC 17 Z9 17 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 EI 1432-1017 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD APR PY 2009 VL 38 IS 4 BP 407 EP 414 DI 10.1007/s00249-008-0384-y PG 8 WC Biophysics SC Biophysics GA 420BJ UT WOS:000264263100006 PM 19048247 ER PT J AU van Kimmenade, RRJ Januzzi, JL AF van Kimmenade, Roland R. J. Januzzi, James L., Jr. TI Whose heart will get broken? Troponin testing and future heart failure SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; POPULATION; PREVALENCE C1 [van Kimmenade, Roland R. J.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 NR 10 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2009 VL 30 IS 7 BP 755 EP 756 DI 10.1093/eurheartj/ehp092 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428ZC UT WOS:000264889600008 PM 19264751 ER PT J AU Kaab, S Darbar, D van Noord, C Dupuis, J Pfeufer, A Newton-Cheh, C Schnabel, R Makino, S Sinner, MF Kannankeril, PJ Beckmann, BM Choudry, S Donahue, BS Heeringa, J Perz, S Lunetta, KL Larson, MG Levy, D MacRae, CA Ruskin, JN Wacker, A Schomig, A Wichmann, HE Steinbeck, G Meitinger, T Uitterlinden, AG Witteman, JCM Roden, DM Benjamin, EJ Ellinor, PT AF Kaab, Stefan Darbar, Dawood van Noord, Charlotte Dupuis, Josee Pfeufer, Arne Newton-Cheh, Christopher Schnabel, Renate Makino, Seiko Sinner, Moritz F. Kannankeril, Prince J. Beckmann, Britt M. Choudry, Subbarao Donahue, Brian S. Heeringa, Jan Perz, Siegfried Lunetta, Kathryn L. Larson, Martin G. Levy, Daniel MacRae, Calum A. Ruskin, Jeremy N. Wacker, Annette Schoemig, Albert Wichmann, H.-Erich Steinbeck, Gerhard Meitinger, Thomas Uitterlinden, Andre G. Witteman, Jacqueline C. M. Roden, Dan M. Benjamin, Emelia J. Ellinor, Patrick T. TI Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation SO EUROPEAN HEART JOURNAL LA English DT Article DE Atrial fibrillation; Genetics; Arrhythmia; Polymorphism; Meta-analysis ID OF-FUNCTION MUTATION; FAMILIAL AGGREGATION; RISK-FACTORS; POPULATION; HEART; PREVALENCE; PITX2; LOCUS; IDENTIFICATION; POLYMORPHISM AB A recent genome-wide association study identified a haplotype block on chromosome 4q25 associated with atrial fibrillation (AF). We sought to replicate this association in four independent cohorts. The Framingham Heart Study and Rotterdam Study are community-based longitudinal studies. The Vanderbilt AF Registry and German AF Network (AFNet) are case-control studies. Participants with AF (n = 3508) were more likely to be male and were older than referent participants (n = 12 173; Framingham 82 +/- 10 vs. 71 +/- 13 years; Rotterdam 73 +/- 8 vs. 69 +/- 9 years; Vanderbilt 54 +/- 14 vs. 57 +/- 14 years; AFNet 62 +/- 12 vs. 49 +/- 14 years). Single nucleotide polymorphism (SNP) rs2200733 was associated with AF in all four cohorts, with odds ratios (ORs) ranging from 1.37 in Rotterdam [95% confidence interval (CI) 1.18-1.59; P = 3.1 x 10(-5)] to 2.52 in AFNet (95% CI 2.22-2.8; P = 1.8 x 10(-49)). There also was a significant association between AF and rs10033464 in Framingham (OR 1.34; 95% CI 1.03-1.75; P = 0.031) and AFNet (OR 1.30; 95% CI 1.13-1.51; P = 0.0002), but not Vanderbilt (OR 1.16; 95% CI 0.86-1.56; P = 0.33). A meta-analysis of the current and prior AF studies revealed an OR of 1.90 (95% CI 1.60-2.26; P = 3.3 x 10(-13)) for rs2200733 and of 1.36 (95% CI 1.26-1.47; P = 6.7 x 10(-15)) for rs10033464. The non-coding SNPs rs2200733 and rs10033464 are strongly associated with AF in four cohorts of European descent. These results confirm the significant relations between AF and intergenic variants on chromosome 4. C1 [Makino, Seiko; Choudry, Subbarao; MacRae, Calum A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kaab, Stefan; Sinner, Moritz F.; Beckmann, Britt M.; Steinbeck, Gerhard] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Darbar, Dawood] Vanderbilt Univ, Sch Med, Div Cardiol, Nashville, TN 37232 USA. [van Noord, Charlotte; Heeringa, Jan] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [van Noord, Charlotte] Dutch Med Evaluat Board, The Hague, Netherlands. [Dupuis, Josee; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee; Newton-Cheh, Christopher; Schnabel, Renate; Lunetta, Kathryn L.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. [Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Klinikum Rechts Isar, D-81675 Munich, Germany. [Pfeufer, Arne; Meitinger, Thomas] Helmholtz Zentrum Munchen Deutsch Forschungszentr, D-85764 Neuherberg, Germany. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. [Donahue, Brian S.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Perz, Siegfried] Helmholtz Zentrum Munchen Deutsch Forschungszentr, Inst Med Informat, D-85764 Neuherberg, Germany. [Larson, Martin G.] Boston Univ, Dept Math Stat, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Ruskin, Jeremy N.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Wacker, Annette] Univ Klin Kinder & Jugendmed, Tubingen, Germany. [Schoemig, Albert] Tech Univ Munich, Kardiol Klin, Deutsches Herzzentrum Munchen, D-80636 Munich, Germany. [Wichmann, H.-Erich] Univ Munich, IBE Chair Epidemiol, Munich, Germany. [Wichmann, H.-Erich] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Cardiol & Prevent Med Div, Boston, MA 02118 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM pellinor@partners.org RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Schnabel, Renate/F-6527-2014; Darbar, Dawood/C-9079-2015; Meitinger, Thomas/O-1318-2015; OI Darbar, Dawood/0000-0002-4103-5977; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23 HL075266, HL 075266, HL 076784, N01 HC 25195, R01 HL075431, R01 HL104156, U01 HL 65962, U01 HL065962, U01 HL065962-08]; NIA NIH HHS [AG 028321]; NINDS NIH HHS [6R01 NS 17950] NR 46 TC 103 Z9 106 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2009 VL 30 IS 7 BP 813 EP 819 DI 10.1093/eurheartj/ehn578 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428ZC UT WOS:000264889600016 PM 19141561 ER PT J AU Brouwer, IA Raitt, MH Dullemeijer, C Kraemer, DF Zock, PL Morris, C Katan, MB Connor, WE Camm, JA Schouten, EG McAnulty, J AF Brouwer, Ingeborg A. Raitt, Merritt H. Dullemeijer, Carla Kraemer, Dale F. Zock, Peter L. Morris, Cynthia Katan, Martijn B. Connor, William E. Camm, John A. Schouten, Evert G. McAnulty, John TI Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators SO EUROPEAN HEART JOURNAL LA English DT Article DE ICD; Arrhythmia; Fish oil; Omega-3 ID POLYUNSATURATED FATTY-ACIDS; REINFARCTION TRIAL DART; CORONARY-HEART-DISEASE; SUDDEN-DEATH; MYOCARDIAL-INFARCTION; RISK; SUPPLEMENTATION; METAANALYSIS; ARRHYTHMIAS; PREVENTION AB To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies. C1 [Brouwer, Ingeborg A.; Dullemeijer, Carla; Schouten, Evert G.] TI Food & Nutr, Wageningen, Netherlands. [Brouwer, Ingeborg A.] Vrije Univ Amsterdam, Inst Hlth Sci, NL-1081 HV Amsterdam, Netherlands. [Raitt, Merritt H.] Portland VA Med Ctr, Portland, OR USA. [Dullemeijer, Carla] Univ Wageningen & Res Ctr, Dept Human Nutr, Wageningen, Netherlands. [Kraemer, Dale F.; Morris, Cynthia] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Kraemer, Dale F.; Morris, Cynthia] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Kraemer, Dale F.] Oregon State Univ, Dept Pharm Practice, Portland, OR USA. [Zock, Peter L.] Unilever Food & Hlth Res Inst, Vlaardingen, Netherlands. [Connor, William E.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Metab & Clin Nutr, Portland, OR 97201 USA. [Camm, John A.] St George Hosp & Med Sch, London, England. [McAnulty, John] Good Samaritan Hosp, Portland, OR 97210 USA. RP Brouwer, IA (reprint author), TI Food & Nutr, Wageningen, Netherlands. EM ingeborg.brouwer@falw.vu.nl OI Raitt, Merritt/0000-0001-5638-7732 FU Wageningen Centre for Food Sciences (WCFS); National Institutes of Health [R01HL61682]; Public Health Service [5 M01 RROO334]; Top Institute Food and Nutrition; TI Food and Nutrition FX The SOFA study was funded by the Wageningen Centre for Food Sciences (WCFS) with an additional grant from the European Union (SEAFOODplus integrated project No. 506359). The Portland study was funded by the National Institutes of Health (grant R01HL61682), Public Health Service (grant 5 M01 RROO334), and Hoffman-LaRoche Inc. The meta- analysis and pooled analysis were funded by Top Institute Food and Nutrition. TI Food and Nutrition, formerly known as WCFS, is a public/private partnership. Partners are major Dutch food companies and research organizations. NR 26 TC 69 Z9 70 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2009 VL 30 IS 7 BP 820 EP 826 DI 10.1093/eurheartj/ehp003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428ZC UT WOS:000264889600017 PM 19196720 ER PT J AU Mahabadi, AA Massaro, JM Rosito, GA Levy, D Murabito, JM Wolf, PA O'Donnell, CJ Fox, CS Hoffmann, U AF Mahabadi, Amir A. Massaro, Joseph M. Rosito, Guido A. Levy, Daniel Murabito, Joanne M. Wolf, Philip A. O'Donnell, Christopher J. Fox, Caroline S. Hoffmann, Udo TI Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Article DE Pericardial fat; Visceral abdominal fat; Cardiovascular disease; Framingham Heart Study; Epidemiology ID EPICARDIAL ADIPOSE-TISSUE; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; METABOLIC SYNDROME; RISK-FACTORS; INSULIN-RESISTANCE; PLASMA-PROTEIN; OBESITY; ADIPONECTIN; CELL AB The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD). Participants from the Framingham Heart Study Offspring cohort underwent abdominal and chest multidetector computed tomography to quantify volumes of pericardial fat, intrathoracic fat, and VAT. Relations between each fat depot and CVD were assessed using logistic regression. The analysis of 1267 participants (mean age 60 years, 53.8% women, 9.7% with prevalent CVD) demonstrated that pericardial fat [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.11-1.57; P = 0.002] and VAT (OR 1.35, 95% CI 1.11-1.57; P = 0.003), but not intrathoracic fat (OR 1.14, 95% CI 0.93-1.39; P = 0.22), were significantly associated with prevalent CVD in age-sex-adjusted models and after adjustment for body mass index and waist circumference. After multivariable adjustment, associations were attenuated (P > 0.14). Only pericardial fat was associated with prevalent myocardial infarction after adjusting for conventional measures of adiposity (OR 1.37, 95% CI 1.03-1.82; P = 0.03). Pericardial fat and VAT, but not intrathoracic fat, are associated with CVD independent of traditional measures of obesity but not after further adjustment for traditional risk factor. Taken together with our prior work, these findings may support the hypothesis that pericardial fat contributes to coronary atherosclerosis. C1 [Mahabadi, Amir A.; Rosito, Guido A.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Murabito, Joanne M.; Wolf, Philip A.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Murabito, Joanne M.; Wolf, Philip A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. [Massaro, Joseph M.; Levy, Daniel; Murabito, Joanne M.; Wolf, Philip A.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rosito, Guido A.] Fed Fdn Sch Med Sci Porto Alegre, Porto Alegre, RS, Brazil. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Murabito, Joanne/0000-0002-0192-7516 NR 36 TC 226 Z9 246 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2009 VL 30 IS 7 BP 850 EP 856 DI 10.1093/eurheartj/ehn573 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428ZC UT WOS:000264889600021 PM 19136488 ER PT J AU Mak, KH Bhatt, DL Shao, M Haffner, SM Hamm, CW Hankey, GJ Johnston, SC Montalescot, G Steg, PG Steinhubl, SR Fox, KAA Topol, EJ AF Mak, Koon-Hou Bhatt, Deepak L. Shao, Mingyuan Haffner, Steven M. Hamm, Christian W. Hankey, Graeme J. Johnston, S. Claiborne Montalescot, Gilles Steg, Philippe Gabriel Steinhubl, Steven R. Fox, Keith A. A. Topol, Eric J. TI The influence of body mass index on mortality and bleeding among patients with or at high-risk of atherothrombotic disease SO EUROPEAN HEART JOURNAL LA English DT Article DE Aspirin; Cardiovascular; Clopidogrel; Myocardial infarction; Obesity; Stroke ID CORONARY-HEART-DISEASE; UNITED-STATES; CARDIOVASCULAR MORTALITY; MYOCARDIAL-INFARCTION; PROSPECTIVE COHORT; OBESITY; ASSOCIATION; OVERWEIGHT; NUTRITION; EVENTS AB We aimed to determine the relationship between body mass index (BMI) and cardiovascular events among individuals with or at-risk of atherothrombotic disease. This was a prospective observational study of 15 532 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who were randomly assigned to clopidogrel or placebo, and followed-up for a median of 28 months for the occurrence of the primary endpoint (cardiovascular death, myocardial infarction, or stroke), all-cause mortality, and bleeding complications. Compared with the highest BMI quartile, the primary endpoint, cardiovascular, and all-cause mortality all occurred more frequently among patients in the lowest BMI quartile (about a third lower). The relationship between continuous BMI and adverse cardiovascular outcomes were presented as two linear spline terms with 29 kg/m(2) as the cut-point for all-cause mortality. Lower BMI was associated with an increase in moderate and severe bleeding complications, largely accounted for by those receiving dual-antiplatelet agents with the highest tertile aspirin dose. Adverse cardiovascular events and bleeding complications occurred more frequently among individuals with or at-risk for atherothrombotic disease and low BMI. Further studies should be directed to these patients to improve outcomes. The CHARISMA trial is registered with ClinicalTrials.gov, NCT00050817. C1 [Mak, Koon-Hou] Gleneagles Med Ctr, Singapore 258499, Singapore. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shao, Mingyuan] Cleveland Clin, Cleveland, OH 44106 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hamm, Christian W.] Kerckhoff Heart Ctr, Bad Nauheim, Germany. [Hankey, Graeme J.] Univ Western Australia, Royal Perth Hosp, Perth, WA 6009, Australia. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Johnston, S. Claiborne] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Montalescot, Gilles] CHU Pitie Salpetriere, Inst Cardiol, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, F-75877 Paris 18, France. [Steinhubl, Steven R.] Geisinger Med Clin, Danville, PA USA. [Steinhubl, Steven R.] Medicines Co, Zurich, Switzerland. [Fox, Keith A. A.] Univ & Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland. [Topol, Eric J.] Scripps Translat Res Inst, La Jolla, CA USA. RP Mak, KH (reprint author), Gleneagles Med Ctr, 6 Napier Rd 08-13, Singapore 258499, Singapore. EM makheart@gmail.com RI Hankey, Graeme /H-4968-2014; OI Hankey, Graeme /0000-0002-6044-7328; Topol, Eric/0000-0002-1478-4729 NR 25 TC 22 Z9 24 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2009 VL 30 IS 7 BP 857 EP 865 DI 10.1093/eurheartj/ehp037 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428ZC UT WOS:000264889600023 PM 19233855 ER PT J AU Nemeth, T Kovacs, M Kertesz, Z Szabo, M Settleman, J Mocsai, A AF Nemeth, T. Kovacs, M. Kertesz, Zs. Szabo, M. Settleman, J. Mocsai, A. TI The role of p190RhoGAP in neutrophils SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Nemeth, T.; Kovacs, M.; Kertesz, Zs.; Szabo, M.; Mocsai, A.] Semmelweis Univ, Sch Med, Dept Physiol, Budapest, Hungary. [Settleman, J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Settleman, J.] Harvard Univ, Sch Med, Charlestown, MA USA. RI Mocsai, Attila/B-2792-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2009 VL 39 SU 1 BP 34 EP 35 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 412UZ UT WOS:000263751000095 ER PT J AU Little, J Higgins, JP Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, MJ Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, AFR Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex F. R. Birkett, Nick TI STrengthening the REporting of Genetic Association studies (STREGA) - an extension of the STROBE statement SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE Epidemiology; gene-disease associations; gene-environment interaction; genetics; genome-wide association; meta-analysis; reporting recommendations; systematic review ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis. C1 [Little, Julian] Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. [Gagnon, France] Univ Toronto, Toronto, ON, Canada. [von Elm, Erik] Univ Bern, Bern, Switzerland. [Khoury, Muin J.; Gwinn, Marta] Natl Off Publ Hlth Genom, Atlanta, GA USA. [Cohen, Barbara] Publ Lib Sci, San Francisco, CA USA. [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zou, Guang Yong] Univ Western Ontario, London, ON, Canada. [van Duijn, Cornelia] European Journal Epidemiol, Rotterdam, Netherlands. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Wells, George; Stewart, Alex F. R.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada. [Higgins, Julian P. T.] MRC Biostat Unit, Cambridge, England. [Ioannidis, John P. A.] Univ Ioannina, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [von Elm, Erik] Univ Med Ctr, Freiburg, Germany. [Davey-Smith, George] Univ Bristol, Bristol, Avon, England. [Zou, Guang Yong] Robarts Res Inst, Ottawa, ON, Canada. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [Paterson, Andrew] Canada Res Chair Genet Complex Dis, Toronto, ON, Canada. [Fortier, Isabel] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Infante-Rivard, Claire] McGill Univ, Montreal, PQ, Canada. RP Little, J (reprint author), Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Stewart, Alexandre/A-5677-2011; Grimshaw, Jeremy/D-8726-2013; McLaughlin, John/E-4577-2013; Zou, Guangyong/K-6408-2013; Paterson, Andrew/A-4088-2011; OI Golding, Jean/0000-0003-2826-3307; Moher , David /0000-0003-2434-4206; Higgins, Julian/0000-0002-8323-2514; Paterson, Andrew/0000-0002-9169-118X; von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Grimshaw, Jeremy/0000-0001-8015-8243 FU Institutes of Genetics and of Nutrition, Metabolism and Diabetes, Canadian Institutes of Health Research; Genome Canada; Biotechnology, Genomics and Population Health Branch, Public Health Agency of Canada; Affymetrix; DNA Genotek; TrialStat!; GeneSens FX Grant support by the Institutes of Genetics and of Nutrition, Metabolism and Diabetes, Canadian Institutes of Health Research; Genome Canada; Biotechnology, Genomics and Population Health Branch, Public Health Agency of Canada; Affymetrix; DNA Genotek; TrialStat!; and GeneSens. The funders had no role in the decision to submit the article or in its preparation. NR 154 TC 101 Z9 114 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2009 VL 39 IS 4 BP 247 EP 266 DI 10.1111/j.1365-2362.2009.02125.x PG 20 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 416QY UT WOS:000264021800001 PM 19297801 ER PT J AU Schytz, HW Wienecke, T Jensen, LT Selb, J Boas, DA Ashina, M AF Schytz, H. W. Wienecke, T. Jensen, L. T. Selb, J. Boas, D. A. Ashina, M. TI Cerebral blood flow assessment with indocyanine green bolus transit detection by near-infrared spectroscopy before and after acetazolamide provocation in humans SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE acetazolamide; blood flow index; cerebral blood flow; indocyanine green; near-infrared spectroscopy; single photon emission computer tomography ID NONINVASIVE MEASUREMENT; CARDIOPULMONARY BYPASS; BRAIN-INJURY; ADULT HEAD; OXYGENATION; TOMOGRAPHY; STROKE; LIGHT AB It is important to find a reliable and bedside method, which can estimate the cerebral blood flow (CBF) of patients in clinical settings. Estimation of CBF by calculating a blood flow index (BFI) using continuous wave near-infrared spectroscopy (CW-NIRS) and indocyanine green (ICG) as an iv tracer has been proposed to be a feasible and promising method. To validate if the BFI method can detect relative changes in CBF we compared data with the established method (133)Xenon single photon emission computer tomography ((133)Xe-SPECT). Ten healthy subjects were investigated before and after a bolus of acetazolamide. NIRS data were obtained using a multi source detector separation configuration in order to assess a corrected BFI (BFI(corr)) value, which attempts to eliminate contamination of skin blood flow. Data obtained showed no significant correlation between CBF changes measured by (133)Xe-SPECT and BFI(corr) (0.133, P = 0.732). After acetazolamide, a 49% increase in CBF was detected using the (133)Xe-SPECT method, whereas no changes in any ICG variables were observed after acetazolamide. The study shows that it is not possible to obtain reliable BFI data, which reflect changes in CBF after acetazolamide infusion, using the CW-NIRS and ICG method. C1 [Schytz, H. W.; Wienecke, T.; Jensen, L. T.; Ashina, M.] Univ Copenhagen, Danish Headache Ctr, DK-2600 Glostrup, Denmark. [Schytz, H. W.; Wienecke, T.; Ashina, M.] Univ Copenhagen, Glostrup Hosp, Fac Hlth Sci, Dept Neurol, DK-2600 Glostrup, Denmark. [Jensen, L. T.] Univ Copenhagen, Glostrup Hosp, Fac Hlth Sci, Dept Clin Physiol & Nucl Med, DK-2600 Glostrup, Denmark. [Selb, J.; Boas, D. A.] Harvard Univ, Photon Migrat Imaging Lab, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging,Sch Med, Charlestown, MA USA. RP Schytz, HW (reprint author), Univ Copenhagen, Danish Headache Ctr, DK-2600 Glostrup, Denmark. EM henrikschytz@dadlnet.dk FU Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS) FX The authors wish to thank laboratory technicians Annette Foldager for her dedicated and excellent assistance. We also want to thank Peter Dalgaard from the Department of Biostatistics, University of Copenhagen for advice with the statistical design of the study. This study was supported by the Lundbeck Foundation via the Lundbeck Foundation Center for Neurovascular Signaling (LUCENS). NR 22 TC 27 Z9 28 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD APR PY 2009 VL 16 IS 4 BP 461 EP 467 DI 10.1111/j.1468-1331.2008.02398.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 421QH UT WOS:000264372900016 PM 19236469 ER PT J AU Tsuchiya, M Sharma, R Tye, CE Sugiyama, T Bartlett, JD AF Tsuchiya, Masahiro Sharma, Ramaswamy Tye, Coralee E. Sugiyama, Toshihiro Bartlett, John D. TI Transforming growth factor-beta 1 expression is up-regulated in maturation-stage enamel organ and may induce ameloblast apoptosis SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE ALC cells; ameloblast; apoptosis; enamel; TGF-beta 1 ID GROWTH-FACTOR-BETA; DEVELOPING RAT MOLARS; TGF-BETA; C-MYC; GENE-EXPRESSION; CELL-DEATH; IMMUNOHISTOCHEMICAL LOCALIZATION; TOOTH MORPHOGENESIS; MESSENGER-RNA; BCL-2 AB Transforming growth factor-beta 1 (TGF-beta 1) regulates a variety of cellular responses that are dependent on the developmental stage and on the origins of the cell or the tissue. In mature tissues, and especially in tissues of epithelial origin, TGF-beta 1 is generally considered to be a growth inhibitor that may also promote apoptosis. The ameloblast cells of the enamel organ epithelium are adjacent to and responsible for the developing enamel layer on unerupted teeth. Once the enamel layer reaches its full thickness, the tall columnar secretory-stage ameloblasts shorten, and a portion of these maturation-stage ameloblasts become apoptotic. Here we investigate whether TGF-beta 1 plays a role in apoptosis of the maturation-stage ameloblasts. We demonstrate in vitro that ameloblast lineage cells are highly susceptible to TGF-beta 1-mediated growth arrest and are prone to TGF-beta 1-mediated cell death/apoptosis. We also demonstrate in vivo that TGF-beta 1 is expressed in the maturation-stage enamel organ at significantly higher levels than in the earlier secretory-stage enamel organ. This increased expression of TGF-beta 1 correlates with an increase in expression of the enamel organ immediate-early stress-response gene and with a decrease in the anti-apoptotic Bcl2 : Bax expression ratio. We conclude that TGF-beta 1 may play an important role in ameloblast apoptosis during the maturation stage of enamel development. C1 [Sharma, Ramaswamy; Tye, Coralee E.; Bartlett, John D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Tsuchiya, Masahiro] Tohoku Univ, Grad Sch Dent, Div Aging & Geriatr Dent, Sendai, Miyagi 980, Japan. [Sugiyama, Toshihiro] Akita Univ, Sch Med, Dept Biochem, Akita 010, Japan. [Tsuchiya, Masahiro; Sharma, Ramaswamy; Tye, Coralee E.; Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Sharma, Ramaswamy/F-8401-2012; OI Tsuchiya, Masahiro/0000-0002-7000-4547 FU National Institute of Dental and Craniofacial Research [DE016276] FX This work was supported by National Institute of Dental and Craniofacial Research grant DE016276 (to JDB). NR 45 TC 14 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD APR PY 2009 VL 117 IS 2 BP 105 EP 112 DI 10.1111/j.1600-0722.2009.00612.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 419ST UT WOS:000264240700002 PM 19320718 ER PT J AU Li, G Passias, P Kozanek, M Shannon, BD Li, GA Villamil, F Bono, CM Harris, M Wood, KB AF Li, Gang Passias, Peter Kozanek, Michal Shannon, Brian D. Li, Guoan Villamil, Fernando Bono, Christopher M. Harris, Mitchel Wood, Kirkham B. TI Interobserver reliability and intraobserver reproducibility of powers ratio for assessment of atlanto-occipital junction: comparison of plain radiography and computed tomography SO EUROPEAN SPINE JOURNAL LA English DT Article DE Powers ratio; Interobserver reliability; Intraobserver reproducibility; Atlanto-occipital junction ID ATLANTO-OCCIPITAL DISLOCATION AB Powers ratio, as assessed on plain radiographs or computed tomography (CT) images, appears to have clinical and prognostic value. To date, the validation of this assessment tool has been limited to a small number of observers at a single site. No study has examined the intraobserver reproducibility and interobserver reliability of the Powers ratio measurement on plain radiographs or CT images among a large cohort of spine surgeons. This type of validation is critical to allow for the broader use of the Powers ratio methodology in research studies and clinical applications. Plain radiographs and spiral CT images of the cervical spine of 32 patients were assessed, and the Powers ratio was determined by five spine surgeons. Each surgeon performed three readings, 7 months apart. In the first round of measurements, the observers used only the Powers' method of instruction. The second and third measurement sets were obtained after an interactive teaching session on the methodology. The order of the images was altered for the second and third set of measurements. The coefficient of variation (Cv) was calculated to determine the intraobserver repeatability and interobserver reliability for each imaging technique. A Bland-Altman plot was then used to assess the agreement between the two imaging techniques. For interobserver reliability, the mean Cv of the Powers ratio was 9.09 and 4.31% for plain radiographs and CT, respectively. The Cv mean value for intraobserver reproducibility averaged 4.95% (range 1.39-9.08) when CT scans were used and 14.17% (range 7.54-34.30) when plain radiographs were used. For intraobserver reproducibility, the lowest and highest Cv mean value of five raters was 1.39 and 9.08% using CT scans and 7.54 and 34.3% using plain radiographs. The Bland-Altman plot, demonstrated that the two methods were in close agreement on the -0.8 and 0.89% interval for limits of agreement (bias +/- A 1.96 sigma). The intraobserver reproducibility and interobserver reliability of Powers ratio measurement was acceptable (< 5%) with CT scans but not with plain radiographs. However, despite the statistically inferior reliability and repeatability, the Bland-Altman plot analysis showed that given the -0.8 and 0.89% limits of agreement, the two methods may be used interchangeably in clinical practice. C1 [Li, Gang; Passias, Peter; Kozanek, Michal; Shannon, Brian D.; Li, Guoan; Villamil, Fernando; Wood, Kirkham B.] Massachusetts Gen Hosp, Dept Orthoped, Spine Serv, Boston, MA 02114 USA. [Li, Gang] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100083, Peoples R China. [Bono, Christopher M.; Harris, Mitchel] Brigham & Womens Hosp, Dept Orthoped, Spine Serv, Boston, MA 02115 USA. RP Wood, KB (reprint author), Massachusetts Gen Hosp, Dept Orthoped, Spine Serv, Boston, MA 02114 USA. EM kbwood@partners.org NR 11 TC 3 Z9 3 U1 0 U2 3 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 APR PY 2009 VL 18 IS 4 BP 577 EP 582 DI 10.1007/s00586-008-0877-5 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 428FY UT WOS:000264834600018 PM 19165510 ER PT J AU Hussein, MRA Ali, HO Abdulwahed, SR Argoby, Y Tobeigei, FH AF Hussein, Mahmoud-Rezk A. Ali, Hayder O. Abdulwahed, Saad R. Argoby, Yahia Tobeigei, Faisal H. TI Calciphylaxis cutis: A case report and review of literature SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE Kidney; Calciphylaxis; Skin ID RENAL-FAILURE; NECROSIS AB Calciphylaxis is a poorly understood syndrome of vascular calcification and skin necrosis. It affects 1-4% of the population with end stage renal disease (ESRD). Disorders implicated in the pathogenesis of calciphylaxis include chronic renal failure, hypercalcemia, hyperphosphatemia, an elevated calcium-phosphate product, and secondary hyperparathyroidism (Essary, L.R. and Wick, M.R. (2000) Cutaneous calciphylaxis. An underrecognized clinicopathologic entity. Am. J. Clin. Pathol. 113, 280-287, Beitz, J.M. (2004) Calciphylaxis: an uncommon but potentially deadly form of skin necrosis. Am. J. Nurs. 104, 36-37.). Although these abnormalities are extremely common in-patients with ESRD, calciphylaxis is relatively rare. The mortality rate of calciphylaxis is about 60-80%. The leading cause of death is sepsis from necrotic skin lesions (Hitti, W. A., Papadimitriou, J.C., Bartlett, S. and Wali, R.K. (2007) Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. Scand. J. Urol. Nephrol. 1-3.). Here, we report a case of calciphylaxis in a 23-year-old female with past history of chronic renal failure, renal transplantation and intake of immunosuppressive drug. The relevant literature was discussed. (C) 2009 Elsevier Inc. All rights reserved. C1 [Abdulwahed, Saad R.] Al Azhar Univ, Dept Radiol, Assiut, Egypt. [Hussein, Mahmoud-Rezk A.] Univ Wisconsin, Sch Med, Madison, WI 53705 USA. [Hussein, Mahmoud-Rezk A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. EM mrcpath17@gmail.com NR 8 TC 10 Z9 10 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD APR PY 2009 VL 86 IS 2 BP 134 EP 135 DI 10.1016/j.yexmp.2009.01.008 PG 2 WC Pathology SC Pathology GA 433KA UT WOS:000265201500010 PM 19348063 ER PT J AU Rhee, DJ Haddadin, RI Kang, MH Oh, DJ AF Rhee, Douglas J. Haddadin, Ramez I. Kang, Min Hyung Oh, Dong-Jin TI Matricellular proteins in the trabecular meshwork SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE trabecular meshwork; matricellular proteins; SPARC; thrombospondin; tenascin; osteopontin; hevin; galectin; extracellular matrix ID GROWTH-FACTOR-BETA; SPARC-NULL MICE; EXTRACELLULAR-MATRIX PROTEINS; EHLERS-DANLOS-SYNDROME; THROMBIN-SENSITIVE PROTEIN; OSTEOPONTIN-DEFICIENT MICE; PIGMENT EPITHELIAL-CELLS; TENASCIN-X DEFICIENCY; CILIARY MUSCLE-CELLS; S-TYPE LECTIN AB The trabecular meshwork is one of the primary tissues of interest in the normal regulation and dysregulation of intraocular pressure (IOP) that is a causative risk factor for primary open-angle glaucoma. Matricellular proteins generally function to allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). In non-ocular tissues, matricellular proteins generally increase fibrosis. Since ECM turnover is very important to the outflow facility, matricellular proteins may have a significant role in the regulation of IOP. The formalized study of matricellular proteins in trabecular meshwork is in its infancy. SPARC, thrombospondins-1 and -2, and tenascins-C and -X, and osteopontin have been localized to varying areas within the trabecular meshwork. Preliminary evidence indicates that SPARC and thrombospondin-1 play a role in the regulation of IOP and possibly the pathophysiology of glaucoma. These data show promise that matricellular proteins are involved in IOP dysregulation and are potential therapeutic targets. Further study is needed to clarify these roles. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Rhee, Douglas J.; Haddadin, Ramez I.; Kang, Min Hyung; Oh, Dong-Jin] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 200 TC 39 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2009 VL 88 IS 4 BP 694 EP 703 DI 10.1016/j.exer.2008.11.032 PG 10 WC Ophthalmology SC Ophthalmology GA 441OH UT WOS:000265778000011 PM 19101543 ER PT J AU Allingham, RR Liu, YT Rhee, DJ AF Allingham, R. Rand Liu, Yutao Rhee, Douglas J. TI The genetics of primary open-angle glaucoma: A review SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE POAG; genetics; genetic linkage; whole genome association; admixture mapping; genetic screening; myocilin; optineurin; WDR36; SNP ID NORMAL-TENSION GLAUCOMA; WIDE SCAN MAPS; OPTINEURIN SEQUENCE VARIATIONS; INCREASES OUTFLOW RESISTANCE; TRABECULAR MESHWORK CELLS; NITRIC-OXIDE SYNTHASE; BLUE MOUNTAINS EYE; S-TRANSFERASE M1; BEAVER-DAM EYE; INTRAOCULAR-PRESSURE AB Glaucoma is the major cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), as the most prevalent form of glaucoma, is a complex inherited disorder and affects more than 2 million individuals in the United States. It has become increasingly clear that a host of genetic as well as environmental factors are likely to contribute to the phenotype. A number of chromosomal and genetic associations have been reported for POAG. This review examines what is currently known about the underlying genetic structure, what remains to be learned, and how this may affect our medical management of this major blinding disease. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Allingham, R. Rand] Duke Univ, Ctr Eye, Durham, NC 27710 USA. [Liu, Yutao] Duke Univ, Duke Ctr Human Genet, Durham, NC 27710 USA. [Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Allingham, RR (reprint author), Duke Univ, Ctr Eye, DUMC Box 3802, Durham, NC 27710 USA. EM allin002@mc.duke.edu NR 143 TC 125 Z9 132 U1 4 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2009 VL 88 IS 4 BP 837 EP 844 DI 10.1016/j.exer.2008.11.003 PG 8 WC Ophthalmology SC Ophthalmology GA 441OH UT WOS:000265778000030 PM 19061886 ER PT J AU Jang, YC Van Remmen, H AF Jang, Youngmok C. Van Remmen, Holly TI The mitochondrial theory of aging: Insight from transgenic and knockout mouse models SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE Mitochondria; Mitochondrial theory of aging; Oxidative stress; Aging; Transgenic and knockout mouse models ID MANGANESE SUPEROXIDE-DISMUTASE; LIFE-SPAN; OXIDATIVE STRESS; DNA-DAMAGE; SKELETAL-MUSCLE; MICE; OVEREXPRESSION; MUTATIONS; BRAIN; RESTRICTION AB A substantial body of evidence has accumulated over the past 35 years in support of a role for oxidative damage to the mitochondrial respiratory chain and mitochondrial DNA in the determination of mammalian lifespan. The goal of this review is to provide a concise summary of recent studies using transgenic and knockout mouse models with altered expression of mitochondrial antioxidant enzymes (MnSOD (Sod2Tg and Sod2(+/-)), thioredoxin 2 (Trx2(+/-)), mitochondrial targeted catalase (mCAT) and mutant mice models that have been genetically manipulated to increase mitochondrial deletions or mutations (Poly(D257A/D257A) mutant mice) to examine the role of mitochondrial oxidative stress in aging. The majority of studies using these strategies do not support a clear role for mitochondrial oxidative stress or a vicious cycle of oxidative damage in the determination of lifespan in mice and furthermore do not support the free radical theory of aging. However, several key questions remain to be addressed and clearly more studies are required to fully understand the role of mitochondria in age-related disease and aging. (C) 2009 Elsevier Inc. All rights reserved. C1 [Jang, Youngmok C.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Jang, Youngmok C.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu NR 42 TC 98 Z9 100 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 2009 VL 44 IS 4 BP 256 EP 260 DI 10.1016/j.exger.2008.12.006 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 435JQ UT WOS:000265340600004 PM 19171187 ER PT J AU Sani, S Ostrem, JL Shimamoto, S Levesque, N Starr, PA AF Sani, Sepehr Ostrem, Jill L. Shimamoto, Shoichi Levesque, Nadja Starr, Philip A. TI Single unit "pauser" characteristics of the globus pallidus pars externa distinguish primary dystonia from secondary dystonia and Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Dystonia; Parkinson's disease; Neuronal pauses; Globus pallidus; Microelectrode recording ID DEEP BRAIN-STIMULATION; BASAL GANGLIA; FUNCTIONAL-ANATOMY; NEURONAL-ACTIVITY; GENERALIZED DYSTONIA; SUBTHALAMIC NUCLEUS; TECHNICAL APPROACH; DYT1 DYSTONIA; IN-VITRO; PALLIDOTOMY AB The presence of high frequency discharge neurons with long periods of silence or "pauses" in the globus pallidus pars externa (GPe) is a unique identifying feature of this nucleus. Prior studies have demonstrated that pause characteristics reflect synaptic inputs into GPe. We hypothesized that GPe pause characteristics should distinguish movement disorders whose basal ganglia network abnormalities are different. We examined Pause characteristics in 224 GPe units in patients with primary generalized dystonia, Parkinson's disease (PD), and secondary dystonia, undergoing single unit microelectrode recording for DBS placement in the awake state. Pauses in neuronal discharge Were identified using the Poisson surprise method. Mean pause length in primary dystonia (606.8373.3) was higher than in PD (557.4366.6) (p < 0.05). Interpause interval (IPI) was lower in primary dystonia (2331.63874.1) than PD (3646.45894.5) (p < 0.01), and mean pause frequency was higher in primary dystonia (0.140.10) than PD (0.070.12) (p < 0.01). Comparison of pause characteristics in primary versus secondary generalized dystonia revealed a significantly longer mean pause length in primary (606.8373.3) than in secondary dystonia (495.6236.5) (p < 0.01). IPI was shorter in primary (2331.6 +/- 3874.1) than in secondary dystonia (3484.5 +/- 3981.6) (p < 0.01). The results show that pause characteristics recorded in the awake human GPe distinguish primary dystonia from Parkinson's disease and secondary dystonia. The differences may reflect increased phasic input from striatal D2 receptor positive cells in primary dystonia, and are consistent with a recent model proposing that GPe provides capacity scaling for cortical input. (c) 2008 Elsevier Inc. All rights reserved. C1 [Sani, Sepehr; Ostrem, Jill L.; Shimamoto, Shoichi; Levesque, Nadja; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Sani, Sepehr; Ostrem, Jill L.; Starr, Philip A.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 533 Parnassus Ave,Box 0445, San Francisco, CA 94143 USA. EM starrp@neurosurg.ucsf.edu FU NINDS NIH HHS [K08 NS002201-05, K08 NS002201] NR 38 TC 10 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2009 VL 216 IS 2 BP 295 EP 299 DI 10.1016/j.expneurol.2008.12.006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 424ZK UT WOS:000264606600008 PM 19146856 ER PT J AU Elangovan, S Srinivasan, S Ayilavarapu, S AF Elangovan, Satheesh Srinivasan, Sreedevi Ayilavarapu, Srinivas TI Novel regenerative strategies to enhance periodontal therapy outcome SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cell therapy; gene therapy; growth factors; regeneration ID BONE MORPHOGENETIC PROTEIN-2; MESENCHYMAL STEM-CELLS; GROWTH FACTOR-BB; GUIDED TISSUE REGENERATION; NEUTROPHIL-MEDIATED DAMAGE; ENAMEL MATRIX PROTEINS; MARROW STROMAL CELLS; GENE-THERAPY; IN-VIVO; LIGAMENT CELLS AB Background: Chronic periodontitis is a widely prevalent inflammatory condition of the supporting tissues of the teeth and is characterized by loss of teeth with an associated risk of systemic complications. Regenerative therapies such as guided tissue and bone regeneration form an important armamentarium in periodontics with a high degree of outcome predictability in certain ideal clinical scenarios. Objective/methods: This review elaborates novel tissue regenerative treatment modalities based on sound understanding of developmental biology, tissue engineering, inflammation and wound healing. We focus on the role of biological mediators such as growth factors, gene-based therapy, cell therapy and pro-resolution lipid mediators in the regeneration of lost bone or periodontium. Results/conclusions: These therapies have the potential to regenerate both periodontium and bone, aiding in the treatment of even clinically challenging cases. C1 [Elangovan, Satheesh] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Div Periodontol, Boston, MA 02115 USA. [Elangovan, Satheesh] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. [Srinivasan, Sreedevi] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Ayilavarapu, Srinivas] Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. RP Elangovan, S (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Div Periodontol, 188 Longwood Ave, Boston, MA 02115 USA. EM Satheesh_Elangovan@hsdm.harvard.edu NR 124 TC 14 Z9 14 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD APR PY 2009 VL 9 IS 4 BP 399 EP 410 DI 10.1517/14712590902778423 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 440CF UT WOS:000265675100003 PM 19344278 ER PT J AU Pascal, L Gay, J Willekens, C Wemeau, M Balkaran, S Robu, D Roccaro, A Morel, P Ghobrial, I Leleu, X AF Pascal, Laurent Gay, Julie Willekens, Christophe Wemeau, Mathieu Balkaran, Sandy Robu, Daniela Roccaro, Aldo Morel, Pierre Ghobrial, Irene Leleu, Xavier TI Bortezomib and Waldenstrom's macroglobulinemia SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE bortezomib; NFkB inhibitor; novel therapy; Waldenstrom's macroglobulinemia ID NF-KAPPA-B; IGM MONOCLONAL GAMMOPATHY; RELAPSED MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; INTERNATIONAL WORKSHOP; PROTEASOME INHIBITOR; CELLS; CANCER; ATP; RECOMMENDATIONS AB Despite advances in therapy, Waldenstrom's macroglobulinemia (WM) remains incurable. Guidelines on therapeutic alternatives in WM recommended the use of alkylating agents, rituximab, nucleoside analogues and anthracyclins either in first line or at relapse and in combination in fit patients. While the overall response rates of combination regimens reached up to 80 - 90% in some studies, the complete response rate is low, no greater than 10 - 20%; and the disease-related median survival for symptomatic patients is approximately 6 years. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, advances were made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. Several preclinical studies have demonstrated that the NF kappa B pathway is a potential target for therapeutics in WM. Bortezomib (Velcade (R)) is the first approved proteasome inhibitor for treating relapse/refractory multiple myeloma and, among other mechanisms of action, significantly inhibits the NFkB pathway. This report provides an update on biological studies and clinical efforts to develop bortezomib as a new treatment of Waldenstrom's macroglobulinemia. C1 [Pascal, Laurent; Gay, Julie; Willekens, Christophe; Wemeau, Mathieu; Balkaran, Sandy; Robu, Daniela; Roccaro, Aldo; Morel, Pierre; Leleu, Xavier] CHRU Lille, Hop Huriez, Serv Malad Sang, F-59037 Lille, France. [Ghobrial, Irene] DFCI, Boston, MA 02115 USA. RP Leleu, X (reprint author), CHRU Lille, Hop Huriez, Serv Malad Sang, Rue Michel Polonovski, F-59037 Lille, France. EM x-leleu@chru-lille.fr OI Pascal, Laurent/0000-0001-7792-3768; Roccaro, Aldo/0000-0002-1872-5128 NR 58 TC 3 Z9 4 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD APR PY 2009 VL 10 IS 5 BP 909 EP 916 DI 10.1517/14656560902800160 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 440CJ UT WOS:000265675700016 PM 19351237 ER PT J AU Finn, RS Zhu, AX AF Finn, Richard S. Zhu, Andrew X. TI Targeting angiogenesis in hepatocellular carcinoma: focus on VEGF and bevacizumab SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE angiogenesis; bevacizumab; hepatocellular carcinoma; targeted therapy ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; TUMOR ANGIOGENESIS; PROGNOSTIC-SIGNIFICANCE; ANTIBODY BEVACIZUMAB; FACTOR RECEPTOR; MOUSE MODELS; IN-VIVO; CANCER; EXPRESSION AB Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and one of the few malignancies with an increasing incidence in the USA. While the relationship between HCC and its inciting risk factors (e.g., hepatitis B, hepatitis C and alcohol liver disease) is well defined, driving genetic alterations are still yet to be identified. Clinically, HCC tends to be hypervascular and, for that reason, transarterial chemoembolization has proven to be effective in managing many patients with localized disease. More recently, angiogenesis has been targeted effectively with pharmacologic strategies, including monoclonal antibodies against VEGF and the VEGF receptor, as well as small-molecule kinase inhibitors of the VEGF receptor. Targeting angiogenesis with these approaches has been validated in several different solid tumors since the initial approval of bevacizumab for advanced colon cancer in 2004. In HCC, only sorafenib has been shown to extend survival in patients with advanced HCC and has opened the door for other anti-angiogenic strategies. Here, we will review the data supporting the targeting of the VEGF axis in HCC and the preclinical and early clinical development of bevacizumab. C1 [Finn, Richard S.] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Finn, RS (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, David Geffen Sch Med, 10833 Conte Ave,11-934 Factor Bldg, Los Angeles, CA 90095 USA. EM rfinn@mednet.ucla.edu NR 45 TC 55 Z9 63 U1 3 U2 6 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD APR PY 2009 VL 9 IS 4 BP 503 EP 509 DI 10.1586/ERA.09.6 PG 7 WC Oncology SC Oncology GA 443GN UT WOS:000265898300016 PM 19374603 ER PT J AU Drappatz, J Norden, AD Wen, PY AF Drappatz, Jan Norden, Andrew D. Wen, Patrick Y. TI Therapeutic strategies for inhibiting invasion in glioblastoma SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE angiogenesis; anti-tenascin antibody; c-met inhibitor; cilengitide; extracellular matrix; glioblastoma; invasion; migration; PI3K inhibitor; scatter factor/hepatocyte growth factor inhibitor; TGF-beta AB Glioblastomas are the most common and lethal form of malignant primary brain tumors. Although some progress has been made, the impact of recent advances in multimodality therapies on clinical outcome has been disappointing, with a median survival of less than 15 months. A major challenge in patients with glioblastomas is the propensity of the tumor to invade into adjacent brain tissue. Invasive tumor cells escape surgical removal and, because of their reduced proliferation rate and increased resistance to apoptosis, they are relatively resistant to radiation therapy and chemotherapy. Recently, there has been important progress in understanding the molecular determinants of glioma invasion and migration. This review will summarize some of the therapeutic strategies for inhibiting invasion in glioblastomas. C1 [Drappatz, Jan; Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Drappatz, Jan; Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. RP Drappatz, J (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, 75 Francis St, Boston, MA 02115 USA. EM jdrappatz@partners.org; anorden@partners.org; pwen@partners.org FU Schering-Plough; Exelixis; Amgen; Novartis; Astra-Zeneca; Genentech; Haley/Cairns Brain Tumor Research Fund; Borhek Brain Tumor Research Fund FX Patrick Wen has received research support from Schering-Plough, Exelixis, Amgen, Novartis, Astra-Zeneca and Genentech. We gratefully acknowledge the support of the support of the Haley/Cairns and Borhek Brain Tumor Research Funds. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 177 TC 43 Z9 43 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 EI 1744-8360 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD APR PY 2009 VL 9 IS 4 BP 519 EP 534 DI 10.1586/ERN.09.10 PG 16 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V39ZP UT WOS:000209449200015 PM 19344303 ER PT J AU Belleannee, C Da Silva, N Shum, W Breton, S AF Belleannee, Clemence Da Silva, Nicolas Shum, Winnie Breton, Sylvie TI Purinergic receptors in mouse and rat epididymis : Role of luminal ATP and adenosine in V-ATPase activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Belleannee, Clemence; Da Silva, Nicolas; Shum, Winnie; Breton, Sylvie] Massachusetts Gen Hosp, Div Nephrol, Ctr Syst Biol, Prog Memb Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 998.37 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502020 ER PT J AU Bonner-Weir, S AF Bonner-Weir, Susan TI Pancreatic regeneration: role of pancreatic progenitors SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 329.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621503461 ER PT J AU Carlson, BA Yoo, MH Kim, JY Shrimali, RK Irons, R Park, JM Hatfield, DL AF Carlson, Bradley A. Yoo, Min-Hyuk Kim, Jin Young Shrimali, Rajeev K. Irons, Robert Park, Jin Mo Hatfield, Dolph L. TI Knockout of the selenocysteine tRNA ([Ser]Sec) gene (Trsp) in mouse macrophages SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Shrimali, Rajeev K.; Irons, Robert; Hatfield, Dolph L.] NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. [Kim, Jin Young] Seoul Natl Univ, Sch Biol Sci, Lab Mol Genet & Genom, Inst Mol Biol & Genet, Seoul, South Korea. [Park, Jin Mo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 346.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502483 ER PT J AU Chen, YX Gelfond, J McManus, LM Shireman, PK AF Chen, Yongxin Gelfond, Jonathan McManus, Linda M. Shireman, Paula K. TI Reproducibility of miRNA Expression by Proliferating C2C12 Cells Using RT-PCR Array SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chen, Yongxin; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 361.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500126 ER PT J AU Eggert, US AF Eggert, Ulrike S. TI Pathway-specific small molecule probes of cytokinesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 196.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500310 ER PT J AU Gentile, NE McKlveen, JM Czambel, RK Karwoski, TE Rubin, RT Rhodes, ME AF Gentile, Natalie E. McKlveen, Jessica M. Czambel, R. Kenneth Karwoski, Tracy E. Rubin, Robert T. Rhodes, Michael E. TI Sexually Diergic Hypothalamic-Pituitary-Adrenal (HPA) Responses to Single-Dose Nicotine, Continuous Nicotine by Osmotic Mini-Pumps, and Nicotine Withdrawal by Single-Dose Mecamylamine in Rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gentile, Natalie E.; McKlveen, Jessica M.; Rhodes, Michael E.] St Vincent Coll, Dept Biol, Latrobe, PA USA. [Czambel, R. Kenneth; Karwoski, Tracy E.] Allegheny Singer Res Inst, Neurosci Res Ctr, Pittsburgh, PA 15212 USA. [Rubin, Robert T.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 941.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621504457 ER PT J AU Goodyear, LJ Koh, HJ Fujii, N Toyoda, T Witczak, CA Middelbeek, JW Jung, M Hirshman, M AF Goodyear, Laurie J. Koh, Ho-Jin Fujii, Nobuharu Toyoda, Taro Witczak, Carol A. Middelbeek, Jan Willem Jung, Michelle Hirshman, Michael TI AMPK: A Critical Metabolic Signal SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Goodyear, Laurie J.; Koh, Ho-Jin; Fujii, Nobuharu; Toyoda, Taro; Witczak, Carol A.; Middelbeek, Jan Willem; Jung, Michelle; Hirshman, Michael] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 93.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505116 ER PT J AU Hickey, M Kuligowski, M Bourges, D Lo, C Kitching, AR AF Hickey, Michael Kuligowski, Michael Bourges, Dorothee Lo, Cecilia Kitching, A. Richard TI Anti-myeloperoxidase antibodies rapidly induce alpha 4 integrin-dependent glomerular neutrophil adhesion SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hickey, Michael; Lo, Cecilia; Kitching, A. Richard] Monash Univ, Ctr Inflammatory Dis, Clayton, Vic 3168, Australia. [Bourges, Dorothee] Bio21 Inst, Parkville, Vic 3010, Australia. [Kuligowski, Michael] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 360.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621503159 ER PT J AU Hung, DT AF Hung, Deborah T. TI Small molecule and genomic approaches to bacterial pathogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hung, Deborah T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 328.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621506102 ER PT J AU Imamura, F Lichtenstein, AH Meigs, JB Dallal, GE Jacques, PF AF Imamura, Fumiaki Lichtenstein, Alice H. Meigs, James B. Dallal, Gerard E. Jacques, Paul F. TI The Association between Alcohol Consumption and Diabetes Risk is Independent of Dietary Pattern SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Imamura, Fumiaki; Lichtenstein, Alice H.; Dallal, Gerard E.; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 229.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502853 ER PT J AU Kendall, RT Lee, MH El-Shewy, HM Janech, MG Luttrell, DK Luttrell, LM AF Kendall, Ryan Thomas Lee, Mi-Hye El-Shewy, Hesham M. Janech, Michael G. Luttrell, Deirdre K. Luttrell, Louis M. TI Biased agonism reveals new G protein-independent AT1a receptor signals SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kendall, Ryan Thomas; Lee, Mi-Hye; El-Shewy, Hesham M.; Janech, Michael G.; Luttrell, Deirdre K.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 880.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502593 ER PT J AU Kolliputi, N Shaik, R Waxman, AB AF Kolliputi, Narasaiah Shaik, Rahamthulla Waxman, Aaron B. TI Inflammasome: A Pivotal Role in hyperoxia-induced acute lung injury? SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kolliputi, Narasaiah; Shaik, Rahamthulla; Waxman, Aaron B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 1025.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500201 ER PT J AU Lee, K Lv, W Ter-Ovanesyan, E Voysey, GE Armoundas, AA Cohen, RJ AF Lee, Kichang Lv, Wener Ter-Ovanesyan, Evgeny Voysey, Graham E. Armoundas, Antonis A. Cohen, Richard J. TI Novel catheter guidance technique to the site of origin of the arrhythmia SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lee, Kichang; Lv, Wener; Ter-Ovanesyan, Evgeny; Cohen, Richard J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Voysey, Graham E.] Infoscitex Corp, Biomed Syst Div, Waltham, MA USA. [Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 624.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621501239 ER PT J AU Martinez, CO McManus, LM Shireman, PK AF Martinez, Carlo Obet McManus, Linda M. Shireman, Paula K. TI Kinetics of myogenic progenitor cell (MPC) expansion and bone marrow-derived cell recruitment in skeletal muscle regeneration SO FASEB JOURNAL LA English DT Meeting Abstract C1 [McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 739.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621504294 ER PT J AU McKeown, NM Liu, E Meigs, JB Rogers, G D'Agostino, R Jacques, P AF McKeown, Nicola Mary Liu, Enju Meigs, James B. Rogers, Gail D'Agostino, Ralph Jacques, Paul TI Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort SO FASEB JOURNAL LA English DT Meeting Abstract C1 [McKeown, Nicola Mary; Liu, Enju; Rogers, Gail; Jacques, Paul] Tufts Univ, JM USDA HNRCA, Boston, MA 02111 USA. [McKeown, Nicola Mary] Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [D'Agostino, Ralph] Boston Univ, CAS Math & Stat, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 229.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500356 ER PT J AU Merkulova, M Hurtado-Lorenzo, A Brown, D Ausiello, D Marshansky, V AF Merkulova, Maria Hurtado-Lorenzo, Andres Brown, Dennis Ausiello, Dennis Marshansky, Vladimir TI V-ATPase/small GTPase/aldolase complex and regulation of endosomal/lysosomal protein degradative pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Merkulova, Maria; Hurtado-Lorenzo, Andres; Brown, Dennis; Ausiello, Dennis; Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Simches Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 877.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505450 ER PT J AU Nanthakumar, NN Meng, D AF Nanthakumar, Nanda N. Meng, Di TI Recovery from DSS-induced intestinal colitis is mediated by MIP2-dependent neutrophil recruitment SO FASEB JOURNAL LA English DT Meeting Abstract C1 MassGen Hosp Children, Pediat GI & Nutr Unit, Boston, MA USA. MassGen Hosp Children, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. MassGen Hosp Children, Pediat GI & Nutr Unit, Charlestown, MA USA. MassGen Hosp Children, Dept Pediat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 976.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505393 ER PT J AU Percival, JM Anderson, KN Huang, PL Froehner, SC AF Percival, Justin Mark Anderson, Kendra N. Huang, Paul L. Froehner, Stanley C. TI Nitric oxide regulates skeletal muscle performance by compartmentalization of nNOS splice variants SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Percival, Justin Mark; Anderson, Kendra N.; Froehner, Stanley C.] Univ Washington, Seattle, WA 98195 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 852.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505735 ER PT J AU Phung, TL Antonello, Z Gerald, D Perruzzi, C Rocuts, A Hochman, M Cunningham, M Mihm, M Benjamin, LE AF Phung, Thuy L. Antonello, Zeus Gerald, Damien Perruzzi, Carole Rocuts, Alexander Hochman, Marcelo Cunningham, Michael Mihm, Martin Benjamin, Laura E. TI PATHOLOGICAL ANGIOGENESIS IN VASCULAR TUMORS IS DRIVEN BY AKT1 AND INHIBITED BY TOPICAL RAPAMYCIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Phung, Thuy L.; Antonello, Zeus; Gerald, Damien; Perruzzi, Carole; Rocuts, Alexander; Benjamin, Laura E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hochman, Marcelo] Hemangioma Int Treatment Ctr, Charlotte, SC USA. [Cunningham, Michael] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Mihm, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 634.13 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621505774 ER PT J AU Shacka, JJ DeWitte, C Roth, KA Ness, JM AF Shacka, John J. DeWitte, Cary Roth, Kevin A. Ness, Jayne M. TI Regulation of Neuron Death in Neonatal Hypoxia-Ischemia SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shacka, John J.; DeWitte, Cary; Roth, Kevin A.; Ness, Jayne M.] Univ Alabama Birmingham, Birmingham, AL USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 235.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621504363 ER PT J AU Shum, W Da Silva, N Brown, D Breton, S AF Shum, Winnie Da Silva, Nicolas Brown, Dennis Breton, Sylvie TI Regulation of vacuolar H plus -ATPase (V-ATPase) recycling via a RhoA-dependent pathway in epididymal clear cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shum, Winnie; Da Silva, Nicolas; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 796.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502072 ER PT J AU Soto-Pina, AE Kadapakkam, S Mehring, C Hinojosa-Laborde, C Strong, R AF Soto-Pina, Alexandra Estela Kadapakkam, Sheela Mehring, Cynthia Hinojosa-Laborde, Carmen Strong, Randy TI Role of adrenal medulla in dexamethasone-induced hypertension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Mehring, Cynthia; Hinojosa-Laborde, Carmen; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Strong, Randy] S Texas Vet Hlth Care Network, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 969.14 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621504136 ER PT J AU Stone, JR Panchenko, MP Silva, N Dombkowski, DM Preffer, FI MacGillivray, TE AF Stone, James R. Panchenko, Mikhail P. Silva, Nilsa Dombkowski, David M. Preffer, Frederic I. MacGillivray, Thomas E. TI Protein kinase CK1 alpha LS mediates hydrogen peroxide stimulated vascular cell proliferation and intimal hyperplasia SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 357.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621502328 ER PT J AU Wey, MCY Fernandez, E Hinojosa-Laborde, C Strong, R AF Wey, Margaret Chia-Ying Fernandez, Elizabeth Hinojosa-Laborde, Carmen Strong, Randy TI Detoxification of Biogenic Aldehydes in Parkinsons Disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wey, Margaret Chia-Ying; Fernandez, Elizabeth; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Wey, Margaret Chia-Ying; Fernandez, Elizabeth; Strong, Randy] S Texas Vet Hlth Care Network, GRECC, San Antonio, TX USA. [Hinojosa-Laborde, Carmen] Univ Texas Hlth Sci Ctr San Antonio, Dept Anesthesiol, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 963.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621503424 ER PT J AU Wick, MJ Barr, EJ Wehling, CA Cool, CD Zamora, M Miller, YE Hersh, LB Voelkel, NF Dempsey, EC AF Wick, Marilee J. Barr, Erica J. Wehling, Carol A. Cool, Carlyne D. Zamora, Marty Miller, York E. Hersh, Louis B. Voelkel, Norbert F. Dempsey, Edward C. TI Lung neprilysin activity and expression are decreased in humans with COPD and pulmonary vascular remodeling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wick, Marilee J.; Barr, Erica J.; Dempsey, Edward C.] Univ Colorado Denver, CVP Res Lab, Aurora, CO USA. [Wick, Marilee J.; Cool, Carlyne D.; Zamora, Marty; Miller, York E.; Voelkel, Norbert F.] Univ Colorado Denver, Div Pulm, Aurora, CO USA. [Wehling, Carol A.; Miller, York E.; Dempsey, Edward C.] Denver VAMC, Denver, CO USA. [Hersh, Louis B.] Univ Kentucky, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 770.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500765 ER PT J AU Zhao, GF Kolliputi, N Zhao, H Beagle, J Yu, LY Syrkina, O Leu, S Hicham, M Hales, C AF Zhao, Gaofeng Kolliputi, Narasaiah Zhao, Hang Beagle, John Yu, Lunyin Syrkina, Olga Leu, Shawwei Hicham, Mrabat Hales, Charles TI heparin inhibits injury-induced femoral artery remodeling in mouse Via CD44 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kolliputi, Narasaiah; Zhao, Hang] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 592.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621501525 ER PT J AU Zou, L AF Zou, Lee TI Revealing the DNA Structural Determinants for ATM Activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Zou, Lee] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2009 VL 23 MA 655.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V27OC UT WOS:000208621500215 ER PT J AU Pearson, KR Hauser, R Cramer, DW Missmer, SA AF Pearson, Kimberly R. Hauser, Russ Cramer, Daniel W. Missmer, Stacey A. TI Point of failure as a predictor of in vitro fertilization treatment discontinuation SO FERTILITY AND STERILITY LA English DT Article ID IVF TREATMENT; DECISION; COUPLES; REASONS AB Among 2,245 women, those who experienced a chemical pregnancy that failed to progress to a clinically recognized pregnancy or a spontaneous abortion on their first IVF cycle were more likely to discontinue IVF treatment than those whose first cycle ended before embryo transfer or who did not have a positive pregnancy test after transfer. However, among women who did continue to a second IVF cycle, those who had at least a chemical pregnancy on the first cycle were more likely to have a live birth on the second attempt than those women who had failed before conception in the first cycle (34% success rate compared with 21%, respectively). (Fertil Steril (R) 2009;91:1483-5. (C)2009 by American Society for Reproductive Medicine.) C1 [Cramer, Daniel W.; Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Missmer, Stacey A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Pearson, Kimberly R.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. [Cramer, Daniel W.; Missmer, Stacey A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Hauser, Russ] Massachusetts Gen Hosp, Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Missmer, SA (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave, Boston, MA 02115 USA. EM stacey.missmer@channing.harvard.edu FU NICHD NIH HHS [R01 HD032153, R01 HD032153-09]; NIEHS NIH HHS [ES013967, R01 ES013967, R01 ES013967-03] NR 10 TC 8 Z9 8 U1 0 U2 0 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 APR PY 2009 VL 91 IS 4 BP 1483 EP 1485 DI 10.1016/j.fertnstert.2008.07.1732 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 432KT UT WOS:000265132600056 PM 18829010 ER PT J AU Babyatsky, MW Bazari, H Del Valle, J AF Babyatsky, Mark W. Bazari, Hasan Del Valle, John TI Response to the Institute of Medicine's Recommendations on Resident Duty Hours: The Medical Residency Program and GI Fellowship Viewpoints SO GASTROENTEROLOGY LA English DT Editorial Material ID WORK HOURS; INTERNS; REGULATIONS; ERRORS; RISK C1 [Babyatsky, Mark W.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Del Valle, John] Univ Michigan Hlth Syst, Dept Internal Med, Residency Program, Ann Arbor, MI USA. RP Babyatsky, MW (reprint author), Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2009 VL 136 IS 4 BP 1145 EP 1147 DI 10.1053/j.gastro.2009.02.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500006 PM 19233326 ER PT J AU El-Serag, HB Lagergren, J AF El-Serag, Hashem B. Lagergren, Jesper TI Alcohol Drinking and the Risk of Barrett's Esophagus and Esophageal Adenocarcinoma SO GASTROENTEROLOGY LA English DT Editorial Material ID GASTRIC CARDIA; REFLUX ESOPHAGITIS; CONSUMPTION; TOBACCO; CANCER C1 [El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [El-Serag, Hashem B.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Lagergren, Jesper] Karolinska Inst, Dept Mol Med & Surg, Unit Esophageal & Gastr Res, Stockholm, Sweden. RP El-Serag, HB (reprint author), Baylor Coll Med, Dept Med, Gastroenterol Sect, 202 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu OI Lagergren, Jesper/0000-0002-5143-5448 FU NCI NIH HHS [R01 CA116845, R01 CA116845-03]; NIDDK NIH HHS [K24 DK078154, K24DK078154-03] NR 13 TC 8 Z9 9 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2009 VL 136 IS 4 BP 1155 EP 1157 DI 10.1053/j.gastro.2009.02.021 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500010 PM 19236968 ER PT J AU Nguyen, DD Snapper, SB AF Nguyen, Deanna D. Snapper, Scott B. TI Targeting Smads to Restore Transforming Growth Factor-beta Signaling and Regulatory T-Cell Function in Inflammatory Bowel Disease SO GASTROENTEROLOGY LA English DT Editorial Material ID TGF-BETA; COLITIS; DIFFERENTIATION; TRANSCRIPTION; SUPPRESSION; INHIBITION; DISRUPTION; MECHANISMS; TOLERANCE; FIBROSIS C1 [Nguyen, Deanna D.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Nguyen, DD (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 8th Floor, Boston, MA 02114 USA. EM dnguyen3@partners.org NR 29 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2009 VL 136 IS 4 BP 1161 EP 1164 DI 10.1053/j.gastro.2009.02.024 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500012 PM 19236965 ER PT J AU Huang, Q Minor, MA Weber, HC AF Huang, Qin Minor, Melissa A. Weber, H. Christian TI Image 3 Cavernous Lymphangioma of the Jejunum SO GASTROENTEROLOGY LA English DT Article C1 [Huang, Qin] VA Boston Healthcare Syst, Dept Pathol & Lab Med, W Roxbury, MA USA. [Minor, Melissa A.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Weber, H. Christian] VA Boston Healthcare Syst, Div Gastroenterol, Jamaica Plain, MA USA. RP Huang, Q (reprint author), VA Boston Healthcare Syst, Dept Pathol & Lab Med, W Roxbury, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2009 VL 136 IS 4 BP 1170 EP + DI 10.1053/j.gastro.2008.09.034 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500016 PM 19254683 ER PT J AU Ogino, S Shima, K Baba, Y Nosho, K Irahara, N Kure, S Chen, L Toyoda, S Kirkner, GJ Wang, L Govannucci, EL Fuchs, CS AF Ogino, Shuji Shima, Kaori Baba, Yoshifumi Nosho, Katsuhiko Irahara, Natsumi Kure, Shoko Chen, Li Toyoda, Saori Kirkner, Gregory J. Wang, Lynn Govannucci, Edward L. Fuchs, Charles S. TI Colorectal Cancer Expression of Peroxisome Proliferator-Activated Receptor gamma (PPARG, PPARgamma) Is Associated With Good Prognosis SO GASTROENTEROLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; HUMAN COLON-CANCER; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; LIGANDS SUPPRESS; SURVIVAL; MUTATION; CIMP; TUMORS; COX-2 AB Background & Aims: The peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. There is controversy over the pro-oncogenic or antioncogenic effects of PPARG, and little is known about its prognostic significance in colon cancer. Methods: Among 470 patients with colorectal. cancer (stages I-M identified in 2 independent prospective cohorts, PPARG expression was detected in 102 tumors (22%) by immunohistochemistry. Cox proportional hazards models were used to compute hazard ratios (HRs) of colorectal cancer-specific and overall mortalities, adjusted for patient characteristics and molecular features including cyclo-oxygenase 2, fatty acid synthase, KRAS, BRAF, PIK3CA, p53, p21,beta-catenin, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island methylation phenotype (CIMP). Results: Compared with patients with PPARG-negative tumors, patients with PPARG-positive tumors had significantly lower overall. mortality, determined by Kaplan-Meier analysis (P = .0047), univariate Cox regression (HR, 0.55; 95% confidence interval [CI], 0.37-0.84; P = .0053), and multivariate analysis (adjusted HR, 0.43; 95% CI, 0.27-0.69; P = .0004). Patients with PPARG-positive tumors experienced lower colorectal cancer-specific mortality (adjusted HR, 0.44; 95% CI, 0.25-0.79; P = .0054). The relationship between PPARG and lower mortality did not appear to be significantly modified by MSI, CIMP, LINE-1, or the other clinical and molecular variables examined (all P(interaction) > .05). Conclusions: Tumor expression of PPARG is independently associated with longer survival of patients. PPARG expression appears to mark an indolent subset of colorectal cancers. C1 [Ogino, Shuji; Shima, Kaori; Baba, Yoshifumi; Nosho, Katsuhiko; Irahara, Natsumi; Kure, Shoko; Toyoda, Saori; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Shima, Kaori; Baba, Yoshifumi; Nosho, Katsuhiko; Irahara, Natsumi; Kure, Shoko; Toyoda, Saori; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Kirkner, Gregory J.; Govannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ogino, Shuji; Govannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji; Chen, Li] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wang, Lynn] Weill Comell Med Coll, Dept Pathol, New York, NY USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA. EM shuji_ogino@dfcl.harvard.edu OI Wang, Y. Lynn/0000-0003-0773-1212 FU National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japanese Society for Promotion of Science FX Supported by the National Institutes of Health (P01 CA87969, P01 CA55075, P50 CA127003, and K07 CA122826 to S.O.), the Bennett Family Fund, the Entertainment Industry Foundation National Colorectal Cancer Research Alliance, and a fellowship grant from the Japanese Society for Promotion of Science (to K.N.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or National Institutes of Health. Funding agencies did not have any role in the design of the study; the collection, analysis, or interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 53 TC 64 Z9 69 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2009 VL 136 IS 4 BP 1242 EP 1250 DI 10.1053/j.gastro.2008.12.048 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500025 PM 19186181 ER PT J AU Brades, S Svensson, CI Steinauer, J Pothoulakis, C Yaksh, TL Mayer, EA AF Brades, Sylvie Svensson, Camilla I. Steinauer, Joanne Pothoulakis, Charalabos Yaksh, Tony L. Mayer, Emeran A. TI Role of Spinal Microglia in Visceral Hyperalgesia and NK1R Up-Regulation in a Rat Model of Chronic Stress SO GASTROENTEROLOGY LA English DT Article ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; P38 MAPK; PROINFLAMMATORY CYTOKINES; MECHANICAL ALLODYNIA; GLIAL ACTIVATION; PATHOLOGICAL PAIN; NEUROPATHIC PAIN; GENE-EXPRESSION AB Background & Aims: Chronic psychological stress is associated with visceral hyperalgesia. and increased expression of spinal NK1 receptors (NK1Rs). We aimed to identify the role of spinal microglia in this process. Methods: Male Wistar rats were exposed to water avoidance (WA) or sham stress 1 hour each day for 10 days and given daily injections of minocycline, the p38 inhibitor SB203580, or saline. Phosphorylation levels of the kinase p38 (P-p38), the microglia marker OX42, NK1R, and I kappa B alpha were assessed by immunoblotting and/or immunostaining of spinal samples collected at day 11. The visceromotor response to colorectal. distention at baseline and following WA were also assayed in rats given injections of minocycline, SB203580, or vehicle. The effects of fractalkine were assessed on the visceromotor response in rats exposed to minocycline or vehicle. Results: P-p38 protein levels and immunoreactivity were increased in stressed rats and colocalized with OX42-positive cells and neurons in the dorsal horn. This increase was reversed by minocycline or SB203580 exposure. Stress-induced increased NK1R expression was blocked by minocycline but not SB203580. WA-induced decreased I kappa B alpha expression was blocked by minocycline and SB203580. WA-induced hyperalgesia was blocked by minocycline and SB203580 intrathecally. Fractalkine-induced hyperalgesia was blocked by minocycline. Conclusions: This is the first demonstration that stress-induced activation of spinal microglia has a key role in visceral hyperalgesia and associated spinal NKIR up-regulation. C1 [Brades, Sylvie] Univ Calif Los Angeles, Ctr Neuroblol Stress, VAGLAHS, Dept Med, Los Angeles, CA 90073 USA. [Brades, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, Ctr Neuroblol Stress, Dept Physiol, Los Angeles, CA 90073 USA. [Pothoulakis, Charalabos] Univ Calif Los Angeles, Ctr Inflammatory Bowel Dis, Div Digest Dis, Los Angeles, CA 90073 USA. [Brades, Sylvie; Mayer, Emeran A.] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Svensson, Camilla I.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Steinauer, Joanne; Yaksh, Tony L.] Univ Calif San Diego, Dept Anesthesiol, San Diego, CA 92103 USA. RP Brades, S (reprint author), Univ Calif Los Angeles, Ctr Neuroblol Stress, VAGLAHS, Dept Med, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sbradesi@ucia.edu RI Yaksh, Tony/D-4119-2009; Svensson, Camilla/C-9511-2014 OI Svensson, Camilla/0000-0001-7980-4631 FU Arthritis Foundation Fellowship; [R21 DK071767]; [P50 DK64539]; [R24 AT00281]; [DK 48351]; [R01 NS16541]; [RO1 DA002110]; [RO1 DK 47343]; [PO1 DK 33506] FX Supported by grants R21 DK071767 (to S.B.), P50 DK64539 (to E.A.M.), R24 AT00281 (to E.A.M.), DK 48351 (to E.A.M.), R01 NS16541 (to T.L.Y.), RO1 DA002110 (to T.L.Y.), RO1 DK 47343 (to C.P.), and PO1 DK 33506 (to C.P.) and an Arthritis Foundation Fellowship (to C.I.S.). NR 43 TC 33 Z9 35 U1 2 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 APR PY 2009 VL 136 IS 4 BP 1339 EP 1348 DI 10.1053/j.gastro.2008.12.044 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 426OB UT WOS:000264716500035 PM 19249394 ER PT J AU Yang, F Green, JJ Dinio, T Keung, L Cho, SW Park, H Langer, R Anderson, DG AF Yang, F. Green, J. J. Dinio, T. Keung, L. Cho, S-W Park, H. Langer, R. Anderson, D. G. TI Gene delivery to human adult and embryonic cell-derived stem cells using biodegradable nanoparticulate polymeric vectors SO GENE THERAPY LA English DT Article DE stem cells; gene delivery; biodegradable; polymeric vectors ID POLY(BETA-AMINO ESTER)S; CATIONIC POLYMERS; PLASMID DNA; THERAPY; TRANSFECTION; LIBRARY; TISSUE; EFFICIENT; NEURONS; MODEL AB Gene delivery to stem cells holds great potential for tissue regeneration and delivery of therapeutic proteins. The major barrier is the lack of safe and efficient delivery methods. Here, we report enhanced gene delivery systems for human stem cells using biodegradable polymeric vectors. A library of poly (beta- amino esters) end-modified derivatives was developed and optimized for high transfection efficiency and low cytotoxicity for three human stem cell lines including human mesenchymal stem cells (hMSCs), human adipose-derived stem cells (hADSCs) and human embryonic stem cell-derived cells (hESCds). In the presence of 10% serum, leading end-modified C32 polymeric vectors exhibited significantly high transfection efficiency in hMSCs (27 +/- 2%), hADSCs (24 +/- 3%) and hESCds (56 +/- 11%), with high cell viability (87 - 97%) achieved in all cell types. Our results show that poly(beta-amino esters) as a class, and end-modified versions of C32 in particular, are efficient polymeric vectors for gene delivery to both adult and embryonic-derived stem cells. C1 [Yang, F.; Green, J. J.; Keung, L.; Cho, S-W; Langer, R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Dinio, T.] Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. [Park, H.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Langer, R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Langer, R.; Anderson, D. G.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Anderson, DG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave,E25-342, Cambridge, MA 02139 USA. EM dgander@mit.edu RI Green, Jordan/B-9001-2009 FU NIH [R01-EB000244-27, R01-DE01651603]; National Institutes of Health for National Research Service [1F32 AR056567-01] FX We thank the NIH (R01-EB000244-27 and R01-DE01651603) for funding. FY gratefully acknowledge the National Institutes of Health for National Research Service Award postdoctoral fellowship (1F32 AR056567-01). We also thank the laboratory of Professor Johnny Huard at the University of Pittsburgh for kindly providing us the DNA plasmid-encoding human vascular endothelial growth factor 165 used in this study. NR 41 TC 64 Z9 64 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2009 VL 16 IS 4 BP 533 EP 546 DI 10.1038/gt.2008.182 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 430WL UT WOS:000265021400011 PM 19129861 ER PT J AU LaRocque, RC Sabeti, P Duggal, P Chowdhury, F Khan, AI Lebrun, LM Harris, JB Ryan, ET Qadri, F Calderwood, SB AF LaRocque, R. C. Sabeti, P. Duggal, P. Chowdhury, F. Khan, A. I. Lebrun, L. M. Harris, J. B. Ryan, E. T. Qadri, F. Calderwood, S. B. TI A variant in long palate, lung and nasal epithelium clone 1 is associated with cholera in a Bangladeshi population SO GENES AND IMMUNITY LA English DT Article DE Vibrio cholerae; cholera; candidate gene; long palate, lung and nasal epithelium clone 1; innate immunity; diarrhea ID CYSTIC-FIBROSIS HETEROZYGOTE; SUSCEPTIBILITY; INFECTION; DIARRHEA AB Vibrio cholerae causes a dehydrating diarrheal illness that can be rapidly fatal in the absence of specific treatment. The organism is an historic scourge and, like similar infectious diseases, may have influenced the evolution of the human genome. We report here the results of the first candidate gene association study of cholera. In a family-based study of 76 pedigrees from Dhaka, Bangladesh, we evaluated the association between cholera and five candidate genes-the cystic fibrosis transmembrane receptor; lactoferrin; long palate, lung and nasal epithelium clone 1 (LPLUNC1); estrogen-related receptor alpha and calcium-activated chloride channel 1. We found a significant association with a marker in the promoter region of LPLUNC1 (rs11906665), a member of a family of evolutionarily conserved innate immunity proteins. An earlier microarray-based study of duodenal biopsies showed significantly increased expression of LPLUNC1 in cholera patients compared with healthy control subjects. Our results suggest that variation in host innate immune responses may influence the outcome of exposure to V. cholerae in an endemic setting. Genes and Immunity (2009) 10, 267-272; doi:10.1038/gene.2009.2; published online 12 February 2009 C1 [LaRocque, R. C.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [LaRocque, R. C.; Ryan, E. T.; Calderwood, S. B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sabeti, P.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Duggal, P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Chowdhury, F.; Khan, A. I.; Qadri, F.] ICDDR B, Dhaka, Bangladesh. [Harris, J. B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ryan, E. T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, S. B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Gray Jackson 520,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org FU Massachusetts General Hospital; Fogarty International Center [K01-TW07144, K01-TW07409]; Howard Hughes Medical Institute; National Human Genome Research Institute of the NIH; National Institute of Allergy and Infectious Diseases [U01-AI58935, U01-AI077883, R03-AI063079]; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (FQ) FX We thank Cherylyn Smith and Liuda Ziagra of the Broad Institute for their work on the genotyping. We are grateful to Elinor Karlsson for a critical reading of the paper. This research was supported by a Claflin Distinguished Scholar Award from the Massachusetts General Hospital (RCL), K01-TW07144 from the Fogarty International Center (RCL), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (RCL), the Intramural Program of the National Human Genome Research Institute of the NIH (PD), K01-TW07409 from the Fogarty International Center (JBH), U01-AI58935 from the National Institute of Allergy and Infectious Diseases (SBC), U01-AI077883 from the National Institute of Allergy and Infectious Diseases (ETR), R03-AI063079 from the National Institute of Allergy and Infectious Diseases (FQ) and the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (FQ). NR 12 TC 19 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD APR PY 2009 VL 10 IS 3 BP 267 EP 272 DI 10.1038/gene.2009.2 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 444DS UT WOS:000265961300009 PM 19212328 ER PT J AU Demichelis, F Setlur, SR Beroukhim, R Perner, S Korbel, JO LaFargue, CJ Pflueger, D Pina, C Hofer, MD Sboner, A Svensson, MA Rickman, DS Urban, A Snyder, M Meyerson, M Lee, C Gerstein, MB Kuefer, R Rubin, MA AF Demichelis, Francesca Setlur, Sunita R. Beroukhim, Rameen Perner, Sven Korbel, Jan O. LaFargue, Christopher J. Pflueger, Dorothee Pina, Cara Hofer, Matthias D. Sboner, Andrea Svensson, Maria A. Rickman, David S. Urban, Alex Snyder, Michael Meyerson, Matthew Lee, Charles Gerstein, Mark B. Kuefer, Rainer Rubin, Mark A. TI Distinct Genomic Aberrations Associated with ERG Rearranged Prostate Cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID TMPRSS2-ERG GENE FUSION; EWS CHIMERIC TRANSCRIPTS; CHROMOSOMAL-ABERRATIONS; EXPRESSION; TUMORS; ARRAY; MCM7; HYBRIDIZATION; TUMORIGENESIS; TRANSLOCATION AB Emerging molecular and clinical data suggest that ETS fusion prostate cancer represents a distinct molecular subclass, driven most commonly by a hormonally regulated promoter and characterized by an aggressive natural history. The study of the genomic landscape of prostate cancer in the light of ETS fusion events is required to understand the foundation of this molecularly and clinically distinct subtype. We performed genome-wide profiling of 49 primary prostate cancers and identified 20 recurrent chromosomal copy number aberrations, mainly occurring as genomic losses. Co-occurring events included losses at 19q13.32 and 1p22.1. We discovered three genomic events associated with ERG rearranged prostate cancer, affecting 6q, 7q, and 16q. 6q loss in nonrearranged prostate cancer is accompanied by gene expression deregulation in an independent dataset and by protein deregulation of MYO6. To analyze copy number alterations within the ETS genes, we performed a comprehensive analysis of all 27 ETS genes and of the 3 Mbp genomic area between ERG and TMPRSS2 (21q) with an unprecedented resolution (30 bp). We demonstrate that high-resolution tiling arrays can be used to pinpoint breakpoints leading to fusion events. This study provides further support to define a distinct molecular subtype of prostate cancer based on the presence of ETS gene rearrangements. (C) 2009 Wiley-Liss, lnc. C1 [Demichelis, Francesca; Perner, Sven; LaFargue, Christopher J.; Pflueger, Dorothee; Svensson, Maria A.; Rickman, David S.; Rubin, Mark A.] Weill Cornell Med Ctr, Dept Pathol & Lab Med, New York, NY 10065 USA. [Demichelis, Francesca] Weill Cornell Med Ctr, Inst Computat Biomed, New York, NY 10065 USA. [Setlur, Sunita R.; Pina, Cara; Hofer, Matthias D.; Lee, Charles] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Beroukhim, Rameen; Meyerson, Matthew] MIT, Broad Inst, Cambridge, MA 02142 USA. [Beroukhim, Rameen; Meyerson, Matthew] Harvard Univ, Cambridge, MA 02142 USA. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Korbel, Jan O.; Sboner, Andrea; Gerstein, Mark B.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Pflueger, Dorothee; Kuefer, Rainer] Univ Hosp Ulm, Dept Urol, D-89075 Ulm, Germany. [Urban, Alex; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Gerstein, Mark B.] Yale Univ, Interdepartmental Program Computat Biol & Bioinfo, New Haven, CT 06520 USA. [Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. RP Rubin, MA (reprint author), Weill Cornell Med Ctr, 1300 York Ave Room C 410-A,Box 69, New York, NY 10021 USA. EM rubinma@med.cornell.edu RI Sboner, Andrea/C-6487-2008; Meyerson, Matthew/E-7123-2012; Korbel, Jan/G-6470-2012; OI Sboner, Andrea/0000-0001-6915-3070; Korbel, Jan/0000-0002-2798-3794; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU The National Cancer Institute [R01CA116337, R01CA125612, R01CA109038]; The Department of Defense [PCO40715] FX Supported by: The National Cancer Institute, Grant numbers: R01CA116337, R01CA125612, R01CA109038. The Department of Defense, Grant number: PCO40715. NR 47 TC 59 Z9 60 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 2009 VL 48 IS 4 BP 366 EP 380 DI 10.1002/gcc.20647 PG 15 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 410JG UT WOS:000263572700007 PM 19156837 ER PT J AU Seale, P Kajimura, S Spiegelman, BM AF Seale, Patrick Kajimura, Shingo Spiegelman, Bruce M. TI Transcriptional control of brown adipocyte development and physiological function-of mice and men SO GENES & DEVELOPMENT LA English DT Review DE PRDM16; FoxC2; brown fat; UCP1; PGC-1 alpha; obesity ID MITOCHONDRIAL UNCOUPLING PROTEIN; ADIPOSE-TISSUE; PPAR-GAMMA; STEM-CELLS; COREPRESSOR RIP140; TRANSGENIC MICE; SKELETAL-MUSCLE; GENE-EXPRESSION; RECEPTOR-GAMMA; WHITE FAT AB The last several years have seen an explosion of information relating to the transcriptional control of brown fat cell development. At the same time, new data have emerged that clearly demonstrate that adult humans do indeed have substantial amounts of functioning brown adipose tissue ( BAT). Together, these advances are stimulating a reassessment of the role of brown adipose tissue in human physiology and pathophysiology. These data have also opened up exciting new opportunities for the development of entirely novel classes of therapeutics for metabolic diseases like obesity and type 2 diabetes. C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIH [DK081605]; Japan Society for the Promotion of Science; Picower foundation FX P. S. is supported by an NIH grant ( DK081605). S. K. is supported by a fellowship from the Japan Society for the Promotion of Science. This work is funded by the Picower foundation and an NIH grant to B. M. S (DK081605). NR 109 TC 143 Z9 147 U1 5 U2 26 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 APR 1 PY 2009 VL 23 IS 7 BP 788 EP 797 DI 10.1101/gad.1779209 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 427MP UT WOS:000264783700003 PM 19339685 ER PT J AU Yoshida, S Bartolini, S Pellman, D AF Yoshida, Satoshi Bartolini, Sara Pellman, David TI Mechanisms for concentrating Rho1 during cytokinesis SO GENES & DEVELOPMENT LA English DT Article DE Rho1; cytokinesis; GEF; polybasic sequence; yeast ID GTP-BINDING PROTEIN; GUANINE-NUCLEOTIDE-EXCHANGE; BUDDING YEAST CYTOKINESIS; CELL INTEGRITY PATHWAY; MAP-KINASE CASCADE; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; ACTIN CYTOSKELETON; CONTROLS ACTOMYOSIN; LOCAL ACTIVATION AB The small GTP-binding protein, Rho1/RhoA plays a central role in cytokinetic actomyosin ring (CAR) assembly and cytokinesis. Concentration of Rho proteins at the division site is a general feature of cytokinesis, yet the mechanisms for recruiting Rho to the division site for cytokinesis remain poorly understood. We find that budding yeast utilizes two mechanisms to concentrate Rho1 at the division site. During anaphase, the primary mechanism for recruiting Rho1 is binding to its guanine nucleotide exchange factors (GEFs). GEF-dependent recruitment requires that Rho1 has the ability to pass through its GDP or unliganded state prior to being GTP-loaded. We were able to test this model by generating viable yeast lacking all identifiable Rho1 GEFs. Later, during septation and abscission, a second GEF-independent mechanism contributes to Rho1 bud neck targeting. This GEF-independent mechanism requires the Rho1 polybasic sequence that binds to acidic phospholipids, including phosphatidylinositol 4,5-bisphosphate (PIP2). This latter mechanism is functionally important because Rho1 activation or increased cellular levels of PIP2 promote cytokinesis in the absence of a contractile ring. These findings comprehensively define the targeting mechanisms of Rho1 essential for cytokinesis in yeast, and are likely to be relevant to cytokinesis in other organisms. C1 [Pellman, David] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu RI Yoshida, Satoshi/C-5016-2011 FU JSPS Fellowship; Charles A. King Trust Fellowship; Howard Hughes Medical Institute FX We thank Y. Ohya, M. Hall, and J. Pringle for the gift of strains and plasmids; Riki Eggert for valuable comments on the manuscript; and K. Kono, B. Atkins, and other members of Pellman laboratory for discussion. This work was supported by an NIH grant to D. P. S. Y. was supported by a JSPS Fellowship and by a Charles A. King Trust Fellowship. D. P. is an investigator of Howard Hughes Medical Institute. NR 60 TC 70 Z9 70 U1 0 U2 2 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 APR 1 PY 2009 VL 23 IS 7 BP 810 EP 823 DI 10.1101/gad.1785209 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 427MP UT WOS:000264783700006 PM 19339687 ER PT J AU Hu, G Kim, J Xu, QK Leng, YM Orkin, SH Elledge, SJ AF Hu, Guang Kim, Jonghwan Xu, Qikai Leng, Yumei Orkin, Stuart H. Elledge, Stephen J. TI A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal SO GENES & DEVELOPMENT LA English DT Article DE ES cells; self-renewal; RNAi; genetic screen ID EMBRYONIC STEM-CELLS; REGULATORY CIRCUITRY; SIGNALING PATHWAYS; CCR4-NOT COMPLEX; PLURIPOTENCY; DIFFERENTIATION; NETWORK; GENES; PROTEINS; INTERFERENCE AB We performed a genome-wide siRNA screen in mouse embryonic stem (ES) cells to identify genes essential for self-renewal, and found 148 genes whose down-regulation caused differentiation. Many of the identified genes function in gene regulation and/or development, and are highly expressed in ES cells and embryonic tissues. We further identified target genes of two transcription regulators Cnot3 and Trim28. We discovered that Cnot3 and Trim28 co-occupy many putative gene promoters with c-Myc and Zfx, but not other pluripotency-associated transcription factors. They form a unique module in the self-renewal transcription network, separate from the core module formed by Nanog, Oct4, and Sox2. The transcriptional targets of this module are enriched for genes involved in cell cycle, cell death, and cancer. This supports the idea that regulatory networks controlling self-renewal in stem cells may also be active in certain cancers and may represent novel anti-cancer targets. Our screen has implicated over 100 new genes in ES cell self-renewal, and illustrates the power of RNAi and forward genetics for the systematic study of self-renewal. C1 [Hu, Guang; Xu, Qikai; Leng, Yumei; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA. [Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Childrens Hosp,Dana Farber Canc Inst,Harvard Stem, Boston, MA 02115 USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 FU Helen Hay Whitney Foundation; Howard Hughes Medical Institute Research Associates FX We thank Dr. Austin G. Smith for the Oct4GiP cells, Rene Maehr for scientific advice, and the Gene Expression Microarray Core at the DFCI for sample processing. G. H. is a fellow of the Helen Hay Whitney Foundation. J. K., Q. X., and Y. L. are Howard Hughes Medical Institute Research Associates. S. J. E. and S. H. O. are Investigators of the Howard Hughes Medical Institute. NR 39 TC 215 Z9 220 U1 0 U2 16 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 APR 1 PY 2009 VL 23 IS 7 BP 837 EP 848 DI 10.1101/gad.1769609 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 427MP UT WOS:000264783700008 PM 19339689 ER PT J AU Bonham, VL Sellers, SL Gallagher, TH Frank, D Odunlami, AO Price, EG Cooper, LA AF Bonham, Vence L. Sellers, Sherrill L. Gallagher, Thomas H. Frank, Danielle Odunlami, Adebola O. Price, Eboni G. Cooper, Lisa A. TI Physicians' attitudes toward race, genetics, and clinical medicine SO GENETICS IN MEDICINE LA English DT Article DE clinical decision making; race; genetic variation; health disparities; physicians' attitudes ID PRIMARY-CARE PHYSICIANS; HEALTH DISPARITIES; HEART-FAILURE; BIOMEDICAL-RESEARCH; AFRICAN-AMERICAN; BLACK PATIENTS; GENOMICS; ASSOCIATION; ETHNICITY; CANCER AB Purpose: This qualitative study explored black and white general internists' attitudes about the relevance of race in clinical care; views of the relationships among race, genetics, and disease; and expectations about the future of genetics and health. Methods: We conducted 10 racially concordant focus groups of primary care physicians in five metropolitan areas in the United States. Ninety board certified or eligible general internists (50 self-identified whites and 40 self-identified blacks) participated in the study, Analysis included a two-stage independent review and adjudication process. Results: Both black and white physicians concluded that the race of the patient is medically relevant but did not agree upon why race is important in clinical decisions. They were reticent to make connections among race, genetics, and disease and asserted that genetics has a limited role in explaining racial differences in health. However, they were enthusiastic about the future of genomic medicine, believing that the main benefit will be the potential to improve the efficacy of commonly used drugs. Conclusions: Understanding the similarities and differences between black and white physicians' attitudes and beliefs about race, health and genetics is important for the translation of genomics to clinical care. Genet Med 2009:11(4): 279-286. C1 [Bonham, Vence L.; Odunlami, Adebola O.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Sellers, Sherrill L.] Univ Wisconsin, Sch Social Work, Madison, WI 53706 USA. [Sellers, Sherrill L.] Miami Univ, Dept Family Studies & Social Work, Oxford, OH 45056 USA. [Gallagher, Thomas H.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Gallagher, Thomas H.] Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. [Frank, Danielle] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Price, Eboni G.] Tulane Univ, Hlth Sci Ctr, Sect Gen Internal Med & Geriatr, New Orleans, LA 70118 USA. [Cooper, Lisa A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. RP Bonham, VL (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr Room B1B55, Bethesda, MD 20892 USA. EM bonhamv@mail.nih.gov OI Price-Haywood, Eboni/0000-0003-2901-3852 FU National Human Genome Research Institute, National Institutes of Health FX The study was Supported (in part) by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The authors thank Elizabeth M. Phillips and Sarah Knerr for their research assistance and Alan M. Guttmacher, MD, and Francis S. Collins, MD, PhD, (National Human Genome Research Institute) for their suggestions in preparing an early draft of this article. NR 40 TC 10 Z9 10 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2009 VL 11 IS 4 BP 279 EP 286 DI 10.1097/GIM.0b013e318195aaf4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 435KT UT WOS:000265343500007 PM 19265721 ER PT J AU Salehi-Had, H Andreoli, CM Andreoli, MT Kloek, CE Mukai, S AF Salehi-Had, Hani Andreoli, Christopher M. Andreoli, Michael T. Kloek, Carolyn E. Mukai, Shizuo TI Visual outcomes of vitreoretinal surgery in eyes with severe open-globe injury presenting with no-light-perception vision SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE Ocular trauma; Open globe injury; Vitreoretinal surgery; No light perception (NLP) ID PENETRATING OCULAR INJURIES; PARS-PLANA VITRECTOMY; SYMPATHETIC OPHTHALMIA; POSTERIOR SEGMENT; TRAUMA; SURVIVAL; CLASSIFICATION; EPIDEMIOLOGY; ENUCLEATION; MANAGEMENT AB Severe ocular trauma causing no light perception (NLP) typically carries a dismal prognosis, and implies no further therapeutic intervention. We have identified a cohort of patients with verified NLP following open-globe injury who have recovered vision of light perception (LP) or better. We evaluated the outcomes of vitreoretinal surgery performed on eyes that were NLP post open-globe injury. Retrospective review of outcomes of secondary vitreoretinal surgery performed at Massachusetts Eye and Ear Infirmary from 1 January 2001 to 31 December 2006 on all cases of open-globe repair (OGR) that had NLP prior to OGR or on the first post-operative day. A total of 648 cases of OGR were performed in the study period. Eighty-eight patients had NLP prior to OGR or on the first post-operative day after OGR. Twenty-three patients from the above group (26.1%) spontaneously recovered a vision of light perception (LP) or better. Eight of the 23 patients had a secondary vitreoretinal surgery. All eyes that did not undergo vitreoretinal surgery returned to NLP or became phthisical within 7 months. Among the eight eyes that underwent surgery, five had improvement, with vision ranging from hand motion to 20/70. Prognostic indicators for successful surgical outcome were hand motion or better vision prior to vitreoretinal surgery, recovery of vision within 5 days of OGR, and vitreoretinal intervention within 5 weeks of the initial open-globe injury. Patients with severe open-globe injury and NLP occasionally recover LP or better vision. These patients may regain useful vision after vitreoretinal surgery if prompt referral and intervention is attempted and if the spontaneous visual recovery occurs within the first week after OGR. C1 [Mukai, Shizuo] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Andreoli, Michael T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Salehi-Had, Hani; Andreoli, Christopher M.; Kloek, Carolyn E.; Mukai, Shizuo] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Mukai, S (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM shizuo_mukai@meei.harvard.edu NR 33 TC 19 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD APR PY 2009 VL 247 IS 4 BP 477 EP 483 DI 10.1007/s00417-009-1035-4 PG 7 WC Ophthalmology SC Ophthalmology GA 414NH UT WOS:000263870500009 PM 19172288 ER PT J AU Werner, RM Konetzka, RT Kruse, GB AF Werner, Rachel M. Konetzka, R. Tamara Kruse, Gregory B. TI Impact of Public Reporting on Unreported Quality of Care SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality of care; postacute care; nursing home quality; public reporting ID UNINTENDED CONSEQUENCES; PERFORMANCE; IMPROVEMENT; MDS AB The impact of quality improvement incentives on nontargeted care is unknown and some have expressed concern that such incentives may be harmful to nontargeted areas of care. Our objective is to examine the effect of publicly reporting quality information on unreported quality of care. The nursing home Minimum Data Set from 1999 to 2005 on all postacute care admissions. We studied 13,683 skilled nursing facilities and examined how unreported aspects of clinical care changed in response to changes in reported care after public reporting was initiated by the Centers for Medicare and Medicaid Services on their website, Nursing Home Compare, in 2002. We find that overall both unreported and reported care improved following the launch of public reporting. Improvements in unreported care were particularly large among facilities with high scores or that significantly improved on reported measures, whereas low-scoring facilities experienced no change or worsening of their unreported quality of care. Public reporting in the setting of postacute care had mixed effects on areas without public reporting, improving in high-ranking facilities, but worsening in low-ranking facilities. While the benefits of public reporting may extend beyond areas that are being directly measured, these initiatives may also widen the gap between high- and low-quality facilities. C1 [Werner, Rachel M.] Univ Penn, Ctr Hlth Equ Res & Promot, Leonard Davis Inst Hlth Econ, Div Gen Internal Med,Philadelphia VAMC,Sch Med, Philadelphia, PA 19104 USA. [Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Kruse, Gregory B.] Univ Penn, Dept Hlth Care Syst, 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 Agency for Healthcare Research and Quality [R01 HS016478-01]; University Research Foundation of the University of Pennsylvania; VA HSR&D Career Development Award; Pennsylvania Department of Health FX Prior dissemination: This research was presented at AcademyHealth, Washington, DC, June 2008 and American Society of Health Economics, Durham NC, June 2008. NR 20 TC 37 Z9 37 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2009 VL 44 IS 2 BP 379 EP 398 DI 10.1111/j.1475-6773.2008.00915.x PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 418QV UT WOS:000264164400005 PM 19178586 ER PT J AU Byrne, MM Daw, CN Nelson, HA Urech, TH Pietz, K Petersen, LA AF Byrne, Margaret M. Daw, Christina N. Nelson, Harlan A. Urech, Tracy H. Pietz, Kenneth Petersen, Laura A. TI Method to Develop Health Care Peer Groups for Quality and Financial Comparisons Across Hospitals SO HEALTH SERVICES RESEARCH LA English DT Article DE Peer groups; cluster analysis; nearest neighbor; Euclidean distance; quality of care comparisons ID CLUSTER-ANALYSIS; PERFORMANCE; COST AB To develop and explore the characteristics of a novel "nearest neighbor" methodology for creating peer groups for health care facilities. Data were obtained from the Department of Veterans Affairs (VA) databases. Peer groups are developed by first calculating the multidimensional Euclidean distance between each of 133 VA medical centers based on 16 facility characteristics. Each medical center then serves as the center for its own peer group, and the nearest neighbor facilities in terms of Euclidean distance comprise the peer facilities. We explore the attributes and characteristics of the nearest neighbor peer groupings. In addition, we construct standard cluster analysis-derived peer groups and compare the characteristics of groupings from the two methodologies. The novel peer group methodology presented here results in groups where each medical center is at the center of its own peer group. Possible advantages over other peer group methodologies are that facilities are never on the "edge" of a group and group size-and thus group dispersion-is determined by the researcher. Peer groups with these characteristics may be more appealing to some researchers and administrators than standard cluster analysis and may thus strengthen organizational buy-in for financial and quality comparisons. C1 [Petersen, Laura A.] Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, Houston, TX 77030 USA. [Byrne, Margaret M.] Univ Miami, Dept Epidemiol & Publ Hlth, Miami, FL USA. [Daw, Christina N.; Urech, Tracy H.; Pietz, Kenneth] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Daw, Christina N.; Urech, Tracy H.; Pietz, Kenneth] Baylor Coll Med, Houston VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Nelson, Harlan A.] InVent Clin Inc, Indianapolis, IN USA. RP Petersen, LA (reprint author), Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM laurap@bcm.edu FU VA [XVA 33-097]; Houston VA HSR&D Center of Excellence [HFP90-020]; National Cancer Institute [K07 CA101812]; Robert Wood Johnson Foundation [045444]; American Heart Association [0540043N] FX Disclaimers: The views expressed are solely of the authors, and do not necessarily represent those of the VA. NR 25 TC 15 Z9 15 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2009 VL 44 IS 2 BP 577 EP 592 DI 10.1111/j.1475-6773.2008.00916.x PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 418QV UT WOS:000264164400015 PM 19178585 ER PT J AU Essa, AS Kramer, JR Graham, DY Treiber, G AF Essa, Abdallah Said Kramer, Jennifer Rosenthal Graham, David Y. Treiber, Gerhard TI Meta-analysis: Four-Drug, Three-Antibiotic, Non-bismuth-Containing "Concomitant Therapy" Versus Triple Therapy for Helicobacter pylori Eradication SO HELICOBACTER LA English DT Article DE Helicobacter pylori; therapy; meta-analysis; amoxicillin; clarithromycin; nitroimidazole; proton pump inhibitor ID QUADRUPLE THERAPY; SEQUENTIAL THERAPY; CURE RATE; INFECTION; REGIMEN; CLARITHROMYCIN; AMOXICILLIN; METRONIDAZOLE; OMEPRAZOLE; MANAGEMENT AB Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy). To compare concomitant therapy with standard triple therapy for H. pylori infection. By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted. We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73-4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95-6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8-92.1%) and PP was 92.9% (95% CI: 90.2-94.8%). Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy. C1 [Essa, Abdallah Said; Kramer, Jennifer Rosenthal; Graham, David Y.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kramer, Jennifer Rosenthal] Michael E DeBakey VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Treiber, Gerhard] Saarland Univ Hosp, Dept Internal Med 2, Homburg, Germany. RP Graham, DY (reprint author), Vet Affairs Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU Office of Research and Development Medical Research Service Department of Veterans Affairs [MRP05-315]; Public Health Service [DK56338]; Texas Medical Center Digestive Diseases Center; NIH; Services Research and Development Service; Egyptian government FX This material is based on the work supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs and by Public Health Service grant DK56338 which funds the Texas Medical Center Digestive Diseases Center, and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH. In the last 3 years, Dr Graham has received small amounts of grant support and/or free drugs or urea breath tests from Meretek, Jannsen/Eisai, and TAP, and BioHit for investigator-initiated and completely investigator-controlled research. Dr Graham is a consultant for Novartis in relation to vaccine development for treatment or prevention of H. pylori infection. Dr Graham is also a paid consultant for Otsuka Pharmaceuticals and until July 2007 was a member of the Board of Directors of Meretek, Diagnostics, the manufacturer of the 13C-urea breath test. Dr Graham also receives royalties on the Baylor College of Medicine patent covering materials related to 13C-urea breath test. Dr Kramer is supported by an MREP Career Development Award from the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs, grant number MRP05-315. Dr Essa was supported in part by a grant from the Egyptian government. NR 31 TC 121 Z9 129 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD APR PY 2009 VL 14 IS 2 BP 109 EP 118 DI 10.1111/j.1523-5378.2009.00671.x PG 10 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 417IW UT WOS:000264070700005 PM 19298338 ER PT J AU Guinan, EC AF Guinan, Eva C. TI Acquired Aplastic Anemia in Childhood SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review DE Aplastic anemia; Immunosuppression; Stem cell transplantation; Marrow failure; Pediatric ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; COLONY-STIMULATING FACTOR; VERSUS-HOST-DISEASE; SAA-WORKING-PARTY; HLA-IDENTICAL SIBLINGS; CLONAL CYTOGENETIC ABNORMALITIES; MATCHED UNRELATED DONORS AB In comparison to past decades, children who have acquired aplastic anemia (AA) enjoy excellent overall survival that reflects improvements in supportive care, more accurate exclusion of children who have alternate diagnoses, and advances in transplantation and immunosuppressive therapy (IST). Matched sibling-donor hematopoietic stem cell transplants (HSCT) routinely provide long-term survival in the range of 90%, and 75% of patients respond to IST. In this latter group, the barriers to overall and complication-free survival include recurrence of AA, clonal evolution with transformation to myelodysplasia/acute myelogenous leukemia, and therapy-related toxicities. Improvements in predicting responses to IST, in alternative-donor HSCT, and in rationalizing therapy by understanding the pathophysiology in individual patients are likely to improve short- and long-term outcomes for these children. C1 [Guinan, Eva C.] Harvard Univ, Harvard Catalyst Lab Innovat Translat Technol, Harvard Catalyst Linkages Program, Sch Med, Boston, MA 02115 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Ctr Clin & Translat Res, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Harvard Univ, Harvard Catalyst Lab Innovat Translat Technol, Harvard Catalyst Linkages Program, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM eva_guinan@dfci.harvard.edu NR 160 TC 12 Z9 14 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2009 VL 23 IS 2 BP 171 EP + DI 10.1016/j.hoc.2009.01.011 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA 435UY UT WOS:000265370000003 PM 19327578 ER PT J AU Finan, KR Kilgore, ML Hawn, MT AF Finan, K. R. Kilgore, M. L. Hawn, M. T. TI Open suture versus mesh repair of primary incisional hernias: a cost-utility analysis SO HERNIA LA English DT Article DE Hernia; Ventral; Surgical mesh; Costs and cost analysis; Cost-benefit analysis; Decision support techniques ID RANDOMIZED CONTROLLED-TRIAL; OPEN VENTRAL HERNIORRHAPHY; TERM-FOLLOW-UP; RISK-FACTORS; POLYPROPYLENE MESH; WOUND-INFECTION; COMPLICATIONS; IMPROVEMENT; EXPERIENCE; RECURRENCE AB Despite 100,000 ventral hernia repairs (VHR) being performed annually, no gold standard for the technique exists. Mesh has been shown to decrease recurrence rates, yet, concerns of increased complications and costs prevent its systematic use. We examined the cost-effectiveness of open suture (OS) versus open mesh (OM) in primary VHR. A decision analysis model from the payer's perspective comparing OS to OM was constructed for calculating the total costs and cost-effectiveness. Probabilities for complications and outcomes were derived from the literature. The costs represented institutional fixed costs. The outcome measure of effectiveness was recurrence. One-way sensitivity analysis and a probabilistic analysis using Monte Carlo simulation were performed. OS was associated with a total cost of $16,355 (+/- 6,041) per repair, while OM was $16,947 (+/- 7,252). At 3-year follow-up, OM was the more effective treatment with 73.8% being recurrence-free, compared with 56.3% in the OS group. The incremental cost to prevent one recurrence by the placement of mesh was $1,878. OM became the less effective treatment strategy when the infection rate exceeded 35%. At a willingness to pay level of $5,500, OM was the more cost-effective treatment strategy. In subjects without contraindication to mesh placement, OM repair is the more effective surgical treatment for VHR, with a lower risk of recurrence at a small cost to the payer. C1 [Finan, K. R.; Hawn, M. T.] Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Kilgore, M. L.] Univ Alabama, Sch Publ Hlth, Dept Hlth Care Org & Policy, Birmingham, AL 35294 USA. [Hawn, M. T.] Birmingham Vet AVairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, KB 417,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu FU Olympus America Inc FX We would like to thank Dr. Miguel Arguedas for his assistance in the decision modeling and Ms. Catherine Vick for her assistance in providing probabilities from the Veterans AVairs Medical Center ventral hernia repair study. K. R. Finan is a research fellow for the Department of Surgery supported by an educational grant funded by Olympus America Inc. This research was presented at the 2005 American College of Surgeons Clinical Congress, Surgical Forum in San Francisco, California, October 2005, and was awarded the Surgeons' Forum on Fundamental Surgical Problems Resident/ Fellow Excellence in Research Award. NR 31 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1265-4906 J9 HERNIA JI Hernia PD APR PY 2009 VL 13 IS 2 BP 173 EP 182 DI 10.1007/s10029-008-0462-1 PG 10 WC Surgery SC Surgery GA 427WW UT WOS:000264810800010 PM 19142563 ER PT J AU Goldenholz, DM Ahlfors, SP Hamalainen, MS Sharon, D Ishitobi, M Vaina, LM Stufflebeam, SM AF Goldenholz, Daniel M. Ahlfors, Seppo P. Haemaelaeinen, Matti S. Sharon, Dahlia Ishitobi, Mamiko Vaina, Lucia M. Stufflebeam, Steven M. TI Mapping the Signal-To-Noise-Ratios of Cortical Sources in Magnetoencephalography and Electroencephalography SO HUMAN BRAIN MAPPING LA English DT Article DE MEG; EEG; epilepsy; forward model; SNR; simulation; dipole; cortex; brain ID TEMPORAL-LOBE EPILEPSY; SURFACE-BASED ANALYSIS; LOCALIZATION ACCURACY; EPILEPTIFORM ACTIVITY; DIPOLE LOCALIZATION; COORDINATE SYSTEM; MEG DATA; EEG; HEAD; RECONSTRUCTION AB Although magnetoencephalography (MEG) and electroencephalograph), (EEG) have been available for decades, their relative merits are still debated. We examined regional differences in signal-to-noise-ratios (SNRs) of cortical sources in MEG and EEG. Data from four subjects were used to simulate focal and extended Sources located on the cortical surface reconstructed from high-resolution magnetic resonance images. The SNR maps for MEG and EEG were found to be complementary. The SNR of deep sources was larger in EEG than in MEG, whereas the opposite was typically the case for Superficial Sources. Overall, the SNR maps were more uniform for EEG than for MEG. When using a noise model based on Uniformly distributed random sources on the cortex, the SNR in MEG was found to be underestimated, compared with the maps obtained with noise estimated from actual recorded MEG and EEG data. With extended Sources, the total area of cortex in which the SNR was higher in EEG than in MEG was larger than with focal sources. Clinically, SNR maps in a patient explained differential sensitivity of MEG and EEG in detecting epileptic activity. Out results emphasize the benefits of recording MEG and EEG simultaneously. Hum Brain Mapp 30:1077-1086, 2009, (C) 2008 Wiey-Liss. Inc. C1 [Goldenholz, Daniel M.; Ahlfors, Seppo P.; Haemaelaeinen, Matti S.; Sharon, Dahlia; Ishitobi, Mamiko; Vaina, Lucia M.; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Goldenholz, Daniel M.; Vaina, Lucia M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Ahlfors, Seppo P.; Haemaelaeinen, Matti S.; Stufflebeam, Steven M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Vaina, Lucia M.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Goldenholz, DM (reprint author), Massachusetts Gen Hosp, Martinos Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM daniel@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016; OI Goldenholz, Daniel/0000-0002-8370-2758 FU National Center for Research Resources [P41RR14074]; NIH [NS37462, NS44623]; Mental Illness and Neuroscience Discovery (MIND) Institute FX Contract grant sponsor: National Center for Research Resources; Contract grant number: P41RR14074; Contract grant sponsor: NIH,Contract grant numbers: NS37462 and NS44623; Contract grant sponsor: Mental Illness and Neuroscience Discovery (MIND) Institute. NR 52 TC 79 Z9 79 U1 0 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2009 VL 30 IS 4 BP 1077 EP 1086 DI 10.1002/hbm.20571 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 426GP UT WOS:000264696300004 PM 18465745 ER PT J AU Auranen, T Nummenmaa, A Vanni, S Vehtari, A Hamalainen, MS Lampinen, J Jaaskelainen, IP AF Auranen, Toni Nummenmaa, Aapo Vanni, Simo Vehtari, Aki Hamalainen, Matti S. Lampinen, Jouko Jaaskelainen, Iiro P. TI Automatic fMRI-Guided MEG Multidipole Localization for Visual Responses SO HUMAN BRAIN MAPPING LA English DT Article DE inverse problem; MEG; fMRI; multimodal brain imaging; dipole analysis; human visual system; Markov chain Monte Carlo ID INFERENCE DIPOLE ANALYSIS; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN ACTIVITY; BAYESIAN-INFERENCE; INVERSE PROBLEM; MONTE-CARLO; SENSORY STIMULATION; CORTICAL AREAS; FUNCTIONAL MRI AB Previously, we introduced the use of individual cortical location and orientation constraints in the spatiotemporal Bayesian dipole analysis setting proposed by Jun et al. ([2005], Neuroimage 28:84-98). However, the model's performance was limited by slow convergence and multimodality of the numerically estimated posterior distribution. In this paper, we present an intuitive way to exploit functional magnetic resonance imaging (fMRI) data in the Markov chain Monte Carlo sampling -based inverse estimation of magnetoencephalographic (MEG) data. We used Simulated MEG and fMRI data to show that the convergence and localization accuracy of the method is significantly improved with the help of fMRI-guided proposal distributions. We further demonstrate, using an identical visual stimulation paradigm in both fMRI and MEG, the usefulness of this type of automated approach when investigating activation patterns with several spatially close and temporally overlapping Sources. Theoretically, the MEG inverse estimates are not biased and should yield the same results even without fMRI information, however, in practice the multimodality of the posterior distribution causes problems due to the limited mixing properties of the sampler. On this account, the algorithm acts perhaps more as a stochastic optimizer than enables a full Bayesian posterior analysis. Hum Brain Mapp 30:1087-1099, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Auranen, Toni; Nummenmaa, Aapo; Vehtari, Aki; Lampinen, Jouko; Jaaskelainen, Iiro P.] Helsinki Univ Technol, Dept Biomed Engn & Computat Sci, FIN-02150 Espoo, Finland. [Auranen, Toni; Nummenmaa, Aapo; Vanni, Simo; Jaaskelainen, Iiro P.] Helsinki Univ Technol, Adv Magnet Imaging Ctr, FIN-02150 Espoo, Finland. [Vanni, Simo] Helsinki Univ Technol, Low Temp Lab, Brain Res Unit, FIN-02150 Espoo, Finland. [Hamalainen, Matti S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hamalainen, Matti S.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Auranen, T (reprint author), Helsinki Univ Technol, Dept Biomed Engn & Computat Sci, POB 9203, FI-02015 Helsinki, Finland. EM toni.auranen@tkk.fi RI Jaaskelainen, Iiro/C-7392-2012; Vehtari, Aki/A-7584-2008; Hamalainen, Matti/C-8507-2013; Vanni, Simo/B-9590-2013; Lampinen, Jouko/D-3927-2014; Auranen, Toni/J-7137-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Vehtari, Aki/0000-0003-2164-9469; FU Academy of Finland, Centre of Excellence [105628, 200521, 206368, 202871, 213464]; Jenny and Antti Wihuri Foundation; The Center for Functional Neuroimaging Technologies; NIH [P41 RR14075]; MIND Institute [DE-FG02-99ER62764] FX Contract grant sponsor: Academy of Finland, Centre of Excellence; Contract grant numbers: 105628, 200521, 206368, 202871, 213464; Contract grant sponsors: Jenny and Antti Wihuri Foundation, The Center for Functional Neuroimaging Technologies; Contract grant sponsor: NIH; Contract grant number: P41 RR14075; Contract grant sponsor: the MIND Institute; Contract grant sponsor: DE-FG02-99ER62764. NR 50 TC 13 Z9 13 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2009 VL 30 IS 4 BP 1087 EP 1099 DI 10.1002/hbm.20570 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 426GP UT WOS:000264696300005 PM 18465749 ER PT J AU Fang, JL Jin, Z Wang, Y Li, K Kong, J Nixon, EE Zeng, YW Ren, YS Tong, HB Wang, YH Wang, P Hui, KKS AF Fang, Jiliang Jin, Zhen Wang, Yin Li, Ke Kong, Jian Nixon, Erika E. Zeng, Yawei Ren, Yanshuang Tong, Haibin Wang, Yinghui Wang, Ping Hui, Kathleen Kin-Sang TI The Salient Characteristics of the Central Effects of Acupuncture Needling: Limbic-Paralimbic-Neocortical Network Modulation SO HUMAN BRAIN MAPPING LA English DT Article CT 36th Annual Meeting of the Society-for-Neuroscience CY OCT 14-18, 2006 CL Atlanta, GA SP Soc Neurosci DE acupuncture; fMRI; limbic-paralimbic-neocortical network; acupoint specificity; needling; deqi ID MEDIAL PREFRONTAL CORTEX; HUMAN BRAIN; FUNCTIONAL MRI; DEFAULT MODE; ELECTROACUPUNCTURE STIMULATION; CORTICAL ACTIVATIONS; IMPLICATED ACUPOINTS; FMRI; PAIN; REAL AB Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. FMRI studies at Hegu (L14) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical System. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures Such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions. Hum Brain Mapp 30:1196-1206, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Fang, Jiliang; Ren, Yanshuang; Tong, Haibin; Wang, Ping] China Acad Chinese Med Sci, Guang An Men Hosp, Dept Radiol, Beijing, Peoples R China. [Fang, Jiliang; Kong, Jian; Nixon, Erika E.; Hui, Kathleen Kin-Sang] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Fang, Jiliang; Kong, Jian; Nixon, Erika E.; Hui, Kathleen Kin-Sang] Harvard Univ, Sch Med, Charlestown, MA USA. [Jin, Zhen; Li, Ke; Zeng, Yawei] Beijing 306 Hosp, Dept Radiol, MRI Div, Beijing, Peoples R China. [Wang, Yin; Wang, Yinghui] China Acad Chinese Med Sci, Guang An Med Hosp, Dept Acupuncture, Beijing, Peoples R China. RP Fang, JL (reprint author), 5 Bei Xian Ge St, Beijing 100053, Peoples R China. EM fang@nmr.mgh.harvard.edu FU NCCIH NIH HHS [5F05 AT003022-02, 5F05 AT003022-01] NR 75 TC 98 Z9 116 U1 1 U2 31 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD APR PY 2009 VL 30 IS 4 BP 1196 EP 1206 DI 10.1002/hbm.20583 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 426GP UT WOS:000264696300014 PM 18571795 ER PT J AU Landsverk, ML Ruzzo, EK Mefford, HC Buysse, K Buchan, JG Eichler, EE Petty, EM Peterson, EA Knutzen, DM Barnett, K Farlow, MR Caress, J Parry, GJ Quan, D Gardner, KL Hong, M Simmons, Z Bird, TD Chance, PF Hannibal, MC AF Landsverk, Megan L. Ruzzo, Elizabeth K. Mefford, Heather C. Buysse, Karen Buchan, Jillian G. Eichler, Evan E. Petty, Elizabeth M. Peterson, Esther A. Knutzen, Dana M. Barnett, Karen Farlow, Martin R. Caress, Judy Parry, Gareth J. Quan, Dianna Gardner, Kathy L. Hong, Ming Simmons, Zachary Bird, Thomas D. Chance, Phillip F. Hannibal, Mark C. TI Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy SO HUMAN MOLECULAR GENETICS LA English DT Article ID BRACHIAL-PLEXUS NEUROPATHY; LDL RECEPTOR GENE; MAMMALIAN SEPTIN; CHROMOSOME 17Q25; HNA LOCUS; EXPRESSION; NEURITIS; PREDILECTION; MICROTUBULES; ORGANIZATION AB Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA. C1 [Landsverk, Megan L.; Ruzzo, Elizabeth K.; Knutzen, Dana M.; Barnett, Karen; Chance, Phillip F.; Hannibal, Mark C.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Mefford, Heather C.; Buysse, Karen; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Chance, Phillip F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Chance, Phillip F.; Hannibal, Mark C.] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Ruzzo, Elizabeth K.] Howard Hughes Med Inst, Seattle, WA 98195 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Petty, Elizabeth M.; Peterson, Esther A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48105 USA. [Farlow, Martin R.; Caress, Judy] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Parry, Gareth J.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Quan, Dianna] Univ Colorado Denver, Dept Neurol, Aurora, CO 80045 USA. [Gardner, Kathy L.] Vet Adm Hosp, Dept Neurol, Pittsburgh, PA 15213 USA. [Gardner, Kathy L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Hong, Ming] Grp Hlth Bellevue Med Ctr, Bellevue, WA 98004 USA. [Simmons, Zachary] Penn State Coll Med, Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Buysse, Karen] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. RP Hannibal, MC (reprint author), HSB RR247,Box 356320,1959 NE Pacific St, Seattle, WA 98195 USA. EM mhanni@u.washington.edu FU National Institutes of Heath (NINDS) [NS38181] FX The work was supported by funds from the National Institutes of Heath (NINDS), (grant number NS38181 to P. F. C. and M.C.H.); The Neuropathy Association, New York, NY ( to P.F.C.); and the Allan and Phyllis Treuer Endowed Chair for Genetics and Development (to P.F.C.). NR 37 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2009 VL 18 IS 7 BP 1200 EP 1208 DI 10.1093/hmg/ddp014 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 421XI UT WOS:000264391200003 PM 19139049 ER PT J AU Girardi, P Pompili, M Innamorati, M Mancini, M Serafini, G Mazzarini, L Del Casale, A Tatarelli, R Baldessarini, RJ AF Girardi, Paolo Pompili, Maurizio Innamorati, Marco Mancini, Michele Serafini, Glanluca Mazzarini, Lorenzo Del Casale, Antonio Tatarelli, Roberto Baldessarini, Ross J. TI Duloxetine in acute major depression: review of comparisons to placebo and standard antidepressants using dissimilar methods SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Review DE antidepressants; depression; duloxetine; meta-analysis; short-term treatment; SNRIs ID SEROTONIN REUPTAKE INHIBITORS; PAROXETINE-CONTROLLED TRIAL; RANDOMIZED CLINICAL-TRIALS; LONG-TERM TREATMENT; DOUBLE-BLIND; 60 MG; ELDERLY-PATIENTS; REMISSION RATES; NON-INFERIORITY; DISORDER AB Background Randomized controlled trials (RCTs) of duloxetine (DLX), an inhibitor of both norepinephrine and serotonin transporters (SNRI), have tested its efficacy in acute major depressive disorder (MDD) versus placebo (PBO) or standard serotonin-reuptake inhibitors (SRIs) and require review, comparing analytical methods. Method Computerized searching to identify reports of RCTs of DLX in adult, acute MDD patients permitted meta-analytic pooling to estimate overall response and remission rates, to compare mixed-model, repeated measures (MMRM) versus last-observations-carried-forward (LOCF) analytical methods, and to assess relations of DLX dose to efficacy and adverse outcomes. Results We identified 17 RCTs involving 22 comparisons (DLX versus PBO [n= 17) and DLX versus an SRI [n = 16]), based on MMRM and LOCF methods that allowed estimates of response ( >= 50% improvement of depression scores) or remission (final depression score <= 7). There was a large overall DLX/PBO contrast (LOCF, RR = 1.42 [CI: 1.31-1.53], p < 0.0001, with a success rate of 65% [11/17]), and somewhat arger effects with MMRM in both response (MMRM: RR = 1.48 [95%Cl: 1.31-1.66] versus LOCF: RR = L41 [CI: 1.28-1.56]; NNT 4.8 versus 6.5) and remission (MMRM: RR = 1.61 [CI: 1.41-1.85] versus LOCF: RR = 1.44 [CI: 1.27-1.63]; NNT = 5.9 versus 8.9). Based on LOCF methods, dropout rates were similar with DLX and PBO (RR = 1.04 [CI: 0.94-1.15]); DLX response was dose-dependent (r = +0.72. p = 0.001), and RCT-dropout rates were inversely related to DLX dose, but possibly artifactually. Limitations RCTs involving DLX are limited, with few direct comparisons to standard antidepressants. Conclusions DLX has good evidence of efficacy in acute, adult MDD, especially at doses of 80-120 mg/day, but remains inadequately tested against standard alternatives. MMRM analyses yielded slightly superior FLX/PBO contrasts than older LOCF methods. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Girardi, Paolo; Pompili, Maurizio; Serafini, Glanluca; Mazzarini, Lorenzo; Del Casale, Antonio; Tatarelli, Roberto] Univ Rome, Dept Psychiat, St Andrea Hosp, I-00189 Rome, Italy. [Pompili, Maurizio; Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Psychopharmacol Program, Belmont, MA 02478 USA. [Pompili, Maurizio; Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Mood & Psychot Disorders Res, Belmont, MA 02478 USA. [Innamorati, Marco] Univ Europea Roma, Rome, Italy. [Mancini, Michele] Eli Lilly Med Ctr, Florence, Italy. RP Pompili, M (reprint author), Univ Rome, Dept Psychiat, St Andrea Hosp, Via Grottarossa 1035, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; OI Innamorati, Marco/0000-0003-1389-2290; Tatarelli, Roberto/0000-0003-4396-2632; Del Casale, Antonio/0000-0003-2427-6944; Pompili, Maurizio/0000-0003-1886-4977 FU Bruce J. Anderson Foundation; McLean Hospital Private Donors' Research Fund FX Supported, in part, by a grant from the Bruce J. Anderson Foundation and the McLean Hospital Private Donors' Research Fund for Psychopharmacology Research (to RJB). NR 62 TC 21 Z9 22 U1 3 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD APR PY 2009 VL 24 IS 3 BP 177 EP 190 DI 10.1002/hup.1005 PG 14 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 435ML UT WOS:000265347900002 PM 19229839 ER PT J AU Henderson, DC Fan, XD Copeland, PM Sharma, B Borba, CP Forstbauer, SI Miley, K Boxill, R Freudenreich, O Cather, C Evins, AE Goff, DC AF Henderson, David C. Fan, Xiaoduo Copeland, Paul M. Sharma, Bikash Borba, Christina P. Forstbauer, Sharon I. Miley, Kate Boxill, Ryan Freudenreich, Oliver Cather, Corrine Evins, Anne E. Goff, Donald C. TI Ziprasidone as an adjuvant for clozapine- or olanzapine-associated medical morbidity in chronic schizophrenia SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE clozapine; olanzapine; ziprasidone; weight; lipids; insulin resistance; schizophrenia ID ATYPICAL ANTIPSYCHOTIC-DRUG; MINIMAL MODEL ANALYSIS; GLUCOSE-TOLERANCE TEST; INDUCED WEIGHT-GAIN; DIABETES-MELLITUS; RISPERIDONE; ABNORMALITIES; OBESITY; LIPIDS; HYPERGLYCEMIA AB Objective This study sought to examine the effect of ziprasidone on olanzapine or clozapine-associated medical morbidity such as insulin resistance, diabetes mellitus (DM) and impaired fasting glucose, obesity, and hyperlipidemia in patients with schizophrenia or schizoaffective disorder. Method This was a 6-week, open label trial of ziprasidone 160 mg/day added to a stable dose of olanzapine or clozapine in 21 schizophrenia or schizoalfective patients with DM, impaired fasting glucose, or insulin resistance. Results Then olanzapine-treated subjects and I I clozapine-treated subjects were enrolled in the Study. There were no significant differences between the two groups at baseline for age, gender, education, ethnicity, BMI, cholesterol levels, or fasting glucose. At week 6. there were no significant changes in weight, BMI, cholesterol levels, or fasting glucose. There was no significant difference in psychotic, negative, or depressive symptoms. QTc: significantly increased at week 2 but not at week 6. Conclusions The addition of 160 mg/day of ziprasidone was well tolerated but did not produce significant improvement in fasting glucose, insulin resistance, hyperlipidemia or lead to weight loss in olanzapine- or clozapine-treated subjects with schizophrenia or schizoaffective disorder. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Henderson, David C.; Fan, Xiaoduo; Sharma, Bikash; Borba, Christina P.; Forstbauer, Sharon I.; Miley, Kate; Boxill, Ryan; Freudenreich, Oliver; Cather, Corrine; Evins, Anne E.; Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Henderson, David C.; Fan, Xiaoduo; Copeland, Paul M.; Freudenreich, Oliver; Cather, Corrine; Evins, Anne E.; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU NIMH NIH HHS [K24 MH002025] NR 39 TC 19 Z9 20 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD APR PY 2009 VL 24 IS 3 BP 225 EP 232 DI 10.1002/hup.1012 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 435ML UT WOS:000265347900007 PM 19283774 ER PT J AU Gong, SP Kim, H Lee, EJ Lee, ST Moon, S Lee, HJ Lim, JM AF Gong, Seung Pyo Kim, Heebal Lee, Eun Ju Lee, Seung Tae Moon, Sunjin Lee, Ho-Joon Lim, Jeong Mook TI Change in gene expression of mouse embryonic stem cells derived from parthenogenetic activation SO HUMAN REPRODUCTION LA English DT Article DE mouse model; embryonic stem cell; normal fertilization; parthenogenesis; gene expression ID PREANTRAL FOLLICLE CULTURE; HUMAN SOMATIC-CELLS; OOCYTE PARTHENOGENESIS; MOLECULAR SIGNATURE; DEFINED FACTORS; LINES; ESTABLISHMENT; FIBROBLASTS; BLASTOCYSTS; GENERATION AB We previously established parthenogenetic mouse embryonic stem cells (ESCs) and this study was subsequently conducted for elucidating the influence of oocyte parthenogenesis on gene expression profile of ESCs. Gene expression of parthenogenetic ESC (pESC)-1 or pESC-2 was separately compared with that of two normally fertilized ESC (nfESC) lines (B6D2F1 and R1 strains), and quantification of mRNA expression was conducted for validating microarray data. In two sets of comparison, reaction of 11 347 and 15 454 gene probes were altered by parthenogenesis, while strain difference changed the expression of 15 750 and 14 944 probes. Level of correlation coefficient was higher in the comparisons between normal fertilization and parthenogenesis (0.974-0.985) than in the comparisons between strains of nfESCs (0.97-0.971). Overall, the expression of 3276-3329 genes was changed after parthenogenesis, and 88% (96/109) of major functional genes differentially (P < 0.01) expressed in one comparison set showed the same change in the other. When we monitored imprinted genes, expression of nine paternal and eight maternal genes were altered after parthenogenesis and 88% (14/16) of these was confirmed by mRNA quantification. The change in gene expression after parthenogenesis was similar to, or less than, the change induced by a strain difference under a certain genetic background. These results may suggest the clinical feasibility of parthenogenesis-derived, pluripotent cells. C1 [Lim, Jeong Mook] Seoul Natl Univ, Gamete & Stem Cell Biotechnol Lab, Dept Agr Biotechnol, Seoul 151921, South Korea. [Lee, Eun Ju] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea. [Lee, Seung Tae] Swiss Fed Inst Technol, Integrat Biosci Inst, Lab Regenerat Med & Pharmacol, CH-1015 Lausanne, Switzerland. [Lee, Ho-Joon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Kim, Heebal; Lim, Jeong Mook] Seoul Natl Univ, Res Inst Agr & Life Sci, Seoul 151742, South Korea. RP Lim, JM (reprint author), Seoul Natl Univ, Gamete & Stem Cell Biotechnol Lab, Dept Agr Biotechnol, Bldg 200 4223,Sillim 9 Dong, Seoul 151921, South Korea. EM limjm@snu.ac.kr OI Moon, Sunjin/0000-0002-3803-6354; Kim, Heebal/0000-0003-3064-1303 FU Korean Government [KRF-2005-041-F00045]; Stem Cell Research Center [SC-5160]; Korean Ministry of Education, Science and Technology [BK21] FX This work was supported ( to H. K.) by the Korea Research Foundation Grand funded by the Korean Government ( MOEHRD, Basic Research Promotion Fund; KRF-2005-041-F00045), and by Stem Cell Research Center (SC-5160) and BK21 program funded by Korean Ministry of Education, Science and Technology. NR 34 TC 10 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2009 VL 24 IS 4 BP 805 EP 814 DI 10.1093/humrep/den388 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 421XO UT WOS:000264391800007 PM 19106175 ER PT J AU Postelnicu, G Zollei, L Fischl, B AF Postelnicu, Gheorghe Zoellei, Lilla Fischl, Bruce TI Combined Volumetric and Surface Registration SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Cortical and subcortical alignment; elastic warp; magnetic resonance imaging (MRI); volumetric registration ID HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; MR-IMAGES; GEOMETRICALLY ACCURATE; COORDINATE SYSTEM; BRAIN IMAGES; SEGMENTATION; MODEL; TRANSFORMATION; DEFORMATIONS AB In this paper, we propose a novel method for the registration of volumetric images of the brain that optimizes the alignment of both cortical and subcortical structures. In order to achieve this, relevant geometrical information is extracted from a surface-based morph and diffused into the volume using the Navier operator of elasticity, resulting in a volumetric warp that aligns cortical folding patterns. This warp field is then refined with an intensity driven optical flow procedure that registers noncortical regions, while preserving the cortical alignment. The result is a combined surface and volume morph (CVS) that accurately registers both cortical and subcortical regions, establishing a single coordinate system suitable for the entire brain. C1 [Postelnicu, Gheorghe; Zoellei, Lilla; Fischl, Bruce] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02176 USA. EM postelni@nmr.mgh.harvard.edu; lzollei@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41 RR014075-098602, P41-RR14075, R01 RR016594, R01 RR016594-01A1, R01 RR16594-01A1, U24 RR021382, U24 RR021382-01]; NIA NIH HHS [R01 AG018386, R01 AG022381, R01 AG022381-01]; NIBIB NIH HHS [R01 EB001550, R01 EB006758, R01 EB006758-01A1, R01EB001550, R01EB006758, U54 EB005149, U54 EB005149-05, U54EB005149]; NINDS NIH HHS [R01 NS052585, R01 NS052585-01, R01 NS052585-01A1] NR 47 TC 52 Z9 52 U1 1 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2009 VL 28 IS 4 BP 508 EP 522 DI 10.1109/TMI.2008.2004426 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 431UR UT WOS:000265090200004 PM 19273000 ER PT J AU Stepp, CE Heaton, JT Rolland, RG Hillman, RE AF Stepp, Cara E. Heaton, James T. Rolland, Rebecca G. Hillman, Robert E. TI Neck and Face Surface Electromyography for Prosthetic Voice Control After Total Laryngectomy SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Biological motor systems; communication aids; electromyography; prosthetics; vocal system ID COMMUNICATION; SPEECH; REHABILITATION; ELECTROLARYNX; QUALITY; THERAPY; MUSCLES AB The electrolarynx (EL) is a common rehabilitative speech aid for individuals who have undergone total laryngectomy, but they typically lack pitch control and require the exclusive use of one hand. The viability of using neck and face surface electromyography (sEMG) to control the onset, offset, and pitch of an EMG-controlled EL (EMG-EL) was studied. Eight individuals who had undergone total laryngectomy produced serial and running speech using a typical handheld EL and the EMG-EL while attending to real-time visual sEMG biofeedback. Running speech tokens produced with the EMG-EL were examined for naturalness by 10 listeners relative to those produced with a typical EL using a visual analog scale. Serial speech performance was assessed as the percentage of words that were fully voiced and pauses that were successfully produced. Results of the visual analog scale assessment indicated that individuals were able to use the EMG-EL without training to produce running speech perceived as natural as that produced with a typical handheld EL. All participants were able to produce running and serial speech with the EMG-EL controlled by sEMG from multiple recording locations, with the superior ventral neck or submental surface locations providing at least one of the two best control locations. C1 [Stepp, Cara E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Heaton, James T.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rolland, Rebecca G.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. RP Stepp, CE (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM cstepp@alum.mit.edu; heaton.james@mgh.harvard.edu; rebecca.givens@aya.yale.edu FU National Institute of Deafness and Other Communication Disorders [R01-DC006449] FX This work was supported in part by the National Institute of Deafness and Other Communication Disorders Grant R01-DC006449. NR 27 TC 12 Z9 14 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD APR PY 2009 VL 17 IS 2 BP 146 EP 155 DI 10.1109/TNSRE.2009.2017805 PG 10 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 435XD UT WOS:000265375700006 PM 19304494 ER PT J AU Adeane, J Malik, WQ Wassell, IJ AF Adeane, J. Malik, W. Q. Wassell, I. J. TI Error performance of ultrawideband spatial multiplexing systems SO IET MICROWAVES ANTENNAS & PROPAGATION LA English DT Article ID DIVERSITY; CHANNELS AB In this paper, a number of ultrawideband (UWB) multiple-input multiple-output ( MIMO) spatial multiplexing systems are presented and their error performance is analysed. For both model-based and measured UWB channels, the performance of various MIMO detectors is evaluated under the multiband orthogonal frequency division multiplexing (MB-OFDM) regime. Contrary to expectation, the results demonstrate that significant spatial diversity can be extracted, in addition to linear data-rate scaling, despite the large frequency diversity inherent in the UWB channel. It is shown that nonlinear detection schemes with reasonable complexity can provide considerable diversity gain, in contrast to well-known linear receivers. Thus, the proposed UWB spatial multiplexing schemes not only increase the data rate but also provide significant diversity gain and improved error rate performance. C1 [Adeane, J.] Fraser Res, Princeton, NJ 08542 USA. [Malik, W. Q.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Malik, W. Q.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Wassell, I. J.] Univ Cambridge, Dept Engn, Cambridge CB3 0FD, England. RP Adeane, J (reprint author), Fraser Res, 182 Nassau St,Suite 301, Princeton, NJ 08542 USA. EM wqm@mit.edu RI Malik, Wasim/C-9982-2011 NR 15 TC 3 Z9 3 U1 0 U2 1 PU INST ENGINEERING TECHNOLOGY-IET PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 1751-8725 J9 IET MICROW ANTENNA P JI IET Microw. Antennas Propag. PD APR PY 2009 VL 3 IS 3 BP 363 EP 371 DI 10.1049/iet-map.2008.0008 PG 9 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 433BE UT WOS:000265177600001 ER PT J AU Clatworthy, AE Lee, JSW Leibman, M Kostun, Z Davidson, AJ Hung, DT AF Clatworthy, Anne E. Lee, Jenny See-Wai Leibman, Mark Kostun, Zachary Davidson, Alan J. Hung, Deborah T. TI Pseudomonas aeruginosa Infection of Zebrafish Involves both Host and Pathogen Determinants SO INFECTION AND IMMUNITY LA English DT Article ID III SECRETION SYSTEM; VIRULENCE FACTORS; BACTERIAL PATHOGENESIS; CAENORHABDITIS-ELEGANS; MODEL HOST; IN-VIVO; EMBRYOS; GENE; LIPOPOLYSACCHARIDE; MYELOPOIESIS AB Zebrafish (Danio rerio) have a number of strengths as a host model for infection, including genetic tractability, a vertebrate immune system similar to that of mammals, ease and scale of laboratory handling, which allows analysis with reasonable throughput, and transparency, which facilitates visualization of the infection. With these advantages in mind, we examined whether zebrafish could be used to study Pseudomonas aeruginosa pathogenesis and found that infection of zebrafish embryos with live P. aeruginosa (PA14 or PAO1) by microinjection results in embryonic death, unlike infection with Escherichia coli or heat-killed P. aeruginosa, which has no effect. Similar to studies with mice, P. aeruginosa mutants deficient in type three secretion (pscD) or quorum sensing (lasR and mvfR) are attenuated in zebrafish embryos infected at 50 h postfertilization (hpf), a developmental stage when both macrophages and neutrophils are present. In contrast, embryos infected at 28 hpf, when only macrophages are initially present, succumb to lethal challenge with far fewer P. aeruginosa cells than those required for embryos infected at 50 hpf, are susceptible to infection with lasR and pscD deletion mutants, and are moderately resistant to infection with an mvfR mutant. Finally, we show that we can control the outcome of infection through the use of morpholinos, which allow us to shift immune cell numbers, or small molecules (antibiotics), which rescue embryos from lethal challenge. Thus, zebrafish are a novel host model that is well suited for studying the interactions among individual pathogenic functions of P. aeruginosa, the role of individual components of host immune defense, and small-molecule modulators of infection. C1 [Clatworthy, Anne E.; Lee, Jenny See-Wai; Leibman, Mark; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Clatworthy, Anne E.; Lee, Jenny See-Wai; Leibman, Mark; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Clatworthy, Anne E.; Lee, Jenny See-Wai; Leibman, Mark; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Clatworthy, Anne E.; Lee, Jenny See-Wai; Leibman, Mark; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Kostun, Zachary; Davidson, Alan J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Kostun, Zachary; Davidson, Alan J.; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu FU Broad Institute; Pew Scholars in Biomedical Sciences Program FX This work was funded by grants from the Broad Institute and the Pew Scholars in Biomedical Sciences Program. NR 54 TC 62 Z9 63 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2009 VL 77 IS 4 BP 1293 EP 1303 DI 10.1128/IAI.01181-08 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 419AM UT WOS:000264191500004 PM 19168742 ER PT J AU Lam, MY Lee, H Bright, R Korzenik, JR Sands, BE AF Lam, Manuel Y. Lee, Hang Bright, Renee Korzenik, Joshua R. Sands, Bruce E. TI Validation of Interactive Voice Response System Administration of the Short Inflammatory Bowel Disease Questionnaire SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; ulcerative colitis; quality of life; health status instrument; interactive voice response system ID QUALITY-OF-LIFE; HEALTH-RELATED QUALITY; ULCERATIVE-COLITIS PATIENTS; CROHNS-DISEASE; RELIABLE MEASURE; ACTIVITY INDEX; IBDQ; TRANSLATION; VERSION; TECHNOLOGY AB Background: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is it written. self-administered instrument measuring quality of life in IBD. We assessed the validity of an interactive voice response system (IVRS) as a new mode of administering the SIBDQ. Methods: An IVRS was designed using prerecorded questions to collect data via touchtone telephone. Subjects with Crohn's disease (CD) or ulcerative colitis (UC) were randomized into 2 groups With different orders of administration: written, self-administered followed by IVRS (S-I) or IVRS followed by written, self-administered (I-S). Half of the S-I group was also randomized to receive a second IVRS. Sixty-four subjects were studied: 30 in S-I. 34 in I-S. Results: The mean SIBDQ scores were not different between written and IVRS modes (P = 0.26) with r = 0.93. IVRS scores were lower in active than inactive CID (36.1 +/- 9.6 versus 54.7 +/- 8.6, P < 0.001) and lower in active than inactive UC (40.8 +/- 9.6 versus 59.8 +/- 10.0. P < 0.001). Mean scores correlated highly with disease activity indices, and were not different between first and second IVRS administrations (P = 0.85) with r = 0.92. IVRS had excellent internal consistency (Cronbach alpha = 0.90). Conclusions: IVRS administration of the SIBDQ yields results similar to written self-administration, with excellent procedural validity, test-retest reliability. and internal consistency. C1 [Lam, Manuel Y.; Korzenik, Joshua R.; Sands, Bruce E.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Lam, Manuel Y.; Korzenik, Joshua R.; Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA. [Lee, Hang] Harvard Univ, Sch Med, Boston, MA USA. [Bright, Renee] Rhode Isl Hosp, Div Gastroenterol, Providence, RI USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Fl, Boston, MA 02114 USA. EM bsands@partners.org FU Crohn's and Colitis Foundation of America through the Centers for Disease Control and Prevention [1 UO1 DP000340-03]; National Institutes of Health [1R21DK078555-01]; Doris Duke Clinical Research Fellowship FX Supported by a grant from the Crohn's and Colitis Foundation of America through the Centers for Disease Control and Prevention (1 UO1 DP000340-03) and the National Institutes of Health (1R21DK078555-01). Manuel Lam was supported by a Doris Duke Clinical Research Fellowship at Harvard Medical School. NR 44 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2009 VL 15 IS 4 BP 599 EP 607 DI 10.1002/ibd.20803 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 428FK UT WOS:000264833200019 PM 19023897 ER PT J AU Kelly, KA Shaw, SY Nahrendorf, M Kristoff, K Aikawa, E Schreiber, SL Clemons, PA Weissleder, R AF Kelly, Kimberly A. Shaw, Stanley Y. Nahrendorf, Matthias Kristoff, Kelly Aikawa, Elena Schreiber, Stuart L. Clemons, Paul A. Weissleder, Ralph TI Unbiased discovery of in vivo imaging probes through in vitro profiling of nanoparticle libraries SO INTEGRATIVE BIOLOGY LA English DT Article ID PHENOTYPIC HETEROGENEITY; MAGNETIC NANOPARTICLES; PHAGE DISPLAY; QUANTUM DOTS; CELL-CULTURE; ENDOTHELIUM; CANCER; EXPRESSION; AGENTS AB In vivo imaging reveals how proteins and cells function as part of complex regulatory networks in intact organisms, and thereby contributes to a systems-level understanding of biological processes. However, the development of novel in vivo imaging probes remains challenging. Most probes are directed against a limited number of pre-specified protein targets; cell-based screens for imaging probes have shown promise, but raise concerns over whether in vitro surrogate cell models recapitulate in vivo phenotypes. Here, we rapidly profile the in vitro binding of nanoparticle imaging probes in multiple samples of defined target vs. background cell types, using primary cell isolates. This approach selects for nanoparticles that show desired targeting effects across all tested members of a class of cells, and decreases the likelihood that an idiosyncratic cell line will unduly skew screening results. To adjust for multiple hypothesis testing, we use permutation methods to identify nanoparticles that best differentiate between the target and background cell classes. (This approach is conceptually analogous to one used for high-dimensionality datasets of genome-wide gene expression, e.g. to identify gene expression signatures that discriminate subclasses of cancer.) We apply this approach to the identification of nanoparticle imaging probes that bind endothelial cells, and validate our in vitro findings in human arterial samples, and by in vivo intravital microscopy in mice. Overall, this work presents a generalizable approach to the unbiased discovery of in vivo imaging probes, and may guide the further development of novel endothelial imaging probes. C1 [Kelly, Kimberly A.; Kristoff, Kelly; Aikawa, Elena; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA 02129 USA. [Kelly, Kimberly A.; Kristoff, Kelly; Aikawa, Elena; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Shaw, Stanley Y.; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. [Shaw, Stanley Y.; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Shaw, Stanley Y.; Schreiber, Stuart L.; Clemons, Paul A.] Broad Inst Harvard, Chem Biol Program, Cambridge, MA 02142 USA. [Shaw, Stanley Y.; Schreiber, Stuart L.; Clemons, Paul A.] MIT, Cambridge, MA 02142 USA. RP Kelly, KA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging, 149 13th St,Rm 5420, Charlestown, MA 02129 USA. EM shaw.stanley@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU NIH [NHLBI U01HL080731, NCI P50CA086355, NCI U54CA119349, NHLBI K08HL077186, NIGMS P20-GM-072029]; Broad Institute of Harvard and MIT; de Gunzburg Family Foundation at Massachusetts General Hospital FX The authors thank L. Josephson, F. Reynolds, R. Kohler, E. Sun, F. Jaffer and Y. Iwamoto for assistance, reagents, and helpful comments. This work was supported by the NIH (NHLBI U01HL080731 to S. Y. S. and R. W., NCI P50CA086355 and NCI U54CA119349 to R. W., NHLBI K08HL077186 to S. Y. S., and NIGMS P20-GM-072029 to P. A. C.), Broad Institute of Harvard and MIT (to S. Y. S., R. W., and S. L. S.), and the de Gunzburg Family Foundation at Massachusetts General Hospital (S. Y. S.). NR 33 TC 9 Z9 9 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PD APR PY 2009 VL 1 IS 4 BP 311 EP 317 DI 10.1039/b821775k PG 7 WC Cell Biology SC Cell Biology GA 459OX UT WOS:000267114100004 PM 20023731 ER PT J AU Marchese, AD Chipman, D de la Oliva, P Kacmarek, RM AF Marchese, Andrew D. Chipman, Daniel de la Oliva, Pedro Kacmarek, Robert M. TI Adult ICU ventilators to provide neonatal ventilation: a lung simulator study SO INTENSIVE CARE MEDICINE LA English DT Article DE Ventilators, mechanical; Neonatal; Respiratory mechanics; Respiration, artificial; Intensive care units; Equipment safety; Models ID PERFORMANCE AB Background: Traditionally, specific ventilators have been manufactured to only provide neonatal mechanical ventilation. However, many of the current generation of ICU ventilators also include a neonatal mode. Methods: Using the IngMar ASL5000 lung simulator the Puritan Bennett 840, the Maquet Servo i, the Viasys AVEA, the GE Engstrom, the Drager Evita XL and Babylog 8000 Plus were evaluated during assisted ventilation in the pressure assist/control mode. Three lung mechanics were set: resistance 50 cmH(2)O/L/s, compliance 2 mL/cmH(2)O; resistance 100 cmH(2)O/L/s, compliance 1 mL/cmH(2)O; and resistance 150 cmH(2)O/L/s, compliance 0.5 mL/cmH(2)O. A maximum negative pressure drop of 4 and 7 cmH(2)O was achieved during simulated inspirations. Each ventilator was evaluated with PEEP 5 cmH(2)O, peak pressure 20 cmH(2)O and inspiratory time 0.3 s and with PEEP 10 cmH(2)O, peak pressure 30 cmH(2)O and inspiratory time 0.4 s. Each ventilator setting was then repeated with a leak of 0.3 L/min at a constant pressure of 5 cmH(2)O. Results: Overall each of the 5 ICU ventilators responded faster or greater than the Babylog with respect to: pressure to trigger (except the Servo i), time to trigger (except the Evita XL), time between trigger and return of pressure to baseline, time from start of breath to 90% of peak pressure (except the Avea) and pressure time product of breath activation. Expiratory tidal volume was also greater with all ICU ventilators except the Avea. Variation in mechanics, leak, PEEP and muscular effort had little effect on these differences. Conclusion: All ICU ventilators tested were able to at least equal the performance of the Babylog 8000 Plus on all variables evaluated. C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Kacmarek, Robert M.] Resp Care Massachusetts Gen Hosp, Anesthesia Harvard Med Sch, Boston, MA USA. [de la Oliva, Pedro] Resp Care Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA USA. [de la Oliva, Pedro] Hosp Univ Materno Infantil La Paz, Pediat Intens Care Unit, Madrid, Spain. [de la Oliva, Pedro] Univ Autonoma Madrid, Dept Pediat, Madrid, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org FU Hamilton Medical; Puritan-Bennett Corp; Respironics Inc.; Viasys, Inc; General Electric; Maquet Medical FX Robert Kacmarek has received research grants and honorariums for lecturing from Hamilton Medical, Puritan-Bennett Corp, Respironics Inc. Viasys, Inc, General Electric, and Maquet Medical. Daniel Chipman has received honorarium form Maquet Medical for lecturing. NR 14 TC 18 Z9 18 U1 2 U2 3 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 APR PY 2009 VL 35 IS 4 BP 631 EP 638 DI 10.1007/s00134-008-1332-0 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 420XE UT WOS:000264321700010 PM 18931831 ER PT J AU Caramez, MP Kacmarek, RM Helmy, M Miyoshi, E Malhotra, A Amato, MBP Harris, RS AF Caramez, Maria Paula Kacmarek, Robert M. Helmy, Mohamed Miyoshi, Eriko Malhotra, Atul Amato, Marcelo B. P. Harris, R. Scott TI A comparison of methods to identify open-lung PEEP SO INTENSIVE CARE MEDICINE LA English DT Article DE Lung injury; ARDS; Recruitment; Lung mechanics; Pressure-volume curve; PEEP ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; FREQUENCY OSCILLATORY VENTILATION; RECRUITMENT MANEUVERS; VOLUME CURVE; MECHANICAL VENTILATION; INJURY; PULMONARY; TRIAL; STRATEGY AB Purpose: Many methods exist in the literature for identifying PEEP to set in ARDS patients following a lung recruitment maneuver (RM). We compared ten published parameters for setting PEEP following a RM. Methods: Lung injury was induced by bilateral lung lavage in 14 female Dorset sheep, yielding a PaO(2) 100-150 mmHg at F(I)O(2) 1.0 and PEEP 5 cmH(2)O. A quasi-static P-V curve was then performed using the supersyringe method; PEEP was set to 20 cmH(2)O and a RM performed with pressure control ventilation (inspiratory pressure set to 40-50 cmH(2)O), until PaO(2) + PaCO(2) > 400 mmHg. Following the RM, a decremental PEEP trial was performed. The PEEP was decreased in 1 cmH(2)O steps every 5 min until 15 cmH(2)O was reached. Parameters measured during the decremental PEEP trial were compared with parameters obtained from the P-V curve. Results: For setting PEEP, maximum dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), and minimum shunt calculated during the decremental PEEP trial, and the lower Pflex and point of maximal compliance increase on the inflation limb of the P-V curve (Pmci,i) were statistically indistinguishable. The PEEP value obtained using the deflation upper Pflex and the point of maximal compliance decrease on the deflation limb were significantly higher, and the true inflection point on the inflation limb and minimum PaCO(2) were significantly lower than the other variables. Conclusion: In this animal model of ARDS, dynamic tidal respiratory compliance, maximum PaO(2), maximum PaO(2) + PaCO(2), minimum shunt, inflation lower Pflex and Pmci,i yield similar values for PEEP following a recruitment maneuver. C1 [Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Caramez, Maria Paula; Kacmarek, Robert M.; Helmy, Mohamed; Miyoshi, Eriko] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care & Resp Care, Boston, MA 02114 USA. [Malhotra, Atul] Brigham & Womens Hosp, Dept Med Pulm Crit Care & Sleep, Boston, MA 02115 USA. [Amato, Marcelo B. P.] Univ Sao Paulo, Hosp Clin, Resp ICU, Dept Pulm, Sao Paulo, Brazil. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM rharris@partners.org FU departmental funds FX This study was funded by departmental funds. Robert Kacmarek has received research grants and honorarium for lecturing from Puritan Bennett, Maquet Medical, Hamilton Medical, and Respironics, Inc. and is a consultant for SpaceLabs Healthcare. NR 32 TC 23 Z9 26 U1 0 U2 3 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 APR PY 2009 VL 35 IS 4 BP 740 EP 747 DI 10.1007/s00134-009-1412-9 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 420XE UT WOS:000264321700025 PM 19183951 ER PT J AU Basile, JN AF Basile, J. N. TI Antihypertensive therapy, new-onset diabetes, and cardiovascular disease SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; RANDOMIZED CONTROLLED-TRIAL; RENIN-ANGIOTENSIN-SYSTEM; ANTI HYPERTENSIVE DRUGS; LIFE-STYLE INTERVENTION; PRESSURE LOWERING ARM; METABOLIC SYNDROME; CARDIAC OUTCOMES; FASTING GLUCOSE; BLOOD-PRESSURE AB Type 2 diabetes mellitus is a worldwide epidemic with considerable health and economic consequences. Diabetes is an important risk factor for cardiovascular disease, which is the leading cause of death in diabetic patients, and decreasing the incidence of diabetes may potentially reduce the burden of cardiovascular disease. This article discusses the clinical trial evidence for modalities associated with a reduction in the risk of new-onset diabetes, with a focus on the role of antihypertensive agents that block the renin-angiotensin system. Lifestyle interventions and the use of antidiabetic, anti-obesity, and lipid-lowering drugs are also reviewed. An unresolved question is whether decreasing the incidence of new-onset diabetes with non-pharmacologic or pharmacologic intervention will also lower the risk of cardiovascular disease. A large ongoing study is investigating whether the treatment with an oral antidiabetic drug or an angiotensin-receptor blocker will reduce the incidence of new-onset diabetes and cardiovascular disease in patients at high risk for developing diabetes. C1 [Basile, J. N.] Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC 29403 USA. [Basile, J. N.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Basile, JN (reprint author), Ralph H Johnson VA Med Ctr, Primary Care Serv Line, 109 Bee St, Charleston, SC 29403 USA. EM jan.basile@va.gov FU Tanja Schub of Landmark Programs FX The author wishes to thank Tanja Schub of Landmark Programs for editorial support. NR 69 TC 7 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD APR PY 2009 VL 63 IS 4 BP 656 EP 666 DI 10.1111/j.1742-1241.2009.02009.x PG 11 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 419SX UT WOS:000264241100019 PM 19220522 ER PT J AU Cummings, DE AF Cummings, D. E. TI Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT 9th and 10th Annual International Symposia of the Merck Frosst/CIHR Research Chair in Obesity CY NOV 15-16, 2007 CL Univ Laval, Quebec City, CANADA SP Merck Frost, CIHR HO Univ Laval DE diabetes; gastric bypass; bariatric surgery; ghrelin; GLP-1 ID DUODENAL-JEJUNAL BYPASS; GLUCAGON-LIKE PEPTIDE-1; GOTO-KAKIZAKI RATS; BETA-CELL FUNCTION; WEIGHT-LOSS; BARIATRIC SURGERY; HYPERINSULINEMIC HYPOGLYCEMIA; ILEAL TRANSPOSITION; RECURRENT HYPOGLYCEMIA; CIRCULATING GHRELIN AB Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weight-independent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM ( before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic beta-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides ( for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment. C1 [Cummings, D. E.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Cummings, D. E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Cummings, DE (reprint author), Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Box 358280,Mail Stop 111, Seattle, WA 98195 USA. EM davidec@u.washington.edu NR 50 TC 101 Z9 103 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2009 VL 33 BP S33 EP S40 DI 10.1038/ijo.2009.15 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 435OR UT WOS:000265353700009 PM 19363506 ER PT J AU Wo, JY Viswanathan, AN AF Wo, Jennifer Y. Viswanathan, Akila N. TI IMPACT OF RADIOTHERAPY ON FERTILITY, PREGNANCY, AND NEONATAL OUTCOMES IN FEMALE CANCER PATIENTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Review DE Fertility; Pregnancy; Neonatal; Radiation therapy; Female ID INDUCED OVARIAN FAILURE; TOTAL-BODY IRRADIATION; LONG-TERM SURVIVORS; CHILDHOOD-CANCER; HODGKINS-DISEASE; WILMS-TUMOR; ABDOMINAL IRRADIATION; RADIATION-THERAPY; LAPAROSCOPIC OOPHOROPEXY; CRANIAL IRRADIATION AB Purpose: Radiation has many potential long-term effects on cancer survivors. Female cancer patients may experience decreased fertility depending on the site irradiated. Oncologists should be aware of these consequences and discuss options for fertility preservation before initiating therapy. Methods and Materials: A comprehensive review of the existing literature was conducted. Studies reporting the outcomes for female patients treated with cranio-spinal, abdominal, or pelvic radiation reporting fertility, pregnancy, or neonatal-related outcomes were reviewed. Results: Cranio-spinal irradiation elicited significant hormonal changes in women that affected their ability to become pregnant later in life. Women treated with abdomino-pelvic radiation have an increased rate of uterine dysfunction leading to miscarriage, preterm labor, low birth weight, and placental abnormalities. Early menopause results from low-dose ovarian radiation. Ovarian transposition may decrease the rates of ovarian dysfunction. Conclusions: There is a dose-dependent relationship between ovarian radiation therapy (RT) and premature menopause. Patients treated with RT must be aware of the impact of treatment on fertility and explore appropriate options. (C) 2009 Elsevier Inc. C1 [Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. [Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wo, Jennifer Y.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM aviswanathan@LROC.harvard.edu OI Viswanathan, Akila/0000-0002-2003-0392 FU NCI NIH HHS [K07 CA117979, K07 CA117979-01, K07 CA117979-02, K07 CA117979-03, K07 CA117979-04] NR 63 TC 76 Z9 79 U1 0 U2 6 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 APR 1 PY 2009 VL 73 IS 5 BP 1304 EP 1312 DI 10.1016/j.ijrobp.2008.12.016 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 426SM UT WOS:000264728000003 PM 19306747 ER PT J AU Sharma, G Mavroidis, C Rege, K Yarmush, ML Budil, D AF Sharma, Gaurav Mavroidis, Constantinos Rege, Kaushal Yarmush, Martin L. Budil, David TI Computational Studies of a Protein-based Nanoactuator for Nanogripping Applications SO INTERNATIONAL JOURNAL OF ROBOTICS RESEARCH LA English DT Article DE nanorobotics; bio-nanotechnology; protein engineering; molecular dynamics ID GCN4 LEUCINE-ZIPPER; MOLECULAR-DYNAMICS SIMULATIONS; CHEMICAL-VAPOR-DEPOSITION; X-RAY-STRUCTURE; COILED-COIL; CARBON NANOTUBES; MICROELECTROMECHANICAL STRUCTURES; ELECTROSTATIC INTERACTIONS; NANO-ACTUATORS; NANOTWEEZERS AB The design hypothesis, architectures, and computational modeling of a novel peptide-based nanoactuator are presented in this paper. We engineered the alpha-helical coiled-coil portion of the yeast transcriptional activator peptide called GCN4 to obtain an environmentally responsive nanoactuator. The dimeric coiled-coil peptide consists of two identical approximately 4.5 nm long and approximately 3 nm wide polypeptide chains. The actuation mechanism depends on the modification of electrostatic charges along the peptide by varying the pH of the solution resulting in the reversible movement of helices and, therefore, creating the motion of an actuator. Using molecular dynamics simulations we showed that pH changes led to a reversible opening of up to 1.5 nm which is approximately 150% of the initial separation of the nanoactuator. We also investigated the forces generated by the nanoactuator upon pH actuation, using a new method based on a modified steered molecular dynamics technique. Owing to its open and close motion resembling that of tweezers, the new nanoactuator can potentially be used as a nanogripper in various nanomanipulation tasks such as detection and removal of heavy metal ions during nanofabrication processes or as a molecular switch. C1 [Sharma, Gaurav; Mavroidis, Constantinos] Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. [Rege, Kaushal; Yarmush, Martin L.] Massachusetts Gen Hosp, CEM, Boston, MA 02114 USA. [Rege, Kaushal; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Budil, David] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. RP Sharma, G (reprint author), Northeastern Univ, Dept Mech & Ind Engn, 360 Huntington Ave, Boston, MA 02115 USA. EM mavro@coe.neu.edu RI Budil, David/A-9931-2012 OI Budil, David/0000-0003-2384-7928 FU NASA Institute for Advanced Concepts (NIAC); National Science Foundation [DMI-0422724] FX The authors would like to thank the NASA Institute for Advanced Concepts (NIAC) Phase II grant and the National Science Foundation ( grant DMI-0422724) for the financial support of this research. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the National Science Foundation. NR 64 TC 4 Z9 4 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0278-3649 EI 1741-3176 J9 INT J ROBOT RES JI Int. J. Robot. Res. PD APR PY 2009 VL 28 IS 4 BP 421 EP 435 DI 10.1177/0278364908100278 PG 15 WC Robotics SC Robotics GA 419YD UT WOS:000264254700002 ER PT J AU Sun, JK Aiello, LP Stockman, M Cavallerano, JD Kopple, A Eagan, S Qin, HJ Kollman, C Beck, RW Glassman, AR AF Sun, Jennifer K. Aiello, Lloyd Paul Stockman, Margaret Cavallerano, Jerry D. Kopple, Ann Eagan, Sharon Qin, Haijing Kollman, Craig Beck, Roy W. Glassman, Adam R. CA Diabet Retinopathy Clinical Res Ne TI Effects of Dilation on Electronic-ETDRS Visual Acuity in Diabetic Patients SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COMPUTERIZED METHOD; PUPIL-DILATION; VISION; ADAPTATION AB PURPOSE. To evaluate the effect of pupillary dilation on electronic-ETDRS visual acuity (EVA) in diabetic subjects and to assess postdilation EVA as a surrogate for predilation VA. METHODS. DRCR.net-protocol refraction and EVA were measured before and after dilation in diabetic subjects by independent, masked examiners. RESULTS. In 129 eyes of 66 subjects, the median (25th, 75th percentiles) predilation EVA score was 69 (54, 86) (Snellen-equivalent 20/40(-1) [20/80(-1), 20/20(-1)]). Predilation VA was >= 20/20, <20/20 to 20/40, <20/40 to 20/80, and <20/80 in 29%, 19%, 26%, and 26% of eyes, respectively. Median EVA change postdilation was -3 letters (-7, 0). The absolute change in EVA score was >= 15 letters (>= 3 ETDRS lines) in 9% of eyes and >= 10 letters (>= 2 ETDRS lines) in 19% of eyes. Extent of change (range +12 to -25 letters) was associated with baseline VA. No relationship was identified between EVA change and gender, race, lens status, refractive error, DR severity, or primary cause of vision loss. CONCLUSIONS. In an optimized clinical trial setting, there is a decline in best corrected EVA after dilation in diabetic subjects. The large range and magnitude of VA change preclude using postdilation EVA as a surrogate for undilated VA. (Invest Ophthalmol Vis Sci. 2009; 50: 1580-1584) DOI: 10.1167/iovs.08-2426 C1 [Sun, Jennifer K.; Aiello, Lloyd Paul; Stockman, Margaret; Cavallerano, Jerry D.; Kopple, Ann; Eagan, Sharon] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.; Aiello, Lloyd Paul; Stockman, Margaret; Cavallerano, Jerry D.; Kopple, Ann; Eagan, Sharon] Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. [Sun, Jennifer K.; Aiello, Lloyd Paul; Cavallerano, Jerry D.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Sun, Jennifer K.; Qin, Haijing; Kollman, Craig; Beck, Roy W.; Glassman, Adam R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. RP Sun, JK (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrx2@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; U.S. Department of Health and Human Services [EY14231, EY14269, EY14229] FX Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services EY14231, EY14269, EY14229. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2009 VL 50 IS 4 BP 1580 EP 1584 DI 10.1167/iovs.08-2426 PG 5 WC Ophthalmology SC Ophthalmology GA 424CP UT WOS:000264543400015 PM 18936147 ER PT J AU Chung, ES Saban, DR Chauhan, SK Dana, R AF Chung, Eui-Sang Saban, Daniel R. Chauhan, Sunil K. Dana, Reza TI Regulation of Blood Vessel versus Lymphatic Vessel Growth in the Cornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FACTOR RECEPTOR-3; GRAFT-REJECTION; MOUSE CORNEA; IN-VITRO; LYMPHANGIOGENESIS; ANGIOGENESIS; VEGF; NEOVASCULARIZATION; TRANSPLANTATION; INFLAMMATION AB PURPOSE. In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea. METHODS. Micropellets loaded with high-dose (80 ng) or low-dose (12.5 ng) basic fibroblast growth factor (bFGF) were placed in BALB/c corneas. Angiogenic responses were analyzed by immunohistochemistry to quantify blood neovessels (BVs) and lymphatic neovessels (LVs) to 3 weeks after implantation. Areas covered by BV and LV were calculated and expressed as a percentage of the total corneal area (percentage BV and percentage LV). Hemangiogenesis (HA) and lymphangiogenesis (LA) were also assessed after antibody blockade of VEGFR-2 or VEGFR-3 RESULTS. Although high-dose bFGF stimulation induced a more potent angiogenic response, the relative LV (RLV = percentage LV/percentage BV X 100) was nearly identical with high- and low-doses of bFGF. Delayed LA responses induced 3 weeks after implantation of high-dose bFGF resulted in a lymphatic vessel-dominant phenotype. Interestingly, the blockade of VEGFR-2 significantly suppressed BV and LV. However, the blockade of VEGFR-3 inhibited only LV (P = 0.0002) without concurrent inhibition of BV (P = 0.79), thereby resulting in a blood vessel-dominant phenotype CONCLUSIONS. An HA-dominant corneal phenotype can be obtained in BALB/c mice 2 weeks after implantation of an 80-ng bFGF micropellet with VEGFR-3 blockade. Alternatively, an LA-dominant corneal phenotype can be obtained 3 weeks after implantation of an 80-ng bFGF micropellet without supplementary modulating agents. These models will be useful in evaluating the differential contribution of BV and LV to a variety of corneal abnormalities, including transplant rejection, wound healing and microbial keratitis. (Invest Ophthalmol Vis Sci. 2009; 50: 1613-1618) DOI:10.1167/iovs.08-2212 C1 [Chung, Eui-Sang; Saban, Daniel R.; Chauhan, Sunil K.; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA. [Chung, Eui-Sang; Saban, Daniel R.; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Chung, Eui-Sang] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Ophthalmol, Seoul, South Korea. [Dana, Reza] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [NEI-RO1-12963]; New England Transplant Research Fund (RD) FX Supported by National Institutes of Health Grant NEI-RO1-12963 (RD) and by the New England Transplant Research Fund (RD). NR 25 TC 23 Z9 25 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 APR PY 2009 VL 50 IS 4 BP 1613 EP 1618 DI 10.1167/iovs.08-2212 PG 6 WC Ophthalmology SC Ophthalmology GA 424CP UT WOS:000264543400020 PM 19029028 ER PT J AU den Hollander, AI McGee, TL Ziviello, C Banfi, S Dryja, TP Gonzalez-Fernandez, F Ghosh, D Berson, EL AF den Hollander, Anneke I. McGee, Terri L. Ziviello, Carmela Banfi, Sandro Dryja, Thaddeus P. Gonzalez-Fernandez, Federico Ghosh, Debashis Berson, Eliot L. TI A Homozygous Missense Mutation in the IRBP Gene (RBP3) Associated with Autosomal Recessive Retinitis Pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINOID-BINDING PROTEIN; SALT-BRIDGE; VITAMIN-A; CHLORAMPHENICOL ACETYLTRANSFERASE; CHOLINE-ACETYLTRANSFERASE; TARGETED DISRUPTION; CRYSTAL-STRUCTURE; FUNCTIONAL UNIT; VISUAL CYCLE; ACTIVE-SITE AB PURPOSE. Interphotoreceptor retinoid-binding protein (IRBP) has been considered essential for normal rod and cone function, as it mediates the transport of retinoids between the photoreceptors and the retinal pigment epithelium. This study was performed to determine whether mutations in the IRBP gene (RBP3) are associated with photoreceptor degeneration. METHODS. A consanguineous family was ascertained in which four children had autosomal recessive retinitis pigmentosa (RP). Homozygosity mapping performed with SNP microarrays revealed only one homozygous region shared by all four affected siblings. Sequencing of RBP3, contained in this region, was performed in this family and others with recessive RP. Screening was also performed on patients with various other forms of retinal degeneration or malfunction. RESULTS. Sequence analysis of RBP3 revealed a homozygous missense mutation (p. Asp1080Asn) in the four affected siblings. The mutation affects a residue that is completely conserved in all four homologous modules of the IRBP protein of vertebrate species and in C-terminal-processing proteases, photosynthesis enzymes found in bacteria, algae, and plants. Based on the previously reported crystal structure of Xenopus IRBP, the authors predict that the Asp1080-mediated conserved salt bridge that appears to participate in scaffolding of the retinol-binding domain is abolished by the mutation. No RBP3 mutations were detected in 395 unrelated patients with recessive or isolate RP or in 680 patients with other forms of hereditary retinal degeneration. CONCLUSIONS. Mutations in RBP3 are an infrequent cause of autosomal recessive RP. The mutation Asp1080Asn may alter the conformation of the IRBP protein by disrupting a conserved salt bridge. (Invest Ophthalmol Vis Sci. 2009; 50: 1864-1872) DOI: 10.1167/iovs.08-2497 C1 [den Hollander, Anneke I.; McGee, Terri L.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab,Study Retinal Degenerat, Boston, MA 02114 USA. [Dryja, Thaddeus P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. [Ziviello, Carmela; Banfi, Sandro] Telethon Inst Genet & Med, Naples, Italy. [Ziviello, Carmela] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy. [Gonzalez-Fernandez, Federico] Vet Affairs Med Ctr, Res Serv, Buffalo, NY USA. [Gonzalez-Fernandez, Federico] SUNY Buffalo, Dept Ophthalmol, Ross Eye Inst, Buffalo, NY USA. [Gonzalez-Fernandez, Federico] SUNY Buffalo, Dept Pathol, Ross Eye Inst, Buffalo, NY USA. [Ghosh, Debashis] Univ Buffalo, Dept Biol Struct, Hauptman Woodward Inst, Buffalo, NY USA. [Ghosh, Debashis] Roswell Pk Canc Inst, Program Mol Pharmacol & Therapeut, Buffalo, NY 14263 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab,Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM linda_berard@meei.harvard.edu RI Hollander, Anneke/N-4911-2014; OI BANFI, Sandro/0000-0002-6541-8833 FU National Institutes of Health [EY00169, EY08683, P30-EY014104, EY009412]; The Foundation Fighting Blindness USA; Research to Prevent Blindness; Netherlands Organisation for Scientific Research [916.56.160]; Italian Telethon Foundation; Royal Netherlands Academy of Arts and Sciences (AIdH); Veterans Affairs FX Supported by National Institutes of Health Grants EY00169, EY08683, and P30-EY014104 and Grant EY009412 (FG-F, DG); The Foundation Fighting Blindness USA; an unrestricted grant (Department of Ophthalmology, Harvard Medical School) and a challenge grant (Department of Ophthalmology, SUNY, Buffalo) from Research to Prevent Blindness; a Netherlands Organisation for Scientific Research Veni Grant 916.56.160 (AIdH); the Italian Telethon Foundation (SB); a Ter Meulen Fund Stipend from the Royal Netherlands Academy of Arts and Sciences (AIdH); and a Merit Review Award from the Veterans Affairs (FG-F). NR 45 TC 38 Z9 39 U1 0 U2 6 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 APR PY 2009 VL 50 IS 4 BP 1864 EP 1872 DI 10.1167/iovs.08-2497 PG 9 WC Ophthalmology SC Ophthalmology GA 424CP UT WOS:000264543400052 PM 19074801 ER PT J AU Kernisan, LP Lee, SJ Boscardin, WJ Landefeld, CS Dudley, RA AF Kernisan, Leslie P. Lee, Sei J. Boscardin, W. John Landefeld, C. Seth Dudley, R. Adams TI Association Between Hospital-Reported Leapfrog Safe Practices Scores and Inpatient Mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AORTIC-ANEURYSM REPAIR; QUALITY-OF-CARE; STANDARDS; RISK; SURGERY; VOLUME AB Context The Leapfrog Hospital Survey allows hospitals to self-report the steps they have taken toward implementing the Safe Practices for Better Healthcare endorsed by the National Quality Forum. The Leapfrog Group currently ranks hospital performance on the safe practices initiative by quartiles and presents this information to the public on its Web site. It is unknown how well a hospital's resulting Safe Practices Score (SPS) correlates with outcomes such as inpatient mortality. Objective To determine the relationship between hospitals' SPSs and risk-adjusted inpatient mortality rates. Design, Setting, and Participants Observational analysis of discharge data for all urban US hospitals completing the 2006 safe practices initiative and identifiable in the Nationwide Inpatient Sample. Leapfrog provided an SPS for each hospital as well as 3 alternative scores based on shorter versions of the original survey. Hierarchical logistic regression was used to determine the relationship between quartiles of SPS and risk-adjusted inpatient mortality, after adjusting for hospital discharge volume and teaching status. Subgroup analyses were performed using data from patients older than 65 years and patients with 5% or greater expected mortality risk. Main Outcome Measures Inpatient risk-adjusted mortality by quartiles of survey score. Results Of 1075 hospitals completing the 2006 Safe Practices Survey, 155 (14%) were identifiable in the National Inpatient Sample (1 772 064 discharges). Raw observed mortality in the primary sample was 2.09%. Fully adjusted mortality rates by quartile of SPS, from lowest to highest, were 1.97% (95% confidence interval [CI], 1.78%-2.18%), 2.04% (95% CI, 1.84%-2.25%), 1.96% (95% CI, 1.77%-2.16%), and 2.00% (95% CI, 1.80%-2.22%) (P=.99 for linear trend). Results were similar in the subgroup analyses. None of the 3 alternative survey scores was associated with risk-adjusted inpatient mortality, although P values for linear trends were lower (. 80, .20, and .11). Conclusion In this sample of hospitals that completed the 2006 Safe Practices Survey, survey scores were not significantly associated with risk-adjusted inpatient mortality. C1 [Dudley, R. Adams] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. [Kernisan, Leslie P.; Lee, Sei J.; Boscardin, W. John; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. [Boscardin, W. John] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94118 USA. [Kernisan, Leslie P.; Lee, Sei J.; Landefeld, C. Seth] San Francisco VA Med Ctr, Natl VA Qual Scholars Program, San Francisco, CA USA. [Lee, Sei J.; Boscardin, W. John; Landefeld, C. Seth] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Landefeld, C. Seth] Stanford Univ, Ctr Adv Study Behav Sci, Palo Alto, CA 94304 USA. RP Dudley, RA (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, 3333 Calif St,Ste 265, San Francisco, CA 94118 USA. EM adams.dudley@ucsf.edu FU National Institute on Aging, National Institutes of Health [2 T32 AG000212-16]; Robert Wood Johnson Foundation FX Funding/Support: This study was supported by the UCSF Division of Geriatrics, the UCSF Institute for Health Policy Studies, and the San Francisco VA Medical Center. Dr Kernisan was supported by T32 research fellowship grant 2 T32 AG000212-16 from the National Institute on Aging, National Institutes of Health, followed by a VA Quality Scholars fellowship. Dr Dudley's work was supported by a Robert Wood Johnson Foundation Investigator Award in Health Policy. This study was also supported by the Leapfrog Group, which provided its data at no cost. NR 30 TC 26 Z9 26 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 2009 VL 301 IS 13 BP 1341 EP 1348 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 426LM UT WOS:000264709800023 PM 19336709 ER PT J AU Werner, RM McNutt, R AF Werner, Rachel M. McNutt, Robert TI A New Strategy to Improve Quality Rewarding Actions Rather Than Measures SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PERFORMANCE-MEASURES; MORTALITY; CARE C1 [Werner, Rachel M.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [McNutt, Robert] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. RP Werner, RM (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 423 Guardian Dr,1230 Blockley Hall, Philadelphia, PA 19104 USA. EM rwerner@mail.med.upenn.edu NR 13 TC 23 Z9 23 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 2009 VL 301 IS 13 BP 1375 EP 1377 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 426LM UT WOS:000264709800028 PM 19336714 ER PT J AU Gruber, J Harvey, AG Wang, PW Brooks, JO Thase, ME Sachs, GS Ketter, TA AF Gruber, June Harvey, Allison G. Wang, Po W. Brooks, John O., III Thase, Michael E. Sachs, Gary S. Ketter, Terence A. TI Sleep functioning in relation to mood, function, and quality of life at entry to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Sleep; STEP-BD ID MANIA; DEPRIVATION; DEPRESSION; ADULTS; QUESTIONNAIRE; CONSEQUENCES; DURATION; INSOMNIA; SCALE AB Background: Sleep disturbance in bipolar disorder can be both a risk factor and symptom of mood episodes. However, the associations among sleep and clinical characteristics, function, and quality of life in bipolar disorder have not been fully investigated. Methods: The prevalence of sleep disturbance, duration, and variability, as well as their associations with mood, function, and quality of life, was determined from 2024 bipolar patients enrolled in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Results: Analyses indicated that 32% of patients were classified as short sleepers, 39% normal sleepers, and 23% long sleepers. Overall, short sleepers demonstrated greater mood elevation, earlier age at onset, and longer illness duration compared to both normal and long sleepers. Both short and long sleepers had greater depressive symptoms, poorer life functioning, and quality of life compared to nor-mal sleepers. Discussion: Sleep duration in bipolar disorder was associated with a more severe symptom presentation, whereas both short and long sleep duration are associated with poorer function and quality of life compared to normal sleep duration. Sleep disturbance could be a trait marker of bipolar disorder, though longitudinal assessments are warranted to assess potential Causal relations and the longer-term implications of sleep disturbance in bipolar disorder. (c) 2008 Elsevier B.V. All rights reserved. C1 [Ketter, Terence A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorders Clin, Stanford, CA 94305 USA. [Gruber, June; Harvey, Allison G.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Brooks, John O., III] Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. [Sachs, Gary S.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Sachs, Gary S.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. RP Ketter, TA (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Bipolar Disorders Clin, 401 Quarry Rd, Stanford, CA 94305 USA. EM tketter@stanford.edu FU NIMH NIH HHS [N01 MH080001, N01MH80001] NR 45 TC 41 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2009 VL 114 IS 1-3 BP 41 EP 49 DI 10.1016/j.jad.2008.06.028 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 419MO UT WOS:000264223900004 PM 18707765 ER PT J AU Marangell, LB Dennehy, EB Miyahara, S Wisniewski, SR Bauer, MS Rapaport, MH Allen, MH AF Marangell, Lauren B. Dennehy, Ellen B. Miyahara, Sachiko Wisniewski, Stephen R. Bauer, Mark S. Rapaport, Mark Hyman Allen, Michael H. TI The functional impact of subsyndromal depressive symptoms in bipolar disorder: Data from STEP-BD SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Subsyndromal depressive symptoms; Depression; Function ID TREATMENT ENHANCEMENT PROGRAM; SOCIAL-ADJUSTMENT; MINOR DEPRESSION; NATURAL-HISTORY; I DISORDER; FOLLOW-UP; IMPAIRMENT; UNIPOLAR; EPISODES; RECOVERY AB Background: This report describes baseline characteristics and functional outcomes of subjects who have prospectively observed subsyndromal symptoms after a major depressive episode (MDE). Methods: All subjects were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We identified subjects with at least 2 years of observation whose prior or current episode was a MDE, and who were in a stable clinical state of either recovered (no more than 2 moderate symptoms for at least 8 weeks), a MDE by DSM-IV criteria, or with continued subsyndromal symptoms. The subsyndromal group was defined a priori as 3 or more moderate affective symptoms but without meeting diagnostic criteria for major depression. Results: The final cohort included 1094 recovered, 112 subsyndromal, and 3 10 individuals in a MDE. The average time spent in each clinical status ranged from 120 to 132 days. The subsyndromal group was most similar to those in a MDE, differing only on the intensity of depressive symptoms and the number of work days missed due to ongoing symptoms. Reported sadness, inability to feel and lassitude were each associated with multiple measures of impairment. Limitations: This study is limited by the cross-sectional approach to defining outcomes. Conclusions: These findings are consistent with studies in unipolar major depression that indicate that functional impairment observed in the context of subsyndromal depressive symptoms is comparable to that of a full episode. This work underscores the need to include subsyndromal symptoms in study outcomes and to target full remission in clinical practice. (c) 2008 Elsevier B.V. All rights reserved. C1 [Marangell, Lauren B.] Baylor Coll Med, Menninger Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. [Marangell, Lauren B.] S Cent Mental Illness Res & Educ Core, Dept Vet Affairs, Houston, TX USA. [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Miyahara, Sachiko; Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Boston, MA USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. [Rapaport, Mark Hyman] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA 90048 USA. [Rapaport, Mark Hyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Allen, Michael H.] Univ Colorado, Denver Depress Ctr, Denver, CO 80202 USA. RP Marangell, LB (reprint author), Eli Lilly & Co, US Med Div, Indianapolis, IN 46285 USA. EM drlauren@lilly.com RI Allen, Michael/A-8776-2011; OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01 MH080001, N01MH80001] NR 36 TC 45 Z9 48 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2009 VL 114 IS 1-3 BP 58 EP 67 DI 10.1016/j.jad.2008.07.006 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 419MO UT WOS:000264223900006 PM 18708263 ER PT J AU Smith, MC Yamashita, TE Bryant, LL Hemphill, L Kutner, JS AF Smith, Marlaine C. Yamashita, Traci E. Bryant, Lucinda L. Hemphill, Linnea Kutner, Jean S. TI Providing Massage Therapy for People with Advanced Cancer: What to Expect SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID AROMATHERAPY MASSAGE; PAIN; CARE AB There is very little information in the literature to prepare massage therapists for what they might expect when they provide treatment to people with advanced cancer in hospice or palliative care. We report an analysis of a subset of data collected from a large multi-site clinical trial of the efficacy of massage therapy for people with advanced cancer. This is the first analysis of empirical data of patient presentation, massage treatment environment, and the characteristics of massage provided for this population. C1 [Smith, Marlaine C.] Florida Atlantic Univ, Christine E Lynn Coll Nursing, Boca Raton, FL 33431 USA. [Yamashita, Traci E.] Univ Colorado, Denver Sch Med, Div Gen Internal Med, Denver, CO 80202 USA. [Bryant, Lucinda L.] Univ Colorado, Denver Sch Med, Dept Prevent Med & Biometr, Denver, CO 80202 USA. [Hemphill, Linnea] Denver Vet Affairs Med Ctr, Dept Nursing, Denver, CO USA. RP Smith, MC (reprint author), Florida Atlantic Univ, Christine E Lynn Coll Nursing, 777 Glades Rd, Boca Raton, FL 33431 USA. EM marlaine.smith@fau.edu FU National Institutes of Health/National Center for Complementary and Alternative Medicine [1R01AT01006-01A2]; Mendel/Asarch Lung Cancer Family Foundation FX This study was funded by grants from the National Institutes of Health/National Center for Complementary and Alternative Medicine (1R01AT01006-01A2) and the Mendel/Asarch Lung Cancer Family Foundation. We acknowledge Biotone (San Diego, CA) for their donation of massage cream for the study. We thank all the staff and volunteers from the hospices for their dedication and hard work, and the participants who gave their precious time. NR 19 TC 8 Z9 8 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD APR PY 2009 VL 15 IS 4 BP 367 EP 371 DI 10.1089/acm.2008.0391 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 436MZ UT WOS:000265419500007 PM 19388858 ER PT J AU Kradin, R AF Kradin, Richard TI The family myth: its deconstruction and replacement with a balanced humanized narrative SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article DE family myth; humanized narrative; puer aeternus; transference resistance AB According to Carl Jung the mythopoeic activities of the collective unconscious contribute to the trajectory of personal individuation (Segal 1998). The 'family myth' represents an imaginal narrative that emphasizes the importance of the family's founders, its collective values, and its position with respect to 'outsiders'. Sigmund Freud identified the importance of the Oedipal myth as the basis of nuclear family dynamics (Rudnytsky 1992); however, the 'myth of the family' represents in reality a 'family of myths', each emphasizing different elements of potential interpersonal dynamics. But whereas some myths foster the child's optimal separation from parental influence and promote the process of individuation, others tend to hinder development. One potentially deleterious form of the family myth tends to serve the narcissistic wishes of parents in their bid to maintain influence over the child by fostering the archetypal features of their role. The children who are the targets of the myth are thwarted in their psychological development by virtue of the fact that they are denied the opportunity to humanize their archetypal projections onto their parent(s). The result is a persistence of childlike attitude with respect to people and situations that they encounter outside the nuclear family. The persistent constellation of the child archetype is evidenced by features of the puer aeternus, with deficits in the ability to work, form stable adult relationships, and create a separate nuclear family. The significance of this type of family myth in the inappropriate preservation of puerile attitudes is examined and the desire of the offending parent(s) to promote their own immortality is explored. The contribution of the myth to the transference and transference resistance is explicated and suggestions are offered with respect to how to approach this critical issue in analysis. C1 [Kradin, Richard] Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. [Kradin, Richard] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kradin, Richard] CG Jung Inst, Boston, MA USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 23 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD APR PY 2009 VL 54 IS 2 BP 217 EP 232 PG 16 WC Psychology, Psychoanalysis SC Psychology GA 426VP UT WOS:000264736600004 PM 19344315 ER PT J AU Fagenholz, PJ Gutman, JA Murray, AF Noble, VE Camargo, CA Harris, NS AF Fagenholz, Peter J. Gutman, Jonathan A. Murray, Alice F. Noble, Vicki E. Camargo, Carlos A., Jr. Harris, N. Stuart TI Optic nerve sheath diameter correlates with the presence and severity of acute mountain sickness: evidence for increased intracranial pressure SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE hypoxia; high altitude ID CEREBROSPINAL-FLUID PRESSURE; HIGH-ALTITUDE ILLNESS; CEREBRAL EDEMA; ULTRASONOGRAPHY; ULTRASOUND; EMERGENCY; INJURY AB Fagenholz PJ, Gutman JA, Murray AF, Noble VE, Camargo CA Jr, Harris NS. Optic nerve sheath diameter correlates with the presence and severity of acute mountain sickness: evidence for increased intracranial pressure. J Appl Physiol 106: 1207-1211, 2009. First published December 31, 2008; doi:10.1152/japplphysiol.01188.2007.-Increased intracranial pressure is suspected in the pathogenesis of acute mountain sickness (AMS), but no studies have correlated it with the presence or severity of AMS. We sought to determine whether increased optic nerve sheath diameter, a surrogate measure of intracranial pressure, is associated with the presence and severity of AMS. We performed a cross-sectional study of travelers ascending through Pheriche, Nepal (4,240 m), from March 3 to May 14, 2006. AMS was assessed using the Lake Louise score. Optic nerve sheath diameter was measured by ultrasound. Ultrasound exams were performed and read by separate blinded observers. Two-hundred eighty seven subjects were enrolled. Ten of these underwent repeat examination. Mean optic nerve sheath diameter was 5.34 mm [95% confidence interval (CI) 5.18-5.51 mm] in the 69 subjects with AMS vs. 4.46 mm (95% CI 4.39-4.54 mm) in the 218 other subjects (P < 0.0001). There was also a positive association between optic nerve sheath diameter and total Lake Louise score (P for trend < 0.0001). In a multivariate logistic regression model of factors associated with AMS, optic nerve sheath diameter was strongly associated with AMS (odds ratio 6.3; 95% CI, 3.7-10.8; P < 0.001). In 10 subjects with repeat examinations, change in Lake Louise score had a strong positive correlation with change in optic nerve sheath diameter (R(2) = 0.84, P < 0.001). Optic nerve sheath diameter, a proxy for intracranial pressure, is associated with the presence and severity of AMS. C1 [Fagenholz, Peter J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Fagenholz, Peter J.; Gutman, Jonathan A.; Murray, Alice F.] Pheriche Clin, Himalayan Rescue Assoc, Spring Season 2006, Nepal. [Gutman, Jonathan A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Med Oncol, Seattle, WA 98195 USA. [Murray, Alice F.] New Royal Infirm Edinburgh, Emergency Dept, Edinburgh, Midlothian, Scotland. [Noble, Vicki E.; Camargo, Carlos A., Jr.; Harris, N. Stuart] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, GRB 425,55 Fruit St, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 28 TC 34 Z9 36 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 2009 VL 106 IS 4 BP 1207 EP 1211 DI 10.1152/japplphysiol.01188.2007 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 427AW UT WOS:000264753000024 PM 19118159 ER PT J AU Belogrudov, GI AF Belogrudov, Grigory I. TI Recent advances in stucture-functional studies of mitochondrial factor B SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Factor B; Energy coupling; ATP synthase complex ID BOVINE HEART-MITOCHONDRIA; COUPLING FACTOR-B; ENERGY-LINKED FUNCTIONS; ATP SYNTHASE; OXIDATIVE-PHOSPHORYLATION; BEEF-HEART; SUBMITOCHONDRIAL PARTICLES; SUBUNIT-E; MEMBRANE; PURIFICATION AB Since the early studies on the resolution and reconstitution of the oxidative phosphorylation system from animal mitochondria, coupling factor B was recognized as an essential component of the machinery responsible for energy-driven ATP synthesis. At the phenomenological level, factor B was agreed to lie at the interface of energy transfer between the respiratory chain and the ATP synthase complex. However, biochemical characterization of the factor B polypeptide has proved difficult. It was not until 1990 that the N-terminal amino acid sequence of bovine mitochondrial factor B was reported, which followed, a decade later, by the report describing the amino acid sequence of full-length human factor B and its functional characterization. The present review summarizes the recent advances in structure-functional studies of factor B, including its recently determined crystal structure at 0.96 resolution. Ectopic expression of human factor B in cultured animal cells has unexpectedly revealed its role in shaping mitochondrial morphology. The supramolecular assembly of ATP synthase as dimer ribbons at highly curved apices of the mitochondrial cristae was recently suggested to optimize ATP synthesis under proton-limited conditions. We propose that the binding of the ATP synthase dimers with factor B tetramers could be a means to enhance the efficiency of the terminal step of oxidative phosphorylation in animal mitochondria. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Belogrudov, GI (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbelo@ucla.edu FU NIH [RO1 GM066085] FX I thank Dr. Youssef Hatefi on whose suggestion I started to work on the factor B project in his laboratory at The Scripps Research Institute in July 2000; my colleagues at the West Los Angeles VA Medical Center for their support and discussions; my outstanding collaborators Drs. John K. Lee and Robert M. Stroud, both of UCSF, on determination bovine factor B crystal structure. I am grateful to the late Professor Yuri A. Ovchinnikov in whose laboratory at the Shemyakin Institute of Bioorganic Chemistry, Moscow, in 1981 I, then a student, first encountered studies on mysterious factor B. This work was supported by NIH RO1 grant GM066085. NR 52 TC 10 Z9 12 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD APR PY 2009 VL 41 IS 2 BP 137 EP 143 DI 10.1007/s10863-009-9210-1 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 460UH UT WOS:000267215700008 PM 19377834 ER PT J AU English, SB Shih, SC Ramoni, MF Smith, LE Butte, AJ AF English, Sangeeta B. Shih, Shou-Ching Ramoni, Marco F. Smith, Lois E. Butte, Atul J. TI Use of Bayesian networks to probabilistically model and improve the likelihood of validation of microarray findings by RT-PCR SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Bioinformatics; Bayesian network; Microarray; RT-PCR; Microarray data ID GENE-EXPRESSION DATA; NORMALIZATION; FRAMEWORK; MODULES; MOUSE AB Though genome-wide technologies, such as microarrays, are widely used, data from these methods are considered noisy: there is still varied Success in downstream biological validation. We report a method that increases the likelihood Of Successfully validating microarray findings using real time RT-PCR. including genes at low expression levels and with small differences. We use a Bayesian network to identify the most relevant sources of noise based on the successes and failures in validation for an initial set of selected genes, and then improve Our subsequent selection of genes for validation based on eliminating these sources of noise. The network displays the significant Sources of noise in an experiment, and scores the likelihood of validation for every gene. We show how the method can significantly increase validation success rates. In conclusion, in this study, we have Successfully added a new automated step to determine the contributory sources of noise that determine successful or unsuccessful downstream biological validation. (C) 2008 Elsevier Inc. All rights reserved. C1 [English, Sangeeta B.; Butte, Atul J.] Stanford Univ, Sch Med, Stanford Ctr Biomed Informat Res BMIR, Stanford, CA 94305 USA. [Shih, Shou-Ching] Beth Israel Deaconess Med Ctr Res N, Dept Pathol, Boston, MA 02215 USA. [Smith, Lois E.] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02115 USA. [Ramoni, Marco F.] Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Ramoni, Marco F.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA. RP English, SB (reprint author), Stanford Univ, Sch Med, Stanford Ctr Biomed Informat Res BMIR, 251 Campus Dr, Stanford, CA 94305 USA. EM english1@stanford.edu FU V. Kann Rasmussen Foundation; National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; National Institute of Allergy and Infectious Diseases; Harvard-MIT Division of Health Sciences and Technology; Lawson Wilkins Pediatric Endocrine Society FX The work was supported by grants from the V. Kann Rasmussen Foundation, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Cancer Institute, National Institute of Allergy and Infectious Diseases, the Harvard-MIT Division of Health Sciences and Technology, and the Lawson Wilkins Pediatric Endocrine Society. NR 32 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2009 VL 42 IS 2 BP 287 EP 295 DI 10.1016/j.jbi.2008.08.009 PG 9 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 429ZO UT WOS:000264958800009 PM 18790084 ER PT J AU Souer, JS Ring, D Matschke, S Audige, L Marent-Huber, M Jupiter, JB AF Souer, J. Sebastiaan Ring, David Matschke, Stefan Audige, Laurent Marent-Huber, Marta Jupiter, Jesse B. CA AOCID Prospective ORIF Distal Radi TI Effect of an Unrepaired Fracture of the Ulnar Styloid Base on Outcome After Plate-and-Screw Fixation of a Distal Radial Fracture SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RADIOULNAR JOINT INSTABILITY; INTRAARTICULAR FRACTURES; EXTERNAL FIXATION; YOUNG-ADULTS; INJURIES; MANAGEMENT; END AB Background: The impact of an unrepaired fracture of the ulnar styloid base on recovery after internal fixation of a fracture of the distal part of the radius is uncertain. We evaluated a series of patients with an internally fixed fracture of the distal part of the radius to test the hypothesis that there is no difference in wrist motion or function scores between those with an untreated fracture of the ulnar styloid base and those with no ulnar fracture. Methods: Two cohorts of seventy-six matched patients, one with a fracture of the ulnar styloid base and the other with no ulnar fracture, were retrospectively analyzed by examining data gathered in a prospective study of plate-and-screw fixation of distal radial fractures. Patients were matched forage, sex, AO fracture type, and injury mechanism. The two cohorts were analyzed for differences in motion, grip strength, pain, the Gartland and Werley score, the DASH (Disabilities of the Arm, Shoulder and Hand) score, and the SF-36 (Short Form-36) score at six, twelve, and twenty-four months postoperatively. In a second analysis, sixty-four patients with <2 mm of displacement of a fracture of the ulnar styloid base were compared with forty-nine patients with greater displacement. Differences between cohorts and within cohorts over time were determined with use of regression analysis and the likelihood ratio test. Results: No significant differences were found between patients with an unrepaired fracture of the ulnar styloid base and those with no ulnar fracture at any of the follow-up intervals. However, a trend was observed toward less grip strength at six months (71% [of that on the contralateral side] compared with 79%; mean difference, -8% [95% confidence interval = -15.3% to -0.6%]; p = 0.03) and less flexion (54 degrees compared with 59 degrees; mean difference, -5 degrees [95% confidence interval = -11.7 degrees to -0.8 degrees]; p = 0.02) and ulnardeviation (32 degrees compared with 36 degrees; mean difference, -4 degrees [95% confidence interval = -70 to -0.1 degrees]; p = 0.05) at twenty-four months after surgery in patients with an untreated fracture of the ulnar styloid base. There were no significant differences with regard to any tested outcome measure between the patients with >= 2 mm of displacement of an unrepaired fracture of the ulnar styloid base and those with less displacement. Conclusions: An unrepaired fracture of the base of the uInar styloid does not appear to influence function or outcome after treatment of a distal radial fracture with plate-and-screw fixation, even when the uInar fracture was initially displaced >= 2 mm. C1 [Souer, J. Sebastiaan] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. RP Souer, JS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI AOCID, AO Foundation/R-6455-2016 NR 27 TC 51 Z9 61 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 APR PY 2009 VL 91A IS 4 BP 830 EP 838 DI 10.2106/JBJS.H.00345 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 428EB UT WOS:000264829700010 PM 19339567 ER PT J AU Barrington, JW Sah, A Malchau, H Burke, DW AF Barrington, John W. Sah, Alexander Malchau, Henrik Burke, Dennis W. TI Contemporary Cruciate-Retaining Total Knee Arthroplasty with a Pegged Tibial Baseplate Results at a Minimum of Ten Years SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FOLLOW-UP; PATELLAR COMPONENT; SURVIVORSHIP; JOINT; STEM AB Background: A total knee arthroplasty with a four-peg tibial baseplate is an uncommonly used contemporary design. Potential advantages of this baseplate include preservation of host bone, compatibility with minimally invasive techniques, and easier removal with revision techniques. The purpose of this study was to determine the long-term results of a contemporary total knee arthroplasty that included a four-peg tibial baseplate. Methods: From February 1995 to December 1996, 127 total knee arthroplasties were performed by one surgeon in 115 patients with an average age of seventy years. Clinical and radiographic evaluations were performed with use of the Knee Society scoring system at a minimum of ten years following replacement. Complications were identified by means of chart review and screening for readmission at surrounding institutions. Results: At the time of follow-up, at a minimum often years after the arthroplasty, thirty patients (with thirty-three involved knees) were documented to have died and four patients (with seven involved knees) could not be located. The next-of-kin of the patients who had died directly confirmed that the knee was unrevised at the time of death. Eighty-seven knees in eighty-one patients remained available for evaluation after a minimum of ten years of follow-up. Two knees had failed: one had a late infection at three years, and one had aseptic loosening at seven years. The rate of survival free of revision at ten years was 97%. Knee Society knee and function scores averaged 94 and 75 points, respectively. None of the remaining knees had radiographic evidence of loosening. Conclusions: This study demonstrated excellent, durable clinical and radiographic results at a minimum of ten years after replacement with this cemented, modular, fixed-bearing, cruciate-retaining total knee prosthesis with a four-peg tibial baseplate. We believe that this design is an acceptable option for total knee arthroplasty. C1 [Sah, Alexander; Malchau, Henrik; Burke, Dennis W.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Barrington, JW (reprint author), Texas Ctr Joint Replacement, 5940 W Parker Rd,100, Plano, TX 75093 USA. EM barringtonj@tcjr.com NR 20 TC 23 Z9 26 U1 2 U2 2 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 APR PY 2009 VL 91A IS 4 BP 874 EP 878 DI 10.2106/JBJS.G.01609 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 428EB UT WOS:000264829700015 PM 19339572 ER PT J AU Kwolek, CJ AF Kwolek, Christopher J. TI Pro: Has Carotid Angioplasty and Stenting Replaced Carotid Endarterectomy as the Treatment of Choice for Carotid Artery Disease? SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE carotid endarterectomy; carotid angioplasty; carotid stenting; carotid artery disease ID STENOSIS EVA-3S TRIAL; PROTECTION; EXPERIENCE; PHASE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Vasc Ctr,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Kwolek, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Vasc Ctr,Div Vasc & Endovasc Surg, 15 Parkman St,WAC 442, Boston, MA 02114 USA. EM ckwolek@partners.org NR 19 TC 1 Z9 1 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD APR PY 2009 VL 23 IS 2 BP 245 EP 247 DI 10.1053/j.jvca.2009.01.024 PG 3 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 430OX UT WOS:000264999500023 PM 19324283 ER PT J AU Liu, YP Seckin, H Izci, Y Du, ZW Yan, YP Baskaya, MK AF Liu, Yi-Ping Seckin, Hakan Izci, Yusuf Du, Zhong Wei Yan, Yi-Ping Baskaya, Mustafa K. TI Neuroprotective effects of mesenchymal stem cells derived from human embryonic stem cells in transient focal cerebral ischemia in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral ischemia; human embryonic stem cells; mesenchymal stem cells; spontaneously hypertensive rats; stroke ID MARROW STROMAL CELLS; HUMAN SOMATIC-CELLS; BONE-MARROW; THERAPEUTIC BENEFIT; HUMAN FIBROBLASTS; DEFINED FACTORS; IN-VITRO; STROKE; DIFFERENTIATION; TRANSPLANTATION AB Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1 mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for beta-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia. C1 [Liu, Yi-Ping; Seckin, Hakan; Izci, Yusuf; Yan, Yi-Ping; Baskaya, Mustafa K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Madison, WI 53792 USA. [Du, Zhong Wei] Univ Wisconsin, Waisman Ctr, Madison, WI 53792 USA. [Baskaya, Mustafa K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Baskaya, MK (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Box 8660 Clin Sci Ctr K4,600 Highland Ave, Madison, WI 53792 USA. EM m.baskaya@neurosurg.wisc.edu NR 40 TC 36 Z9 39 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2009 VL 29 IS 4 BP 780 EP 791 DI 10.1038/jcbfm.2009.1 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 426XM UT WOS:000264741700013 PM 19209181 ER PT J AU Henry, CA Shervin, D Neumeyer, A Steingard, R Spybrook, J Choueiri, R Bauman, M AF Henry, Charles A. Shervin, David Neumeyer, Ann Steingard, Ronald Spybrook, Jessaca Choueiri, Roula Bauman, Margaret TI Retrial of Selective Serotonin Reuptake Inhibitors in Children with Pervasive Developmental Disorders: A Retrospective Chart Review SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID INTOLERANT DEPRESSED-PATIENTS; AUTISTIC SPECTRUM DISORDERS; CITALOPRAM TREATMENT; DOUBLE-BLIND; REPETITIVE BEHAVIORS; RESISTANT DEPRESSION; FLUOXETINE TREATMENT; MENTAL-RETARDATION; ADULTS; CLOMIPRAMINE AB Background: Youths with pervasive developmental disorders (PDDs) often have symptoms that fail to respond to selective serotonin reuptake inhibitor (SSRI) treatment. These children may be given a subsequent trial of another SSRI. This study reports on the outcome of PDD youths who received a second SSRI trial after an initial treatment failure. Methods: Clinic charts were reviewed for 22 outpatient youths with a DSM-IV diagnosis of a PDD who were treated with an SSRI after an initial failure with a previous SSRI. Response for the second SSRI trial was determined using the Clinical Global Impressions-Improvement Scale (CGI-I). Treatment indications, symptom severity, demographic data, and side effects were recorded. Results: For the second SSRI trial, 31.8% of the subjects were rated as much improved on the CGI-I scale and determined to be responders, with 68.2% of the subjects demonstrating activation side effects. 90% of subjects demonstrated activation side effects when data from both SSRI trials were combined. There were no statistically significant associations between outcome of the second SSRI trial and clinical/demographic variables. Conclusions: A second trial of an SSRI after an initial SSRI treatment failure was often unsuccessful in children and adolescents with PDDs. Activation side effects were common. Because alternative treatments in this population are limited, a second trial of an SSRI may still be considered. The study was limited by its retrospective design and by its small sample size. C1 [Henry, Charles A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Shervin, David; Neumeyer, Ann; Choueiri, Roula; Bauman, Margaret] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Steingard, Ronald] Univ Massachusetts, Dept Psychiat, Worcester, MA 01605 USA. [Spybrook, Jessaca] Western Michigan Univ, Evaluat Ctr, Kalamazoo, MI 49008 USA. RP Henry, CA (reprint author), 1 Brookline Pl,Suite 426, Brookline, MA 02445 USA. EM charles_henry@hms.harvard.edu NR 43 TC 6 Z9 6 U1 2 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD APR PY 2009 VL 19 IS 2 BP 111 EP 117 DI 10.1089/cap.2008.037 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 432LZ UT WOS:000265136900002 PM 19364289 ER PT J AU Burnett-Bowie, SAM Saag, K Sebba, A de Papp, AE Chen, E Rosenberg, E Greenspan, SL AF Burnett-Bowie, Sherri-Ann M. Saag, Kenneth Sebba, Anthony de Papp, Anne E. Chen, Erluo Rosenberg, Elizabeth Greenspan, Susan L. TI Prediction of Changes in Bone Mineral Density in Postmenopausal Women Treated with Once-Weekly Bisphosphonates SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VERTEBRAL FRACTURE RISK; HORMONE REPLACEMENT THERAPY; RANDOMIZED CLINICAL-TRIAL; LONG-TERM RESPONSE; RISEDRONATE 35 MG; BIOCHEMICAL MARKERS; ELDERLY-WOMEN; ALENDRONATE THERAPY; NONVERTEBRAL FRACTURES; ANTIRESORPTIVE AGENTS AB Background: In clinical practice, bone mineral density (BMD) determined by dual-energy x-ray absorptiometry is used to monitor response to osteoporosis therapy. However, 1 to 2 yr are usually required to assess patients' BMD responses. The possibility of earlier indicators of a response or nonresponse to treatment, such as changes in bone turnover markers (BTMs), is of interest to physicians and patients. Methods: In this post hoc analysis of women treated with once-weekly bisphosphonates, we examined the association of tertile percentage change from baseline in BTMs at 3 or 6 months and association of several baseline clinical characteristics with 24-month percentage change from baseline in BMD and with percentage of patients showing BMD nonresponse ( defined as BMD loss at two or more of four sites) at 24 months. Multivariable analysis was performed to determine which factors were independently associated with BMD nonresponse. Results: Patients in the tertile with the greatest decrease in each of the BTMs had the greatest mean increase in BMD and the lowest percentage of BMD nonresponders at 24 months. Several characteristics were independently associated with BMD nonresponse, including smaller 3-month reductions from baseline in serum C-terminal telopeptide of type 1 collagen, bone-specific alkaline phosphatase, and N-terminal propeptide of type 1 procollagen; younger age of menopause; a family history of osteoporosis; and higher baseline trochanteric BMD. Baseline BTMs were not predictive of 24-month BMD response to therapy. The strongest associations were for changes in BTMs with treatment. Conclusion: In groups of patients, short-term changes in markers of bone turnover appear to be predictors of longer term BMD response and nonresponse to bisphosphonate therapy. (J Clin Endocrinol Metab 94: 1097-1103, 2009) C1 [Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Saag, Kenneth] Univ Alabama, Birmingham, AL 35294 USA. [Sebba, Anthony] Arthrit Associates, Palm Harbor, FL 34684 USA. [de Papp, Anne E.; Chen, Erluo; Rosenberg, Elizabeth] Merck & Co Inc, N Wales, PA 19454 USA. [Greenspan, Susan L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Burnett-Bowie, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM sburnett-bowie@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU Merck Co., Inc. [NCT00092014] FX Disclosure Summary: S. M. B. and S. L. G. have nothing to declare. K. S. has received research grants, honoraria, and consulting fees from Merck & Co., Inc. A. S. has received honoraria and consulting fees from Merck & Co., Inc. A.E.d.P.,E.C., and E. R. are employees of Merck & Co., Inc, the sponsor of the study. NR 41 TC 7 Z9 8 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2009 VL 94 IS 4 BP 1097 EP 1103 DI 10.1210/jc.2008-1122 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432PB UT WOS:000265145100011 PM 19141590 ER PT J AU Lee, CG Carr, MC Murdoch, SJ Mitchell, E Woods, NF Wener, MH Chandler, WL Boyko, EJ Brunzell, JD AF Lee, Christine G. Carr, Molly C. Murdoch, Susan J. Mitchell, Ellen Woods, Nancy F. Wener, Mark H. Chandler, Wayne L. Boyko, Edward J. Brunzell, John D. TI Adipokines, Inflammation, and Visceral Adiposity across the Menopausal Transition: A Prospective Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; C-REACTIVE PROTEIN; SERUM-AMYLOID-A; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; FAT DISTRIBUTION; PLASMA-LEVELS; RISK-FACTORS AB Context: Postmenopausal women have greater visceral adiposity compared with premenopausal women. Adipokines are associated with increased adiposity, insulin resistance, and atherosclerosis. Objective: The objective of the study was to assess changes in adipokines and inflammatory markers through the menopausal transition and correlate them with changes in visceral adiposity. Design and Setting: This was a prospective cohort study of women through the menopausal transition conducted at the University of Washington. Participants: Sixty-nine healthy women were followed up longitudinally from premenopausal (aged 45-55 yr) to postmenopausal status (aged 49-60 yr). Outcome: On premenopausal and postmenopausal visits, fasting blood was drawn for adiponectin, leptin, serum amyloid A (SAA), C-reactive protein (CRP), monocyte-chemotactic protein-1, tissue plasminogen activator antigen (tPA), IL-6, and TNF-alpha. Body composition measures were assessed by body mass index, whole-body dual x-ray absorptiometry scan, and computed tomography scan of the abdomen at the lumbar 4-5 level. Results: Women had a statistically significant increase in SAA, tPA, monocyte-chemotactic protein-1, and adiponectin between the two measurement occasions (P = 0.04, P = 0.02, P = 0.001, and P < 0.001, respectively). The increase in intraabdominal fat was correlated positively with the change in SAA (r = 0.31, P = 0.02), CRP (r = 0.56, P < 0.001), tPA (r = 0.40, P = 0.002), and leptin (r = 0.41, P = 0.002) and negatively correlated with the change in adiponectin (r = -0.37, P = 0.005). After adjustment for change in sc abdominal fat, the correlation between change in CRP, tPA, leptin, and adiponectin remained significantly associated with change in intraabdominal fat. Conclusions: Women going through the menopausal transition have deleterious changes in inflammatory markers and adipokines that correlate with increased visceral adiposity. (J Clin Endocrinol Metab 94: 1104 - 1110, 2009) C1 [Lee, Christine G.; Carr, Molly C.; Murdoch, Susan J.; Brunzell, John D.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Med Ctr, Seattle, WA 98195 USA. [Mitchell, Ellen; Woods, Nancy F.] Univ Washington, Dept Family & Child Nursing, Seattle, WA 98195 USA. [Wener, Mark H.; Chandler, Wayne L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Lee, CG (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Med Ctr, 1959 NE Pacific St,Box 356426, Seattle, WA 98195 USA. FU National Institutes of Health [HL30086, HL64322, NR04141, RR16067]; Bristol Myers Squibb Foundation; University of Washington Clinical Nutrition Research Unit [DK35816]; University of Washington General Clinical Research Center [M01-RR-00037]; University of Washington Diabetes Endocrinology Research Center; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK-17047] FX The authors thank Linda Floyd for her assistance with participant recruitment and management and Steve Hashimoto and Alegria Aquino-Albers for their technical expertise. We are indebted to the participants for their dedication and contribution to this study. Laboratory assays performed at the University of Washington were processed by Dr. Wayne Chandler and Dr. Mark Wener (Department of Laboratory Medicine) and the Clinical Nutrition Research Unit Core Laboratory. Adiponectin assays were performed in the laboratories of Dr. Peter J. Havel, D. V. M., Ph. D. (University of California, Davis, Department of Nutrition).; Address all correspondence and requests for reprints to: Christine G. Lee, M. D., Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, 1959 NE Pacific Street, Box 356426, Seattle, Washington 98195-4626.; This work was supported by National Institutes of Health Grants HL30086, HL64322, and NR04141, and K23 Grant RR16067 ( to M. C. C.) and a grant from the Bristol Myers Squibb Foundation. These studies were performed with the support of the University of Washington Clinical Nutrition Research Unit (DK35816), the University of Washington General Clinical Research Center (M01-RR-00037), and the University of Washington Diabetes Endocrinology Research Center, which is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases Grant P30 DK-17047.; Present address for M. C. C.: Wyeth Research, Collegeville, Pennsylvania.; Disclosure Summary: C. G. L., S.J.M., E. M., N.F.W., M. H. W., W. L. C., E.J.B., and J.D.B. have nothing to declare. M. C. C. worked on this study while employed at the University of Washington Medical Center. NR 36 TC 89 Z9 92 U1 2 U2 5 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 APR PY 2009 VL 94 IS 4 BP 1104 EP 1110 DI 10.1210/jc.2008-0701 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432PB UT WOS:000265145100012 PM 19126626 ER PT J AU Mulligan, K Khatami, H Schwarz, JM Sakkas, GK DePaoli, AM Tai, VW Wen, MJ Lee, GA Grunfeld, C Schambelan, M AF Mulligan, Kathleen Khatami, Hootan Schwarz, Jean-Marc Sakkas, Giorgos K. DePaoli, Alex M. Tai, Viva W. Wen, Michael J. Lee, Grace A. Grunfeld, Carl Schambelan, Morris TI The Effects of Recombinant Human Leptin on Visceral Fat, Dyslipidemia, and Insulin Resistance in Patients with Human Immunodeficiency Virus-Associated Lipoatrophy and Hypoleptinemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIV-INFECTED PATIENTS; HUMAN GROWTH-HORMONE; ISOTOPOMER DISTRIBUTION ANALYSIS; ADIPOSE-TISSUE; DIABETES-MELLITUS; CONTROLLED-TRIAL; GENERALIZED LIPODYSTROPHY; CONGENITAL LIPODYSTROPHY; ANTIRETROVIRAL THERAPY; REPLACEMENT THERAPY AB Context: Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities. Objective: The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and hypoleptinemia. Design: This was a 6-month, open-label, proof-of-principle pilot study. Setting: Metabolicward studies were performed before and 3 and 6 months after leptin treatment. Participants: Participants included eight HIV-infected men with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum leptin less than 3 ng/ml. Intervention: Recombinant human leptin was given by sc injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods). Outcome Measures: Measuresincluded fat distribution by magnetic resonance imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity by euglycemic hyperinsulinemic clamp; endogenous glucose production, gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope tracer studies; oral glucose tolerance testing; liver fat by proton magnetic resonance spectroscopy; and safety. Results: Visceral fat decreased by 32%(P = 0.001) with no changes in peripheral fat. There were significant decreases in fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002), and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin decreased. Endogenous glucose production decreased during fasting and hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity. Leptin was well tolerated but decreased lean mass. Conclusions: Leptin treatment was associated with marked improvement in dyslipidemia. Hepatic insulin sensitivity improved and lipolysis decreased. Visceral fat decreased with no exacerbation of peripheral lipoatrophy. Results from this pilot study suggest that leptin warrants further study in patients with HIV-associated lipoatrophy. (J Clin Endocrinol Metab 94: 1137 - 1144, 2009) C1 [Mulligan, Kathleen; Khatami, Hootan; Schwarz, Jean-Marc; Sakkas, Giorgos K.; Tai, Viva W.; Wen, Michael J.; Schambelan, Morris] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Mulligan, Kathleen; Khatami, Hootan; Schwarz, Jean-Marc; Sakkas, Giorgos K.; Tai, Viva W.; Wen, Michael J.; Lee, Grace A.; Grunfeld, Carl; Schambelan, Morris] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Schwarz, Jean-Marc] Touro Univ, Dept Basic Sci, Vallejo, CA 94592 USA. [DePaoli, Alex M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Lee, Grace A.; Grunfeld, Carl] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Mulligan, K (reprint author), San Francisco Gen Hosp, Bldg 30,Room 3501K,1001 Potrero Ave, San Francisco, CA 94110 USA. EM kathleen.mulligan@ucsf.edu FU National Institutes of Health [DK63640, DK54615, DK66999, RR-00083]; University of California Universitywide AIDS Research Program [CF02-SF-302]; Amgen, Inc.; Amylin Pharmaceuticals, Inc. FX Disclosure Summary: H. K., J.-M. S., G. K. S., V. W. T., M.J.W., G. A. L., and C. G. have nothing to declare. K. M. and M. S. received consulting fees from Amgen Inc. and Amylin, Inc. M. S. received the drug used in this National Institutes of Health-funded study and a small research grant from Amgen; the latter was transferred to Amylin. A. M. D. was employed at Amgen Inc. at the time of this research. NR 47 TC 63 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2009 VL 94 IS 4 BP 1137 EP 1144 DI 10.1210/jc.2008-1588 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432PB UT WOS:000265145100017 PM 19174500 ER PT J AU White, HK Petrie, CD Landschulz, W MacLean, D Taylor, A Lyles, K Wei, JY Hoffman, AR Salvatori, R Ettinger, MP Morey, MC Blackman, MR Merriam, GR AF White, Heidi K. Petrie, Charles D. Landschulz, William MacLean, David Taylor, Ann Lyles, Kenneth Wei, Jeanne Y. Hoffman, Andrew R. Salvatori, Roberto Ettinger, Mark P. Morey, Miriam C. Blackman, Marc R. Merriam, George R. CA Capromorelin Study Grp TI Effects of an Oral Growth Hormone Secretagogue in Older Adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; BODY-COMPOSITION; FACTOR-I; INSULIN SENSITIVITY; ELDERLY-PEOPLE; MEN; DISABILITY; SECRETION; GHRELIN AB lContext: GH secretion declines with age, possibly contributing to reduced muscle mass, strength, and function. GH secretagogues (GHS) may increase muscle mass and physical performance. Objectives/Design: We conducted a randomized, double-masked, placebo-controlled, multicenter study to investigate the hormonal, body composition, and physical performance effects and the safety of the orally active GHS capromorelin in older adults with mild functional limitation. Intervention/Participants: A total of 395 men and women aged 65-84 yr were randomized for an intended 2 yr of treatment to four dosing groups (10 mg three times/week, 3 mg twice a day, 10 mg each night, and 10 mg twice a day) or placebo. Although the study was terminated early according to predetermined treatment effect criteria, 315 subjects completed 6 months of treatment, and 284 completed 12 months. Results: A sustained dose-related rise in IGF-I concentrations occurred in all active treatment groups. Each capromorelin dose prompted a rise in peak nocturnal GH, which was greatest with the least frequent dosing. At 6 months, body weight increased 1.4 kg in subjects receiving capromorelin and decreased 0.2 kg in those receiving placebo (P = 0.006). Lean body mass increased 1.4 vs. 0.3 kg (P = 0.001), and tandem walk improved by 0.9 sec (P = 0.02) in the pooled treatment vs. placebo groups. By 12 months, stair climb also improved (P = 0.04). Adverse events included fatigue, insomnia, and small increases in fasting glucose, glycosylated hemoglobin, and indices of insulin resistance. Conclusions: In healthy older adults at risk for functional decline, administration of the oral GHS capromorelin may improve body composition and physical function. (J Clin Endocrinol Metab 94: 1198-1206, 2009) C1 [White, Heidi K.; Lyles, Kenneth; Morey, Miriam C.] Duke Univ, Sch Med, Durham, NC 27710 USA. [White, Heidi K.; Lyles, Kenneth; Morey, Miriam C.] Durham Vet Affairs VA Med Ctr, GRECC, Durham, NC 27710 USA. [Petrie, Charles D.] Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. [Landschulz, William] Eli Lilly & Co, Endocrine Clin Res, Indianapolis, IN 46285 USA. [MacLean, David] Brown Univ, Sch Med, Providence, RI 02912 USA. [Taylor, Ann] Novartis, Cambridge, MA 02139 USA. [Wei, Jeanne Y.] Cent Arkansas Vet Affairs VA Healthcare Syst, GRECC, Little Rock, AR 72205 USA. [Wei, Jeanne Y.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Hoffman, Andrew R.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Hoffman, Andrew R.] Stanford Univ, Palo Alto, CA 94304 USA. [Salvatori, Roberto] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Ettinger, Mark P.] Radiant Res & Reg Osteoporosis Ctr, Stuart, FL 34996 USA. [Blackman, Marc R.] Washington DC VA Med Ctr, Washington, DC 20422 USA. [Merriam, George R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. [Merriam, George R.] Univ Washington, Sch Med, Seattle, WA 98493 USA. [Merriam, George R.] Univ Washington, Sch Med, Tacoma, WA 98493 USA. [Merriam, George R.] VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. RP White, HK (reprint author), Duke Univ, Sch Med, Box 3003, Durham, NC 27710 USA. EM White031@mc.duke.edu FU Pfizer Global Research Development; Veterans Health Administration FX We thank Maria Fiatarone-Singh, Ph.D., who was instrumental in the planning of study entry criteria and physical performance endpoints developed in phase IIa studies that preceded this reported investigation. Other members of the Capromorelin Study Group were: Drs. William Hall, Robert Lang, Marco Pahor, William Pettit, Sherwyn L. Schwartz, Stuart Weiss, and Barbara Troupin. Clinical trial training support was provided by Kolette Fly, Al Kraska, and Nikos Kolivodiakos from Pfizer Global Research& Development. Statistical analysis and programming support was provided by Robert D. Chew, Ph.D., Chitra Lele, Shirsendu Sarkar, Urszula Masiukiewicz, and Andrea Flower from Pfizer Global Research & Development. The Duke Clinical Research Institute provided supervision and monitoring of five of the 12 research sites. We thank Colleen Carney, Ann Hill, Monica Kletke, Sheila Cole, and members of the Lake Worth, Florida, Radiant Research site for excellent support in the conduct of this protocol. We also gratefully acknowledge the contributions of the late Elizabeth C. Clipp, Ph.D., of Duke University.; Address all correspondence and requests for reprints to: Heidi K. White, M. D., M. H. S., Duke University School of Medicine, Box 3003, Durham, North Carolina 27710. E-mail: White031@mc.duke.edu.; This study was supported by Pfizer Global Research Development, which discovered and developed capromorelin, and by the Veterans Health Administration.; Trial Registration: Clinical Trials.gov Identifier: NCT00527046. Disclosure Summary: C. D. P. is employed by Pfizer and holds stock in the company. W. L., D. M., and A. T. were employed by Pfizer during this research study. H. K. W., K. L., J.Y.W., A. R. H., R. S., M. P. E., M. C. M., M. R. B., and G. R. M. received grant support for this research study from Pfizer, Inc. (October 1, 1999 to December 31, 2001). NR 49 TC 56 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2009 VL 94 IS 4 BP 1198 EP 1206 DI 10.1210/jc.2008-0632 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432PB UT WOS:000265145100025 PM 19174493 ER PT J AU Lawson, EA Misra, M Meenaghan, E Rosenblum, L Donoho, DA Herzog, D Klibanski, A Miller, KK AF Lawson, E. A. Misra, M. Meenaghan, E. Rosenblum, L. Donoho, D. A. Herzog, D. Klibanski, A. Miller, K. K. TI Adrenal Glucocorticoid and Androgen Precursor Dissociation in Anorexia Nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ORAL-CONTRACEPTIVES; BINDING GLOBULIN; RANDOMIZED TRIAL; BONE METABOLISM; NORMAL-WEIGHT; HUMAN-PLASMA; YOUNG-WOMEN; DEHYDROEPIANDROSTERONE; SECRETION; CORTISOL AB Context: Anorexia nervosa is characterized by hypogonadism and relative hypercortisolemia. We have demonstrated that free testosterone levels are low in women with anorexia nervosa, with the lowest levels in those receiving oral contraceptives (OCPs), and that dehydroepiandrosterone (DHEA) sulfate is reduced only in those receiving OCPs. Objective: The aim of the study was to determine whether adrenal steroidogenesis dysregulation contributes to decreased androgen levels in anorexia nervosa. Design and Setting: We conducted a cross-sectional study in a General Clinical Research Center. Study Participants: We studied 20 women with anorexia nervosa [10 women with anorexia nervosa receiving OCPs (AN+E) and 10 not receiving OCPs (AN+E)] and 20 healthy controls [10 healthy controls receiving OCPs (HC+E) and 10 not receiving OCPs (HC-E)]. Main Outcome Measures: We measured DHEA and cortisol levels in response to 250-mu g cosyntropin stimulation after 1-mg overnight dexamethasone suppression. Results: Mean basal and stimulated, peak stimulated, and area under the curve (AUC) cortisol levels were higher in AN-E than HC-E, but mean basal and stimulated, peak and AUCDHEA were comparable. Mean AUC and peak cortisol were higher and DHEA AUC was lower in AN+E than AN-E. However, after controlling for cortisol binding globulin levels, peak and AUC cortisol were comparable between AN+E and AN-E. After controlling for albumin levels, AUC DHEA was comparable between AN+E and AN-E. Conclusions: Adrenal glucocorticoid and androgen precursor secretion are dissociated in anorexia nervosa, with relative hypercortisolemia and a preservation of DHEA secretion. Reduced DHEA response to cosyntropin in women receiving OCPs is attributable to decreased albumin levels. In the setting of relative hypercortisolemia, reduced adrenal androgen precursor secretion is not a mechanism underlying low testosterone levels in anorexia nervosa. (J Clin Endocrinol Metab 94: 1367-1371, 2009) C1 [Lawson, E. A.; Misra, M.; Rosenblum, L.; Donoho, D. A.; Klibanski, A.; Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lawson, E. A.; Misra, M.; Meenaghan, E.; Rosenblum, L.; Donoho, D. A.; Klibanski, A.; Miller, K. K.] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. [Herzog, D.] Massachusetts Gen Hosp, Dept Psychiat, Harris Ctr, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU National Institutes of Health [NIH-R01-DK52625, MO1 RR01066] FX This work was supported by National Institutes of Health Grants NIH-R01-DK52625 and MO1 RR01066. NR 22 TC 23 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2009 VL 94 IS 4 BP 1367 EP 1371 DI 10.1210/jc.2008-2558 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432PB UT WOS:000265145100050 PM 19158192 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Hospitalization for Inflammatory Bowel Disease in the United States Between 1970 and 2004 SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE epidemiology; incidence; mortality; prevalence; time trends ID CROHNS-DISEASE; ULCERATIVE-COLITIS; PREVALENCE; TRENDS; RATES; EPIDEMIOLOGY; SURGERY; COUNTY AB Aim: The aim of the study was to use hospitalization data for the analysis of inflammatory bowel disease time trends in the United States. Methods: US hospital utilization data were available for individual years from 1970 to 2004 through the National Hospital Discharge Survey. Age-specific rates of hospitalization were Calculated for consecutive 5-year periods. Results: An increase in the rates of hospitalization for Crohn's disease was most pronounced in the age group 65+ followed by the age group 45 to 64. By contradistinction, the rates in the youngest age group 0 to 44 stayed largely unchanged. In ulcerative colitis, a significant increase in hospitalization rates was limited to the oldest age group, whereas the rates in the middle and young age group remained unchanged. Conclusions: Extrapolation of the current trends suggests that in the future the hospitalization for inflammatory bowel disease may start to level off. This may occur earlier and be more pronounced in younger age groups and patients with ulcerative colitis than Crohn's disease. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-G1,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 16 TC 16 Z9 16 U1 0 U2 1 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 APR PY 2009 VL 43 IS 4 BP 297 EP 300 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439MM UT WOS:000265631200002 PM 18936713 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Analysis of Recent Papers in Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] Univ Nevada, Div Cardiol, Div Gen Internal Med, Sch Med, Reno, NV 89557 USA. [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC 29403 USA. [Basile, Jan N.] Med Univ S Carolina, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD APR PY 2009 VL 11 IS 4 BP 238 EP 240 DI 10.1111/j.1751-7176.2009.00105.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 432PM UT WOS:000265146200010 PM 19368588 ER PT J AU Lewis, DA Sweet, RA AF Lewis, David A. Sweet, Robert A. TI Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID DENDRITIC SPINE DENSITY; MISMATCH NEGATIVITY GENERATION; DORSOLATERAL PREFRONTAL CORTEX; PRIMARY AUDITORY-CORTEX; CORTICAL PYRAMIDAL NEURONS; MESSENGER-RNA EXPRESSION; O-METHYLTRANSFERASE COMT; NMDA RECEPTOR SUBUNITS; WORKING-MEMORY; GENE-EXPRESSION AB Schizophrenia is a severe disorder that disrupts the function of multiple brain systems, resulting in impaired social and occupational functioning. The etiology and pathogenesis of schizophrenia appear to involve the interplay of a potentially large number of genetic liabilities and adverse environmental events that disrupt brain developmental pathways. In this Review, we discuss a strategy for determining how particular common and core clinical features of the illness are associated with pathophysiology in certain circuits of the cerebral cortex. The identification of molecular alterations in these circuits is providing critical insights for the rational development of new therapeutic interventions. C1 [Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. RP Lewis, DA (reprint author), Univ Pittsburgh, Dept Psychiat, W1651 Biomed Sci Tower,3811 Ohara St, Pittsburgh, PA 15213 USA. EM lewisda@upmc.edu RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU National Institute of Mental Health [MH043784, MH045156, MH084053, MH071533] FX Cited work conducted by the authors was supported by NIH grants MH043784, MH045156, MH084053, and MH071533 from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the NIH. The authors thank Mary Brady for preparation of the figures, Lindsay Karr for preparation of the manuscript, and Guillermo Gonzalez-Burgos and David Volk for helpful comments. NR 125 TC 115 Z9 117 U1 4 U2 15 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 APR PY 2009 VL 119 IS 4 BP 706 EP 716 DI 10.1172/JCI37335 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 428EF UT WOS:000264830100006 PM 19339762 ER PT J AU Mercher, T Raffel, GD Moore, SA Cornejo, MG Baudry-Bluteau, D Cagnard, N Jesneck, JL Pikman, Y Cullen, D Williams, IR Akashi, K Shigematsu, H Bourquin, JP Giovannini, M Vainchenker, W Levine, RL Lee, BH Bernard, OA Gilliland, DG AF Mercher, Thomas Raffel, Glen D. Moore, Sandra A. Cornejo, Melanie G. Baudry-Bluteau, Dominique Cagnard, Nicolas Jesneck, Jonathan L. Pikman, Yana Cullen, Dana Williams, Ifor R. Akashi, Koichi Shigematsu, Hirokazu Bourquin, Jean-Pierre Giovannini, Marco Vainchenker, William Levine, Ross L. Lee, Benjamin H. Bernard, Olivier A. Gilliland, D. Gary TI The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE MEGAKARYOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PLATELET PRODUCTION; SIGNALING PATHWAY; GATA3 EXPRESSION; NOTCH; DIFFERENTIATION; THROMBOPOIETIN; MUTATIONS; BIOLOGY AB Acute megakaryoblastic leukemia (AMKL) is a font of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two-megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin K J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus oncogene (MPL) efficiently induced a short-latency AMKL that recapitulated all the features of human AMKL, including megakaryoblast hyperproliferation and maturation block, thrombocytopenia, organomegaly, and extensive fibrosis. Our results establish that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL. C1 [Bernard, Olivier A.] Tour Pasteur Hop Necker, INSERM, EM10210, F-75743 Paris 15, France. [Mercher, Thomas; Raffel, Glen D.; Moore, Sandra A.; Cornejo, Melanie G.; Pikman, Yana; Cullen, Dana; Levine, Ross L.; Lee, Benjamin H.; Gilliland, D. Gary] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Hematol,Med Sch, Boston, MA 02115 USA. [Jesneck, Jonathan L.; Akashi, Koichi; Shigematsu, Hirokazu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Ifor R.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Bourquin, Jean-Pierre] Univ Zurich, Childrens Hosp, Dept Oncol, Zurich, Switzerland. [Giovannini, Marco] Fdn Jean Dausset CEPH, INSERM, U674, Paris, France. [Vainchenker, William] Univ Paris 11, Inst Gustave Roussy, INSERM, U790, Villejuif, France. [Gilliland, D. Gary] Howard Hughes Med Inst, Cambridge, MA USA. RP Bernard, OA (reprint author), Tour Pasteur Hop Necker, INSERM, EM10210, 149 Rue Sevres, F-75743 Paris 15, France. EM olivier.bernard@rics.bwh.harvard.edu; ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011; Mercher, Thomas/J-2446-2014; Bernard, Olivier/E-5721-2016; OI Williams, Ifor/0000-0002-8810-2911; Mercher, Thomas/0000-0003-1552-087X; Bluteau, Dominique/0000-0002-6530-2363; Pikman, Yana/0000-0002-5336-0216 FU NIH [DK50654, CA66996, U01 CA105423]; Leukemia and Lymphoma Society; INSERM and Ligue Nationale Contre le Cancer - Equipe Labellisee; Howard Hughes Medical Institute; Leukemia and Lymphoma Society [3431-06] FX We are very grateful to Evelyne Lauret and Olivier Albagli for the generous gift of the dnRBPJ construct. We also thank Catherine Lavau, Richard Monni, Genevieve Courtois, Sebastien Malinge., Christine Ragu, Kelly Morgan, Guido Posern, Gerlinde Wernig, and Michael G. Kharas for helpful discussions; Martine Mauchauffe, Michiko Kawakira, Sid Puram, and Rachel Okabe for technical Support; and Jeffery L. Kutok and the Brigham and Women's Hospital Pathology Core Facility for histopathology analysis. This work was supported in part by NIH grants DK50654, CA66996, and U01 CA105423; The Leukemia and Lymphoma Society (to D.G. Gilliland); and INSERM and Ligue Nationale Contre le Cancer - Equipe Labellisee (to O.A. Bernard). D.G. Gilliland is a Doris Duke Foundation Distinguished Clinical Scientist and an investigator of the Howard Hughes Medical Institute. T. Mercher is the recipient of a Special Fellow Grant from The Leukemia and Lymphoma Society (3431-06). NR 55 TC 52 Z9 52 U1 0 U2 5 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 APR PY 2009 VL 119 IS 4 BP 852 EP 864 DI 10.1172/JCI35901 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 428EF UT WOS:000264830100023 PM 19287095 ER PT J AU Edmondson, AC Brown, RJ Kathiresan, S Cupples, LA Demissie, S Manning, AK Jensen, MK Rimm, EB Wang, J Rodrigues, A Bamba, V Khetarpal, SA Wolfe, ML DerOhannessian, S Li, MY Reilly, MP Aberle, J Evans, D Hegele, RA Rader, DJ AF Edmondson, Andrew C. Brown, Robert J. Kathiresan, Sekar Cupples, L. Adrienne Demissie, Serkalem Manning, Alisa Knodle Jensen, Majken K. Rimm, Eric B. Wang, Jian Rodrigues, Amrith Bamba, Vaneeta Khetarpal, Sumeet A. Wolfe, Megan L. DerOhannessian, Stephanie Li, Mingyao Reilly, Muredach P. Aberle, Jens Evans, David Hegele, Robert A. Rader, Daniel J. TI Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; CASSETTE TRANSPORTER 1; TANGIER-DISEASE; MYOCARDIAL-INFARCTION; GENETIC-VARIANTS; ARTERY-DISEASE; PLASMA-LEVELS; LIPID-LEVELS; ASSOCIATION AB Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C. C1 [Edmondson, Andrew C.; Brown, Robert J.; Rodrigues, Amrith; Bamba, Vaneeta; Khetarpal, Sumeet A.; Wolfe, Megan L.; DerOhannessian, Stephanie; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA USA. [Kathiresan, Sekar] Broad Inst Ctr Genotyping & Anal Harvard, Cambridge, MA USA. [Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA. [Kathiresan, Sekar; Rimm, Eric B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Cupples, L. Adrienne; Demissie, Serkalem; Manning, Alisa Knodle] Boston Univ, Boston, MA 02215 USA. [Cupples, L. Adrienne; Demissie, Serkalem; Manning, Alisa Knodle] Framingham Heart Dis Epidemiol Study, Boston, MA USA. [Jensen, Majken K.; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, Jian; Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Wang, Jian; Hegele, Robert A.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Aberle, Jens; Evans, David] Univ Klinikum Hamburg Eppendorf, Endokrinol & Stoffwechsel Med Klin 3, Zentrum Innere Med, Hamburg, Germany. RP Rader, DJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, 654 BRB2-3 Labs,421 Curie Blvd, Philadelphia, PA 19104 USA. EM rader@mail.med.upenn.edu RI Edmondson, Andrew/D-1110-2009; Hegele, Robert/G-3301-2011; OI Cupples, L. Adrienne/0000-0003-0273-7965 FU National Center for Research Resources [U54 RR020278]; National Heart, Lung and Blood Institute [N01-HC-25195]; Heart and Stroke Foundation of Canada; Doris Duke Charitable Foundation; Ontario Genomics Institute; Department of Medicine at Boston University School of Medicine and Boston Medical Center FX We would like to acknowledge expert technical support from the London Regional Genornics Centre. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources. This work was supported by an National Heart, Lung and Blood Institute Ruth L. Kirschstein National Research Service Award for Individual Predoctoral MD/PhD Fellows (F30, to A.C. Edmondson), a Research Fellowship of the Heart and Stroke Foundation of Canada (to R.J. Brown), a Doris Duke Charitable Foundation Distinguished Clinical Scientist Award (to DJ. Rader), and support front Genome Canada through the Ontario Genomics Institute (to R.A. Hegele). The FHS of the National Heart, Lung and Blood Institute of the NIH and Boston University School of Medicine is supported by the National Heart, Lung and Blood Institute's FHS (contract no. N01-HC-25195). A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. We would also like to thank the individuals and families From all of these studies for their participation as well as the referring physicians both in and outside the University of Pennsylvania Health System, and in particular, John Hoekstra and James Under-berg for their help with recruitment of the HHDL study. NR 58 TC 112 Z9 117 U1 0 U2 4 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 APR PY 2009 VL 119 IS 4 BP 1042 EP 1050 DI 10.1172/JCI37176 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 428EF UT WOS:000264830100040 PM 19287092 ER PT J AU Insull, W Basile, JN Vo, AN Jiang, P Thakkar, R Padley, RJ AF Insull, William, Jr. Basile, Jan N. Vo, Anthony N. Jiang, Ping Thakkar, Roopal Padley, Robert J. TI Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: The SUPREME Study SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Dyslipidemia; High-density lipoprotein; Niacin; PROBE; Statin ID CORONARY-HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; PLASMA LIPOPROTEIN(A); HDL CHOLESTEROL; DOUBLE-BLIND; PREVENTION; EVENTS; FRAMINGHAM; PROJECT; TRIALS AB BACKGROUND: Aggressive treatment of low-density lipoprotein cholesterol (LDL-C) fails to prevent most cardiovascular (CV) events. Concurrent treatment of LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) should be considered in patients with dyslipidemia. OBJECTIVE: The efficacy and safety of a proprietary niacin extended-release and simvastatin (NER/S) combination were compared to atorvastatin monotherapy in a Multicenter, Prospective, Randomized (3:2), Open-label. Blinded Endpoint (PROBE) study. METHODS: Following >= 4 weeks without lipid-modifying therapies, 193 patients with dyslipidemia were treated with NER/S (n = 114 1000/40 mg/day, weeks 1 to 4 2000/40 mg/day weeks 5 to 12) or atorvastatin (n = 79: 40 mg/day, weeks 1 to 12). RESULTS: Compared to atorvastatin, NER/S had a larger beneficial effect oil HDL-C (primary end point: 30.1 +/- 2.3% and 9.4 +/- 2.6%, respectively P <.001), TG (P =.02) and lipoprotein(a) (Lp[a]: P <.001), and similar effects on LDL-C and non-HDL-C. Two-thirds of patients treated with NER/S concurrently attained LDL-C (CV risk-adjusted goals), HDL-C (>= 40 mg/dL), and TG (< 150 mg/dL) targets, compared to one-third of patients treated with atorvastatin (P <.001). Flushing was the most common treatment-emergent adverse event (TEAE) (67.5% NER/S and 10.1% atorvastatin P <.001). Seventy-five percent Of flushing episodes were mild to moderate. More patients treated with NER/S discontinued due to TEAEs (21.1% and 3.8%; P <.001); the most common TEAE was flushing. CONCLUSION: Compared to atorvastatin, NER/S provided Superior improvements in HDL-C, TG. and Lp(a) and comparable improvements in non-HDL-C and LDL-C. Treatment with NER/S should be considered for patients with dyslipidemia requiring comprehensive lipid control. (c) 2009 National Lipid Association. All rights reserved. C1 [Insull, William, Jr.] Baylor Coll Med, Methodist Hosp, Lipid Res Clin, Houston, TX 77030 USA. [Basile, Jan N.] Ralph H Johnson Vet Aftairs Med Ctr, Charleston, SC USA. [Vo, Anthony N.] Long Beach Vet Affairs Med Ctr, Long Beach, CA USA. [Jiang, Ping; Thakkar, Roopal; Padley, Robert J.] Abbott, Abbott Pk, IL USA. RP Insull, W (reprint author), Baylor Coll Med, Methodist Hosp, Lipid Res Clin, 1790 Dryden Rd,Room 8-08, Houston, TX 77030 USA. EM winsull@bcm.edu FU Abbott; Abbott Laboratories [NCT00465088] FX Abbott is the financial sponsor of the SUPREME clinical trial. Abbott also provided financial support for a medical writer who provided editorial assistance during development of this work. Dr. Insull is a consultant for Abbott Laboratories (previously Kos Pharmaceuticals). Clinical Trials Identifier: NCT00465088. NR 30 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD APR PY 2009 VL 3 IS 2 BP 109 EP 118 DI 10.1016/j.jacl.2009.02.009 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 464VU UT WOS:000267537400008 PM 21291800 ER PT J AU Ellis, MW Griffith, ME Jorgensen, JH Hospenthal, DR Mende, K Patterson, JE AF Ellis, Michael W. Griffith, Matthew E. Jorgensen, James H. Hospenthal, Duane R. Mende, Katrin Patterson, Jan E. TI Presence and Molecular Epidemiology of Virulence Factors in Methicillin-Resistant Staphylococcus aureus Strains Colonizing and Infecting Soldiers SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; FIELD GEL-ELECTROPHORESIS; CATABOLIC MOBILE ELEMENT; NECROTIZING PNEUMONIA; NASAL CARRIAGE; UNITED-STATES; COLONIZATION; EMERGENCE; GENES; CLONE AB Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of skin and soft-tissue infections (SSTI). The understanding of the molecular epidemiology and virulence of MRSA continues to expand. From January 2005 to December 2005, we screened soldiers for MRSA nasal colonization, administered a demographic questionnaire, and monitored them prospectively for SSTI. All MRSA isolates underwent molecular analysis, which included pulsed-filed gel electrophoresis (PFGE) and PCR for Panton-Valentine leukocidin (PVL), the arginine catabolic mobile element (ACME), and the staphylococcal cassette chromosome mec (SCCmec). Of the 3,447 soldiers screened, 134 (3.9%) had MRSA colonization. Of the 3,066 (89%) who completed the study, 39 developed culture-confirmed MRSA abscesses. Clone USA300 represented 53% of colonizing isolates but was responsible for 97% of the abscesses (P < 0.001). Unlike colonizing isolates, isolates positive for USA300, PVL, ACME, and type IV SCCmec were significantly associated with MRSA abscess isolates. As determined by multivariate analysis, risk factors for MRSA colonization were a history of SSTI and a history of hospitalization. Although various MRSA strains may colonize soldiers, USA300 is the most virulent when evaluated prospectively, and PVL, ACME, and type IV SCCmec are associated with these abscesses. C1 [Ellis, Michael W.; Griffith, Matthew E.; Hospenthal, Duane R.] Brooke Army Med Ctr, Dept Med Infect Dis, San Antonio, TX USA. [Jorgensen, James H.; Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Infect Dis, San Antonio, TX 78229 USA. [Ellis, Michael W.] Uniformed Serv Univ Hlth Sci, Dept Med Infect Dis, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Patterson, Jan E.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ellis, MW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med Infect Dis, Infect Dis Clin Res Program, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM michael.w.ellis@us.army.mil RI Valle, Ruben/A-7512-2013 NR 46 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2009 VL 47 IS 4 BP 940 EP 945 DI 10.1128/JCM.02352-08 PG 6 WC Microbiology SC Microbiology GA 427RS UT WOS:000264797000011 PM 19213694 ER PT J AU Hochster, H Weller, E Gascoyne, RD Habermann, TM Gordon, LI Ryan, T Zhang, LJ Colocci, N Frankel, S Horning, SJ AF Hochster, Howard Weller, Edie Gascoyne, Randy D. Habermann, Thomas M. Gordon, Leo I. Ryan, Theresa Zhang, Lijun Colocci, Natalia Frankel, Stanley Horning, Sandra J. TI Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study SO JOURNAL OF CLINICAL ONCOLOGY 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 ID NON-HODGKINS-LYMPHOMA; ADVANCED FOLLICULAR LYMPHOMA; LOW-GRADE; SIGNIFICANTLY INCREASES; ADVANCED-STAGE; TRIAL; INTERFERON; THERAPY; CHEMOTHERAPY; 1ST-LINE AB Purpose To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma. Patients and Methods Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m(2) once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point. Results Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 x 10(-1)0 [all patients]) and 64% MR v 33% OBS ( HR = 0.4; P = 9.2 x 10(-8) [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03). Conclusion The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS. C1 [Hochster, Howard] NYU, Inst Canc, Med Ctr, New York, NY 10016 USA. Dana Farber Canc Inst, Ctr Stat, Boston, MA 02115 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Mayo Clin, Rochester, MN USA. Northwestern Univ, Chicago, IL 60611 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Maryland, Baltimore, MD 21201 USA. RP Hochster, H (reprint author), NYU, Inst Canc, Med Ctr, 160 E 34th St, New York, NY 10016 USA. EM howard.hochster@med.nyu.edu OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [CA13650, CA21115, CA23318, CA32291, CA66636, U10 CA013650, U10 CA021115, U10 CA023318, U10 CA032291, U10 CA066636, U24 CA114737] NR 27 TC 160 Z9 163 U1 0 U2 2 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 APR 1 PY 2009 VL 27 IS 10 BP 1607 EP 1614 DI 10.1200/JCO.2008.17.1561 PG 8 WC Oncology SC Oncology GA 447MB UT WOS:000266194100015 PM 19255334 ER PT J AU Arora, M Weisdorf, DJ Spellman, SR Haagenson, MD Klein, JP Hurley, CK Selby, GB Antin, JH Kernan, NA Kollman, C Nademanee, A McGlave, P Horowitz, MM Petersdorf, EW AF Arora, Mukta Weisdorf, Daniel J. Spellman, Stephen R. Haagenson, Michael D. Klein, John P. Hurley, Carolyn K. Selby, George B. Antin, Joseph H. Kernan, Nancy A. Kollman, Craig Nademanee, Auayporn McGlave, Philip Horowitz, Mary M. Petersdorf, Effie W. TI HLA-Identical Sibling Compared With 8/8 Matched and Mismatched Unrelated Donor Bone Marrow Transplant for Chronic Phase Chronic Myeloid Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol ID HEMATOPOIETIC-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; CLASS-I; CORD BLOOD; HIGH-RISK; IMPACT; RECIPIENT; SURVIVAL; IMATINIB AB Purpose Transplantation of hematopoietic stem cells from an unrelated donor (URD) is an option for many patients who do not have an HLA-identical sibling donor (MSD). Current criteria for the selection of URDs include consideration for HLA alleles determined by high resolution typing methods, with preference for allele-matched donors. However, the utility and outcome associated with transplants from URDs compared with those from MSDs remains undefined. Patients and Methods We examined clinical outcome after patients received bone marrow transplants (BMTs) from MSDs; HLA-A, -B, -C, and DRB1 allele-matched URDs (8/8); and HLA-mismatched URDs in a homogeneous population of patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) where a strong allogeneic effect and hence a lower risk of relapse is anticipated. Transplantation outcomes were compared between 1,052 URD and 3,514 MSD BMT recipients with CML in CP1. Results Five-year overall survival and leukemia-free survival (LFS) after receipt of BMTs from 8/8 matched URDs were worse than those after receipt of BMTs from MSDs (5-year survival, 55% v 63%; RR, 1.35; 95% CI, 1.17 to 1.56; P < .001; LFS, 50% v 55%; RR, 1.21; 95% CI, 1.06 to 1.40; P = .006). Survival was progressively worse with greater degrees of mismatch. Similar and low risk of relapse were observed after receipt of transplant from either MSD or URD. Conclusion In this homogeneous cohort of good risk patients with CML in CP1, 5-year overall survival and LFS after receipt of transplant from 8/8 allele-matched donors were modestly though significantly worse than those after receipt of transplant from MSDs. Additive adverse effects of multilocus mismatching are not well tolerated and should be avoided if possible. C1 [Arora, Mukta] Univ Minnesota, Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN 55455 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Georgetown Univ, Washington, DC USA. Univ Oklahoma, Oklahoma City, OK USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Jaeb Ctr Hlth Res, Tampa, FL USA. City Hope Med Grp, Duarte, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Arora, M (reprint author), Univ Minnesota, Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, Mayo Med Code 480,420 Delaware St SE, Minneapolis, MN 55455 USA. EM arora005@umn.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NCI NIH HHS [U24 CA076518] NR 34 TC 55 Z9 57 U1 1 U2 4 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 APR 1 PY 2009 VL 27 IS 10 BP 1644 EP 1652 DI 10.1200/JCO.2008.18.7740 PG 9 WC Oncology SC Oncology GA 447MB UT WOS:000266194100020 PM 19224849 ER PT J AU Arpino, PA Thompson, BT AF Arpino, P. A. Thompson, B. T. TI Safety of enteral naloxone for the reversal of opiate-induced constipation in the intensive care unit SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article; Proceedings Paper CT 42nd Midyear Clinical Meeting of the American-Society-of-Health-System-Pharmacists CY DEC 02-06, 2007 CL Las Vegas, NV SP Amer Soc Hlth Syst Pharmacists DE constipation; intensive care unit; naloxone; safety ID OPIOID-INDUCED CONSTIPATION; ORAL NALOXONE; ANALGESIA; PATIENT AB Background: Opiates are the mainstay of analgesia in the intensive care unit (ICU). Unfortunately, constipation is a common adverse effect associated with opioid use. Naloxone is a pure opiate antagonist that is frequently utilized in practice for the prophylaxis or treatment of opiate-induced constipation in the ICU. Despite extensive first pass metabolism in the liver there remains the potential for opiate reversal after oral administration. We sought to assess the safety of enteral naloxone in the ICU for the treatment of opiate-induced constipation. Methods: Patients who were ordered enteral naloxone while in the ICU were identified through the Pharmacy's computer system. Patients were included in the data analysis if they had received at least one dose of enteral naloxone and had received standing opiates for at least 48 h prior to the initial naloxone dose. Patients were excluded from data analysis if the Richmond agitation-sedation scale (RASS) score was not utilized, they were paralysed or the medical record indicated that extubation was planned within the following 24 h. Data points were recorder at the following times with respect to each naloxone dose administered; time -2, -1, 0, 1, 2 and 4 h. The following data points were collected before and after each naloxone dose; blood pressure, heart rate, respiratory rate, RASS score, pain assessment score (recorded as present or absent), midazolam dose, propofol dose and fentanyl dose. In order to assess for possible opiate reversal the peak fentanyl, propofol and midazolam dose, vital sign value, RASS score and pain score were compared before and after each dose of naloxone. Results: The mean naloxone dose was 3.6 +/- 0.9 mg. There was no significant change in RASS score around the naloxone doses, -2.9 +/- 1.4 before and -2.8 +/- 1.6 after (P = 0.28). There were no significant changes in mean fentanyl, propofol or midazolam dose around naloxone administration. There were also no significant changes in heart rate, blood pressure and respiratory rate or in the presence of pain. Conclusion: These results demonstrate that the administration of enteral naloxone to patients on intravenous opiates in the ICU setting was not associated with changes in sedation score, vital signs, fentanyl dose, midazolam dose or propofol dose. C1 [Arpino, P. A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Dept Med, Med Intens Care Unit, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Arpino, PA (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM parpino@partners.org NR 12 TC 6 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD APR PY 2009 VL 34 IS 2 BP 171 EP 175 DI 10.1111/j.1365-2710.2008.00982.x PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 452OR UT WOS:000266551300004 PM 19250137 ER PT J AU Weiss, AP Guidi, J Fava, M AF Weiss, Anthony P. Guidi, Jenny Fava, Maurizio TI Closing the Efficacy-Effectiveness Gap: Translating Both the What and the How From Randomized Controlled Trials to Clinical Practice SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID MENTAL-HEALTH-SERVICES; STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; MEDICATION ALGORITHM PROJECT; ROUTINE OUTCOME MEASUREMENT; MEASUREMENT-BASED CARE; MAJOR DEPRESSION; UNITED-STATES; MANAGEMENT; RATIONALE C1 [Weiss, Anthony P.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Weiss, Anthony P.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Weiss, Anthony P.] Partners Psychiat & Mental Hlth, Div Hlth Serv Res, Boston, MA USA. [Guidi, Jenny] Univ Bologna, Dept Psychol, Bologna, Italy. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 34, Boston, MA 02114 USA. EM aweiss@partners.org NR 45 TC 11 Z9 11 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2009 VL 70 IS 4 BP 446 EP 449 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 438IX UT WOS:000265550200001 PM 19403096 ER PT J AU Altshuler, LL Post, RM Hellemann, G Leverich, GS Nolen, WA Frye, MA Keck, PE Kupka, RW Grunze, H McElroy, SL Sugar, CA Suppes, T AF Altshuler, Lori L. Post, Robert M. Hellemann, Gerhard Leverich, Gabriele S. Nolen, Willem A. Frye, Mark A. Keck, Paul E., Jr. Kupka, Ralph W. Grunze, Heinz McElroy, Susan L. Sugar, Catherine A. Suppes, Trisha TI Impact of Antidepressant Continuation After Acute Positive or Partial Treatment Response for Bipolar Depression: A Blinded, Randomized Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID LITHIUM-CARBONATE; MOOD STABILIZERS; IMIPRAMINE; UNIPOLAR; ILLNESS; VENLAFAXINE; MANIA; DISCONTINUATION; COMBINATION; GUIDELINES AB Objective: To assess long-term outcome in bipolar disorder, subjects were prospectively followed after receiving acute treatment for bipolar depression. Method: Eighty-three outpatients with DSM-IV bipolar depression who were enrolled between March 1996 and November 2002 and were treated in a 10-week acute double-blind antidepressant treatment trial agreed to participate in a 1-year double-blind continuation of their medication. In the acute antidepressant treatment trial, subjects were treated with a mood stabilizer plus 1 of 3 randomly assigned antidepressants. Sixty-one subjects had attained an acute positive antidepressant response (50% improvement on the Inventory for Depressive Symptomatology [IDS] or 2-point improvement on the Clinical Global Impression for Bipolar Disorder [CGI-BP]) and 22 subjects achieved only acute partial improvement at the end of the 10-week acute trial. In the blinded continuation phase immediately following the acute trial, subjects continued on the same medications and were rated monthly for up to I year using the IDS, CGI-BP, and the Young Mania Rating scale. Results: At study endpoint, 42 (69%) of the 61 acute positive responders maintained positive response and 32 (53%) achieved remission. Compared to the acute positive responders, 6 (27%) of the 22 acute partial responders had achieved positive treatment response at study endpoint (p <.001). Eight acute positive responders (13%) and 5 acute partial responders (22%) developed mania. Conclusion: Patients who achieve a positive acute antidepressant response to 10 weeks of antidepressant treatment adjunctive to a mood stabilizer will probably maintain response with the same continued treatment. Patients who achieve only a partial acute antidepressant response are less likely to further improve when the same treatment is sustained. The switch rate into mania for patients being treated with an antidepressant adjunctive to a mood stabilizer is not higher than the reported rate for patients on mood stabilizer monotherapy. C1 [Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychiat, W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Altshuler, Lori L.; Hellemann, Gerhard] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Post, Robert M.; Leverich, Gabriele S.] Bipolar Collaborat Network, Bethesda, MD USA. [Post, Robert M.] George Washington Sch Med, Washington, DC USA. [Nolen, Willem A.] Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, Utrecht, Netherlands. [Kupka, Ralph W.] Altrech Inst Mental Hlth Care, Utrecht, Netherlands. [Frye, Mark A.] Mayo Coll Med, Genom Express & Neuropsychiat Evaluat Unit, Mayo Mood Disorder Clin & Res Program, Rochester, MN USA. [Keck, Paul E., Jr.; McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. [Keck, Paul E., Jr.; McElroy, Susan L.] HOPE, Frances Lindner Ctr, Cincinnati, OH USA. [Grunze, Heinz] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Suppes, Trisha] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Nolen, Willem/E-9006-2014 FU The Stanley Medical Research Institute; National Institute of Mental Health, Bethesda; Stanley Foundation Bipolar Network; GlaxoSmithKline, Philadelphia; Pfizer, New York, NY; Wyeth, Madison, NJ FX The authors gratefully acknowledge the support of The Stanley Medical Research Institute and the National Institute of Mental Health, Bethesda, Md., in the conduct of this research and the support of a grant from the Stanley Foundation Bipolar Network- (Dr Grunze). Drug and matching placebo were generously supplied by GlaxoSmithKline, Philadelphia, Pa. (bupropion); Pfizer, New York, NY (sertraline): and Wyeth, Madison, NJ (venlafaxine). NR 37 TC 35 Z9 35 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2009 VL 70 IS 4 BP 450 EP 457 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 438IX UT WOS:000265550200002 PM 19358785 ER PT J AU Zisook, S Kasckow, JW Golshan, S Fellows, I Solorzano, E Lehman, D Mohamed, S Jeste, DV AF Zisook, Sidney Kasckow, John W. Golshan, Shahrokh Fellows, Ian Solorzano, Ellen Lehman, David Mohamed, Somaia Jeste, Dilip V. TI Citalopram Augmentation for Subsyndromal Symptoms of Depression in Middle-Aged and Older Outpatients With Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITOR; DOUBLE-BLIND; NEGATIVE SYMPTOMS; RATING-SCALE; CLINICAL-SIGNIFICANCE; FLUOXETINE; SUICIDE; PREVALENCE; VALIDATION; IMIPRAMINE AB Background: Subsyndromal symptoms of depression (SSD) in older outpatients with schizophrenia are common and clinically important. While many physicians prescribe antidepressants to patients with schizophrenia and schizoaffective disorder who have SSD, evidence for their effectiveness and safety has been meager. We describe a randomized placebo-controlled trial of citalopram in 198 patients. Method: Participants in this 2-site study, conducted from September 1, 200 1, to August 31, 2007, were men and women with DSM-IV schizophrenia or schizoaffective disorder who were 40 years of age or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current antipsychotic medication. Analysis of covariance was used to compare improvement in scores on the Hamilton Rating Scale for Depression and Calgary Depression Rating Scale between treatment groups; secondary efficacy analyses compared improvement in several other dimensions of schizophrenia. Results: Augmentation with citalopram was significantly more effective than with placebo in improving depressive (p = .002) and negative (p = .049) symptoms, mental functioning (p = .000), and quality of life (p = .046). There were no significant differences between citalopram and placebo in suicidal ideation, positive symptoms, cognition, general medical health, physical functioning, or symptoms of movement disorders. No adverse events were more frequent in participants receiving citalopram than in those receiving placebo, and only 4 participants from each treatment group terminated early because of side effects. Conclusions: Subsyndromal symptoms of depression in middle aged and older patients with schizophrenia responded to treatment with citalopram with lessening of depressive symptoms and improved functioning and quality of life. It may be important for clinicians to identify and treat SSD in middle-aged and older patients with chronic schizophrenia. C1 [Zisook, Sidney; Golshan, Shahrokh; Fellows, Ian] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. [Solorzano, Ellen; Lehman, David; Jeste, Dilip V.] Vet Affairs San Diego Hlth Care Syst, San Diego, CA USA. [Kasckow, John W.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Kasckow, John W.] MIRECC, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Mohamed, Somaia] MIRECC, VISN 1, Vet Affairs NE Program Evaluat Ctr, New Haven, CT USA. [Mohamed, Somaia] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM szisook@ucsd.edu FU National Institute of Mental Health (NIMH) [RO-1 MH063931, MH66248, MH19934, P30 MH080002, R01 MH6398]; Department of Veterans Affairs FX This work was supported by National Institute of Mental Health (NIMH) grant RO-1 MH063931 Citalopram Augmentation of Older Patients with Schizophrenia (S. Zisook, principal investigator), and NIMH grants MH66248, MH19934, and P30 MH080002 and the Department of Veterans Affairs. Dr. Kasckow was supported by NIMH grant R01 MH6398, the VISN 4 MIRECC, and a VISN 4 Competitive Pilot Project Fund award. NR 50 TC 31 Z9 32 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2009 VL 70 IS 4 BP 562 EP 571 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 438IX UT WOS:000265550200013 PM 19192468 ER PT J AU Henderson, DC Fan, XD Copeland, PM Sharma, B Borba, CP Boxill, R Freudenreich, O Cather, C Evins, AE Goff, DC AF Henderson, David C. Fan, Xiaoduo Copeland, Paul M. Sharma, Bikash Borba, Christina P. Boxill, Ryan Freudenreich, Oliver Cather, Corinne Evins, A. Eden Goff, Donald C. TI Aripiprazole Added to Overweight and Obese Olanzapine-Treated Schizophrenia Patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE aripiprazole; olanzapine; schizophrenia; lipid metabolism; medical morbidity ID INDUCED WEIGHT-GAIN; MINIMAL MODEL ANALYSIS; GLUCOSE-TOLERANCE TEST; DOUBLE-BLIND; TRIGLYCERIDE LEVELS; 1ST-EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC TREATMENT; INSULIN-RESISTANCE; PARTIAL AGONIST; RECEPTOR AB Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance, and diabetes mellitus. There are few options for olanzapine responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo-controlled, double-blind crossover study that examined 15 mg/d aripiprazoles, effects on weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment, there were significant decreases in weight (P = 0.003) and body mass index (P = 0.004) compared with placebo. Total serum cholesterol (P = 0.208), high-density lipoprotein cholesterol (HDL-C; P = 0.99), HDL-2 (P = 0.08), HDL-3 (P = 0.495), and low-density lipoprotein cholesterol (P = 0.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (P = 0.001), total very low-density lipoprotein cholesterol (VLDL-C; P = 0.01), and VLDL-1C and VLDL-2C (P = 0.012) decreased significantly during the aripiprazole treatment phase. The VLDL-3C tended lower during aripiprazole, but the decrease was not significant (P = 0.062). There was a decrease in C-reactive protein comparing aripiprazole treatment to placebo, although it did not reach significance (P = 0.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity. C1 [Henderson, David C.; Fan, Xiaoduo; Sharma, Bikash; Borba, Christina P.; Boxill, Ryan; Freudenreich, Oliver; Cather, Corinne; Evins, A. Eden; Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Henderson, David C.; Fan, Xiaoduo; Copeland, Paul M.; Boxill, Ryan; Freudenreich, Oliver; Cather, Corinne; Evins, A. Eden; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU Solvay; Honorarium; Bristol-Myers Squibb; Janssen L.P.; Pfizer Inc; Solvay Pharmaceuticals; Covance; Primedia; Reed Medical Education; Cephalon; Xenoport; Dainippon Sumitomo; Solvay/Wyeth; Organon; Proteus; Genactics; Forest Laboratories; Xytis; MedReviews; LLC; Vanda Pharmaceuticals; Eli Lilly; Merck; Takeda; Sanofi-Aventis; GSK; NIDA CDDC FX Dr Henderson, Research Grant: Solvay, Takeda; Honorarium; Bristol-Myers Squibb, Janssen L.P., Pfizer Inc and Solvay Pharmaceuticals, and Covance, Primedia, Reed Medical Education. Dr Goff Research support: Pfizer, Cephalon, Janssen; Honorarium: Xenoport, Dainippon Sumitomo, Solvay/Wyeth, Bristol-Meyer Squibb, Organon, Proteus, Genactics, Forest Laboratories, Xytis, MedReviews, LLC, and Vanda Pharmaceuticals, Primedia, Reed Medical Education. Dr Copeland, Honorarium: Eli Lilly, Merck, Takeda, and Sanofi-Aventis. Dr Fan, Research support: Eli Lilly; Honorarium: Eli Lilly. Dr Freudenreich, Research support: Cephalon; Honorarium: Primedia and Reed Medical Education. Dr Evins, Research support: Pfizer, GSK, and NIDA CDDC. Dr Boxill, Dr Cather, Dr Sharma and Ms Borba report no disclosures. NR 44 TC 41 Z9 45 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2009 VL 29 IS 2 BP 165 EP 169 DI 10.1097/JCP.0b013e31819a8dbe PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 420BO UT WOS:000264263600009 PM 19512978 ER PT J AU Ito, K Mihm, MC AF Ito, Keigo Mihm, Martin C. TI Pigmented epithelioid melanocytoma: report of first Japanese cases previously diagnosed as cellular blue nevus SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ANIMAL-TYPE MELANOMA; MALIGNANT-MELANOMA; NEOPLASMS; TUMOR AB The term 'pigmented epithelioid melanocytoma (PEM)' was recently used for borderline melanocytic tumor/low-grade melanoma including cases previously diagnosed as human animal-type melanoma and epithelioid blue nevus. No Japanese cases have been reported. We reviewed 219 cases previously diagnosed as blue nevus in Japan. Common blue nevus was identified in 154 cases and cellular blue nevus in 65 cases. We have found two Japanese cases of PEM previously diagnosed as cellular blue nevus. Two patients were female. The age at presentation was 32 and 28 years. Two lesions were on the buttock. Two cases fulfilled histological criteria proposed for PEM. There is no evidence of recurrence or metastases. PEM is a distinct melanocytic tumor and the unifying diagnostic term. PEM is present in Japanese, but these cases may be previously diagnosed as cellular blue nevus. Japanese pathologists should recognize a new concept of PEM, and when they make a diagnosis of PEM, they should be recommended sentinel lymph node sampling. Ito K, Mihm MC. Pigmented epithelioid melanocytoma: report of first Japanese cases previously diagnosed as cellular blue nevus.J Cutan Pathol 2009; 36: 439-443. (C) 2008 Blackwell Munksgaard. C1 [Ito, Keigo] Jikei Univ, Dept Dermatol, Sch Med, Minato Ku, Tokyo 1058461, Japan. [Ito, Keigo] Sapporo Inst Dermatopathol, Sapporo, Hokkaido, Japan. [Ito, Keigo; Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. RP Ito, K (reprint author), Jikei Univ, Dept Dermatol, Sch Med, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan. EM keigo@jikei.ac.jp NR 12 TC 9 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 2009 VL 36 IS 4 BP 439 EP 443 DI 10.1111/j.1600-0560.2008.01071.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 412WD UT WOS:000263754000007 PM 19278429 ER PT J AU Tye, CE Pham, CT Simmer, JP Bartlett, JD AF Tye, C. E. Pham, C. T. Simmer, J. P. Bartlett, J. D. TI DPPI May Activate KLK4 during Enamel Formation SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; dipeptidyl peptidase I; kallikrein-4; amelogenesis; mineralization ID DIPEPTIDYL-PEPTIDASE-I; PAPILLON-LEFEVRE-SYNDROME; CATHEPSIN-C GENE; AMELOGENESIS-IMPERFECTA; KALLIKREIN-4; EXPRESSION; MUTATIONS; ARTHRITIS; COLLAGEN; ENZYME AB Kallikrein-4 (KLK4) is a serine protease expressed during enamel maturation, and proteolytic processing of the enamel matrix by KLK4 is critical for proper enamel formation. KLK4 is secreted as an inactive zymogen (pro-KLK4), and identification of its activator remains elusive. Dipeptidyl peptidase I (DPPI) is a cysteine aminopeptidase that can activate several serine proteases. In this study, we sought to examine DPPI expression in mouse enamel organ and determine if DPPI could activate KLK4. Real-time PCR showed DPPI expression throughout amelogenesis, with highest expression at maturation, and immunohistochemical staining of mouse incisors confirmed DPPI expression by ameloblasts. We demonstrate in vitro that DPPI activates pro-KLK4 to cleave a fluorogenic peptide containing a KLK4 cleavage site. Examination of mature enamel from DPPI null mice by FTIR showed no significant accumulation of protein; however, microhardness testing revealed that loss of DPPI expression significantly reduced enamel hardness. C1 [Tye, C. E.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. [Tye, C. E.; Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Pham, C. T.] Washington Univ, Div Rheumatol, Dept Internal Med, St Louis, MO USA. [Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. 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 FU National Institute of Dental and Craniofacial Research [DE016276]; National Institute of Allergy and Infectious Diseases [AI049261]; National Institutes of Health, Bethesda, MD, USA [20892] FX This investigation was supported by Research Grants DE016276 from the National Institute of Dental and Craniofacial Research ( J. D. B.) and AI049261 from the National Institute of Allergy and Infectious Diseases ( C. T. P.), National Institutes of Health, Bethesda, MD 20892, USA. NR 26 TC 14 Z9 17 U1 0 U2 1 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 APR PY 2009 VL 88 IS 4 BP 323 EP 327 DI 10.1177/0022034509334240 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 450XF UT WOS:000266434000005 PM 19407151 ER PT J AU Nagaya, M Katsuta, H Kaneto, H Bonner-Weir, S Weir, GC AF Nagaya, Masaki Katsuta, Hitoshi Kaneto, Hideaki Bonner-Weir, Susan Weir, Gordon C. TI Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BETA-CELLS; RAT CHOLANGIOCYTES; NONHUMAN-PRIMATES; PANCREATIC TISSUE; PRECURSOR CELLS; PORCINE ISLETS; MURINE LIVER; STEM-CELLS; EXPRESSION; ENDOCRINE AB Transdifferentiation of cells from a patients own liver into pancreatic beta-cells could be useful for beta-cell replacement. We hypothesized that intrahepatic biliary epithelial cells (IHBECs) could become a new source of insulin-producing cells. IHBECs isolated from adult mice were expanded using our novel culture method termed, collagen-embedded floating culture method (CEFCM). With CEFCM, IHBECs formed three-dimensional ductal cysts and rapidly expanded their number by about 15-fold within 2 weeks. Over 90% of cells were positive for cytokeratin 7 and 19. At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. After 7 additional days in serum- and insulin-free differentiation medium (DM), cell phenotypes were determined by RT-PCR, immunostaining and ELISA for insulin. In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. About 3% of 4000 cells counted in PDX-1/VP16 transduced cultures stained strongly for C-peptide Suggesting that a subpopulation may have the capacity for differentiation. Transduced cells released insulin (Ad-PDX-1 0.08 +/- 0.05, Ad-NEUROD 0.33 +/- 0.09, Ad-PDX-1/VP16 0.37 +/- 0-14 ng/1 x 10(5) cells after 48 h in Culture). IHBECs can be markedly expanded, and then with molecular manipulation a subpopulation of these cells can differentiate towards a beta-cell phenotype. This approach may lead to a new source of beta-cells that can be used for transplantation in diabetes. Journal of Endocrinology (2009) 201, 37-47 C1 [Nagaya, Masaki; Katsuta, Hitoshi; Bonner-Weir, Susan; Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Div Res, Boston, MA 02215 USA. [Nagaya, Masaki; Katsuta, Hitoshi; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Kaneto, Hideaki] Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Osaka 5650871, Japan. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU National institutes of Health [DK-66056]; Juvenile Diabetes Research Foundation; Diabetes Research and Wellness Foundation; Diabetes and Endocrinology Research Center (DERC) [DK 36836]; St Marianna University FX M N was the recipient of a scholarship front St Marianna University. NR 46 TC 33 Z9 40 U1 0 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD APR PY 2009 VL 201 IS 1 BP 37 EP 47 DI 10.1677/JOE-08-0482 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 530YM UT WOS:000272628900004 PM 19168505 ER PT J AU Volpp, KG Troxel, A Long, J Ibrahaim, S Appleby, D Smith, J Jaskowiak, J Wang, P Holmes, JH Frosch, D Armstrong, K Helweg-Larsen, M Doshi, J Kumanyika, S Enge, K Townsend, R Joshi, N Kimmel, SE AF Volpp, K. G. Troxel, A. Long, J. Ibrahaim, S. Appleby, D. Smith, J. Jaskowiak, J. Wang, P. Holmes, J. H. Frosch, D. Armstrong, K. Helweg-Larsen, M. Doshi, J. Kumanyika, S. Enge, K. Townsend, R. Joshi, N. Kimmel, S. E. TI A RANDOMIZED CONTROLLED TRIAL OF COPAYMENT REDUCTIONS FOR BLOOD PRESSURE MEDICATION: THE COLLABORATION IN HYPERTENSION TO REDUCE DISPARITIES (CHORD) TRIAL SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Volpp, K. G.; Troxel, A.; Long, J.; Armstrong, K.; Doshi, J.; Kimmel, S. E.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Volpp, K. G.; Long, J.; Armstrong, K.] Philadelphia Vet Affairs Med Ctr, CHERP, Philadelphia, PA USA. [Ibrahaim, S.] Vet Adm Hosp, CHERP, Pittsburgh, PA USA. [Smith, J.] Cheyney Univ, Cheyney, PA USA. [Frosch, D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Helweg-Larsen, M.; Enge, K.] Dickinson Coll, Carlisle, PA 17013 USA. [Joshi, N.] Pinnacle Hlth, Harrisburg, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 9 EP 10 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000024 ER PT J AU Steinman, M Patil, S Kamat, P Knight, S AF Steinman, M. Patil, S. Kamat, P. Knight, S. TI A TAXONOMY OF REASONS FOR NOT PRESCRIBING GUIDELINE-RECOMMENDED MEDICATIONS: RESULTS FROM PHYSICIAN FOCUS GROUPS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Steinman, M.; Patil, S.; Kamat, P.; Knight, S.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 10 EP 11 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000027 ER PT J AU Lopez, L Pabon-Nau, LP Hicks, LS AF Lopez, L. Pabon-Nau, L. P. Hicks, L. S. TI ACCULTURATION AND SELF-REPORTED HYPERTENSION AND DIABETES IN LATINO SUBGROUPS: THE CALIFORNIA HEALTH INTERVIEW SURVEY 2001-2005 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Lopez, L.; Hicks, L. S.] Harvard Univ, Boston, MA 02115 USA. [Pabon-Nau, L. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 12 EP 13 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000032 ER PT J AU Gopal, RK Yamashita, TE Prochazka, AV AF Gopal, R. K. Yamashita, T. E. Prochazka, A. V. TI AMBULATORY CARE PROVIDERS' WORK ENVIRONMENT ASSOCIATED WITH POOR QUALITY OF CARE AND PROVIDER BURNOUT. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Gopal, R. K.; Prochazka, A. V.] Denver VAMC, Denver, CO USA. [Yamashita, T. E.] Univ Colorado, Sch Med, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 18 EP 19 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000048 ER PT J AU Renfrew, MR Cohen, MJ Roger, P Betancourt, JR Liang, S Tan-Mcgrory, A Green, AR AF Renfrew, M. R. Cohen, M. J. Roger, P. Betancourt, J. R. Liang, S. Tan-Mcgrory, A. Green, A. R. TI BARRIERS TO CARE FOR CAMBODIAN PATIENTS WITH DIABETES: RESULTS FROM A QUALITATIVE STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Renfrew, M. R.; Betancourt, J. R.; Tan-Mcgrory, A.; Green, A. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cohen, M. J.] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Chelsea, MA USA. [Roger, P.] Massachusetts Gen Hosp, Revere, MA USA. [Liang, S.] Lowell Community Hlth Ctr, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 29 EP 30 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000079 ER PT J AU Percac-Lima, S Aldrich, LS Gamba, GB Bearse, AM Atlas, SJ AF Percac-Lima, S. Aldrich, L. S. Gamba, G. B. Bearse, A. M. Atlas, S. J. TI BARRIERS TO FOLLOW-UP OF AN ABNORMAL PAP SMEAR IN LATINA WOMEN REFERRED FOR COLPOSCOPY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Percac-Lima, S.; Gamba, G. B.] Massachusetts Gen Hosp, Chelsea, MA USA. [Aldrich, L. S.; Bearse, A. M.; Atlas, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 30 EP 30 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000080 ER PT J AU Paidisetty, S Broyles, LM Forman, SD Gordon, AJ AF Paidisetty, S. Broyles, L. M. Forman, S. D. Gordon, A. J. TI BUPRENORPHINE AND METHADONE OPIOID AGONIST THERAPY: DIFFERENCES IN PATIENT ENROLLMENT CHARACTERISTICS WITHIN A VA MEDICAL CENTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Forman, S. D.; Gordon, A. J.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 35 EP 36 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000095 ER PT J AU Dick, JF Wipf, JE Wilper, AP Smith, CS AF Dick, J. F. Wipf, J. E. Wilper, A. P. Smith, C. S. TI CAN RESIDENCY PROGRAM CURRICULA ENHANCE SELECTION OF PRIMARY CARE CAREERS? FACTORS AFFECTING PRIMARY CARE CAREER CHOICE IN ONE INTERNAL MEDICINE TRAINING PROGRAM. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Dick, J. F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Wipf, J. E.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Wilper, A. P.; Smith, C. S.] Univ Washington, Boise VA Med Ctr, Boise, ID USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 37 EP 37 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000100 ER PT J AU Cohen, BE Ren, L Bertenthal, D Seal, KH AF Cohen, B. E. Ren, L. Bertenthal, D. Seal, K. H. TI CARDIAC RISK FACTORS IN IRAQ AND AFGHANISTAN VETERANS USING VA HEALTHCARE: ASSOCIATION WITH MENTAL HEALTH DIAGNOSES SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Cohen, B. E.; Ren, L.; Bertenthal, D.; Seal, K. H.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 38 EP 38 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000102 ER PT J AU Volpp, K Konetzka, T Zhu, J Lindrooth, R AF Volpp, K. Konetzka, T. Zhu, J. Lindrooth, R. TI CHANGES OVER TIME IN HOSPITAL PROFITABILITY BY SERVICE LINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Volpp, K.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, K.] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA USA. [Konetzka, T.] Univ Chicago, Chicago, IL 60637 USA. [Zhu, J.] Univ Penn, Philadelphia, PA 19104 USA. [Lindrooth, R.] Med Univ S Carolina, Charleston, SC 29425 USA. RI Lindrooth, Richard/J-8607-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 40 EP 41 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000108 ER PT J AU Baggett, TP Rigotti, NA AF Baggett, T. P. Rigotti, N. A. TI CIGARETTE SMOKING, ADVICE TO QUIT, AND SMOKING CESSATION IN A NATIONAL SAMPLE OF HOMELESS ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Baggett, T. P.; Rigotti, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 41 EP 42 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000111 ER PT J AU Siegel, LC Lawler, E Gaziano, J AF Siegel, L. C. Lawler, E. Gaziano, J. TI CLINICAL FACTORS ASSOCIATED WITH RECEIPT OF A PRESCRIPTION FOR A FIBRATE OR NIACIN AMONG DIABETIC VETERANS IN NEW ENGLAND SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Siegel, L. C.; Lawler, E.; Gaziano, J.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 42 EP 42 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000112 ER PT J AU Kapoor, A Chuang, W Radhakrishnan, N Smith, KJ Berlowitz, DR Segal, JB Katz, JN Losina, E AF Kapoor, A. Chuang, W. Radhakrishnan, N. Smith, K. J. Berlowitz, D. R. Segal, J. B. Katz, J. N. Losina, E. TI COMPARING COST-EFFECTIVENESS RESULTS ACROSS MULTIPLE STUDIES OF VTE PROPHYLAXIS WITH INDEPENDENT MODELING TO STANDARDIZE HORIZON LENGTH AND EFFECTIVENESS UNITS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Kapoor, A.; Radhakrishnan, N.] Boston Univ, Sch Med, Hosp Med Unit, Boston, MA 02118 USA. [Chuang, W.] Massachusetts Gen Hosp, Hosp Med Grp, Boston, MA 02114 USA. [Smith, K. J.] Univ Pittsburgh, Sch Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. [Berlowitz, D. R.] Bedford VA Med Ctr, Bedford, MA USA. [Segal, J. B.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Katz, J. N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Katz, J. N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Losina, E.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RI Segal, Jodi/A-2863-2009 OI Segal, Jodi/0000-0003-3978-9662 NR 0 TC 0 Z9 0 U1 0 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 APR PY 2009 VL 24 SU 1 BP 46 EP 47 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000123 ER PT J AU Gordon, WJ Polansky, JM Boscardin, J Fung, K Steinman, M AF Gordon, W. J. Polansky, J. M. Boscardin, J. Fung, K. Steinman, M. TI CORONARY RISK ASSESSMENT BY POINT-BASED VS. EQUATION-BASED FRAMINGHAM MODELS: SIGNIFICANT IMPLICATIONS FOR CLINICAL CARE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Gordon, W. J.] Weill Cornell Med Coll, New York, NY USA. [Polansky, J. M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Boscardin, J.; Steinman, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fung, K.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 48 EP 49 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000128 ER PT J AU Liebschutz, JM Schwartz, SL Hoyte, J James, TL Conoscenti, L Harper, D Killebrew, D Muhammad, L Christian, A Bishop, R AF Liebschutz, J. M. Schwartz, S. L. Hoyte, J. James, T. L. Conoscenti, L. Harper, D. Killebrew, D. Muhammad, L. Christian, A. Bishop, R. TI DE-CONSTRUCTING THE WALLS BETWEEN INJURY AND CARE: EXPERIENCES OF BLACK MALE VICTIMS OF VIOLENCE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Liebschutz, J. M.] Boston Univ, Boston, MA 02215 USA. [Schwartz, S. L.; James, T. L.; Muhammad, L.; Christian, A.; Bishop, R.] Boston Med Ctr, Boston, MA USA. [Hoyte, J.] Tufts Univ, Medford, MA 02155 USA. [Conoscenti, L.] Boston VA Healthcare Syst, Boston, MA USA. [Harper, D.; Killebrew, D.] Pyramid Builders, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 51 EP 52 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000136 ER PT J AU Pabon-Nau, LP Meigs, JB Grant, RW AF Pabon-Nau, L. P. Meigs, J. B. Grant, R. W. TI DECLINING HEALTH STATUS BY YEARS IN US AMONG HISPANIC ADULTS: THE NATIONAL HEALTH INTERVIEW SURVEY 2000-2005 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Pabon-Nau, L. P.; Meigs, J. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grant, R. W.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 51 EP 51 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000135 ER PT J AU Singh, H Davis, T Khan, MM Thomas, EJ AF Singh, H. Davis, T. Khan, M. M. Thomas, E. J. TI DETECTION OF DIAGNOSTIC ERRORS USING ELECTRONIC HEALTH RECORDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Singh, H.; Davis, T.; Khan, M. M.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Singh, H.; Davis, T.; Khan, M. M.] Baylor Coll Med, Houston, TX 77030 USA. [Thomas, E. J.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 53 EP 53 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000140 ER PT J AU Safford, MM Petersen, NJ Funkhouser, E Agee, BS Houston, TK AF Safford, M. M. Petersen, N. J. Funkhouser, E. Agee, B. S. Houston, T. K. TI DIMINISHING RETURNS: MORE BLOOD PRESSURE MEDICATIONS INCREASE CHANCES OF RUNNING OUT OF MEDICINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Safford, M. M.; Funkhouser, E.] Univ Alabama, Birmingham, AL USA. [Petersen, N. J.] Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Agee, B. S.; Houston, T. K.] Birmingham VA Med Ctr, Birmingham, AL USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 56 EP 56 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000150 ER PT J AU Hausmann, LR Mor, MK Geng, M Kresevic, D Grant, R Ibrahim, S AF Hausmann, L. R. Mor, M. K. Geng, M. Kresevic, D. Grant, R. Ibrahim, S. TI DISCRIMINATION IN HEALTH CARE AND PATIENT WILLINGNESS TO UNDERGO JOINT REPLACEMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Hausmann, L. R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Mor, M. K.; Geng, M.; Ibrahim, S.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Mor, M. K.; Geng, M.; Ibrahim, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Kresevic, D.; Grant, R.] Vet Affairs Med Ctr, Louis Stokes Cleveland Dept, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 57 EP 57 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000152 ER PT J AU Fihn, SD Rumsfeld, J Diehr, PH Mcdonell, M Stadius, M Gerrity, M Larsen, G Heidenreich, PA Bryson, C AF Fihn, S. D. Rumsfeld, J. Diehr, P. H. Mcdonell, M. Stadius, M. Gerrity, M. Larsen, G. Heidenreich, P. A. Bryson, C. TI EFFECT OF A COLLABORATIVE CARE INTERVENTION ON PATIENTS WITH ISCHEMIC HEART DISEASE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Fihn, S. D.] VA Off Qual & Performance, Seattle, WA USA. [Rumsfeld, J.] Eastern Colorado Hlth Care Syst, Denver, CO USA. [Diehr, P. H.] Univ Washington, Seattle, WA 98195 USA. [Mcdonell, M.; Stadius, M.; Bryson, C.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Gerrity, M.; Larsen, G.] VA Portland, Portland, OR USA. [Heidenreich, P. A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 64 EP 64 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000171 ER PT J AU Prochazka, AV Fink, AS Henderson, W Bartenfeld, D Nyirenda, C AF Prochazka, A. V. Fink, A. S. Henderson, W. Bartenfeld, D. Nyirenda, C. TI EFFECT OF REPEAT BACK ON PATIENT PERCEPTIONS OF INFORMED CONSENT FOR SURGERY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Prochazka, A. V.] Denver VA Med Ctr, Denver, CO USA. [Fink, A. S.] Atlanta VAMC, Decatur, GA USA. [Henderson, W.; Nyirenda, C.] Univ Colorado Denver, Aurora, CO USA. [Bartenfeld, D.] Atlanta VAMC, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 65 EP 66 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000176 ER PT J AU Kelley, AS Wenger, NS Sarkisian, CA AF Kelley, A. S. Wenger, N. S. Sarkisian, C. A. TI END OF LIFE PREFERENCES AND PLANNING AMONG OLDER LATINOS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Sarkisian, C. A.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 69 EP 69 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000187 ER PT J AU Bryson, CL Au, DH Blough, DK Fihn, SD Jackson, GL Piette, JD Maciejewski, ML Perkins, MW Sharp, ND Liu, C AF Bryson, C. L. Au, D. H. Blough, D. K. Fihn, S. D. Jackson, G. L. Piette, J. D. Maciejewski, M. L. Perkins, M. W. Sharp, N. D. Liu, C. TI FACILITY LEVEL VARIATION IN ADHERENCE TO ORAL DIABETES MEDICATIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Bryson, C. L.; Au, D. H.; Perkins, M. W.; Sharp, N. D.; Liu, C.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Blough, D. K.] Univ Washington, Seattle, WA 98195 USA. [Fihn, S. D.] VA Off Qual & Performance, Washington, DC USA. [Jackson, G. L.; Maciejewski, M. L.] Durham VA Med Ctr, Durham, NC USA. [Piette, J. D.] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 73 EP 74 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000198 ER PT J AU Deep, KS Volandes, AE Murphy, K Hunter, A AF Deep, K. S. Volandes, A. E. Murphy, K. Hunter, A. TI EXPLORING THE DECISION MAKING OF PATIENTS USING VIDEO IMAGES OF ADVANCED DEMENTIA. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Deep, K. S.; Murphy, K.; Hunter, A.] Univ Kentucky, Lexington, KY USA. [Volandes, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 73 EP 73 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000196 ER PT J AU Schiesser, R Espadas, D Petersen, LA Singh, H AF Schiesser, R. Espadas, D. Petersen, L. A. Singh, H. TI FOLLOW-UP OF ELECTRONIC CONSULTATION REQUESTS IN A MULTISPECIALTY OUTPATIENT CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Espadas, D.] Michael E DeBakey Vet Affairs Med Ctr, Patient Safety Ctr Inquiry Improve Outpatient Saf, Houston HSR&D Ctr Excellence, Houston, TX USA. [Petersen, L. A.; Singh, H.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 77 EP 77 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000207 ER PT J AU Majesko, AA Boudreau, R Geng, M Kwoh, K Garvin, J Ibrahim, S AF Majesko, A. A. Boudreau, R. Geng, M. Kwoh, K. Garvin, J. Ibrahim, S. TI GENDER AND HIP/KNEE TOTAL ARTHROPLASTY: MORTALITY, COMPLICATIONS AND REVISION RATES IN THE STATE OF PENNSYLVANIA. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Majesko, A. A.] Univ Pittsburgh, VAPHS, Pittsburgh, PA USA. [Geng, M.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Garvin, J.] VA HSR&D Ctr Hlth Equity Res & Promot CHERP, Philadelphia, PA USA. [Ibrahim, S.] Vet Affairs Healthcare Syst Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 79 EP 80 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000214 ER PT J AU Chen, LM Zheng, J Jha, AK AF Chen, L. M. Zheng, J. Jha, A. K. TI HIGH COST INPATIENTS: THEIR PATIENT AND HOSPITAL CHARACTERISTICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Chen, L. M.; Jha, A. K.] VA Boston Healthcare Syst, Boston, MA USA. [Zheng, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 85 EP 85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000230 ER PT J AU Seal, KH Cohen, B Ren, L Tarasovsky, G Burt, M Redden, N Abadjian, L AF Seal, K. H. Cohen, B. Ren, L. Tarasovsky, G. Burt, M. Redden, N. Abadjian, L. TI HIGH-RISK ALCOHOL USE AND SUBSTANCE MISUSE AMONG IRAQ AND AFGHANISTAN VETERANS: HIGH PREVALENCE AND ASSOCIATED MENTAL DISORDERS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Seal, K. H.; Ren, L.; Tarasovsky, G.; Burt, M.; Redden, N.; Abadjian, L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cohen, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 86 EP 86 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000232 ER PT J AU Tello, MA Jenckes, MW Gaver, J Anderson, J Moore, RD Chander, G AF Tello, M. A. Jenckes, M. W. Gaver, J. Anderson, J. Moore, R. D. Chander, G. TI HIV WOMEN'S HEALTH: BARRIERS TO RECOMMENDED GYNECOLOGIC CARE IN AN URBAN HIV CLINIC SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Tello, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jenckes, M. W.; Gaver, J.; Anderson, J.; Moore, R. D.; Chander, G.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 87 EP 87 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000235 ER PT J AU Bemben, W Gordon, AJ AF Bemben, W. Gordon, A. J. TI HOMELESS MEDICAL OUTREACH: A SYSTEMATIC NARRATIVE REVIEW AND CLIENT AND STAKEHOLDER PERCEPTIONS FOR IMPLEMENTATION IN ANCHORAGE ALASKA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Gordon, A. J.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 88 EP 88 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000237 ER PT J AU Korthuis, T Saha, S Moore, RD Cohn, JA Sharp, V Mccarty, D Beach, MC AF Korthuis, T. Saha, S. Moore, R. D. Cohn, J. A. Sharp, V. Mccarty, D. Beach, M. C. TI ILLICIT DRUG USE AND QUALITY OF PATIENT-PROVIDER COMMUNICATION IN HIV CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Korthuis, T.; Mccarty, D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 95 EP 96 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000257 ER PT J AU Fischer, MA Stedman, M Lii, J Kaushal, R Weissman, J AF Fischer, M. A. Stedman, M. Lii, J. Kaushal, R. Weissman, J. TI IMPACT OF ELECTRONIC PRESCRIBING IN COMMUNITY-BASED PRACTICES ON POTENTIAL DRUG-DRUG INTERACTIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Fischer, M. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kaushal, R.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Weissman, J.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Weissman, J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 98 EP 99 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000264 ER PT J AU Mehta, K Fung, K Kistler, C Chang, A Walter, L AF Mehta, K. Fung, K. Kistler, C. Chang, A. Walter, L. TI IMPACT OF COGNITIVE IMPAIRMENT ON SCREENING MAMMOGRAPHY USE IN OLDER US WOMEN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Mehta, K.; Kistler, C.; Chang, A.; Walter, L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fung, K.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2009 VL 24 SU 1 BP 98 EP 98 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000263 ER PT J AU Percac-Lima, S Grant, RW Green, A Ashburner, JM Gamba, GB Oo, S Richter, JM Atlas, SJ AF Percac-Lima, S. Grant, R. W. Green, A. Ashburner, J. M. Gamba, G. B. Oo, S. Richter, J. M. Atlas, S. J. TI IMPROVING SCREENING COLONOSCOPY RATES IN UNDERSERVED POPULATION - NAVIGATOR INTERVENTIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Percac-Lima, S.; Gamba, G. B.; Oo, S.] Massachusetts Gen Hosp, Chelsea, MA USA. [Grant, R. W.; Green, A.; Ashburner, J. M.; Richter, J. M.; Atlas, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 103 EP 103 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000275 ER PT J AU Rahilly-Tierney, CR Sesso, H Bowman, TS Luc, D Gaziano, J AF Rahilly-Tierney, C. R. Sesso, H. Bowman, T. S. Luc, D. Gaziano, J. TI LIFESTYLE PREDICTORS OF 14-YEAR CHANGE IN HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IN MALE PHYSICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Rahilly-Tierney, C. R.] VA Boston Healthcare, Jamaica Plain, MA USA. [Gaziano, J.] Brigham & Womens Hosp, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02115 USA. [Bowman, T. S.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 116 EP 116 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000309 ER PT J AU Bautista, MK Garvan, CW Beyth, RJ Kwoh, K Harris, TB Nevitt, MC Shorr, RI AF Bautista, M. K. Garvan, C. W. Beyth, R. J. Kwoh, K. Harris, T. B. Nevitt, M. C. Shorr, R. I. TI LOW LITERACY PREDICTS UTILIZATION OF TOTAL KNEE ARTHROPLASTY IN OLDER ADULTS WITH KNEE PAIN: FINDINGS FROM THE HEALTH, AGING AND BODY COMPOSITION STUDY. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Bautista, M. K.; Beyth, R. J.; Shorr, R. I.] Univ Florida, Dept Aging, NF SGVHS GRECC, Gainesville, FL USA. [Garvan, C. W.] Univ Florida, Coll Educ, Gainesville, FL USA. [Kwoh, K.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. [Harris, T. B.] NIH, Chevy Chase, MD USA. [Nevitt, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 117 EP 118 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000313 ER PT J AU Singh, H Hirani, K Kadiyala, H Rudomiotov, O Davis, T Khan, MM Wahls, T AF Singh, H. Hirani, K. Kadiyala, H. Rudomiotov, O. Davis, T. Khan, M. M. Wahls, T. TI LUNG CANCER DIAGNOSIS IN THE ERA OF ELECTRONIC MEDICAL RECORDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Singh, H.; Davis, T.] Michael E DeBakey Vet Affairs Med Ctr, Houston VA HSR&D, Houston, TX USA. [Singh, H.; Davis, T.] Baylor Coll Med, Houston, TX 77030 USA. [Rudomiotov, O.; Wahls, T.] Iowa City Vet Adm Med Ctr, Iowa City, IA USA. [Rudomiotov, O.; Wahls, T.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 118 EP 119 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000315 ER PT J AU Krebs, EE Becker, WC Zerzan, J Mccoy, K Sutherland, J Bair, MJ AF Krebs, E. E. Becker, W. C. Zerzan, J. Mccoy, K. Sutherland, J. Bair, M. J. TI MORTALITY AMONG VA PATIENTS PRESCRIBED METHADONE AND MORPHINE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Krebs, E. E.; Mccoy, K.; Bair, M. J.] Roudebush VA Ctr Excellence Implementing Evidence, Indianapolis, IN USA. [Becker, W. C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Zerzan, J.] Univ Colorado, Aurora, CO USA. [Sutherland, J.] Dartmouth Med Sch, Hanover, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 124 EP 125 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000332 ER PT J AU Salanitro, A Funkhouser, E Allison, JJ Halanych, JH Houston, TK Litaker, M Levine, DA Safford, MM AF Salanitro, A. Funkhouser, E. Allison, J. J. Halanych, J. H. Houston, T. K. Litaker, M. Levine, D. A. Safford, M. M. TI MULTIPLE UNCONTROLLED COMORBID CONDITIONS AND MEDICATION INTENSIFICATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Salanitro, A.; Houston, T. K.] Birmingham VA Med Ctr, Birmingham, AL USA. [Funkhouser, E.; Allison, J. J.; Halanych, J. H.; Litaker, M.; Safford, M. M.] Univ Alabama, Birmingham, AL USA. [Levine, D. A.] Ohio State Univ, Columbus, OH 43210 USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 125 EP 126 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000335 ER PT J AU Long, JA Lurie, N Escarce, J Montagnet, C Armstrong, K AF Long, J. A. Lurie, N. Escarce, J. Montagnet, C. Armstrong, K. TI NEIGHBORHOOD DISADVANTAGE, RACE, AND PROSTATE CANCER PRESENTATION, TREATMENT, AND MORTALITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Long, J. A.] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Lurie, N.] RAND, Arlington, VA USA. [Escarce, J.] RAND, Los Angeles, CA USA. [Montagnet, C.; Armstrong, K.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 126 EP 126 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000337 ER PT J AU Starrels, JL Becker, WC Li, X Weiner, MG Turner, BJ AF Starrels, J. L. Becker, W. C. Li, X. Weiner, M. G. Turner, B. J. TI OPIOID RISK MANAGEMENT IN A COHORT OF PRIMARY CARE PATIENTS WITH CHRONIC NON-CANCER PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Starrels, J. L.; Li, X.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Becker, W. C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Weiner, M. G.; Turner, B. J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 128 EP 128 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000341 ER PT J AU Pirraglia, PA Greenwald, D Welsh, D Kilbourne, A AF Pirraglia, P. A. Greenwald, D. Welsh, D. Kilbourne, A. TI ORGANIZATIONAL CHARACTERISTICS ASSOCIATED WITH CO-LOCATION OF GENERAL MEDICAL SERVICES IN MENTAL HEALTH PROGRAMS FOR VETERANS WITH SEVERE MENTAL ILLNESS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Pirraglia, P. A.] Providence VA Med Ctr, Providence, RI USA. [Greenwald, D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Welsh, D.; Kilbourne, A.] VA Natl Serious Mental Illness Treatment Res & Ev, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 129 EP 129 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000343 ER PT J AU Bokhour, BG Solomon, J Cohn, EC Cortes, D Elwy, A Haidet, P Katz, LA Borzecki, A Green, AR Kressin, NR AF Bokhour, B. G. Solomon, J. Cohn, E. C. Cortes, D. Elwy, A. Haidet, P. Katz, L. A. Borzecki, A. Green, A. R. Kressin, N. R. TI PATIENT PERSPECTIVES ON MANAGING HYPERTENSION: DEVELOPING A NEW CONCEPTUAL MODEL OF PATIENT BEHAVIOR SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Bokhour, B. G.; Solomon, J.; Elwy, A.] VA New England Healthcare Syst, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Cohn, E. C.] Boston Univ, Sargent Coll Hlth Profess, Boston, MA 02215 USA. [Cortes, D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Haidet, P.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Katz, L. A.] New York Harbor VA Healthcare Syst, Larchmont, NY USA. [Green, A. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kressin, N. R.] Boston Univ, Bedford, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 134 EP 134 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000357 ER PT J AU Kelley, AS Ettner, SL Wenger, NS Sarkisian, CA AF Kelley, A. S. Ettner, S. L. Wenger, N. S. Sarkisian, C. A. TI PATIENT-LEVEL DETERMINANTS OF DYING IN THE HOSPITAL AMONG HRS DECEDENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Sarkisian, C. A.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 135 EP 135 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000359 ER PT J AU Ling, B Hausmann, L Mor, MK Geng, M Ibrahim, S AF Ling, B. Hausmann, L. Mor, M. K. Geng, M. Ibrahim, S. TI PATIENT-PROVIDER COMMUNICATION AND INFORMED DECISION MAKING FOR PATIENTS WITH KNEE OR HIP OSTEOARTHRITIS IN THE ORTHOPEDIC SETTING WITHIN THE VA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Ling, B.; Hausmann, L.; Mor, M. K.; Geng, M.; Ibrahim, S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ling, B.; Hausmann, L.; Mor, M. K.; Geng, M.; Ibrahim, S.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 136 EP 136 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000361 ER PT J AU Cohen, BE Marmar, C Neylan, T Nelson, S Ali, S Whooley, MA AF Cohen, B. E. Marmar, C. Neylan, T. Nelson, S. Ali, S. Whooley, M. A. TI POST-TRAUMATIC STRESS DISORDER AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH HEART DISEASE: FINDINGS FROM THE HEART AND SOUL STUDY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Cohen, B. E.; Marmar, C.; Neylan, T.; Nelson, S.; Ali, S.; Whooley, M. A.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000375 ER PT J AU Harris, DP Chodosh, J Vassar, SD Vickrey, BG Shapiro, MF AF Harris, D. P. Chodosh, J. Vassar, S. D. Vickrey, B. G. Shapiro, M. F. TI PRIMARY CARE PROVIDERS' VIEW OF CHALLENGES AND REWARDS OF DEMENTIA CARE RELATIVE TO OTHER CONDITIONS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Vickrey, B. G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Chodosh, J.] Greater Los Angeles Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. [Shapiro, M. F.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 146 EP 146 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000389 ER PT J AU Linsky, A Gupta, K Lawler, E Fonda, J Sokolovskaya, G Hermos, J AF Linsky, A. Gupta, K. Lawler, E. Fonda, J. Sokolovskaya, G. Hermos, J. TI PROTON PUMP INHIBITORS AND RISK FOR RECURRENT CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Linsky, A.] Boston Med Ctr, Boston, MA USA. [Gupta, K.; Hermos, J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gupta, K.; Lawler, E.; Fonda, J.; Sokolovskaya, G.; Hermos, J.] VA Boston Healthcare Syst, MAVERIC, VA Cooperat Studies Program, Boston, MA USA. [Lawler, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 148 EP 149 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000395 ER PT J AU Farmer, MF Yano, EM Sherman, S Mitchell, MN Riopelle, DD AF Farmer, M. F. Yano, E. M. Sherman, S. Mitchell, M. N. Riopelle, D. D. TI QUALITY IMPROVEMENT METHODS USED TO PROMOTE ADHERENCE TO GUIDELINES FOR SMOKING CESSATION TREATMENT SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Farmer, M. F.; Yano, E. M.; Mitchell, M. N.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Sherman, S.] NYU, Sch Med, New York, NY USA. [Riopelle, D. D.] VA Greater Los Angeles HSR&D Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 153 EP 153 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000406 ER PT J AU Saha, S Newman, P Morse, E AF Saha, S. Newman, P. Morse, E. TI RACE CONCORDANCE AND PATIENT DECISION-MAKING: A STUDY USING STANDARDIZED PHYSICIANS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Newman, P.; Morse, E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 155 EP 155 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000411 ER PT J AU Lopez, L Wilper, A Green, AR Betancourt, J AF Lopez, L. Wilper, A. Green, A. R. Betancourt, J. TI RACIAL AND GENDER DIFFERENCES IN EMERGENCY ROOM TRIAGE ASSESSMENT AND TEST ORDERING FOR CHEST PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Lopez, L.] Harvard Univ, Boston, MA 02115 USA. [Wilper, A.] Univ Washington, Boise, ID USA. [Green, A. R.; Betancourt, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 156 EP 156 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000414 ER PT J AU Green, AR Renfrew, MR Horta, A Chase, BB Sanchez, E Figueroa, JF Betancourt, JR AF Green, A. R. Renfrew, M. R. Horta, A. Chase, B. B. Sanchez, E. Figueroa, J. F. Betancourt, J. R. TI REDUCING RACIAL AND ETHNIC DISPARITIES IN DIABETES: RESULTS FROM AN INNOVATIVE AND CULTURALLY COMPETENT QUALITY IMPROVEMENT PROGRAM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Green, A. R.; Renfrew, M. R.; Betancourt, J. R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Horta, A.; Chase, B. B.; Sanchez, E.] Massachusetts Gen Hosp, Chelsea, MA USA. [Figueroa, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 160 EP 160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000425 ER PT J AU Sinha, S Schwartz, MD Ross, JS AF Sinha, S. Schwartz, M. D. Ross, J. S. TI SELF-REPORTED AND ACTUAL BETA-BLOCKER PRESCRIBING FOR HF PATIENTS: PHYSICIAN PREDICTORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Sinha, S.] James J Peters VA Med Ctr, Bronx, NY USA. [Schwartz, M. D.] NYU, New York, NY USA. [Ross, J. S.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 168 EP 168 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000448 ER PT J AU Chen, LM Jha, AK AF Chen, L. M. Jha, A. K. TI SOLO PRACTICES: THEIR PATIENTS, QUALITY OF CARE, AND RESOURCE USE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Chen, L. M.; Jha, A. K.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 172 EP 173 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000459 ER PT J AU Starrels, JL Becker, WC Alford, DP Williams, AR Turner, BJ AF Starrels, J. L. Becker, W. C. Alford, D. P. Williams, A. R. Turner, B. J. TI SYSTEMATIC REVIEW: PREVALENCE AND EFFECTIVENESS OF IMPLEMENTING OPIOID TREATMENT AGREEMENTS FOR PRIMARY CARE PATIENTS WITH CHRONIC PAIN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Starrels, J. L.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Starrels, J. L.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Becker, W. C.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Alford, D. P.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Williams, A. R.; Turner, B. J.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 176 EP 176 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000469 ER PT J AU Nelson, K Lurie, N Escarce, J Taylor, L Lynne, M Fihn, SD AF Nelson, K. Lurie, N. Escarce, J. Taylor, L. Lynne, M. Fihn, S. D. TI THE IMPACT OF NEIGHBORHOOD ENVIRONMENT ON VETERAN HEALTH STATUS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Nelson, K.; Fihn, S. D.] Univ Washington, Seattle, WA 98195 USA. [Lurie, N.] RAND Corp, Arlington, VA USA. [Escarce, J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Taylor, L.; Lynne, M.] VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 186 EP 187 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000497 ER PT J AU Snyder, CF Frick, KD Herbert, RJ Blackford, AL Neville, BA Carducci, MA Earle, CC AF Snyder, C. F. Frick, K. D. Herbert, R. J. Blackford, A. L. Neville, B. A. Carducci, M. A. Earle, C. C. TI THE PRIMARY CARE PROVIDER'S (PCP) ROLE IN THE CARE OF PROSTATE CANCER SURVIVORS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Snyder, C. F.; Frick, K. D.; Herbert, R. J.; Blackford, A. L.; Carducci, M. A.] Johns Hopkins Univ, Baltimore, MD USA. [Neville, B. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Earle, C. C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 190 EP 190 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000506 ER PT J AU Desroches, CM David, B Campbell, EG Vogeli, C Karen, D Zheng, J Jha, AK AF Desroches, C. M. David, B. Campbell, E. G. Vogeli, C. Karen, D. Zheng, J. Jha, A. K. TI THE RELATIONSHIP BETWEEN THE USE OF ELECTRONIC HEALTH RECORDS AND QUALITY OF CARE IN US HOSPITALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Desroches, C. M.; Campbell, E. G.; Vogeli, C.; Karen, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [David, B.] Inst Hlth Policy, MGH, Boston, MA USA. [Zheng, J.; Jha, A. K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 193 EP 193 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000514 ER PT J AU Hong, CS Atlas, SJ Chang, Y Ashburner, J Barry, MJ Grant, RW AF Hong, C. S. Atlas, S. J. Chang, Y. Ashburner, J. Barry, M. J. Grant, R. W. TI THE RELATIONSHIP BETWEEN PHYSICIAN QUALITY MEASURES AND PATIENT PANEL CHARACTERISTICS IN A LARGE ACADEMIC HEALTH CARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Hong, C. S.; Grant, R. W.] Harvard Univ, Boston, MA 02115 USA. [Atlas, S. J.; Chang, Y.; Ashburner, J.; Barry, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 193 EP 193 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000513 ER PT J AU Baggett, TP Rigotti, NA AF Baggett, T. P. Rigotti, N. A. TI THE UNMET HEALTH CARE NEEDS OF HOMELESS ADULTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Baggett, T. P.; Rigotti, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 195 EP 195 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000520 ER PT J AU Jha, AK Desroches, CM Campbell, EG Donelan, K Ferris, TG Shields, A Rosenbaum, S Blumenthal, D AF Jha, A. K. Desroches, C. M. Campbell, E. G. Donelan, K. Ferris, T. G. Shields, A. Rosenbaum, S. Blumenthal, D. TI THE USE OF ELECTRONIC HEALTH RECORDS IN US HOSPITALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Jha, A. K.] Harvard Univ, Boston, MA 02115 USA. [Desroches, C. M.; Campbell, E. G.; Donelan, K.; Ferris, T. G.; Shields, A.; Blumenthal, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenbaum, S.] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2009 VL 24 SU 1 BP 195 EP 196 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000521 ER PT J AU Rose, AJ Berlowitz, DR Manze, M Orner, MB Kressin, NR AF Rose, A. J. Berlowitz, D. R. Manze, M. Orner, M. B. Kressin, N. R. TI TREATMENT INTENSIFICATION IMPROVES BLOOD PRESSURE CONTROL BOTH IN ADHERENT AND NON-ADHERENT PATIENTS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Rose, A. J.; Berlowitz, D. R.; Orner, M. B.] Bedford VA Med Ctr, Bedford, MA USA. [Manze, M.] Boston Univ, Boston, MA 02215 USA. [Kressin, N. R.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 201 EP 201 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000533 ER PT J AU Cohen, MJ Mccannon, JB Edgman-Levitan, S Kormos, WA AF Cohen, M. J. Mccannon, J. B. Edgman-Levitan, S. Kormos, W. A. TI UNDERSTANDING BARRIERS TO COMPLETING ADVANCE CARE DIRECTIVES IN TWO CULTURALLY DIVERSE PRIMARY CARE SETTINGS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Cohen, M. J.] Massachusetts Gen Hosp, Chelsea, MA USA. [Mccannon, J. B.] Massachusetts Gen Hosp, Revere, MA USA. [Edgman-Levitan, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kormos, W. A.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 203 EP 203 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000540 ER PT J AU Korthuis, T Saha, S Moore, RD Cohn, JA Sharp, V Mccarty, D Beach, MC AF Korthuis, T. Saha, S. Moore, R. D. Cohn, J. A. Sharp, V. Mccarty, D. Beach, M. C. TI UNHEALTHY ALCOHOL USE AND QUALITY OF PATIENT-PROVIDER COMMUNICATION IN HIV CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Korthuis, T.; Mccarty, D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Moore, R. D.; Beach, M. C.] Johns Hopkins Univ, Baltimore, MD USA. [Cohn, J. A.] Wayne State Univ, Detroit, MI USA. [Sharp, V.] St Lukes Roosevelt Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 205 EP 205 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000545 ER PT J AU Salanitro, A Castiglioni, A Willett, LL Shewchuk, RM Qu, H Heudebert, GR Centor, RM AF Salanitro, A. Castiglioni, A. Willett, L. L. Shewchuk, R. M. Qu, H. Heudebert, G. R. Centor, R. M. TI USING COGNITIVE MAPPING TO IDENTIFY FACULTY PERSPECTIVES FOR SUCCESSFUL WARD ATTENDING ROUNDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Castiglioni, A.] Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 209 EP 209 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000554 ER PT J AU Salanitro, A Estrada, CA Safford, MM Curry, W Houston, TK Williams, J Ovalle, F Allison, JJ AF Salanitro, A. Estrada, C. A. Safford, M. M. Curry, W. Houston, T. K. Williams, J. Ovalle, F. Allison, J. J. TI USING PATIENT COMPLEXITY TO INFORM PHYSICIAN PROFILES IN THE PAY-FOR-PERFORMANCE ERA SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Salanitro, A.; Estrada, C. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Safford, M. M.; Curry, W.; Houston, T. K.; Williams, J.; Ovalle, F.; Allison, J. J.] Univ Alabama, Birmingham, AL USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 211 EP 212 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000561 ER PT J AU Gellad, WF Lowe, JC Good, CB AF Gellad, W. F. Lowe, J. C. Good, C. B. TI VARIATION IN PRESCRIPTION DRUG SPENDING IN THE VA HEALTHCARE SYSTEM AND THE RELATIONSHIP TO QUALITY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Gellad, W. F.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, W. F.] RAND Hlth, Pittsburgh, PA USA. [Lowe, J. C.] VHA Pharm Benefits Management, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000565 ER PT J AU Kim, AE Kamyab, K Zhu, J Volpp, K AF Kim, A. E. Kamyab, K. Zhu, J. Volpp, K. TI WHY ARE FINANCIAL INCENTIVES NOT EFFECTIVE AT INFLUENCING SOME SMOKERS TO QUIT? RESULTS FROM A PROCESS EVALUATION SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Kim, A. E.; Kamyab, K.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Zhu, J.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Volpp, K.] Univ Penn, Sch Med, Ctr Hlth Incent, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Volpp, K.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, K.] Philadelphia VA Med Cen, CHERP, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 219 EP 220 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000582 ER PT J AU Yano, EM Bean-Mayberry, B Ash, DR Canelo, IA Washington, DL AF Yano, E. M. Bean-Mayberry, B. Ash, D. Rose Canelo, I. A. Washington, D. L. TI WOMEN AND WAR: HOW ARE VETERANS HEALTH ADMINISTRATION (VA) FACILITIES ADAPTING TO THEIR CHANGING DEMOGRAPHICS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Yano, E. M.; Bean-Mayberry, B.; Ash, D. Rose; Canelo, I. A.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Washington, D. L.] VA Greater Los Angeles HSR&D Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 220 EP 221 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000584 ER PT J AU Bradley, SM Atanous, A Karani, R AF Bradley, S. M. Atanous, A. Karani, R. TI IMPACT OF A STUDENT-DIRECTED FALL RISK MODULE IN AMBULATORY GERIATRICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Bradley, S. M.; Karani, R.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. [Atanous, A.] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 229 EP 230 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000608 ER PT J AU Thompson, RW Krauthamer, MB Iezzoni, LI AF Thompson, R. W. Krauthamer, M. B. Iezzoni, L. I. TI THE HEALTH POLICY SEMINAR FOR RESIDENTS: AN INNOVATIVE CURRICULUM TO INCREASE RESIDENT UNDERSTANDING OF THE US HEALTHCARE SYSTEM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Thompson, R. W.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Krauthamer, M. B.] Dept Vet Affairs, Women Vet Hlth Strateg Hlth Care Grp, Washington, DC USA. [Iezzoni, L. I.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 245 EP 245 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000646 ER PT J AU Stahl, J Balasubramanian, H Banerjee, R Denton, B AF Stahl, J. Balasubramanian, H. Banerjee, R. Denton, B. TI IMPROVING CLINICAL ACCESS AND CONTINUITY THROUGH PHYSICIAN PANEL RE-DESIGN SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Stahl, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Balasubramanian, H.] Univ Massachusetts, Amherst, MA 01003 USA. [Banerjee, R.] Mayo Clin, Rochester, MN USA. [Denton, B.] N Carolina State Univ, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 254 EP 254 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000670 ER PT J AU Russell, SL AF Russell, S. L. TI TRAINEE SAFETY AT HOME AND ABROAD: A PRACTICE INNOVATION IN RESOURCE-POOR HOSPITAL SETTINGS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Russell, S. L.] Massachusetts Gen Hosp, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 260 EP 260 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000686 ER PT J AU Stahl, JE Holt, J Gagliano, N AF Stahl, J. E. Holt, J. Gagliano, N. TI USING RFID IN THE OUTPATIENT SETTING: INITIAL EXPERIENCE COMPARING 2 CLINICS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Stahl, J. E.] Harvard Univ, Boston, MA 02115 USA. [Holt, J.; Gagliano, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 261 EP 261 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000688 ER PT J AU Carruthers, RL Finn, KM AF Carruthers, R. L. Finn, K. M. TI A FAMILIAR FACE IN A FOREIGN PLACE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Carruthers, R. L.; Finn, K. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 274 EP 274 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000723 ER PT J AU Fung, PH Kolpakchi, AL Lu, L AF Fung, P. H. Kolpakchi, A. L. Lu, L. TI A LETHAL RASH SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Fung, P. H.; Lu, L.] Baylor Coll Med, Houston, TX 77030 USA. [Kolpakchi, A. L.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 274 EP 275 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000724 ER PT J AU Kunkel, DC Cheng, ET AF Kunkel, D. C. Cheng, E. T. TI ASBESTOS: INSULATING YOU FROM THE CORRECT DIAGNOSIS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Kunkel, D. C.] Cedars Sinai Internal Med Residency Program, Los Angeles, CA USA. [Cheng, E. T.] Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 293 EP 293 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000774 ER PT J AU Arnaout, R Wright, DE AF Arnaout, R. Wright, D. E. TI BACK TO THE HEART OF THE MATTER SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Arnaout, R.; Wright, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 294 EP 295 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000778 ER PT J AU Gupta, R Puig, A AF Gupta, R. Puig, A. TI THE PERFECT STORM: ACUTE CHYLOMICRONEMIA PRESENTING WITH ERUPTIVE XANTHOMAS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Gupta, R.; Puig, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 367 EP 367 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000975 ER PT J AU Helmer, D Kolpakchi, A AF Helmer, D. Kolpakchi, A. TI TO CARE FOR HIM WHO SHALL HAVE BORNE THE BATTLE SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Helmer, D.; Kolpakchi, A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 369 EP 370 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000981 ER PT J AU Defonseka, AM Cheng, ET AF Defonseka, A. M. Cheng, E. T. TI UNEXPECTED FALLS: AN UNUSUAL MANIFESTATION OF HEPATIC ENCEPHALOPATHY TRIGGERED BY ANTI-VIRAL THERAPY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Defonseka, A. M.; Cheng, E. T.] Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2009 VL 24 SU 1 BP 371 EP 371 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382000986 ER PT J AU Lal, S Chiappa, V AF Lal, S. Chiappa, V. TI WHY DOES THIS 28 YEAR OLD MALE HAVE CONGESTIVE HEART FAILURE? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med C1 [Lal, S.] Harvard Univ, Sch Med, Boston, MA USA. [Chiappa, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2009 VL 24 SU 1 BP 377 EP 377 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 435ZI UT WOS:000265382001001 ER PT J AU Au, DH Bryson, CL Chien, JW Sun, HL Udris, EM Evans, LE Bradley, KA AF Au, David H. Bryson, Christopher L. Chien, Jason W. Sun, Haili Udris, Edmunds M. Evans, Laura E. Bradley, Katharine A. TI The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; exacerbation; smoking cessation ID LUNG-FUNCTION; AIRWAY INFLAMMATION; COST-EFFECTIVENESS; HEALTH; COPD; SMOKERS; INTERVENTION; SYMPTOMS; SPUTUM; PREVENTION AB Smoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations. We sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations. We assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation. We performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US. In comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75-0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit < 1 year, 1.04; 95% CI 0.87-1.26; 1-5 years 0.93, 95% CI 0.79-1.08; 5-10 years 0.84, 95% CI 0.70-1.00; a parts per thousand yen10 years 0.65, 95% CI 0.58-0.74; linear trend < 0.001). Smoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence. C1 [Au, David H.; Bryson, Christopher L.; Sun, Haili; Udris, Edmunds M.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Au, David H.; Bryson, Christopher L.; Chien, Jason W.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Chien, Jason W.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Evans, Laura E.] NYU, Dept Med, New York, NY 10016 USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way 152, Seattle, WA 98108 USA. EM dau@u.washington.edu FU Department of Veterans Affairs [IAC 05-206, IIR-99-376]; VA Career Development Award [RCS 03-177] FX David Au had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was funded by the Department of Veterans Affairs: IAC 05-206 and IIR-99-376. Dr. Bryson is funded by a VA Career Development Award (RCS 03-177). NR 37 TC 36 Z9 36 U1 2 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 APR PY 2009 VL 24 IS 4 BP 457 EP 463 DI 10.1007/s11606-009-0907-y PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 423GJ UT WOS:000264484500003 PM 19194768 ER PT J AU Wong, MD Ettner, SL Boscardin, WJ Shapiro, MF AF Wong, Mitchell D. Ettner, Susan L. Boscardin, W. John Shapiro, Martin F. TI The Contribution of Cancer Incidence, Stage at Diagnosis and Survival to Racial Differences in Years of Life Expectancy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE racial differences; cancer mortality; survival; life expectancy ID LOCALIZED PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; UNITED-STATES; LUNG-CANCER; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; WHITE WOMEN; BLACK; MORTALITY AB African Americans have higher cancer mortality rates than whites. Understanding the relative contribution of cancer incidence, stage at diagnosis and survival after diagnosis to the racial gap in life expectancy has important implications for directing future health disparity interventions toward cancer prevention, screening and treatment. We estimated the degree to which higher cancer mortality among African Americans is due to higher incidence rates, later stage at diagnosis or worse survival after diagnosis. Stochastic model of cancer incidence and survival after diagnosis. Surveillance and Epidemiology End Result cancer registry and National Health Interview Survey data. Life expectancy if African Americans had the same cancer incidence, stage and survival after diagnosis as white adults. African-American men and women live 1.47 and 0.91 fewer years, respectively, than whites as the result of all cancers combined. Among men, racial differences in cancer incidence, stage at diagnosis and survival after diagnosis account for 1.12 (95% CI: 0.52 to 1.36), 0.17 (95% CI: -0.03 to 0.33) and 0.21 (95% CI: 0.05 to 0.34) years of the racial gap in life expectancy, respectively. Among women, incidence, stage and survival after diagnosis account for 0.41 (95% CI: -0.29 to 0.60), 0.26 (95% CI: -0.06 to 0.40) and 0.31 (95% CI: 0.05 to 0.40) years, respectively. Differences in stage had a smaller impact on the life expectancy gap compared with the impact of incidence. Differences in cancer survival after diagnosis had a significant impact for only two cancers-breast (0.14 years; 95% CI: 0.05 to 0.16) and prostate (0.05 years; 95% CI 0.01 to 0.09). In addition to breast and colorectal cancer screening, national efforts to reduce disparities in life expectancy should also target cancer prevention, perhaps through smoking cessation, and differences in survival after diagnosis among persons with breast and prostate cancer. C1 [Wong, Mitchell D.; Ettner, Susan L.; Shapiro, Martin F.] Univ Calif Los Angeles, Div GIM HSR, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Boscardin, W. John] San Francisco Vet Adm Med Ctr, Div Geriatr, San Francisco, CA USA. RP Wong, MD (reprint author), Univ Calif Los Angeles, Div GIM HSR, David Geffen Sch Med, 911 Broxton Ave,Suite 101, Los Angeles, CA 90024 USA. EM mitchellwong@mednet.ucla.edu OI Wong, Mitchell/0000-0002-4800-8410 FU National Institute on Aging [1K08AG/HS21616-05]; Pfizer Scholars Grant; National Institutes of Minority Health and Health Disparities [1P20MD000148-01] FX This work was supported by a K08 Mentored Scientist Award (1K08AG/HS21616-05) from the National Institute on Aging, a Pfizer Scholars Grant in Clinical Epidemiology and Doris Duke Charitable Foundation Clinical Scientist Development Award to Dr. Wong and the UCLA-Drew Project Export from the National Institutes of Minority Health and Health Disparities (1P20MD000148-01). NR 51 TC 15 Z9 15 U1 2 U2 6 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 APR PY 2009 VL 24 IS 4 BP 475 EP 481 DI 10.1007/s11606-009-0912-1 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 423GJ UT WOS:000264484500006 PM 19189193 ER PT J AU Halpin, CF Iezzoni, LI Rauch, S AF Halpin, Christopher F. Iezzoni, Lisa I. Rauch, Steven TI Medical Record Documentation of Patients' Hearing Loss by Physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hearing loss; electronic medical record; patient communication ID HARD-OF-HEARING AB Anecdotal evidence suggests that hearing loss, even when sufficient to prevent full access to spoken communication, often is underreported by patients and not documented by physicians. No published studies have investigated this issue quantitatively. To assess the documentation of hearing loss in comprehensive physician notes in cases where the patients are known to have substantial binaural loss. Electronic medical record (EMR) notes for 100 consecutive patients with substantial binaural hearing loss were reviewed retrospectively at a large academic medical center. All records reviewed were created within 2 years before the patient's audiometry. Comprehensive physician notes containing the headings "History" and "Physical Exam" were examined for documentation of hearing loss and scored as: no mention of loss; finding of loss; or hearing reported as normal. Consecutive adult patients with substantial binaural hearing loss by audiometry who also had a comprehensive medical assessment in their electronic medical record created within 2 years before audiometry. Thirty-six percent of EMRs had no mention of hearing loss, 28% reported some loss, and 36% percent indicated that hearing was normal. Substantial hearing loss, sufficient to prevent effective communication in the medical setting, often is underdocumented in medical records. C1 [Halpin, Christopher F.] Harvard Univ, Sch Med, Dept Audiol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Iezzoni, Lisa I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. [Rauch, Steven] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Halpin, CF (reprint author), Harvard Univ, Sch Med, Dept Audiol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM cfhalpin@meei.harvard.edu NR 6 TC 6 Z9 6 U1 0 U2 0 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 APR PY 2009 VL 24 IS 4 BP 517 EP 519 DI 10.1007/s11606-009-0911-2 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 423GJ UT WOS:000264484500013 PM 19184241 ER PT J AU Rivier, D Paula, JS Kim, E Dohlman, CH Grosskreutz, CL AF Rivier, Delphine Paula, Jayter S. Kim, Eva Dohlman, Claes H. Grosskreutz, Cynthia L. TI Glaucoma and Keratoprosthesis Surgery Role of Adjunctive Cyclophotocoagulation SO JOURNAL OF GLAUCOMA LA English DT Article DE glaucoma; keratoprosthesis; diode laser transscleral cyclophotocoagulation ID DIODE-LASER CYCLOPHOTOCOAGULATION; INTRAOCULAR-PRESSURE; REFRACTORY GLAUCOMA; PENETRATING KERATOPLASTY; PHOTOCOAGULATION; PALPATION; SHUNT AB Purpose: To evaluate the efficacy and safety of diode laser transscleral cyclophotocoagulation (DLTSC) to control intraocular pressure (IOP) in keratoprosthesis patients with uncontrolled glaucoma. Patients and Methods: Between 1993 and 2007, 18 eyes of 18 patients underwent DLTSC, either before (n = 3), during (n = I), or after (n = 14) keratoprosthesis surgery. Keratoprosthesis type 1 was used in 72%. All but one of these patients received an Ahmed Glaucoma Valve, either with or after the keratoprosthesis placement. Best-corrected visual acuity, IOP (assessed by digital palpation), number of medications, and complications were recorded preoperatively, at day 7, at 1, 3, and 6 months then every 6 months postoperatively. Results: Mean follow-tip was 26.6 +/- 19.6 months (mean +/- SD) and mean age was 50.1 +/- 15.6 years. Glaucoma was identified in 1 I eyes before keratoprosthesis surgery and in 7 eyes after. Mean postoperative IOP was significantly reduced at 6, 12, 24, 36, and 48 months after DLTSC. DLTSC was repeated in 6 eyes. At final visit, mean best-corrected visual acuity was not decreased and there were no statistically significant differences in the number of glaucoma medications. Two patients had complications after DLTSC: a conjunctival dehiscence and a fungal endophthalmitis. Conclusions: DLTSC has beneficial long-term effects in the control of IOP and can be considered in the management of keratoprosthesis patients with refractory glaucoma. C1 [Grosskreutz, Cynthia L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Consultat Serv, Boston, MA 02114 USA. [Dohlman, Claes H.] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. [Rivier, Delphine] Univ Lausanne, Dept Ophthalmol, Jules Gonin Eye Hosp, Lausanne, Switzerland. [Paula, Jayter S.] Univ Sao Paulo, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, Sch Med Ribeirao Preto, Sao Paulo, Brazil. RP Grosskreutz, CL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu RI PAULA, JAYTER/D-1249-2013 OI PAULA, JAYTER/0000-0002-8111-3810 NR 21 TC 25 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD APR-MAY PY 2009 VL 18 IS 4 BP 321 EP 324 PG 4 WC Ophthalmology SC Ophthalmology GA 434JL UT WOS:000265270900011 PM 19365199 ER PT J AU Mirza, A Jupiter, JB Reinhart, MK Meyer, P AF Mirza, Ather Jupiter, Jesse B. Reinhart, Mary Kate Meyer, Patricia TI Fractures of the Distal Radius Treated With Cross-Pin Fixation and a Nonbridging External Fixator, the CPX System: A Preliminary Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fractures; nonbridging external fixator; Cross-Pin fixator system ID DISPLACED INTRAARTICULAR FRACTURES; REDISPLACED UNSTABLE FRACTURES; INTERNAL-FIXATION; COLLES FRACTURES; OPEN REDUCTION; YOUNG-ADULTS; ARTICULAR FRACTURES; WRIST FRACTURES; ULNAR VARIANCE; END AB Purpose To present the preliminary findings of distal radius fractures (DRF) treated with percutaneous cross-pin fixation and a nonbridging external fixator, the Cross-Pin Fixation (CPX) system. Methods Thirty-five consecutive patients with 37 DRFs were selected from a series of 51 DRFs for closed reduction, percutaneous pinning, and external fixation with the CPX system. Outcome was determined by studying (1) radiological measurements of radial height, palmar tilt, radial inclination and ulnar variance (UV); (2) grip and pinch strength; (3) wrist active range of motion; and (4) patient outcome instruments-the Patient-Rated Wrist Hand Evaluation and the Disabilities of the Arm, Shoulder, and Hand. Results We are reporting, on 21 patients, 13 females and 8 males, mean age 54 years (range, 27 to 87 y) with AO type fractures A2, B2, B3, C1, C2, and C3. Follow-up was a minimum of I year (range, 12 to 36 months). Wrist rehabilitation began at a mean of 10 days (range, 4 to 16 d) after surgery. There was no loss of reduction. Final mean grip and lateral pinch strength recovered 86% and 94%, respectively, and active range of motion increased to a minimum of 89% of the noninjured side. Disabilities of the Arm, Shoulder, and Hand showed change in functional status (minimal detectable change at 95% confidence level) at 4 and 12 weeks. The Patient-Rated Wrist Hand Evaluation results reported resumption of usual activities in the early postoperative period. One patient developed type I complex regional pain syndrome, which resolved, and one patient had residual transient mild superficial radial nerve sensitivity. There were no pin track infections, nonunions, or tendon injuries. All patients returned to their prior employment and activities. Conclusions The CPX system is a minimally invasive technique of closed reduction and internal fixation for displaced reducible extra-articular and nondisplaced and displaced reducible intraarticular fractures of the distal radius, allowing rehabilitation of the wrist and resumption of usual activities while maintaining fracture reduction. (J Hand Surg 2009;34A:603-616 Copyright (c) 2009 by the American Society for Surgery of the Hand. All rights reserved.) C1 St Catherine Siena Med Ctr, Smithtown, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Long Isl Hand Rehabil Ctr, Smithtown, NY USA. RP Mirza, A (reprint author), 290 E Main St,Suite 200, Smithtown, NY 11787 USA. EM amirza@amsurgical.com NR 83 TC 8 Z9 11 U1 1 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2009 VL 34A IS 4 BP 603 EP 616 DI 10.1016/j.jhsa.2008.12.020 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 430OQ UT WOS:000264998800002 PM 19345862 ER PT J AU Ring, D AF Ring, David TI Open Reduction and Internal Fixation of an Apparent Capitellar Fracture Using an Extended Lateral Exposure SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Capitellum and trochlear fractures; open reduction and internal fixation; extended lateral exposure of the elbow ID DISTAL HUMERAL FRACTURES; CAPITULUM HUMERI; MANAGEMENT AB Apparent fractures of the capitellum are often more complex involving the trochlea and the posterior aspect of the lateral column. Many of these fractures can be addressed through an extended lateral exposure, but fixation techniques specific to small, nearly entirely articular fragments will be necessary. When the fracture fragments do not fit, there is usually posterior impaction of the lateral column and sometimes the posterior trochlea. (J Hand Surg 2009: 34A.-739-744. (c) 2009 Published by Elsevier Inc. on. behalf of the American Society for Surgery of the Hand.) C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Trauma Serv, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Trauma Serv, Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 21 TC 5 Z9 8 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD APR PY 2009 VL 34A IS 4 BP 739 EP 744 DI 10.1016/j.jhsa.2009.01.026 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 430OQ UT WOS:000264998800022 PM 19345881 ER PT J AU Kim, KA Lin, W Tai, AW Shao, RX Weinberg, E Borges, CB Bhan, AK Zheng, H Kamegaya, Y Chung, RT AF Kim, Kyung-Ah Lin, Wenyu Tai, Andrew W. Shao, Run-Xuan Weinberg, Ethan De Sa Borges, Carolina B. Bhan, Atul K. Zheng, Hui Kamegaya, Yoshitaka Chung, Raymond T. TI Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection SO JOURNAL OF HEPATOLOGY LA English DT Article DE Suppressor of cytokine signaling 3; Hepatitis C virus; HCV/HIV coinfection; Race; Immunohistochemistry; Signal transducer and activator of transcription 1 ID C VIRUS-INFECTION; ALPHA-2A PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; ANTIVIRAL THERAPY; CYTOKINE SIGNALING-3; GENE-EXPRESSION; INTERFERON; SUPPRESSOR; CYTOKINE-SIGNALING-3; POLYMORPHISMS AB Background/Aims: The response rates of HCV infection to interferon therapy vary depending on viral and host factors. We hypothesized that key regulators of the IFN signaling pathway are predictive of treatment outcome. Methods: We measured the expression of signal transducer and activator of transcription 1 (STAT1) and suppressor of cytokine signaling 3 (SOCS3) in pretreatment liver biopsies. Staining quantitation was compared to treatment outcomes. Results:Forty-nine patients with HCV and 25 patients with HCV/HIV infection treated with peginterferon/ribavirin were analyzed. Pretreatment hepatic SOCS3 expression was higher in non-responders than responders. Genotype 1 responders had similar levels of SOCS3 as genotype 213 responders. African Americans (AA) had higher hepatic SOCS3 than non-AA. Pretreatment hepatic SOCS3 was the most powerful independent predictor of sustained virologic response (SVR), even more so than genotype by logistic regression analysis. Failure to achieve SVR and AA race were independently associated with high hepatic SOCS3 levels. The hepatic expression of STAT-1 did not differ between responders and non-responders. Conclusions: Our data indicate that hepatic SOCS3 is a stronger baseline predictor of antiviral response than viral genotype. Poor response to antiviral therapy in AA may be associated with higher hepatic SOCS3 expression. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Kim, Kyung-Ah; Lin, Wenyu; Tai, Andrew W.; Shao, Run-Xuan; Weinberg, Ethan; De Sa Borges, Carolina B.; Kamegaya, Yoshitaka; Chung, Raymond T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Kim, Kyung-Ah] Inje Univ, Ilsan Paik Hosp, Dept Med, Goyang, South Korea. [Zheng, Hui] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat,Dept Med, Boston, MA 02114 USA. [Bhan, Atul K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org OI Tai, Andrew/0000-0002-6877-450X FU NIH [AI38858, AI38855] FX We gratefully acknowledge the NIAID-AIDS Clinical Trials Group for biopsy material For these studies (NIH AI38858 and AI38855). NR 21 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2009 VL 50 IS 4 BP 705 EP 711 DI 10.1016/j.jhep.2008.12.021 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 437UO UT WOS:000265512600014 PM 19231005 ER PT J AU Chen, LM Freitag, MH Franco, M Sullivan, CD Dickson, C Brancati, FL AF Chen, Lena M. Freitag, Michael H. Franco, Manuel Sullivan, Christopher D. Dickson, Conan Brancati, Frederick L. TI Natural History of Late Discharges from a General Medical Ward SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE discharge; efficiency; length of stay; patient flow ID LENGTH-OF-STAY; RANDOMIZED CLINICAL-TRIAL; PSYCHIATRIC COMORBIDITY; EMERGENCY-DEPARTMENTS; REGIONAL-VARIATIONS; HOSPITAL DISCHARGE; HEART-FAILURE; UNITED-STATES; CARE; HEALTH AB BACKGROUND: Slow hospital discharges reduce efficiency and compromise care for patients awaiting a bed. Although efficient discharge is a widely held goal, the natural history of the discharge process has not been well Studied. OBJECTIVE: To describe the discharge process and identify factors associated with longer and later discharges. DESIGN: Prospective cohort study. SETTING: A general medicine ward without house-staff coverage, in a tertiary care hospital (The Johns Hopkins Hospital) in Baltimore, Maryland, from January 1, 2005 to April 30, 2005. PATIENTS: Two hundred and nine consecutively discharged adult inpatients. MEASUREMENTS: Discharge time (primary outcome) and discharge duration (secondary outcome). RESULTS: Median discharge time was 3:09 PM (25th% to 75th%: 1:08 to 5:00 PM) In adjusted analysis, discharge time was associated with ambulance used on discharge (1.5 hours), prescriptions filled prior to discharge (1.4 hours), subspecialty Consult prior to discharge (1.2 hours), and procedure prior to discharge (1.1 hours). Median duration of the discharge process was 7 hours 34 minutes (25th% to 75th%: 4.0 to 22.0 hours). Discharge duration was associated with discharge to a location other than home (28.9 hours), and with need for consultation (14.8 hours) or a procedure (13.4 hours) prior to discharge (all P values < 0.05). CONCLUSIONS: Discharge time and duration have wide variability Longer and later discharges were associated with procedures and Consults. Successful efforts to decrease time of discharge will require broad institutional effort to improve delivery of interdepartmental services. Journal of Hospital Medicine 2009;4:226-233. (C) 2009 Society of Hospital Medicine. C1 [Chen, Lena M.] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. [Freitag, Michael H.] Univ Bayreuth, Inst Med Management & Gesundheitswissensch, Bayreuth, Germany. [Franco, Manuel; Brancati, Frederick L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Dickson, Conan] Johns Hopkins Hlth Syst, Operat Support, Baltimore, MD USA. [Brancati, Frederick L.] Johns Hopkins Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Sullivan, Christopher D.] Excela Hlth, Greensburg, PA USA. RP Chen, LM (reprint author), VA Boston Healthcare Syst, MAVERIC, 150 S Huntington Ave,151 MAV, Boston, MA 02130 USA. EM lmchen@partners.org RI Freitag, Michael/G-4887-2011 OI Freitag, Michael/0000-0002-7572-2011 FU Johns Hopkins Center for Innovation in Quality Patient Care and the Johns Hopkins Department of Medicine FX Supported by the Johns Hopkins Center for Innovation in Quality Patient Care and the Johns Hopkins Department of Medicine. This material is in part the result of work supported with resources and the use of facilities at the Boston VA Medical Center. Earlier versions of the abstract were presented at: Kongress der Deutschen Gesellschaft fur Innere Medizin, April 22-26, 2006; Society of Hospital Medicine Annual Meeting, May 3-5, 2006; and Johns Hopkins Department of Medicine Research Retreat, April 2005. NR 46 TC 4 Z9 4 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD APR PY 2009 VL 4 IS 4 BP 226 EP 233 DI 10.1002/jhm.413 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 440LG UT WOS:000265701200005 PM 19388081 ER PT J AU Krum, H Swergold, G Curtis, SP Kaur, A Wang, HW Smugar, SS Weir, MR Laine, L Brater, DC Cannon, CP AF Krum, Henry Swergold, Gary Curtis, Sean P. Kaur, Amarjot Wang, Hongwei Smugar, Steven S. Weir, Matthew R. Laine, Loren Brater, D. Craig Cannon, Christopher P. TI Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study SO JOURNAL OF HYPERTENSION LA English DT Article DE antihypertensive drugs; blood pressure; calcium channel blockers; diclofenac; etoricoxib; hypertension; multivariate analysis; NSAID; risk factor ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 INHIBITORS; CARDIOVASCULAR OUTCOMES; SYSTOLIC HYPERTENSION; TRIAL; METAANALYSIS; ARTHRITIS; EVENTS; DESIGN AB Objective To evaluate the hypertensive effects of etoricoxib and diclofenac relative to baseline hypertension risk factors in arthritis patients. Methods Multivariate analysis of data from the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) study (n = 23 504). We evaluated risk factors for change in systolic blood pressure (BP) (SBP) and diastolic BP (DBP) at 4 months versus baseline; exceeding predefined limits of change (PLoC) in BID anytime during the study; and the effect of concomitant anti hypertensive class on SBP and exceeding SBP PLoC. Results Increased SBP was most highly associated with history of hypertension (+3.04 mmHg; P<0.0001), as were increased DBP (+1.28 mmHg; P<0.0001), and exceeding DBP PLoC [odds ratio (OR) = 1.83; P<0.0001]. Exceeding SBP PLoC (OR = 1.50; P<0.0001) was most highly associated with age at least 65 years. Etoricoxib (vs. diclofenac) was also significantly associated with increased SBP (P<0.0001), DPB (P<0.0001 to P = 0.0015), and exceeding SBP PLoC (P<0.0001 to P=0.002). Compared with no antihypertensive medication, background calcium channel blockers (CCB) were associated with a small, nonsignificant decrease in SBP (-0.60 mmHg) and no increased odds of exceeding SBP PLoC [OR = 1.00 (95% Cl 0.71, 1.42)]. All other antihypertensive classes were associated with either no change or numerically or statistically significantly increased SBP and increased odds of exceeding PLoC. Conclusion History of hypertension and age at least 65 years were most strongly associated with increased BID. Treatment with etoricoxib vs. diclofenac was also a significant factor for increased BID. CCBs appear to maintain antihypertensive effects with concurrent NSAID therapy better than other examined anti hypertensive drug classes. J Hypertens 27:886-893 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Swergold, Gary; Curtis, Sean P.; Kaur, Amarjot; Wang, Hongwei; Smugar, Steven S.] Merck Res Labs, Rahway, NJ USA. [Weir, Matthew R.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Laine, Loren] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Brater, D. Craig] Indiana Univ, Sch Med, Indianapolis, IN USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Krum, H (reprint author), Monash Univ, Alfred Hosp, Dept Epidemiol & Prevent Med, Monash Ctr Cardiovas Res & Educ Therapeut, Melbourne, Vic 3004, Australia. EM henry.krum@med.monash.edu.au FU Merck Co., Inc FX The original Study and Current analyses were funded by Merck & Co., Inc. NR 17 TC 20 Z9 21 U1 0 U2 0 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 APR PY 2009 VL 27 IS 4 BP 886 EP 893 DI 10.1097/HJH.0b013e328325d831 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436ZT UT WOS:000265455800031 PM 19516186 ER PT J AU Ahmed, F Friend, S Barteneva, N Lieberman, J AF Ahmed, Fariyal Friend, Sherree Barteneva, Natasha Lieberman, Judy TI PD-1 traffics to the immunological synapse along the plasma membrane to inhibit CTL cytotoxicity and cytokine secretion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ahmed, Fariyal; Barteneva, Natasha; Lieberman, Judy] Harvard Med Sch, Immune Dis Inst, Boston, MA USA. [Friend, Sherree] AMNIS Corp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 44.25 PG 2 WC Immunology SC Immunology GA V44QN UT WOS:000209763600359 ER PT J AU Ahmed, F Friend, S George, TC Barteneva, N Lieberman, J AF Ahmed, Fariyal Friend, Sherree George, Thaddeus C. Barteneva, Natasha Lieberman, Judy TI Numbers matter: quantitative and dynamic analysis of the formation of a mature immunological synapse using imaging flow cytometry SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Ahmed, Fariyal; Barteneva, Natasha; Lieberman, Judy] Harvard Med Sch, Immune Dis Inst, Boston, MA USA. [Friend, Sherree; George, Thaddeus C.] Amnis Corp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 42.15 PG 2 WC Immunology SC Immunology GA V44QN UT WOS:000209763600324 ER PT J AU Akondy, RS Miller, JD Doho, G Wu, H Zilliox, M de Rio, C Mulligan, MJ Edupuganti, S Haining, WN Ahmed, R AF Akondy, Rama S. Miller, Joseph D. Doho, Gregory Wu, Hong Zilliox, Michael de Rio, Carlos Mulligan, Mark J. Edupuganti, Srilatha Haining, W. Nicholas Ahmed, Rafi TI Molecular signature of human virus specific effector CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akondy, Rama S.; Miller, Joseph D.; Doho, Gregory; Wu, Hong; Zilliox, Michael; de Rio, Carlos; Mulligan, Mark J.; Edupuganti, Srilatha; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Akondy, Rama S.; Miller, Joseph D.; Doho, Gregory; Wu, Hong; Zilliox, Michael; de Rio, Carlos; Mulligan, Mark J.; Edupuganti, Srilatha; Ahmed, Rafi] Emory Univ, Sch Med, Hope Clin, Atlanta, GA USA. [Haining, W. Nicholas] Dana Farber Canc Inst, Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 83.20 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601204 ER PT J AU Bender, TP Allman, DM Rajewsky, K Fahl, SP AF Bender, Timothy P. Allman, David M. Rajewsky, Klaus Fahl, Shawn P. TI c-Myb is crucial for B-lymphocyte development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Bender, Timothy P.; Fahl, Shawn P.] Univ Virginia, Sch Med, Microbiol, Charlottesville, VA 22908 USA. [Allman, David M.] Univ Penn, Sch Med, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Rajewsky, Klaus] Harvard Med Sch, Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763603048 ER PT J AU Denzin, LK Yi, W Wucherpfennig, KW Sant'Angelo, DB AF Denzin, Lisa K. Yi, Woelsung Wucherpfennig, Kai W. Sant'Angelo, Derek B. TI Modulating MHC Class II Antigen Processing in Dendritic Cells Prevents Diabetes in NOD mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Denzin, Lisa K.; Yi, Woelsung; Sant'Angelo, Derek B.] Sloan Kettering Inst, Immunol Program, New York, NY USA. [Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 78.25 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601086 ER PT J AU Gong, D Benarafa, C Hartshorn, KL Remold-O'Donnell, E AF Gong, Dapeng Benarafa, Charaf Hartshorn, Kevan L. Remold-O'Donnell, Eileen TI The neutrophil serine protease inhibitor SerpinB1 protects against inflammatory lung injury and morbidity in influenza virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Gong, Dapeng; Benarafa, Charaf; Remold-O'Donnell, Eileen] Immune Dis Inst, Boston, MA USA. [Gong, Dapeng; Benarafa, Charaf; Remold-O'Donnell, Eileen] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 43.10 PG 2 WC Immunology SC Immunology GA V44QN UT WOS:000209763600346 ER PT J AU Hsu, HC Wang, J Wu, Q Li, J Yang, P Li, H Mountz, JD AF Hsu, Hui-Chen Wang, John Wu, Qi Li, Jun Yang, PingAr Li, Hao Mountz, John D. TI Migration of marginal zone precursor B cells into the T-cell zone promoted by interferon-alpha induces a T-dependent germinal center response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Hsu, Hui-Chen; Wang, John; Wu, Qi; Li, Jun; Yang, PingAr; Li, Hao; Mountz, John D.] Univ Alabama Birmingham, Med, Birmingham, AL USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 99.33 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602071 ER PT J AU Kerdiles, YM Beisner, DR Tinoco, R Dejean, AS Castrillon, DH DePinho, RA Hedrick, SM AF Kerdiles, Yann M. Beisner, Daniel R. Tinoco, Roberto Dejean, Anne S. Castrillon, Diego H. DePinho, Ronald A. Hedrick, Stephen M. TI Foxol links trafficking and survival of nave T cells through regulation of L-selectin, Ccr7 and IL-7Ra expression SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kerdiles, Yann M.; Beisner, Daniel R.; Tinoco, Roberto; Dejean, Anne S.; Hedrick, Stephen M.] UCSD, Cellular & Mol Med, La Jolla, CA USA. [Castrillon, Diego H.; DePinho, Ronald A.] Harvard Med Sch, Dana Farber Canc Inst, Med & Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 82.17 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601184 ER PT J AU Kim, ST Takeuchi, K Sun, ZYJ Touma, M Wagner, G Reinherz, EL AF Kim, Sun Taek Takeuchi, Koh Sun, Zhen-Yu J. Touma, Maki Wagner, Gerhard Reinherz, Ellis L. TI Dynamic alpha beta T cell receptor quaternary structure is linked to its mechanosensor function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Sun Taek; Touma, Maki; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Sun Taek; Takeuchi, Koh; Sun, Zhen-Yu J.; Touma, Maki; Wagner, Gerhard; Reinherz, Ellis L.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 33.27 PG 2 WC Immunology SC Immunology GA V44QN UT WOS:000209763600016 ER PT J AU Kim, YA Carroll, MC AF Kim, Young-A Carroll, Michael C. TI Visualizing interactions of antigen, B cells and FDC in vitro SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Kim, Young-A; Carroll, Michael C.] Harvard Med Sch, IDI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 84.23 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601233 ER PT J AU Lucas, CL Fehr, T Haspot, F Sykes, M AF Lucas, Carrie L. Fehr, Thomas Haspot, Fabienne Sykes, Megan TI CD40L-specific mAb mediates its tolerogenic effects through engagement of FcgRIIB, not via depletion of activated T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Lucas, Carrie L.; Fehr, Thomas; Haspot, Fabienne; Sykes, Megan] Harvard Med Sch, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 141.17 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763603106 ER PT J AU Salinthone, S Schillace, RV Yadav, V Marracci, G Bourdette, D Carr, DW AF Salinthone, Sonemany Schillace, Robynn V. Yadav, Vijayshree Marracci, Gail Bourdette, Dennis Carr, Daniel W. TI The natural antioxidant lipoic acid (LA) alters immune cell function: implications for multiple sclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Salinthone, Sonemany; Schillace, Robynn V.; Marracci, Gail; Bourdette, Dennis; Carr, Daniel W.] Portland VA Med Ctr, Res & Dev, Portland, OR USA. [Salinthone, Sonemany; Schillace, Robynn V.; Yadav, Vijayshree; Marracci, Gail; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 50.3 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763601059 ER PT J AU Singh, SK Suresh, MV Hammond, DJ Takahashi, K Agrawal, A AF Singh, Sanjay K. Suresh, Madathilparambil V. Hammond, David J. Takahashi, Kazue Agrawal, Alok TI Activation of mouse complement C3 by human C-reactive protein SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Singh, Sanjay K.; Suresh, Madathilparambil V.; Hammond, David J.; Agrawal, Alok] East Tennessee State Univ, Pharmacol, Johnson City, TN USA. [Takahashi, Kazue] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 134.59 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602352 ER PT J AU Zhang, X Mathenia, J Reyes-Cortes, E Molano, I Gilkeson, G AF Zhang, Xian Mathenia, Jeremy Reyes-Cortes, Emmanuel Molano, Ivan Gilkeson, Gary TI Effects of expression Fli1 transcription factor on lupus disease development in NZM2410 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhang, Xian; Mathenia, Jeremy; Reyes-Cortes, Emmanuel; Molano, Ivan; Gilkeson, Gary] Med Univ South Carolina, Med, Charleston, SC USA. [Zhang, Xian; Gilkeson, Gary] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 PG 1 WC Immunology SC Immunology GA V44QN UT WOS:000209763602084 ER PT J AU Zuleger, CL Macklin, MD Pei, QL Newton, MA Albertini, MR AF Zuleger, Cindy L. Macklin, Michael D. Pei, Qinglin Newton, Michael A. Albertini, Mark R. TI Identification of in vivo 6-thioguanine-resistant T cells reactive to melanoma-associated antigens SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zuleger, Cindy L.; Macklin, Michael D.; Newton, Michael A.; Albertini, Mark R.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53706 USA. [Pei, Qinglin; Newton, Michael A.] Univ Wisconsin, Sch Med & Publ Hlth, Stat, Madison, WI USA. [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2009 VL 182 SU 1 MA 40.15 PG 2 WC Immunology SC Immunology GA V44QN UT WOS:000209763600243 ER PT J AU Marjamaa, A Newton-Cheh, C Porthan, K Reunanen, A Lahermo, P Vaananen, H Jula, A Karanko, H Swan, H Toivonen, L Nieminen, MS Viitasalo, M Peltonen, L Oikarinen, L Palotie, A Kontula, K Salomaa, V AF Marjamaa, A. Newton-Cheh, C. Porthan, K. Reunanen, A. Lahermo, P. Vaananen, H. Jula, A. Karanko, H. Swan, H. Toivonen, L. Nieminen, M. S. Viitasalo, M. Peltonen, L. Oikarinen, L. Palotie, A. Kontula, K. Salomaa, V. TI Common candidate gene variants are associated with QT interval duration in the general population SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE epidemiology; genetics; KCNE1; long-QT syndrome; QT interval ID SINGLE NUCLEOTIDE POLYMORPHISMS; TORSADES-DE-POINTES; ION-CHANNEL; CARDIAC REPOLARIZATION; SUDDEN-DEATH; HEALTHY POPULATION; RISK-FACTOR; KCNH2 HERG; PROLONGATION; SCN5A AB QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample. We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI-TOF mass spectrometry. ECG parameters were measured from digital 12-lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population. The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT(Nc) interval (P = 3.6 x 10(-11)) in gender-pooled analysis. In agreement with previous studies, we replicated the association with QT(Nc) interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P = 4.7 x 10(-5)], KCNH2 K897T [-2.6 ms (SE 0.5) or -0.14 SD, P = 2.1 x 10(-7)] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P = 3.2 x 10(-24)] under additive models. We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, gender- and heart rate-adjusted QT interval and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval. C1 [Marjamaa, A.; Kontula, K.] Univ Helsinki, Res Program Mol Med, Biomed Helsinki, FIN-00290 Helsinki, Finland. [Newton-Cheh, C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Porthan, K.; Swan, H.; Toivonen, L.; Nieminen, M. S.; Viitasalo, M.; Oikarinen, L.] Univ Helsinki, Dept Cardiol, FIN-00290 Helsinki, Finland. [Reunanen, A.; Jula, A.; Karanko, H.; Peltonen, L.; Salomaa, V.] Natl Publ Hlth Inst, Helsinki, Finland. [Lahermo, P.; Palotie, A.] Univ Helsinki, Finnish Genome Ctr, FIN-00290 Helsinki, Finland. [Vaananen, H.] Helsinki Univ Technol, Biomed Engn Lab, FIN-02150 Espoo, Finland. [Kontula, K.] Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland. RP Kontula, K (reprint author), Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland. EM kimmo.kontula@hus.fi RI Vaananen, Heikki/F-7013-2012 OI Vaananen, Heikki/0000-0001-8649-1047 FU Sigrid Juselius Foundation; Finnish Academy; Finska LAkaresAlskapet Foundation; Biomedicum Helsinki Foundation; NIH [K23HL080025]; Aarne Koskelo Foundation; Finnish Foundation for Cardiovascular Research; Ida Montin Foundation; Paavo and Eila Salonen Foundation FX Susanna Tverin, Pirkko Alha, Harri Rissanen, Anu Yliperttula and Sirkka Ekstrom are acknowledged for skilful technical assistance. The study was financially supported by grants from the Sigrid Juselius Foundation and the Finnish Academy to Dr Kontula. Dr Marjamaa has received funding from the Finska LAkaresAlskapet Foundation and Biomedicum Helsinki Foundation. Dr Newton-Cheh is supported by NIH K23HL080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award and a Burroughs Wellcome Fund Career Award for Medical Scientists. Dr Porthan has received funding from the Aarne Koskelo Foundation, the Finnish Foundation for Cardiovascular Research, the Ida Montin Foundation, the Paavo and Eila Salonen Foundation. NR 58 TC 31 Z9 31 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD APR PY 2009 VL 265 IS 4 BP 448 EP 458 DI 10.1111/j.1365-2796.2008.02026.x PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 417KV UT WOS:000264075800004 PM 19019189 ER PT J AU Korngold, EC Inglessis, I Garasic, JM AF Korngold, Ethan C. Inglessis, Ignacio Garasic, Joseph M. TI A Novel Technique for 14 French Arteriotomy Closure after Percutaneous Aortic Valvuloplasty Using Two Mynx Closure Devices SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article AB Management of large bore arterial access sites often represents a challenge during interventional procedures, and usually requires prolonged manual compression, though suture-mediated closure techniques have been described. We report our experience in using the Mynx vascular closure device to close a 14 French femoral arteriotomy in two patients undergoing percutaneous balloon aortic valvuloplasty. (J Interven Cardiol 2009;22:179-183). C1 [Korngold, Ethan C.; Inglessis, Ignacio; Garasic, Joseph M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Garasic, JM (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bigelow 800, Boston, MA 02114 USA. EM jgarasic@partners.org NR 7 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD APR PY 2009 VL 22 IS 2 BP 179 EP 183 DI 10.1111/j.1540-8183.2008.00402.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 428XJ UT WOS:000264885100015 PM 18973504 ER PT J AU Bangalore, S Bhatt, DL AF Bangalore, Sripal Bhatt, Deepak L. TI Left Ventricular Hypertrophy Regression after Percutaneous Aortic Valve Replacement - A Sign of More Good Things to Come? SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material ID HIGH-RISK PATIENTS; HEART-VALVE; STENOSIS; IMPLANTATION; PROSTHESIS; FEASIBILITY; RETROGRADE; SIZE; 1ST-IN-MAN; EXPERIENCE C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM dlbhattmd@alum.mit.edu RI Bangalore, Sripal/B-6246-2013 NR 36 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD APR PY 2009 VL 21 IS 4 BP 156 EP 158 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 687VO UT WOS:000284806500005 ER PT J AU Bashir, MM Sharma, MR Werth, VP AF Bashir, Muhammad M. Sharma, Meena R. Werth, Victoria P. TI UVB and Proinflammatory Cytokines Synergistically Activate TNF-alpha Production in Keratinocytes through Enhanced Gene Transcription SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MESSENGER-RNA; HUMAN SKIN; ULTRAVIOLET-LIGHT; FACTOR PROMOTER; OVARIAN-CANCER; GROWTH-FACTOR; IN-VITRO; EXPRESSION AB UVB irradiation potently induces cytokines in the skin, including IL-1 alpha and tumor necrosis factor-alpha (TNF-alpha). The mechanism for TNF-alpha induction in UVB-irradiated keratinocytes is not clear. In this study, we explored the effects of UVB and cytokines, alone or in combination in human keratinocytes. Keratinocytes were sham-or UVB-irradiated with 30 mJ cm(-2), and then incubated in the absence or presence of IFN-alpha 2b, TNF-alpha, or IL-1 alpha. UVB and IL-1 alpha treatment synergistically enhanced TNF-alpha secretion and mRNA levels in human keratinocytes, similar to the findings reported previously in human fibroblasts. Exogenous recombinant TNF-alpha up-regulates its own mRNA level. However, addition of IFN-alpha 2b did not show any additive effect on TNF-alpha mRNA induction. To understand the regulation of TNF-alpha mRNA by UVB, with or without IL-1 alpha, we examined the transcription rate and half-life of TNF-alpha mRNA. Treatment of keratinocytes with IL-1 alpha or UVB alone increased TNF-alpha gene transcription 4- to 5-fold over sham treatment, and TNF-alpha gene transcription increased 11-fold in cells treated with UVB plus IL-1 alpha over sham. UVB with IL-1 alpha did not enhance the half-life of TNF-alpha mRNA over that seen with UVB alone. In conclusion, TNF-alpha expression in primary keratinocytes is upregulated transcriptionally by UVB and IL-1 alpha. C1 [Bashir, Muhammad M.; Sharma, Meena R.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Bashir, Muhammad M.; Sharma, Meena R.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia VA Med Ctr, 2 Rhoads Pavil,36th & Spruce Sts, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [P30 AR057217, P30 AR057217-01] NR 52 TC 34 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 IS 4 BP 994 EP 1001 DI 10.1038/jid.2008.332 PG 8 WC Dermatology SC Dermatology GA 430MW UT WOS:000264994200024 PM 19005488 ER PT J AU Braunstein, I Goodman, NG Rosenbach, M Okawa, J Kovarik, C Prak, ETL Werth, V AF Braunstein, I. Goodman, N. G. Rosenbach, M. Okawa, J. Kovarik, C. Prak, E. T. Luning Werth, V. TI Changes in the circulating leukocyte profile of subjects on lenalidomide for cutaneous lupus erythematosus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Braunstein, I.; Werth, V.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Braunstein, I.; Goodman, N. G.; Rosenbach, M.; Okawa, J.; Kovarik, C.; Prak, E. T. Luning; Werth, V.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 257 BP S43 EP S43 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000255 ER PT J AU Chang, LM Schaffer, L Head, SR Werth, VP AF Chang, L. M. Schaffer, L. Head, S. R. Werth, V. P. TI The molecular basis for increased dermal content of hyaluronic acid and chondroitin sulfate in cutaneous lupus erythematosus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Chang, L. M.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Chang, L. M.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Schaffer, L.; Head, S. R.] Consortium Funct Glyc, La Jolla, CA USA. [Schaffer, L.; Head, S. R.] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 70 BP S12 EP S12 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000071 ER PT J AU Chren, MM Torres, JS Stuart, SE Labrador, RJ Bertenthal, D Boscardin, WJ AF Chren, M. M. Torres, J. S. Stuart, S. E. Labrador, R. J. Bertenthal, D. Boscardin, W. J. TI Tumor recurrence after treatment of keratinocyte carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Chren, M. M.; Boscardin, W. J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chren, M. M.; Torres, J. S.; Stuart, S. E.; Labrador, R. J.; Bertenthal, D.; Boscardin, W. J.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 384 BP S64 EP S64 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000384 ER PT J AU Jalili, A Wagner, C Mertz, KD Pashenkov, M Lupien, M Goiser, M Brunet, J Ramaswamy, S Golub, TR Stingl, G Wagner, SN AF Jalili, A. Wagner, C. Mertz, K. D. Pashenkov, M. Lupien, M. Goiser, M. Brunet, J. Ramaswamy, S. Golub, T. R. Stingl, G. Wagner, S. N. TI AP-1 inhibition identifies cooperation of INK4 and Cip/Kip signaling pathways to suppress human melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Jalili, A.; Wagner, C.; Mertz, K. D.; Goiser, M.; Stingl, G.; Wagner, S. N.] Hosp Lainz, Dept Dermatol, Div Immunol Allergy & Infect Dis, Vienna, Austria. [Pashenkov, M.] Inst Immunol, Clin Immunol Lab, Moscow, Russia. [Lupien, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Brunet, J.; Golub, T. R.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Brunet, J.; Golub, T. R.] Harvard Univ, Cambridge, MA 02138 USA. [Ramaswamy, S.] Massachusetts Gen Hosp, Ctr Canc Res, Dept Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 845 BP S141 EP S141 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000843 ER PT J AU Katiyar, SK Katiyar, N Xu, H Meeran, SM AF Katiyar, S. K. Katiyar, N. Xu, H. Meeran, S. M. TI Interleukin-12-deficiency enhances 12-O-tetradecanoylphorbol-13-acetate-induced skin tumor promotion and malignant progression of papillomas to carcinomas in DMBA-initiated mouse skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Katiyar, S. K.; Katiyar, N.; Xu, H.; Meeran, S. M.] Univ Alabama, Birmingham, AL USA. [Katiyar, S. K.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 145 BP S25 EP S25 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000145 ER PT J AU Mairhofer, D Nazarian, RM Lobo, A Geller, RJ Mihm, MC Trautinger, F AF Mairhofer, D. Nazarian, R. M. Lobo, A. Geller, R. J. Mihm, M. C. Trautinger, F. TI Expression of the 27 kD and 90 kD heat shock proteins in psoriatic skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Mairhofer, D.; Trautinger, F.] Karl Landsteiner Inst Dermatol Res, St Polten, Austria. [Mairhofer, D.; Trautinger, F.] Landesklinikum St Poelten, St Polten, Austria. [Nazarian, R. M.; Lobo, A.; Mihm, M. C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Geller, R. J.] Emerson Hosp, Concord, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 69 BP S12 EP S12 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000068 ER PT J AU Meeran, SM Punathil, T Katiyar, S Elmets, CA Katiyar, SK AF Meeran, S. M. Punathil, T. Katiyar, S. Elmets, C. A. Katiyar, S. K. TI Inhibition of angiogenesis in UV-induced skin tumors by drinking green tea polyphenols requires IL-12 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Meeran, S. M.; Punathil, T.; Katiyar, S.; Elmets, C. A.; Katiyar, S. K.] Univ Alabama, Birmingham, AL USA. [Elmets, C. A.; Katiyar, S. K.] Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 752 BP S126 EP S126 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000754 ER PT J AU Mukhopadhyay, A Krishnaswami, SR Haigis, KM Yu, BD AF Mukhopadhyay, A. Krishnaswami, S. R. Haigis, K. M. Yu, B. D. TI Mouse models of RAS/MAPK syndromes reveal opposing effects of RAS on hair and skin development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dermatol C1 [Mukhopadhyay, A.; Krishnaswami, S. R.; Yu, B. D.] Univ Calif San Diego, Dept Med, Div Dermatol, San Diego, CA 92103 USA. [Haigis, K. M.] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 SU 1 MA 598 BP S100 EP S100 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000599 ER PT J AU Seidler, EM Kimball, AB AF Seidler, E. M. Kimball, A. B. TI Psoriasis is associated with disruption in religious affiliation and marital status during early adulthood SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Seidler, E. M.; Kimball, A. B.] Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 389 BP S65 EP S65 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000387 ER PT J AU Sharma, MR Werth, B LoMonico, J Werth, VP AF Sharma, M. R. Werth, B. LoMonico, J. Werth, V. P. TI Effect of Etanercept, TNF-alpha blocker on TNF-alpha-mediated photodamage/photoaging SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Sharma, M. R.; Werth, B.; LoMonico, J.; Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Sharma, M. R.; Werth, V. P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 773 BP S129 EP S129 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000771 ER PT J AU Souza, RC Cimbalista, M Carvalho, VO Lima, HC AF Souza, R. C. Cimbalista, M. Carvalho, V. O. Lima, H. C. TI Dynamic area telethermometry determines the skin inflammatory response intensity induced by imiquimod on human basal cell carcinoma treatment SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Souza, R. C.] Fac Evangel Parana, Curitiba, Parana, Brazil. [Cimbalista, M.] Thermotronics, Curitiba, Parana, Brazil. [Carvalho, V. O.; Lima, H. C.] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Lima, H. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lima, Hermenio/G-5379-2010; Lima, Hermenio/A-1616-2010; Carvalho, Vania/H-1870-2013 OI Lima, Hermenio/0000-0003-0950-3731; Carvalho, Vania/0000-0002-4578-8781 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 333 BP S56 EP S56 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000332 ER PT J AU Tsao, S Yao, M Henry, FP Tsao, H Redmond, RW Kochevar, IE AF Tsao, S. Yao, M. Henry, F. P. Tsao, H. Redmond, R. W. Kochevar, I. E. TI Photochemical tissue bonding for closure of excision wounds: a first-in-human clinical trial SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Yao, M.; Henry, F. P.; Tsao, H.; Redmond, R. W.; Kochevar, I. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 279 BP S47 EP S47 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000278 ER PT J AU Yoo, JY Pancir, DL Kimball, AB AF Yoo, J. Y. Pancir, D. L. Kimball, A. B. TI Patient preferences for dermatology visits SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Yoo, J. Y.; Pancir, D. L.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 355 BP S60 EP S60 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000355 ER PT J AU Zuo, Y Zhuang, DZ Han, R Isaac, G Manning, JJ Mckee, M Welti, R Brissette, JL Fitzgerald, ML Freeman, MW AF Zuo, Y. Zhuang, D. Z. Han, R. Isaac, G. Manning, J. J. Mckee, M. Welti, R. Brissette, J. L. Fitzgerald, M. L. Freeman, M. W. TI ABCA12 maintains the epidermal lipid barrier SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-of-Investigative-Dermatology CY MAY 06-09, 2009 CL Montreal, CANADA SP Soc Investigat Dematol C1 [Zuo, Y.; Zhuang, D. Z.; Manning, J. J.; Fitzgerald, M. L.; Freeman, M. W.] Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. [Zuo, Y.; Zhuang, D. Z.; Manning, J. J.; Fitzgerald, M. L.; Freeman, M. W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Han, R.; Brissette, J. L.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Mckee, M.] Massachusetts Gen Hosp, Ctr Membrane Biol, Boston, MA 02114 USA. [Isaac, G.; Welti, R.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2009 VL 129 MA 539 BP S90 EP S90 PG 1 WC Dermatology SC Dermatology GA 430MU UT WOS:000264994000537 ER PT J AU Zhang, L Wang, ZH Sagotsky, JA Deisboeck, TS AF Zhang, Le Wang, Zhihui Sagotsky, Jonathan A. Deisboeck, Thomas S. TI Multiscale agent-based cancer modeling SO JOURNAL OF MATHEMATICAL BIOLOGY LA English DT Article DE Computational systems biology; Agent-based modeling; Tumor simulation ID EPIDERMAL-GROWTH-FACTOR; CYLINDRICAL SKIN-STRUCTURE; BRAIN-TUMORS; MULTICELLULAR PATTERNS; MATHEMATICAL-MODEL; NUMERICAL-METHOD; CLINICAL-TRIALS; TIME-SERIES; INVASION; GLIOBLASTOMA AB Agent-based modeling (ABM) is an in silico technique that is being used in a variety of research areas such as in social sciences, economics and increasingly in biomedicine as an interdisciplinary tool to study the dynamics of complex systems. Here, we describe its applicability to integrative tumor biology research by introducing a multi-scale tumor modeling platform that understands brain cancer as a complex dynamic biosystem. We summarize significant findings of this work, and discuss both challenges and future directions for ABM in the field of cancer research. C1 [Zhang, Le; Wang, Zhihui; Sagotsky, Jonathan A.; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, E 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU NIH [CA 085139, CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology FX This work has been supported in part by NIH grants CA 085139 and CA 113004 and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. NR 56 TC 55 Z9 57 U1 0 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0303-6812 EI 1432-1416 J9 J MATH BIOL JI J. Math. Biol. PD APR PY 2009 VL 58 IS 4-5 BP 545 EP 559 DI 10.1007/s00285-008-0211-1 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 394WA UT WOS:000262482600004 PM 18787828 ER PT J AU Miller, DT Shen, Y Weiss, LA Korn, J Anselm, I Bridgemohan, C Cox, GF Dickinson, H Gentile, J Harris, DJ Hegde, V Hundley, R Khwaja, O Kothare, S Luedke, C Nasir, R Poduri, A Prasad, K Raffalli, P Reinhard, A Smith, SE Sobeih, MM Soul, JS Stoler, J Takeoka, M Tan, WH Thakuria, J Wolff, R Yusupov, R Gusella, JF Daly, MJ Wu, BL AF Miller, D. T. Shen, Y. Weiss, L. A. Korn, J. Anselm, I. Bridgemohan, C. Cox, G. F. Dickinson, H. Gentile, J. Harris, D. J. Hegde, V. Hundley, R. Khwaja, O. Kothare, S. Luedke, C. Nasir, R. Poduri, A. Prasad, K. Raffalli, P. Reinhard, A. Smith, S. E. Sobeih, M. M. Soul, J. S. Stoler, J. Takeoka, M. Tan, W-H Thakuria, J. Wolff, R. Yusupov, R. Gusella, J. F. Daly, M. J. Wu, B-L TI Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; OBSESSIVE-COMPULSIVE DISORDER; JUVENILE MYOCLONIC EPILEPSY; (AC)N DINUCLEOTIDE REPEAT; RECEPTOR SUBUNIT GENE; PRADER-WILLI-SYNDROME; BIPOLAR DISORDER; LINKAGE DISEQUILIBRIUM; CHROMOSOME 15Q13-14; PARTIAL DUPLICATION AB Background: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. Patients: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. Results: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers similar to 1.5 Mb (chr15: 28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover similar to 500 kb (chr15: 28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. Conclusions: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome. C1 [Miller, D. T.; Shen, Y.; Weiss, L. A.; Anselm, I.; Bridgemohan, C.; Cox, G. F.; Gentile, J.; Harris, D. J.; Hegde, V.; Hundley, R.; Khwaja, O.; Kothare, S.; Luedke, C.; Nasir, R.; Poduri, A.; Prasad, K.; Raffalli, P.; Smith, S. E.; Sobeih, M. M.; Soul, J. S.; Stoler, J.; Takeoka, M.; Tan, W-H; Thakuria, J.; Wolff, R.; Yusupov, R.; Gusella, J. F.; Daly, M. J.; Wu, B-L] Harvard Univ, Sch Med, Boston, MA USA. [Miller, D. T.; Shen, Y.; Weiss, L. A.; Khwaja, O.; Nasir, R.; Sobeih, M. M.; Gusella, J. F.; Daly, M. J.; Wu, B-L] Autism Consortium, Boston, MA USA. [Shen, Y.; Weiss, L. A.; Gusella, J. F.; Daly, M. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Korn, J.; Daly, M. J.; Wu, B-L] Broad Inst Harvard & MIT, Cambridge, MA USA. [Anselm, I.; Khwaja, O.; Kothare, S.; Poduri, A.; Prasad, K.; Raffalli, P.; Sobeih, M. M.; Soul, J. S.; Takeoka, M.; Wolff, R.] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Bridgemohan, C.; Hundley, R.; Nasir, R.] Childrens Hosp Boston, Div Dev Med, Boston, MA 02115 USA. [Cox, G. F.; Smith, S. E.] Genzyme Corp, Cambridge, MA USA. [Dickinson, H.] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Gentile, J.] Childrens Hosp Boston, Dept Psychiat, Boston, MA 02115 USA. [Kothare, S.; Takeoka, M.] Childrens Hosp Boston, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA. [Luedke, C.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Miller, D. T.; Shen, Y.; Reinhard, A.; Wu, B-L] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. [Miller, D. T.; Cox, G. F.; Gentile, J.; Harris, D. J.; Hegde, V.; Reinhard, A.; Smith, S. E.; Stoler, J.; Tan, W-H; Thakuria, J.; Yusupov, R.] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. RP Wu, BL (reprint author), Childrens Hosp Boston, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bai-lin.wu@childrens.harvard.edu OI Prasad, Konasale/0000-0003-0245-1393 FU Children's Tumor Foundation; Ruth L Kirschstein National Research Service Award; National Institutes of Health [P01-GM061354]; NARSAD Distinguished Investigator Award; Harvard Scholars in Clinical Science [RRO22292-07]; Autism Consortium and the Ellison Foundation; NIH-CETT Program; MDA Foundation FX We acknowledge the following sources of financial support: Young Investigator Award from the Children's Tumor Foundation (to YS). Ruth L Kirschstein National Research Service Award (to LAW); National Institutes of Health grant P01-GM061354, Autism Speaks, and NARSAD Distinguished Investigator Award (to JFG), Harvard Scholars in Clinical Science Program K30 grant RRO22292-07 (to JT), grants from the Autism Consortium and the Ellison Foundation (to MJD), and grants from the NIH-CETT Program and the MDA Foundation (to BLW). NR 48 TC 193 Z9 196 U1 1 U2 20 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2009 VL 46 IS 4 BP 242 EP 248 DI 10.1136/jmg.2008.059907 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 430TH UT WOS:000265011000004 PM 18805830 ER PT J AU Singh, H Fox, SA Petersen, NJ Shethia, A Street, RL AF Singh, Hardeep Fox, Sarah A. Petersen, Nancy J. Shethia, Anila Street, Richard L., Jr. TI Older Patients' Enthusiasm to Use Electronic Mail to Communicate With Their Physicians: Cross-Sectional Survey SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Electronic mail; doctor-patient communication; Internet; doctor-patient relationship ID MEDICAL ENCOUNTER; HEALTH-CARE; EMAIL; INTERNET; DIVIDE; ACCESS AB Background: Recent evidence indicates increased access to and use of Internet and non-healthcare-related email by older patients. Because email adoption could potentially reduce some of the disparities faced by this age group, there is a need to understand factors determining older patients' enthusiasm to use email to communicate with their physicians. Electronic mail (email) represents a means of communication that, coupled with face-to-face communication, could enhance quality of care for older patients. Objective: Testa model to determine factors associated with older patients' enthusiasm to use email to communicate with their physicians. Methods: We conducted a secondary data analysis of survey data collected in 2003 for two large, longitudinal, randomized controlled trials. Logistic-regression models were used to model the dichotomous outcome of patient enthusiasm for using email to communicate with their physicians. Explanatory variables included demographic characteristics, health status, use of email with people other than their physician, characteristics of the physician-patient relationship, and physician enthusiasm to use email with patients. Results: Participants included a pooled sample of 4059 patients over 65 years of age and their respective physicians (n = 181) from community-based practices in Southern California. Although only 52 (1.3%) patient respondents reported that they communicated with their physician by email, about half (49.3%) expressed enthusiasm about the possibility of using it. Odds of being enthusiastic decreased with increased age (by 0.97 for each year over 66) but were significantly higher in African Americans (OR = 2.1, CI = 1.42 - 3.06), Hispanics (OR = 1.6, CI = 1.26 - 2.14) and men (OR = 1.3, CI = 1.1 - 1.5). A perception of better communication skills of their physician, lower quality of interaction with physician in traditional face-to-face encounters, and physician enthusiasm to use email with patients were significantly associated with an enthusiasm to use email. Patients who did not use email at all were less enthusiastic compared to those who used email for other reasons. Half of the physician respondents were not enthusiastic about communicating with patients using email. Conclusions: Despite perceived barriers such as limited access to the Internet, older patients seem to want to use email to communicate with their physicians. C1 [Singh, Hardeep; Petersen, Nancy J.; Shethia, Anila; Street, Richard L., Jr.] Michael E DeBakey VA Med Ctr, Ctr Excellence, Houston VA Hlth Serv Res & Dev HSR&D, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Nancy J.; Shethia, Anila; Street, Richard L., Jr.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Singh, Hardeep] Michael E DeBakey VA Med Ctr, Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX USA. [Fox, Sarah A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Ctr Community Patnerships Hlth Promot, Los Angeles, CA 90095 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU National Cancer Institute [RO1CA74322]; Houston VA HSR&D Center of Excellence [HFP90-020] FX The study was supported by a grant from the National Cancer Institute (NCI RO1CA74322) and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). These sources had no role in study design or execution, collection of data, writing the manuscript, or the decision to submit the manuscript for publication. 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 29 TC 30 Z9 30 U1 4 U2 8 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD APR-JUN PY 2009 VL 11 IS 2 AR e18 DI 10.2196/jmir.1143 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 556YT UT WOS:000274632700004 PM 19632972 ER PT J AU Hasman, H Pachucki, CT Unal, A Nguyen, D Devlin, T Peeples, ME Kwilas, SA AF Hasman, Hatice Pachucki, Constance T. Unal, Arife Nguyen, Diep Devlin, Troy Peeples, Mark E. Kwilas, Steven A. TI Aetiology of influenza-like illness in adults includes parainfluenzavirus type 4 SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID RESPIRATORY-SYNCYTIAL-VIRUS; REVERSE TRANSCRIPTION-PCR; CLINICAL-SAMPLES; HUMAN METAPNEUMOVIRUS; PEDIATRIC-PATIENTS; INFECTIONS; IDENTIFICATION; DIAGNOSIS; CHILDREN; ASSAYS AB Influenza viruses cause significant morbidity and mortality in adults each winter. At the same time, other respiratory viruses circulate and cause respiratory illness with influenza-like symptoms. Human respiratory syncytial virus (HRSV), human parainfluenza viruses (HPIV) and human metapneumovirus have all been associated with morbidity and mortality in adults, including nosocomial infections. This study evaluated 154 respiratory specimens collected from adults with influenza-like/acute respiratory illness (ILI) seen at the Edward Hines Jr VA Hospital, Hines, IL, USA, during two successive winters, 1998-1999 and 1999-2000. The samples were tested for ten viruses in two nested multiplex RT-PCRs. One to three respiratory viruses were detected in 68% of the samples. As expected, influenza A virus (FLU-A) infections were most common (50% of the samples), followed by HRSV-A (16%). Surprisingly, HPIV-4 infections (5.8%) were the third most prevalent. Mixed infections were also relatively common (11%). When present, HPIV infections were approximately three times more likely to be included in a mixed infection than FLU-A or HRSV. Mixed infections and HPIV-4 are likely to be missed using rapid diagnostic tests. This study confirms that ILI in adults and the elderly can be caused by HRSV and HPIVs, including HPIV-4, which co-circulate with FLU-A. C1 [Hasman, Hatice; Peeples, Mark E.] Rush Univ, Coll Med, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Hasman, Hatice] Sisli Etfal Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey. [Pachucki, Constance T.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Infect Dis Sect, Hines, IL 60141 USA. [Nguyen, Diep; Devlin, Troy] Rush Univ, Coll Hlth Sci, Dept Med Technol, Chicago, IL 60612 USA. [Peeples, Mark E.; Kwilas, Steven A.] Rush Univ, Grad Coll, Div Immunol, Chicago, IL 60612 USA. [Unal, Arife; Peeples, Mark E.; Kwilas, Steven A.] Ohio State Univ, Nationwide Childrens Hosp, Coll Med, Sect Vaccines & Immun,Res Inst,Dept Pediat, Columbus, OH 43205 USA. RP Peeples, ME (reprint author), Rush Univ, Coll Med, Dept Immunol & Microbiol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM mark.peeples@nationwidechildrens.org FU National Institutes of Health (NIH), USA [A1047213] FX We thank the Clinical Microbiology Laboratory at the Rush University Medical Center; Richard Compans, Peter Collins, Robert Lamb, Guy Boivin and Dean Erdman for the standard viruses; Barbara Newton, Stephanie Downing and Anumeha Gupta for their excellent technical help; Doug Salamon and Amy Leber for helpful discussions; and Mayte Coiras for helpful discussions and reagents. This work was supported by National Institutes of Health (NIH), USA, grant A1047213. NR 26 TC 20 Z9 20 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD APR PY 2009 VL 58 IS 4 BP 408 EP 413 DI 10.1099/jmm.0.006098-0 PG 6 WC Microbiology SC Microbiology GA 429GJ UT WOS:000264908600004 PM 19273634 ER PT J AU Chang, MH Plata, C Zandi-Nejad, K Sindic, A Sussman, CR Mercado, A Broumand, V Raghuram, V Mount, DB Romero, MF AF Chang, Min-Hwang Plata, Consuelo Zandi-Nejad, Kambiz Sindic, Aleksandra Sussman, Caroline R. Mercado, Adriana Broumand, Vadjista Raghuram, Viswanathan Mount, David B. Romero, Michael F. TI Slc26a9-Anion Exchanger, Channel and Na+ Transporter SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Intracellular pH; Cl-; Na+; HCO3-; Xenopus oocyte expression; Epithelial localization ID CONGENITAL CHLORIDE DIARRHEA; ELECTROGENIC NA+-HCO3-COTRANSPORTER; DYSPLASIA SULFATE TRANSPORTER; PUTATIVE ANION TRANSPORTER; DEPENDENT HCO3-TRANSPORT; DIASTROPHIC DYSPLASIA; CL-/HCO3-EXCHANGE; CYSTIC-FIBROSIS; RAT-KIDNEY; MOLECULAR CHARACTERIZATION AB The SLC26 gene family encodes anion transporters with diverse functional attributes: (a) anion exchanger, (b) anion sensor, and (c) anion conductance (likely channel). We have cloned and studied Slc26a9, a paralogue expressed mostly in lung and stomach. Immunohistochemistry shows that Slc26a9 is present at apical and intracellular membranes of lung and stomach epithelia. Using expression in Xenopus laevis oocytes and ion-sensitive microelectrodes, we discovered that Slc26a9 has a novel function not found in any other Slc26 proteins: cation coupling. Intracellular pH and voltage measurements show that Slc26a9 is a nCl(-)-HCO (3) (-) exchanger, suggesting roles in gastric HCl secretion or pulmonary HCO (3) (-) secretion; Na+ electrodes and uptakes reveal that Slc26a9 has a cation dependence. Single-channel measurements indicate that Slc26a9 displays discrete open and closed states. These experiments show that Slc26a9 has three discrete physiological modes: nCl(-)-HCO (3) (-) exchanger, Cl- channel, and Na+-anion cotransporter. Thus, the Slc26a9 transporter channel is uniquely suited for dynamic and tissue-specific physiology or regulation in epithelial tissues. C1 [Chang, Min-Hwang; Sindic, Aleksandra; Sussman, Caroline R.; Romero, Michael F.] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA. [Chang, Min-Hwang; Plata, Consuelo; Sindic, Aleksandra; Sussman, Caroline R.; Romero, Michael F.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Plata, Consuelo] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. [Zandi-Nejad, Kambiz; Mercado, Adriana; Broumand, Vadjista; Mount, David B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Sindic, Aleksandra] Univ Zagreb, Croatian Inst Brain Res, Sch Med, Zagreb 41000, Croatia. [Raghuram, Viswanathan] NHLBI, NIH, Bethesda, MD 20892 USA. [Mount, David B.] VA Boston Healthcare Syst, Div Renal, Boston, MA 02132 USA. RP Romero, MF (reprint author), Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, 200 1st St SW, Rochester, MN 55905 USA. EM romero.michael@mayo.edu RI Plata, Consuelo/M-4482-2015 OI Plata, Consuelo/0000-0001-9340-8950 FU NIH [DK056218, DK060845, EY017732, DK038226, DK070756, DK57708, F32-DK65482]; Veterans Administration; Wadsworth Foundation; American Heart Association; Cystic Fibrosis Foundation [RO-MERO-06GO, SINDIC-06F0] FX We thank N. Angle, G. Babcock, L. Song, Q. Xie, R. Welch, and M. Sanders for excellent technical support. We thank Dr. S. Muallem for the Slc26a7 cDNA. We also thank Drs. S. W. Jones and C. Objero-Paz for discussions and initial patch experiments. This work was supported by NIH Grants DK056218, DK060845, and EY017732 (M. F. R.); DK038226, DK070756, and DK57708 (D. B. M.); and F32-DK65482 (V.B.). Other funding includes an Advanced Career Development Award from the Veterans Administration (DBM); the Wadsworth Foundation & American Heart Association (AHA; C. R. S.); a postdoctoral fellowship from the AHA (M.-H.C. and K.Z.); and the Cystic Fibrosis Foundation (RO-MERO-06GO and SINDIC-06F0). NR 58 TC 35 Z9 37 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD APR PY 2009 VL 228 IS 3 BP 125 EP 140 DI 10.1007/s00232-009-9165-5 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 445GT UT WOS:000266039200001 PM 19365592 ER PT J AU Boisseau, CL Thompson-Brenner, H Eddy, KT Satir, DA AF Boisseau, Christina L. Thompson-Brenner, Heather Eddy, Kamryn T. Satir, Dana A. TI Impulsivity and Personality Variables in Adolescents With Eating Disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Eating disorder; adolescence; impulsivity; personality; subtype ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; AXIS-II; CLINICIAN REPORT; PATHOLOGY; BEHAVIOR; SUBTYPES; TRAITS; ABUSE; PSYCHOPATHOLOGY AB Impulsivity among individuals with eating disorders (EDs) is associated with severe comorbidities and poor treatment Outcome. However, research investigating the construct of impulsivity in EDs is limited. The objectives of the present study were to characterize multiple dimensions of impulsivity in adolescents with EDs; determine if differences in impulsivity were associated with ED diagnosis and/or broader personality traits; and explore the relationship between impulsivity and etiologically significant variables. Experienced clinicians from a practice-research network provided data on ED symptoms, impulsive characteristics, personality pathology, The Diagnostic and Statistical Manual of Mental Disorders comorbidity, and family and developmental history for 120 adolescent patients with EDs. Three distinct types of impulsivity were identified: general, acting out, and aggressive/destructive. The impulsivity types showed specific relationships to ED diagnosis, broader personality factors, individual histories of adverse (traumatic) events, and family histories of externalizing disorders, supporting the importance of taking, assessing, and addressing impulsivity in ED research and treatment. C1 [Boisseau, Christina L.; Thompson-Brenner, Heather; Satir, Dana A.] Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Boisseau, CL (reprint author), Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, 648 Beacon St, Boston, MA 02215 USA. EM tinalb@bu.edu FU American Psychoanalytic Association FX Supported by a grant from the American Psychoanalytic Association to (D.A.S.), NR 64 TC 11 Z9 12 U1 1 U2 3 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 APR PY 2009 VL 197 IS 4 BP 251 EP 259 DI 10.1097/NMD.0b013e31819d96c0 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 434BG UT WOS:000265249600006 PM 19363381 ER PT J AU Norden, AD Drappatz, J Muzikansky, A David, K Gerard, M McNamara, MB Phan, P Ross, A Kesari, S Wen, PY AF Norden, Andrew D. Drappatz, Jan Muzikansky, Alona David, Karly Gerard, Mary McNamara, M. Brenna Phan, Phuong Ross, Ainsley Kesari, Santosh Wen, Patrick Y. TI An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Malignant glioma; Anti-angiogenic therapy; Progression-free survival ID HIGH-GRADE GLIOMAS; PHASE-II TRIAL; GLIOBLASTOMA-MULTIFORME; RESPONSE CRITERIA; 1ST RELAPSE; BEVACIZUMAB; CHEMOTHERAPY; TEMOZOLOMIDE; MULTICENTER; IRINOTECAN AB Recent clinical trial results suggest that anti-angiogenic therapy may be effective against recurrent malignant glioma. Though these treatments prolong progression-free survival, the extent to which they prolong overall survival is unknown. We pooled data from 34 patients treated at a single institution on phase II clinical trials of bevacizumab and cediranib, and we compared these data to 18 patients treated on clinical trials of cytotoxic chemotherapies. In univariate and multivariate analyses, treatment group was a significant predictor of progression-free but not overall survival. Median progression-free survival was 8 vs. 22 weeks in patients treated with cytotoxic as compared to anti-angiogenic therapy (P = 0.01). Median overall survival was nearly identical in the two groups (39 vs. 37 weeks). The results of this exploratory analysis suggest that anti-angiogenic therapy may fail to prolong overall survival in patients with recurrent malignant glioma. If this conclusion proves correct, progression-free survival may be an inappropriate endpoint for phase II trials of anti-angiogenic therapies. C1 [Norden, Andrew D.; Drappatz, Jan; David, Karly; Gerard, Mary; McNamara, M. Brenna; Phan, Phuong; Ross, Ainsley; Kesari, Santosh; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. [Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Norden, AD (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St, Boston, MA 02115 USA. EM anorden@partners.org RI Kesari, Santosh/E-8461-2013 NR 20 TC 70 Z9 71 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2009 VL 92 IS 2 BP 149 EP 155 DI 10.1007/s11060-008-9745-8 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 411KC UT WOS:000263647500004 PM 19043778 ER PT J AU Fadul, CE Wen, PY Kim, L Olson, JJ AF Fadul, Camilo E. Wen, Patrick Y. Kim, Lyndon Olson, Jeffrey J. TI Cytotoxic chemotherapeutic management of newly diagnosed glioblastoma multiforme (vol 89, pg 339, 2008) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Correction C1 [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. [Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Neurooncol Program, Norris Cotton Canc Ctr, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA. [Kim, Lyndon] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Olson, JJ (reprint author), Emory Univ, Sch Med, Dept Neurosurg, 1365B Clifton Rd NE,Ste 6200, Atlanta, GA 30322 USA. EM jeffrey.olson@emoryhealthcare.org NR 1 TC 0 Z9 0 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 APR PY 2009 VL 92 IS 2 BP 239 EP 239 DI 10.1007/s11060-008-9776-1 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 411KC UT WOS:000263647500016 ER PT J AU Dabus, G Nogueira, RG AF Dabus, Guilherme Nogueira, Raul G. TI Empty Microcatheter Technique for the Deployment of a Self-Expanding Stent to Treat Refractory Middle Cerebral Artery Occlusion in the Setting of Severe Proximal Tortuosity SO JOURNAL OF NEUROIMAGING LA English DT Article DE Acute stroke; neurointervention; stent; endovascular treatment; intra-arterial recanalization ID ACUTE ISCHEMIC-STROKE; MECHANICAL CLOT DISRUPTION; INTRAARTERIAL THROMBOLYSIS; RECANALIZATION; ANGIOPLASTY; THERAPY; EXPERIENCE; EFFICACY; REMOVAL; SAFETY AB We report a case of an acute middle cerebral artery (M2 segment) occlusion that was refractory to intravenous tissue plasminogen activator (IV t-PA), thrombectomy with the Merci((R)) device, intra-arterial infusion of urokinase and eptifibatide, and balloon angioplasty. The artery was so tortuous that over-the-wire stent placement failed and a salvage technique was required to place the self-expanding stent. J Neuroimaging 2009;19:164-168. C1 [Dabus, Guilherme; Nogueira, Raul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc & Crit Care Neurol, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB-2-241, Boston, MA 02114 USA. EM rnogueira@partners.org NR 22 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2009 VL 19 IS 2 BP 164 EP 168 DI 10.1111/j.1552-6569.2008.00252.x PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 424KV UT WOS:000264566500009 PM 18393952 ER PT J AU Nogueira, RG Baccin, CE Rabinov, JD Pryor, JC Buonanno, FS Hirsch, JA AF Nogueira, Raul G. Baccin, Carlos E. Rabinov, James D. Pryor, Johnny C. Buonanno, Ferdinando S. Hirsch, Joshua A. TI Reversible Parkinsonism After Treatment of Dural Arteriovenous Fistula SO JOURNAL OF NEUROIMAGING LA English DT Article DE Dural arteriovenous fistula; AVM; parkinsonism; reversible ID DEMENTIA AB The most common causes of parkinsonism are degenerative and irreversible. Structural causes of reversible parkinsonism are exceptionally rare, but have been reported in association with deep cerebral venous thrombosis and dural arteriovenous fistula (DAVF). We now report a case of parkinsonian syndrome reversed by treatment of a dural arteriovenous malformation. Case report with retrospective review of relevant clinical, imaging, and treatment data. A 79-year-old man presented with complaints of a slowly progressive parkinsonian syndrome and tinnitus. Brain magnetic resonance imaging (MRI) showed numerous serpiginous flow voids highly suggestive of a vascular malformation. Cerebral angiography revealed a Cognard grade IIa + b left transverse sinus DAVF. The patient underwent combined endovascular and surgical treatment in three stages over a week's time, with total obliteration of the DAVF and complete normalization of his symptoms and neurological examination. Although rare, DAVF should always be considered as a potential cause of progressive parkinsonism. This diagnosis is of great importance because of its potential reversibility. J Neuroimaging 2009;19:183-184. C1 [Nogueira, Raul G.; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurocrit Care & Vasc Neurol Sect,Dept Neurol, Boston, MA 02114 USA. [Nogueira, Raul G.; Baccin, Carlos E.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Endovasc Neurosurg Intervent Neuroradiol Sect, Sch Med,Dept Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.; Baccin, Carlos E.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Endovasc Neurosurg Intervent Neuroradiol Sect, Sch Med,Dept Radiol, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurocrit Care & Vasc Neurol Sect,Dept Neurol, Blake 12,Room 1291,55 Fruit St, Boston, MA 02114 USA. EM rnogueira@partners.org NR 7 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 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2009 VL 19 IS 2 BP 183 EP 184 DI 10.1111/j.1552-6569.2007.00237.x PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 424KV UT WOS:000264566500013 PM 18681932 ER PT J AU Kleinschmidt-DeMasters, BK Cummings, TJ Hulette, CM Morgenlander, JC Corboy, JR AF Kleinschmidt-DeMasters, Bette Kay Cummings, Thomas J. Hulette, Christine M. Morgenlander, Joel C. Corboy, John R. TI Adult Cases of Leukoencephalopathy, Cerebral Calcifications, and Cysts: Expanding the Spectrum of the Disorder SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Angiomatous malformation; Cerebral calcification; Cerebroretinal microangiopathy; Leukoencephalopathy; Pilocytic astrocytoma; Rosenthal fibers; Vasculitis; Vasculopathy ID CEREBRORETINAL MICROANGIOPATHY; BRAIN AB Leukoencephalopathy with cerebral calcifications and cysts (LCC) was first reported in children who developed cognitive decline and variable extrapyramidal, cerebellar, and pyramidal signs.. with or without seizures. Leukoencephalopathy with cerebral calcifications and cysts is characterized by progressive formation of brain cysts that can generate a mass effect simulating a neoplasm. Retinal changes that overlap with Coats disease, a microangiopathy with retinal telangiectasias and exudates, may also Occur. We and others have reported LCC cases in adults. Neuroimaging shows diffuse leukoencephalopathy, multifocal calcifications especially of deep gray and white matter, multifocal enhancement, and variably sized cysts that may require surgical decompression. Biopsies adjacent to cysts have shown angiomatous and/or severely hyalinized blood vessels surrounded by myelin loss and gliosis, calcifications, and Rosenthal fibers. We report 2 additional adult-onset cases of LCC. Case I is a 40-year-old mail who developed neurological symptoms and cirrhosis and died of acute gastrointestinal bleeding, fie had numerous retinal microinfarcts at autopsy. Case 2 is a 55-year-old woman who was found by chance to have LCC; one and a half years later, her Course remains benign. These cases expand the spectrum Of adult-onset LCC, the etiology of which is unknown. C1 [Kleinschmidt-DeMasters, Bette Kay] Univ Colorado, Dept Pathol, Aurora, CO USA. [Kleinschmidt-DeMasters, Bette Kay; Corboy, John R.] Univ Colorado, Dept Pathol, Aurora, CO USA. [Kleinschmidt-DeMasters, Bette Kay] Univ Colorado, Dept Neurosurg, Aurora, CO USA. [Corboy, John R.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Cummings, Thomas J.; Hulette, Christine M.] Duke Univ Hlth Syst, Dept Pathol, Durham, NC USA. [Morgenlander, Joel C.] Duke Univ Hlth Syst, Dept Med Neurol, Durham, NC USA. RP Kleinschmidt-DeMasters, BK (reprint author), UCDHSC, Dept Surg Pathol, Mail Stop B216,12631 E 17th Ave, Aurora, CO 80045 USA. EM bk.demasters@ucdenver.edu NR 13 TC 17 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 2009 VL 68 IS 4 BP 432 EP 439 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 427VT UT WOS:000264807900010 PM 19287308 ER PT J AU Fried, SI Lasker, ACW Desai, NJ Eddington, DK Rizzo, JF AF Fried, Shelley I. Lasker, Aaron C. W. Desai, Neal J. Eddington, Donald K. Rizzo, Joseph F., III TI Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ACTION-POTENTIAL INITIATION; GATED ION CHANNELS; RETINITIS-PIGMENTOSA; MORPHOMETRIC-ANALYSIS; PYRAMIDAL NEURONS; RABBIT RETINA; PERCEPTUAL THRESHOLDS; VISUAL-PERCEPTION; RECEPTIVE-FIELDS; MAMMALIAN RETINA AB Fried SI, Lasker ACW, Desai NJ, Eddington DK, Rizzo JF 3rd. Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells. J Neurophysiol 101: 1972-1987, 2009. First published February 4, 2009; doi:10.1152/jn.91081.2008. Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 mu m from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed. C1 [Fried, Shelley I.; Lasker, Aaron C. W.; Desai, Neal J.; Rizzo, Joseph F., III] VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Eddington, Donald K.] MIT, Elect Res Lab, Boston, MA USA. [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept NeuroOphthalmol, Boston, MA 02114 USA. RP Fried, SI (reprint author), VA Healthcare Syst, Ctr Innovat Visual Rehabil, Room 8B-74, Boston, MA 02130 USA. EM sfried1@partners.org FU Department of Defense Congressionally Directed Medical Research Programs [PR-064790]; Veterans Administration Center FX This work was supported by Department of Defense Congressionally Directed Medical Research Programs Grant PR-064790 to S. Fried and a Veterans Administration Center grant to J. Rizzo. NR 74 TC 103 Z9 104 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2009 VL 101 IS 4 BP 1972 EP 1987 DI 10.1152/jn.91081.2008 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 422ZA UT WOS:000264465000028 PM 19193771 ER PT J AU Gao, YJ Zhang, L Samad, OA Suter, MR Yasuhiko, K Xu, ZZ Park, JY Lind, AL Ma, Q Ji, RR AF Gao, Yong-Jing Zhang, Ling Samad, Omar Abdel Suter, Marc R. Yasuhiko, Kawasaki Xu, Zhen-Zhong Park, Jong-Yeon Lind, Anne-Li Ma, Qiufu Ji, Ru-Rong TI JNK-Induced MCP-1 Production in Spinal Cord Astrocytes Contributes to Central Sensitization and Neuropathic Pain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; TUMOR-NECROSIS-FACTOR; DORSAL-ROOT GANGLIA; PERIPHERAL-NERVE INJURY; PRIMARY SENSORY NEURONS; TERMINAL KINASE JNK; MECHANICAL ALLODYNIA; FACTOR-ALPHA; CHEMOKINE RECEPTORS; GLIAL ACTIVATION AB Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha(TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd] pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management. C1 [Gao, Yong-Jing; Zhang, Ling; Suter, Marc R.; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ji, Ru-Rong] Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, Boston, MA 02115 USA. [Samad, Omar Abdel; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Samad, Omar Abdel; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ji, RR (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Pain Res Ctr, 75 Francis St,Med Res Bldg,Room 604, Boston, MA 02115 USA. EM rrji@zeus.bwh.harvard.edu RI samad, omar/K-1921-2012; GAO, YONG-JING/E-6939-2015; OI GAO, YONG-JING/0000-0002-7432-7458; Park, Jong Yeon/0000-0003-0588-1903; Ji, Ru-Rong/0000-0002-9355-3688 FU FIC NIH HHS [R03 TW007180, R03 TW007180-03, TW7180]; NIDCR NIH HHS [DE17794, R01 DE013843, R01 DE017794, R01 DE017794-03, R01 DE018025]; NINDS NIH HHS [NS54932, R01 NS047710, R01 NS054932, R01 NS054932-03] NR 77 TC 236 Z9 259 U1 5 U2 24 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2009 VL 29 IS 13 BP 4096 EP 4108 DI 10.1523/JNEUROSCI.3623-08.2009 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 427GJ UT WOS:000264767500014 PM 19339605 ER PT J AU Ikeuchi, Y Stegmuller, J Netherton, S Huynh, MA Masu, M Frank, D Bonni, S Bonni, A AF Ikeuchi, Yoshiho Stegmueller, Judith Netherton, Stuart Huynh, Mai Anh Masu, Masayuki Frank, David Bonni, Shirin Bonni, Azad TI A SnoN-Ccd1 Pathway Promotes Axonal Morphogenesis in the Mammalian Brain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MOUSE COILED-COIL-DIX1 CCD1; POSITIVE REGULATOR; TGF-BETA; GROWTH; CDH1-APC; SNON; IDENTIFICATION; EXPRESSION; RESPONSES; SURVIVAL AB The transcriptional corepressor SnoN is a critical regulator of axonal morphogenesis, but how SnoN drives axonal growth is unknown. Here, we report that gene-profiling analyses in cerebellar granule neurons reveal that the large majority of genes altered upon SnoN knockdown are surprisingly downregulated, suggesting that SnoN may activate transcription in neurons. Accordingly, we find that the transcriptional coactivator p300 interacts with SnoN, and p300 plays a critical role in SnoN-induced axon growth. We also identify the gene encoding the signaling scaffold protein Ccd1 as a critical target of SnoN in neurons. Ccd1 localizes to the actin cytoskeleton, is enriched at axon terminals in neurons, and activates the axon growth-promoting kinase JNK (c-Jun N-terminal protein kinase). Knockdown of Ccd1 in neurons reduces axonal length and suppresses the ability of SnoN to promote axonal growth. Importantly, Ccd1 knockdown in rat pups profoundly impairs the formation of granule neuron parallel fiber axons in the rat cerebellar cortex in vivo. These findings define a novel SnoN-Ccd1 link that promotes axonal growth in the mammalian brain, with important implications for axonal development and regeneration. C1 [Ikeuchi, Yoshiho; Stegmueller, Judith; Huynh, Mai Anh; Bonni, Azad] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Netherton, Stuart; Bonni, Shirin] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Netherton, Stuart; Bonni, Shirin] Univ Calgary, Fac Med, So Alberta Canc Res Inst, Calgary, AB T2N 4N1, Canada. [Frank, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Masu, Masayuki] Univ Tsukuba, Inst Basic Med Sci, Dept Mol Neurobiol, Tsukuba, Ibaraki 3058575, Japan. RP Bonni, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM azad_bonni@hms.harvard.edu RI ikeuchi, yoshiho/C-1713-2014 OI ikeuchi, yoshiho/0000-0002-2829-3840 FU National Institutes of Health (NIH) [NS051255, GM077226]; Harvard Medical School-Merck-Sponsored Research Program; Alberta Cancer Research Institute; Uehara Memorial Foundation; Naito Foundation; Human Frontier Science Program; Charles A. King Trust; Alberta Heritage Foundation for Medical Research (AHFMR) FX This work was supported by National Institutes of Health (NIH) Grant NS051255 (A.B.), the Harvard Medical School-Merck-Sponsored Research Program (A.B.), the Alberta Cancer Research Institute (ACRI; S.B.), the Uehara Memorial Foundation (Y.I.), the Naito Foundation (Y.I.), the Human Frontier Science Program (Y.I.), a Charles A. King Trust (Bank of America, Cotrustee) Postdoctoral Fellowship (J.S.), and NIH Training Grant GM077226 (M.A.H.). S.B. is an Alberta Heritage Foundation for Medical Research (AHFMR) Scholar. S.N. is an AHFMR and ACRI Postdoctoral Fellow. We thank Samantha Keough for technical assistance, Genevieve Konopka for helpful discussions, Sheng-Cai Lin for providing the pSuper/ccd1i plasmid, and Zhen-Ge Luo for providing the Dvl-myc expression plasmid. NR 25 TC 34 Z9 36 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2009 VL 29 IS 13 BP 4312 EP 4321 DI 10.1523/JNEUROSCI.0126-09.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 427GJ UT WOS:000264767500034 PM 19339625 ER PT J AU Nahed, BV Ferreira, M Naunheim, MR Kahle, KT Proctor, MR Smith, ER AF Nahed, Brian V. Ferreira, Manuel, Jr. Naunheim, Matthew R. Kahle, Kristopher T. Proctor, Mark R. Smith, Edward R. TI Intracranial vasospasm with subsequent stroke after traumatic subarachnoid hemorrhage in a 22-month-old child Case report SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE angiogram; stroke; subarachnoid hemorrhage; traumatic brain injury; vasospasm ID CEREBRAL VASOSPASM; BRAIN-INJURY; ANEURYSMS; PREVENTION; HYPERVOLEMIA; HYPERTENSION; ADOLESCENTS; TOMOGRAPHY; THERAPY; PATIENT AB Clinical and radiographic evidence of subarachnoid hemorrhage (SAH)-related vasospasm is rare in children and has not been reported in infants. In this report the authors present the case of a 22-month-old child who developed clinically symptomatic, radiographically identifiable vasospasm after traumatic SAH. To the authors' knowledge, this is the first report of vasospasm associated with SAH in a child this young. This 22-month-old boy fell and had a dense SAH. He had a history of surgically corrected craniosynostosis and nonsymptomatic ventriculomegaly. The boy was evaluated for occult vascular lesions using imaging; none were found and normal vessel caliber was noted. Ten days later, the child developed left-sided weakness and a right middle cerebral artery infarct was identified. Evaluation disclosed significant intracranial vasospasm. This diagnosis was supported by findings on CT angiography, transcranial Doppler ultrasonography, MR imaging, and conventional angiography. The child was treated using intraarterial verapamil with a good result, as well as with conventional intensive care measures to reduce vasospasm. This report documents the first known case of intracranial vasospasm with stroke after SAH in a patient under the age of 2 years. This finding is important because it demonstrates that the entity of SAH-associated vasospasni can affect the very young, widening the spectrum of ages susceptible to this condition. This case is also important because it demonstrates that even very young children can respond to conventional therapeutic interventions such as intraarterial verapamil. Thus,, clinicians need to be alert to the possibility of vasospasm as a potential diagnosis when evaluating Young children with SAH. (DOI: 10.3171/2008.12.PEDS08206) C1 [Ferreira, Manuel, Jr.; Proctor, Mark R.; Smith, Edward R.] Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Nahed, Brian V.; Ferreira, Manuel, Jr.; Naunheim, Matthew R.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Smith, ER (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. EM edward.smith@childrens.harvard.edu NR 24 TC 3 Z9 4 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROS-PEDIATR JI J. Neurosurg.-Pediatr. PD APR PY 2009 VL 3 IS 4 BP 311 EP 315 DI 10.3171/2008.12.PEDS08206 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 424UT UT WOS:000264594500013 PM 19338410 ER PT J AU Cohen, SP Wang, SX Chen, LC Kurihara, C McKnight, G Marcuson, M Mao, JR AF Cohen, Steven P. Wang, Shuxing Chen, Lucy Kurihara, Connie McKnight, Geselle Marcuson, Matthew Mao, Jianren TI An Intravenous Ketamine Test as a Predictive Response Tool in Opioid-Exposed Patients with Persistent Pain SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Dextromethorphan; infusion test; ketamine; N-methyl-D-aspartate; opioid; predictive value; tolerance ID ORAL DEXTROMETHORPHAN TREATMENT; ASPARTATE RECEPTOR ANTAGONISTS; NEUROPATHIC PAIN; DOUBLE-BLIND; CANCER PAIN; POSTHERPETIC NEURALGIA; FIBROMYALGIA SYNDROME; SUBSEQUENT RESPONSE; DIABETIC-NEUROPATHY; TEMPORAL SUMMATION AB Chronic pain patients who are treated with opioid therapy represent a significant challenge to medical professionals. When. pain recurs in the face of a, previously effective opioid regimen, treatment options include (lose escalation., opioid rotation, drug holidays, and the addition Of adjuvants. Some experts advocate the use of N-methyl-D-aspartate receptor (NMDA-R) antagonists to combat tolerance. Recently the use of an, intravenous (i.v.) ketamine infusion to Predict the response to a dextromethorphan (DX) treatment trial has been described. In this study, 56 opioid-exposed patients with recurrent pain were treated with a low-dose (0.1 mg/kg) i.v. ketamine test followed by a DX treatment course. Using previously designated cutoff values for a positive response to ketamine (67% or more pain relief) and DX (50% or more pain relief), the sensitivity, specificity, positive predictive value, and negative Predictive value for an i.v. ketamine infusion to predict subsequent response to DX treatment were 72%, 68%, 52%, and 85%, respectively. The observed agreement between. an.,algesic responses was 78%, indicating a highly significant correlation (r = 0.54, P = 0.0001). Subgroup classification in the response to either ketamine or DX classification revealed no significant differences treatment, based on pain classification (i.e., nociceptive, neuropathic, or mixed) or placebo response. In contrast, a weaker correlation between ketamine and DX response was found in subjects requiring high-dose rather than low-dose opioid therapy. A significant correlation also was noted between. the development of side effects for the two NMDA-R antagonists. Based on These results, we conclude that an i.v. ketamine test may be a valuable toot in predicting subsequent response to DX treatment in opioid-exposed patients. with Persistent pain, J Pain Symptom Manage 2009;37:698-708. (C) 2009 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Cohen, Steven P.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, Baltimore, MD USA. [Marcuson, Matthew] Natl Naval Med Ctr, Bethesda, MD USA. [Cohen, Steven P.; Kurihara, Connie; McKnight, Geselle] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Wang, Shuxing; Chen, Lucy; Mao, Jianren] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Ctr Translat Pain Res, Boston, MA 02114 USA. RP Cohen, SP (reprint author), Johns Hopkins Pain Management Div, 550 N Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen40@jhmi.edu NR 48 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2009 VL 37 IS 4 BP 698 EP 708 DI 10.1016/j.jpainsymman.2008.03.018 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 433SH UT WOS:000265225600010 PM 18789637 ER PT J AU Jacobsen, J AF Jacobsen, Juliet TI Topical Opioids for Pain #185 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID ANALGESIC EFFICACY; MORPHINE; ULCERS; GEL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM JJACOBSEN@PARTNERS.ORG NR 14 TC 2 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD APR PY 2009 VL 12 IS 4 BP 380 EP 381 DI 10.1089/jpm.2009.9642 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 425HD UT WOS:000264626700024 PM 19327077 ER PT J AU Kleinman, RE AF Kleinman, Ronald E. TI THE PROTEIN REQUIREMENT OF INFANTS SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Kleinman, Ronald E.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2009 VL 154 IS 4 BP 556 EP 556 DI 10.1016/j.jpeds.2008.09.046 PG 1 WC Pediatrics SC Pediatrics GA 427VU UT WOS:000264808000021 ER PT J AU Broder-Fingert, S Crowley, WF Boepple, PA AF Broder-Fingert, Sarabeth Crowley, William F. Boepple, Paul A. TI Safety of Frequent Venous Blood Sampling in a Pediatric Research Population SO JOURNAL OF PEDIATRICS LA English DT Article ID ERYTHROPOIESIS AB Objective To monitor hematological indices in otherwise healthy children with central precocious puberty who underwent frequent venous sampling as part of a longitudinal clinical research study. Study design Thirty-four female subjects underwent frequent venous sampling (every 10-20 minutes for 8-16 hours) every 6 months for >= 3 years during and after their treatment with a gonadotropin-releasing hormone analogue. Hemoglobin (Hgb), mean corpuscular volume, and ferritin levels were measured before and after each phlebotomy session. Results At baseline, the average Hgb level was 12.5 +/- 0.7 g/L. At the conclusion of the first sampling session, the Hgb level fell 1.2 +/- 0.1 g/L, remaining within the reference range for age. At the 3-month follow-up, there was complete recovery of Hgb (12.6 +/- 0.2 g/L). Longitudinal evaluation every 6 months for as long as 3 years showed no significant differences in Hgb, mean corpuscular volume, or ferritin levels from baseline. No clinically significant adverse effects attributable to phlebotomy were reported. Conclusion When appropriate safety guidelines were followed, both acute and long-term frequent venous sampling in a pediatric population was safe. Guidelines include monitoring of hematological indices, phlebotomy volume < 10 mL/kg/24 hours, and iron replacement. (J Pediatr 2009;154:578-81) C1 [Broder-Fingert, Sarabeth; Crowley, William F.; Boepple, Paul A.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Broder-Fingert, Sarabeth; Crowley, William F.; Boepple, Paul A.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Dept Med, Boston, MA 02114 USA. [Boepple, Paul A.] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Boepple, Paul A.] Massachusetts Gen Hosp Children, Ctr Diabet, Boston, MA USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, 55 Fruit St,Bartlett Hall Extens 511, Boston, MA 02114 USA. EM sbroder-finger@partners.org OI Broder-Fingert, Sarabeth/0000-0002-0932-4461 FU NCRR NIH HHS [M01 RR001066-26, RR-01066, RR-08847, M01 RR001066]; NICHD NIH HHS [HD-18169, R01 HD018169-12] NR 11 TC 6 Z9 6 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2009 VL 154 IS 4 BP 578 EP 581 DI 10.1016/j.jpeds.2008.10.007 PG 4 WC Pediatrics SC Pediatrics GA 427VU UT WOS:000264808000026 PM 19026428 ER PT J AU Kaya, AI Ugur, O Oner, SS Bastepe, M Onaran, HO AF Kaya, A. I. Ugur, Oe Oener, S. S. Bastepe, M. Onaran, H. O. TI Coupling of beta 2-Adrenoceptors to XL alpha(s) and G alpha(s): A New Insight into Ligand-Induced G Protein Activation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID XL-ALPHA-S; SIGNAL-TRANSDUCTION; SPLICE VARIANTS; RECEPTOR ACTIVITY; GNAS GENE; SUBUNIT; MODEL; CYCLASE; LONG AB G alpha(s) and extra-large G alpha(s) (XL alpha(s)) can both transduce receptor activation into intracellular cAMP generation. It is unknown, however, whether these two GNAS-locus products display distinct properties with respect to receptor coupling. Here, we show that XL alpha(s) couples to the beta 2-adrenoceptor more efficiently than G alpha(s). In transfected human embryonic kidney 293 cells and mouse embryonic fibroblasts null for both G alpha(s) and XL alpha(s) (2B2 cells), basal cAMP accumulation mediated by XL alpha(s) was higher than that mediated by G alpha(s). Inverse agonist treatment reduced G alpha(s)-mediated basal activity, whereas its effect was markedly blunted on XL alpha(s)-mediated basal activity. Rank order of ligand efficacies regarding cAMP accumulation was the same when the receptor was coupled to XL alpha(s) or G alpha(s). However, ligand-induced and XL alpha(s)-mediated cAMP generation was higher than that mediated by G alpha(s). The relatively high efficiency of XL alpha(s)-mediated cAMP generation was conditional, disappearing with increased level of receptor expression or increased efficacy of ligand. Full-agonist responses in XL alpha(s)- and G alpha(s)-expressing cells were comparable even at low receptor levels, whereas partial agonist responses became comparable only when the receptor expression was increased (>3 pmol/mg). Radioligand binding studies showed that the high-affinity component in agonist binding to beta 2-adrenoceptor was more pronounced in cells expressing XL alpha(s) than those expressing G alpha(s). We discuss these findings in the framework of current receptor-G protein activation models and offer an extended ternary complex model that can fully explain our observations. C1 [Kaya, A. I.; Ugur, Oe; Oener, S. S.; Onaran, H. O.] Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. [Kaya, A. I.] Ankara Univ, Inst Biotechnol, TR-06100 Ankara, Turkey. [Onaran, H. O.] Mol Biol & Technol Dev Unit, Ankara, Turkey. [Bastepe, M.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, M.] Harvard Univ, Sch Med, Boston, MA USA. RP Onaran, HO (reprint author), Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. EM onaran@medicine.ankara.edu.tr RI Oner, Sukru/K-8032-2012 FU Turkish Scientific and Technical Research Council [104s472, 107s086]; Ankara University Research Fund [BAP 2002 0809 088]; Ankara University Biotechnology Institute [103]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK073911] FX This work was supported in part by the Turkish Scientific and Technical Research Council [Grants 104s472, 107s086]; the Ankara University Research Fund [Grant BAP 2002 0809 088]; the Ankara University Biotechnology Institute [Grant 103]; and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK073911]. NR 32 TC 11 Z9 11 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2009 VL 329 IS 1 BP 350 EP 359 DI 10.1124/jpet.108.149989 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 426KW UT WOS:000264708200039 PM 19144685 ER PT J AU Netherland, J Botsko, M Egan, JE Saxon, AJ Cunningham, CO Finkelstein, R Gourevitch, MN Renner, JA Sohler, N Sullivan, LE Weiss, L Fiellin, DA AF Netherland, Julie Botsko, Michael Egan, James E. Saxon, Andrew J. Cunningham, Chinazo O. Finkelstein, Ruth Gourevitch, Mark N. Renner, John A. Sohler, Nancy Sullivan, Lynn E. Weiss, Linda Fiellin, David A. CA BHIVES Collaborative TI Factors affecting willingness to provide buprenorphine treatment SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Buprenorphine; Opioid-related disorders; HIV; Physician's practice patterns; Willingness ID OFFICE-BASED TREATMENT; PRIMARY-CARE; OPIOID DEPENDENCE; METHADONE-MAINTENANCE; MEDICAL MAINTENANCE; HEROIN DEPENDENCE; OPIATE ADDICTION; RANDOMIZED-TRIAL; GENERAL-PRACTICE; DRUG-ABUSE AB Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit tune; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine. (C) 2009 Elsevier Inc. All rights reserved. C1 [Netherland, Julie; Finkelstein, Ruth] New York Acad Med, Div Hlth Policy, New York, NY 10029 USA. [Botsko, Michael; Egan, James E.; Weiss, Linda] New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY 10029 USA. [Saxon, Andrew J.] Univ Washington, Addict Care Line VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Cunningham, Chinazo O.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Gourevitch, Mark N.] NYU, Sch Med, Div Gen Internal Med, New York, NY 10016 USA. [Renner, John A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Renner, John A.] VA Boston Healthcare Syst, Boston, MA 02152 USA. [Sohler, Nancy] CUNY, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA. [Sullivan, Lynn E.; Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Netherland, J (reprint author), New York Acad Med, Div Hlth Policy, 1216 5th Ave, New York, NY 10029 USA. EM jnetherland@nyam.org OI Fiellin, David/0000-0002-4006-010X; Gourevitch, Marc/0000-0001-6865-2126 FU NIDA NIH HHS [R25 DA023021, R25 DA023021-03]; PHS HHS [H97HA03795] NR 47 TC 55 Z9 55 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2009 VL 36 IS 3 BP 244 EP 251 DI 10.1016/j.jsat.2008.06.006 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 423QE UT WOS:000264510000002 PM 18715741 ER PT J AU Harris, AHS Humphreys, K Bowe, T Kivlahan, DR Finney, JW AF Harris, Alex H. S. Humphreys, Keith Bowe, Thomas Kivlahan, Daniel R. Finney, John W. TI Measuring the quality of substance use disorder treatment: Evaluating the validity of the Department of Veterans Affairs continuity of care performance measure SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Health care delivery; Substance use disorder services; Veterans; Performance measures; Standards of quality; Continuity of care; Continuing care ID ADDICTION SEVERITY INDEX; PATTERN-MIXTURE MODELS; MISSING DATA; FOLLOW-UP; ABUSE TREATMENT; TREATMENT OUTCOMES; CHANGE SCORES; INDICATORS; REGRESSION; RETENTION AB This study examined the patient- and facility-level associations between the continuity of care performance measure adopted by the Department of Veterans Affairs (VA) and improvements in self-administered Addiction Severity Index (ASI) composites and other indicators of problematic substance use. Up to 50 patients from each of a nationally representative sample of 109 VA substance use disorder (SUD) treatment programs at 73 VA facilities were assessed at intake and posttreatment. The continuity of care performance measure specifies that patients should receive at least two SUD outpatient visits in each of the three consecutive 30-day periods after they qualify as new SUD patients. In analyses adjusting for baseline characteristics, meeting the continuity of care performance measure was not associated with patient-level improvements in the ASI alcohol or drug composites, days of alcohol intoxication, or days of substance-related problems. Facility-level rates of continuity of care were negatively associated with improvements in ASI alcohol and drug composites. The continuity of care performance measure derived from prior patient-level evidence did not discriminate facility-level performance as predicted. Translating research into process-of-care quality measures requires postconstruction validation. Published by Elsevier Inc. C1 [Harris, Alex H. S.; Humphreys, Keith; Bowe, Thomas; Finney, John W.] Dept Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Harris, Alex H. S.; Humphreys, Keith; Bowe, Thomas; Finney, John W.] Stanford Univ, Sch Med, Menlo Pk, CA 94025 USA. [Kivlahan, Daniel R.] Univ Washington, Sch Med, Seattle, WA 98108 USA. [Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Qual Enhancement Res Initiat, Subst Use Disorder Ctr, Seattle, WA 98108 USA. RP Harris, AHS (reprint author), Dept Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,MPD 152, Menlo Pk, CA 94025 USA. EM alexander.harris2@va.gov NR 47 TC 22 Z9 22 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2009 VL 36 IS 3 BP 294 EP 305 DI 10.1016/j.jsat.2008.05.011 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 423QE UT WOS:000264510000006 PM 18835678 ER PT J AU Adegbola, A AF Adegbola, Abidemi TI The Troubled Dream of Genetic Medicine: Ethnicity and Innovation in Tay-Sachs, Cystic Fibrosis, and Sickle Cell Disease. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Adegbola, Abidemi] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Adegbola, A (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM adegbola@chgr.mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2009 VL 48 IS 4 BP 452 EP 453 DI 10.1097/01.CHI.0b013e31819a1c1c PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 423PI UT WOS:000264507800014 ER PT J AU Liu, H AF Liu, Howard TI Parenting, Inc. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Liu, Howard] Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. RP Liu, H (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. EM hliu@partners.org 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 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2009 VL 48 IS 4 BP 454 EP 455 DI 10.1097/01.CHI.0000314066.27532.dc PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 423PI UT WOS:000264507800016 ER PT J AU Lee, HJ Chapa, D Kao, CW Jones, D Kapustin, J Smith, J Krichten, C Donner, T Thomas, SA Friedmann, E AF Lee, Hyeon-Joo Chapa, Deborah Kao, Chi-Wen Jones, Deborah Kapustin, Jane Smith, Jamie Krichten, Cathy Donner, Thomas Thomas, Sue A. Friedmann, Erika TI Depression, quality of life, and glycemic control in individuals with type 2 diabetes SO JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS LA English DT Article DE A1C; retinopathy; neuropathy; depression; quality of life; HbA1c ID PLACEBO-CONTROLLED TRIAL; PRIMARY-CARE PATIENTS; AFRICAN-AMERICANS; COMORBID DEPRESSION; METABOLIC-CONTROL; GLUCOSE CONTROL; DOUBLE-BLIND; SELF-CARE; SYMPTOMS; MELLITUS AB The purpose of this article is to evaluate the contributions of diabetic complications to depression beyond the contributions of demographic characteristics in patients with type 2 diabetes. Further, this article evaluates the contributions of diabetic complications, depression, and quality of life to A1C (also know as HbA1c) beyond the contributions of demographic characteristics in individuals with type 2 diabetes. A cross-sectional survey of 55 individuals with type 2 diabetes attending an inner city diabetes specialty clinic. Patients completed the Beck Depression Inventory - II, the Inventory of Depressive Symptomatology Self-Report, the Medical Outcome Study Short Form-36, and a demographic questionnaire. A1C and diabetes-related comorbidities were obtained from the patients' medical records. Being younger and female were associated with depression in individuals with type 2 diabetes. After controlling for age and gender, neuropathy tended to add to the prediction of depression; other comorbidities did not. Being black was associated with poor diabetic control (A1C > 7). After controlling for race, neuropathy and retinopathy predicted poor diabetes control and depression tended to predict poor diabetes control. Given the high prevalence of depression, the relationship of depression with poor diabetic self-care and medication adherence, and the increased cost of treatment for patients with depression among individuals with type 2 diabetes, assessment of depression is crucial. Further research is needed to establish effective treatment of depression and its effect on glycemic control in patients with type 2 diabetes. C1 [Lee, Hyeon-Joo; Jones, Deborah; Kapustin, Jane; Smith, Jamie; Thomas, Sue A.; Friedmann, Erika] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Chapa, Deborah] Florida Gulf Coast Univ, Sch Nursing, Ft Myers, FL USA. [Kao, Chi-Wen] Natl Def Med Ctr, Sch Nursing, Taipei, Taiwan. [Krichten, Cathy] Univ Maryland, Joslin Diabet Ctr, Baltimore, MD 21201 USA. [Donner, Thomas] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. RP Friedmann, E (reprint author), Univ Maryland, Sch Nursing, 655 W Lombard St, Baltimore, MD 21201 USA. EM friedmann@son.umaryland.edu OI Friedmann, Erika/0000-0003-2924-0449 NR 57 TC 18 Z9 20 U1 7 U2 21 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1041-2972 J9 J AM ACAD NURSE PRAC JI J. Am. Acad. Nurse Pract. PD APR PY 2009 VL 21 IS 4 BP 214 EP 224 DI 10.1111/j.1745-7599.2009.00396.x PG 11 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 428WN UT WOS:000264882500004 PM 19366380 ER PT J AU Simovitch, R Sanders, B Ozbaydar, M Lavery, K Warner, JJP AF Simovitch, Ryan Sanders, Brett Ozbaydar, Mehmet Lavery, Kyle Warner, Jon J. P. TI Acromioclavicular Joint Injuries: Diagnosis and Management SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID CORACOCLAVICULAR LIGAMENT RECONSTRUCTION; FOREIGN-BODY REACTION; NONOPERATIVE TREATMENT; CONSERVATIVE TREATMENT; COMPLETE DISLOCATION; CORACOID PROCESS; CLAVICLE; SEPARATIONS; AUGMENTATION; ANATOMY AB Acromioclavicular joint injuries represent nearly half of all athletic shoulder injuries, often resulting from a fall onto the tip of the shoulder with the arm in adduction. Stability of this joint depends on the integrity of the acromioclavicular ligaments and capsule as well as the coracoclavicular ligaments and the trapezius and deltoid muscles. Along with clinical examination for tenderness and instability, radiographic examination is critical in the evaluation of acromioclavicular joint injuries. Nonsurgical treatment is indicated for type I and II injuries; surgery is almost always recommended for type IV, V, and VI injuries. Management of type III injuries remains controversial, with nonsurgical treatment favored in most instances and reconstruction of the acromioclavicular joint reserved for symptomatic instability. Recommended techniques for stabilization in cases of acute and late symptomatic instability include screw fixation of the coracoid process to the clavicle, coracoacromial ligament transfer, and coracoclavicular ligament reconstruction. Biomechanical studies have demonstrated that anatomic acromioclavicular joint reconstruction is the most effective treatment for persistent instability. C1 [Simovitch, Ryan] Palm Beach Orthopaed Inst, Palm Beach Gardens, FL 33410 USA. [Sanders, Brett] Ctr Sports Med & Orthopaed, Chattanooga, TN USA. [Ozbaydar, Mehmet; Lavery, Kyle; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Simovitch, R (reprint author), Palm Beach Orthopaed Inst, Suite 500,3401 PGA Blvd, Palm Beach Gardens, FL 33410 USA. RI Ozbaydar, Mehmet/D-7391-2016 NR 63 TC 54 Z9 59 U1 1 U2 12 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 APR PY 2009 VL 17 IS 4 BP 207 EP 219 PG 13 WC Orthopedics SC Orthopedics GA 424TZ UT WOS:000264592500002 PM 19307670 ER PT J AU Hwang, DK Oakey, J Toner, M Arthur, JA Anseth, KS Lee, S Zeiger, A Van Vliet, KJ Doyle, PS AF Hwang, Dae Kun Oakey, John Toner, Mehmet Arthur, Jeffrey A. Anseth, Kristi S. Lee, Sunyoung Zeiger, Adam Van Vliet, Krystyn J. Doyle, Patrick S. TI Stop-Flow Lithography for the Production of Shape-Evolving Degradable Microgel Particles SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID B-PLA HYDROGEL; STATISTICAL KINETIC-MODEL; PEG HYDROGELS; CONTROLLED-RELEASE; ENCAPSULATING CHONDROCYTES; MICROFLUIDIC DEVICE; BULK DEGRADATION; MICROSTRUCTURES; FABRICATION; GENERATION AB Microgel particles capable of bulk degradation have been synthesized from a solution of diacrylated triblock copolymer composed of poly(ethylene glycol) and poly(lactic acid) in a microfluidic device using stop-flow lithography (SFL). It has been previously demonstrated that SFL can be used to fabricate particles with precise control over particle size and shape. Here, we have fabricated hydrogel particles of varying size and shape and examined their mass-loss and swelling behavior histologically and mechanically. We report that these features, as well as degradation behavior of the hydrogel particles may be tailored with SFL. By reducing the applied UV dose during fabrication, hydrogel particles can be made to exhibit a distinct deviation from the classical erosion profiles of bulk-degrading hydrogels. At higher UV doses, a saturation in cross-linking density occurs and bulk-degrading behavior is observed. Finally, we synthesized multifunctional composite particles, providing unique features not found in homogeneous hydrogels. C1 [Hwang, Dae Kun; Doyle, Patrick S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Lee, Sunyoung; Zeiger, Adam; Van Vliet, Krystyn J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Oakey, John; Toner, Mehmet] Harvard Univ, Sch Med, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. [Oakey, John; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med, Charlestown, MA 02129 USA. [Oakey, John; Toner, Mehmet] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Arthur, Jeffrey A.; Anseth, Kristi S.] Univ Colorado, Dept Chem & Biol Engn, Boulder, CO 80403 USA. RP Doyle, PS (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM pdoyle@mit.edu FU NSF NIRT [CTS-0304128]; Natural Sciences and Engineering Research Council of Canada (NSERC) [NIH-P41EB002503] FX We gratefully acknowledge the support of NSF NIRT Grant No. CTS-0304128 and the Singapore-MIT Alliance (SMA-II, CPE Program) for this project. D.K.H. acknowledges the support from the Natural Sciences and Engineering Research Council of Canada (NSERC) for a NSERC Postdoctoral Fellowship. J.O.. acknowledges funding under NIH-P41EB002503. NR 38 TC 65 Z9 65 U1 5 U2 56 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 1 PY 2009 VL 131 IS 12 BP 4499 EP 4504 DI 10.1021/ja809256d PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 427QD UT WOS:000264792900061 PM 19215127 ER PT J AU McKeown, NM Meigs, JB Liu, SM Rogers, G Yoshida, M Saltzman, E Jacques, PF AF McKeown, Nicola M. Meigs, James B. Liu, Simin Rogers, Gail Yoshida, Makiko Saltzman, Edward Jacques, Paul F. TI Dietary Carbohydrates and Cardiovascular Disease Risk Factors in the Framingham Offspring Cohort SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE dietary glycemic index; CVD risk factors; diet ID LOW-GLYCEMIC-INDEX; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE ATHEROSCLEROSIS; BODY-FAT DISTRIBUTION; MIDDLE-AGED WOMEN; LIPID PROFILE; FIBER INTAKE AB Objective: Evidence from observational studies has suggested that carbohydrate quality rather than absolute intake is associated with greater risk of chronic diseases. The aim of this study was to examine the relationship between carbohydrate intake and dietary glycemic index and several cardiovascular disease risk factors. Methods: We examined cross-sectional associations between total carbohydrate and dietary glycemic index (GI) intakes and several cardiovascular disease risk factors (CVD) in a sample of 2,941 Framingham Offspring Participants. CVD risk factors included waist, blood pressure, lipids, fasting insulin, fasting glucose, and the insulin sensitivity index (ISI(0.120)). Dietary intake was assessed by a food frequency questionnaire (FFQ) and categorized by quintiles of dietary intake. Results: After adjustment for potential confounding factors, dietary GI was positively associated with fasting triglycerides (mean: 115mg/dL in the lowest and 127 mg/dL in the highest quintile of intake; P for trend < 0.001), fasting insulin (26.8 and 28.9 mu u/mL, respectively, P for trend < 0.0001), and inversely associated with HDL cholesterol (49 and 47 mg/dL, respectively, P for trend 0.003) and ISI(0.120) (26.8 and 25.1, P for trend <0.001). There was no significant relationship between dietary GI and waist circumference, total cholesterol, LDL cholesterol and fasting glucose. Intakes of total carbohydrate were inversely associated with waist circumference and HDL cholesterol, and positively associated with fasting triglycerides. Conclusion: These cross-sectional findings support the hypothesis that a high GI diet unfavorably affects CVD risk factors and therefore, substitution of high with low GI dietary carbohydrates may have reduce the risk of CVD. C1 [McKeown, Nicola M.] Tufts Univ, Nutr Epidemiol Program, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, 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. [Liu, Simin] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA. [Liu, Simin] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP McKeown, NM (reprint author), Tufts Univ, Nutr Epidemiol Program, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM nicola.mckeown@tufts.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU U.S. Department of Agriculture [58-1950-7-707]; Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health [N01-HC-25195]; American Diabetes Association; American Heart Association FX Financial support: Supported in part by the U.S. Department of Agriculture, under agreement No. 58-1950-7-707 and support from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health (Contract No. N01-HC-25195): Dr Meigs is supported by an American Diabetes Association Career Development Award. Dr. McKeown is supported in part by a scientist development award from the American Heart Association. NR 70 TC 28 Z9 29 U1 1 U2 9 PU AMER COLLEGE NUTRITION PI CLEARWATER PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD APR PY 2009 VL 28 IS 2 BP 150 EP 158 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 580TN UT WOS:000276473300003 PM 19828900 ER PT J AU Schnelle, JF Simmons, SF Beuscher, L Peterson, EN Habermann, R Leung, F AF Schnelle, John F. Simmons, Sandra F. Beuscher, Linda Peterson, Emily N. Habermann, Ralf Leung, Felix TI Prevalence of Constipation Symptoms in Fecally Incontinent Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Constipation; fecal incontinence; nursing home ID MANAGEMENT AB To determine the prevalence of constipation symptoms and the effects of a brief toileting assistance trial on constipation in a sample of fecally incontinent nursing home (NH) residents. Observational study. Five NHs. One hundred eleven fecally incontinent NH residents. Research staff measured bowel movement frequency every 2 hours for 10 days. The following week, residents were offered toileting assistance every 2 hours for 2 days to determine resident straining, time required for a bowel movement, and resident perceptions of feeling empty after a bowel movement. Constipation data were abstracted from the medical record. The frequency of bowel movements during usual NH care was low (mean=0.32 per person per day), and most episodes were incontinent. The frequency of bowel movements increased significantly, to 0.82 per person per day, and most episodes were continent during the 2 days that research staff provided toileting assistance. Eleven percent of residents showed evidence of straining, and 21% of the time after a continent bowel movement, residents reported not feeling empty. Five percent of participants had medical record or Minimum Data Set documentation indicative of constipation symptoms. Low rates of bowel movements during the day that are potentially indicative of constipation were immediately improved during a 2-day trial of toileting assistance in approximately 68% of the residents, although other symptoms of constipation remained in a subset of residents who increased toileting frequency. C1 [Schnelle, John F.; Simmons, Sandra F.; Beuscher, Linda; Peterson, Emily N.] Vanderbilt Univ, Div Gen Internal Med & Publ Hlth, Ctr Qual Aging, Sch Med, Nashville, TN 37232 USA. [Beuscher, Linda] Vanderbilt Univ, Sch Nursing, Nashville, TN 37232 USA. [Habermann, Ralf] Vanderbilt Univ, Div Gen Internal Med & Publ Hlth, Vanderbilt Senior Care ACE Unit, Nashville, TN 37232 USA. [Schnelle, John F.; Simmons, Sandra F.] Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Nashville, TN 37212 USA. [Leung, Felix] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Schnelle, JF (reprint author), Vanderbilt Univ, Med Ctr, 1161 21st Ave S,S-1121 Med Ctr N, Nashville, TN 37232 USA. EM John.Schnelle@vanderbilt.edu FU National Institutes of Health (NIH), [RO1 AG023555]; NIH FX This research was supported by Grant RO1 AG023555 from the National Institutes of Health (NIH), John F. Schnelle, Principal Investigator. We extend thanks to the following valuable research team members: Roberta McCord, Sonia Meador, Clayton Ellis, and Christie Young.; Conflict of Interest: 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 paper.; Author Contributions: Dr. Schnelle was the principle investigator and took primary lead in the development of all aspects of the paper listed under ths category. The other authors contributed to writing, data analysis, conceptualization, or all three.; Sponsor's Role: NIH who funded and approved the trial. NR 14 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2009 VL 57 IS 4 BP 647 EP 652 DI 10.1111/j.1532-5415.2009.02215.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 428WT UT WOS:000264883500009 PM 19392956 ER PT J AU Weinstein, AM Barton, C Ross, L Kramer, JH Yaffe, K AF Weinstein, Andrea M. Barton, Cynthia Ross, Leslie Kramer, Joel H. Yaffe, Kristine TI Treatment Practices of Mild Cognitive Impairment in California Alzheimer's Disease Centers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Academy-of-Neurology CY APR 12-19, 2008 CL Chicago, IL SP Amer Acad Neurol DE Alzheimer's disease; mild cognitive impairment; aging; medications; cholinesterase inhibitors ID RANDOMIZED CONTROLLED-TRIAL; VASCULAR DEMENTIA; VITAMIN-E; DIAGNOSIS; DECLINE; SUPPLEMENTATION; HOMOCYSTEINE; PREVALENCE; DONEPEZIL; CRITERIA AB To examine "real world" treatments for patients with mild cognitive impairment (MCI). Cross-sectional. California Department of Public Health Alzheimer's Disease (AD) Research Centers of California. Five hundred seventy-eight patients diagnosed with MCI. All patients underwent comprehensive neurological and neuropsychological evaluations. Logistic regression models were used to determine patient characteristics associated with use of anti-AD medications, statins, antioxidants, and folic acid. One hundred sixty-six patients (28.7%) were taking anti-AD medications; use was associated with greater functional impairment, higher education, MCI subtype, and older age (P <.05 for all). Two hundred fifty-two patients (43.6%) were taking statins; use was associated with diabetes mellitus, hypertension, myocardial infarct, male sex, and MCI subtype (P <.05 for all). One hundred fifteen patients (19.9%) were taking antioxidants; use was associated with higher education and diabetes mellitus and varied according to site (P <.05 for all). Thirty-seven patients (6.4%) were taking folic acid; use was associated with nonwhite race, male sex, and greater functional impairment (P <.05 for all). This study suggests that patients with MCI are frequently being treated with "off label" cholinesterase inhibitors and memantine, as well as other possible cognition-enhancing drugs. Further investigation of the effect of treatment patterns on the clinical course of MCI is needed. C1 [Weinstein, Andrea M.; Barton, Cynthia; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Weinstein, Andrea M.] No Calif Inst Res & Educ, San Francisco, CA USA. [Barton, Cynthia; Ross, Leslie; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Sch Nursing, Dept Psychiat, San Francisco, CA 94121 USA. [Barton, Cynthia; Ross, Leslie; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Sch Nursing, Dept Neurol, San Francisco, CA 94121 USA. [Barton, Cynthia; Ross, Leslie; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Sch Nursing, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Nursing, Inst Hlth & Aging, San Francisco, CA 94121 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Sch Nursing, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU NIA NIH HHS [K24 AG031155-01, 1K24AG031155-01, K24 AG031155] NR 30 TC 19 Z9 19 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2009 VL 57 IS 4 BP 686 EP 690 DI 10.1111/j.1532-5415.2009.02200.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 428WT UT WOS:000264883500016 PM 19392962 ER PT J AU Siever, LJ Weinstein, LN AF Siever, Larry J. Weinstein, Lissa N. TI THE NEUROBIOLOGY OF PERSONALITY DISORDERS: IMPLICATIONS FOR PSYCHOANALYSIS SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Review ID SOCIAL ANXIETY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; VISUOSPATIAL WORKING-MEMORY; C/T PROMOTER POLYMORPHISMS; DRD4 GENE POLYMORPHISM; MONOAMINE-OXIDASE-A; SCHIZOTYPAL-PERSONALITY; BORDERLINE PERSONALITY; ATTACHMENT DISORGANIZATION; IMPULSIVE AGGRESSION AB As advances in neuroscience have furthered our understanding of the role of brain circuitry, genetics, stress, and neuromodulators in the regulation of normal behavior and in the pathogenesis of psychopathology, an increasing appreciation of the role of neurobiology in individual differences in personality and their pathology in personality disorders has emerged. Individual differences in the regulation and organization of cognitive processes, affective reactivity, impulse/action patterns, and anxiety may in the extreme provide susceptibilities to personality disorders such as borderline and schizotypal personality disorder. A low threshold for impulsive aggression, as observed in borderline and antisocial personality disorders, may be related to excessive amygdala reactivity, reduced prefrontal inhibition, and diminished serotonergic facilitation of prefrontal controls. Affective instability may be mediated by excessive limbic reactivity in gabaminergic/glutamatergic/cholinergic circuits, resulting in an increased sensitivity or reactivity to environmental emotional stimuli as in borderline personality disorder and other cluster B personality disorders. Disturbances in cognitive organization and information processing may contribute to the detachment, desynchrony with the environment, and cognitive/perceptional distortions of cluster A or schizophrenia spectrum personality disorders. A low threshold for anxiety may contribute to the avoidant, dependent, and compulsive behaviors observed in cluster C personality disorders. These alterations in critical regulatory domains will influence how representations of self and others are internalized. Aspects of neurobiological functioning themselves become cognized through the medium of figurative language into an ongoing narrative of the self, one that can be transformed through the analytic process, allowing for the modulation of genetic/biological thresholds. C1 [Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Siever, Larry J.] VISN 3 Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. [Weinstein, Lissa N.] CUNY City Coll, Doctoral Program Clin Psychol, New York, NY USA. RP Siever, LJ (reprint author), Dept Psychiat OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM larry.siever@va.gov FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH56140] NR 140 TC 24 Z9 25 U1 4 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD APR PY 2009 VL 57 IS 2 BP 361 EP 398 DI 10.1177/0003065109333502 PG 38 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 458DM UT WOS:000266994400005 PM 19516057 ER PT J AU Porcerelli, J Dauphin, B Ablon, JS Leitman, S Bambery, M AF Porcerelli, John Dauphin, Barry Ablon, J. Stuart Leitman, Susan Bambery, Michael TI PSYCHOANALYSIS OF AVOIDANT PERSONALITY DISORDER: A SYSTEMATIC CASE STUDY OF PROCESS AND OUTCOME SO JOURNAL OF THE AMERICAN PSYCHOANALYTIC ASSOCIATION LA English DT Meeting Abstract ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; NATIONAL INSTITUTE; PSYCHOTHERAPY; THERAPY; DEPRESSION C1 [Porcerelli, John] Wayne State Univ, Sch Med, Detroit, MI 48202 USA. [Dauphin, Barry; Bambery, Michael] Univ Detroit Mercy, Detroit, MI 48221 USA. [Ablon, J. Stuart] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ablon, J. Stuart] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM jporcer@med.wayne.edu NR 11 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-0651 J9 J AM PSYCHOANAL ASS JI J. Am. Psychoanal. Assoc. PD APR PY 2009 VL 57 IS 2 BP 444 EP 449 PG 6 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA 458DM UT WOS:000266994400013 PM 19516064 ER PT J AU Adams, MS AF Adams, Mark S. TI The Cardiac Sonographer in the Operating Room: Who's Left Holding the Probe? SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID ECHOCARDIOGRAPHY; GUIDELINES; RECOMMENDATIONS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, MS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2009 VL 22 IS 4 BP 36A EP 37A DI 10.1016/j.echo.2009.02.017 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 427YL UT WOS:000264814900002 PM 19345301 ER PT J AU Yared, K Solis, J Passeri, J King, MEE Levine, RA AF Yared, Kibar Solis, Jorge Passeri, Jonathan King, Mary Etta E. Levine, Robert A. TI Three-Dimensional Echocardiographic Assessment of Acquired Left Ventricular to Right Atrial Shunt (Gerbode Defect) SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Aortic valve replacement; Gerbode defect; Three-dimensional echocardiography AB A 60-year-old man was readmitted 1 year after bioprosthetic aortic valve replacement for recurrent endocarditis. Transthoracic 2-dimensional color Doppler revealed a novel finding of a left-to-right shunt from the left ventricular outflow tract to the right atrium immediately superior to the septal leaflet of the tricuspid valve consistent with an acquired Gerbode defect. Real-time 3-dimensional echocardiography was used to accurately delineate the course of the shunt. To avoid overestimating right ventricular systolic pressure by mistaking such a shunt for an eccentric jet of tricuspid regurgitation, it is important to accurately differentiate the two. Real-time 3-dimensional echocardiography now provides rapid, detailed 3-dimensional appreciation of the origin and course of such shunts with easy facility of orienting views to the flows of interest by cropping. Such information can help design optimal surgical or catheter-based therapy. (J Am Soc Echocardiogr 2009;22:435.e1-e3.) C1 [Yared, Kibar; Solis, Jorge; Passeri, Jonathan; King, Mary Etta E.; Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Yared, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM kyared@partners.org FU NHLBI NIH HHS [K24 HL067434-08, K24 HL067434] NR 2 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2009 VL 22 IS 4 AR 435.e1 DI 10.1016/j.echo.2008.12.026 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 427YL UT WOS:000264814900026 PM 19201573 ER PT J AU Fried, L AF Fried, Linda TI Are We Ready to Screen the General Population for Microalbuminuria? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR OUTCOMES; DIABETIC NEPHROPATHY; COST-EFFECTIVENESS; PREVENTION; RAMIPRIL; EVENTS; PROTEINURIA; INHIBITION; FOSINOPRIL C1 [Fried, Linda] Univ Pittsburgh, Dept Med, Sch Med, Renal Sect,VA Pittsburgh Healthcare Syst,Renal El, Pittsburgh, PA 15240 USA. [Fried, Linda] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Fried, L (reprint author), Univ Pittsburgh, Dept Med, Sch Med, Renal Sect,VA Pittsburgh Healthcare Syst,Renal El, Univ Dr, Pittsburgh, PA 15240 USA. EM linda.fried@va.gov NR 15 TC 22 Z9 27 U1 1 U2 1 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 APR PY 2009 VL 20 IS 4 BP 686 EP 688 DI 10.1681/ASN.2009020147 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 428ER UT WOS:000264831300004 PM 19279125 ER PT J AU Chan, KE Lazarus, JM Thadhani, R Hakim, RM AF Chan, Kevin E. Lazarus, J. Michael Thadhani, Ravi Hakim, Raymond M. TI Anticoagulant and Antiplatelet Usage Associates with Mortality among Hemodialysis Patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; COLLEGE-OF-CARDIOLOGY; ADMINISTRATIVE DATA; VASCULAR CALCIFICATION; CARDIOVASCULAR-DISEASE; WARFARIN; COMORBIDITY; PREVENTION; SURVIVAL AB Many prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. This retrospective cohort study examined whether use of warfarin, clopidogrel, and/or aspirin affected survival in 41,425 incident hemodialysis patients during 5 yr of follow-up. The prescription frequencies for warfarin, clopidogrel, and aspirin were 8.3, 10.0, and 30.4%, respectively, during the first 90 d of initiating chronic hemodialysis. Compared with the 24,740 patients receiving none of these medications, Cox proportional hazards analysis suggested that exposure to these medications was associated with increased risk for mortality (warfarin hazard ratio [HR] 1.27 [95% confidence interval (CI) 1.18 to 1.37]; clopidogrel HR 1.24 [95% CI 1.13 to 1.35]; and aspirin HR 1.06 [95% CI 1.01 to 1.11]). The increased mortality associated with warfarin or clopidogrel use remained in stratified analyses. A covariate- and propensity-adjusted time-varying analysis, which accounted for longitudinal changes in prescription, produced similar results. In addition, matching for treatment facility and attending physician revealed similar associations between prescription and mortality. We conclude that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients. Given the possibility of confounding by indication, randomized trials are needed to determine definitively the risk and benefit of these medications. C1 [Chan, Kevin E.; Lazarus, J. Michael; Hakim, Raymond M.] Fresenius Med Care NA, Waltham, MA USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Chan, KE (reprint author), 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com NR 48 TC 95 Z9 97 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2009 VL 20 IS 4 BP 872 EP 881 DI 10.1681/ASN.2008080824 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 428ER UT WOS:000264831300025 PM 19297555 ER PT J AU Migita, T Ruiz, S Fornari, A Fiorentino, M Priolo, C Zadra, G Inazuka, F Grisanzio, C Palescandolo, E Shin, E Fiore, C Xie, W Kung, AL Febbo, PG Subramanian, A Mucci, L Ma, J Signoretti, S Stampfer, M Hahn, WC Finn, S Loda, M AF Migita, Toshiro Ruiz, Stacey Fornari, Alessandro Fiorentino, Michelangelo Priolo, Carmen Zadra, Giorgia Inazuka, Fumika Grisanzio, Chiara Palescandolo, Emanuele Shin, Eyoung Fiore, Christopher Xie, Wanling Kung, Andrew L. Febbo, Phillip G. Subramanian, Aravind Mucci, Lorelei Ma, Jing Signoretti, Sabina Stampfer, Meir Hahn, William C. Finn, Stephen Loda, Massimo TI Fatty Acid Synthase: A Metabolic Enzyme and Candidate Oncogene in Prostate Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-MASS INDEX; ANTITUMOR-ACTIVITY; EPITHELIAL-CELLS; UNITED-STATES; WEIGHT CHANGE; FOLLOW-UP; INHIBITION; APOPTOSIS; EXPRESSION; GROWTH AB Overexpression of the fatty acid synthase (FASN) gene has been implicated in prostate carcinogenesis. We sought to directly assess the oncogenic potential of FASN. We used immortalized human prostate epithelial cells (iPrECs), androgen receptor-overexpressing iPrECs (AR-iPrEC), and human prostate adenocarcinoma LNCaP cells that stably overexpressed FASN for cell proliferation assays, soft agar assays, and tests of tumor formation in immunodeficient mice. Transgenic mice expressing FASN in the prostate were generated to assess the effects of FASN on prostate histology. Apoptosis was evaluated by Hoechst 33342 staining and by fluorescence-activated cell sorting in iPrEC-FASN cells treated with stimulators of the intrinsic and extrinsic pathways of apoptosis (ie, camptothecin and anti-Fas antibody, respectively) or with a small interfering RNA (siRNA) targeting FASN. FASN expression was compared with the apoptotic index assessed by the terminal deoxynucleotidyltransferase-mediated UTP end-labeling method in 745 human prostate cancer samples by using the least squares means procedure. All statistical tests were two-sided. Forced expression of FASN in iPrECs, AR-iPrECs, and LNCaP cells increased cell proliferation and soft agar growth. iPrECs that expressed both FASN and androgen receptor (AR) formed invasive adenocarcinomas in immunodeficient mice (12 of 14 mice injected formed tumors vs 0 of 14 mice injected with AR-iPrEC expressing empty vector (P < .001, Fisher exact test); however, iPrECs that expressed only FASN did not. Transgenic expression of FASN in mice resulted in prostate intraepithelial neoplasia, the incidence of which increased from 10% in 8- to 16-week-old mice to 44% in mice aged 7 months or more (P = .0028, Fisher exact test), but not in invasive tumors. In LNCaP cells, siRNA-mediated silencing of FASN resulted in apoptosis. FASN overexpression protected iPrECs from apoptosis induced by camptothecin but did not protect iPrECs from Fas receptor-induced apoptosis. In human prostate cancer specimens, FASN expression was inversely associated with the apoptotic rate (mean percentage of apoptotic cells, lowest vs highest quartile of FASN expression: 2.76 vs 1.34, difference = 1.41, 95% confidence interval = 0.45 to 2.39, P(trend) = .0046). These observations suggest that FASN can act as a prostate cancer oncogene in the presence of AR and that FASN exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis. C1 [Migita, Toshiro; Fornari, Alessandro; Fiorentino, Michelangelo; Priolo, Carmen; Zadra, Giorgia; Inazuka, Fumika; Grisanzio, Chiara; Palescandolo, Emanuele; Shin, Eyoung; Fiore, Christopher; Xie, Wanling; Signoretti, Sabina; Hahn, William C.; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Grisanzio, Chiara; Signoretti, Sabina; Finn, Stephen; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Finn, Stephen; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Mucci, Lorelei; Ma, Jing; Stampfer, Meir] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Mucci, Lorelei; Ma, Jing; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kung, Andrew L.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Febbo, Phillip G.] Duke Inst Genome Sci, Durham, NC USA. [Subramanian, Aravind; Hahn, William C.; Loda, Massimo] Broad Inst Harvard, Boston, MA USA. [Subramanian, Aravind; Hahn, William C.; Loda, Massimo] MIT, Boston, MA USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, D1536,44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X; Finn, Stephen/0000-0002-8628-5814 FU Prostate Cancer Foundation; National Cancer Institute [RO1CA131945, PO1CA89021, P50 CA90381, CA55075]; Dana Farber Cancer Institute-Novartis Drug Development Program; Linda and Arthur Gelb Center for Translational Research; Nuclea Biomarkers; Loda laboratory; Samuel Waxman Foundation [SPA P01-Waxman-CS01]; American-Italian Cancer Foundation FX Support for this work (to M. L.) was obtained from the Prostate Cancer Foundation, the National Cancer Institute (RO1CA131945, PO1CA89021, P50 CA90381, and CA55075), Dana Farber Cancer Institute-Novartis Drug Development Program, the Linda and Arthur Gelb Center for Translational Research, a gift from Nuclea Biomarkers to the Jimmy Fund and the Loda laboratory, and the Samuel Waxman Foundation (SPA P01-Waxman-CS01). E. P. and G. Z. are supported by a fellowship of the American-Italian Cancer Foundation. NR 60 TC 155 Z9 160 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 1 PY 2009 VL 101 IS 7 BP 519 EP 532 DI 10.1093/jnci/djp030 PG 14 WC Oncology SC Oncology GA 428ZP UT WOS:000264890900012 PM 19318631 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI SPIKES for Difficult Conversations with Cancer Patients SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2009 VL 7 IS 4 BP 341 EP 341 PG 1 WC Oncology SC Oncology GA 499ZE UT WOS:000270264800001 PM 19406038 ER PT J AU Benson, AB Abrams, TA Ben-Josef, E Bloomston, PM Botha, JF Clary, BM Covey, A Curley, SA D'Angelica, MI Davila, R Ensminger, WD Gibbs, JF Laheru, D Malafa, MP Marrero, J Meranze, SG Mulvihill, SJ Park, JO Posey, JA Sachdev, J Salem, R Sigurdson, ER Sofocleous, C AF Benson, Al B., III Abrams, Thomas A. Ben-Josef, Edgar Bloomston, P. Mark Botha, Jean F. Clary, Bryan M. Covey, Anne Curley, Steven A. D'Angelica, Michael I. Davila, Rene Ensminger, William D. Gibbs, John F. Laheru, Daniel Malafa, Mokenge P. Marrero, Jorge Meranze, Steven G. Mulvihill, Sean J. Park, James O. Posey, James A. Sachdev, Jasgit Salem, Riad Sigurdson, Elin R. Sofocleous, Constantinos TI Hepatobiliary Cancers SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; hepatocellular carcinoma; hepatitis; cirrhosis; surgical resection; gallbladder cancer; cholangiocarcinomas; transplantation; tumor ablation; chemoembolization; chemotherapy; biologic therapy ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RANDOMIZED CONTROLLED-TRIAL; BILIARY-TRACT CARCINOMA; NONALCOHOLIC FATTY LIVER; PHASE-II TRIAL; POSITRON-EMISSION-TOMOGRAPHY; LONG-TERM SURVIVAL; 7 STAGING SYSTEMS; NONRESECTABLE HILAR CHOLANGIOCARCINOMA; PERCUTANEOUS RADIOFREQUENCY ABLATION C1 [Benson, Al B., III; Salem, Riad] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Abrams, Thomas A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Ben-Josef, Edgar; Ensminger, William D.; Marrero, Jorge] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Bloomston, P. Mark] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Botha, Jean F.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Lincoln, NE USA. [Curley, Steven A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Davila, Rene; Sachdev, Jasgit] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Laheru, Daniel] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Mulvihill, Sean J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Park, James O.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Posey, James A.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Benson, AB (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. FU NCI NIH HHS [P30 CA006973] NR 228 TC 182 Z9 193 U1 1 U2 8 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2009 VL 7 IS 4 BP 350 EP 391 PG 42 WC Oncology SC Oncology GA 499ZE UT WOS:000270264800002 PM 19406039 ER PT J AU Levy, MH Back, A Benedetti, C Billings, JA Block, S Boston, B Bruera, E Dy, S Eberle, C Foley, KM Karver, SB Knight, SJ Misra, S Ritchie, CS Spiegel, D Sutton, L Urba, S Von Roenn, JH Weinstein, SM AF Levy, Michael H. Back, Anthony Benedetti, Costantino Billings, J. Andrew Block, Susan Boston, Barry Bruera, Eduardo Dy, Sydney Eberle, Catherine Foley, Kathleen M. Karver, Sloan Beth Knight, Sara J. Misra, Sumathi Ritchie, Christine S. Spiegel, David Sutton, Linda Urba, Susan Von Roenn, Jamie H. Weinstein, Sharon M. TI Palliative Care SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; palliative care; end-of-life issues; death and dying; hospice care; supportive care; advance directives; terminal care ID CELL LUNG-CANCER; OPIOID-INDUCED CONSTIPATION; OF-LIFE CARE; UNREALISTIC EXPECTATIONS; SUPPORTIVE ONCOLOGY; BOWEL OBSTRUCTION; ADVANCED ILLNESS; CONTROLLED-TRIAL; END; THERAPY C1 [Back, Anthony] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Benedetti, Costantino] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Block, Susan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Boston, Barry] Univ Tennessee, St Jude Childrens Res Hosp, Ctr Canc, Knoxville, TN 37996 USA. [Bruera, Eduardo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dy, Sydney] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Eberle, Catherine] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Lincoln, NE USA. [Foley, Kathleen M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Knight, Sara J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Misra, Sumathi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ritchie, Christine S.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Spiegel, David] Stanford Comprehens Canc Ctr, Stanford, CA USA. [Urba, Susan] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Von Roenn, Jamie H.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Weinstein, Sharon M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. NR 77 TC 75 Z9 77 U1 2 U2 4 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2009 VL 7 IS 4 BP 436 EP 473 PG 38 WC Oncology SC Oncology GA 499ZE UT WOS:000270264800006 PM 19406043 ER PT J AU Jacobsen, J Jackson, VA AF Jacobsen, Juliet Jackson, Vicki A. TI A Communication Approach for Oncologists: Understanding Patient Coping and Communicating About Bad News, Palliative Care, and Hospice SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Communication; end-of-life; palliative care; hospice ID DISCUSSING PROGNOSIS; NURSING-HOMES; ILL PATIENTS; PHYSICIANS; HOPE; LIFE; END; INFORMATION; CAREGIVERS; CANCER AB Oncologists frequently approach patients to discuss difficult topics, such as bad news about cancer progression and referrals to palliative care and hospice. To communicate effectively in these difficult situations, it is helpful to assess what the patient knows and wants to know about their disease in general and, specifically, their prognosis. Although some patients fully accept the diagnosis of cancer and cope well, most patients struggle with how best to cope. This struggle often manifests itself with the patient vacillating between unrealistic hopes for longevity while also indicating prognostic awareness by talking about funeral plans. Although this coping is normal, it is difficult for most clinicians to interpret. This article presents a framework for understanding normal patient coping and gives specific examples of how to talk with these patients during difficult transitions, such as times of disease progression, and about referral to hospice and palliative care. (JNCCN 2009;7:475480) C1 [Jacobsen, Juliet; Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Palliat Care Serv, Boston, MA 02114 USA. RP Jacobsen, J (reprint author), Massachusetts Gen Hosp, Dept Med, Palliat Care Serv, Founders 600,55 Fruit St, Boston, MA 02114 USA. EM jjacobsen@partners.org NR 38 TC 6 Z9 8 U1 1 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD APR PY 2009 VL 7 IS 4 BP 475 EP 480 PG 6 WC Oncology SC Oncology GA 499ZE UT WOS:000270264800007 PM 19406044 ER PT J AU Slatore, CG Au, DH Hollingworth, W AF Slatore, Christopher G. Au, David H. Hollingworth, William TI Cost-Effectiveness of a Smoking Cessation Program Implemented at the Time of Surgery for Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Cost-effectiveness; QALY; Smoking cessation program; Non-small cell lung cancer ID QUALITY-OF-LIFE; RANDOMIZED CLINICAL-TRIAL; PULMONARY COMPLICATIONS; POSTOPERATIVE COMPLICATIONS; SURGICAL-PATIENTS; SURVIVAL; INTERVENTION; RESECTION; STAGE; GUIDELINES AB Background: Many patients are active smokers at the time of a diagnosis Of Surgically resectable lung cancer. Perioperative smoking cessation is associated with improved survival, but the cost-effectiveness of a smoking cessation program initiated immediately before surgery is unknown. Methods: We developed a decision analytic Markov model to evaluate the incremental cost-effectiveness of a formal smoking cessation program. The parameter estimates were taken from the available literature. The model included the cost and effectiveness of the smoking cessation program, cost and incidence of perioperative complications, postoperative mortality, and utility measured in quality adjusted life years (QALY). Dollars per QALY and life year were calculated and one-way sensitivity analyses were performed. Results: The cost/QALY and cost/life year were $16,415 and $45,629 at 1 year after surgery and $2609 and $2703 at 5 years, respectively. Most sensitivity analyses showed the 1 year postsurgery cost/QALY estimates were less than $50,000, and all were less than $12,000 at 5 years. Cost-effectiveness estimates were most sensitive to the frequency of perioperative complications and the estimated short-term utility estimates. Conclusion: A smoking cessation program initiated before Surgical lung resection is cost-effective at both I and 5 years postsurgery. Providers should encourage patients who are still smoking to engage in formal smoking cessation programs. C1 [Slatore, Christopher G.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Slatore, Christopher G.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Hollingworth, William] Univ Bristol, Dept Social Med, Bristol, Avon, England. RP Slatore, CG (reprint author), 1959 NE Pacific St,Campus Box 356522, Seattle, WA 98195 USA. EM cslatore@u.washington.edu OI Slatore, Christopher/0000-0003-0958-8122 FU National Institutes of Health [CA130328] FX This work was performed at Health Services Research and Development, VA Puget Sound Health Care System, Seattle, WA. Dr. Slatore was funded by the National Institutes of Health (CA130328) for his work on a separate project. NR 41 TC 15 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2009 VL 4 IS 4 BP 499 EP 504 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 425BD UT WOS:000264611100010 PM 19204575 ER PT J AU Horn, L Bernardo, P Sandler, A Wagner, H Levitan, N Levitt, ML Johnson, DH AF Horn, Leora Bernardo, Patricia Sandler, Alan Wagner, Henry Levitan, Nathan Levitt, Mark L. Johnson, David H. TI A Phase II Study of Paclitaxel plus Etoposide plus Cisplatin plus Concurrent Radiation Therapy for Previously Untreated Limited Stage Small Cell Lung Cancer (E2596) A Trial of the Eastern Cooperative Oncology Group SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Small cell lung cancer; Paclitaxel and etoposide-cisplatin; Radiotherapy ID DAILY THORACIC RADIOTHERAPY; COLONY-STIMULATING FACTOR; COMBINED-MODALITY TREATMENT; LEUKEMIA GROUP-B; RANDOMIZED TRIAL; CHEMOTHERAPY; METAANALYSIS; VINCRISTINE; IRRADIATION; CYCLOPHOSPHAMIDE AB Introduction: To determine the 1-year survival, response rate, and toxicity for patients with limited stage small cell lung cancer treated with the combination of cisplatin plus etoposide plus paclitaxel with delayed concurrent (starting with cycle 3) high dose thoracic radiotherapy. Patients and Methods: Patients with previously untreated limited stage small cell lung cancer, Easter Cooperative Oncology Group performance status of 0-2 and adequate organ function were eligible. Cycles I and 2 of chemotherapy consisted of paclitaxel 170 mg/m(2) intravenous day 1, etoposide 80 mg/m(2) intravenous days I to 3, and cisplatin 60 mg/m(2) intravenous clay 1 followed by filgrastim 5 mu g/kg Subcutaneously days 4 to 13. Cycles 3 and 4 of chemotherapy consisted of a reduced close of paclitaxel 135 mg/m(2) intravenous day 1, and the same dose of etoposide and cisplatin with concurrent thoracic radiation therapy 1.8 Gy in 35 fractions (total 63 Gy) administered over 7 weeks. Results: Sixty-three patients were entered, 61 patients were eligible. The most common grade 4 toxicity seen was granulocytopenia (62%). Nonhematologic toxicities included febrile neutropenia in 19% of patients, grade 3 and 4 esophagitis in 32% of patients, and grade 3 peripheral neuropathy in 14% of patients. Two patients suffered lethal toxicities. The overall response rate was 79%. The 1-year Survival rate was 64%. The median overall survival was 15.7 months, and the median progression-free survival was 8.6 months. Conclusions: The combination of cisplatin plus etoposide plus paclitaxel chemotherapy and concurrent delayed thoracic radiotherapy as administered in this trial provide no apparent advantage with respect to response, local control, or Survival compared with historical controls. C1 [Horn, Leora; Sandler, Alan; Johnson, David H.] Vanderbilt Univ, Dept Hematol Oncol, Nashville, TN USA. [Bernardo, Patricia] Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. [Wagner, Henry] Penn State Canc Inst, Hershey, PA USA. [Levitan, Nathan] Univ Hosp Case Med Ctr, Dept Med, Div Hematol Oncol, Cleveland, OH USA. [Levitt, Mark L.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Horn, L (reprint author), 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM leora.horn@vanderbilt.edu FU National Cancer Institute, National Institutes of Health. and the Department of Health and Human Services [CA23318, CA66636, CA21115, CA14548, CA49957] FX Supported, in part, by Public Health Service Grants CA23318, CA66636, CA21115, CA14548, CA49957 and from the National Cancer Institute, National Institutes of Health. and the Department of Health and Human Services. NR 45 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD APR PY 2009 VL 4 IS 4 BP 527 EP 533 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 425BD UT WOS:000264611100015 PM 19240650 ER PT J AU Velmahos, GC Tabbara, M Spaniolas, K Duggan, M Alam, HB Serra, M Sun, LP de Luis, J AF Velmahos, George C. Tabbara, Malek Spaniolas, Konstantinos Duggan, Michael Alam, Hasan B. Serra, Marco Sun, Liping de Luis, Javier TI Self-Expanding Hemostatic Polymer for Control of Exsanguinating Extremity Bleeding SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Extremity bleeding; Expanding polymer; Exsanguinating injuries ID LETHAL GROIN INJURY; HEMORRHAGE MODEL; LIVER-INJURY; BLOOD-LOSS; SWINE; AGENT; DRESSINGS; SURVIVAL; BANDAGE AB Background: Prehospital management of exsanguinating extremity injuries (EEI) includes direct compression or tourniquets or both. Direct compression may be ineffective in deep wounds and requires a person committed to compressing. Tourniquets may cause severe ischemic damage and may be ineffective in proximal wounds. This study aims to examine a new self-expanding hemostatic polymer (SEHP) for control of EEI. In contact with blood, the polymer absorbs the aqueous component of blood and exerts a tamponade effect by expanding against the walls of the wound cavity. Methods: Twenty-one pigs were subjected to a validated and reproducible model of lethal proximal extremity injury by transecting soft tissues and the femoral vessels. The pigs were left to bleed uncontrollably for 3 minutes and then randomized to receive either a standard compression dressing (Control group, N = 10) or SEHP (SEHP group, N = 11). After 5 minutes of manual compression, the dressing or SEHP were left in the wound and the animals resuscitated more than 2 hours. One animal in each group died soon after the injury before application of the dressings and was removed from final analysis. Results: SEHP animals had lower blood loss (1358 mL +/- 97 mL) than the Control animals (2028 mL +/- 177 mL, p = 0.006). The mortality was 55% in the Control group and 0% in the SEHP group (p = 0.006). Conclusion: SEHP is a novel, light, and portable material to control EEI effectively. It does not require another person for compression nor does it compromise the circulation. As EEI occurs with alarming g frequency in the battlefield, SEHP may not only present an optimal hemostatic method for military applications but also be useful in the civilian prehospital setting. C1 [Velmahos, George C.; Tabbara, Malek; Spaniolas, Konstantinos; Duggan, Michael; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Serra, Marco; Sun, Liping; de Luis, Javier] Payload Syst Inc, Boston, MA USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI Tabbara, Malek/0000-0003-1046-7803 FU SBIR [W81XWH-05-C-0044] FX Supported by SBIR W81XWH-05-C-0044. NR 16 TC 7 Z9 8 U1 0 U2 9 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 APR PY 2009 VL 66 IS 4 BP 984 EP 988 DI 10.1097/TA.0b013e31819ce457 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 431KI UT WOS:000265059800005 PM 19359903 ER PT J AU Manolakaki, D Velmahos, GC Spaniolas, K de Moya, M Alam, HB AF Manolakaki, Dimitra Velmahos, George C. Spaniolas, Konstantinos de Moya, Marc Alam, Hasan B. TI Early Magnetic Resonance Imaging Is Unnecessary In Patients With Traumatic Brain Injury SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Magnetic resonance imaging; Traumatic brain injury; head CT scan ID MINOR HEAD-INJURY; COMPUTED-TOMOGRAPHY AB Introduction: Computed tomography (CT) is routinely performed in traumatic brain injury (TBI). Magnetic resonance imaging (MRI) is considered more sensitive than CT for subtle abnormalities. Because CT does not always explain the posttraumatic neurologic examination, MRI is being performed with increasing frequency. Although MRI at a later stage may be of significant prognostic value, the role of early MRI is questionable. Our objective was to evaluate the role of early MRI in the initial management of patients with TBI. Methods: This is a 3-year prospective study (January 2005-December 2007) of adult patients with TBI who, in addition to CT, had MRI of the head within 48 hours of admission to the hospital. The findings from the two imaging studies were compared. The outcome was any change in management based on MRI findings. Results: We identified 123 trauma patients who had MRI within 18 hours +/- 14.5 hours of CT (median: 12 hours). In 82 (67%) patients, the findings of CT and MRI were identical. In the remaining 41 patients there were discrepancies between CT and MRI 35 patients had slight differences in the location or size of the lesions found and six had minor brain lesion detected by MRI and not CT. Compared with patients who had identical CT and MRI, those who showed differences in the two tests had higher severity of head in-jury, lower initial blood pressure, and a higher rate of intubation. Based on CT findings, 78 (63%) patients received TBI-related interventions: 8 craniotomies, 12 intracranial pressure monitoring catheters, 14 mannitol infusions, and 72 antiepileptic medications. There was no change in treatment because of MRI. Conclusion: Early MRI may be superior to CT in describing subtle TBI findings, but this information does not affect management. Head CT is the only imaging test necessary in the first 48 hours after TBI. C1 Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 12 TC 12 Z9 12 U1 0 U2 1 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 APR PY 2009 VL 66 IS 4 BP 1008 EP 1012 DI 10.1097/TA.0b013e31819adba2 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 431KI UT WOS:000265059800011 PM 19359907 ER PT J AU Yin, HN Chai, JK Yu, YM Shen, CA Wu, YQ Yao, YM Liu, H Liang, LM Tompkins, RG Sheng, ZY AF Yin, Hui-Nan Chai, Jia-Ke Yu, Yong-Ming Shen, Chuan-An Wu, Yan-Qiu Yao, Yong-Ming Liu, Hui Liang, Li-Ming Tompkins, Ronald G. Sheng, Zhi-Yong TI Regulation of Signaling Pathways Downstream of IGF-I/Insulin by Androgen in Skeletal Muscle of Glucocorticoid-Treated Rats SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Protein kinase B (Akt); p70 Ribosomal protein S6 kinase (p70S6K); Glycogen synthase kinase-3 beta (GSK-3 beta); Muscle atrophy F-box (MAFbx); Muscle RING finger-1 (MuRF1) ID FOXO TRANSCRIPTION FACTORS; I MESSENGER-RNA; PROTEIN-DEGRADATION; UBIQUITIN LIGASES; MYOTUBE HYPERTROPHY; DIAPHRAGM MUSCLE; BURN INJURY; ATROPHY; EXPRESSION; ATROGIN-1 AB Background: The mechanisms by which androgens ameliorate glucocorticoid-induced muscle wasting are still under investigation. In the present study, we tested the hypothesis that androgen's effects in reversing muscle wasting are related to activating the signaling pathways downstream of insulin-like growth factor-1 (IGF-I)/insulin. Methods: Forty female Sprague-Dawley rats were randomly divided into four groups: control group, dexamethasone (DEX) group, testosterone (TES) group, and TES + DEX group. Each group was injected with saline or DEX (0.1 mg/100 g/d) for 10 days and sesame oil or TES (0.5 mg/100 g/d) for 13 days. Several downstream targets of IGF-I/insulin in skeletal muscle including protein kinase B (Akt), p70 ribosomal protein S6 kinase (p70S6K), and glycogen synthase kinase-3 beta (GSK-3 beta) that are associated with protein synthesis were examined. Two proteolysis-related ubiquitin E3-ligases, muscle atrophy F-box, and muscle RING finger-1 that are also regulated by IGF-I/insulin were also assessed. Results: TES attenuated gastrocnemius muscle atrophy induced by DEX. TES prevented the DEX-induced decrease of IGF-I expression in gastrocnemius muscle, but not in serum. TES ameliorated DEX-induced dephosphorylation of Akt and p70S6K and promoted the phosphorylation of GSK-3 beta in gastrocnemius muscle. The total amount of Akt, p70S6K, or GSK-3 beta proteins was not changed among these groups. TES did not show any effects on the DEX-induced upregulation of muscle atrophy F-box, and muscle RING finger-I mRNA in gastrocnemius muscle. Conclusion: This findings suggest that the effects of TES in reversing DEX-induced muscle atrophy are related to signaling pathways downstream of IGF-I/insulin that are associated with protein synthesis. C1 [Yin, Hui-Nan; Chai, Jia-Ke; Shen, Chuan-An; Wu, Yan-Qiu; Yao, Yong-Ming; Liu, Hui; Liang, Li-Ming; Sheng, Zhi-Yong] PLA, Gen Hosp, Affiliated Hosp 1, Dept Burns & Plast Surg,Burns Inst, Beijing 100037, Peoples R China. Harvard Univ, Sch Med, Boston, MA USA. [Yao, Yong-Ming; Tompkins, Ronald G.] Massachusetts Gen Hosp, Shriners Burns Inst, Dept Surg, Boston, MA 02114 USA. RP Chai, JK (reprint author), PLA, Gen Hosp, Affiliated Hosp 1, Dept Burns & Plast Surg,Burns Inst, Beijing 100037, Peoples R China. EM cjk304@126.com FU National Natural Science Foundation (China) [30571919]; Natural Science Foundation of Beijing (China) [7072077] FX Supported by grants from the National Natural Science Foundation (China, no. 30571919), and the Natural Science Foundation of Beijing (China, no. 7072077). NR 45 TC 19 Z9 20 U1 1 U2 3 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 APR PY 2009 VL 66 IS 4 BP 1083 EP 1090 DI 10.1097/TA.0b013e31817e7420 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 431KI UT WOS:000265059800024 PM 19359918 ER PT J AU Eisner, BH Kambadakone, A Monga, M Anderson, JK Thoreson, AA Lee, H Dretler, SP Sahani, DV AF Eisner, Brian H. Kambadakone, Avinash Monga, Manoj Anderson, James K. Thoreson, Andrew A. Lee, Hang Dretler, Stephen P. Sahani, Dushyant V. TI Computerized Tomography Magnified Bone Windows are Superior to Standard Soft Tissue Windows for Accurate Measurement of Stone Size: An In Vitro and Clinical Study SO JOURNAL OF UROLOGY LA English DT Article DE urinary calculi; tomography; x-ray computed; uric acid; calcium oxalate ID UNENHANCED HELICAL CT; INTRAVENOUS UROGRAPHY; URETERAL CALCULI; PASSAGE AB Purpose: We determined the most accurate method of measuring urinary stones on computerized tomography. Materials and Methods: For the in vitro portion of the study 24 calculi, including 12 calcium oxalate monohydrate and 12 uric acid stones, that had been previously collected at our clinic were measured manually with hand calipers as the gold standard measurement. The calculi were then embedded into human kidney-sized potatoes and scanned using 64-slice multidetector computerized tomography. Computerized tomography measurements were performed at 4 window settings, including standard soft tissue windows (window width-320 and window length-50), standard bone windows (window width-1120 and window length-300), 5.13x magnified soft tissue windows and 5.13x magnified bone windows. Maximum stone dimensions were recorded. For the in vivo portion of the study 41 patients with distal ureteral stones who underwent noncontrast computerized tomography and subsequently spontaneously passed the stones were analyzed. All analyzed stones were 100% calcium oxalate monochydrate or mixed, calcium based stones. Stones were prospectively collected at the clinic and the largest diameter was measured with digital calipers as the gold standard. This was compared to computerized tomography measurements using 4.0x magnified soft tissue windows and 4.0x magnified bone windows. Statistical comparisons were performed using Pearson's correlation and paired t test. Results: In the in vitro portion of the study the most accurate measurements were obtained using 5.13x magnified bone windows with a mean 0.13 mm difference from caliper measurement (p = 0.6). Measurements performed in the soft tissue window with and without magnification, and in the bone window without magnification were significantly different from hand caliper measurements (mean difference 1.2, 1.9 and 1.4 mm, p = 0.003, <0.001 and 0.0002, respectively). When comparing measurement errors between stones of different composition in vitro, the error for calcium oxalate calculi was significantly different from the gold standard for all methods except bone window settings with magnification. For uric acid calculi the measurement error was observed only in standard soft tissue window settings. In vivo 4.0x magnified bone windows was superior to 4.0x magnified soft tissue windows in measurement accuracy. Magnified bone window measurements were not statistically different from digital caliper measurements (mean underestimation vs digital caliper 0.3 mm, p = 0.4), while magnified soft tissue windows were statistically distinct (mean underestimation 1.4 mm, p = 0.001). Conclusions: In this study magnified bone windows were the most accurate method of stone measurements in vitro and in vivo. Therefore, we recommend the routine use of magnified bone windows for computerized tomography measurement of stones. In vitro the measurement error in calcium oxalate stones was greater than that in uric acid stones, suggesting that stone composition may be responsible for measurement inaccuracies. C1 [Eisner, Brian H.; Dretler, Stephen P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Kambadakone, Avinash; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. [Monga, Manoj; Anderson, James K.] Univ Minnesota, Dept Urol, Minneapolis, MN USA. [Thoreson, Andrew A.] Univ Minnesota, Dept Radiol, Minneapolis, MN USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 13 TC 29 Z9 29 U1 0 U2 2 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 APR PY 2009 VL 181 IS 4 BP 1710 EP 1715 DI 10.1016/j.juro.2008.11.116 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 422SO UT WOS:000264448200065 PM 19230922 ER PT J AU Kundu, S Itkin, M Gervais, DA Krishnamurthy, VN Wallace, MJ Cardella, JF Rubin, DL Langlotz, CP AF Kundu, Sanjoy Itkin, Maxim Gervais, Debra A. Krishnamurthy, Venkataramu N. Wallace, Michael J. Cardella, John F. Rubin, Daniel L. Langlotz, Curtis P. TI The IR Radlex Project: An Interventional Radiology Lexicon-A Collaborative Project of the Radiological Society of North America and the Society of Interventional Radiology SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 [Kundu, Sanjoy] Vein Inst Toronto, Toronto, ON, Canada. [Itkin, Maxim; Langlotz, Curtis P.] Univ Penn, Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. [Itkin, Maxim] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Gastrointestinal Genitourinary Div, Boston, MA 02114 USA. [Krishnamurthy, Venkataramu N.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Wallace, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rubin, Daniel L.] Natl Ctr Biomed Ontol, Dept Radiol, Stanford, CA USA. [Rubin, Daniel L.] Natl Ctr Biomed Ontol, Dept Med Biomed Informat, Stanford, CA USA. RP Kundu, S (reprint author), Soc Intervent Radiol, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM kundu40@hotmail.com NR 7 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2009 VL 20 IS 4 BP 433 EP 435 DI 10.1016/j.jvir.2008.10.022 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 429ZJ UT WOS:000264958300001 PM 19081735 ER PT J AU Sapkota, BH Hirsch, AE Yoo, AJ Hornicek, FJ Raskin, KA Rosenthal, DI Growney, ML Hirsch, JA AF Sapkota, Bishnu H. Hirsch, Ariel E. Yoo, Albert J. Hornicek, Francis J. Raskin, Kevin A. Rosenthal, Daniel I. Growney, Marion L. Hirsch, Joshua A. TI Treatment of Metastatic Carcinoma to the Hip with CT-guided Percutaneous Acetabuloplasty: Report of Four Cases SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID VERTEBRAL AUGMENTATION; BREAST-CANCER; DISEASE; BONE; INJECTION; CEMENT AB Percutaneous acetabuloplasty (PA) is a promising treatment for painful metastatic lesions of the acetabulum. Four patients were treated with injection of the bone cement polymethylmethacrylate directly into the lesion. After the procedure, all four patients had improvement or relief of their pain and were able to resume weight-bearing activities. The procedure was well tolerated by each patient without morbidity. PA appears to be a reasonable palliative procedure for painful and fragile hips associated with metastatic bone disease. C1 [Sapkota, Bishnu H.; Yoo, Albert J.; Growney, Marion L.; Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neurointervent Radiol, Boston, MA 02114 USA. [Rosenthal, Daniel I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Ariel E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Hornicek, Francis J.; Raskin, Kevin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Oncol, Boston, MA 02114 USA. RP Hirsch, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neurointervent Radiol, 55 Fruit St,GRB 241, Boston, MA 02114 USA. EM jahirsch@partners.org NR 15 TC 10 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2009 VL 20 IS 4 BP 548 EP 552 DI 10.1016/j.jvir.2008.11.008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 429ZJ UT WOS:000264958300018 PM 19112031 ER PT J AU Alatrakchi, N Koziel, M AF Alatrakchi, Nadia Koziel, Margaret TI Regulatory T cells and viral liver disease SO JOURNAL OF VIRAL HEPATITIS LA English DT Review DE CD4+CD25+Treg; CD8 Treg; HBV; HCV; Liver disease; TGF-beta ID C VIRUS-INFECTION; GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR FOXP3; IN-VITRO PROLIFERATION; HEPATIC STELLATE CELLS; TGF-BETA; IMMUNE-RESPONSE; SELF-TOLERANCE; IMMUNOLOGICAL-TOLERANCE; SUPPRESSOR LYMPHOCYTES AB Important questions remain on the role of T cells in progression of hepatitis virus-mediated liver pathogenesis: are T cells 'Good or Bad'? How could one maintain a beneficial balance, in which regulatory T-cell (Treg) populations might play an important role? Treg are a heterogeneous population of cells, including the classical CD4+CD25+ subset expressing the transcription factor Foxp3, CD4 T cells secreting IL-10 (Tr1) or TGF-beta (Th3), but also some CD8 T cells, double negative T cells and gamma delta T cells. The role of Treg in viral hepatitis, particularly HBV and HCV, seems to range from suppressing T-cell responses directed against hepatitis viruses to down-regulating the immune responses causing the liver damage. Questions also remain unresolved on which Treg populations are important and how to establish a beneficial balance, mostly due to the difficulties in studying the heterogeneous Treg populations but also due to the problem accessing liver, the principal target of hepatitis viruses. Here, we will review progress to date on understanding Treg populations in regard to viral hepatitis. C1 [Alatrakchi, Nadia] BIDMC, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Alatrakchi, N (reprint author), BIDMC, Div Infect Dis, 330 Brookline Ave,Dana RW 66 3C, Boston, MA 02115 USA. EM nalatrak@bidmc.harvard.edu FU BIDMC Liver Center [U19 AI066313] FX This publication was supported by the BIDMC Liver Center U19 AI066313. We thank Dr Mark Exley for his careful input to the review. NR 78 TC 60 Z9 65 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD APR PY 2009 VL 16 IS 4 BP 223 EP 229 DI 10.1111/j.1365-2893.2009.01081.x PG 7 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 412YL UT WOS:000263760000001 PM 19222744 ER PT J AU Smith, SL Shioda, T AF Smith, Shannon L. Shioda, Toshi TI Advantages of COS-1 monkey kidney epithelial cells as packaging host for small-volume production of high-quality recombinant lentiviruses SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Lentivirus; HEK293T; COS-1; Packaging cell ID LARGE-SCALE PRODUCTION; WISKOTT-ALDRICH-SYNDROME; EFFICIENT GENE-TRANSFER; IN-VIVO; TRANSIENT TRANSFECTION; RETROVIRAL VECTORS; RNA-INTERFERENCE; HIGH-TITER; EX-VIVO; THERAPY AB The HEK293T human embryonic kidney cells have been used widely as a packaging host for transfection-based production of recombinant lentiviruses. The present study describes advantages of using COS-1 African green monkey kidney cells versus HEK293T cells as a packaging host for small-volume production of high-quality recombinant lentiviruses. The particle performance index, defined as the ratio of infection-competent viral particles to the total number of particles, was three- to four-fold greater in transfection supernatants generated using COS-1 cells than that generated using HEK293T cells. Adhesion of HEK293T cells to the cell culture-treated plastic surface was weak, causing significant HEK293T cell contamination in the transfection supernatants produced by laboratory automation using the 96-well cell culture plates. In contrast, COS-1 cells adhered strongly to the plastic surface, and cell contamination was not detected in the transfection supernatants. These results suggest that COS-1 cells may be a useful alternative packaging host for use for automated generation of large numbers of high-quality lentivirus reagents, particularly because they eliminate the need for additional purification steps to remove viral particles from cell culture supernatant. (C) 2008 Elsevier B.V. All rights reserved. C1 [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc Res, Mol Profiling Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Profiling Lab, Charlestown, MA 02129 USA. EM tshioda@partners.org FU Genetic Profiling and Cancer fund; Mel's Bracelet Gift awarded FX This study was supported by the Genetic Profiling and Cancer fund and Mel's Bracelet Gift awarded to T.S. NR 52 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 2009 VL 157 IS 1 BP 47 EP 54 DI 10.1016/j.jviromet.2008.12.002 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 425VY UT WOS:000264667000007 PM 19118578 ER PT J AU Chen, H Piechocka-Trocha, A Miura, T Brockman, MA Julg, BD Baker, BM Rothchild, AC Block, BL Schneidewind, A Koibuchi, T Pereyra, F Allen, TM Walker, BD AF Chen, Huabiao Piechocka-Trocha, Alicja Miura, Toshiyuki Brockman, Mark A. Julg, Boris D. Baker, Brett M. Rothchild, Alissa C. Block, Brian L. Schneidewind, Arne Koibuchi, Tomohiko Pereyra, Florencia Allen, Todd M. Walker, Bruce D. TI Differential Neutralization of Human Immunodeficiency Virus (HIV) Replication in Autologous CD4 T Cells by HIV-Specific Cytotoxic T Lymphocytes SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL LOAD; INFECTED-CELLS; TYPE-1 ENVELOPE; TCR REPERTOIRE; IN-VITRO; EX-VIVO; ESCAPE; RESPONSES; NONPROGRESSORS; EXPRESSION AB Defining the antiviral efficacy of CD8 T cells is important for immunogen design, and yet most current assays do not measure the ability of responses to neutralize infectious virus. Here we show that human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) clones and cell lines derived from infected persons and targeting diverse epitopes differ by over 1,000-fold in their ability to retard infectious virus replication in autologous CD4 T cells during a 7-day period in vitro, despite comparable activity as assessed by gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay. Cell lines derived from peripheral blood mononuclear cells stimulated in vitro with peptides representing targeted Gag epitopes consistently neutralized HIV better than Env-specific lines from the same person, although ineffective inhibition of virus replication is not a universal characteristic of Env-specific responses at the clonal level. Gag-specific cell lines were of higher avidity than Env-specific lines, although avidity did not correlate with the ability of Gag- or Env-specific lines to contain HIV replication. The greatest inhibition was observed with cell lines restricted by the protective HLA alleles B*27 and B*57, but stimulation with targeted Gag epitopes resulted in greater inhibition than did stimulation with targeted Env epitopes even in non-B*27/B*57 subjects. These results assessing functional virus neutralization by HIV-specific CD8 T cells indicate that there are marked epitope- and allele-specific differences in virus neutralization by in vitro-expanded CD8 T cells, a finding not revealed by standard IFN-gamma ELISPOT assay currently in use in vaccine trials, which may be of critical importance in immunogen design and testing of candidate AIDS vaccines. C1 [Chen, Huabiao; Piechocka-Trocha, Alicja; Miura, Toshiyuki; Brockman, Mark A.; Julg, Boris D.; Baker, Brett M.; Rothchild, Alissa C.; Block, Brian L.; Schneidewind, Arne; Koibuchi, Tomohiko; Pereyra, Florencia; Allen, Todd M.; Walker, Bruce D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. [Chen, Huabiao; Piechocka-Trocha, Alicja; Miura, Toshiyuki; Brockman, Mark A.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brockman, Mark/0000-0001-6432-1426 FU Harvard University Center for AIDS Research; International AIDS Vaccine Initiative; Bill and Melinda Gates Foundation; Doris Duke Charitable Foundation; NIH; Howard Hughes Medical Institute; Mark and Lisa Schwartz Foundation FX This work was supported by the Harvard University Center for AIDS Research and the International AIDS Vaccine Initiative and by grants from the Bill and Melinda Gates Foundation (B. D. W), the Doris Duke Charitable Foundation (B. D. W.), the NIH (B. D. W. and T. M. A.), the Howard Hughes Medical Institute (B. D. W.), and the Mark and Lisa Schwartz Foundation. NR 39 TC 63 Z9 64 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2009 VL 83 IS 7 BP 3138 EP 3149 DI 10.1128/JVI.02073-08 PG 12 WC Virology SC Virology GA 417AE UT WOS:000264046000032 PM 19158248 ER PT J AU Miura, T Brumme, CJ Brockman, MA Brumme, ZL Pereyra, F Block, BL Trocha, A John, M Mallal, S Harrigan, PR Walker, BD AF Miura, Toshiyuki Brumme, Chanson J. Brockman, Mark A. Brumme, Zabrina L. Pereyra, Florencia Block, Brian L. Trocha, Alicja John, Mina Mallal, Simon Harrigan, P. Richard Walker, Bruce D. TI HLA-Associated Viral Mutations Are Common in Human Immunodeficiency Virus Type 1 Elite Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HIV-1 INFECTION; CELL RESPONSES; ESCAPE MUTATIONS; REPLICATION; GAG; VIREMIA; SUPPRESSORS; SELECTION; VARIANTS AB Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8(+) T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC, compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HIV-1 infection. C1 [Miura, Toshiyuki; Brumme, Chanson J.; Brockman, Mark A.; Brumme, Zabrina L.; Pereyra, Florencia; Trocha, Alicja; Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Miura, Toshiyuki; Brockman, Mark A.; Brumme, Zabrina L.; Pereyra, Florencia; Block, Brian L.; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. [Miura, Toshiyuki; Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [John, Mina; Mallal, Simon] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. [John, Mina; Mallal, Simon] Murdoch Univ, Perth, WA, Australia. [Harrigan, P. Richard] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Harrigan, P. Richard] Univ British Columbia, Fac Med, Div Aids, Vancouver, BC, Canada. RP Miura, T (reprint author), Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Infect Dis, Tokyo 1088639, Japan. EM miura523@hotmail.com; bwalker@partners.org OI Brumme, Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426 FU NIAID/NIH [AI028568, AI030914]; Howard Hughes Medical Institute; Harvard University Center for AIDS Research FX This work was supported by grants AI028568 and AI030914 from the NIAID/NIH, the Howard Hughes Medical Institute, the Harvard University Center for AIDS Research, a gift from the Mark and Lisa Schwartz Foundation, the International AIDS Vaccine Initiative, and the Bill and Melinda Gates Foundation. NR 33 TC 51 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2009 VL 83 IS 7 BP 3407 EP 3412 DI 10.1128/JVI.02459-08 PG 6 WC Virology SC Virology GA 417AE UT WOS:000264046000058 PM 19153230 ER PT J AU Shifren, JL Johannes, CB Monz, BU Russo, PA Bennett, L Rosen, R AF Shifren, Jan L. Johannes, Catherine B. Monz, Brigitta U. Russo, Patricia A. Bennett, Lee Rosen, Ray TI Help-Seeking Behavior of Women with Self-Reported Distressing Sexual Problems SO JOURNAL OF WOMENS HEALTH LA English DT Article ID UNITED-STATES; GENERAL-PRACTITIONER; OLDER-PEOPLE; PRIMARY-CARE; DYSFUNCTION; HEALTH; PREVALENCE; NEED; RELIABILITY; ATTITUDES AB Objective: The objective was to describe the healthcare and information-seeking behavior of women with self-reported sexual problems and accompanying sexually related personal distress identified from a large, population-based U. S. survey. Methods: Women (n = 3,239) aged >= 18 years with self-reported sexual problems of desire, arousal, and/or orgasm accompanied by sexually related personal distress were identified from a cross-sectional mailed survey of 50,002 U. S. households sampled from a national research panel. Healthcare and information-seeking behavior was examined as four ordered categories: sought formal medical advice, sought informal advice, sought information from anonymous sources, and did not seek help or information. Correlates of help seeking for each type of distressing sexual problem were modeled with multivariable proportional odds regression. Results: Just over a third of women with any distressing sexual problems had sought formal care, most often from a gynecologist or primary care physician; about 80% of the time, the woman, rather than the physician, initiated the conversation. Only 6% of women who sought medical advice scheduled a visit specifically for a sexual problem. Factors related to help seeking were having a current partner and interacting with the heathcare system. Barriers were poor self-perceived health and embarrassment about discussing sexual topics with a physician. Conclusions: Our results suggest inadequacies in the U. S. medical care system in addressing sexual problems in women. Gynecologists and primary care physicians, by including discussions about sexual health during routine visits, can increase the likelihood that adequate care can be offered. C1 [Shifren, Jan L.] Massachusetts Gen Hosp, Vincent OBGYN Serv, Boston, MA 02114 USA. [Johannes, Catherine B.] RTI Hlth Solut, Waltham, MA USA. [Monz, Brigitta U.] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Russo, Patricia A.] PRC Hlth Serv Res & Management Consulting, Washington, DC USA. [Bennett, Lee] RTI Hlth Solut, Res Triangle Pk, NC USA. [Rosen, Ray] New England Res Inst, Watertown, MA 02172 USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent OBGYN Serv, 55 Fruit St,Yawkey 10-A, Boston, MA 02114 USA. EM jshifren@partners.org FU Boehringer Ingelheim GmbH FX We thank TNS Healthcare, Inc., especially Kerri Lehrhaupt, for their contribution. Funding was provided by Boehringer Ingelheim GmbH. NR 25 TC 45 Z9 45 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2009 VL 18 IS 4 BP 461 EP 468 DI 10.1089/jwh.2008.1133 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 431QL UT WOS:000265077800006 PM 19361312 ER PT J AU Hanlon, JT Boudreau, RM Roumani, YF Newman, AB Ruby, CM Wright, RM Hilmer, SN Shorr, RI Bauer, DC Simonsick, EM Studenski, SA AF Hanlon, Joseph T. Boudreau, Robert M. Roumani, Yazan F. Newman, Anne B. Ruby, Christine M. Wright, Rollin M. Hilmer, Sarah N. Shorr, Ronald I. Bauer, Douglas C. Simonsick, Eleanor M. Studenski, Stephanie A. CA Health ABC Study TI Number and Dosage of Central Nervous System Medications on Recurrent Falls in Community Elders: The Health, Aging and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aged; Falls; Central nervous system medications ID OLDER-ADULTS; PEOPLE; DRUGS; RISK; HOME; METAANALYSIS; ANALGESICS; WITHDRAWAL; CONSENSUS; EUROPE AB Few studies have examined the risk of multiple or high doses of combined central nervous system (CNS) medication use for recurrent falls in the elderly. The study objective was to evaluate whether multiple- or high-dose CNS medication use in older adults was associated with a higher risk of recurrent (>= 2) falls. This longitudinal cohort study included 3,055 participants from the Health, Aging and Body Composition study who were well functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, antidepressants) was determined annually (except Year 4) during in-person interviews. The number and summated standard daily doses (SDDs; low, medium, and high) of CNS medications were computed. Falls 1 year later were ascertained annually for 5 years. For a period of 5 years, as many as 24.1% of CNS medication users took 2+ agents annually, whereas as no more than 18.9% of CNS medication users took high doses annually (3+ SDDs). Yearly, as many as 9.7% of participants reported recurrent falls. Multivariable Generalized Estimating Equation analyses showed that multiple CNS medication users compared with never users had an increased risk of sustaining 2+ falls (adjusted odds ratio [OR] 1.95; 95% confidence interval [CI] 1.35-2.81). Those taking high (3+) CNS SDDs also exhibited an increased risk of 2+ falls (adjusted OR 2.89; 95% CI 1.96-4.25). Higher total daily doses of CNS medications were associated with recurrent falls. Further studies are needed to determine the impact of reducing the number of CNS medications and/or dosage on recurrent falls. C1 [Hanlon, Joseph T.; Roumani, Yazan F.; Newman, Anne B.; Wright, Rollin M.; Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Ruby, Christine M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Geriatr Res Educ, Pittsburgh, PA USA. [Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Clin, Pittsburgh, PA USA. [Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Hilmer, Sarah N.] Royal N Shore Hosp, St Leonards, NSW, Australia. [Hilmer, Sarah N.] Univ Sydney, Sydney, NSW 2006, Australia. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst Geriatr Res Edu, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Sch Med, Dept Geriatr Med, Kaufman Med Bldg,Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM hanlonj@dom.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Hilmer, Sarah/0000-0002-5970-1501; Boudreau, Robert/0000-0003-0162-5187 FU National Institute of Aging [R01AG027017, P30AG024827, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health FX This study was primarily supported by National Institute of Aging grants (R01AG027017; P30AG024827, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106). This research was supported in part by the Intramural Research program of the National Institutes of Health, National Institute on Aging. NR 39 TC 63 Z9 64 U1 2 U2 4 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2009 VL 64 IS 4 BP 492 EP 498 DI 10.1093/gerona/gln043 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 421XD UT WOS:000264390700011 PM 19196642 ER PT J AU Teerlink, JR Metra, M Felker, GM Ponikowski, P Voors, AA Weatherley, BD Marmor, A Katz, A Grzybowski, J Unemori, E Teichman, SL Cotter, G AF Teerlink, John R. Metra, Marco Felker, G. Michael Ponikowski, Piotr Voors, Adriaan A. Weatherley, Beth Davison Marmor, Alon Katz, Amos Grzybowski, Jacek Unemori, Elaine Teichman, Sam L. Cotter, Gad TI Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study SO LANCET LA English DT Article ID RENAL VASODILATION; CONSCIOUS RATS; PREGNANCY HORMONE; CLINICAL-TRIALS; PEPTIDE; HYPERFILTRATION; HEMODYNAMICS; ANTAGONIST; ENDOTHELIN; TEZOSENTAN AB Background Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion Of placebo (n=62) or relaxin 10 mu g/kg (n=40), 30 mu g/kg (n=43), 100 mu g/kg (n=39), or 250 mu g/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806. Findings In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 mu g/kg per day group, 42 in the relaxin 30 mu g/kg per day group, 37 in the relaxin 100 mu g/kg per day group, and 49 in the relaxin 250 mu g/kg per day group. Dyspnoea improved with relaxin 30 mu g/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mmxh [SD 87121 vs 4622 mmxh [90031; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% Cl 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups. Interpretation When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety. C1 [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Metra, Marco] Univ Brescia, Dept Expt & Appl Sci, Sect Cardiovasc Dis, Brescia, Italy. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Mil Hosp, Dept Cardiol, Dept Hlth Sci, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Weatherley, Beth Davison; Cotter, Gad] Momentum Res, Durham, NC USA. [Marmor, Alon] Ziv Med Ctr, Inst Heart, Safed, Israel. [Katz, Amos] Barzilai Govt Hosp, Dept Cardiol, Ashqelon, Israel. [Grzybowski, Jacek] Inst Cardiol, Dept Gen Cardiol, Warsaw, Poland. [Unemori, Elaine; Teichman, Sam L.] Corthera, San Mateo, CA USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol 111C,4150 Clemet St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Katz, Amos/E-6261-2011; Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568 FU Corthera (USA) FX The Pre-RELAX-AHF study is supported by Corthera (USA). NR 29 TC 201 Z9 212 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR-MAY PY 2009 VL 373 IS 9673 BP 1429 EP 1439 DI 10.1016/S0140-6736(09)60622-X PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 437QL UT WOS:000265501900031 PM 19329178 ER PT J AU Khosroshahi, A Stone, JR Pratt, DS Deshpande, V Stone, JH AF Khosroshahi, Arezou Stone, James R. Pratt, Daniel S. Deshpande, Vikram Stone, John H. TI Painless jaundice with serial multi-organ dysfunction SO LANCET LA English DT Editorial Material ID AUTOIMMUNE PANCREATITIS; DISEASE C1 [Khosroshahi, Arezou] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Rheumatol Unit, Boston, MA 02114 USA. [Stone, James R.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pratt, Daniel S.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Khosroshahi, A (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Rheumatol Unit, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM akhosroshahi@partners.org NR 5 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR-MAY PY 2009 VL 373 IS 9673 BP 1494 EP 1494 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 437QL UT WOS:000265501900038 PM 19394539 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Incidence of Perioperative Airway Complications in Patients With Previous Medialization Thyroplasty SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triological-Society CY JAN 24-25, 2009 CL Boston, MA SP Triol Soc DE Endotracheal intubation; laryngeal mask airway; medialization thyroplasty; perioperative airway complications; unilateral vocal fold paralysis ID ENDOTRACHEAL INTUBATION; SURGICAL-TREATMENT; I THYROPLASTY; SURGERY; PHONOSURGERY; LARYNX AB Objectives/Hypothesis: Determine the incidence and characterize perioperative airway complications in patients who have undergone medialization thyroplasty (MT) and subsequently undergo procedures requiring anesthesia. Study Design: Retrospective review of post-MT anesthesia encounters in a large academic hospital. Methods: A series of post-MT patients was reviewed, identifying anesthesia encounters undergoing endotracheal intubation (ETI) or laryngeal mask airway (LMA) placement. Details on the perioperative course of each encounter were extracted and examined for evidence of airway complications. The incidence of airway obstruction and need for airway intervention were determined and compared to those of control patients matched for type of procedure. Relationships between complications and perioperative management were analyzed. Results: A total of 74 anesthesia encounters were identified among 219 post-MT patients. Perioperative airway complications among post-MT patients arose in five procedures (6.8%; 95% CI: 1.0-12.4%). Stridor in the operating or recovery room was exhibited three times, with all episodes requiring nebulized racemic epinephrine and intravenous steroids for resolution of symptoms. One patient underwent an urgent tracheotomy for severe stridor leading to airway compromise in the recovery room. Immediately after induction with an LMA, one patient failed to maintain oxygen saturations above 90% and consequently required conversion to ETI. Among 79 matched controls without prior MT, no perioperative complications (0%) occurred (P = .027). Conclusions: The incidence of perioperative airway complications in post-MT patients is non-neglible and may be serious. Surgical, anesthesia, and recovery room staff should be made aware of the significantly increased risk of airway complications in post-MT patients. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 17 TC 5 Z9 5 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2009 VL 119 IS 4 BP 675 EP 678 DI 10.1002/lary.20156 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 442CJ UT WOS:000265817100010 PM 19274729 ER PT J AU Kumai, Y Kobler, JB Park, H Lopez-Guerra, G Karajanagi, S Herrera, VLM Zeitels, SM AF Kumai, Yoshihiko Kobler, James B. Park, Hyoungshin Lopez-Guerra, Gerardo Karajanagi, Sandeep Herrera, Victoria L. M. Zeitels, Steven M. TI Crosstalk Between Adipose-Derived Stem/Stromal Cells and Vocal Fold Fibroblasts In Vitro SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 111th Annual Meeting of the Triological-Society CY MAY 03-04, 2008 CL Orlando, FL SP Triol Soc DE Adipose-derived stem cells; fibroblast; vocal fold scar; coculture; crosstalk; ferret ID STROMAL CELLS; STEM-CELLS; EXTRACELLULAR-MATRIX; RABBIT MODEL; TISSUE; BIOMECHANICS; PREVENTION AB Objectives/Hypothesis: To explore adipose-derived stem cell/fibroblast interactions as a potential remodeling pathway for vocal fold scar. Study Design: Fibroblasts and adipose-derived stem/stromal cells (ASCs) were cultured alone and in combination in a cell-contact-independent paracrine system. Analyses of cell proliferation, and the production of hyaluronic acid (HA) and collagen were performed on samples collected on days 1, 3, and 7. Methods: Normal fibroblasts (NFs) were isolated bilaterally from the subepithelial lamina propria of two normal ferret vocal folds. Scar fibroblasts (SFs) were isolated from vocal folds that were electrocauterized 2 weeks before harvest. ASCs were isolated from lipoaspirated subcutaneous abdominal fat of two ferrets. A transwell cell-contact-independent cell communication culturing system was used for coculture experiments. Cells were seeded at 50,000/well in both monoculture and coculture experiments. Results: In monoculture, SFs proliferated faster and produced less HA and more collagen than NFs at day 7 (P < .05). In SF/ASC coculture, SF proliferation was diminished and collagen production at day 7 decreased (P < .05). HA production did not differ between monoculture and coculture conditions. Conclusions: Normal and scar-tissue-derived vocal fold fibroblasts maintain phenotypic differences in culture, thus validating this in vitro scar model. In between SFs and ASCa, leading to less collagen secretion. The data support the hypothesis that ASCs can induce favorable remodeling of scarred vocal folds in vivo by their interactions with endogenous fibroblasts. C1 [Kobler, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil,Lary, Boston, MA 02114 USA. [Karajanagi, Sandeep] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Herrera, Victoria L. M.] Boston Univ, Sch Med, Dept Med, Sect Mol Med, Boston, MA 02118 USA. [Herrera, Victoria L. M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Kobler, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Laryngeal Surg & Voice Rehabil,Lary, 55 Fruit St,620 Thier, Boston, MA 02114 USA. OI Lopez-Guerra, Gerardo/0000-0003-0305-4680 NR 15 TC 20 Z9 20 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2009 VL 119 IS 4 BP 799 EP 805 DI 10.1002/lary.20149 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 442CJ UT WOS:000265817100030 PM 19263411 ER PT J AU Yamaura, M Yao, M Yaroslavsky, I Cohen, R Smotrich, M Kochevar, IE AF Yamaura, Maki Yao, Min Yaroslavsky, Ilya Cohen, Richard Smotrich, Michael Kochevar, Irene E. TI Low Level Light Effects on Inflammatory Cytokine Production by Rheumatoid Arthritis Synoviocytes SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE inflammation; IL-1 beta; low level light therapy; synoviocytes; rheumatoid arthritis; TNF-alpha ID POWER LASER IRRADIATION; TNF-ALPHA LEVELS; NF-KAPPA-B; INFRARED RADIATION; HUMAN FIBROBLASTS; THERAPY; MECHANISMS; IL-1-BETA; TOXICITY; PATHWAY AB Background and Objective: Low level light therapy (LLLT) is being evaluated for treating chronic and acute pain associated with rheumatoid arthritis (RA) and other inflammatory diseases. The mechanisms underlying the effectiveness of LLLT for pain relief in RA are not clear. The objectives of this study were to determine whether LLLT decreased production of pro-inflammatory cytokines by cells from RA joints, and, if so, to identify cellular mechanisms. Study Design/Materials and Methods: Synoviocytes from RA patients were treated with 810 nm radiation before or after addition of tumor necrosis factor-alpha (TNF-alpha). mRNA for TNF-alpha, interleukin (IL)-1 beta, IL-6, and IL-8 was measured after 30, 60, and 180 minutes using RT-PCR. Intracellular and extracellular protein levels for 12 cytokines/chemokines were measured at 4, 8, and 24 hours using multiplexed ELISA. NF-kappa B activation was detected using Western blotting to follow degradation of I kappa B alpha and nuclear localization of the p65 subunit of NF-kappa B. Results: Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the mRNA level of TNF-alpha and IL-1 beta in RA synoviocytes. This treatment using 25 J/cm2 also decreases the intracellular levels of TNF-alpha, IL-1 beta, and IL-8 protein but did not affect the levels of seven other cytokines/ chemokines. TNF-alpha-induced activation of NF-kappa B is not altered by 810 nm radiation using 25 J/cm(2). Conclusions: The mechanism for relieving joint pain in RA by LLLT may involve reducing the level of proinflammatory cytokines/chemokines produced by synoviocytes. This mechanism may be more general and underlie the beneficial effects of LLLT on other inflammatory conditions. Lasers Surg. Med. 41:282-290, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Yamaura, Maki; Yao, Min; Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yaroslavsky, Ilya; Cohen, Richard; Smotrich, Michael] Palomar Med Technol Inc, Burlington, MA 01803 USA. [Kochevar, Irene E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Thier 212, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU Palomar Medical Technologies FX Contract grant sponsor: Palomar Medical Technologies. NR 32 TC 41 Z9 48 U1 1 U2 6 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 APR PY 2009 VL 41 IS 4 BP 282 EP 290 DI 10.1002/lsm.20766 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 436HS UT WOS:000265404000006 PM 19347944 ER PT J AU Kepler, GM Banksa, HT Davidian, M Rosenberg, ES AF Kepler, G. M. Banksa, H. T. Davidian, M. Rosenberg, E. S. TI A model for HCMV infection in immunosuppressed patients SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE HCMV; CMV; Herpes; Transplantation; Mathematical model; Immunosuppression ID ORGAN TRANSPLANT RECIPIENTS; POLYMERASE-CHAIN-REACTION; HUMAN CYTOMEGALOVIRUS; PCR ASSAY; T-CELLS; DYNAMICS; VIRUS; REACTIVATION; DISEASE; LOAD AB We propose a model for HCMV infection in healthy and immunosuppressed patients. First, we present the biological model and formulate a system of ordinary differential equations to describe the pathogenesis of primary HCMV infection in immunocompetent and immunosuppressed individuals. We then investigate how clinical data can be applied to this model. Approximate parameter values for the model are derived from data available in the literature and from mathematical and physiological considerations. Simulations with the approximated parameter values demonstrates that the model is capable of describing primary, latent, and secondary (reactivated) HCMV infection. Reactivation simulations with this model provide a window into the dynamics of HCMV infection in (D-R+) transplant situations, where latently-infected recipients (R+) receive transplant tissue from HCMV-naive donors (D-). (C) 2008 Elsevier Ltd. All rights reserved. C1 [Kepler, G. M.; Banksa, H. T.; Davidian, M.; Rosenberg, E. S.] N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. [Kepler, G. M.; Banksa, H. T.; Davidian, M.; Rosenberg, E. S.] N Carolina State Univ, Ctr Quantitat Sci Biomed, Raleigh, NC 27695 USA. [Rosenberg, E. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenberg, E. S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Banksa, HT (reprint author), N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. EM gmkepler@ncsu.edu; htbanks@ncsu.edu; davidian@ncsu.edu; erosenberg1@partners1.org FU National Institute of Allergy and Infectious Diseases [R01AI071915-07] FX This research was supported in part by Grant Number R01AI071915-07 from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the NIH. NR 37 TC 7 Z9 8 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD APR PY 2009 VL 49 IS 7-8 BP 1653 EP 1663 DI 10.1016/j.mcm.2008.06.003 PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 414VI UT WOS:000263892900034 PM 20161307 ER PT J AU Marzetti, E Carter, CS Wohlgemuth, SE Lees, HA Giovannini, S Anderson, B Quinn, LS Leeuwenburgh, C AF Marzetti, Emanuele Carter, Christy S. Wohlgemuth, Stephanie E. Lees, Hazel A. Giovannini, Silvia Anderson, Barbara Quinn, LeBris S. Leeuwenburgh, Christiaan TI Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Sarcopenia; Interleukin-15; Tumor necrosis factor-alpha; Calorie restriction; Apoptosis ID NECROSIS-FACTOR-ALPHA; X-LINKED INHIBITOR; TUMOR-BEARING RATS; SKELETAL-MUSCLE; TNF-ALPHA; AGED RATS; INTERLEUKIN-15 PROTECTS; PHYSICAL PERFORMANCE; DNA FRAGMENTATION; SOLEUS MUSCLE AB TNF-alpha-mediated apoptosis is enhanced in aged rodent muscles, suggesting that this pathway may be involved in sarcopenia. Interleukin-15 (IL-15), a muscle-derived anabolic cytokine, mitigates muscle wasting and apoptosis in cachectic rats. This effect is thought to occur through inhibition of TNF-alpha-triggered apoptosis. We investigated IL-15 signaling and the TNF-a-mediated pathway of apoptosis in the gastrocnemius muscle of Fischer344xBrown Norway rats across the ages of 8, 18, 29 and 37 months, in relation to life-long calorie restriction (CR, 40% calorie intake reduction). Aging caused loss of muscle mass and increased apoptotic DNA fragmentation, which were mitigated by CR. Protein levels of IL-15 and mRNA abundance of IL-15 receptor a-chain decreased in senescent ad libitum (AL) fed rats, but were maintained in CR rodents. Elevations of TNF-alpha, TNF-receptor 1, cleaved caspase-8 and -3 were observed at advanced age in AL rats. These changes were prevented or mitigated by CR. Our results indicate that aging is associated with decreased IL-15 signaling in rat gastrocnemius muscle, which may contribute to sarcopenia partly through enhanced TNF-a-mediated apoptosis. Preservation of IL-15 signaling by CR may therefore represent a further mechanism contributing to the anti-aging effect of this dietary intervention in skeletal muscle. Published by Elsevier Ireland Ltd. C1 [Marzetti, Emanuele; Carter, Christy S.; Wohlgemuth, Stephanie E.; Lees, Hazel A.; Giovannini, Silvia; Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr Res, Inst Aging, Div Biol Aging, Gainesville, FL 32610 USA. [Marzetti, Emanuele; Giovannini, Silvia] Univ Cattolica Sacro Cuore, Dept Gerontol Geriatr & Physiat, I-00168 Rome, Italy. [Carter, Christy S.] Malcom Randall Vet Affairs Med Ctr, GRECC, Gainesville, FL 32608 USA. [Anderson, Barbara; Quinn, LeBris S.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. [Anderson, Barbara; Quinn, LeBris S.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Marzetti, E (reprint author), Univ Florida, Dept Aging & Geriatr Res, Inst Aging, Div Biol Aging, 1600 SW Archer Rd,Room P1-09,POB 100143, Gainesville, FL 32610 USA. EM emarzetti@aging.ufl.edu; cleeuwen@aging.ufl.edu RI Carter, Christy/E-6630-2011; Marzetti, Emanuele/A-9430-2010; Giovannini, Silvia/J-2955-2012 OI Marzetti, Emanuele/0000-0001-9567-6983; Giovannini, Silvia/0000-0001-9125-752X FU USDA Cooperative State Research, Education, and Extension Service Animal Growth and Nutrient Utilization Program [2005-35206-15264]; Department of Veterans Affairs; University of Florida Institute; Claude D. Pepper Older Americans Independence Center [1 P30 AG028740]; [NIA R01-AG17994]; [AG21042]; [NIH R01-AG024526-02]; [NIH R01-AG024136] FX This research was supported by grants to CL (NIA R01-AG17994 and AG21042), CC (NIH R01-AG024526-02) and LQ (NIH R01-AG024136 and National Research Initiative Competitive Grant 2005-35206-15264 from the USDA Cooperative State Research, Education, and Extension Service Animal Growth and Nutrient Utilization Program), and by the Department of Veterans Affairs. EM, SW and HL are supported by the University of Florida Institute on Aging and Claude D. Pepper Older Americans Independence Center (1 P30 AG028740). The authors wish to thank Dr. Michael Daniels for assisting with the statistical analysis, and Drs. Tim Hofer and Stephane Servais for their critical input in the conduct of the study. NR 64 TC 48 Z9 50 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR PY 2009 VL 130 IS 4 BP 272 EP 280 DI 10.1016/j.mad.2008.12.008 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 423RF UT WOS:000264512700010 PM 19396981 ER PT J AU Thorpe, CT Bryson, CL Maciejewski, ML Bosworth, HB AF Thorpe, Carolyn T. Bryson, Chris L. Maciejewski, Mathew L. Bosworth, Hayden B. TI Medication Acquisition and Self-Reported Adherence in Veterans With Hypertension SO MEDICAL CARE LA English DT Article; Proceedings Paper CT AcademyHealth Annual Research Meeting CY JUN 08-10, 2008 CL Washington, DC DE medication acquisition; refill adherence; self-report; hypertension ID BLOOD-PRESSURE CONTROL; HEALTH-CARE-SYSTEM; REFILL ADHERENCE; PHARMACY RECORDS; OLDER-ADULTS; THERAPY; ASSOCIATION; PERSISTENCE; VALIDATION; VALIDITY AB Objectives: To examine factors associated with oversupply and undersupply of antihypertensive medication, and examine evidence for medication acquisition as distinct from self-reported adherence. Research Design: Analysis of pharmacy refill records, medical charts, and in-person interviews. Subjects: Five hundred sixty-two male veterans with hypertension enrolled in a randomized controlled trial to improve BP control. Measures: Patients were classified as having undersupply (<0.80), appropriate supply (>= 0.80 and <= 1.20), or oversupply (>1.20) of antihypertensive medication in the 90 days before trial enrollment based on the ReComp algorithm. Determination of BP control was based on clinic measurements at enrollment. Demographic, clinical, psychosocial, and behavioral factors relevant to medication-taking behavior and BP were assessed at enrollment. Results: Twenty-three percent of the patients had undersupply, 47% had appropriate Supply, and 30% had oversupply of antihypertensive medication. Multinomial logistic regression revealed that using fewer classes of antihypertensive medications and greater perceived adherence barriers were independently associated with greater likelihood of undersupply. Current employment was associated with decreased likelihood of oversupply, and greater comorbidity and being married were associated with increased likelihood of oversupply. Agreement between ReComp and self-reported adherence was poor (kappa = 0.19 P < 0.001). Undersupply, oversupply, and self-reported nonadherence were all independently associated with decreased likelihood of BP control after adjusting for each other and patient factors. Conclusions: Antihypertensive oversupply was common and may arise front different circumstances than Undersupply. Measures of medication acquisition and self-reported adherence appear to provide distinct, complementary information about patients' medication-taking behavior. C1 [Thorpe, Carolyn T.] Univ Wisconsin, Dept Populat Hlth Sci, Hlth Innovat Program, Madison, WI 53792 USA. [Bryson, Chris L.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA USA. [Bryson, Chris L.] Univ Washington, Dept Med, Seattle, WA USA. [Maciejewski, Mathew L.; Bosworth, Hayden B.] Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Mathew L.; Bosworth, Hayden B.] Duke Univ, Dept Med, Durham, NC USA. [Bosworth, Hayden B.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Bosworth, Hayden B.] Duke Univ, Ctr Aging & Human Dev, Durham, NC USA. RP Thorpe, CT (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, Hlth Innovat Program, E5-724 CSC,600 Highland Ave, Madison, WI 53792 USA. EM cthorpe@wisc.edu NR 49 TC 30 Z9 30 U1 1 U2 6 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 APR PY 2009 VL 47 IS 4 BP 474 EP 481 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 425ER UT WOS:000264620300014 PM 19330891 ER PT J AU Bokhour, BG Pugh, MJ Rao, JK Avetisyan, R Berlowitz, DR Kazis, LE AF Bokhour, Barbara G. Pugh, Mary Jo Rao, Jaya K. Avetisyan, Ruzan Berlowitz, Dan R. Kazis, Lewis E. TI Improving Methods for Measuring Quality of Care A Patient-Centered Approach in Chronic Disease SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med DE quality indicators; patient-centered care; chronic disease; epilepsy; qualitative methods ID HEALTH-CARE; PATIENTS PERSPECTIVE; EPILEPSY; INTERVENTIONS; PERCEPTIONS; DEPRESSION; IMPACT; VIEWS; AGREE AB As health care systems seek to provide patient-centered care as a cornerstone of quality, how to measure this aspect of quality has become a concern. Previous development of quality indicators for treating individual chronic disease has rarely included patient perspectives on quality of care. Using epilepsy as an exemplar, the authors sought to develop an approach to measuring patient-centered quality of care. They conducted six focus groups with adults with epilepsy. Using qualitative methods, the authors initially identified 10 patient-generated quality indicators, 5 of which were subsequently rated, along with literature-based quality indicators, by an expert panel using a modified RAND appropriateness methodology. The authors discuss similarities and differences in aspects of care patients and providers value as essential for good quality. The process presented in this article may serve as a model for incorporating patient perceptions of quality into the future development of quality indicators for chronic diseases. C1 [Bokhour, Barbara G.; Berlowitz, Dan R.; Kazis, Lewis E.] Edith Nourse Rogers Mem Vet Aff Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Bokhour, Barbara G.; Avetisyan, Ruzan; Berlowitz, Dan R.; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Pugh, Mary Jo] S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat Implementat Ctr, Res Enhancement Award Program, San Antonio, TX USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Rao, Jaya K.] Ctr Dis Control & Prevent, Healthy Aging Program, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Rao, Jaya K.] Emory Univ, Sch Med, Atlanta, GA USA. RP Bokhour, BG (reprint author), Edith Nourse Rogers Mem Vet Aff Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. OI Bokhour, Barbara/0000-0001-8238-0745; Kazis, Lewis/0000-0003-1800-5849 FU PHS HHS [ASPH S3492] NR 45 TC 15 Z9 15 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD APR PY 2009 VL 66 IS 2 BP 147 EP 166 DI 10.1177/1077558708327174 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 420JD UT WOS:000264284700002 PM 19074307 ER PT J AU Riboldi, M Gierga, DP Chen, GTY Baroni, G AF Riboldi, Marco Gierga, David P. Chen, George T. Y. Baroni, Guido TI Accuracy in breast shape alignment with 3D surface fitting algorithms SO MEDICAL PHYSICS LA English DT Article DE image texture; medical image processing; optimisation; phantoms; radiation therapy; surface fitting; surface topography measurement ID INITIAL CLINICAL-EXPERIENCE; PATIENT SETUP; REGISTRATION TECHNIQUES; RADIATION-THERAPY; IMAGING-SYSTEM; RADIOTHERAPY; IRRADIATION; CANCER AB Surface imaging is in use in radiotherapy clinical practice for patient setup optimization and monitoring. Breast alignment is accomplished by searching for a tentative spatial correspondence between the reference and daily surface shape models. In this study, the authors quantify whole breast shape alignment by relying on texture features digitized on 3D surface models. Texture feature localization was validated through repeated measurements in a silicone breast phantom, mounted on a high precision mechanical stage. Clinical investigations on breast shape alignment included 133 fractions in 18 patients treated with accelerated partial breast irradiation. The breast shape was detected with a 3D video based surface imaging system so that breathing was compensated. An in-house algorithm for breast alignment, based on surface fitting constrained by nipple matching (constrained surface fitting), was applied. Results were compared with a commercial software where no constraints are utilized (unconstrained surface fitting). Texture feature localization was validated within 2 mm in each anatomical direction. Clinical data show that unconstrained surface fitting achieves adequate accuracy in most cases, though nipple mismatch is considerably higher than residual surface distances (3.9 mm vs 0.6 mm on average). Outliers beyond 1 cm can be experienced as the result of a degenerate surface fit, where unconstrained surface fitting is not sufficient to establish spatial correspondence. In the constrained surface fitting algorithm, average surface mismatch within 1 mm was obtained when nipple position was forced to match in the [1.5; 5] mm range. In conclusion, optimal results can be obtained by trading off the desired overall surface congruence vs matching of selected landmarks (constraint). Constrained surface fitting is put forward to represent an improvement in setup accuracy for those applications where whole breast positional reproducibility is an issue. C1 [Riboldi, Marco; Baroni, Guido] Politecn Milano Univ, Dept Bioengn, TBMLab, I-20133 Milan, Italy. [Gierga, David P.; Chen, George T. Y.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gierga, David P.; Chen, George T. Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Riboldi, M (reprint author), Politecn Milano Univ, Dept Bioengn, TBMLab, I-20133 Milan, Italy. EM marco.riboldi@polimi.it RI Baroni, Guido/D-3012-2011; Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU Roberto Rocca Foundation FX The authors acknowledge the Roberto Rocca Foundation for the support. Thanks to Lisa Storey (Carnegie Mellon University) for the help in software development. NR 25 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2009 VL 36 IS 4 BP 1193 EP 1198 DI 10.1118/1.3086079 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 426UP UT WOS:000264733800018 PM 19472625 ER PT J AU Iqbal, N Cardillo, S Volger, S Bloedon, LT Anderson, RA Boston, R Szapary, PO AF Iqbal, Nayyar Cardillo, Serena Volger, Sheri Bloedon, LeAnne T. Anderson, Richard A. Boston, Raymond Szapary, Philippe O. TI Chromium Picolinate Does Not Improve Key Features of Metabolic Syndrome in Obese Nondiabetic Adults SO METABOLIC SYNDROME AND RELATED DISORDERS LA English DT Article CT 66th Annual Meeting of the American-Diabetes-Association CY JUN 09-13, 2006 CL Washington, DC SP Amer Diabet Assoc ID INSULIN SENSITIVITY; GLUCOSE-METABOLISM; BODY-WEIGHT; OLDER MEN; SUPPLEMENTATION; METAANALYSIS; CHOLESTEROL; PARAMETERS; NONOBESE; HEALTHY AB Background: The use of chromium-containing dietary supplements is widespread among patients with type 2 diabetes. Chromium's effects in patients at high risk for developing diabetes, especially those with metabolic syndrome, is unknown. The objective of this study was to determine the effects of chromium picolinate (CrPic) on glucose metabolism in patients with metabolic syndrome. Method: A double-blind, placebo-controlled, randomized trial was conducted at a U. S. academic medical center. Sixty three patients with National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)-defined metabolic syndrome were included. The primary end point was a change in the insulin sensitivity index derived from a frequently sampled intravenous glucose tolerance test. Prespecified secondary end points included changes in other measurements of glucose metabolism, oxidative stress, fasting serum lipids, and high sensitivity C-reactive protein. Results: After 16 weeks of CrPic treatment, there was no significant change in insulin sensitivity index between groups (P = 0.14). However, CrPic increased acute insulin response to glucose (P = 0.02). CrPic had no significant effect on other measures of glucose metabolism, body weight, serum lipids, or measures of inflammation and oxidative stress. Conclusion: CrPic at 1000 mu g/day does not improve key features of the metabolic syndrome in obese nondiabetic patients. C1 [Szapary, Philippe O.] Univ Penn Hlth Syst, Philadelphia Heart Inst, Div Gen Internal Med, Inst Translat Med & Therapeut,CRIP,Dept Med, Philadelphia, PA 19104 USA. [Iqbal, Nayyar; Cardillo, Serena] Univ Penn Hlth Syst, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Volger, Sheri; Bloedon, LeAnne T.; Szapary, Philippe O.] Univ Penn Hlth Syst, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Iqbal, Nayyar] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Boston, Raymond] Univ Penn, Sch Vet Med, Dept Clin Studies, Biostat Sect,New Bolton Ctr, Kennett Sq, PA 19348 USA. [Anderson, Richard A.] USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Szapary, PO (reprint author), Univ Penn Hlth Syst, Philadelphia Heart Inst, Div Gen Internal Med, Inst Translat Med & Therapeut,CRIP,Dept Med, Suite 2A,39th & Market St, Philadelphia, PA 19104 USA. EM philippe.szapary@uphs.upenn.edu OI volger, sheri/0000-0002-1689-1173 FU NCCIH NIH HHS [K-23 AT-00058]; NCRR NIH HHS [M01-RR00040]; NIDDK NIH HHS [R21DK067241] NR 31 TC 33 Z9 35 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-4196 J9 METAB SYNDR RELAT D JI Metab. Syndr. Relat. Disord. PD APR PY 2009 VL 7 IS 2 BP 143 EP 150 DI 10.1089/met.2008.0048 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 438XP UT WOS:000265589900010 PM 19422140 ER PT J AU Makimura, H Wei, J Dolan-Looby, SE Ricchiuti, V Grinspoon, S AF Makimura, Hideo Wei, Jeffrey Dolan-Looby, Sara E. Ricchiuti, Vincent Grinspoon, Steven TI Retinol-bindifig protein levels are increased in association-with gonadotropin levels in healthy women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ABDOMINAL FAT DISTRIBUTION; PITUITARY-ADIPOSE AXIS; INSULIN-RESISTANCE; SERUM RETINOL-BINDING-PROTEIN-4; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; MENOPAUSAL STATUS; PLASMA-PROTEIN; INFLAMMATION AB Recent studies have demonstrated an association between retinol-binding protein (RBP4) and insulin resistance. Retinol-binding protein is decreased in women and elevated in polycystic ovary syndrome. However, prior studies have not investigated the relationship between RBP4, gonadal steroids, and gonadotropins in healthy women. The aim of this study was to determine the RBP4 levels in a cohort of healthy women with a range of body mass indices and glucose tolerances to investigate the relationship between RBP4, gonadotropin levels, and menopausal status. Serum RBP4 levels were measured by enzyme-linked immunosorbent assay and quantitative Western blot in 88 healthy women (aged 24-59 years) from the general community in a cross-sectional study. Retinol-binding protein was higher in postmenopausal compared with premenopausal women (26.1 +/- 2.1 vs 19.3 +/- 0.5 mu g/mL, P = .001). In univariate analysis, RBP4 was associated with follicle-stimulating hormone (r = 0.37, P = .0004), luteinizing hormone (r = 0.3, P = .005), and sex hormone-binding globulin (r = 0.24, P = .03) and trended to significance with estradiol (P = .09) but not with free testosterone or dehydroepiandrosterone sulfate. Retinol-binding protein was also associated with insulin at 2 hours during an oral glucose tolerance test (r = 0.24, P = .03) and the area under the curve for insulin during the oral glucose tolerance test (r = 0.26, P = .02). In multivariate regression modeling, both follicle-stimulating hormone (P = .03) and luteinizing lion-none (P = .04) remained significantly associated with RBP4 after controlling for estradiol, sex hormone-binding globulin, insulin area under the curve, cholesterol, triglycerides, waist-to-hip ratio, and tumor necrosis factor a. Retinol-binding protein was not associated with inflammatory markers or with carotid intima-media thickness. Therefore, RBP4 is higher in postmenopausal women and is associated with gonadotropin concentrations in healthy women. (C) 2009 Elsevier Inc. All rights reserved. C1 [Makimura, Hideo; Wei, Jeffrey; Dolan-Looby, Sara E.; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Makimura, Hideo; Wei, Jeffrey; Dolan-Looby, Sara E.; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Makimura, Hideo; Wei, Jeffrey; Dolan-Looby, Sara E.; Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ricchiuti, Vincent] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ricchiuti, Vincent] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM hmakimura@partners.org FU National Institutes of Health [K24DK064545] FX This work was supported in part by National Institutes of Health grant K24DK064545 (S.G.). NR 33 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2009 VL 58 IS 4 BP 479 EP 487 DI 10.1016/j.metabol.2008.11.004 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 429QV UT WOS:000264936100008 PM 19303967 ER PT J AU Weinrauch, LA Bayliss, G Gleason, RE Lee, AT D'Elia, JA AF Weinrauch, Larry A. Bayliss, George Gleason, Ray E. Lee, Annette T. D'Elia, John A. TI Utilization of an abbreviated diabetes impact management scale to assess change in subjective disability during a, trial of pulsatile insulin delivery demonstrates benefit SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol ID QUALITY-OF-LIFE; SUBTLE NEUROLOGICAL ABNORMALITIES; MELLITUS; PANCREAS; INFUSION; ADULTS AB A prospective interventional study of pulsatile intravenous insulin infusion therapy has demonstrated reduction of left ventricular mass and blunting of progression of diabetic nephropathy. We anticipated that improvements in objective parameters would be associated with similar improvement measurable by the self-administered Diabetes Impact Management Scale (DIMS). The DIMS was administered at baseline and 12 months for 19 participants randomized to receive either standard insulin treatment of 3 to 4 injections of insulin daily or insulin treatment plus an additional day per week of 3 intravenous pulses over an 8 hour period. For standard vs pulsed intravenous insulin therapy, mean baseline scores were similar for the 12 total questions as well as the groups of 7 questions with emotional content and 5 with physical (neurologic) content. Mean study group scores at 1 year and changes over 1 year were not significantly different for the 7 questions with emotional content (P = .3143, .7574). Score results for the 5 questions related to neurologic status at 1 year and changes over 1 year were significantly different between patients with standard and with pulsed insulin therapy (P = .0144, 0.0004). Pulsatile intravenous insulin, when added to standard multiple-dose insulin therapy, was demonstrated to improve subjective perception of neurologic disability on repeated use of an abbreviated form of the DIMS. (C) 2009 Elsevier Inc. All rights reserved. C1 [Weinrauch, Larry A.; D'Elia, John A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.; Bayliss, George; D'Elia, John A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.] Mt Auburn Hosp, Boston, MA 02215 USA. [Weinrauch, Larry A.; Bayliss, George; Gleason, Ray E.; D'Elia, John A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lee, Annette T.] N Shore Univ Hosp, Manhasset, NY 11030 USA. EM lweinrauch@hms.harvard.edu OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 21 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2009 VL 58 IS 4 BP 488 EP 491 DI 10.1016/j.metabol.2008.11.006 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 429QV UT WOS:000264936100009 PM 19303968 ER PT J AU Weinrauch, LA Bayliss, G Gleason, RE Lee, AT D'Elia, JA AF Weinrauch, Larry A. Bayliss, George Gleason, Ray E. Lee, Annette T. D'Elia, John A. TI A pilot study to assess utility of changes in elements of the Diabetes Impact Management Scale in evaluating diabetic patients for progressive nephropathy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol ID QUALITY-OF-LIFE; RENAL-INSUFFICIENCY; KIDNEY-DISEASE; MELLITUS; SINGLE AB A prospective study involving the use of the Diabetes Impact Management Scale (DIMS) in individuals with diabetic nephropathy as part of an interventional study of pulsatile intravenous insulin infusion therapy is used to define the utility of repeated subjective DIMS testing. We hypothesized that repeated use of such an evaluation would correlate well with other objective end points. The DIMS was administered at baseline and 12 months for 19 participants randomized to receive either standard insulin treatment of 3 to 4 injections of insulin daily or standard insulin treatment plus an additional day per week of 3 intravenous pulses over an 8-hour period. Measures of glycemic control, renal function, hemostatic factors, hemodynamics, left ventricular mass, and function were assessed at baseline and 12 months. Of 44 questions on impact of diabetes management, only 12(5 reflecting physical and 7 reflecting emotional status) showed significant change from baseline to 1 year. Changes in the 5 physical questions related to neurologic status correlated with stable creatinine (P = .0001). stable creatinine clearance (P = .0001), and decrease in left ventricular hypertrophy (P = .0117). Repeated use of an abbreviated, standardized subjective instrument uncovered changes in quality of life that correlated with differences in renal function and left ventricular mass over 12 months. Further use of such and instrument may help us focus treatment for maximum impact. (C) 2009 Elsevier Inc. All rights reserved. C1 [Weinrauch, Larry A.; D'Elia, John A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.; Bayliss, George; D'Elia, John A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Weinrauch, Larry A.; Lee, Annette T.] Mt Auburn Hosp, Boston, MA 02215 USA. [Weinrauch, Larry A.; Bayliss, George; Gleason, Ray E.; D'Elia, John A.] Harvard Univ, Sch Med, Cambridge, MA 02472 USA. [Lee, Annette T.] N Shore Univ Hosp, Manhasset, NY 11030 USA. RP Weinrauch, LA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM lweinrauch@hms.harvard.edu OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 21 TC 1 Z9 1 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2009 VL 58 IS 4 BP 492 EP 496 DI 10.1016/j.metabol.2008.11.005 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 429QV UT WOS:000264936100010 PM 19303969 ER PT J AU Pamir, N McMillen, TS Li, YI Lai, CM Wong, H LeBoeuf, RC AF Pamir, Nathalie McMillen, Timothy S. Li, Yu-I Lai, Ching-Mei Wong, Howard LeBoeuf, Renee C. TI Overexpression of apolipoprotein A5 in mice is not protective against body weight gain and aberrant glucose homeostasis SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DIET-INDUCED OBESITY; HIGH-FAT-DIET; PLASMA TRIGLYCERIDE CONCENTRATIONS; LDL PARTICLE-SIZE; INSULIN-RESISTANCE; LIPOPROTEIN-LIPASE; RICH LIPOPROTEINS; LEPTIN RESISTANCE; SEXUAL-DIMORPHISM; C57BL/6J MICE AB Apolipoprotein As (APOA5) is expressed primarily in the liver and modulates plasma triglyceride levels in mice and humans. Mice overexpressing APOA5 exhibit reduced plasma trigglyceride levels. Because there is a tight association between plasma triglyceride concentration and traits of the metabolic syndrome, we used transgenic mice overexprcssing human APOA5 to test the concept that these Mice would be protected from diet-induced obesity and insulin resistance. Male and female transgenic and wild-type mice on the FVB/N genetic background were fed standard rodent chow or a diet rich in fat and sucrose for 18 weeks, during which time clinical phenotypes associated with obesity and glucose homeostasis were measured. We found that APOA5 transgenic (A5tg) mice were resistant to diet-induced changes in plasma triglyceride but not total cholesterol levels. Body weights were similar between the genotypes for females and males, although male A5tg mice showed a modest but significant increase in the relative size of inguinal fat pads. Although male A5tg mice showed a significantly increased ratio of plasma glucose to insulin, profiles Of glucose clearance as evaluated after injections of glucose or insulin failed to reveal any differences between genotypes, Overall, our data showed that there was no advantage to responses to diet-induced obesity with chronic reduction of plasma triglyceride levels as mediated by overexpression of APOA5. (C) 2009 Elsevier Inc. All rights reserved. C1 [Pamir, Nathalie; McMillen, Timothy S.; Li, Yu-I; LeBoeuf, Renee C.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Lai, Ching-Mei; Wong, Howard] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Lai, Ching-Mei; Wong, Howard] Vet Adm Greater Los Angeles Healthcare Syst, Lipid Res Lab, Los Angeles, CA USA. RP LeBoeuf, RC (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. EM leboeuf@u.washington.edu RI Pamir, Nathalie/H-5234-2013; OI LI, YU-I/0000-0002-9888-1541 FU National Institutes of Health [RO1 DK063159]; VA Merit Review Grant (HW) FX This work was supported by grants from the National Institutes of Health (RO1 DK063159 [RCL]) and a VA Merit Review Grant (HW). NR 51 TC 13 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2009 VL 58 IS 4 BP 560 EP 567 DI 10.1016/j.metabol.2008.11.018 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 429QV UT WOS:000264936100020 PM 19303979 ER PT J AU Engelman, A AF Engelman, Alan TI Mechanistic and pharmacological analyses of HIV-1 integration Introduction SO METHODS LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL DNA INTEGRATION; ACTIVE ANTIRETROVIRAL THERAPY; PROTEIN IN-VITRO; VIRAL-DNA; PREINTEGRATION COMPLEXES; CONCERTED INTEGRATION; TYPE-1 INTEGRASE; FUSION PROTEINS; STRAND-TRANSFER AB Significant advances have transpired in the human immunodeficiency Virus type I (HIV-1) integration field in recent years. Considering its essential nature, integrase has long been a target of interest for antiviral drug development. The most significant advance was the approval of the Merck compound raltegravir, the first licensed integrase inhibitor, in October 2007. Another milestone was the identification and characterization of specific nucleoprotein complexes that mediate integrase 3' processing and DNA strand transfer activities in vitro. Genome-wide distribution analyses have furthermore revealed that different retroviruses differentially target distinctive regions of chromatin during integration. For examples, lentiviruses favor actively transcribed genes whereas gammaretroviruses Such as Moloney murine leukemia virus prefer transcriptional start sites. Though the underlying mechanisms are unknown for most retroviruses, the lentiviral preference is in large part guided through the interaction with the integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75. Experimental methods that formed the foundations for each of these advances, as well as other techniques topical to the study of HIV-1 integration, are described in this issue of Methods. (C) 2009 Elsevier Inc. All rights reserved. C1 [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Engelman, Alan] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, 44 Binney St,CLSB-1010, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [R01 AI039394, R01 AI052014-07, R37 AI039394, R01 AI039394-13, R01 AI052014] NR 108 TC 2 Z9 2 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 1046-2023 J9 METHODS JI Methods PD APR PY 2009 VL 47 IS 4 BP 225 EP 228 DI 10.1016/j.ymeth.2009.03.018 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442AR UT WOS:000265812600001 PM 19389610 ER PT J AU Lohr, J Knoechel, B Caretto, D Abbas, AK AF Lohr, Jens Knoechel, Birgit Caretto, David Abbas, Abul K. TI Balance of Th1 and Th17 effector and peripheral regulatory T cells SO MICROBES AND INFECTION LA English DT Article DE Interferon-gamma; IL-17; FoxP3; Th17 cells; Th1 cells; Regulatory T cells ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; VERSUS-HOST-DISEASE; INTERLEUKIN-17 FAMILY; CYTOKINE MILIEU; TGF-BETA; IN-VIVO; IL-17; INFLAMMATION; GENERATION; ARTHRITIS AB Transfer of antigen-specific T cells into antigen-expressing lymphopenic recipients leads to the sequential generation of Th1 and Th17 effector and protective CD25(+)FoxP3(+) regulatory cells in the periphery with surprisingly different kinetics. Such an experimental model is potentially valuable for defining the stimuli that regulate lineage decision and plasticity of various T cell effectors and peripheral regulatory T cells. Our studies have shown that IL-17 production occurs rapidly and declines within the first week with the appearance of IFN-gamma producing T cells. Regulatory T cells appear during the recovery phase of the disease. The factors that mediate this complex differentiation originating from a starting naive T cell population remain to be defined. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Lohr, Jens; Knoechel, Birgit; Caretto, David; Abbas, Abul K.] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. [Lohr, Jens] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Knoechel, Birgit] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Abbas, AK (reprint author), Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. EM abul.abbas@ucsf.edu FU NIAID NIH HHS [R01 AI073656-02, R01 AI064677-05, P01 AI035297-17] NR 33 TC 20 Z9 21 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2009 VL 11 IS 5 BP 589 EP 593 DI 10.1016/j.micinf.2009.04.012 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 468RZ UT WOS:000267839100008 PM 19376259 ER PT J AU Oh-Hora, M Rao, A AF Oh-hora, Masatsugu Rao, Anjana TI The calcium/NFAT pathway: role in development and function of regulatory T cells SO MICROBES AND INFECTION LA English DT Article DE Calcium; Foxp3; Stim1 ID CA2+ STORE DEPLETION; CRAC CHANNEL; PLASMA-MEMBRANE; SENSOR STIM1; LYMPHOCYTE-ACTIVATION; AUTOIMMUNE ARTHRITIS; PORE SUBUNIT; MICE LACKING; B-CELLS; FOXP3 AB Calcium signals are essential for diverse cellular functions in the immune system. Sustained Ca(2+) entry is necessary for complete and long-lasting activation of calcineurin/NFAT pathways. A growing number of studies have emphasized that Ca(2+)/Calcineurin/NFAT pathway is crucial for both development and function of regulatory T cells. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Oh-hora, Masatsugu] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Oh-Hora, M (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Rm 136,Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM ohora.gcoe@tmd.ac.jp FU NIH; JDRF; Uehara Memorial Foundation FX This work was supported by NIH and JDRF grants (to A.R.). M.O. was supported by a research fellowship from the Uehara Memorial Foundation. NR 62 TC 23 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2009 VL 11 IS 5 BP 612 EP 619 DI 10.1016/j.micinf.2009.04.008 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 468RZ UT WOS:000267839100011 PM 19375514 ER PT J AU Lauwers, GY Forcione, DG Nishioka, NS Deshpande, V Lisovsky, MY Brugge, WR Mino-Kenudson, M AF Lauwers, Gregory Y. Forcione, David G. Nishioka, Norman S. Deshpande, Vikram Lisovsky, Mikhail Y. Brugge, William R. Mino-Kenudson, Mari TI Novel endoscopic therapeutic modalities for superficial neoplasms arising in Barrett's esophagus: a primer for surgical pathologists SO MODERN PATHOLOGY LA English DT Article DE Barrett's esophagus; high-grade dysplasia; intramucosal adenocarcinoma; endoscopic therapy ID HIGH-GRADE DYSPLASIA; PHOTODYNAMIC THERAPY; MUCOSAL RESECTION; EARLY ADENOCARCINOMA; EARLY CANCER; FOLLOW-UP; 5-AMINOLEVULINIC ACID; SQUAMOUS REEPITHILIALIZATION; INTRAMUCOSAL ADENOCARCINOMA; CIRCUMFERENTIAL ABLATION AB This review introduces some of the novel endoscopic modalities used for the treatment of superficial neoplasms arising in the setting of Barrett's esophagus, namely endoscopic mucosal resection and photodynamic therapy. We describe the appropriate technical details for pathologists to know to effectively communicate with the gastroenterologists as well as the pitfalls in the evaluation of endoscopic mucosal resection specimens and post photodynamic therapy follow-up biopsies. C1 [Lauwers, Gregory Y.; Deshpande, Vikram; Lisovsky, Mikhail Y.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Unit, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Forcione, David G.; Nishioka, Norman S.; Deshpande, Vikram; Lisovsky, Mikhail Y.; Brugge, William R.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Forcione, David G.; Nishioka, Norman S.; Brugge, William R.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Unit, 55 Fruit St,WRN 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 74 TC 7 Z9 8 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2009 VL 22 IS 4 BP 489 EP 498 DI 10.1038/modpathol.2009.4 PG 10 WC Pathology SC Pathology GA 426VJ UT WOS:000264736000001 PM 19287464 ER PT J AU Nazarian, RM Kapur, P Rakheja, D Piris, A Duncan, LM Mihm, MC Hoang, MP AF Nazarian, Rosalynn M. Kapur, Payal Rakheja, Dinesh Piris, Adriano Duncan, Lyn M. Mihm, Martin C., Jr. Hoang, Mai P. TI Atypical and malignant hidradenomas: a histological and immunohistochemical study SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 07-13, 2009 CL Boston, MA SP US & Canadian Acad Pathol DE malignant hidradenoma; atypical hidradenoma; Ki-67; phosphorylated histone H3; epidermal growth factor receptor; Her2/neu ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; TYROSINE KINASE INHIBITORS; CLEAR CELL HIDRADENOMA; LUNG-CANCER; ECCRINE ACROSPIROMAS; NODULAR HIDRADENOMA; BREAST-CANCER; HIDRADENOCARCINOMA; KI-67; EXPRESSION AB The histological features of atypical hidradenoma are worrisome for increased risk of recurrence and possible malignant potential; however, earlier studies with immunohistochemistry or patient follow-up have not been reported. In addition, immunohistochemical analysis of hidradenocarcinoma exists in the literature mainly as case reports and as a single series of six cases. We compare the histological features and Ki-67, phosphorylated histone H3, epidermal growth factor receptor, and Her2/neu expression profiles of 15 atypical and 15 malignant hidradenomas with those of benign hidradenoma and metastasizing adnexal carcinomas. Infiltrative growth pattern, deep extension, necrosis, nuclear pleomorphism, and >= 4 mitoses per 10 high-power fields are specific features of hidradenocarcinomas. Significant difference in mean Ki-67% was observed between benign and malignant hidradenomas (P < 0.001), benign and metastasizing adnexal carcinomas (0.002), atypical and malignant hidradenomas (P < 0.001), and between atypical hidradenomas and metastasizing adnexal carcinomas ( 0.002). Significant difference in mean phosphorylated histone H3% was observed between benign and malignant hidradenomas (P < 0.001), benign and metastasizing adnexal carcinomas (0.003), atypical and malignant hidradenomas (P < 0.001), and between atypical hidradenomas and metastasizing adnexal carcinomas (P < 0.001). Mean epidermal growth factor receptor total score was significantly different in benign and atypical hidradenoma when compared with that in metastasizing adnexal carcinoma (P=0.014 and 0.019, respectively). Equivocal or 2+ Her2/neu positivity was observed in one hidradenocarcinoma and in two metastasizing adnexal carcinomas. Receiver operating characteristic curve analysis for Ki-67 and phosphorylated histone H3% positivity reveals statistically significant criterion values of > 11.425 and > 0.7, respectively, for distinguishing malignant hidradenomas from atypical hidradenomas. Despite the presence of some worrisome histological features, the significantly different immunoprofile from the malignant counterpart suggests that atypical hidradenomas are likely to recur but are unlikely to metastasize. A tumor with Ki-67 > 11% and/or phosphorylated histone H3 > 0.7% would likely be a malignant rather than an atypical hidradenoma. The infrequent Her2/neu overexpression in hidradenocarcinoma suggests its limited therapeutic role. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. [Nazarian, Rosalynn M.; Piris, Adriano; Duncan, Lyn M.; Mihm, Martin C., Jr.; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. [Kapur, Payal; Rakheja, Dinesh] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Rakheja, Dinesh] Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 30 TC 22 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2009 VL 22 IS 4 BP 600 EP 610 DI 10.1038/modpathol.2009.18 PG 11 WC Pathology SC Pathology GA 426VJ UT WOS:000264736000013 PM 19252473 ER PT J AU Lafleur, MA Xu, DS Hemler, ME AF Lafleur, Marc A. Xu, Daosong Hemler, Martin E. TI Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BREAST-CANCER CELLS; ENDOTHELIAL-CELLS; 1-MATRIX METALLOPROTEINASE; CD81 FUNCTION; MT1-MMP; INVASION; MICE; PROGRESSION; EXPRESSION; INTEGRIN AB Membrane type-1 matrix metalloproteinase (MT1-MMP) supports tumor cell invasion through extracellular matrix barriers containing fibrin, collagen, fibronectin, and other proteins. Here, we show that simultaneous knockdown of two or three members of the tetraspanin family (CD9, CD81, and TSPAN12) markedly decreases MT1-MMP proteolytic functions in cancer cells. Affected functions include fibronectin proteolysis, invasion and growth in three-dimensional fibrin and collagen gels, and MMP-2 activation. Tetraspanin proteins (CD9, CD81, and TSPAN2) selectively coimmunoprecipitate and colocalize with MT1-MMP. Although tetraspanins do not affect the initial biosynthesis of MT1-MMP, they do protect the newly synthesized protein from lysosomal degradation and support its delivery to the cell surface. Interfering with MT1-MMP-tetraspanin collaboration may be a useful therapeutic approach to limit cancer cell invasion and metastasis. C1 [Lafleur, Marc A.; Xu, Daosong; Hemler, Martin E.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu FU National Institutes of Health [GM-38903]; Canadian Institutes of Health Research (CIHR) FX This work was supported by National Institutes of Health grant GM-38903 and a Canadian Institutes of Health Research (CIHR) fellowship (to M.A.L.). NR 52 TC 44 Z9 47 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2009 VL 20 IS 7 BP 2030 EP 2040 DI 10.1091/mbc.E08-11-1149 PG 11 WC Cell Biology SC Cell Biology GA 427AO UT WOS:000264752100013 PM 19211836 ER PT J AU Dejmek, J Iglehart, JD Lazaro, JB AF Dejmek, Janna Iglehart, J. Dirk Lazaro, Jean-Bernard TI DNA-Dependent Protein Kinase (DNA-PK)-Dependent Cisplatin-Induced Loss of Nucleolar Facilitator of Chromatin Transcription (FACT) and Regulation of Cisplatin Sensitivity by DNA-PK and FACT SO MOLECULAR CANCER RESEARCH LA English DT Article ID WERNER-SYNDROME PROTEIN; KU; PHOSPHORYLATION; RESISTANCE; DYNAMICS; REPAIR; DAMAGE; LOCALIZATION; INHIBITOR; PATHWAYS AB Both the Ku subunit of the DNA-dependent protein kinase (DNA-PK) and the facilitator of chromatin transcription (FACT) complex reportedly bind cisplatin-DNA adducts. For this study, we developed an immunocytochemical assay based on detergent extraction allowing unveiling nucleolar subpopulations of proteins present in both the nucleoplasm and the nucleolus. Immunofluorescence analysis in various human cancer cell lines and immunoblotting of isolated nucleoli show that DNA-PK catalytic subunit (DNA-PKcs), Ku86, the Werner syndrome protein (WRN), and the structure-specific recognition protein 1 (SSRP1) subunit of FACT colocalize in the nucleolus and exit the nucleolus after cisplatin treatment. Nucleolar localization of Ku is also lost after y or UV irradiation and exposure to DNA-damaging drugs, such as actinomycin D, mitomycin C, hydroxyurea, and doxorubicin. Ku86 and WRN leave the nucleolus after exposure to low (>1 mu g/mL) doses of cisplatin. In contrast, the SSRP1 association with the nucleolus was disrupted only by high (50-100 mu g/mL) doses of cisplatin. Both cisplatin-induced loss of nucleolar SSRP1 and DNA-PK activation are suppressed by pretreatment of the cells with wortmannin or the DNA-PK inhibitor NU7026 but not by the phosphatidylinositol 3-kinase inhibitor LY294002. In the same conditions, kinase inhibitors did not alter the exit of DNA-PKcs and WRN, suggesting that different mechanisms regulate the exit of DNA-PK/WRN and FACT from the nucleolus. Furthermore, RNA silencing of DNA-PKcs blocked the cisplatin-induced exit of nucleolar SSRP1. Finally, silencing of DNA-PKcs or SSRP1 by short hairpin RNA significantly increased the sensitivity of cancer cells to cisplatin. (Mol Cancer Res 2009;7(4):581-91) C1 [Dejmek, Janna; Iglehart, J. Dirk; Lazaro, Jean-Bernard] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Dejmek, Janna; Iglehart, J. Dirk; Lazaro, Jean-Bernard] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Lazaro, JB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St,Smith 1058, Boston, MA 02115 USA. EM jiglehart@partners.org; Jean-bernard_lazaro@dfci.harvard.edu FU Dana-Farber Cancer Institute; Catt Family Foundation; Cabot Family Charitable Trust; Marsha Rivkin Center for Ovarian Cancer Research; Friends of Dana-Farber; Lund University (Sweden); Swedish Society for Medical Research FX Woman's Cancers Program at Dana-Farber Cancer Institute, Catt Family Foundation, Cabot Family Charitable Trust, Marsha Rivkin Center for Ovarian Cancer Research, and Friends of Dana-Farber (J-B. Lazaro). J. Dejmek is a fellowship recipient of Lund University (Sweden) and the Swedish Society for Medical Research. NR 37 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2009 VL 7 IS 4 BP 581 EP 591 DI 10.1159/1541-7786.MCR-08-0049 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 435CY UT WOS:000265322400013 PM 19372586 ER PT J AU Park, J Lee, DS Christakis, NA Barabasi, AL AF Park, Juyong Lee, Deok-Sun Christakis, Nicholas A. Barabasi, Albert-Laszlo TI The impact of cellular networks on disease comorbidity SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE cellular networks; comorbidity; database; population-level statistics ID PROTEIN INTERACTION NETWORK; BIOLOGY; CANCER; CELLS; ERA AB The impact of disease-causing defects is often not limited to the products of a mutated gene but, thanks to interactions between the molecular components, may also affect other cellular functions, resulting in potential comorbidity effects. By combining information on cellular interactions, disease-gene associations, and population-level disease patterns extracted from Medicare data, we find statistically significant correlations between the underlying structure of cellular networks and disease comorbidity patterns in the human population. Our results indicate that such a combination of population-level data and cellular network information could help build novel hypotheses about disease mechanisms. Molecular Systems Biology 7 April 2009; doi:10.1038/msb.2009.16 C1 [Park, Juyong; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Dept Phys, Boston, MA 02115 USA. [Park, Juyong; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Dept Biol, Boston, MA 02115 USA. [Park, Juyong; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Dept Comp Sci, Boston, MA 02115 USA. [Park, Juyong; Lee, Deok-Sun; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lee, Deok-Sun] Inha Univ, Dept Nat Med Sci, Inchon, South Korea. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Park, J (reprint author), Northeastern Univ, Ctr Complex Network Res, Dept Phys, 360 Huntington Ave, Boston, MA 02115 USA. EM perturbation@gmail.com; barabasi@gmail.com RI Christakis, Nicholas/C-3205-2009; Lee, Deok-Sun/D-1335-2011; Park, Juyong/I-2290-2012 FU JSMF [220020084]; NSF ITR [DMR-0426737]; NIH [CEGS-1P50HG4233/CFDA, U01 A1070499-01/111620-2, U56 CA113004] FX We thank Quan Zhong, Cesar Hidalgo, Nick Blumm, and Marc Vidal for useful discussions. This research was supported by JSMF 220020084, NSF ITR DMR-0426737, NIH CEGS-1P50HG4233/CFDA #93.172, NIH U01 A1070499-01/111620-2, and NIH U56 CA113004/sub MGH. NR 28 TC 91 Z9 93 U1 2 U2 15 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 APR PY 2009 VL 5 AR 262 DI 10.1038/msb.2009.16 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 445PI UT WOS:000266062400007 PM 19357641 ER PT J AU Chadderton, N Millington-Ward, S Palfi, A O'Reilly, M Tuohy, G Humphries, MM Li, T Humphries, P Kenna, PF Farrar, GJ AF Chadderton, Naomi Millington-Ward, Sophia Palfi, Arpad O'Reilly, Mary Tuohy, Gearoid Humphries, Marian M. Li, Tiansen Humphries, Peter Kenna, Paul F. Farrar, G. Jane TI Improved Retinal Function in a Mouse Model of Dominant Retinitis Pigmentosa Following AAV-delivered Gene Therapy SO MOLECULAR THERAPY LA English DT Article ID LEBERS CONGENITAL AMAUROSIS; RHODOPSIN MUTATION; RNA INTERFERENCE; PHOTORECEPTOR CELLS; RIBOZYME RESCUE; TRANSGENIC MICE; DEGENERATION; REPLACEMENT; LOCALIZATION; PRESERVATION AB Mutational heterogeneity represents one of the greatest barriers impeding the progress toward the clinic of gene therapies for many dominantly inherited disorders. A general strategy of gene suppression in conjunction with replacement has been proposed to overcome this mutational heterogeneity. In the current study, various aspects of this strategy are explored for a dominant form of the retinal degeneration, retinitis pigmentosa (RP), caused by mutations in the rhodopsin gene (RHO-adRP). While >200 mutations have been identified in rhodopsin ( RHO), in principle, suppression and replacement may be employed to provide a single mutation-independent therapeutic for this form of the disorder. In the study we demonstrate in a transgenic mouse simulating human RHO-adRP that RNA interference-based suppression, together with gene replacement utilizing the endogenous mouse gene as the replacement, provides significant benefit as evaluated by electroretinography (ERG). Moreover, this is mirrored histologically by preservation of photoreceptors. AAV-based vectors were utilized for in vivo delivery of the therapy to the target cell type, the photoreceptors. The results demonstrate that RNAi-based mutation-independent suppression and replacement can provide benefit for RHO-adRP and promote the therapeutic approach as potentially beneficial for other autosomal dominantly inherited disorders. C1 [Chadderton, Naomi; Millington-Ward, Sophia; Palfi, Arpad; O'Reilly, Mary; Tuohy, Gearoid; Humphries, Marian M.; Humphries, Peter; Kenna, Paul F.; Farrar, G. Jane] Trinity Coll Dublin, Smurfit Inst Genet, Dept Genet, Dublin 2, Ireland. [Li, Tiansen] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Kenna, Paul F.] Eye & Ear Hosp, Res Fdn, Dublin, Ireland. RP Chadderton, N (reprint author), Trinity Coll Dublin, Smurfit Inst Genet, Dept Genet, Dublin 2, Ireland. EM chaddern@tcd.ie RI Palfi, Arpad/C-5541-2009; chadderton, naomi/A-6953-2010; Farrar, G Jane/B-9832-2011 OI Palfi, Arpad/0000-0003-3517-3932; FU Science Foundation Ireland,; Fighting Blindness Ireland, Enterprise Ireland; European Union [RETNET MRT-CT2003-504003, EviGenoRet LSHG-CT-2005-512036] FX We thank Prof. Thaddeus Dryja (Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston) for providing the NHR mouse; Dr Fernandez (Flow Cytometry Core Facility in University College, Dublin) for assisting with FACS analysis; Prof. R. S. Molday (University of British Colombia, Vancouver BC, CA) for the two rhodopsin primary antibodies; and the staff of the Bioresources Unit, Trinity College, Dublin. The research was supported by grant awards from Science Foundation Ireland, Fighting Blindness Ireland, Enterprise Ireland, the 6th Framework Programs of the European Union (RETNET MRT-CT2003-504003, EviGenoRet LSHG-CT-2005-512036). NR 43 TC 66 Z9 67 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2009 VL 17 IS 4 BP 593 EP 599 DI 10.1038/mt.2008.301 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 426ZR UT WOS:000264748000004 PM 19174761 ER PT J AU Deng, J Shoemaker, R Xie, B Gore, A LeProust, EM Antosiewicz-Bourget, J Egli, D Maherali, N Park, IH Yu, JY Daley, GQ Eggan, K Hochedlinger, K Thomson, J Wang, W Gao, Y Zhang, K AF Deng, Jie Shoemaker, Robert Xie, Bin Gore, Athurva LeProust, Emily M. Antosiewicz-Bourget, Jessica Egli, Dieter Maherali, Nimet Park, In-Hyun Yu, Junying Daley, George Q. Eggan, Kevin Hochedlinger, Konrad Thomson, James Wang, Wei Gao, Yuan Zhang, Kun TI Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; PLURIPOTENT; ARABIDOPSIS; EPIGENOME; PATTERNS; SYSTEM; ARRAYS; LINES; MAPS AB Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets. We report a method to specifically capture an arbitrary subset of genomic targets for single-molecule bisulfite sequencing for digital quantification of DNA methylation at single-nucleotide resolution. A set of similar to 30,000 padlock probes was designed to assess methylation of similar to 66,000 CpG sites within 2,020 CpG islands on human chromosome 12, chromosome 20, and 34 selected regions. To investigate epigenetic differences associated with dedifferentiation, we compared methylation in three human fibroblast lines and eight human pluripotent stem cell lines. Chromosome-wide methylation patterns were similar among all lines studied, but cytosine methylation was slightly more prevalent in the pluripotent cells than in the fibroblasts. Induced pluripotent stem (iPS) cells appeared to display more methylation than embryonic stem cells. We found 288 regions methylated differently in fibroblasts and pluripotent cells. This targeted approach should be particularly useful for analyzing DNA methylation in large genomes. C1 [Deng, Jie; Gore, Athurva; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Shoemaker, Robert; Wang, Wei] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Xie, Bin; Gao, Yuan] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA USA. [Gao, Yuan] Virginia Commonwealth Univ, Dept Comp Sci, Richmond, VA USA. [LeProust, Emily M.] Agilent Technol, Genom Solut Unit, Santa Clara, CA USA. [Antosiewicz-Bourget, Jessica; Yu, Junying; Thomson, James] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA. [Egli, Dieter; Eggan, Kevin] Harvard Univ, Stowers Med Inst, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Egli, Dieter; Eggan, Kevin] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Maherali, Nimet; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Maherali, Nimet; Hochedlinger, Konrad] Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA USA. [Park, In-Hyun; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In-Hyun; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhang, K (reprint author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. EM ygao@vcu.edu; kzhang@bioeng.ucsd.edu RI Gao, Yuan/E-1706-2011 FU NIDA NIH HHS [R01 DA025779, R01 DA025779-01, R01-DA025779] NR 31 TC 288 Z9 298 U1 7 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2009 VL 27 IS 4 BP 353 EP 360 DI 10.1038/nbt.1530 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 430EO UT WOS:000264971800021 PM 19330000 ER PT J AU Ball, MP Li, JB Gao, Y Lee, JH LeProust, EM Park, IH Xie, B Daley, GQ Church, GM AF Ball, Madeleine P. Li, Jin Billy Gao, Yuan Lee, Je-Hyuk LeProust, Emily M. Park, In-Hyun Xie, Bin Daley, George Q. Church, George M. TI Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells SO NATURE BIOTECHNOLOGY LA English DT Article ID DNA METHYLATION; ARABIDOPSIS; GENERATION; RESOLUTION; TRANSCRIPTION; PLURIPOTENT; EPIGENETICS; METHYLOME; PROBES; MAPS AB Studies of epigenetic modifications would benefit from improved methods for high-throughput methylation profiling. We introduce two complementary approaches that use next-generation sequencing technology to detect cytosine methylation. In the first method, we designed similar to 10,000 bisulfite padlock probes to profile similar to 7,000 CpG locations distributed over the ENCODE pilot project regions and applied them to human B-lymphocytes, fibroblasts and induced pluripotent stem cells. This unbiased choice of targets takes advantage of existing expression and chromatin immunoprecipitation data and enabled us to observe a pattern of low promoter methylation and high gene-body methylation in highly expressed genes. The second method, methyl-sensitive cut counting, generated nontargeted genome-scale data for similar to 1.4 million HpaII sites in the DNA of B-lymphocytes and confirmed that gene-body methylation in highly expressed genes is a consistent phenomenon throughout the human genome. Our observations highlight the usefulness of techniques that are not inherently or intentionally biased towards particular subsets like CpG islands or promoter regions. C1 [Ball, Madeleine P.; Li, Jin Billy; Lee, Je-Hyuk; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Ball, Madeleine P.; Li, Jin Billy; Lee, Je-Hyuk; Church, George M.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Gao, Yuan; Xie, Bin] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA USA. [LeProust, Emily M.] Agilent Technol, Genom Solut Unit, Santa Clara, CA USA. [Park, In-Hyun; Daley, George Q.] Childrens Hosp, Dept Med, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Park, In-Hyun; Daley, George Q.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Church, GM (reprint author), Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. EM jli@genetics.med.harvard.edu; gmc@harvard.edu RI Gao, Yuan/E-1706-2011; OI Ball, Madeleine/0000-0003-0544-5925 FU NHGRI-Centers of Excellence in Genomic Science FX We thank Kun Zhang for discussion throughout this work; Wei Lin for help with computational design; Andrew Chess and Ravid Straussman for discussion and critical reading of the manuscript; Harvard Biopolymers Facility for Solexa sequencing; and Harvard Partners Center for Genetics and Genomics for gene expression profiling. This work was supported by the NHGRI-Centers of Excellence in Genomic Science (to G. M. C.). NR 41 TC 496 Z9 512 U1 9 U2 70 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2009 VL 27 IS 4 BP 361 EP 368 DI 10.1038/nbt.1533 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 430EO UT WOS:000264971800022 PM 19329998 ER PT J AU Lefkimmiatis, K Srikanthan, M Maiellaro, I Moyer, MP Curci, S Hofer, AM AF Lefkimmiatis, Konstantinos Srikanthan, Meera Maiellaro, Isabella Moyer, Mary Pat Curci, Silvana Hofer, Aldebaran M. TI Store-operated cyclic AMP signalling mediated by STIM1 SO NATURE CELL BIOLOGY LA English DT Article ID PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; CA2+ STORE; FLUORESCENT PROTEIN; INTRACELLULAR CA2+; CAPACITATIVE CA2+; CRAC CHANNEL; I-CRAC; CAMP; CALCIUM AB Depletion of Ca(2+) from the endoplasmic reticulum ( ER) results in activation of plasma membrane Ca(2+) entry channels. This 'store-operated' process requires translocation of a transmembrane ER Ca(2+) sensor protein, stromal interaction molecule 1 (STIM1), to sites closely apposed to Ca(2+) channels at the cell surface. However, it is not known whether a reduction in Ca(2+) stores is coupled to other signalling pathways by this mechanism. We found that lowering the concentration of free Ca(2+) in the ER, independently of the cytosolic Ca(2+) concentration, also led to recruitment of adenylyl cyclases. This resulted in enhanced cAMP accumulation and PKA activation, measured using FRET-based cAMP indicators. Translocation of STIM1 was required for efficient coupling of ER Ca(2+) depletion to adenylyl cyclase activity. We propose the existence of a pathway (store-operated cAMP signalling or SOcAMPS) in which the content of internal Ca(2+) stores is directly connected to cAMP signalling through a process that involves STIM1. C1 [Lefkimmiatis, Konstantinos; Srikanthan, Meera; Maiellaro, Isabella; Curci, Silvana; Hofer, Aldebaran M.] Brigham & Womens Hosp, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. [Lefkimmiatis, Konstantinos; Srikanthan, Meera; Maiellaro, Isabella; Curci, Silvana; Hofer, Aldebaran M.] Brigham & Womens Hosp, Dept Surg, W Roxbury, MA 02132 USA. [Lefkimmiatis, Konstantinos; Srikanthan, Meera; Maiellaro, Isabella; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, W Roxbury, MA 02132 USA. [Moyer, Mary Pat] INCELL Corp LLC, San Antonio, TX 78249 USA. RP Hofer, AM (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM ahofer@rics.bwh.harvard.edu RI Lefkimmiatis, Konstantinos/I-1239-2016 OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866 FU Department of Veteran's Affairs; Harvard Digestive Diseases Center; American Heart Association FX We are grateful to the following individuals for their kind gifts of plasmids: Kees Jalink for the Epac sensor, Roger Tsien for mCherry, Jin Zhang for AKAR3, Marie Dziadek and Lorna Johnstone for STIM1 and STIM2, Masaru Okabe for pCX-EGFP, and Tobias Meyer for YFP-STIM1, YFP-STIM1D76A, and YFP-STIM2 constructs. We thank Jessica Roy for technical assistance and Drs. Dheeraj Pelluru, Eberhard Fromter and Raj K. Goyal for helpful comments. This study was supported by a Merit Review award from the Department of Veteran's Affairs (A.M.H.) and by an NIH Center grant from the Harvard Digestive Diseases Center (to A.M. H.). K.L. is the recipient of an American Heart Association Postdoctoral Fellowship award.. NR 53 TC 85 Z9 88 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2009 VL 11 IS 4 BP 433 EP U164 DI 10.1038/ncb1850 PG 20 WC Cell Biology SC Cell Biology GA 434HD UT WOS:000265264900013 PM 19287379 ER PT J AU Yeh, JRJ Munson, KM Elagib, KE Goldfarb, AN Sweetser, DA Peterson, RT AF Yeh, Jing-Ruey J. Munson, Kathleen M. Elagib, Kamaleldin E. Goldfarb, Adam N. Sweetser, David A. Peterson, Randall T. TI Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GLYCOGEN-SYNTHASE KINASE-3; PROSTAGLANDIN E-2; VALPROIC ACID; INTESTINAL POLYPOSIS; PROGENITOR CELLS; GENE DISRUPTION; KNOCKOUT MICE; BETA-CATENIN; COLON-CANCER AB It has been proposed that inhibitors of an oncogene's effects on multipotent hematopoietic progenitor cell differentiation may change the properties of the leukemic stem cells and complement the clinical use of cytotoxic drugs. Using zebrafish, we developed a robust in vivo hematopoietic differentiation assay that reflects the activity of the oncogene AML1-ETO. Screening for modifiers of AML1-ETO-mediated hematopoietic dysregulation uncovered unexpected roles of COX-2- and beta-catenin-dependent pathways in AML1-ETO function. This approach may open doors for developing therapeutics targeting oncogene function within leukemic stem cells. C1 [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Sweetser, David A.; Peterson, Randall T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Yeh, Jing-Ruey J.; Munson, Kathleen M.; Peterson, Randall T.] MIT & Harvard, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Elagib, Kamaleldin E.; Goldfarb, Adam N.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Sweetser, David A.] Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Dept Pediat, Boston, MA 02114 USA. RP Yeh, JRJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, 149 13th St, Charlestown, MA 02129 USA. EM jyeh1@partners.org; peterson@cvrc.mgh.harvard.edu FU National Institute of Aging [AG031300]; National Cancer Institute [CA118498]; Mattina Proctor Foundation; Claflin Distinguished Scholar Award FX We thank E. R. Plovie and M. N. Rivera (Massachusetts General Hospital) and H. Clevers (Hubrecht Institute) for providing reagents, and C. L. Tsai, C. Sachidanandan and the members of the Developmental Biology Laboratory for helpful discussion. J.- R.J.Y. is supported by a Career Development Award (AG031300) from the National Institute of Aging. The authors received financial support from the National Cancer Institute (CA118498 to R. T. P.), the Mattina Proctor Foundation (to D. A. S) and the Claflin Distinguished Scholar Award (to J.- R. J. Y.). NR 50 TC 83 Z9 87 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD APR PY 2009 VL 5 IS 4 BP 236 EP 243 DI 10.1038/nchembio.147 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 422KH UT WOS:000264426100012 PM 19172146 ER PT J AU Newton-Cheh, C Eijgelsheim, M Rice, KM de Bakker, PIW Yin, XY Estrada, K Bis, JC Marciante, K Rivadeneira, F Noseworthy, PA Sotoodehnia, N Smith, NL Rotter, JI Kors, JA Witteman, JCM Hofman, A Heckbert, SR O'Donnell, CJ Uitterlinden, AG Psaty, BM Lumley, T Larson, MG Stricker, BHC AF Newton-Cheh, Christopher Eijgelsheim, Mark Rice, Kenneth M. de Bakker, Paul I. W. Yin, Xiaoyan Estrada, Karol Bis, Joshua C. Marciante, Kristin Rivadeneira, Fernando Noseworthy, Peter A. Sotoodehnia, Nona Smith, Nicholas L. Rotter, Jerome I. Kors, Jan A. Witteman, Jacqueline C. M. Hofman, Albert Heckbert, Susan R. O'Donnell, Christopher J. Uitterlinden, Andre G. Psaty, Bruce M. Lumley, Thomas Larson, Martin G. Stricker, Bruno H. Ch TI Common variants at ten loci influence QT interval duration in the QTGEN Study SO NATURE GENETICS LA English DT Article ID SUDDEN CARDIAC DEATH; GENOME-WIDE ASSOCIATION; NOS1 REGULATOR NOS1AP; PHOSPHOLAMBAN GENE; HEART; REPOLARIZATION; FRAMINGHAM; SCN5A; KCNH2; POLYMORPHISM AB QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes. Associations were found at five newly identified loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6.5% of the variation in QT interval. These results, together with an accompanying paper, offer insights into myocardial repolarization and suggest candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias. C1 [Newton-Cheh, Christopher; Noseworthy, Peter A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher; de Bakker, Paul I. W.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Newton-Cheh, Christopher; de Bakker, Paul I. W.] MIT, Cambridge, MA 02139 USA. [Newton-Cheh, Christopher; Yin, Xiaoyan; O'Donnell, Christopher J.; Larson, Martin G.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Eijgelsheim, Mark; Rivadeneira, Fernando; Witteman, Jacqueline C. M.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. Ch] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rice, Kenneth M.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H. Ch] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Bis, Joshua C.; Marciante, Kristin; Sotoodehnia, Nona; Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Dept Med, Sch Med, Div Cardiol, Seattle, WA 98195 USA. [Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Vet Adm Off Res & Dev, Seattle Epidemiol Res Ctr, Seattle, WA USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Kors, Jan A.; Stricker, Bruno H. Ch] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Witteman, Jacqueline C. M.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H. Ch] Netherlands Genom Initiat Sponsored Netherlands C, NL-3000 CA Rotterdam, Netherlands. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. EM b.stricker@erasmusmc.nl RI Rice, Kenneth/A-4150-2013; de Bakker, Paul/B-8730-2009; Rivadeneira, Fernando/O-5385-2015; OI Rice, Kenneth/0000-0001-5779-4495; de Bakker, Paul/0000-0001-7735-7858; Rivadeneira, Fernando/0000-0001-9435-9441; Larson, Martin/0000-0002-9631-1254 FU Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine [N01-HC-25195]; Affymetrix [N02-HL-6-4278]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund; Department of Medicine at Boston University School of Medicine; Boston Medical Center; Pfizer; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports, the European Commission (DG XII); Municipality of Rotterdam; Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; CHS [N01-HC85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; National Institute of Neurological Disorders and Stroke [U01 HL080295, R01 HL087652]; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology); US National Institutes of Health [K23-HL-080025]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Burroughs Wellcome Fund Career Award; Netherlands Heart Foundation [2007B221] FX The Framingham Heart Study work was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine (contract #N01-HC-25195), its contract with Affymetrix for genotyping services (contract #N02-HL-6-4278), and the Doris Duke Charitable Foundation (C.N.-C.) and Burroughs Wellcome Fund (C.N.-C.). The Framingham analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The measurement of ECG intervals in Framingham Heart Study generation 1 and 2 samples was done by eResearch Technology and supported by an unrestricted grant from Pfizer. The measurement of ECG intervals in the Framingham Heart Study generation 3 sample was completed by A. Hirji and S. Kovvali using AMPS software provided through an unrestricted academic license by Analyzing Medical Parameters for Solutions (A.M.P.S., LLC). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (#175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), and the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project #050-060-810. The CHS research reported in this article was supported by contract numbers N01-HC85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00069 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The authors acknowledge the essential role of the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium in development and support of this manuscript. CHARGE members include the Netherland's Rotterdam Study, the NHLBI's Atherosclerosis Risk in Communities (ARIC) Study, Cardiovascular Health Study (CHS) and Framingham Heart Study (FHS), and the NIA's Iceland Age, Gene/Environment Susceptibility (AGES) Study. C. N.-C. is supported by US National Institutes of Health grant K23-HL-080025, a Doris Duke Charitable Foundation Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists. M. E.; is funded by the Netherlands Heart Foundation (#2007221). J.I.R. is supported by the Cedars-Sinai Board of Governors' Chair in Medical Genetics. The authors wish to thank the following people: G. Crawford and C. Guiducci (Broad Institute of Harvard and Massachusetts Institute of Technology) who completed the Sequenom-based technical validation genotyping of the Framingham Heart Study samples; P. Arp and M. Jhamai (Erasmus Medical Center) for Illumina array genotyping and Taqman-based technical validation genotyping of the Rotterdam Study samples; and Dr. M. Moorhouse, M. Verkerk and S. Bervoets (Erasmus Medical Center) for database management in the Rotterdam Study; and the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The QTGEN consortium would like to thank the QTSCD consortium for the opportunity to exchange top results pre-publication. NR 45 TC 239 Z9 245 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 2009 VL 41 IS 4 BP 399 EP 406 DI 10.1038/ng.364 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 425TC UT WOS:000264659000012 PM 19305408 ER PT J AU Kilpivaara, O Mukherjee, S Schram, AM Wadleigh, M Mullally, A Ebert, BL Bass, A Marubayashi, S Heguy, A Garcia-Manero, G Kantarjian, H Offit, K Stone, RM Gilliland, DG Klein, RJ Levine, RL AF Kilpivaara, Outi Mukherjee, Semanti Schram, Alison M. Wadleigh, Martha Mullally, Ann Ebert, Benjamin L. Bass, Adam Marubayashi, Sachie Heguy, Adriana Garcia-Manero, Guillermo Kantarjian, Hagop Offit, Kenneth Stone, Richard M. Gilliland, D. Gary Klein, Robert J. Levine, Ross L. TI A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; SUSCEPTIBILITY LOCI; ACTIVATING MUTATION; FAMILIAL RISKS; DISORDERS; CLONALITY; DISEASE AB Polycythemia vera, essential thrombocythemia and primary myelofibrosis are myeloproliferative neoplasms (MPN) characterized by multilineage clonal hematopoiesis(1-5). Given that the identical somatic activating mutation in the JAK2 tyrosine kinase gene (JAK2(V617F)) is observed in most individuals with polycythemia vera, essential thrombocythemia and primary myelofibrosis(6-10), there likely are additional genetic events that contribute to the pathogenesis of these phenotypically distinct disorders. Moreover, family members of individuals with MPN are at higher risk for the development of MPN, consistent with the existence of MPN predisposition loci(11). We hypothesized that germline variation contributes to MPN predisposition and phenotypic pleiotropy. Genome-wide analysis identified an allele in the JAK2 locus (rs10974944) that predisposes to the development of JAK2(V617F)-positive MPN, as well as three previously unknown MPN modifier loci. We found that JAK2(V617F) is preferentially acquired in cis with the predisposition allele. These data suggest that germline variation is an important contributor to MPN phenotype and predisposition. C1 [Mukherjee, Semanti; Klein, Robert J.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. [Kilpivaara, Outi; Schram, Alison M.; Marubayashi, Sachie; Heguy, Adriana; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Mukherjee, Semanti] Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY USA. [Wadleigh, Martha; Mullally, Ann; Bass, Adam; Stone, Richard M.; Gilliland, D. Gary] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mullally, Ann; Ebert, Benjamin L.; Gilliland, D. Gary] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Ebert, Benjamin L.; Bass, Adam; Gilliland, D. Gary] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Ebert, Benjamin L.; Bass, Adam; Gilliland, D. Gary] MIT, Cambridge, MA 02139 USA. [Garcia-Manero, Guillermo; Kantarjian, Hagop] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Gilliland, D. Gary] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. [Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. RP Klein, RJ (reprint author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. EM kleinr@mskcc.org; leviner@mskcc.org RI Klein, Robert/K-1888-2013; OI Klein, Robert/0000-0003-3539-5391; Schram, Alison/0000-0002-6070-2413 FU Wellcome Trust [076113]; National Institutes of Health; Starr Cancer Consortium; Myeloproliferative Disorders Foundation; Howard Hughes Medical Institute; Doris Duke Charitable Foundation; Kristen Amico Sesselman Leukemia Research Fund; Academy of Finland; US National Institutes of Health [P30 CA008748]; Geoffrey Beene Junior Chair at Memorial Sloan Kettering Cancer Center FX We would like to acknowledge the subjects who have contributed to our understanding of these disorders. We thank S. Thomas, I. Dolgalev and T. Landers for assistance with high-throughput resequencing, A. Viale for assistance with JAK2 expression analysis, and T. Kirchhoff for advice and suggestions. This study makes use of data generated by the Wellcome Trust Case-Control Consortium; a full list of the investigators who contributed to the generation of the data are available from http://www.wtccc.org.uk and funding was provided by the Wellcome Trust under award 076113. This work was supported by grants from the National Institutes of Health, the Starr Cancer Consortium, the Myeloproliferative Disorders Foundation, the Howard Hughes Medical Institute, the Doris Duke Charitable Foundation and the Kristen Amico Sesselman Leukemia Research Fund. O.K. is supported by a grant from the Academy of Finland. D.G.G. is an Investigator of the Howard Hughes Medical Institute and is a Doris Duke Charitable Foundation Distinguished Clinical Scientist. Work in the laboratory of R.J.K. is supported by Memorial Sloan Kettering Cancer Center through US National Institutes of Health grant P30 CA008748. R. L. L. is an Early Career Award recipient of the Howard Hughes Medical Institute and a Clinical Scientist Development Award recipient of the Doris Duke Charitable Foundation and is the Geoffrey Beene Junior Chair at Memorial Sloan Kettering Cancer Center. NR 28 TC 183 Z9 187 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2009 VL 41 IS 4 BP 455 EP 459 DI 10.1038/ng.342 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 425TC UT WOS:000264659000020 PM 19287384 ER PT J AU Andriopoulos, B Corradini, E Xia, Y Faasse, SA Chen, SZ Grgurevic, L Knutson, MD Pietrangelo, A Vukicevic, S Lin, HY Babitt, JL AF Andriopoulos, Billy, Jr. Corradini, Elena Xia, Yin Faasse, Sarah A. Chen, Shanzhuo Grgurevic, Lovorka Knutson, Mitchell D. Pietrangelo, Antonello Vukicevic, Slobodan Lin, Herbert Y. Babitt, Jodie L. TI BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism SO NATURE GENETICS LA English DT Article ID MORPHOGENETIC PROTEIN CORECEPTOR; ANTIMICROBIAL PEPTIDE HEPCIDIN; GUIDANCE MOLECULE RGMA; JUVENILE HEMOCHROMATOSIS; HEREDITARY HEMOCHROMATOSIS; GENE-EXPRESSION; MOUSE-LIVER; BONE; OVERLOAD; INFLAMMATION AB Juvenile hemochromatosis is an iron-overload disorder caused by mutations in the genes encoding the major iron regulatory hormone hepcidin ( HAMP) 1 and hemojuvelin (HFE2)(2). We have previously shown that hemojuvelin is a co-receptor for bone morphogenetic proteins (BMPs) and that BMP signals regulate hepcidin expression and iron metabolism(3,4). However, the endogenous BMP regulator(s) of hepcidin in vivo is unknown. Here we show that compared with soluble hemojuvelin (HJV.Fc), the homologous DRAGON.Fc is a more potent inhibitor of BMP2 or BMP4 but a less potent inhibitor of BMP6 in vitro. In vivo, HJV.Fc or a neutralizing antibody to BMP6 inhibits hepcidin expression and increases serum iron, whereas DRAGON.Fc has no effect. Notably, Bmp6-null mice have a phenotype resembling hereditary hemochromatosis, with reduced hepcidin expression and tissue iron overload. Finally, we demonstrate a physical interaction between HJV.Fc and BMP6, and we show that BMP6 increases hepcidin expression and reduces serum iron in mice. These data support a key role for BMP6 as a ligand for hemojuvelin and an endogenous regulator of hepcidin expression and iron metabolism in vivo. C1 [Andriopoulos, Billy, Jr.; Corradini, Elena; Xia, Yin; Faasse, Sarah A.; Chen, Shanzhuo; Lin, Herbert Y.; Babitt, Jodie L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Div Nephrol,Program Membrane Biol, Boston, MA 02115 USA. [Corradini, Elena; Pietrangelo, Antonello] Univ Hosp Modena & Reggio Emilia, Ctr Hemochromatosis, Modena, Italy. [Grgurevic, Lovorka; Vukicevic, Slobodan] Univ Zagreb, Sch Med, Lab Mineralized Tissues, Zagreb 41000, Croatia. [Knutson, Mitchell D.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. RP Babitt, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Div Nephrol,Program Membrane Biol, Boston, MA 02115 USA. EM babitt.jodie@mgh.harvard.edu RI Corradini, Elena/O-4167-2016; Pietrangelo, Antonello/K-1517-2016 OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo, Antonello/0000-0002-7411-935X FU Associazione Modenese per le Malattie del Fegato; Croatian Ministry of Science, Education, and Sport; US National Institutes of Health [RO1 DK-69533, RO1 DK-071837]; National Institutes of Health [K08 DK-075846]; Massachusetts General Hospital FX We thank V. Rosen for kindly providing BMP2 for our study. We thank L. M. Russo for assistance with animal work. E.C. was supported in part by the Associazione Modenese per le Malattie del Fegato. S.V. was supported in part by the Croatian Ministry of Science, Education, and Sport. H.Y.L. was supported in part by US National Institutes of Health grants RO1 DK-69533 and RO1 DK-071837. J.L.B. was supported in part by National Institutes of Health grant K08 DK-075846 and by a Claflin Distinguished Scholar Award from the Massachusetts General Hospital. NR 30 TC 355 Z9 361 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2009 VL 41 IS 4 BP 482 EP 487 DI 10.1038/ng.335 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 425TC UT WOS:000264659000025 PM 19252486 ER PT J AU Shoelson, SE Goldfine, AB AF Shoelson, Steven E. Goldfine, Allison B. TI Fanning the flames of obesity-induced inflammation SO NATURE MEDICINE LA English DT Editorial Material ID INDUCED INSULIN-RESISTANCE; DIABETES-MELLITUS; IKK-BETA; DISEASE; EXPRESSION C1 [Shoelson, Steven E.; Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Shoelson, Steven E.; Goldfine, Allison B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM steven.shoelson@joslin.harvard.edu FU NCRR NIH HHS [M01 RR001032, M01 RR002635]; NHLBI NIH HHS [P50 HL083813]; NIDDK NIH HHS [R01 DK073547, P30 DK036836, R01 DK043123, R01 DK045943, R01 DK051729, R01 DK095327, R37 DK051729, RC4 DK090792, U01 DK074556] NR 14 TC 60 Z9 62 U1 0 U2 2 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 APR PY 2009 VL 15 IS 4 BP 373 EP 374 DI 10.1038/nm0409-373 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 429RG UT WOS:000264937200019 PM 19350009 ER PT J AU Linden, ML Heynen, AJ Haslinger, RH Bear, MF AF Linden, Monica L. Heynen, Arnold J. Haslinger, Robert H. Bear, Mark F. TI Thalamic activity that drives visual cortical plasticity SO NATURE NEUROSCIENCE LA English DT Article ID MONOCULAR DEPRIVATION; DEPENDENT PLASTICITY; NEURONAL-ACTIVITY; OCULAR DOMINANCE; CORTEX; CAT AB Manipulations of activity in one retina can profoundly affect binocular connections in the visual cortex. Retinal activity is relayed to the cortex by the dorsal lateral geniculate nucleus (dLGN). We compared the qualities and amount of activity in the dLGN following monocular eyelid closure and monocular retinal inactivation in awake mice. Our findings substantially alter the interpretation of previous studies and define the afferent activity patterns that trigger cortical plasticity. C1 [Linden, Monica L.; Haslinger, Robert H.; Bear, Mark F.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Linden, Monica L.; Heynen, Arnold J.; Bear, Mark F.] Picower Inst Learning & Memory, Howard Hughes Med Inst, Cambridge, MA USA. [Haslinger, Robert H.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Bear, MF (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM mbear@mit.edu FU National Eye Institute; US National Institute of Neurological Disorders and Stroke FX We thank M. Shuler, J. Coleman, M. Lamprecht, B. Blais, H. Shouval, E. Sklar, K. Oram and S. Meagher. This work was partly supported by grants from the National Eye Institute and a National Research Service Award fellowship from the US National Institute of Neurological Disorders and Stroke (M. L. L.). NR 14 TC 40 Z9 40 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2009 VL 12 IS 4 BP 390 EP 392 DI 10.1038/nn.2284 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 424JN UT WOS:000264563100011 PM 19252494 ER PT J AU Chan, JA Balasubramanian, S Witt, RM Nazemi, KJ Choi, Y Pazyra-Murphy, MF Walsh, CO Thompson, M Segal, RA AF Chan, Jennifer A. Balasubramanian, Srividya Witt, Rochelle M. Nazemi, Kellie J. Choi, Yoojin Pazyra-Murphy, Maria F. Walsh, Carolyn O. Thompson, Margaret Segal, Rosalind A. TI Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses SO NATURE NEUROSCIENCE LA English DT Article ID CELL-CYCLE PROGRESSION; GLYPICAN DALLY-LIKE; NEURAL STEM-CELLS; HEPARAN-SULFATE; NEURONAL PRECURSORS; SIGNALING PATHWAYS; GENE-FUNCTION; SELF-RENEWAL; PROLIFERATION; DROSOPHILA AB Sonic Hedgehog (Shh) has dual roles in vertebrate development, promoting progenitor cell proliferation and inducing tissue patterning. We found that the mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan interactions in a mouse model, we found that binding of Shh to proteoglycans was required for proliferation of neural stem/precursor cells, but not for tissue patterning. Shh-proteoglycan interactions regulated both spatial and temporal features of Shh signaling. Proteoglycans localized Shh to specialized mitogenic niches and also acted at the single-cell level to regulate the duration of Shh signaling, thereby promoting a gene expression program that is important for cell division. Because activation of the Shh pathway is a feature of diverse human cancers, selective stimulation of proliferation by Shh-proteoglycan interactions may also figure prominently in neoplastic growth. C1 [Chan, Jennifer A.; Balasubramanian, Srividya; Witt, Rochelle M.; Nazemi, Kellie J.; Choi, Yoojin; Pazyra-Murphy, Maria F.; Walsh, Carolyn O.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Balasubramanian, Srividya; Witt, Rochelle M.; Nazemi, Kellie J.; Choi, Yoojin; Pazyra-Murphy, Maria F.; Walsh, Carolyn O.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Chan, Jennifer A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Thompson, Margaret] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU US National Institutes of Health; Dana Farber Cancer Institute Mahoney Center for Neuro-Oncology; Musella Foundation; Quan Fellowship; Children's Hospital Mental Retardation and Developmental Disabilities Research Center; Harvard NeuroDiscovery Center FX We thank J. Despinoy for excellent assistance, C. Stiles, D. Rowitch, M. Greenberg and members of the Segal laboratory for helpful discussions, and D. Rowitch, Q. Ma, P. Chuang, D. Paul, S. O'Gorman, P. Silver and A. McMahon for reagents. This work was supported by the US National Institutes of Health (J. A. C., R. A. S. and S. B.), the Dana Farber Cancer Institute Mahoney Center for Neuro-Oncology (J. A. C.), the Musella Foundation (K. J. N.), the Quan Fellowship (R. M. W.), the Children's Hospital Mental Retardation and Developmental Disabilities Research Center and the Harvard NeuroDiscovery Center. NR 50 TC 46 Z9 46 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2009 VL 12 IS 4 BP 409 EP 417 DI 10.1038/nn.2287 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 424JN UT WOS:000264563100015 PM 19287388 ER PT J AU Woo, J Kwon, SK Choi, S Kim, S Lee, JR Dunah, AW Sheng, M Kim, E AF Woo, Jooyeon Kwon, Seok-Kyu Choi, Seungwon Kim, Seho Lee, Jae-Ran Dunah, Anthone W. Sheng, Morgan Kim, Eunjoon TI Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses SO NATURE NEUROSCIENCE LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LIPRIN-ALPHA; NEURITE OUTGROWTH; NERVOUS-SYSTEM; BETA-NEUREXINS; RECEPTOR; LIGAND; MOLECULES; NETRIN; DIFFERENTIATION AB Synaptic adhesion molecules regulate multiple steps of synapse formation and maturation. The great diversity of neuronal synapses predicts the presence of a large number of adhesion molecules that control synapse formation through trans-synaptic and heterophilic adhesion. We identified a previously unknown trans-synaptic interaction between netrin-G ligand-3 (NGL-3), a postsynaptic density (PSD) 95-interacting postsynaptic adhesion molecule, and leukocyte common antigen-related (LAR), a receptor protein tyrosine phosphatase. NGL-3 and LAR expressed in heterologous cells induced pre-and postsynaptic differentiation in contacting axons and dendrites of cocultured rat hippocampal neurons, respectively. Neuronal overexpression of NGL-3 increased presynaptic contacts on dendrites of transfected neurons. Direct aggregation of NGL-3 on dendrites induced coclustering of excitatory postsynaptic proteins. Knockdown of NGL-3 reduced the number and function of excitatory synapses. Competitive inhibition by soluble LAR reduced NGL-3-induced presynaptic differentiation. These results suggest that the trans-synaptic adhesion between NGL-3 and LAR regulates excitatory synapse formation in a bidirectional manner. C1 [Woo, Jooyeon; Kwon, Seok-Kyu; Choi, Seungwon; Kim, Seho; Lee, Jae-Ran; Kim, Eunjoon] Korea Adv Inst Sci & Technol, Natl Creat Res Initiat Ctr Synaptogenis, Taejon 305701, South Korea. [Woo, Jooyeon; Kwon, Seok-Kyu; Choi, Seungwon; Kim, Seho; Lee, Jae-Ran; Kim, Eunjoon] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. [Dunah, Anthone W.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Dunah, Anthone W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Sheng, Morgan] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA USA. RP Kim, E (reprint author), Korea Adv Inst Sci & Technol, Natl Creat Res Initiat Ctr Synaptogenis, Taejon 305701, South Korea. EM kime@kaist.ac.kr RI Kim, Eunjoon/C-1566-2011 FU Korean Ministry of Science and Technology FX We would like to thank A. M. Craig for neurexin 1 alpha, 2 alpha, 3 alpha and 1 beta cDNAs, T. Biederer for SynCAM 1, Y.-P. Hsueh for Syndecan-2, P. Maness for NCAM-140, J. Ko for quantitative analysis, J. Nam for SALM4, M.-H. Kim for the mini analysis program, and Y.-G. Oh, M.-S. Baek, M. Ryu and J.-G. Jung for the help with antibody generation. This work was supported by the National Creative Research Initiative Program of the Korean Ministry of Science and Technology (E. K.). NR 50 TC 92 Z9 95 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2009 VL 12 IS 4 BP 428 EP 437 DI 10.1038/nn.2279 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 424JN UT WOS:000264563100017 PM 19252495 ER PT J AU Polyak, K Weinberg, RA AF Polyak, Kornelia Weinberg, Robert A. TI Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits SO NATURE REVIEWS CANCER LA English DT Review ID BREAST-CANCER CELLS; DISSEMINATED TUMOR-CELLS; E-CADHERIN; DNA METHYLATION; COLORECTAL-CANCER; EPIGENETIC INACTIVATION; DOWN-REGULATION; CARCINOMA PROGRESSION; SIGNALING PATHWAY; GENE-EXPRESSION AB Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients. C1 [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Weinberg, Robert A.] Whitehead Inst Biomed Res, Ludwig MIT Ctr Mol Oncol, Cambridge, MA 02142 USA. [Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Kornelia.Polyak@dfci.harvard.edu FU National Institute of Health [P50 CA89393, PO1 CA80111, U54 CA 126515]; Breast Cancer Research program [W81XWH-07-1-0294, BC073843]; American Cancer Society [RSG-05-154-01-MGO]; Breast Cancer Research Foundation; Ludwig Fund for Cancer Research; Advanced Medical Research Foundation FX We thank members of our laboratories for their critical reading of this manuscript and useful discussions. Research related to EMT in our laboratories is supported by National Institute of Health P50 CA89393 and PO1 CA80111 ( K. P. and R. A. W.), U54 CA 126515 ( R. A. W.), DoD Breast Cancer Research program W81XWH-07-1-0294 (K. P.) and BC073843 (R. A. W.), American Cancer Society RSG-05-154-01-MGO (K. P.), Breast Cancer Research Foundation (K. P. and R. A. W.), Ludwig Fund for Cancer Research (R. A. W.), and the Advanced Medical Research Foundation (R. A. W.). R. A. W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Cancer Research Professor. NR 87 TC 1512 Z9 1570 U1 33 U2 224 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 APR PY 2009 VL 9 IS 4 BP 265 EP 273 DI 10.1038/nrc2620 PG 9 WC Oncology SC Oncology GA 423MQ UT WOS:000264500800011 PM 19262571 ER PT J AU Crimi, E Ignarro, LJ Cacciatore, F Napoli, C AF Crimi, Ettore Ignarro, Louis J. Cacciatore, Francesco Napoli, Claudio TI Mechanisms by which exercise training benefits patients with heart failure SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR FUNCTION; QUALITY-OF-LIFE; SKELETAL-MUSCLE METABOLISM; SYMPATHETIC-NERVE ACTIVITY; BRAIN NATRIURETIC PEPTIDE; CORONARY-ARTERY-DISEASE; FAILING HUMAN HEART; FACTOR-I EXPRESSION; PHYSICAL-ACTIVITY AB Clinical consequences of heart failure are fatigue, dyspnea, and progressive impairment of exercise tolerance. regular exercise training is associated with health-improving effects. in patients with stable heart failure, exercise training can relieve symptoms, improve exercise capacity and quality of life, as well as reduce hospitalization and, to some extent, risk of mortality. Progressive exercise training is associated with pulmonary, cardiovascular, and skeletal muscle metabolic adaptations that increase oxygen delivery and energy production. This review focuses on current knowledge of mechanisms by which progressive and moderate exercise training can have sustained beneficial effects on patients with heart failure. C1 [Crimi, Ettore] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Ignarro, Louis J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Cacciatore, Francesco] Cardiovasc Rehabil Fdn Salvatore Mauge, IRCCS, Ist Sci Telese Terme & Campoli BN, San Giovanni Rotondo, Italy. [Napoli, Claudio] Univ Naples 2, Sch Med 1, Dept Gen Pathol, Clin Pathol & Excellence Res Ctr Cardiovasc Dis, Naples, Italy. RP Crimi, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM ecrimi@partners.org; claudio.napoli@unina2.it OI Napoli, Claudio/0000-0002-5455-555X FU Italian Ministery of University and research 2006 [PriN 2006]; Italian Ministery of Health 2006 FX Supported in part by a grant from the Italian Ministery of University and research 2006 (PriN 2006, Principal investigator: Prof Napoli) and ricerca Finalizzata from Italian Ministery of Health 2006 (Principal investigator: Dr Cacciatore). NR 148 TC 57 Z9 59 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD APR PY 2009 VL 6 IS 4 BP 292 EP 300 DI 10.1038/nrcardio.2009.8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 442PQ UT WOS:000265853500007 PM 19352333 ER PT J AU Heney, NM Kaufman, DS Shipley, WU AF Heney, Niall M. Kaufman, Donald S. Shipley, William U. TI Selective bladder-preserving therapy for muscle-invasive cancer SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL RESECTION; RADIATION-THERAPY; ONCOLOGY-GROUP; PRESERVATION; CONSERVATION AB Transurethral resection of the bladder and adjuvant chemoradiation can permit eradication of the tumor and micrometastases. close monitoring by sequential cystoscopy and biopsy can achieve similar survival outcomes to radical cystectomy, and could avoid invasive treatment. C1 [Heney, Niall M.; Kaufman, Donald S.; Shipley, William U.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM wshipley@partners.org NR 11 TC 2 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2009 VL 6 IS 4 BP 193 EP 194 DI 10.1038/nrclinonc.2009.21 PG 2 WC Oncology SC Oncology GA 442PS UT WOS:000265853700006 PM 19333224 ER PT J AU Gerstner, ER Duda, DG di Tomaso, E Ryg, PA Loeffler, JS Sorensen, AG Ivy, P Jain, RK Batchelor, TT AF Gerstner, Elizabeth R. Duda, Dan G. di Tomaso, Emmanuelle Ryg, Peter A. Loeffler, Jay S. Sorensen, A. Gregory Ivy, Percy Jain, Rakesh K. Batchelor, Tracy T. TI VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL-GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; APPARENT DIFFUSION-COEFFICIENT; TYROSINE KINASE INHIBITOR; MAGNETIC-RESONANCE; TUMOR ANGIOGENESIS; IN-VIVO; BARRIER PERMEABILITY; PERITUMORAL EDEMA; OVARIAN-CARCINOMA AB Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. in addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. C1 [Gerstner, Elizabeth R.; Ryg, Peter A.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurol, Ctr Biomarkers & Imaging, Boston, MA 02114 USA. [Duda, Dan G.; di Tomaso, Emmanuelle; Loeffler, Jay S.; Jain, Rakesh K.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Ctr Biomarkers & Imaging, Boston, MA 02114 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Biomarkers & Imaging, Boston, MA 02114 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Neurooncol, Yawkey Bldg,9th Floor,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [P01 CA080124, R01 CA159258] NR 62 TC 75 Z9 79 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2009 VL 6 IS 4 BP 229 EP 236 DI 10.1038/nrclinonc.2009.14 PG 8 WC Oncology SC Oncology GA 442PS UT WOS:000265853700011 PM 19333229 ER PT J AU Jensen, BC Swigart, PM Simpson, PC AF Jensen, Brian C. Swigart, Philip M. Simpson, Paul C. TI Ten commercial antibodies for alpha-1-adrenergic receptor subtypes are nonspecific SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE Alpha-1-adrenoceptor; Antibodies; Subtypes ID BLOOD-PRESSURE; KNOCKOUT; ALPHA-1D; ARTERIES; MICE AB Commercial antibodies are used widely to quantify and localize the alpha 1-adrenergic receptor (AR) subtypes, alpha 1A, alpha 1B, and alpha 1D. We tested ten antibodies, from abcam and Santa Cruz, using western blot with heart and brain tissue from wild-type (WT) mice and mice with systemic knockout (KO) of one or all three subtypes. We found that none of the antibodies detected a band in WT that was absent in the appropriate KO or in the KO that was null for all alpha 1-ARs (ABDKO). We conclude that the antibodies we tested are not specific for alpha 1-ARs. These results raise caution with prior studies using these reagents. For now, competition radioligand binding is the only reliable approach to quantify the alpha 1-AR subtype proteins. Receptor protein localization remains a challenge. C1 [Jensen, Brian C.; Swigart, Philip M.; Simpson, Paul C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Jensen, Brian C.; Swigart, Philip M.; Simpson, Paul C.] San Francisco VA Med Ctr, Res Serv, San Francisco, CA 94121 USA. [Jensen, Brian C.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Simpson, Paul C.] Univ Calif San Francisco, Dept Med, Inst Cardiovasc Res, San Francisco, CA 94143 USA. RP Simpson, PC (reprint author), San Francisco VA Med Ctr, Cardiol Sect, 111-C-8,4150 Clement St, San Francisco, CA 94121 USA. EM paul.simpson@ucsf.edu FU United States Department of Veterans Affairs Research Service; NIH; GlaxoSmithKline Research Foundation FX We appreciate the support of the United States Department of Veterans Affairs Research Service, the NIH, and the GlaxoSmithKline Research Foundation. NR 10 TC 86 Z9 86 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD APR PY 2009 VL 379 IS 4 BP 409 EP 412 DI 10.1007/s00210-008-0368-6 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 423KF UT WOS:000264494500011 PM 18989658 ER PT J AU Sauvageot, CME Weatherbee, JL Kesari, S Winters, SE Barnes, J Dellagatta, J Ramakrishna, NR Stiles, CD Kung, ALJ Kieran, MW Wen, PYC AF Sauvageot, Claire Marie-Elisabeth Weatherbee, Jessica Leigh Kesari, Santosh Winters, Susan Elizabeth Barnes, Jessica Dellagatta, Jamie Ramakrishna, Naren Raj Stiles, Charles Dean Kung, Andrew Li-Jen Kieran, Mark W. Wen, Patrick Yung Chih TI Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells SO NEURO-ONCOLOGY LA English DT Article DE 17-AAG; gliomas; radiosensitizer; stem cells ID EPIDERMAL-GROWTH-FACTOR; CONFERS ENHANCED TUMORIGENICITY; HUMAN GLIOBLASTOMA-MULTIFORME; ACTIVATED PROTEIN-KINASE; FACTOR RECEPTOR GENE; HUMAN-BRAIN-TUMORS; LUNG-CANCER CELLS; IN-VIVO; SIGNAL-TRANSDUCTION; MALIGNANT GLIOMA AB Glioblastoma multiforme (GBM) arises from genetic and signaling abnormalities in components of signal transduction pathways involved in proliferation, survival, and the cell cycle axis. Studies to date with single-agent targeted molecular therapy have revealed only modest effects in attenuating the growth of these tumors, suggesting that targeting multiple aberrant pathways may be more beneficial. Heat-shock protein 90 (HSP90) is a molecular chaperone that is involved in the conformational maturation of a defined group of client proteins, many of which are deregulated in GBM. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a well-characterized HSP90 inhibitor that should be able to target many of the aberrant signal transduction pathways in GBM. We assessed the ability of 17-AAG to inhibit the growth of glioma cell lines and glioma stem cells both in vitro and in vivo and assessed its ability to synergize with radiation and/or temozolomide, the standard therapies for GBM. Our results reveal that 17-AAG is able to inhibit the growth of both human glioma cell lines and glioma stem cells in vitro and is able to target the appropriate proteins within these cells. In addition, 17-AAG can inhibit the growth of intracranial tumors and can synergize with radiation both in tissue culture and in intracranial tumors. This compound was not found to synergize with temozolomide in any of our models of gliomas. Our results suggest that HSP90 inhibitors like 17-AAG may have therapeutic potential in GBM, either as a single agent or in combination with radiation. Neuro-Oncology 11, 109-121, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00062, August 5, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-060) C1 [Sauvageot, Claire Marie-Elisabeth; Weatherbee, Jessica Leigh; Winters, Susan Elizabeth; Stiles, Charles Dean] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Barnes, Jessica; Kung, Andrew Li-Jen; Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wen, Patrick Yung Chih] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sauvageot, Claire Marie-Elisabeth; Kesari, Santosh; Wen, Patrick Yung Chih] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Ramakrishna, Naren Raj] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Sauvageot, Claire Marie-Elisabeth; Kesari, Santosh; Ramakrishna, Naren Raj; Stiles, Charles Dean; Kung, Andrew Li-Jen; Kieran, Mark W.; Wen, Patrick Yung Chih] Harvard Univ, Sch Med, Boston, MA USA. RP Sauvageot, CME (reprint author), Dana Farber Canc Inst, Dept Canc Biol, SM1070,44 Binney St, Boston, MA 02115 USA. EM claire_sauvageot@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013 FU Solomon and Marlene Finvarb Brain Tumor Research Fund; Mark Richard Kolitz/American Brain Tumor Association Grant; Stop and Shop Pediatric Brain Tumor Program; C.J. Buckley Brain Tumor Research Fund FX We acknowledge the following sources of funding: the Solomon and Marlene Finvarb Brain Tumor Research Fund, the Mark Richard Kolitz/American Brain Tumor Association Grant, the Stop and Shop Pediatric Brain Tumor Program, and the C.J. Buckley Brain Tumor Research Fund. NR 68 TC 53 Z9 57 U1 2 U2 9 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2009 VL 11 IS 2 BP 109 EP 121 DI 10.1215/15228517-2008-060 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 430MS UT WOS:000264993800003 PM 18682579 ER PT J AU Zhu, JJ Gerstner, ER Engler, DA Mrugala, MM Nugent, W Nierenberg, K Hochberg, FH Betensky, RA Batchelor, TT AF Zhu, Jay-Jiguang Gerstner, Elizabeth R. Engler, David A. Mrugala, Maciej M. Nugent, Whitney Nierenberg, Kristin Hochberg, Fred H. Betensky, Rebecca A. Batchelor, Tracy T. TI High-dose methotrexate for elderly patients with primary CNS lymphoma SO NEURO-ONCOLOGY LA English DT Article DE chemotherapy; elderly; high-dose methotrexate; primary CNS lymphoma ID NERVOUS-SYSTEM LYMPHOMA; DEFERRED RADIOTHERAPY; PHASE-II; INITIAL TREATMENT; CHEMOTHERAPY; THERAPY; MULTICENTER; OLDER AB The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age >= 70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL. Neuro-Oncology 11, 211-215, 2009 (Posted to Neuro-Oncology [serial online], Doc. D07-00248, August 29, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-067) C1 [Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med,Dept Neurol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Zhu, Jay-Jiguang] Tufts Univ New England Med Ctr, Dept Neurol, Boston, MA USA. [Zhu, Jay-Jiguang] Tufts Univ New England Med Ctr, Dept Hematol, Boston, MA USA. [Zhu, Jay-Jiguang] Tufts Univ New England Med Ctr, Dept Oncol, Boston, MA USA. [Engler, David A.; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Engler, David A.; Betensky, Rebecca A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med,Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU Richard and Nancy Simches Endowed Fund for Brain Tumor Research at the Massachusetts General Hospital; National Institutes of Health [KCA125440A] FX This work was supported by the Richard and Nancy Simches Endowed Fund for Brain Tumor Research at the Massachusetts General Hospital and by National Institutes of Health grant KCA125440A (T.T.B.). NR 23 TC 42 Z9 42 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2009 VL 11 IS 2 BP 211 EP 215 DI 10.1215/15228517-2008-067 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 430MS UT WOS:000264993800014 PM 18757775 ER PT J AU Furnari, F Inda, MD Bonavia, R Mukasa, A Narita, Y Nishikawa, R Chin, L Cavenee, W AF Furnari, Frank Inda, Maria del Mar Bonavia, Rudy Mukasa, Akitake Narita, Yoshitake Nishikawa, Ryo Chin, Lynda Cavenee, Webster TI THE ROLE OF EGF RECEPTOR HETEROGENEITY IN DRIVING GLIOMA DEVELOPMENT SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Conference on Brain Tumor Research and Therapy CY JUN 09-12, 2008 CL Tokyo, JAPAN C1 [Furnari, Frank; Inda, Maria del Mar; Bonavia, Rudy; Mukasa, Akitake; Narita, Yoshitake; Cavenee, Webster] Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92103 USA. [Nishikawa, Ryo] Saitama Med Sch, Saitama, Japan. [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2009 VL 11 IS 2 BP 218 EP 218 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 430MS UT WOS:000264993800016 ER PT J AU Wen, P Chang, S Kuhn, J Lamborn, K Robins, HI Yung, A Gilbert, MR Cloughesy, T Lieberman, F DeAngelis, L Abrey, L Drappatz, J Kesari, S Dancey, J Prados, MD AF Wen, Patrick Chang, Susan Kuhn, John Lamborn, Kathleen Robins, H. Ian Yung, Alfred Gilbert, Mark R. Cloughesy, Timothy Lieberman, Frank DeAngelis, Lisa Abrey, Lauren Drappatz, Jan Kesari, Santosh Dancey, Janet Prados, Michel D. TI PHASE I/II STUDY OF ERLOTINIB AND CCI-779 (TEMSIROLIMUS) FOR PATIENTS WITH RECURRENT MALIGNANT GLIOMAS (NABTC 04-02) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Conference on Brain Tumor Research and Therapy CY JUN 09-12, 2008 CL Tokyo, JAPAN C1 [Wen, Patrick; Drappatz, Jan; Kesari, Santosh] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Chang, Susan; Lamborn, Kathleen; Prados, Michel D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kuhn, John] Univ Texas San Antonio, San Antonio, TX USA. [Yung, Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [DeAngelis, Lisa; Abrey, Lauren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Dancey, Janet] NCI, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2009 VL 11 IS 2 BP 232 EP 232 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 430MS UT WOS:000264993800077 ER PT J AU Kieran, MW AF Kieran, Mark W. TI RESULTS FROM A SINGLE-ARM, MULTI-INSTITUTIONAL PHASE II STUDY OF MULTIAGENT INTRATHECAL AND SYSTEMIC CHEMOTHERAPY WITH AGE- AND RISK-ADAPTED RADIATION THERAPY FOR CHILDREN WITH NEWLY DIAGNOSED CNS ATYPICAL TERATOID/RHABDOID TUMOR SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 17th International Conference on Brain Tumor Research and Therapy CY JUN 09-12, 2008 CL Tokyo, JAPAN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2009 VL 11 IS 2 BP 234 EP 234 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 430MS UT WOS:000264993800084 ER PT J AU Haroutunian, V Katsel, P Schmeidler, J AF Haroutunian, Vahram Katsel, Pavel Schmeidler, James TI Transcriptional vulnerability of brain regions in Alzheimer's disease and dementia SO NEUROBIOLOGY OF AGING LA English DT Article DE Gene expression; Microarray; Alzheimer's disease; Dementia; Cerebral cortex; Hippocampus ID GENE-EXPRESSION; STEREOLOGIC ANALYSIS; ENTORHINAL CORTEX; ELDERLY SUBJECTS; MICROARRAY; SCHIZOPHRENIA; PLAQUES; TANGLES; CA1; NORMALIZATION AB This study determined (a) the association between stages of Alzheimer's disease (AD) and overall gene expression change, and (b) brain regions of greatest vulnerability to transcriptional change as the disease progressed. Fifteen cerebrocortical sites and the hippocampus were examined in persons with either no cognitive impairment or neuropathology, or with only AD-associated lesions. Cases were stratified into groups of 7 19 based on the degree of cognitive impairment (clinical dementia rating scale, CDR); neurofibrillary tangle distribution and severity (Braak staging) or density of cerebrocortical neuritic plaque (NP; grouping by NP density). Transcriptional change was assessed by Affymetrix U 133 mRNA microarray analysis. The results suggested that (a) gene expression changes in the temporal and prefrontal cortices tire more closely related to disease severity than other regions examined; (b) more genes are down-regulated at,my given disease severity stage than up-regulated; (c) the degree of gene expression change in a given regions depends oil the disease severity classification scheme used; and (d) the classification of cases by CDR provides a more orderly gradient of gene expression change in most brain regions than Braak staging or NP grouping. (C) 2007 Elsevier Inc. All rights reserved. C1 [Haroutunian, Vahram; Katsel, Pavel; Schmeidler, James] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, MIRECC, Bronx, NY 10468 USA. RP Haroutunian, V (reprint author), Bronx VA Med Ctr, 4F-33B,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU [AG02219] FX Supported by AG02219 (VH). NR 50 TC 29 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2009 VL 30 IS 4 BP 561 EP 573 DI 10.1016/j.neurobiolaging.2007.07.021 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 424PT UT WOS:000264579500012 PM 17845826 ER PT J AU Yaffe, K Lindquist, K Sen, S Cauley, J Ferrell, R Penninx, B Harris, T Li, RL Cummings, SR AF Yaffe, Kristine Lindquist, Karla Sen, Saunak Cauley, Jane Ferrell, Robert Penninx, Brenda Harris, Tamara Li, Rongling Cummings, Steven R. CA Hlth ABC Study TI Estrogen receptor genotype and risk of cognitive impairment in elders: Findings from the Health ABC study SO NEUROBIOLOGY OF AGING LA English DT Article DE Estrogen; Dementia; Genetics; Aging ID ALPHA GENE POLYMORPHISMS; SPORADIC ALZHEIMERS-DISEASE; CENTRAL-NERVOUS-SYSTEM; POSTMENOPAUSAL WOMEN; CAUCASIAN WOMEN; MESSENGER-RNA; HUMAN BRAIN; ASSOCIATION; BETA; ESR1 AB Objective: To determine whether variants in the estrogen receptors 1 (alpha) and 2 (beta) (ESR1 and ESR2) genes are associated with cognitive impairment in non-demented elderly men and women. Background: Several single nucleotide polymorphisms (SNPs) on ESR1 and ESR2 genes have been associated with a range of hormone sensitive diseases such as breast cancer and osteoporosis. Genetic variations in ESR may also influence cognitive aging but are less studied, especially among men. Methods: We studied 2527 participants enrolled in an ongoing prospective study of community-dwelling elders. Four SNPs from ESR1 and four from ESR2 were analyzed. We measured cognitive function with the Modified Mini-Mental Status Examination (3MS) at baseline and biannually cognitive impairment was defined as it decline of live or more points over 4 years. We calculated odds of developing cognitive impairment across SNPS using gender-stratified logistic regression and adjusted analyses for age, education, baseline 3MS score and in addition for race. Results: One thousand three hundred and forty-three women (mean age 73.4) and 1184 men (mean age 73.7) comprised Our cohort. Among women, after multivariate adjustment, two of the ESR1 SNPs (rs8179176, rs9340799) and two of the ESR2 SNPs (rs1256065, rs1256030) were associated with likelihood of developing cognitive impairment., although the association for rs8179176 was of trend level significance. In men, one of the ESR1 SNPs (rs729524) and two of the ESR2 (rs1255998, rs1256030) were associated with cognitive impairment. Further adjustment for race attenuated the results somewhat. There was no association between any ESR SNP and level of bioavailable estradiol but testosterone level did vary among two of the SNPs (p < 0.05). Conclusion: We found that among non-demented Community elders, several SNPs in the ESR1 and ESR2 genes were associated with risk of developing cognitive impairment. These findings suggest that estrogen receptor genetic variants may play it role in cognitive aging. (C) 2007 Elsevier Inc. All rights reserved. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat & Neurol, Sch Med, San Francisco, CA 94121 USA. [Yaffe, Kristine; Sen, Saunak] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Lindquist, Karla] Univ Calif San Francisco, Dept Geriatr, Sch Med, San Francisco, CA 94121 USA. [Yaffe, Kristine; Sen, Saunak] San Francisco VA Med Ctr, San Francisco, CA USA. [Cauley, Jane] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ferrell, Robert] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Penninx, Brenda] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, EMGO Inst, Amsterdam, Netherlands. [Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Li, Rongling] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Ctr Genom & Bioinformat, Memphis, TN 38163 USA. [Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat & Neurol, Sch Med, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM Kristine.yaffe@uesf.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIH, National Institute on Aging; [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG6-2106]; [R01-AG021918] FX Funded by N01-AG-6-2101, N01-AG-6-2103, N01-AG6-2106 and R01-AG021918. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 31 TC 37 Z9 38 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2009 VL 30 IS 4 BP 607 EP 614 DI 10.1016/j.neurobiolaging.2007.08.003 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 424PT UT WOS:000264579500016 PM 17889406 ER PT J AU Sciamanna, G Bonsi, P Tassone, A Cuomo, D Tscherter, A Viscomi, MT Martella, G Sharma, N Bernardi, G Standaert, DG Pisani, A AF Sciamanna, Giuseppe Bonsi, Paola Tassone, Annalisa Cuomo, Dario Tscherter, Anne Viscomi, Maria Teresa Martella, Giuseppina Sharma, Nutan Bernardi, Giorgio Standaert, David G. Pisani, Antonio TI Impaired striatal D2 receptor function leads to enhanced GABA transmission in a mouse model of DYT1 dystonia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Electrophysiology; Dystonia; D2 dopamine receptor; Medium Spiny neurons; Fast-spiking interneuron ID D-2 DOPAMINE-RECEPTORS; FAST-SPIKING INTERNEURONS; MEDIUM SPINY NEURONS; CHOLINERGIC INTERNEURONS; RAT NEOSTRIATUM; SYNAPTIC-TRANSMISSION; PROJECTION NEURONS; INHIBITORY CONTROL; TORSION DYSTONIA; GENE-EXPRESSION AB DYT1 dystonia is caused by a deletion in a glutamic acid residue in the C-terminus of the protein torsinA, whose function is still largely unknown. Alterations in GABAergic signaling have been involved in the pathogenesis of dystonia. We recorded GABA- and glutamate-mediated synaptic currents from a striatal slice preparation obtained from a mouse model of DYT1 dystonia. In medium spiny neurons (MSNs) from mice expressing human mutant torsinA (hMT), we observed a significantly higher frequency, but not amplitude, of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature currents (mIPSCs), whereas glutamate-dependent spontaneous excitatory synaptic currents (sEPSCs) were normal. No alterations were found in mice overexpressing normal human torsinA (hWT). To identify the possible sources of the increased GABAergic tone, we recorded GABAergic Fast-Spiking (FS) interneurons that exert a feed-forward inhibition on MSNs. However, both sEPSC and slPSC recorded from hMT FS interneurons were comparable to hWT and non-transgenic (NT) mice. In physiological conditions, dopamine (DA) D2 receptor act presynaptically to reduce striatal GABA release. Of note, application of the D2-like receptor agonist quinpirole failed to reduce the frequency of sIPSCs in MSNs from hMT as compared to hWT and NT mice. Likewise, the inhibitory effect of quinpirole was lost on evoked IPSCs both in MSNs and FS interneurons from hMT mice. Our findings demonstrate a disinhibition of striatal GABAergic synaptic activity, that can be at least partially attributed to a D2 DA receptor dysfunction. (C) 2009 Elsevier Inc. All rights reserved. C1 [Sciamanna, Giuseppe; Cuomo, Dario; Tscherter, Anne; Martella, Giuseppina; Bernardi, Giorgio; Pisani, Antonio] Univ Roma Tor Vergata, Dept Neurosci, I-00133 Rome, Italy. [Sciamanna, Giuseppe; Bonsi, Paola; Tassone, Annalisa; Cuomo, Dario; Tscherter, Anne; Viscomi, Maria Teresa; Martella, Giuseppina; Bernardi, Giorgio; Pisani, Antonio] IRCCS, Fdn Santa Lucia, I-00143 Rome, Italy. [Sharma, Nutan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Standaert, David G.] Univ Alabama, Birmingham, AL USA. RP Pisani, A (reprint author), Univ Roma Tor Vergata, Dept Neurosci, Via Montpellier 1, I-00133 Rome, Italy. EM pisani@uniroma2.it RI Viscomi, Maria Teresa/G-4173-2011; Sciamanna, Giuseppe/B-6553-2013; Tassone, Annalisa/J-9950-2016; Bonsi, Paola/K-4688-2012; OI Viscomi, Maria Teresa/0000-0002-9096-4967; Sciamanna, Giuseppe/0000-0002-0070-1638; Tassone, Annalisa/0000-0001-9643-2446; Bonsi, Paola/0000-0001-5940-9028; Tscherter, Anne/0000-0002-6972-482X; Standaert, David/0000-0003-2921-8348 FU Bachmann-Strauss Dystonia & Parkinson's Foundation; Dystonia Medical Research Foundation; Ministero Salute; Istituto Superiore Sanita; NIH [NS37409, NIH K08 NS044272] FX This work was supported by grants from Bachmann-Strauss Dystonia & Parkinson's Foundation and Dystonia Medical Research Foundation to AP; Ministero Salute (Progetto Finalizzato and Articolo 56) to GB and AP; Istituto Superiore Sanita (Malattie Rare) to AP; NIH grants NS37409 to DGS; NIH K08 NS044272 to NS. NR 47 TC 44 Z9 44 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2009 VL 34 IS 1 BP 133 EP 145 DI 10.1016/j.nbd.2009.01.001 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 429ZE UT WOS:000264957800014 PM 19187797 ER PT J AU McCann, CM Waterman, P Figueiredo, JL Aikawa, E Weissleder, R Chen, JW AF McCann, Corey M. Waterman, Peter Figueiredo, Jose-Luiz Aikawa, Elena Weissleder, Ralph Chen, John W. TI Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy SO NEUROIMAGE LA English DT Article ID IN-VIVO; MOLECULAR TOMOGRAPHY; PROTEASE ACTIVITY; CANCER; PROBES; VISUALIZATION; TUMORS; LIGHT AB Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor molecular function in living animals using specific fluorescent probes. However, macroscopic imaging methods such as FMT generally exhibit low anatomical details. To overcome this, we report a quantitative technique to image both structure and function by combining FMT and magnetic resonance (MR) imaging. We show that FMT-MR imaging can produce three-dimensional, multimodal images of living mouse brains allowing for serial monitoring of tumor morphology and protease activity. Combined FMT-MR tumor imaging provides a unique in vivo diagnostic parameter, protease activity concentration (PAC), which reflects histological changes in tumors and is significantly altered by systemic chemotherapy. Alterations in this diagnostic parameter are detectable early after chemotherapy and correlate with subsequent tumor growth, predicting tumor response to chemotherapy. Our results reveal that combined FMT-MR imaging of fluorescent molecular probes could be valuable for brain tumor drug development and other neurological and somatic imaging applications. (c) 2008 Elsevier Inc. All rights reserved. C1 [Chen, John W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol,Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Chen, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol,Ctr Mol Imaging Res, Room 8222,185 Cambridge St, Boston, MA 02114 USA. EM chenjo@helix.mgh.harvard.edu FU National Institute of Health [5KO8-HL081170, RO1-EB006432] FX This work was supported in part by the National Institute of Health 5KO8-HL081170 (J.W.C.) and RO1-EB006432 (R. W.). We thank Y. Iwamato, T. Sponholtz, C. Rangel, C. Kaufman, A. Yu, and J. Chan for experimental assistance, N. Sergeyev for chemical synthesis, and C. Vinegoni, J. C. Tapia, N. Kasthuri and J. Lichtman for useful discussions. NR 37 TC 46 Z9 47 U1 2 U2 6 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 APR 1 PY 2009 VL 45 IS 2 BP 360 EP 369 DI 10.1016/j.neuroimage.2008.12.022 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KS UT WOS:000263863000015 PM 19154791 ER PT J AU Voineskos, AN O'Donnell, LJ Lobaugh, NJ Markant, D Ameis, SH Niethammer, M Mulsant, BH Pollock, BG Kennedy, JL Westin, CF Shenton, ME AF Voineskos, Aristotle N. O'Donnell, Lauren J. Lobaugh, Nancy J. Markant, Doug Ameis, Stephanie H. Niethammer, Marc Mulsant, Benoit H. Pollock, Bruce G. Kennedy, James L. Westin, Carl Fredrik Shenton, Martha E. TI Quantitative examination of a novel clustering method using magnetic resonance diffusion tensor tractography SO NEUROIMAGE LA English DT Article DE Diffusion tensor imaging; Tractography; Streamline; Clustering; Region of interest; Schizophrenia ID WHITE-MATTER; CORPUS-CALLOSUM; MRI; SEGMENTATION AB MR diffusion tensor imaging (DTI) can measure and visualize organization of white matter fibre tracts in vivo. DTI is a relatively new imaging technique, and new tools developed for quantifying fibre tracts require evaluation. The purpose of this study was to compare the reliability of a novel clustering approach with a multiple region of interest (MROI) approach in both healthy and disease (schizophrenia) populations. DTI images were acquired in 20 participants (n = 10 patients with schizophrenia: 56 +/- 15 years; n = 10 controls: 51 +/- 20 years) (1.5 T GE system) with diffusion gradients applied in 23 non-collinear directions, repeated three times. Whole brain seeding and creation of fibre tracts were then performed. Interrater reliability of the clustering approach, and the MROI approach, were each evaluated and the methods compared. There was high spatial (voxel-based) agreement within and between the clustering and MROI methods. Fractional anisotropy, trace, and radial and axial diffusivity values showed high intraclass correlation (p<0.001 for all tracts) for each approach. Differences in scalar indices of diffusion between the clustering and MROI approach were minimal. The excellent interrater reliability of the clustering method and high agreement with the MROI method, quantitatively and spatially, indicates that the clustering method can be used with confidence. The clustering method avoids biases of ROI drawing and placement, and, not limited by a priori predictions, may be a more robust and efficient way to identify and measure white matter tracts of interest. (c) 2008 Elsevier Inc. All rights reserved. C1 [Markant, Doug; Shenton, Martha E.] Harvard Univ, Psychiat Neuroimaging Lab, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02215 USA. [Voineskos, Aristotle N.; Mulsant, Benoit H.; Pollock, Bruce G.] Univ Toronto, Geriatr Mental Hlth Program, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Voineskos, Aristotle N.; Ameis, Stephanie H.; Kennedy, James L.] Univ Toronto, Dept Neurosci, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [O'Donnell, Lauren J.] Harvard Univ, Golby Lab, Dept Neurosurg, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Lobaugh, Nancy J.] Univ Toronto, Dept Med, Sunnybrook Hlth Sci Ctr, Toronto, ON M5S 1A1, Canada. [Niethammer, Marc] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA. [Niethammer, Marc] Univ N Carolina, Biomed Imaging Res Ctr, Chapel Hill, NC USA. [Westin, Carl Fredrik] Harvard Univ, Brigham & Womens Hosp, Lab Math Imaging, Dept Radiol, Cambridge, MA 02138 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA. RP Shenton, ME (reprint author), Harvard Univ, Psychiat Neuroimaging Lab, Dept Psychiat, Brigham & Womens Hosp, 3rd Floor,1249 Boylston St, Boston, MA 02215 USA. EM martha_shenton@hms.harvard.edu RI Voineskos, Aristotle/J-5014-2013; OI O'Donnell, Lauren Jean/0000-0003-0197-7801 FU Canadian Institutes of Health Research Clinician Scientist Award (ANV); National Institutes of Health [U41-RR019703]; Brain Science Foundation [NIH R01 MH074794, NIH P41 RR13218, R01 MH 50740, NIH 1P50 MH08272, U54GM072977-01 NIG/HS NIH]; Sandra A. Rotman Research Institute (BGP) FX The authors would also like to thank Dielle Miranda for her assistance in this project. NR 21 TC 28 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2009 VL 45 IS 2 BP 370 EP 376 DI 10.1016/j.neuroimage.2008.12.028 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KS UT WOS:000263863000016 PM 19159690 ER PT J AU Radhakrishnan, H Vanduffel, W Deng, HP Ekstrom, L Boas, DA Franceschini, MA AF Radhakrishnan, Harsha Vanduffel, Wim Deng, Hong Ping Ekstrom, Leeland Boas, David A. Franceschini, Maria Angela TI Fast optical signal not detected in awake behaving monkeys SO NEUROIMAGE LA English DT Article ID ADULT HUMAN HEAD; BRAIN-FUNCTION; VISUAL-CORTEX; NONINVASIVE DETECTION; PHOTON MIGRATION; LIGHT-SCATTERING; EVENT; NERVE; FREQUENCY; RESPONSES AB While the ability of near-infrared spectroscopy (NIRS) to measure cerebral hemodynamic evoked responses (slow optical signal) is well established, its ability to measure non-invasively the 'fast optical signal' is still controversial. Here, we aim to determine the feasibility of performing NIRS measurements of the 'fast optical signal' or Event-Related Optical Signals (EROS) under optimal experimental conditions in awake behaving macaque monkeys. These monkeys were implanted with a 'recording well' to expose the dura above the primary visual cortex (V1). A custom-made optical probe was inserted and fixed into the well. The close proximity of the probe to the brain maximized the sensitivity to changes in optical properties in the cortex. Motion artifacts were minimized by physical restraint of the head. Full-field contrast-reversing checkerboard stimuli were presented to monkeys trained to perform a visual fixation task. In separate sessions, two NIRS systems (CW4 and ISS FD oximeter), which previously showed the ability to measure the fast signal in human, were used. In some sessions EEG was acquired simultaneously with the optical signal. The increased sensitivity to cortical optical changes with our experimental setup was quantified with 3D Monte Carlo simulations on a segmented MRI monkey head. Averages of thousands of stimuli in the same animal, or grand averages across the two animals and across repeated sessions, did not lead to detection of the fast optical signal using either amplitude or phase of the optical signal. Hemodynamic responses and visual evoked potentials were instead always detected with single trials or averages of a few stimuli. Based on these negative results, despite the optimal experimental conditions, we doubt the usefulness of non-invasive fast optical signal measurements with NIRS. (c) 2008 Elsevier Inc. All rights reserved. C1 [Radhakrishnan, Harsha; Vanduffel, Wim; Deng, Hong Ping; Ekstrom, Leeland; Boas, David A.; Franceschini, Maria Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Vanduffel, Wim; Boas, David A.; Franceschini, Maria Angela] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neurofysiol & Psychofysiol, B-3000 Louvain, Belgium. [Ekstrom, Leeland; Boas, David A.; Franceschini, Maria Angela] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ekstrom, Leeland] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Radhakrishnan, H (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149,13th St,Rm 2277, Charlestown, MA 02129 USA. EM harsha@nmr.mgh.harvard.edu RI Radhakrishnan, Harsha/K-5557-2012 FU US National Institutes of Health (NIH) [R01-EB001954, R01-EB000790, R01-EY017081]; Human Frontiers Science Program (HFSPO), GSKE [IUAP 5/04, EF/05/014]; N.C.R.R. grant [P41RR14075]; MIND Institute FX This research is supported by the US National Institutes of Health (NIH) grant R01-EB001954, R01-EB000790 and R01-EY017081, the Human Frontiers Science Program (HFSPO), GSKE, IUAP 5/04, and EF/05/014. The Martinos Center is supported by N.C.R.R. grant P41RR14075 and the MIND Institute. NR 38 TC 23 Z9 23 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2009 VL 45 IS 2 BP 410 EP 419 DI 10.1016/j.neuroimage.2008.12.014 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 414KS UT WOS:000263863000020 PM 19150500 ER PT J AU Ben-Haim, S Asaad, WF Gale, JT Eskandar, EN AF Ben-Haim, Sharona Asaad, Wael F. Gale, John T. Eskandar, Emad N. TI RISK FACTORS FOR HEMORRHAGE DURING MICROELECTRODE-GUIDED DEEP BRAIN STIMULATION AND THE INTRODUCTION OF AN IMPROVED MICROELECTRODE DESIGN SO NEUROSURGERY LA English DT Article DE Deep brain stimulation; Hemorrhage; Microelectrode design; Microelectrode recording ID PARKINSONS-DISEASE; POSTEROVENTRAL PALLIDOTOMY; SUBTHALAMIC NUCLEUS; MOVEMENT-DISORDERS; COMPLICATIONS; SURGERY; SELECTION AB OBJECTIVE: Hemorrhage is an infrequent but potentially devastating complication of deep brain stimulation (DBS) surgery. We examined the factors associated with hemorrhage after DBS surgery and evaluated a modified microelectrode design that may improve the safety of this procedure. METHODS: All microelectrode-guided DBS procedures performed at our institution between January 2000 and March 2008 were included in this study. A new microelectrode design with decreased diameter was introduced in May 2004, and data from the 2 types of electrodes were compared. RESULTS: We examined 246 microelectrode-guided lead implantations in 130 patients. Postoperative imaging revealed 7 hemorrhages (2.8%). Five of the 7 (2.0%) resulted in focal neurological deficits, all of which resolved within 1 month with the exception of I patient lost to follow-up. The new microelectrode design significantly decreased the number of hemorrhages (P = 0.04). A surgical trajectory traversing the ventricle also contributed significantly to the overall hemorrhage rate (P = 0.02) and specifically to the intraventricular hemorrhage rate (P = 0.01). In addition, the new microelectrode design significantly decreased the rate of intraventricular hemorrhage, given a ventricular penetration (P = 0.01). The mean age of patients with hemorrhage was significantly higher than that of patients without hemorrhage (P = 0.02). Hypertension, sex, and number of microelectrodes passed did not significantly contribute to hemorrhage rates in our population. CONCLUSION: The rate of complications after DBS surgery is not uniformly distributed across all cases. In particular, the rates of hemorrhage were increased in older patients. Importantly, transventricular electrode trajectories appeared to increase the risk of hemorrhage. A new microelectrode design minimizing the volume of brain parenchyma penetrated during microelectrode recording leads to decreased rates of hemorrhage, particularly if the ventricles are breached. C1 [Ben-Haim, Sharona; Asaad, Wael F.; Gale, John T.; Eskandar, Emad N.] Harvard Univ, Dept Neurosurg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Dept Neurosurg, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,ACC-331, Boston, MA 02114 USA. EM eeskandar@partners.org RI Asaad, Wael/I-8485-2012 OI Asaad, Wael/0000-0003-4406-9096 NR 26 TC 50 Z9 51 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X EI 1524-4040 J9 NEUROSURGERY JI Neurosurgery PD APR PY 2009 VL 64 IS 4 BP 754 EP 762 DI 10.1227/01.NEU.0000339173.77240.34 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 427MN UT WOS:000264783500044 PM 19349834 ER PT J AU Lim, DA Larson, PS AF Lim, Daniel A. Larson, Paul S. TI Intraoperative MRI in Functional Neurosurgery Preface SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Lim, Daniel A.] San Francisco VA Med Ctr, Neurosurg Sect, Surg Serv, Dept Vet Affairs, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Lim, DA (reprint author), San Francisco VA Med Ctr, Neurosurg Sect, Surg Serv, Dept Vet Affairs, 4150 Clement St, San Francisco, CA 94121 USA. EM LimD@neurosurg.ucsf.edu; LarsonP@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425 NR 0 TC 0 Z9 0 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2009 VL 20 IS 2 BP XI EP XI DI 10.1016/j.nec.2009.04.014 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 480HM UT WOS:000268724500001 PM 19555874 ER PT J AU Roskom, J Swistowski, A Zeng, XM Lim, DA AF Roskom, Joshua Swistowski, Andrzej Zeng, Xianmin Lim, Daniel A. TI Future Directions: Use of Interventional MRI for Cell-Based Therapy of Parkinson Disease SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Embryonic stem cells; Induced pluripotent stem cells; Cell transplantation; Parkinson's disease; Dopamine neurons; Interventional MRI ID EMBRYONIC STEM-CELLS; DOPAMINE NEURONS; IN-VITRO; ELECTROPHYSIOLOGICAL GUIDANCE; NIGRAL TRANSPLANTS; LEVODOPA THERAPY; TECHNICAL NOTE; DIFFERENTIATION; GENERATION; IMPLANTATION AB Transplantation of neural cells for the treatment of neurologic disorders has garnered much attention and considerable enthusiasm from patients and physicians alike. Cell-based therapies have been proposed for a wide range of central nervous system pathologies ranging from stroke and trauma to demyelinating disorders and neurodegenerative diseases. Notably, cell transplantation for Parkinson disease (PD) has become even more attractive with the rapid advances in derivation of dopaminergic neurons from human embryonic stem cells. This article briefly reviews some of the relevant issues regarding the transplantation of cells for treatment of PD and hypothesizes how interventional MRI may be useful to optimize the surgical delivery of cells for PD and other central nervous system disorders. C1 [Lim, Daniel A.] San Francisco VA Med Ctr, Neurosurg Sect, Dept Vet Affairs, Surg Serv, San Francisco, CA 94121 USA. [Lim, Daniel A.] Dept Vet Affairs, San Francisco Vet Affairs Med Ctr, Surg Serv, Neurosurg Sect, San Francisco, CA 94121 USA. [Roskom, Joshua] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Swistowski, Andrzej] Buck Inst Age Res, Novato, CA 94945 USA. [Zeng, Xianmin] Buck Inst Age Res, N Bay Calif Inst Regenerat Med, Shared Res Lab Stem Cells & Aging, Novato, CA 94945 USA. RP Lim, DA (reprint author), San Francisco VA Med Ctr, Neurosurg Sect, Dept Vet Affairs, Surg Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM limd@neurosurg.ucsf.edu OI Lim, Daniel/0000-0001-7221-3425 NR 46 TC 4 Z9 4 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2009 VL 20 IS 2 BP 225 EP + DI 10.1016/j.nec.2009.04.005 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 480HM UT WOS:000268724500012 PM 19555884 ER PT J AU Loscher, W Cole, AJ McLean, MJ AF Loescher, Wolfgang Cole, Andrew J. McLean, Michael J. TI Commentary: Physical Approaches for the Treatment of Epilepsy: Electrical and Magnetic Stimulation and Cooling SO NEUROTHERAPEUTICS LA English DT Editorial Material DE Brain stimulation; vagus nerve; hypothermia; neuromodulation; seizures ID VAGUS NERVE-STIMULATION; DEEP BRAIN-STIMULATION; INDUCED HYPOTHERMIA; SEIZURES; TRIAL; DEPRESSION; THERAPY; TDCS; RAT AB Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function. C1 [Loescher, Wolfgang] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, D-30559 Hannover, Germany. [Loescher, Wolfgang] Ctr Syst Neurosci, D-30559 Hannover, Germany. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [McLean, Michael J.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37212 USA. RP Loscher, W (reprint author), Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Bunteweg 17, D-30559 Hannover, Germany. EM wolfgang.loescher@tiho-hannover.de NR 34 TC 4 Z9 5 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2009 VL 6 IS 2 BP 258 EP 262 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 425TL UT WOS:000264659900007 PM 19332318 ER PT J AU Thompson, K AF Thompson, Kerry TI Transplantation of GABA-Producing Cells for Seizure Control in Models of Temporal Lobe Epilepsy SO NEUROTHERAPEUTICS LA English DT Article CT 4th Workshop on New Horizons in the Development of Antiepileptic Drugs CY MAR 05-07, 2008 CL Dublin, IRELAND DE GABA; cell transplantation; temporal lobe epilepsy; seizures; genetic engineering ID GLUTAMIC-ACID DECARBOXYLASE; NEURAL PROGENITOR CELLS; EMBRYONIC STEM-CELLS; ADENOSINE-RELEASING CELLS; FETAL GABAERGIC NEURONS; PARKINSONS-DISEASE; DENTATE GYRUS; KINDLING EPILEPSY; STATUS EPILEPTICUS; INTRANIGRAL TRANSPLANTS AB A high percentage of patients with temporal lobe epilepsy (TLE) are refractory to conventional pharmacotherapy. The progressive neurodegenerative processes associated with a lifetime of uncontrolled seizures mandate the development of alternative approaches to treat this disease. Transplantation of inhibitory cells has been suggested as a potential therapeutic strategy to achieve seizure suppression in humans with intractable TLE. Preclinical investigations over 20 years have demonstrated that multiple cell types from several sources can produce anticonvulsant, and antiepileptogenic, effects in animal models of TLE. Transplanting GABA-producing cells, in particular, has been shown to reduce seizures in several well-established models. This review addresses experimentation using different sources of transplantable GABAergic cells, highlighting progress with fetal tissue, neural cell lines, and stem cells. Regardless of the source of the GABAergic cells used in seizure studies, common challenges have emerged. Several variables influence the anticonvulsant potential of GABA-producing cells. For example, tissue availability, graft survival, immunogenicity, tumorigenicity, and varying levels of cell migration, differentiation, and integration into functional circuits and the microenvironment provided by sclerotic tissue all contribute to the efficacy of transplanted cells. The challenge of understanding how all of these variables work in concert, in a disease process that has no well-established etiology, suggests that there is still much basic research to be done before rational cell-based therapies can be developed for TLE. C1 [Thompson, Kerry] Occidental Coll, Dept Biol, Los Angeles, CA 90041 USA. [Thompson, Kerry] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90012 USA. RP Thompson, K (reprint author), Occidental Coll, Dept Biol, 1600 Campus Rd, Los Angeles, CA 90041 USA. EM kthompson@oxy.edu NR 108 TC 24 Z9 25 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD APR PY 2009 VL 6 IS 2 BP 284 EP 294 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 425TL UT WOS:000264659900010 PM 19332321 ER PT J AU Fan, Q Zhang, F Barrett, B Ren, KQ Andreassen, PR AF Fan, Qiang Zhang, Fan Barrett, Briana Ren, Keqin Andreassen, Paul R. TI A role for monoubiquitinated FANCD2 at telomeres in ALT cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROMYELOCYTIC LEUKEMIA BODIES; DOUBLE-STRAND BREAKS; ABERRANT HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA PROTEIN; DNA-DAMAGE RESPONSE; MAMMALIAN-CELLS; SYNDROME HELICASE; NEGATIVE CELLS; CANCER-CELLS; PATHWAY AB Both Fanconi anemia (FA) and telomere dysfunction are associated with chromosome instability and an increased risk of cancer. Because of these similarities, we have investigated whether there is a relationship between the FA protein, FANCD2 and telomeres. We find that FANCD2 nuclear foci colocalize with telomeres and PML bodies in immortalized telomerase-negative cells. These cells maintain telomeres by alternative lengthening of telomeres (ALT). In contrast, FANCD2 does not colocalize with telomeres or PML bodies in cells which express telomerase. Using a siRNA approach we find that FANCA and FANCL, which are components of the FA nuclear core complex, regulate FANCD2 monoubiquitination and the telomeric localization of FANCD2 in ALT cells. Transient depletion of FANCD2, or FANCA, results in a dramatic loss of detectable telomeres in ALT cells but not in telomerase-expressing cells. Furthermore, telomere loss following depletion of these proteins in ALT cells is associated with decreased homologous recombination between telomeres (T-SCE). Thus, the FA pathway has a novel function in ALT telomere maintenance related to DNA repair. ALT telomere maintenance is therefore one mechanism by which monoubiquitinated FANCD2 may promote genetic stability. C1 [Fan, Qiang; Zhang, Fan; Ren, Keqin; Andreassen, Paul R.] Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Dept Pediat,Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Barrett, Briana] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Andreassen, PR (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Res Fdn, Dept Pediat,Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. EM paul.andreassen@cchmc.org FU Leukemia and Lymphoma Society; Cincinnati Children's Hospital Medical Center; NIH [R01 HL085587] FX This work was supported in part, by a Special Fellow grant from the Leukemia and Lymphoma Society, a Trustee grant from Cincinnati Children's Hospital Medical Center, and NIH R01 HL085587 (P.R.A.). Funding for open access charge: NIH R01 HL085587. NR 66 TC 38 Z9 40 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2009 VL 37 IS 6 BP 1740 EP 1754 DI 10.1093/nar/gkn995 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431XF UT WOS:000265097400010 PM 19129235 ER EF