FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rached, MT Kode, A Xu, LL Yoshikawa, Y Paik, JH DePinho, RA Kousteni, S AF Rached, Marie-Therese Kode, Aruna Xu, Lili Yoshikawa, Yoshihiro Paik, Ji-Hye DePinho, Ronald A. Kousteni, Stavroula TI FoxO1 Is a Positive Regulator of Bone Formation by Favoring Protein Synthesis and Resistance to Oxidative Stress in Osteoblasts SO CELL METABOLISM LA English DT Article ID TRANSCRIPTION FACTORS; SIGNALING PATHWAY; REDOX REGULATION; SEX STEROIDS; LIFE-SPAN; MICE; AGE; CELLS; DIFFERENTIATION; METABOLISM AB Osteoporosis, a disease of low bone mass, is associated with decreased osteoblast numbers and increased levels of oxidative stress within osteoblasts. Since transcription factors of the FoxO family confer stress resistance, we investigated their potential impact on skeletal integrity. Here we employ cell-specific deletion and molecular analyses to show that, among the three FoxO proteins, only FoxO1 is required for proliferation and redox balance in osteoblasts and thereby controls bone formation. FoxO1 regulation of osteoblast proliferation occurs through its interaction with ATF4, a transcription factor regulating amino acid import, as well as through its regulation of a stress-dependent pathway influencing p53 signaling. Accordingly, decreasing oxidative stress levels or increasing protein intake normalizes bone formation and bone mass in mice lacking FoxO1 specifically in osteoblasts. These results identify FoxO1 as a crucial regulator of osteoblast physiology and provide a direct mechanistic link between oxidative stress and the regulation of bone remodeling. C1 [Rached, Marie-Therese; Kode, Aruna; Xu, Lili; Yoshikawa, Yoshihiro; Kousteni, Stavroula] Columbia Univ, Coll Phys & Surg, Div Endocrinol, Dept Med, New York, NY 10032 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. RP Kousteni, S (reprint author), Columbia Univ, Coll Phys & Surg, Div Endocrinol, Dept Med, New York, NY 10032 USA. EM sk2836@columbia.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] [DK063608-07]; National Institutes of Health [R01 AR055931, R01 AR054447] FX The authors are grateful to Dr. Gerard Karsenty for helpful discussions, for critical reading of the manuscript, and for providing ATF4-deficient osteoblasts. We are also thankful to Dr. John P. Bilezikian and Dr. Patricia Ducy for helpful discussions, Dr. John Manavalan for help with measurements of ROS levels in osteoblasts, Dr. Li Qiang for help with the adenoviral infections, and Charles Duncan for technical assistance. We are thankful to the histology facility of the Diabetes and Endocrinology Research Center (DERC) of Columbia University Medical Center (supported by National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] DK063608-07) for help with histological analysis. S.K. is indebted to Dr. Vijay Yadav for his generous help and constant availability throughout this project. This work was supported by the National Institutes of Health (R01 AR055931 and R01 AR054447 to S.K.). NR 42 TC 99 Z9 104 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD FEB 3 PY 2010 VL 11 IS 2 BP 147 EP 160 DI 10.1016/j.cmet.2010.01.001 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 555ON UT WOS:000274521900007 PM 20142102 ER PT J AU Guo, J Liu, ML Yang, DH Bouxsein, ML Saito, H Galvin, RJS Kuhstoss, SA Thomas, CC Schipani, E Baron, R Bringhurst, FR Kronenberg, HM AF Guo, Jun Liu, Minlin Yang, Dehong Bouxsein, Mary L. Saito, Hiroaki Galvin, R. J. Sells Kuhstoss, Stuart A. Thomas, Clare C. Schipani, Ernestina Baron, Roland Bringhurst, F. Richard Kronenberg, Henry M. TI Suppression of Wnt Signaling by Dkk1 Attenuates PTH-Mediated Stromal Cell Response and New Bone Formation SO CELL METABOLISM LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; PARATHYROID-HORMONE; BETA-CATENIN; IN-VIVO; OSTEOBLASTIC CELLS; HEAD INDUCTION; INHIBITION; DIFFERENTIATION; PHOSPHORYLATION; KINASE AB Parathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in osteoblasts. To determine whether this suppression is essential for PTH-mediated Wnt signaling and bone formation, we examined mice that overexpress Dkk1 in osteoblasts (Dkk1 mice). Dkk1 mice were osteopenic due to abnormal osteoblast and osteoclast activity. When fed a low-calcium diet, and in two other models of hyperparathyroidism, these mice failed to develop the peritrabecular stromal cell response ("osteitis fibrosis") and new bone formation seen in wild-type mice. Despite these effects of Dkk1 overexpression, PTH still activated Wnt signaling in Dkk1 mice and in osteoblastic cells cultured from these mice. In cultured MC3T3E1 preosteoblastic cells, PTH dramatically suppressed Dkk1 expression, induced PKA-mediated phosphorylation of beta-catenin, and significantly enhanced Lef1 expression. Our findings indicate that the full actions of PTH require intact Wnt signaling but that PTH can activate the Wnt pathway despite overexpression of Dkk1. C1 [Guo, Jun; Liu, Minlin; Yang, Dehong; Thomas, Clare C.; Schipani, Ernestina; Bringhurst, F. Richard; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. [Galvin, R. J. Sells; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. [Galvin, R. J. Sells; Kuhstoss, Stuart A.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU National Heart, Lung, and Blood Institute (NHLBI) [HL081030] FX We thank Venkatesh Krishnan for useful discussion regarding the anti-Dkk1 study. This work was supported by a grant to H.M.K. from the National Heart, Lung, and Blood Institute (NHLBI) Specialized Center for Cell-Based Therapy (HL081030). NR 40 TC 94 Z9 104 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD FEB 3 PY 2010 VL 11 IS 2 BP 161 EP 171 DI 10.1016/j.cmet.2009.12.007 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 555ON UT WOS:000274521900008 PM 20142103 ER PT J AU Chan, MC Hilyard, AC Wu, C Davis, BN Hill, NS Lal, A Lieberman, J Lagna, G Hata, A AF Chan, Mun Chun Hilyard, Aaron C. Wu, Connie Davis, Brandi N. Hill, Nicholas S. Lal, Ashish Lieberman, Judy Lagna, Giorgio Hata, Akiko TI Molecular basis for antagonism between PDGF and the TGF beta family of signalling pathways by control of miR-24 expression SO EMBO JOURNAL LA English DT Article DE BMP; microRNA; PDGF; TGF beta; vascular smooth-muscle cell ID MUSCLE-CELL PROLIFERATION; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL ACTIVITY; UBIQUITIN LIGASE; MICRO-RNA; GROWTH; TRB3; RECEPTOR; ATHEROSCLEROSIS; HYPERTENSION AB Modulation of the vascular smooth-muscle-cell (vSMC) phenotype from a quiescent 'contractile' phenotype to a proliferative 'synthetic' phenotype has been implicated in vascular injury repair, as well as pathogenesis of vascular proliferative diseases. Both bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF beta)-signalling pathways promote a contractile phenotype, while the platelet-derived growth factor-BB (PDGF-BB)-signalling pathway promotes a switch to the synthetic phenotype. Here we show that PDGF-BB induces microRNA-24 (miR-24), which in turn leads to downregulation of Tribbles-like protein-3 (Trb3). Repression of Trb3 coincides with reduced expression of Smad proteins and decrease in BMP and TGF beta signalling, promoting a synthetic phenotype in vSMCs. Inhibition of miR-24 by antisense oligonuclotides abrogates the downregulation of Trb3 as well as pro-synthetic activity of the PDGF-signalling pathway. Thus, this study provides a molecular basis for the antagonism between the PDGF and TGF beta pathways, and its effect on the control of the vSMC phenotype. The EMBO Journal (2010) 29, 559-573. doi:10.1038/emboj.2009.370; Published online 17 December 2009 C1 [Chan, Mun Chun; Hilyard, Aaron C.; Lagna, Giorgio; Hata, Akiko] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Wu, Connie; Davis, Brandi N.; Hata, Akiko] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Hill, Nicholas S.] Tufts Med Ctr, Pulm Crit Care & Sleep Div, Boston, MA 02111 USA. [Lal, Ashish; Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA. [Lal, Ashish; Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. RP Hata, A (reprint author), Tufts Med Ctr, Mol Cardiol Res Inst, 800 Washington St,Box 8486, Boston, MA 02111 USA. EM akiko.hata@tufts.edu RI Davis-Dusenbery, Brandi/N-2798-2013; Lieberman, Judy/A-2717-2015 OI Davis-Dusenbery, Brandi/0000-0001-7811-8613; FU National Institutes of Health [HD042149, HL082854, HL086572]; American Heart Association FX We thank Dr P ten Dijke for antibodies and R Warburton and F Celestin for technical assistance. We also thank the members of the Hata and Lagna laboratory for critical discussion. This work was supported by grants from the National Institutes of Health (HD042149 and HL082854) to AH and (HL086572) to GL. M-CC is a recipient of a postdoctoral fellowship from the American Heart Association. NR 41 TC 119 Z9 125 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 2010 VL 29 IS 3 BP 559 EP 573 DI 10.1038/emboj.2009.370 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 551TO UT WOS:000274233400005 PM 20019669 ER PT J AU Xing, Y Bocking, T Wolf, M Grigorieff, N Kirchhausen, T Harrison, SC AF Xing, Yi Boecking, Till Wolf, Matthias Grigorieff, Nikolaus Kirchhausen, Tomas Harrison, Stephen C. TI Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly SO EMBO JOURNAL LA English DT Article DE chaperone; clathrin-coated vesicle; electron cryomicroscopy; membrane traffic ID MOLECULAR CHAPERONE; ELECTRON CRYOMICROSCOPY; INTERDOMAIN LINKER; SUBSTRATE-BINDING; PROTEIN; HSP70; VESICLES; RESOLUTION; ATPASE; MEMBRANE AB The chaperone Hsc70 drives the clathrin assembly-disassembly cycle forward by stimulating dissociation of a clathrin lattice. A J-domain containing co-chaperone, auxilin, associates with a freshly budded clathrin-coated vesicle, or with an in vitro assembled clathrin coat, and recruits Hsc70 to its specific heavy-chain-binding site. We have determined by electron cryomicroscopy (cryoEM), at about 11 angstrom resolution, the structure of a clathrin coat (in the D6-barrel form) with specifically bound Hsc70 and auxilin. The Hsc70 binds a previously analysed site near the C-terminus of the heavy chain, with a stoichiometry of about one per three-fold vertex. Its binding is accompanied by a distortion of the clathrin lattice, detected by a change in the axial ratio of the D6 barrel. We propose that when Hsc70, recruited to a position close to its target by the auxilin J-domain, splits ATP, it clamps firmly onto its heavy-chain site and locks in place a transient fluctuation. Accumulation of the local strain thus imposed at multiple vertices can then lead to disassembly. The EMBO Journal (2010) 29, 655-665. doi:10.1038/emboj.2009.383; Published online 24 December 2009 C1 [Xing, Yi; Wolf, Matthias; Harrison, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Jack & Eileen Connors Struct Biol Lab, Boston, MA 02115 USA. [Boecking, Till; Kirchhausen, Tomas] Harvard Univ, Sch Med, Program Cellular & Mol Med, Dept Cell Biol, Boston, MA 02115 USA. [Boecking, Till; Kirchhausen, Tomas] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp, Boston, MA 02115 USA. [Grigorieff, Nikolaus] Brandeis Univ, Howard Hughes Med Inst, Rosenstiel Basic Med Res Ctr, Waltham, MA 02254 USA. [Harrison, Stephen C.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Harrison, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Jack & Eileen Connors Struct Biol Lab, 250 Longwood Ave, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu OI Bocking, Till/0000-0003-1165-3122 FU NIH [GM-36548, GM-62580]; Human Frontier Science Program Fellowship FX We thank Werner Boll for help with clathrin preparations; Yifan Cheng and Zhongli Li for instruction and assistance with EM data collection; Tom Walz for access to the Tecnai F20 microscope. The work was supported by NIH Ruth Kirschstein National Research Service Award (to YX), by a Human Frontier Science Program Fellowship (to TB) and by NIH grants GM-36548 (to TK) and GM-62580 (to NG and SCH). NG and SCH are Investigators in the Howard Hughes Medical Institute. NR 54 TC 48 Z9 48 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 2010 VL 29 IS 3 BP 655 EP 665 DI 10.1038/emboj.2009.383 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 551TO UT WOS:000274233400013 PM 20033059 ER PT J AU Xie, C Zhu, JH Chen, X Mi, LZ Nishida, N Springer, TA AF Xie, Can Zhu, Jianghai Chen, Xing Mi, Lizhi Nishida, Noritaka Springer, Timothy A. TI Structure of an integrin with an alpha I domain, complement receptor type 4 SO EMBO JOURNAL LA English DT Article DE alpha I domain; integrin; structure ID ALPHA(L)BETA(2) HYBRID DOMAIN; CRYSTAL-STRUCTURE; EXTENDED CONFORMATIONS; EXTRACELLULAR SEGMENT; LIGAND-BINDING; ACTIVATION; SUBUNIT; PROTEIN; ALPHA-V-BETA-3; RECOGNITION AB We report the structure of an integrin with an alpha I domain, alpha(X)beta(2), the complement receptor type 4. It was earlier expected that a fixed orientation between the aI domain and the beta-propeller domain in which it is inserted would be required for allosteric signal transmission. However, the alpha I domain is highly flexible, enabling two beta I domain conformational states to couple to three alpha I domain states, and greater accessibility for ligand recognition. Although alpha(X)beta(2) is bent similarly to integrins that lack alpha I domains, the terminal domains of the alpha-and beta-legs, calf-2 and beta-tail, are oriented differently than in alpha I-less integrins. Linkers extending to the transmembrane domains are unstructured. Previous mutations in the beta(2)-tail domain support the importance of extension, rather than a deadbolt, in integrin activation. The locations of further activating mutations and antibody epitopes show the critical role of extension, and conversion from the closed to the open headpiece conformation, in integrin activation. Differences among 10 molecules in crystal lattices provide unprecedented information on interdomain flexibility important for modelling integrin extension and activation. The EMBO Journal (2010) 29, 666-679. doi:10.1038/emboj.2009.367; Published online 24 December 2009 C1 [Springer, Timothy A.] Childrens Hosp, Dept Pathol, Program Cellular & Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Childrens Hosp, Dept Pathol, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Nishida, Noritaka/E-7087-2010; Zhu, Jianghai/B-7339-2014; Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU NIH [AI 72765] FX The work is supported by NIH grant AI 72765. NR 51 TC 80 Z9 84 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 3 PY 2010 VL 29 IS 3 BP 666 EP 679 DI 10.1038/emboj.2009.367 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 551TO UT WOS:000274233400014 PM 20033057 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Ca2+ Influx through NMDA-Gated Channels Activates ATP-Sensitive K+ Currents through a Nitric Oxide-cGMP Pathway in Subthalamic Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID METHYL-D-ASPARTATE; CEREBELLAR GRANULE CELLS; PARS COMPACTA NEURONS; SUBSTANTIA-NIGRA; DOPAMINE NEURONS; GUINEA-PIG; IN-VITRO; PARKINSONS-DISEASE; HIPPOCAMPAL-NEURONS; POTASSIUM CHANNELS AB Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons has been correlated with the bradykinesia and rigidity seen in Parkinson's disease. Consequently, there is much interest in characterizing mechanisms that promote burst firing, such as the regulation of NMDA receptor function. Using whole-cell recording techniques in rat brain slices, we report that inward currents evoked by NMDA are greatly potentiated by ATP-sensitive K+ (K-ATP) channel blocking agents in STN neurons but not in dopamine neurons in the substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP interaction may exert an important influence on basal ganglia output and thereby affect the clinical expression of Parkinson's disease. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Shen, KZ (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM shenk@ohsu.edu FU National Institutes of Health [NS38715]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by National Institutes of Health Grant NS38715 and the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. We also thank Dr. Anne I. Taupignon for helpful comments on the data. NR 60 TC 20 Z9 20 U1 0 U2 3 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 FEB 3 PY 2010 VL 30 IS 5 BP 1882 EP 1893 DI 10.1523/JNEUROSCI.3200-09.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 551XM UT WOS:000274246700031 PM 20130197 ER PT J AU Cardoso, F Bedard, PL Winer, EP Pagani, O Senkus-Konefka, E Fallowfield, LJ Kyriakides, S Costa, A Cufer, T Albain, KS AF Cardoso, Fatima Bedard, Philippe L. Winer, Eric P. Pagani, Olivia Senkus-Konefka, Elzbieta Fallowfield, Lesley J. Kyriakides, Stella Costa, Alberto Cufer, Tanja Albain, Kathy S. CA ESO-MBC Task Force TI Re: International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Cardoso, Fatima] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Winer, Eric P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Pagani, Olivia] Osped Italiano, Dept Med Oncol, Oncol Inst So Switzerland, Lugano, Switzerland. [Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Pagani, Olivia; Costa, Alberto] European Sch Oncol, Milan, Italy. [Senkus-Konefka, Elzbieta] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Fallowfield, Lesley J.] Univ Sussex, Brighton & Sussex Med Sch, Brighton, E Sussex, England. [Kyriakides, Stella] European Breast Canc Coalit, Nicosia, Cyprus. [Cufer, Tanja] Univ Clin Golnik, Dept Med Oncol, Golnik, Slovenia. [Albain, Kathy S.] Loyola Univ, Dept Med Oncol, Chicago Stritch Sch Med, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Cardoso, F (reprint author), Inst Jules Bordet, Dept Med Oncol, Blvd Waterloo 125, B-1000 Brussels, Belgium. EM fatima.cardoso@bordet.be NR 1 TC 0 Z9 0 U1 0 U2 4 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 FEB 3 PY 2010 VL 102 IS 3 BP 207 EP 208 DI 10.1093/jnci/djp484 PG 2 WC Oncology SC Oncology GA 553DM UT WOS:000274345800012 ER PT J AU Miotto, O Heiny, AT Albrecht, R Garcia-Sastre, A Tan, TW August, JT Brusic, V AF Miotto, Olivo Heiny, A. T. Albrecht, Randy Garcia-Sastre, Adolfo Tan, Tin Wee August, J. Thomas Brusic, Vladimir TI Complete-Proteome Mapping of Human Influenza A Adaptive Mutations: Implications for Human Transmissibility of Zoonotic Strains SO PLOS ONE LA English DT Article ID VIRUS NS1 PROTEIN; HOST-RANGE RESTRICTION; NUCLEAR EXPORT SIGNAL; AVIAN INFLUENZA; RNA-POLYMERASE; PANDEMIC INFLUENZA; SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; VACCINE TARGETS; HIGH VIRULENCE AB Background: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings: We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear unstable, suggesting low pandemic potential of H5N1 in its current form. In addition, adaptation signatures indicate that pandemic H1N1/09 strain possesses multiple human-transmissibility mutations, though not an unusually high number with respect to swine strains that infected humans in the past. Adaptation signatures provide a novel tool for identifying zoonotic strains with the potential to infect humans. C1 [Miotto, Olivo] Univ Oxford, Ctr Genom & Global Hlth, Oxford, England. [Miotto, Olivo] Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand. [Heiny, A. T.; Tan, Tin Wee] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117595, Singapore. [Albrecht, Randy; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Emerging Pathogens Inst, New York, NY USA. [August, J. Thomas] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. RP Miotto, O (reprint author), Univ Oxford, Ctr Genom & Global Hlth, Oxford, England. EM olivo.miotto@ndm.ox.ac.uk RI Tan, Tin Wee/B-8963-2009; OI Tan, Tin Wee/0000-0002-4062-2854; Miotto, Olivo/0000-0001-8060-6771; Albrecht, Randy/0000-0003-4008-503X; Garcia-Sastre, Adolfo/0000-0002-6551-1827 FU Medical Research Council, United Kingdom; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, United States of America [5 U19 AI56541, HHSN2662-00400085C, HHSN2662-00700010C]; EC [FP6-2004-IST-4] FX The authors acknowledge support by the Medical Research Council, United Kingdom; Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, United States of America, under Grant No. 5 U19 AI56541 and Contract Nos. HHSN2662-00400085C and HHSN2662-00700010C. VB acknowledges support in part by the ImmunoGrid project, under EC contract FP6-2004-IST-4, NO 028069. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 43 Z9 43 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD FEB 3 PY 2010 VL 5 IS 2 AR e9025 DI 10.1371/journal.pone.0009025 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 554ZA UT WOS:000274474200012 PM 20140252 ER PT J AU Schnoll, RA Patterson, F Wileyto, EP Heitjan, DF Shields, AE Asch, DA Lerman, C AF Schnoll, Robert A. Patterson, Freda Wileyto, E. Paul Heitjan, Daniel F. Shields, Alexandra E. Asch, David A. Lerman, Caryn TI Effectiveness of Extended-Duration Transdermal Nicotine Therapy A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SUSTAINED-RELEASE BUPROPION; RECEPTOR PARTIAL AGONIST; SMOKING-CESSATION; REPLACEMENT THERAPY; COST-EFFECTIVENESS; SMOKERS; PATCH; INTERVENTIONS; VARENICLINE; ABSTINENCE AB Background: Tobacco dependence is a chronic, relapsing condition that may require extended treatment. Objective: To assess whether extended-duration transdermal nicotine therapy increases abstinence from tobacco more than standard-duration therapy in adult smokers. Design: Parallel randomized, placebo-controlled trial from September 2004 to February 2008. Participants and all research personnel except the database manager were blinded to randomization. (ClinicalTrials.gov registration number: NCT00364156) Setting: Academic center. Participants: 568 adult smokers. Intervention: In an unstratified small block-randomization scheme, participants were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks). Measurements: The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52. Secondary outcomes were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, and side effects and adherence. Results: At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6% vs. 20.3%; odds ratio, 1.81 95% CI, 1.23 to 2.66]; P = 0.002), prolonged abstinence (41.5% vs. 26.9%; odds ratio, 1.97 [CI, 1.38 to 2.82]; P = 0.001), and continuous abstinence (19.2% vs. 12.6%; odds ratio, 1.64 [CI, 1.04 to 2.60]; P = 0.032) versus standard therapy. Extended therapy reduced the risk for lapse (hazard ratio, 0.77 [CI, 0.63 to 0.95]; P = 0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [CI, 1.17 to 1.84]; P = 0.001). Time to relapse was slower with extended versus standard therapy (hazard ratio, 0.50 [CI, 0.35 to 0.73]; P < 0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P = 0.027). No differences in side effects and adverse events between groups were found at the extended-treatment assessment. Limitation: The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment, and differences in adherence across treatment groups were detected. Conclusion: Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy. C1 [Schnoll, Robert A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schnoll, RA (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Suite 4100, Philadelphia, PA 19104 USA. EM schnoll@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU National Cancer Institute; National Institute on Drug Abuse [P50 CA/DA84718, P50 CA143187] FX Grant Support: By a Transdisciplinary Tobacco Use Research Center Grant from the National Cancer Institute and the National Institute on Drug Abuse (P50 CA/DA84718 and P50 CA143187). NR 41 TC 56 Z9 56 U1 2 U2 12 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 2 PY 2010 VL 152 IS 3 BP 144 EP U4 DI 10.7326/0003-4819-152-3-201002020-00005 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 552WN UT WOS:000274324600002 PM 20124230 ER PT J AU Garg, S Ahnen, DJ AF Garg, Samita Ahnen, Dennis J. TI Is Computed Tomographic Colonography Being Held to a Higher Standard? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID COLONOSCOPIC MISS RATES; SERVICES TASK-FORCE; CT COLONOGRAPHY; COLORECTAL-CANCER; EXTRACOLONIC FINDINGS; ASYMPTOMATIC ADULTS; POPULATION; ADENOMAS; NEOPLASIA AB Recent guidelines for colorectal cancer screening have reached different conclusions on whether computed tomographic colonography (CTC) is an acceptable screening option, and the Centers for Medicare & Medicaid Services recently decided not to cover CTC screening. The rationale against recommending or covering CTC screening includes concerns about radiation exposure, false-negative rates for small polyps, the discovery of extracolonic findings, variability in performance, a lack of targeted studies, a higher adenoma rate in the Medicare-eligible age group, and an absence of evidence that covering CTC would increase overall screening rates. Similar concerns can be raised for other recommended and covered colon cancer screening tests, but it seems that CTC is being held to a new and higher standard. C1 Univ Colorado, Ctr Canc, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Colorado Denver, Sch Med, Denver, CO USA. RP Ahnen, DJ (reprint author), Denver Vet Affairs Med Ctr 111E, 1055 Clermont St, Denver, CO 80220 USA. EM dennis.ahnen@ucdenver.edu NR 24 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 2 PY 2010 VL 152 IS 3 BP 178 EP 181 DI 10.7326/0003-4819-152-3-201002020-00009 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 552WN UT WOS:000274324600006 PM 20124234 ER PT J AU Silberman, GA Fan, THM Liu, H Jiao, Z Xiao, HD Lovelock, JD Boulden, BM Widder, J Fredd, S Bernstein, KE Wolska, BM Dikalov, S Harrison, DG Dudley, SC AF Silberman, Gad A. Fan, Tai-Hwang M. Liu, Hong Jiao, Zhe Xiao, Hong D. Lovelock, Joshua D. Boulden, Beth M. Widder, Julian Fredd, Scott Bernstein, Kenneth E. Wolska, Beata M. Dikalov, Sergey Harrison, David G. Dudley, Samuel C., Jr. TI Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction SO CIRCULATION LA English DT Article DE diastole; heart failure; nitric oxide; nitric oxide synthase ID HEART-FAILURE; ANGIOTENSIN-II; EJECTION FRACTION; HYPERTROPHIC CARDIOMYOPATHY; DOPPLER-ECHOCARDIOGRAPHY; CARDIOVASCULAR-DISEASE; VENTRICULAR MYOCYTES; MYOCARDIAL-FUNCTION; FLOW PROPAGATION; TETRAHYDROBIOPTERIN AB Background-Heart failure with preserved ejection fraction is 1 consequence of hypertension and is caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because NO synthase (NOS) becomes uncoupled when oxidative depletion of its cofactor tetrahydrobiopterin (BH(4)) occurs. Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction. Methods and Results-In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH(4), and uncoupled NOS. Compared with sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled-release deoxycorticosterone acetate pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and dephosphorylated phospholamban. Feeding hypertensive mice BH(4) (5 mg/d), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH(4) stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with short-term BH(4) treatment. Targeted cardiac overexpression of angiotensin-converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension. Conclusions-Cardiac oxidation, independently of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH(4) may represent a possible treatment for diastolic dysfunction. (Circulation. 2010;121:519-528.) C1 [Liu, Hong; Jiao, Zhe; Lovelock, Joshua D.; Boulden, Beth M.; Dudley, Samuel C., Jr.] Univ Illinois, Cardiol Sect, Chicago, IL 60612 USA. [Silberman, Gad A.; Fan, Tai-Hwang M.; Liu, Hong; Jiao, Zhe; Boulden, Beth M.; Widder, Julian; Fredd, Scott; Dikalov, Sergey; Harrison, David G.; Dudley, Samuel C., Jr.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. [Fan, Tai-Hwang M.; Harrison, David G.; Dudley, Samuel C., Jr.] Atlanta VA Med Ctr, Atlanta, GA USA. [Xiao, Hong D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Bernstein, Kenneth E.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Liu, Hong; Jiao, Zhe; Lovelock, Joshua D.; Wolska, Beata M.; Dudley, Samuel C., Jr.] Jesse Brown VA Med Ctr, Chicago, IL USA. RP Dudley, SC (reprint author), Univ Illinois, Cardiol Sect, 840 S Wood St,MC 715, Chicago, IL 60612 USA. EM scdudley@uic.edu RI Warren, Beth/B-6918-2017; OI Warren, Beth/0000-0003-4416-3031; Bernstein, Kenneth/0000-0001-8097-3272 FU National Institutes of Health (NIH) [R01 HL085520, R01 HL085558, R01 HL073753, R01 DK39777, R01 DK51445, 5 F32 HL086232-02, R01 HL79032]; American Heart Association Established Investigator Award [0440164N]; Veterans Affairs MERIT; American Heart Association Scientist Development FX Dr Dudley is supported by National Institutes of Health (NIH) grants R01 HL085520, R01 HL085558, and R01 HL073753; American Heart Association Established Investigator Award 0440164N; and a Veterans Affairs MERIT grant. Dr Bernstein is supported by NIH grants R01 DK39777, R01 HL085558, and R01 DK51445. Dr Silberman is supported by NIH grant 5 F32 HL086232-02. Dr Xiao is supported by an American Heart Association Scientist Development Award. Dr Wolska is supported by NIH grant R01 HL79032. NR 49 TC 113 Z9 117 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 2 PY 2010 VL 121 IS 4 BP 519 EP U89 DI 10.1161/CIRCULATIONAHA.109.883777 PG 31 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 550TY UT WOS:000274154300010 PM 20083682 ER PT J AU Clower, CV Chatterjee, D Wang, ZX Cantley, LC Heiden, MGV Krainer, AR AF Clower, Cynthia V. Chatterjee, Deblina Wang, Zhenxun Cantley, Lewis C. Heiden, Matthew G. Vander Krainer, Adrian R. TI The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aerobic glycolysis; cancer; RNA splicing ID ALLOSTERIC REGULATION; BINDING-PROTEIN; TUMOR-GROWTH; CANCER; GENE; M2; ISOZYMES AB Cancer cells preferentially metabolize glucose by aerobic glycolysis, characterized by increased lactate production. This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons. We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during terminal differentiation of muscle cells, and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms. We further show that the M1-specific exon is actively repressed in cancer-cell lines-although some M1 mRNA is expressed in cell lines derived from brain tumors- and demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to this control. Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production. These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis. C1 [Chatterjee, Deblina; Wang, Zhenxun; Krainer, Adrian R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Clower, Cynthia V.; Cantley, Lewis C.; Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Div Signal Transduct, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Clower, Cynthia V.; Cantley, Lewis C.; Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Chatterjee, Deblina; Krainer, Adrian R.] SUNY Stony Brook, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA. [Wang, Zhenxun; Krainer, Adrian R.] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. [Heiden, Matthew G. Vander] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Krainer, AR (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. EM krainer@cshl.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Krainer, Adrian/0000-0001-9024-9501 FU Starr Cancer Consortium; National Institutes of Health; National Science Scholarship FX We thank Chaolin Zhang, Martin Ackerman, Rotem Karni, Zuo Zhang, Yimin Hua, Mads Jensen, and Shuying Sun for helpful discussions and reagents. This work was supported by a grant from the Starr Cancer Consortium to A. R. K. and L. C. C. A Ruth L. Kirschstein National Research Service Award from the National Institutes of Health was received by C. V. C. A National Science Scholarship administered by the Agency for Science, Technology, and Research, Singapore was received by Z.W. NR 30 TC 145 Z9 154 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP 1894 EP 1899 DI 10.1073/pnas.0914845107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300019 PM 20133837 ER PT J AU Estes, KA Dunbar, TL Powell, JR Ausubel, FM Troemel, ER AF Estes, Kathleen A. Dunbar, Tiffany L. Powell, Jennifer R. Ausubel, Frederick M. Troemel, Emily R. TI bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; pathogenesis; intestine; host-pathogen interactions ID INNATE IMMUNE-SYSTEM; PATHOGENESIS; RECOGNITION; BACTERIAL; RECEPTORS; EVOLUTION; VIRULENCE; PATTERNS; PATHWAY; MODEL AB Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wildtype P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen. C1 [Estes, Kathleen A.; Dunbar, Tiffany L.; Troemel, Emily R.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92093 USA. [Powell, Jennifer R.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Powell, Jennifer R.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Troemel, ER (reprint author), Univ Calif San Diego, Div Biol Sci, San Diego, CA 92093 USA. EM etroemel@ucsd.edu FU Leukemia/Lymphoma Society; Moores Cancer Center Institutional Research; National Research Service; National Institutes of Health [P01 AI044220, R01 AI064332] FX We thank David Simon and Sean Curran for the transcription factor RNAi library, Zhi Yan for excellent technical support, and the National BioResource Project from Japan for the zip-2(tm4067) deletion. We thank the Caenorhabditis Genetics Center for some strains described in this paper. This work was supported by a Leukemia/Lymphoma Society Fellowship and a Moores Cancer Center Institutional Research Grant (to E. R. T.), a National Research Service Award (to J.P.), and National Institutes of Health Grants P01 AI044220 and R01 AI064332 (to F. M. A.). NR 28 TC 56 Z9 78 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 2 PY 2010 VL 107 IS 5 BP 2153 EP 2158 DI 10.1073/pnas.0914643107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552MV UT WOS:000274296300064 PM 20133860 ER PT J AU Gordon, JA Hayden, EM Ahmed, RA Pawlowski, JB Khoury, KN Oriol, NE AF Gordon, James A. Hayden, Emily M. Ahmed, Rami A. Pawlowski, John B. Khoury, Kimberly N. Oriol, Nancy E. TI Early Bedside Care During Preclinical Medical Education: Can Technology-Enhanced Patient Simulation Advance the Flexnerian Ideal? SO ACADEMIC MEDICINE LA English DT Article ID BIOMEDICAL KNOWLEDGE; STUDENTS; SCHOOL AB Flexner wanted medical students to study at the patient bedside-a remarkable innovation in his time-so that they could apply science to clinical care under the watchful eye of senior physicians. Ever since his report, medical schools have reserved the latter years of their curricula for such an "advanced" apprenticeship, providing clinical clerkship experiences only after an initial period of instruction in basic medical sciences. Although Flexner codified the segregation of preclinical and clinical instruction, he was committed to ensuring that both domains were integrated into a modern medical education. The aspiration to fully integrate preclinical and clinical instruction continues to drive medical education reform even to this day. In this article, the authors revisit the original justification for sequential preclinical clinical instruction and argue that modern, technology-enhanced patient simulation platforms are uniquely powerful for fostering simultaneous integration of preclinical-clinical content in a way that Flexner would have applauded. To date, medical educators tend to focus on using technology-enhanced medical simulation in clinical and postgraduate medical education; few have devoted significant attention to using immersive clinical simulation among preclinical students. The authors present an argument for the use of dynamic robot-mannequins in teaching basic medical science, and describe their experience with simulator-based preclinical instruction at Harvard Medical School. They discuss common misconceptions and barriers to the approach, describe their curricular responses to the technique, and articulate a unifying theory of cognitive and emotional learning that broadens the view of what is possible, feasible, and desirable with simulator-based medical education. Acad Med. 2010; 85: 370-377. C1 [Gordon, James A.] Harvard Univ, Gilbert Program Med Simulat, Sch Med, Boston, MA 02114 USA. [Gordon, James A.] Massachusetts Gen Hosp, Div Med Simulat, Dept Emergency Med, Boston, MA 02114 USA. [Ahmed, Rami A.] Summa Hlth Syst, Akron, OH USA. [Pawlowski, John B.] Beth Israel Deaconess Med Ctr, Thorac Anesthesia Div, Dept Anesthesia, Boston, MA 02215 USA. RP Gordon, JA (reprint author), Harvard Univ, Gilbert Program Med Simulat, Sch Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgordon3@partners.org NR 33 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2010 VL 85 IS 2 BP 370 EP 377 DI 10.1097/ACM.0b013e3181c88d74 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 576GF UT WOS:000276131700037 PM 20107370 ER PT J AU Eckenhoff, RG Xi, J Shimaoka, M Bhattacharji, A Covarrubias, M Dailey, WP AF Eckenhoff, Roderic G. Xi, Jin Shimaoka, Motomu Bhattacharji, Aditya Covarrubias, Manuel Dailey, William P. TI Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Anesthesia; Shaw2 K(+) channel; integrin I domain; photoaffinity labeling; binding; apoferritin ID NEURONAL K+ CHANNEL; INTEGRIN LFA-1; BINDING; IDENTIFICATION; ACTIVATION; HALOTHANE; PROTEINS; FEATURES; SITE AB Volatility and low-affinity hamper an ability to define molecular targets of the inhaled anesthetics. Photolabels have proven to be a useful approach in this regard, although none have closely mimicked contemporary drugs. We report here the synthesis and validation of azi-isoflurane, a compound constructed by adding a diazirinyl moiety to the methyl carbon of the commonly used general anesthetic isoflurane. Azi-isoflurane is slightly more hydrophobic than isoflurane, and more potent in tadpoles. This novel compound inhibits Shaw2 K(+) channel currents similarly to isoflurane and binds to apoferritin with enhanced affinity. Finally, when irradiated at 300 nm, azi-isoflurane adducts to residues known to line isoflurane-binding sites in apoferritin and integrin LFA-1, the only proteins with isoflurane binding sites defined by crystallography. This reagent should allow rapid discovery of isoflurane molecular targets and binding sites within those targets. C1 [Eckenhoff, Roderic G.; Xi, Jin] Univ Penn, Dept Anesthesiol & Crit Care, Sch Med, Philadelphia, PA 19104 USA. [Dailey, William P.] Univ Penn, Dept Chem, Sch Arts & Sci, Philadelphia, PA 19104 USA. [Shimaoka, Motomu] Childrens Hosp, Immune Dis Inst Mol & Cellular Med, Boston, MA 02115 USA. [Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Bhattacharji, Aditya; Covarrubias, Manuel] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Eckenhoff, RG (reprint author), 3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM Roderic.eckenhoff@uphs.upenn.edu FU NIH [P01GM55876, R01AI063421, R01AA010615]; [P30CA016520]; [ES013508-04] FX Major funding was from NIH Grants P01GM55876 (R.G.E.), R01AI063421 (M.S.), and R01AA010615 (MC.).; The authors thank Michael Hall for assistance with synthesis, and mass spectrometry analysis was provided by Proteomics Core Facility, University of Pennsylvania, supported by grants P30CA016520 and ES013508-04. NR 24 TC 14 Z9 14 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD FEB PY 2010 VL 1 IS 2 BP 139 EP 145 DI 10.1021/cn900014m PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 600IZ UT WOS:000277980700007 PM 20228895 ER PT J AU Kleiner, MT Ilyas, AM Jupiter, JB AF Kleiner, M. T. Ilyas, A. M. Jupiter, J. B. TI Radial Head Arthroplasty SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID POSTEROLATERAL ROTATORY INSTABILITY; POSTERIOR INTEROSSEOUS NERVE; UNSTABLE ELBOW FRACTURES; COMMINUTED FRACTURES; INTERNAL-FIXATION; VALGUS STABILITY; PROSTHESIS; REPLACEMENT; DISLOCATION; RESECTION AB In conclusion, radial head fractures with 3 or more fragments have a high incidence of complications when treated with ORIF including hardware failure, malunion, nonunion, and the need for re-operation. Radial head arthroplasty has demonstrated good success in the treatment of complex, comminuted radial head fractures which are not amenable to non-opeative treatment or ORIF Success can be optimized by diligent surgical dissection, avoiding inadvertent nerve injury, placement of an appropriately sized implant, repair of associated injuries, and early protected motion. C1 [Kleiner, M. T.] Temple Univ Hosp & Med Sch, Dept Orthoped Surg, Philadelphia, PA 19140 USA. [Ilyas, A. M.] Orthopaed Surg Temple Univ Hosp, Temple Hand Ctr, Philadelphia, PA USA. [Jupiter, J. B.] Orthopaed Surg Harvard Med Sch, Hand & Upper Extrem Serv, Massachusetts Gen Hosp, Boston, MA USA. RP Kleiner, MT (reprint author), Temple Univ Hosp & Med Sch, Dept Orthoped Surg, Philadelphia, PA 19140 USA. NR 46 TC 3 Z9 3 U1 0 U2 0 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR JI Acta Chir. Orthop. Traumatol. Cechoslov. PD FEB PY 2010 VL 77 IS 1 BP 7 EP 12 PG 6 WC Orthopedics SC Orthopedics GA 567XS UT WOS:000275482700001 PM 20214854 ER PT J AU Vavvas, D Huynh, N Pasquale, L Berson, EL AF Vavvas, Demetrios Huynh, Nancy Pasquale, Louis Berson, Eliot L. TI Progressive hydroxychloroquine toxicity mimicking low-tension glaucoma after discontinuation of the drug SO ACTA OPHTHALMOLOGICA LA English DT Article ID RETINOPATHY C1 [Vavvas, Demetrios; Huynh, Nancy; Pasquale, Louis; Berson, Eliot L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Vavvas, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 3 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD FEB PY 2010 VL 88 IS 1 BP 156 EP 157 DI 10.1111/j.1755-3768.2008.01359.x PG 2 WC Ophthalmology SC Ophthalmology GA 550XY UT WOS:000274168900028 PM 18937815 ER PT J AU Van de Velde, SK Hosseini, A Kozanek, M Gill, TJ Rubash, HE Li, GA AF Van de Velde, Samuel K. Hosseini, Ali Kozanek, Michal Gill, Thomas J. Rubash, Harry E. Li, Guoan TI Application guidelines for dynamic knee joint analysis with a dual fluoroscopic imaging system SO ACTA ORTHOPAEDICA BELGICA LA English DT Article DE fluoroscopy; Magnetic Resonance (MR), kinematics; joint biomechanics; gait analysis ID IN-VIVO; KINEMATICS; ARTHROPLASTY; MOTIONS; FEMUR; GAIT AB The widespread availability of mobile digital fluoroscopic systems with dynamic imaging capabilities places this type of motion analysis within reach of many research groups. With the addition of the second fluoroscope though, and the incorporation of a treadmill to analyze gait, the fluoroscopic analysis technique, which was once it rather straightforward method, has become more complex. Therefore, the purpose of the present manuscript was to provide a comprehensive review of the various processes that are associated with the dynamic knee joint motion analysis, including patient selection. construction of three-dimensional knee models, fluoroscopic scanning, and matching. C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR055612, R01 AR052408] NR 25 TC 4 Z9 4 U1 0 U2 5 PU ACTA MEDICA BELGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138-A, B-1180 BRUSSELS, BELGIUM SN 0001-6462 J9 ACTA ORTHOP BELG JI Acta Orthop. Belg. PD FEB PY 2010 VL 76 IS 1 BP 107 EP 113 PG 7 WC Orthopedics SC Orthopedics GA 562FK UT WOS:000275035000019 PM 20306974 ER PT J AU Zhang, Y Fraser, JA Schwiening, C Zhang, Y Killeen, MJ Grace, AA Huang, CLH AF Zhang, Y. Fraser, J. A. Schwiening, C. Zhang, Y. Killeen, M. J. Grace, A. A. Huang, C. L. -H. TI Acute atrial arrhythmogenesis in murine hearts following enhanced extracellular Ca2+entry depends on intracellular Ca2+stores SO ACTA PHYSIOLOGICA LA English DT Article DE atrial arrhythmogenesis; Ca2+homeostasis; calcium entry; murine hearts; store calcium ID CARDIAC RYANODINE RECEPTOR; SARCOPLASMIC-RETICULUM CA2+-ATPASE; CYCLOPIAZONIC ACID INHIBITION; CALCIUM-CHANNEL; VENTRICULAR MYOCYTES; DOWN-REGULATION; OPEN PROBABILITY; CA2+ CHANNELS; FIBRILLATION; MODEL AB Aim: To investigate the effect of increases in extracellular Ca2+ entry produced by the L-type Ca2+ channel agonist FPL-64176 (FPL) upon acute atrial arrhythmogenesis in intact Langendorff-perfused mouse hearts and its dependence upon diastolic Ca2+ release from sarcoplasmic reticular Ca2+ stores. Methods: Confocal microscope studies of Fluo-3 fluorescence in isolated atrial myocytes were performed in parallel with electrophysiological examination of Langendorff-perfused mouse hearts. Results: Atrial myocytes m) initially showed (< 10 min) frequent, often multiple, diastolic peaks following the evoked Ca2+ transients whose amplitudes remained close to control values. With continued pacing (> 10 min) this reverted to a regular pattern of evoked transients with increased amplitudes but in which diastolic peaks were absent. Higher FPL concentrations (1.0 mu m) produced sustained and irregular patterns of cytosolic Ca2+ activity, independent of pacing. Nifedipine (0.5 mu m), and caffeine (1.0 mm) and cyclopiazonic acid (CPA) (0.15 mu m) pre-treatments respectively produced immediate and gradual reductions in the F/F(0) peaks. Such nifedipine and caffeine, or CPA pre-treatments, abolished, or reduced, the effects of 0.1 and 1.0 mu m FPL on cytosolic Ca2+ signals. FPL (1.0 mu m) increased the incidence of atrial tachycardia and fibrillation in intact Langendorff-perfused hearts without altering atrial effective refractory periods. These effects were inhibited by nifedipine and caffeine, and reduced by CPA. Conclusion: Enhanced extracellular Ca2+ entry exerts acute atrial arrhythmogenic effects that is nevertheless dependent upon diastolic Ca2+ release. These findings complement reports that associate established, chronic, atrial arrhythmogenesis with decreased overall inward Ca2+ current. C1 [Zhang, Y.; Fraser, J. A.; Schwiening, C.; Huang, C. L. -H.] Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. [Zhang, Y.] Xi An Jiao Tong Univ, Hosp 1, Dept Paediat, Xian 710049, Peoples R China. [Zhang, Y.; Grace, A. A.] Univ Cambridge, Dept Biochem, Cambridge CB2 3EG, England. [Killeen, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Killeen, M. J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Huang, CLH (reprint author), Univ Cambridge, Physiol Lab, Downing St, Cambridge CB2 3EG, England. EM clh11@cam.ac.uk OI Fraser, James/0000-0002-6505-1883 FU British Heart Foundation; Medical Research Council; Wellcome Trust; Biotechnology and Biological Sciences Research Council, UK; National Natural Science Foundation of China (NSFC) [30371571, 30672209]; PRC; Helen Kirkland Fund for Cardiac Research; Department for Education and Skills of the United Kingdom; China Scholarship Council; Avrith Studentship FX This study was supported by grants from the British Heart Foundation, the Medical Research Council, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, UK and the National Natural Science Foundation of China (NSFC 30371571 and 30672209), PRC and the Helen Kirkland Fund for Cardiac Research. Y.H.Z. thanks the Department for Education and Skills of the United Kingdom and the China Scholarship Council for support and M.J.K. thanks the Physiological Laboratory for the award of an Avrith Studentship. NR 69 TC 9 Z9 9 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD FEB PY 2010 VL 198 IS 2 BP 143 EP 158 DI 10.1111/j.1748-1716.2009.02055.x PG 16 WC Physiology SC Physiology GA 541VU UT WOS:000273449900004 PM 19886909 ER PT J AU Plebani, JG Tirado, CF Pettinati, HM Kampman, KM Volpicelli, JR Oslin, DW AF Plebani, Jennifer G. Tirado, Carlos F. Pettinati, Helen M. Kampman, Kyle M. Volpicelli, Joseph R. Oslin, David W. TI Combined effects of alcohol and hepatitis C: A secondary analysis of alcohol use biomarkers and high-risk behaviors from two medication trials for alcohol dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE Hepatitis C; Alcohol dependence; CDT (carbohydrate-deficient transferrin); GGT (gamma glutamyl transpeptidase); Risk-assessment ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; ADDICTION SEVERITY INDEX; GAMMA-GLUTAMYL-TRANSFERASE; LIVER-DISEASE; VIRUS-INFECTION; HIV-INFECTION; UNITED-STATES; DRUG-USERS; ABUSE; NALTREXONE AB Objectives: The goal of this secondary analysis was to examine the combined effects of HCV infection and recent alcohol use on baseline biologic markers of alcohol consumption in two outpatient medication trials for alcohol dependence. In addition. the relationship between Hepatitis C virus (HCV) infection and behavioral risk factors for HCV infection in these clinical populations were examined. Methods: Data (n=345) from two randomized, placebo-controlled trials of naltrexone and psychosocial treatment for alcohol dependence (Study 1, n=212) and comorbid alcohol and cocaine dependence (Study 11, n=133) were used to examine baseline measures of HCV risk behaviors (injection drug use, needle sharing), and biomarkers of alcohol use (AST, ALT, GGT and CDT) were compared by HCV serostatus first within each study and then across studies, Results: Although groups had differing sociodemographic profiles (as indicated by race, marital status, level of education) Subjects in Study I exhibited no statistically significant differences from the Study 11 cohort in HCV prevalence (12.7 vs. 20.0%. p=0.07), lifetime history of injection drug use (13.8 vs. 22.0%, p=0.74), lifetime history of needle sharing (9.1 vs. 18.0%, p=0.62). As such, the data from both studies were analyzed together. Regardless of drinking status. HCV infection was significantly associated with an upward shift in the baseline level of ALT, AST, and GGT (p<0.006 for all measures) and a downward shift in baseline CDT (p=0.002). When using standard laboratory cutoff values to determine clinically significant elevations, HCV seropositivity was significantly associated with elevations in ALT, AST, GGT (p <0.001), and with decreases in CDT (p=.002). Conclusions: These data emphasize the importance of evaluating HCV infection and HCV risk behaviors at intake in medication trials for alcohol dependence and also raise questions regarding the use of cutoff scores for ALT. AST, GGT and CDT levels as biologic markers of alcohol use in subjects when HCV status is unknown. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Plebani, Jennifer G.; Pettinati, Helen M.; Kampman, Kyle M.; Volpicelli, Joseph R.; Oslin, David W.] Univ Penn, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. [Oslin, David W.] Univ Penn, Sect Geriatr Psychiat, Dept Psychiat, Philadelphia, PA 19104 USA. [Oslin, David W.] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. [Tirado, Carlos F.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Div Addict, Dallas, TX 75390 USA. RP Plebani, JG (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM plebani_j@mail.trc.upenn.edu FU National institute of Alcoholism and Alcohol Abuse (NIAAA) [ROIAA007517]; National Institute of Drug Abuse (NIDA) [P60DA05187, ST32DA007241] FX Supported, in part, by grants from the National institute of Alcoholism and Alcohol Abuse (NIAAA) ROIAA007517. and National Institute of Drug Abuse (NIDA) P60DA05187 and ST32DA007241. NR 39 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2010 VL 35 IS 2 BP 123 EP 128 DI 10.1016/j.addbeh.2009.09.012 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 532QD UT WOS:000272763600008 PM 19783106 ER PT J AU Xian, Y Pan, WQ Peterson, ED Heidenreich, PA Cannon, CP Hernandez, AF Friedman, B Holloway, RG Fonarow, GC AF Xian, Ying Pan, Wenqin Peterson, Eric D. Heidenreich, Paul A. Cannon, Christopher P. Hernandez, Adrian F. Friedman, Bruce Holloway, Robert G. Fonarow, Gregg C. CA GWTG Steering Comm Hosp TI Are quality improvements associated with the Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) program sustained over time?: A longitudinal comparison of GWTG-CAD hospitals versus non-GWTG-CAD hospitals SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; AMERICAN-HEART-ASSOCIATION; MEDICARE PATIENTS; CARE AB Background Previous reports have demonstrated that participation in GWTG-CAD, a national quality initiative of the American Heart Association, is associated with improved guideline adherence for patients hospitalized with CAD. We sought to establish whether these benefits from participation in GWTG-CAD were sustained over time. Methods We used the Centers for Medicare and Medicaid Services Hospital Compare database to examine 6 performance measures and one composite score for 3 consecutive 12-month periods including aspirin and beta-blocker on arrival/discharge, angiotensin-converting enzyme inhibitor (ACE-I) for left ventricular systolic dysfunction (LVSD), and adult smoking cessation counseling. The differences in guideline adherence between the GWTG-CAD hospitals (n = 440, 439, 429) and non-GWTG-CAD hospitals (n = 2,438, 2,268, 2,140) were evaluated for each 12-month period. A multivariate mixed-effects model was used to estimate the independent effect of GWTG-CAD over time adjusting for hospital characteristics. Results Compared with non-GWTG hospitals, the GWTG-CAD hospitals demonstrated higher guideline adherence for 6 performance measures. The largest differences existed for (1) aspirin at arrival (2.3%, 2.1%, and 1.6% for each 12-month period, respectively), (2) aspirin at discharge (3.4%, 2.2%, and 2.3%), (3) beta-blocker at arrival ( 3.4%, 2.9%, and 2.6%), and (4) beta-blocker at discharge (2.8%, 1.8%, and 1.5%). In multivariate analysis, the GWTG-CAD hospitals were independently associated with better adherence for 4 of the 6 measures (the exceptions were ACE-I for LVSD and smoking cessation counseling). Superior performance was also found for the composite measures. Although there was some narrowing between groups, GWTG-CAD hospitals maintained superior guideline adherence than non-GWTG-CAD hospitals for the entire 3-year period (adjusted differences 1.8%, 1.6%, and 1.4%). Conclusions Hospitals participating in GWTG-CAD had modestly superior acute cardiac care and secondary prevention measures performance relative to non-GWTG-CAD. These benefits of GWTG-CAD participation were sustained over time and independent of hospital characteristics. (Am Heart J 2010; 159: 207-14.) C1 [Xian, Ying] Univ Rochester, Med Ctr, Dept Community & Prevent Med, Rochester, NY 14642 USA. [Pan, Wenqin; Peterson, Eric D.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Pan, Wenqin; Peterson, Eric D.; Hernandez, Adrian F.] Duke Univ, Med Ctr, Durham, NC USA. [Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Cannon, Christopher P.] Harvard Univ, Boston, MA 02115 USA. [Cannon, Christopher P.] TIMI Grp, Boston, MA USA. RP Xian, Y (reprint author), Univ Rochester, Med Ctr, Dept Community & Prevent Med, 601 Elmwood Ave,Box 644, Rochester, NY 14642 USA. EM ying_xian@urmc.rochester.edu RI Hernandez, Adrian F./A-7818-2016 OI Heidenreich, Paul/0000-0001-7730-8490; Hernandez, Adrian F./0000-0003-3387-9616 NR 14 TC 27 Z9 28 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2010 VL 159 IS 2 DI 10.1016/j.ahj.2009.11.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 552JX UT WOS:000274287200007 PM 20152218 ER PT J AU Park, JK Kim, TH Ko, CC Garcia-Godoy, F Kim, HI Kwon, YH AF Park, Jeong-Kil Kim, Tae-Hyong Ko, Ching-Chang Garcia-Godoy, Franklin Kim, Hyung-Il Kwon, Yong Hoon TI Effect of staining solutions on discoloration of resin nanocomposites SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID AESTHETIC RESTORATIVE MATERIALS; COLOR STABILITY; SURFACE-ROUGHNESS; COMPOSITE RESINS; SUSCEPTIBILITY; FOOD; TEA AB Purpose: To examine the effect of staining solutions on the discoloration of resin nanocomposites. Methods: Three resin nanocomposites (Ceram X, Grandio, and Filtek Z350) were light cured for 40 seconds at a light intensity of 1000 mW/cm(2). The color of the specimens was measured in %R (reflectance) mode before and after immersing the specimens in four different test solutions [distilled water (DW), coffee (CF), 50% ethanol (50ET) and brewed green tea (GT)] for 7 hours/day over a 3-week period. The color difference (Delta E*) was obtained based on the CIEL*a*b* color coordinate values. Results: The specimens immersed in DW, 50ET and GT showed a slight increase in L* value. However, the samples immersed in CF showed a decrease in the L* value and an increase in the b* value. CF induced a significant color change (Delta E*: 3.1-5.6) in most specimens but the other solutions induced only a slight color change. Overall, coffee caused unacceptable color changes to the resin nanocomposites. (Am J Dem 2010;23:39-42). C1 [Park, Jeong-Kil; Kim, Tae-Hyong] Pusan Natl Univ, Dept Conservat Dent, Yangsan, South Korea. [Kim, Hyung-Il] Pusan Natl Univ, Dept Dent Mat, Sch Dent, Yangsan, South Korea. [Kim, Hyung-Il] Pusan Natl Univ, Med Res Inst, Yangsan, South Korea. [Ko, Ching-Chang] Univ N Carolina, Sch Dent, Dept Orthodont, Chapel Hill, NC 27599 USA. [Garcia-Godoy, Franklin] Univ Tennessee, Coll Dent, Memphis, TN USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Park, JK (reprint author), Pusan Natl Univ, Dept Conservat Dent, Yangsan, South Korea. FU Pusan National University [2007-34] FX This study was supported by Medical Research Institute Grant (2007-34), Pusan National University. NR 25 TC 4 Z9 4 U1 1 U2 1 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD FEB PY 2010 VL 23 IS 1 BP 39 EP 42 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 574DR UT WOS:000275969400008 PM 20437726 ER PT J AU Barnes, DE Haight, TJ Mehta, KM Carlson, MC Kuller, LH Tager, IB AF Barnes, Deborah E. Haight, Thaddeus J. Mehta, Kala M. Carlson, Michelle C. Kuller, Lewis H. Tager, Ira B. TI Secondhand Smoke, Vascular Disease, and Dementia Incidence: Findings From the Cardiovascular Health Cognition Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; dementia; longitudinal studies; models; statistical; tobacco smoke pollution ID MARGINAL STRUCTURAL MODELS; ALZHEIMERS-DISEASE; CAUSAL INFERENCE; TOBACCO-SMOKE; RISK-FACTORS; BRAIN; PERFORMANCE; EXPOSURE; NICOTINE; ASSOCIATION AB Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16-25 years) and high (> 25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with > 25 years of SHS exposure and > 25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0-15 years) SHS exposure and < 25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD. C1 [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Mehta, Kala M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA. [Mehta, Kala M.] San Francisco VA Med Ctr, Dept Geriatr, San Francisco, CA USA. [Haight, Thaddeus J.; Tager, Ira B.] Univ Calif Berkeley, Dept Epidemiol & Biostat, Berkeley, CA 94720 USA. [Carlson, Michelle C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Carlson, Michelle C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kuller, Lewis H.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM deborah.barnes@ucsf.edu FU National Institutes of Health, National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01 AG15928-02]; Flight Attendants Medical Research Institute; K01 Career Development Award [K01 AG024069] FX This work was supported by the National Institutes of Health (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133 and grant U01 HL080295 from the National Heart, Lung, and Blood Institute, with an additional contribution from the National Institute of Neurological Disorders and Stroke. The Cardiovascular Health Cognition Study was supported by a grant from the National Institute on Aging (R01 AG15928-02). Additional support for this study was provided by the Flight Attendants Medical Research Institute. Dr. Barnes was supported in part by a K01 Career Development Award (K01 AG024069). NR 49 TC 22 Z9 24 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2010 VL 171 IS 3 BP 292 EP 302 DI 10.1093/aje/kwp376 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 547DN UT WOS:000273866000005 PM 20051462 ER PT J AU Saad, RJ Rao, SSC Koch, KL Kuo, B Parkman, HP McCallum, RW Sitrin, MD Wilding, GE Semler, JR Chey, WD AF Saad, Richard J. Rao, Satish S. C. Koch, Kenneth L. Kuo, Braden Parkman, Henry P. McCallum, Richard W. Sitrin, Michael D. Wilding, Gregory E. Semler, Jack R. Chey, William D. TI Do Stool Form and Frequency Correlate With Whole-Gut and Colonic Transit? Results From a Multicenter Study in Constipated Individuals and Healthy Controls SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FUNCTIONAL BOWEL DISORDERS; TIME; POPULATION; QUESTIONNAIRE; PATTERNS; CAPSULE; SCALE; GUIDE; TESTS AB OBJECTIVES: Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults. METHODS: A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis. RESULTS: In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r = -0.61, P < 0.0001) or ROM (-0.45, P = 0.0016), as well as colonic transit measured by WMC (-0.62, P < 0.0001). A Bristol stool form value < 3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with < 3 bowel movements per week. CONCLUSIONS: Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency. C1 [Saad, Richard J.; Chey, William D.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Rao, Satish S. C.] Univ Iowa, Iowa City, IA USA. [Koch, Kenneth L.] Wake Forest Univ, Gastroenterol Sect, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Kuo, Braden] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Parkman, Henry P.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [McCallum, Richard W.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Sitrin, Michael D.; Wilding, Gregory E.] SUNY Buffalo, Buffalo, NY 14260 USA. [Semler, Jack R.] SmartPill Corp, Buffalo, NY USA. RP Saad, RJ (reprint author), Univ Michigan, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rsaad@umich.edu FU SmartPill Corporation, Buffalo, NY FX The clinical trial of the WMC from which this post hoc analysis was performed was supported by the SmartPill Corporation, Buffalo, NY. NR 29 TC 62 Z9 63 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2010 VL 105 IS 2 BP 403 EP 411 DI 10.1038/ajg.2009.612 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 554RP UT WOS:000274452400022 PM 19888202 ER PT J AU Ogino, S Nosho, K Irahara, N Shima, K Baba, Y Kirkner, GJ Mino-Kenudson, M Giovannucci, EL Meyerhardt, JA Fuchs, CS AF Ogino, Shuji Nosho, Katsuhiko Irahara, Natsumi Shima, Kaori Baba, Yoshifumi Kirkner, Gregory J. Mino-Kenudson, Mari Giovannucci, Edward L. Meyerhardt, Jeffrey A. Fuchs, Charles S. TI Negative Lymph Node Count Is Associated With Survival of Colorectal Cancer Patients, Independent of Tumoral Molecular Alterations and Lymphocytic Reaction SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; POSITIVE COLON-CANCER; MICROSATELLITE INSTABILITY; LINE-1 HYPOMETHYLATION; MINIMUM NUMBER; BRAF MUTATION; RATIO; PROGNOSIS; CIMP AB OBJECTIVES: The number of recovered lymph nodes is associated with good prognosis among colon cancer patients undergoing surgical resection. However, little has been known on prognostic significance of lymph node count after adjusting for host immune response to tumor and tumoral molecular alterations, both of which are associated with the lymph node count and patient survival. METHODS: Among 716 colorectal cancers (stages 1-4) in two independent prospective cohorts, we examined patient survival in relation to the negative lymph node count and lymph node ratio (LNR; positive to total lymph node counts). Cox proportional hazard models were used to compute hazard ratio of deaths, adjusted for patient, specimen, and tumoral characteristics, including lymphocytic reactions, KRAS and BRAF mutations, p53 expression, microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and LINE-1 methylation. RESULTS: Compared with patients with 0-3 negative lymph nodes, patients with 7-12 and >= 13 negative nodes experienced a significant reduction in cancer-specific and overall mortality in Kaplan-Meier analysis (log-rank P < 0.0001), univariate Cox regression (P trend < 0.0001), and multivariate analysis (P trend < 0.0003), independent of potential confounders examined. The benefit associated with the negative node count was apparent across all stages, although the effect was significantly greater in stages 1-2 than stages 3-4 (P(interaction) = 0.002). In both stage 3 and stage 4, smaller LNR was associated with improved survival (log-rank P < 0.0001). CONCLUSIONS: The negative lymph node count is associated with improved survival of colorectal cancer patients, independent of lymphocytic reactions to tumor and tumoral molecular features including MSI, CIMP, LINE-1 hypomethylation and BRAF mutation. C1 [Ogino, Shuji; Nosho, Katsuhiko; Irahara, Natsumi; Shima, Kaori; Baba, Yoshifumi; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji; Nosho, Katsuhiko; Irahara, Natsumi; Shima, Kaori; Baba, Yoshifumi; Kirkner, Gregory J.; Mino-Kenudson, Mari; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Mol Oncol Pathol, Dana Farber Canc Inst,Med Sch, 44 Binney St,Room JF 215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science FX This work was supported by the US National Institutes of Health (P01 CA87969 to S. Hankinson, P01 CA55075 to W. Willett, P50 CA127003 to C. S. F., and K07 CA122826 to S. O.) and in part by the Bennett Family Fund and the Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA). K. N. was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or NIH. 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 51 TC 41 Z9 44 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2010 VL 105 IS 2 BP 420 EP 433 DI 10.1038/ajg.2009.578 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 554RP UT WOS:000274452400024 PM 19809407 ER PT J AU Papachristou, GI Muddana, V Yadav, D O'Connell, M Sanders, MK Slivka, A Whitcomb, DC AF Papachristou, Georgios I. Muddana, Venkata Yadav, Dhiraj O'Connell, Michael Sanders, Michael K. Slivka, Adam Whitcomb, David C. TI Comparison of BISAP, Ranson's, APACHE-II, and CTSI Scores in Predicting Organ Failure, Complications, and Mortality in Acute Pancreatitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY RESPONSE; SEVERITY; DYSFUNCTION; MARKERS AB OBJECTIVES: Identification of patients at risk for severe disease early in the course of acute pancreatitis (AP) is an important step to guiding management and improving outcomes. A new prognostic scoring system, the bedside index for severity in AP (BISAP), has been proposed as an accurate method for early identification of patients at risk for in-hospital mortality. The aim of this study was to compare BISAP (blood urea nitrogen > 25 mg/dl, impaired mental status, systemic inflammatory response syndrome (SIRS), age > 60 years, and pleural effusions) with the "traditional" multifactorial scoring systems: Ranson's, Acute Physiology and Chronic Health Examination (APACHE)-II, and computed tomography severity index (CTSI) in predicting severity, pancreatic necrosis (PNec), and mortality in a prospective cohort of patients with AP. METHODS: Extensive demographic, radiographic, and laboratory data from consecutive patients with AP admitted or transferred to our institution was collected between June 2003 and September 2007. The BISAP and APACHE-II scores were calculated using data from the first 24 h from admission. Predictive accuracy of the scoring systems was measured by the area under the receiver-operating curve (AUC). RESULTS: There were 185 patients with AP (mean age 51.7, 51% males), of which 73% underwent contrast-enhanced CT scan. Forty patients developed organ failure and were classified as severe AP (SAP; 22%). Thirty-six developed PNec (19%), and 7 died (mortality 3.8%). The number of patients with a BISAP score of >= 3 was 26; Ranson's = 3 was 47, APACHE-II = 8 was 66, and CTSI = 3 was 59. Of the seven patients that died, one had a BISAP score of 1, two had a score of 2, and four had a score of 3. AUCs for BISAP, Ranson's, APACHE-II, and CTSI in predicting SAP are 0.81 (confidence interval (CI) 0.74-0.87), 0.94 (CI 0.89-0.97), 0.78 (CI 0.71-0.84), and 0.84 (CI 0.76-0.89), respectively. CONCLUSIONS: We confirmed that the BISAP score is an accurate means for risk stratification in patients with AP. Its components are clinically relevant and easy to obtain. The prognostic accuracy of BISAP is similar to those of the other scoring systems. We conclude that simple scoring systems may have reached their maximal utility and novel models are needed to further improve predictive accuracy. C1 [Papachristou, Georgios I.; Muddana, Venkata; Yadav, Dhiraj; O'Connell, Michael; Sanders, Michael K.; Slivka, Adam; Whitcomb, David C.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Dept Med, Pittsburgh, PA USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Dept Med, Pittsburgh, PA USA. [Whitcomb, David C.] Univ Pittsburgh, Dept Cell Biol & Physiol, Sch Med, Pittsburgh, PA USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), UPMC Presbyterian, Dept Med, M2 C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM papachri@pitt.edu FU A Stars and Stripes Healthcare Network FX This work was supported by the VA Stars and Stripes Healthcare Network 2007 Competitive Pilot Project Fund (GIP). NR 23 TC 122 Z9 150 U1 0 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2010 VL 105 IS 2 BP 435 EP 441 DI 10.1038/ajg.2009.622 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 554RP UT WOS:000274452400025 PM 19861954 ER PT J AU Singh, H Petersen, LA El-Serag, HB AF Singh, Hardeep Petersen, Laura A. El-Serag, Hashem B. TI A Paradigm Shift Is Required to Facilitate Recognition of Iron Deficiency Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID COMMUNICATION C1 [Singh, Hardeep; Petersen, Laura A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Laura A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. RP Singh, H (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston VA HSR&D Ctr Excellence, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hardeeps@bcm.edu NR 3 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2010 VL 105 IS 2 BP 470 EP 470 DI 10.1038/ajg.2009.595 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 554RP UT WOS:000274452400034 ER PT J AU Hanlon, JT AF Hanlon, Joseph T. TI Perspective: Is Pharmacy Ready for the Baby Boomers? SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Editorial Material ID EDUCATION; CARE C1 [Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Med, Sch Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu FU AHRQ HHS [R01 HS017695]; NIA NIH HHS [K07AG033174, P30AG024827, P30 AG024827, R01AG027017, T32 AG021885, 3U01AG012553-15A1S1, R01AG034056]; NIMH NIH HHS [R34 MH082682]; NINR NIH HHS [R01 NR010135] NR 14 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD FEB PY 2010 VL 8 IS 1 BP 1 EP 3 DI 10.1016/j.amjopharm.2010.02.001 PG 3 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 563HL UT WOS:000275118700001 PM 20226389 ER PT J AU Fung, HB Monteagudo-Chu, MO AF Fung, Horatio B. Monteagudo-Chu, Maricelle O. TI Community-Acquired Pneumonia in the Elderly SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Review DE community-acquired pneumonia; pneumonia; pneumonia prevention; elderly ID RESPIRATORY-TRACT INFECTIONS; RISK-FACTORS; ASPIRATION PNEUMONIA; OLDER-ADULTS; HOSPITALIZED-PATIENTS; CAUSATIVE ORGANISMS; IMPROVING OUTCOMES; ACE-INHIBITORS; SWITCH THERAPY; POPULATION AB Background: Community-acquired pneumonia (CAP) is a frequent cause of hospitalization and death among the elderly. Objective: This article reviews information on CAP among the elderly, including age-related changes, predisposing risk factors, causes, treatment strategies, and prevention. Methods: Searches of MEDLINE (January 1990-November 2009), International Pharmaceutical Abstracts (January 1990-November 2009), and Google Scholar were conducted using the terms community-acquired pneumonia, pneumonia, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Studies that reported diagnostic criteria as well as the treatment outcomes achieved in adult patients with CAP were selected for this review. Results: Three practice guidelines, 5 reviews, and 43 Studies on CAP in the elderly were identified in the literature search. Based on those publications, risk factors that predispose the elderly to pneumonia include comorbid conditions, poor functional and nutritional status, consumption of alcohol, and smoking. The clinical presentation of pneumonia in the elderly (>= 65 years of age) may be Subtle, lacking the typical acute symptoms (fever, cough, dyspnea and purulent Sputum) observed in younger adults. Pneumonia should be suspected in all elderly patients who have fever, altered mental status, or a sudden decline in functional status, with or without lower respiratory tract symptoms such as cough, purulent sputum, and dyspnea. Treatment of CAP in the elderly should be guided by the latest recommendations of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS), along with consideration of local rates and patterns of antimicrobial resistance, as well as individual patient risk factors for acquiring less common or more resistant pathogens. Recommended empiric antimicrobial regimens generally consist of either a beta-lactam Plus a macrolide or a respiratory fluoroquinolone alone. Adherence to the IDSA/ATS guidelines has been found to improve in-hospital mortality (adherence vs nonadherence, 8%; 95% CI, 7%-10% vs 17%; 95% CI, 14%-20%; P < 0.01), length of hospital stay (8 days; interquartile range [IQR], 5-15 vs 10 days; IQR, 6-24 days, respectively; P < 0.01), and time to clinical stability in elderly patients with CAP (percentage of stable patients by day 7, 71%; 95% CI, 68%-74% vs 57%; 95% CI, 53%-61%, respectively; P < 0.01). All elderly patients should be vaccinated against pneumococcal disease and influenza based on recommendations from the Centers for Disease Control and Prevention. Lifestyle modifications and nutritional support are also important elements in the prevention of pneumonia in the elderly. Conclusion: Adherence to established guidelines, along with customization of antimicrobial therapy based on local rates and patterns of resistance and patient-specific risk factors, likely will improve the treatment outcome of elderly patients with CAR (Am J Geriatr Pharmacother. 2010;8:47-62) (C) 2010 Excerpta Medica Inc. C1 [Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Serv Pharm, Bronx, NY 10468 USA. [Monteagudo-Chu, Maricelle O.] Kingsbrook Jewish Med Ctr, Dept Pharm, Brooklyn, NY USA. RP Fung, HB (reprint author), James J Peters Vet Affairs Med Ctr, Serv Pharm, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM horatio.fung@va.gov NR 76 TC 28 Z9 35 U1 1 U2 11 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD FEB PY 2010 VL 8 IS 1 BP 47 EP 62 DI 10.1016/j.amjopharm.2010.01.003 PG 16 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 563HL UT WOS:000275118700004 PM 20226392 ER PT J AU Marcum, ZA Handler, SM Boyce, R Gellad, W Hanlon, JT AF Marcum, Zachary A. Handler, Steven M. Boyce, Richard Gellad, Walid Hanlon, Joseph T. TI Medication Misadventures in the Elderly: A Year in Review SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY LA English DT Review DE medication errors; medication adherence; monitoring; adverse drug events; aged; computerized physician order entry ID INAPPROPRIATE DRUG-USE; OLDER-ADULTS; PREDICTIVE-VALIDITY; SAFETY ALERTS; HOSPITALIZATION; DISCREPANCIES; ADHERENCE; RISK; CARE; ASSOCIATION AB Objective: This paper reviews recent articles examining medication misadventures that can be defined as medication errors and adverse drug events in the elderly. Methods: MEDLINE and International Pharmaceutical Abstracts were searched for articles published in English in 2009 using a combination of the terms medication errors, medication adherence, suboptimal prescribing, monitoring, adverse drug events, adverse drug withdrawal events, therapeutic failure, and aged. A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify, additional publications. Those studies that described unique approaches to evaluating medication misadventures in the elderly were included in the review. Results: The search identified 5 unique Studies relating to medication misadventures in the elderly. A cross-sectional Study found that a new 8-item paper-and-pencil adherence survey-the Morisky Medication Adherence Scale-was significantly associated with antihypertensive drug pharmacy refill adherence (P < 0.05). A cross-sectional study of medication discrepancies that occurred during transition from the hospital to a nursing home found discrepancies in almost 75% of patients. A randomized controlled trial of a computer-generated decision Support intervention to reduce potentially inappropriate prescribing in an emergency department found that the intervention was associated with a significant reduction in prescriptions for such medications (P = 0.02). One study found that patients who were taking digoxin and had been hospitalized during the previous 2 months were at significantly increased risk for additional hospitalizations due to digoxin toxicity. A survey study of Medicare beneficiaries found that use of multiple types of inappropriate medications was a risk factor for self-reported adverse drug events, independent of the number of medications taken. Conclusion: Data from these recently published studies could be used to guide the development and evaluation of quality improvement, research, or clinical practice initiatives. (Am J Geriatr Pharmacother. 2010;8:77-85) (C) 2010 Excerpta Medica Inc. C1 [Marcum, Zachary A.; Handler, Steven M.; Gellad, Walid; Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Handler, Steven M.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Handler, Steven M.; Boyce, Richard] Univ Pittsburgh, Dept Biomed Informat, Sch Med, Pittsburgh, PA 15213 USA. [Gellad, Walid; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Med, Sch Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu OI Handler, Steven/0000-0002-3940-3224 FU National Institute of Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695]; Veterans Affairs Health Services Research [HR-06-062]; National Institutes of Health Roadmap Multidisciplinary Clinical Research Career Development Award [K12 RR023267] FX This study was supported by National Institute of Aging grants (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), an Agency for Healthcare Research and Quality grant (R01 HS017695), a Veterans Affairs Health Services Research grant (HR-06-062), and a National Institutes of Health Roadmap Multidisciplinary Clinical Research Career Development Award grant (K12 RR023267). Dr. Hanlon is Co-Editor-in-Clilef of The American Journal of Geriatric Pharmacotherapy. The authors have indicated that they have no other conflicts of interest regarding the content of this article. NR 30 TC 10 Z9 12 U1 1 U2 13 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1543-5946 J9 AM J GERIATR PHARMAC JI Am. J. Geriatr. Pharmacother. PD FEB PY 2010 VL 8 IS 1 BP 77 EP 85 DI 10.1016/j.amjopharm.2010.02.002 PG 9 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 563HL UT WOS:000275118700007 PM 20226395 ER PT J AU Petrie, JL Segal, AR AF Petrie, Jennifer L. Segal, Alissa R. TI Clinical pharmacy services provided to asthma patients in a school-based clinic SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID EDUCATION; CHILDREN; PROGRAM C1 [Petrie, Jennifer L.] Univ Wyoming, Sch Pharm, Laramie, WY 82071 USA. [Segal, Alissa R.] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. [Segal, Alissa R.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Petrie, JL (reprint author), Univ Wyoming, Sch Pharm, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jpetrie@uwyo.edu NR 12 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 1 PY 2010 VL 67 IS 3 BP 185 EP + DI 10.2146/ajhp080616 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 549JW UT WOS:000274045400008 PM 20101059 ER PT J AU Lane, AA Van Cott, EM Dey, BR AF Lane, Andrew A. Van Cott, Elizabeth M. Dey, Bimalangshu R. TI von Willebrand disease type 2N: Uncovering a congenital bleeding disorder in a patient with hepatitis C, cirrhosis, and coagulopathy SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID FACTOR-VIII; PATHOPHYSIOLOGY; BINDING C1 [Lane, Andrew A.; Dey, Bimalangshu R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Dey, BR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, 55 Fruit St, Boston, MA 02114 USA. EM bdey@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2010 VL 85 IS 2 BP 134 EP 135 DI 10.1002/ajh.21590 PG 2 WC Hematology SC Hematology GA 550WD UT WOS:000274162500014 PM 20095032 ER PT J AU Grace, RF Su, H Sena, L Poussaint, TY Heeney, MM Gutierrez, A AF Grace, Rachael F. Su, Henry Sena, Laureen Poussaint, Tina Young Heeney, Matthew M. Gutierrez, Alejandro TI Resolution of cerebral artery stenosis in a child with sickle cell anemia treated with hydroxyurea SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID TRANSCRANIAL DOPPLER ULTRASONOGRAPHY; RECURRENT STROKE; DISEASE; PREVENTION; TRANSFUSIONS; TCD; VASCULOPATHY; SONOGRAPHY; THERAPY; RISK C1 [Grace, Rachael F.; Heeney, Matthew M.; Gutierrez, Alejandro] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grace, Rachael F.; Heeney, Matthew M.; Gutierrez, Alejandro] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Su, Henry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sena, Laureen; Poussaint, Tina Young] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Gutierrez, A (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alejandro_gutierrez@dfci.harvard.edu RI Heeney, Matthew/J-6838-2015; OI Heeney, Matthew/0000-0002-1104-6843; Grace, Fergal/0000-0002-3144-5999; Gutierrez, Alejandro/0000-0002-0249-9007 NR 28 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2010 VL 85 IS 2 BP 135 EP 137 DI 10.1002/ajh.21596 PG 3 WC Hematology SC Hematology GA 550WD UT WOS:000274162500015 PM 20052745 ER PT J AU Deming, D Silverman, E AF Deming, Dustin Silverman, Elizabeth TI Pasteurella multocida tracheobronchitis in a patient with CLL on rituximab SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; LYMPHOMA; SEPSIS C1 [Deming, Dustin; Silverman, Elizabeth] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Silverman, Elizabeth] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Hematol Oncol Sect, Madison, WI USA. RP Deming, D (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53706 USA. NR 11 TC 2 Z9 2 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2010 VL 85 IS 2 BP 144 EP 145 DI 10.1002/ajh.21592 PG 2 WC Hematology SC Hematology GA 550WD UT WOS:000274162500019 PM 20033893 ER PT J AU Valente, S Saunders, J AF Valente, Sharon Saunders, Judith TI Psychiatric Nurses' Expertise, Interest in End-of-Life Care, and Requests for Continuing Education on End of Life SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE end-of-life; psychiatric nursing skills; continuing education ID PALLIATIVE CARE; NEEDS AB Background: The time before dying can be extremely challenging and stressful. Gaps in end-of-life care include inadequate communication, education about end-of-life options, symptom control, and management of common mental illnesses (eg, mood disorders, dementia), and death anxiety. Psychiatric nurses are in a pivotal position to help address these gaps and improve end-of-life care. Psychiatric nurses can facilitate communication about end of life, educate patients about options, and provide consultation, assessment, and management of common psychosocial needs (eg, mood disorders, grief, and loss). Objective: This survey examined psychiatric nurses' perspectives of their skills, knowledge, expertise, continuing education needs, and recommendations for the role of the psychiatric nurse. Study design: Using a descriptive design, we surveyed a convenience sample of psychiatric nurses from the American Psychiatric Nurses Association. Results: Psychiatric nurses reported they were skilled in discussions of difficult topics, evaluation of mental status, and assessment and management of mood disorders, grief, and suicide risk. However, nurses asked for continuing education in focusing these skills for end of life, knowing the needs of the dying patient, and differentiating depression and dementia at end of life. Requests for continuing education on end-of-life care included issues about how to apply these psychiatric skills and knowledge to the dying patient and their families. Conclusions: Psychiatric nurses have skills and knowledge to reduce the gaps in end-of-life care. Many request continuing education to assist them to expand and focus their knowledge to use their psychosocial skills and to develop a specialty area in end-of-life care.. C1 [Valente, Sharon] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Saunders, Judith] Vet Affairs Greater Los Angeles Healthcare Syst, Pasadena, CA USA. RP Valente, S (reprint author), 346 N Bowling Green Way, Los Angeles, CA 90049 USA. EM sharonvalente725@hotmail.com NR 20 TC 3 Z9 3 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD FEB-MAR PY 2010 VL 27 IS 1 BP 24 EP 30 DI 10.1177/1049909109341873 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551GA UT WOS:000274193800004 PM 19789391 ER PT J AU Weiner, DE Watnick, SG AF Weiner, Daniel E. Watnick, Suzanne G. TI The 2009 Proposed Rule for Prospective ESRD Payment: Historical Perspectives and Public Policies-Bundle Up! SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; RENAL-DISEASE PATIENTS; UNITED-STATES; DIALYSIS; HEMODIALYSIS; MEDICARE; QUALITY; HEALTH; LIFE C1 [Weiner, Daniel E.] Tufts Med Ctr, Boston, MA 02111 USA. [Watnick, Suzanne G.] Portland VA Med Ctr, Portland, OR USA. RP Weiner, DE (reprint author), Tufts Med Ctr, 800 Washington St,Box 391, Boston, MA 02111 USA. EM dweiner@tuftsmedicalcenter.org NR 22 TC 5 Z9 6 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2010 VL 55 IS 2 BP 217 EP 222 DI 10.1053/j.ajkd.2009.12.005 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 555TA UT WOS:000274537000006 PM 20116682 ER PT J AU Fischer, MJ Stroupe, KT Kaufman, JS O'Hare, AM Browning, MM Huo, ZP Hynes, DM AF Fischer, Michael J. Stroupe, Kevin T. Kaufman, James S. O'Hare, Ann M. Browning, Margaret M. Huo, Zhiping Hynes, Denise M. TI Predialysis Nephrology Care Among Older Veterans Using Department of Veterans Affairs or Medicare-Covered Services SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CHRONIC KIDNEY-DISEASE; RENAL REPLACEMENT THERAPY; PRE-ESRD CARE; HEALTH-CARE; PATIENT OUTCOMES; REFERRED LATE; ESTIMATED GFR; MORTALITY; PREDICTORS; CONTINUITY AB Objective: To examine the effect of exclusive and dual use of Department of Veterans Affairs (VA) and Medicare healthcare systems on outpatient predialysis nephrology care. Study Design: Retrospective cohort study. Methods: Receipt, timeliness, and intensity of predialysis nephrology care were evaluated among 8033 veterans who initiated dialysis in 2000 and 2001 and were eligible for both VA and Medicare coverage in the 12 months preceding dialysis initiation. Propensity scores were incorporated into analyses to minimize potential selection bias from nonrandom veteran allocation to healthcare systems. Results: Among the cohort, 17.4% were users of VA services only (VA-only users), 38.5% were users of Medicare-covered services only (Medicare-only users), and 44.1% were users of both VA and Medicare-covered services (dual users). Sixty-six percent of VA-only and dual users and 58.1% of Medicare-only users received predialysis nephrology care. Compared with Medicare-only users, dual users were more likely (risk ratio [RR], 1.12; 95% confidence interval [CI], 1.07-1.17) and VA-only users were as likely (RR, 0.98; 95% CI, 0.88-1.08) to have received predialysis nephrology care. Compared with Medicare-only use, VA-only use (RR, 0.63; 95% CI, 0.50-0.81) and dual use (RR, 0.78; 95% CI, 0.70-0.88) were associated with a lower likelihood of late nephrology care (< 3 months before dialysis initiation). Conclusions: More than one-third of older veterans initiating dialysis do not receive nephrology care beforehand. Dual use of VA and Medicare-covered services was associated with greater receipt and favorable timeliness of predialysis nephrology care, while use of only Medicare-covered services was associated with late predialysis nephrology care. Further studies to identify reasons for system-level variations in access to predialysis nephrology care may assist in identifying opportunities for improvement. (Am J Manag Care. 2010; 16(2): e57-e66) C1 [Fischer, Michael J.; Stroupe, Kevin T.; Browning, Margaret M.; Huo, Zhiping; Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Fischer, Michael J.] Jesse Brown VA Med Ctr, Div Nephrol, Chicago, IL USA. [Fischer, Michael J.] Univ Illinois, Div Nephrol, Chicago, IL USA. [Hynes, Denise M.] Univ Illinois, Div Hlth Promot Res, Chicago, IL USA. [Stroupe, Kevin T.] Northwestern Univ, Div Gen Internal Med, Chicago, IL 60611 USA. [Kaufman, James S.] Boston VA Med Ctr, Div Nephrol, Boston, MA USA. [Kaufman, James S.] Boston Univ, Boston, MA 02215 USA. [O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA USA. RP Fischer, MJ (reprint author), Edward Hines Jr VA Med Ctr, Ctr Management Complex Chron Care, 5000 S 5th Ave,151H, Hines, IL 60141 USA. EM fischerm@uic.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 02-244, IIR 20-016]; National Kidney Foundation of Illinois; National Institutes of Health (NIH) [K23AG28980] FX The authors received funding support for this research project from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (VA HSR&D IIR 02-244 and IIR 20-016 to KTS, MMB, and DMH; VA HSR&D Research Career Scientist Award to DMH; and VA HSR&D Career Development Award to MJF); from the National Kidney Foundation of Illinois (to MJF); and from the National Institutes of Health (NIH K23AG28980 to AMO). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or Health Services Research and Development Service. NR 52 TC 10 Z9 10 U1 0 U2 2 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2010 VL 16 IS 2 BP E57 EP E66 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 556KW UT WOS:000274590800012 PM 20148611 ER PT J AU Epstein, AJ Rosenquist, JN AF Epstein, Andrew J. Rosenquist, J. Niels TI Tell Me Something New: Report Cards and the Referring Physician SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID SURGERY C1 [Epstein, Andrew J.] Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06520 USA. [Epstein, Andrew J.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Rosenquist, J. Niels] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Rosenquist, J. Niels] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Epstein, AJ (reprint author), Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06520 USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2010 VL 123 IS 2 BP 99 EP 100 DI 10.1016/j.amjmed.2009.08.010 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 553DO UT WOS:000274346200002 PM 20103013 ER PT J AU Robson, CD Rahbar, R Vargas, SO Marcus, KJ Mack, JW Licameli, GR Grier, HE AF Robson, C. D. Rahbar, R. Vargas, S. O. Marcus, K. J. Mack, J. W. Licameli, G. R. Grier, H. E. TI Sinonasal and Laryngeal Carcinoma in Children: Correlation of Imaging Characteristics with Clinicopathologic and Cytogenetic Features SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID TUMORS; TRACT; NECK; HEAD AB BACKGROUND AND PURPOSE: Pediatric upper airway carcinoma is uncommon, symptoms are nonspecific, and diagnosis is often delayed. In this study, we describe the imaging, cytogenetics, and clinical courses of 4 patients with pediatric upper airway carcinoma. MATERIALS AND METHODS: Four patients with upper airway carcinoma were identified during a 2.5-year period. CT (n = 4) and MR imaging (n = 3) studies, tumor histopathologic features and cytogenetics, patient treatment, and clinical course were reviewed. RESULTS: Patients were aged 12 to 15 years. One tumor involved the larynx with poorly defined margins and heterogeneous enhancement; 1 heterogeneously enhancing tumor involved the epiglottis with necrotic cervical lymphadenopathy. There were 2 enhancing sinonasal tumors with bony destruction in 1 tumor. Tumors had a relatively short relaxation time on FSEIR MR imaging. Histopathologic examination revealed poorly differentiated squamous cell carcinoma (n = 3) and well-differentiated squamous cell carcinoma (n = 1). Cytogenetic analysis revealed chromosomal abnormalities in 3 tumors: 2 showed a chromosomal translocation t(15;19), and 1 showed a chromosomal translocation t(1;5) and loss of a portion of chromosome 22q. Results of in situ hybridization for EBV were negative (n = 3). Treatment included tumor resection (n = 2), chemotherapy (n = 4), and radiation therapy (n = 3). Patients with t(15;19) died months after diagnosis. Two patients were alive at 8-year follow-up. CONCLUSIONS: Childhood carcinoma of the upper airway is uncommon but should be considered in the diagnosis of upper airway tumors that display aggressive imaging characteristics. Carcinoma with t(15;19) is rare but has been reported, usually in young patients with midline carcinoma of the neck or mediastinum, with a rapidly fatal course. C1 [Robson, C. D.] Childrens Hosp, Neuroradiol Div, Dept Radiol, Boston, MA 02115 USA. [Rahbar, R.; Licameli, G. R.] Childrens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. [Vargas, S. O.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Marcus, K. J.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Mack, J. W.; Grier, H. E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Robson, C. D.; Rahbar, R.; Vargas, S. O.; Marcus, K. J.; Mack, J. W.; Licameli, G. R.; Grier, H. E.] Harvard Univ, Sch Med, Boston, MA USA. RP Robson, CD (reprint author), Childrens Hosp, Neuroradiol Div, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM caroline.robson@tch.harvard.edu OI Robson, Caroline/0000-0001-5592-249X NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2010 VL 31 IS 2 BP 257 EP 261 DI 10.3174/ajnr.A1800 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 563NX UT WOS:000275140500011 PM 19779003 ER PT J AU Wei, SC Ulmer, S Lev, MH Pomerantz, SR Gonzalez, RG Henson, JW AF Wei, S. C. Ulmer, S. Lev, M. H. Pomerantz, S. R. Gonzalez, R. G. Henson, J. W. TI Value of Coronal Reformations in the CT Evaluation of Acute Head Trauma SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INJURY AB BACKGROUND AND PURPOSE: Routine axial CT images may not be ideally suited for detecting ICH in transversely oriented locations such as the floor of the anterior and middle cranial fossas and vertex. This study was performed to evaluate whether coronal reformations improve detection of ICH in NCCT performed for head trauma. MATERIALS AND METHODS: All patients undergoing a first NCCT in the ED for evaluation of head trauma were included prospectively during a 6-month interval. NCCT images were reconstructed into standard 5-mm axial datasets and were also reformatted into coronal datasets of 5-mm sections and 2.5-mm intervals. Thirty-two of 213 (15%) scans were interpreted as showing traumatic ICH. These cases were interspersed with 30 studies without ICH. Cases were reviewed for the presence and location of ICH by 2 staff neuroradiologists. RESULTS: Of 213 patients, 32 NCCTs demonstrated ICH (a total of 104 foci). Fifteen of 104 (14%) ICHs (8 patients) were detected solely on coronal images. Locations included the floor of the anterior and middle cranial fossas, vertex, corpus callosum, falx, tentorium, and occipital convexity. Coronal reformations allowed exclusion of suspicious findings on axial images in 14 instances (7 patients). Coronal images aided interpretation in 29/104 (28%) findings. CONCLUSIONS: Coronal reformations improve the detection of ICH over axial images alone, especially for lesions that lie in the axial plane immediately adjacent to bony surfaces. The use of coronal reformations should be considered in the routine interpretation of head CT examinations performed for the evaluation of head trauma. C1 [Wei, S. C.; Ulmer, S.; Lev, M. H.; Pomerantz, S. R.; Gonzalez, R. G.; Henson, J. W.] Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. [Henson, J. W.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM mlev@partners.org; john.henson@swedish.org NR 12 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 2010 VL 31 IS 2 BP 334 EP 339 DI 10.3174/ajnr.A1824 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 563NX UT WOS:000275140500026 PM 19797789 ER PT J AU Joffe, H Petrillo, L Viguera, A Koukopoulos, A Silver-Heilman, K Farrell, A Yu, G Silver, M Cohen, LS AF Joffe, Hadine Petrillo, Laura Viguera, Adele Koukopoulos, Alexia Silver-Heilman, Kate Farrell, Adriann Yu, Gary Silver, Michael Cohen, Lee S. TI Eszopiclone improves insomnia and depressive and anxious symptoms in perimenopausal and postmenopausal women with hot flashes: a randomized, double-blinded, placebo-controlled crossover trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE eszopiclone; insomnia; menopause; randomized clinical trial; vasomotor symptoms ID QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; MENOPAUSAL TRANSITION; NIGHTLY TREATMENT; SLEEP; EFFICACY; QUESTIONNAIRE; DISABILITY; DISORDER; HORMONES AB OBJECTIVE: Menopause-associated insomnia is commonly associated with other symptoms (hot flashes, depression, anxiety). Given frequent symptom cooccurrence, therapies targeting sleep may provide an important approach to treatment during midlife. STUDY DESIGN: Peri/postmenopausal women (40-65 years old) with sleep-onset and/or sleep-maintenance insomnia cooccurring with hot flashes and depressive and/or anxiety symptoms were randomized to eszopiclone 3 mg orally or placebo in a double-blinded, crossover 11 week trial. Changes in the Insomnia Severity Index (ISI) scale and secondary outcomes (diary-based sleep parameters, depression/anxiety, hot flashes, quality of life) were analyzed using repeated-measure linear models. RESULTS: Of 59 women, 46 (78%) completed the study. Eszopiclone reduced ISI scores by 8.7 +/- 1.4 more points than placebo (P < .0001). Eszopiclone improved (P < .05) all sleep parameters, depressive symptoms, anxiety symptoms, quality of life, and nighttime but not daytime hot flashes. CONCLUSION: Eszopiclone treats insomnia and cooccurring menopause-related symptoms. Our results provide evidence that hypnotic therapies may improve multiple domains of well-being during midlife. C1 [Joffe, Hadine; Petrillo, Laura; Viguera, Adele; Koukopoulos, Alexia; Silver-Heilman, Kate; Farrell, Adriann; Yu, Gary; Silver, Michael; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program,Med Sch, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program,Med Sch, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM hjoffe@partners.org FU Sepracor Inc, Marlborough, MA FX This study was supported in part by Sepracor Inc, Marlborough, MA. NR 37 TC 3 Z9 4 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2010 VL 202 IS 2 AR 171.e1 DI 10.1016/j.ajog.2009.10.868 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 549BS UT WOS:000274017000029 PM 20035910 ER PT J AU Ament, JD Stryjewski, TP Ciolino, JB Todani, A Chodosh, J Dohlman, CH AF Ament, Jared D. Stryjewski, Tomasz P. Ciolino, Joseph B. Todani, Amit Chodosh, James Dohlman, Claes H. TI Cost-Effectiveness of the Boston Keratoprosthesis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; CATARACT-SURGERY; PENETRATING KERATOPLASTY; UTILITY ANALYSIS; EFFECTIVENESS THRESHOLD; BLINDNESS; NEPAL; CHEMOPROPHYLAXIS; DECISIONS; NICE AB PURPOSE: To conduct a cost-utility analysis and determine the cost-effectiveness of the Boston Keratoprosthesis (Boston Kpro). DESIGN: Retrospective cohort study. METHODS: SETTING: The Massachusetts Eye and Ear Infirmary corneal service. PATIENTS: Inclusion required a minimum 2-year follow-up. Patients with autoimmune diseases and chemical burns were excluded. Eighty-two patients were included with various indications for surgery. INTERVENTION: The keratoprosthesis is a collar button-shaped polymethylmethacrylate (PMMA) device consisting of 2 curved plates sandwiched around a corneal donor (allo)graft. The device is assembled intraoperatively and sutured to a patient's eye after removing the diseased cornea. MAIN OUTCOME MEASURES: Average cost-effectiveness of the keratoprosthesis was determined by cost-utility analysis, using expected-value calculations and time-tradeoff utilities. The comparative effectiveness, or gain in quality-adjusted life years (QALYs), was also sought. Cost-effectiveness was compared to recently published data on penetrating keratoplasty (PK). RESULTS: A total discounted incremental QALY gain for the Boston Kpro of 0.763 correlated with a conferred QALY gain of 20.3% for the average patient. The average cost-effectiveness of the keratoprosthesis was $16 140 per QALY. CONCLUSIONS: Comparable to corneal transplantation, with a cost-effectiveness between $12 000 and $16 000 per QALY, the keratoprosthesis can be considered highly cost-effective. (Am J Ophthalmol 2010;149: 221-228. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Ament, Jared D.; Stryjewski, Tomasz P.; Ciolino, Joseph B.; Todani, Amit; Chodosh, James; Dohlman, Claes H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Ament, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jared_ament@meei.harvard.edu NR 41 TC 20 Z9 20 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2010 VL 149 IS 2 BP 221 EP 228 DI 10.1016/j.ajo.2009.08.027 PG 8 WC Ophthalmology SC Ophthalmology GA 551OU UT WOS:000274219700009 PM 19939347 ER PT J AU Treebak, JT Taylor, EB Witczak, CA An, D Toyoda, T Koh, HJ Xie, JX Feener, EP Wojtaszewski, JFP Hirshman, MF Goodyear, LJ AF Treebak, Jonas T. Taylor, Eric B. Witczak, Carol A. An, Ding Toyoda, Taro Koh, Ho-Jin Xie, Jianxin Feener, Edward P. Wojtaszewski, Jorgen F. P. Hirshman, Michael F. Goodyear, Laurie J. TI Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE mass spectrometry; AS160; glucose metabolism ID STIMULATED GLUT4 TRANSLOCATION; AS160 PHOSPHORYLATION; GLUCOSE-UPTAKE; SUBSTRATE-SPECIFICITY; AKT SUBSTRATE; INSULIN; CONTRACTION; DOMAIN; TRANSPORT; AICAR AB Treebak JT, Taylor EB, Witczak CA, An D, Toyoda T, Koh HJ, Xie J, Feener EP, Wojtaszewski JF, Hirshman MF, Goodyear LJ. Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle. Am J Physiol Cell Physiol 298: C377-C385, 2010. First published November 18, 2009; doi: 10.1152/ajpcell.00297.2009.-TBC1D4 ( also known as AS160) regulates glucose transporter 4 (GLUT4) translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of serine (S)/threonine (T) residues by upstream kinases resulting in inactivation of Rab-GTPase-activating protein (Rab-GAP) activity leading to GLUT4 mobilization. The majority of known phosphorylation sites on TBC1D4 lie within the Akt consensus motif and are phosphorylated by insulin stimulation. However, the 5'-AMP-activated protein kinase ( AMPK) and other kinases may also phosphorylate TBC1D4, and therefore we hypothesized the presence of additional phosphorylation sites. Mouse skeletal muscles were contracted or stimulated with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), and muscle lysates were subjected to mass spectrometry analyses resulting in identification of novel putative phosphorylation sites on TBC1D4. The surrounding amino acid sequence predicted that S711 would be recognized by AMPK. Using a phosphospecific antibody against S711, we found that AICAR and contraction increased S711 phosphorylation in mouse skeletal muscle, and this increase was abolished in muscle-specific AMPK alpha 2 kinase-dead transgenic mice. Exercise in human vastus lateralis muscle also increased TBC1D4 S711 phosphorylation. Recombinant AMPK, but not Akt1, Akt2, or PKC zeta, phosphorylated purified muscle TBC1D4 on S711 in vitro. Interestingly, S711 was also phosphorylated in response to insulin in an Akt2- and rapamycin-independent, but a wortmannin-sensitive, manner, suggesting this site is regulated by one or more additional upstream kinases. Despite increased S711 phosphorylation with AICAR, contraction, and insulin, mutation of S711 to alanine did not alter glucose uptake in response to these stimuli. S711 is a novel TBC1D4 phosphorylation site regulated by AMPK in skeletal muscle. C1 [Treebak, Jonas T.; Taylor, Eric B.; Witczak, Carol A.; An, Ding; Toyoda, Taro; Koh, Ho-Jin; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. [Treebak, Jonas T.; Wojtaszewski, Jorgen F. P.] Univ Copenhagen, Dept Exercise & Sport Sci, Mol Physiol Grp, Copenhagen Muscle Res Ctr, Copenhagen, Denmark. [Xie, Jianxin] Cell Signaling Technol, Danvers, MA USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Wojtaszewski, Jorgen /P-6583-2014; Treebak, Jonas/B-4521-2017 OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Treebak, Jonas/0000-0003-1488-7012 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01-AR-42238, R01-AR-45670]; Joslin Diabetes Center; Diabetes Endocrinology Research Centers (DERC) [P30-DK-36836]; Novo Nordisk Foundation; Danish Medical Research Council; Danish Diabetes Association; European Commission [LSHM-CT-2004-005272]; Individual Ruth L. Kirschstein National Research Service [F32-DK-075851]; National Institutes of Health [AR-056298]; Canadian Institutes of Health Research; Canadian Diabetes Association; American Physiological Society FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grants R01-AR-42238 and R01-AR-45670 ( L.J. Goodyear), funding from the Graetz Challenge Grant of the Joslin Diabetes Center ( L. J. Goodyear), and Diabetes Endocrinology Research Centers (DERC) Grant P30-DK-36836 ( Joslin Diabetes Center). Additional support was from the Novo Nordisk Foundation ( J. F. P. Wojtaszewski), the Danish Medical Research Council ( J. F. P. Wojtaszewski), the Danish Diabetes Association ( J. F. P. Wojtaszewski), and an integrated project (LSHM-CT-2004-005272) funded by the European Commission ( J. F. P. Wojtaszewski). E. B. Taylor was supported by an Individual Ruth L. Kirschstein National Research Service Award (F32-DK-075851), C. A. Witczak by a National Institutes of Health K99/R00 Pathway to Independence Award (AR-056298), D. An from fellowships from the Canadian Institutes of Health Research and the Canadian Diabetes Association, T. Toyoda from an American Diabetes Association Mentor-based Award ( to L. J. Goodyear), and H. J. Koh from an American Physiological Society Postdoctoral Fellowship in Physiological Genomics. NR 42 TC 41 Z9 41 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2010 VL 298 IS 2 BP C377 EP C385 DI 10.1152/ajpcell.00297.2009 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 547DP UT WOS:000273866200018 PM 19923418 ER PT J AU Sajan, MP Bandyopadhyay, G Miura, A Standaert, ML Nimal, S Longnus, SL Van Obberghen, E Hainault, I Foufelle, F Kahn, R Braun, U Leitges, M Farese, RV AF Sajan, M. P. Bandyopadhyay, G. Miura, A. Standaert, M. L. Nimal, S. Longnus, S. L. Van Obberghen, E. Hainault, I. Foufelle, F. Kahn, R. Braun, U. Leitges, M. Farese, R. V. TI AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE tissue-specific atypical PKC activation by AMPK; primacy of AMPK in muscle atypical PKC activation; redundant activation of atypical PKC during exercise ID PROTEIN-KINASE-C; SKELETAL-MUSCLE; INSULIN; ZETA; PYK2; PHOSPHATIDYLINOSITOL-3,4,5-(PO4)(3); PHOSPHORYLATION; ROSIGLITAZONE; METABOLISM; EXPRESSION AB Sajan MP, Bandyopadhyay G, Miura A, Standaert ML, Nimal S, Longnus SL, Van Obberghen E, Hainault I, Foufelle F, Kahn R, Braun U, Leitges M, Farese RV. AICAR and metformin, but not exercise, increase muscle glucose transport through AMPK-, ERK-, and PDK1-dependent activation of atypical PKC. Am J Physiol Endocrinol Metab 298: E179-E192, 2010. First published November 3, 2009; doi:10.1152/ajpendo.00392.2009.-Activators of 5'-AMP-activated protein kinase (AMPK) 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), metformin, and exercise activate atypical protein kinase C (aPKC) and ERK and stimulate glucose transport in muscle by uncertain mechanisms. Here, in cultured L6 myotubes: AICAR-and metformin-induced activation of AMPK was required for activation of aPKC and ERK; aPKC activation involved and required phosphoinositide-dependent kinase 1 (PDK1) phosphorylation of Thr410-PKC-zeta; aPKC Thr410 phosphorylation and activation also required MEK1-dependent ERK; and glucose transport effects of AICAR and metformin were inhibited by expression of dominant-negative AMPK, kinase-inactive PDK1, MEK1 inhibitors, kinase-inactive PKC-zeta, and RNA interference (RNAi)-mediated knockdown of PKC-zeta. In mice, muscle-specific aPKC (PKC-lambda) depletion by conditional gene targeting impaired AICAR-stimulated glucose disposal and stimulatory effects of both AICAR and metformin on 2-deoxyglucose/glucose uptake in muscle in vivo and AICAR stimulation of 2-[(3)H]deoxyglucose uptake in isolated extensor digitorum longus muscle; however, AMPK activation was unimpaired. In marked contrast to AICAR and metformin, treadmill exercise-induced stimulation of 2-deoxyglucose/glucose uptake was not inhibited in aPKC-knockout mice. Finally, in intact rodents, AICAR and metformin activated aPKC in muscle, but not in liver, despite activating AMPK in both tissues. The findings demonstrate that in muscle AICAR and metformin activate aPKC via sequential activation of AMPK, ERK, and PDK1 and the AMPK/ERK/PDK1/aPKC pathway is required for metformin-and AICAR-stimulated increases in glucose transport. On the other hand, although aPKC is activated by treadmill exercise, this activation is not required for exercise-induced increases in glucose transport, and therefore may be a redundant mechanism. C1 [Sajan, M. P.; Bandyopadhyay, G.; Miura, A.; Standaert, M. L.; Farese, R. V.] Univ S Florida, Coll Med, James A Haley Vet Hosp, Res Serv, Tampa, FL USA. [Longnus, S. L.; Van Obberghen, E.] Fac Med Nice, INSERM, Inst Federatif Rech 50, U145, F-06034 Nice, France. [Hainault, I.; Foufelle, F.] Univ Paris 06, INSERM, Ctr Rech Biomed Cordeliers, U671, Paris, France. [Sajan, M. P.; Bandyopadhyay, G.; Miura, A.; Standaert, M. L.; Farese, R. V.] Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. [Kahn, R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, R.] Harvard Univ, Sch Med, Boston, MA USA. [Braun, U.; Leitges, M.] Ctr Biotechnol, Oslo, Norway. [Nimal, S.; Farese, R. V.] Roskamp Inst, Sarasota, FL USA. RP Farese, RV (reprint author), James A Haley Vet Med Ctr, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM rfarese@health.usf.edu RI Farese, Robert/B-3605-2015 FU Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases [DK-38079, DK-30136] FX This work was supported by funds from the Department of Veterans Affairs Merit Review Program (R. V. Farese) and National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-38079 (R. V. Farese) and DK-30136 (C. R. Kahn). NR 28 TC 34 Z9 35 U1 1 U2 5 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 FEB PY 2010 VL 298 IS 2 BP E179 EP E192 DI 10.1152/ajpendo.00392.2009 PG 14 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 544YB UT WOS:000273695500005 PM 19887597 ER PT J AU Bradshaw, AD Baicu, CF Rentz, TJ Van Laer, AO Bonnema, DD Zile, MR AF Bradshaw, Amy D. Baicu, Catalin F. Rentz, Tyler J. Van Laer, An O. Bonnema, D. Dirk Zile, Michael R. TI Age-dependent alterations in fibrillar collagen content and myocardial diastolic function: role of SPARC in post-synthetic procollagen processing SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE secreted protein acidic and rich in cysteine; aging ID CHRONIC HEART-FAILURE; NULL MICE; MATRIX METALLOPROTEINASES; GENE-EXPRESSION; MESSENGER-RNA; DYSFUNCTION; PROTEIN; FIBROBLASTS; HYPERTENSION; ANGIOGENESIS AB Bradshaw AD, Baicu CF, Rentz TJ, Van Laer AO, Bonnema DD, Zile MR. Age-dependent alterations in fibrillar collagen content and myocardial diastolic function: role of SPARC in post-synthetic procollagen processing. Am J Physiol Heart Circ Physiol 298: H614-H622, 2010. First published December 11, 2009; doi:10.1152/ajpheart.00474.2009.-Advanced age, independent of concurrent cardiovascular disease, can be associated with increased extracellular matrix (ECM) fibrillar collagen content and abnormal diastolic function. However, the mechanisms causing this left ventricular (LV) remodeling remain incompletely defined. We hypothesized that one determinant of age-dependent remodeling is a change in the extent to which newly synthesized procollagen is processed into mature collagen fibrils. We further hypothesized that secreted protein acidic and rich in cysteine (SPARC) plays a key role in the changes in post-synthetic procollagen processing that occur in the aged myocardium. Young (3 mo old) and old (18-24 mo old) wild-type (WT) and SPARC-null mice were studied. LV collagen content was measured histologically by collagen volume fraction, collagen composition was measured by hydroxyproline assay as soluble collagen (1 M NaCl extractable) versus insoluble collagen (mature cross-linked), and collagen morphological structure was examined by scanning electron microscopy. SPARC expression was measured by immunoblot analysis. LV and myocardial structure and function were assessed using echocardiographic and papillary muscle experiments. In WT mice, advanced age increased SPARC expression, myocardial diastolic stiffness, fibrillar collagen content, and insoluble collagen. In SPARC-null mice, advanced age also increased myocardial diastolic stiffness, fibrillar collagen content, and insoluble collagen but significantly less than those seen in WT old mice. As a result, insoluble collagen and myocardial diastolic stiffness were lower in old SPARC-null mice (1.36 +/- 0.08 mg hydroxyproline/g dry wt and 0.04 +/- 0.005) than in old WT mice (1.70 +/- 0.10 mg hydroxyproline/g dry wt and 0.07 +/- 0.005, P < 0.05). In conclusion, the absence of SPARC reduced age-dependent alterations in ECM fibrillar collagen and diastolic function. These data support the hypothesis that SPARC plays a key role in post-synthetic procollagen processing and contributes to the increase in collagen content found in the aged myocardium. C1 [Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Gazes Strom Thurmond Res Bldg,114 Doughty St,Rm 2, Charleston, SC 29425 USA. EM bradshad@musc.edu FU Department of Veterans Affairs; National Heart, Lung, and Blood Institute [PO1-HL-48788] FX This work was supported by the Research Service of the Department of Veterans Affairs (to M. R. Zile and A. D. Bradshaw) and by National Heart, Lung, and Blood Institute Grant PO1-HL-48788 (to M. R. Zile). NR 49 TC 57 Z9 57 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 FEB PY 2010 VL 298 IS 2 BP H614 EP H622 DI 10.1152/ajpheart.00474.2009 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 546AW UT WOS:000273780400040 PM 20008277 ER PT J AU Chirinos, JA Segers, P Raina, A Saif, H Swillens, A Gupta, AK Townsend, R Emmi, AG Kirkpatrick, JN Keane, MG Ferrari, VA Wiegers, SE Sutton, MGSJ AF Chirinos, Julio A. Segers, Patrick Raina, Amresh Saif, Hassam Swillens, Abigail Gupta, Amit K. Townsend, Raymond Emmi, Anthony G., Jr. Kirkpatrick, James N. Keane, Martin G. Ferrari, Victor A. Wiegers, Susan E. Sutton, Martin G. St. John TI Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE arterial load; arterial compliance; wave reflections; aortic stiffness ID BLOOD-PRESSURE RESPONSES; WAVE REFLECTION; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR HEALTH; INPUT IMPEDANCE; HEART-DISEASE; HYPERTROPHY; STIFFNESS; STRESS; RISK AB Chirinos JA, Segers P, Raina A, Saif H, Swillens A, Gupta AK, Townsend R, Emmi AG, Jr., Kirkpatrick JN, Keane MG, Ferrari VA, Wiegers SE, Sutton MG. Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension. Am J Physiol Heart Circ Physiol 298: H320-H330, 2010. First published December 4, 2009; doi:10.1152/ajpheart.00334.2009.-Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P <= 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension. C1 [Chirinos, Julio A.] Philadelphia VA Med Ctr, Div Cardiol, Philadelphia, PA 19104 USA. [Chirinos, Julio A.; Raina, Amresh; Saif, Hassam; Gupta, Amit K.; Townsend, Raymond; Emmi, Anthony G., Jr.; Kirkpatrick, James N.; Keane, Martin G.; Ferrari, Victor A.; Wiegers, Susan E.; Sutton, Martin G. St. John] Univ Penn, Philadelphia, PA 19104 USA. [Segers, Patrick; Swillens, Abigail] Univ Ghent, IBiTech, B-9000 Ghent, Belgium. RP Chirinos, JA (reprint author), Philadelphia VA Med Ctr, Div Cardiol, 8B111,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM Julio.chirinos@uphs.upenn.edu RI Gupta, amit/B-3831-2012; Santana, Fabio/C-8745-2012 NR 34 TC 23 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2010 VL 298 IS 2 BP H320 EP H330 DI 10.1152/ajpheart.00334.2009 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 546AW UT WOS:000273780400005 PM 19966060 ER PT J AU Brooks, VL Mulvaney, JM Azar, AS Zhao, D Goldman, RK AF Brooks, Virginia L. Mulvaney, Julia M. Azar, Afaf S. Zhao, Ding Goldman, Robert K. TI Pregnancy impairs baroreflex control of heart rate in rats: role of insulin sensitivity SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hyperinsulinemic-euglycemic clamp; mean arterial pressure; telemetry; spontaneous baroreflex sensitivity; insulin resistance ID SYMPATHETIC-NERVE ACTIVITY; GLUCOSE CLAMP TECHNIQUE; CONSCIOUS RATS; ARTERIAL BAROREFLEX; BARORECEPTOR REFLEX; BLOOD-PRESSURE; AUTONOMIC FUNCTION; NITRIC-OXIDE; BRAIN; OXYTOCIN AB Brooks VL, Mulvaney JM, Azar AS, Zhao D, Goldman RK. Pregnancy impairs baroreflex control of heart rate in rats: role of insulin sensitivity. Am J Physiol Regul Integr Comp Physiol 298: R419-R426, 2010. First published November 25, 2009; doi:10.1152/ajpregu.00441.2009.-Recent studies in rabbits suggest that insulin resistance and reduced brain insulin contribute to impaired baroreflex control of heart rate (HR) during pregnancy; however, the mechanisms are unknown. The rat model is ideal to investigate these mechanisms because much is known about rat brain baroreflex neuro-circuitry and insulin receptor locations. However, it is unclear in rats whether pregnancy impairs the HR baroreflex or whether insulin resistance is involved. Therefore, this study tested the hypothesis that in rats pregnancy decreases HR baroreflex sensitivity (BRS) and that this decrease is related to concurrent decreases in insulin sensitivity (IS). BRS was quantified before, during, and after pregnancy using complementary methods: 1) spontaneous BRS (sBRS) derived from sequence method analysis of telemetric, continuous arterial pressure recordings; and 2) maximal BRS of complete sigmoidal baroreflex relationships. IS was measured (hyperinsulinemic euglycemic clamp) to determine whether BRS and IS change in parallel. sBRS was reduced at midgestation [pregnancy day 10 (P10)], returned to nonpregnant (NP) levels on P18, and fell again at late gestation (P20) (sBRS in ms/mmHg: NP, 1.66 +/- 0.04; P10, 1.17 +/- 0.11; P18, 1.55 +/- 0.12; P20, 1.31 +/- 0.05; n = 5; P < 0.05). Similar triphasic patterns were observed for both maximal BRS [in beats.min(-1).mmHg(-1): NP, 4.45 +/- 0.52 (n = 10); P11-12, 2.76 +/- 0.11 (n = 7); P17-18, 3.79 +/- 0.14 (n = 5); P19-20, 2.32 +/- 0.40 (n = 8); P < 0.0001] and previous and current measurements of IS (in mg glucose.kg(-1).min(-1): NP, 32 +/- 2; P19-20, 15 +/- 1; P < 0.0005). Furthermore, during pregnancy, the standard deviation (SD) of MAP increased, and the SD of HR decreased, indirectly suggesting baroreflex impairment. sBRS increased transiently during parturition, and sBRS, maximal BRS, and IS normalized 3-4 days postpartum. In conclusion, pregnancy decreases HR BRS in rats. The parallel temporal changes in BRS and IS suggest a mechanistic link. C1 [Goldman, Robert K.] Portland VA Med Ctr, Dept Surg, Portland, OR 97239 USA. [Brooks, Virginia L.; Mulvaney, Julia M.; Azar, Afaf S.; Zhao, Ding] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Goldman, RK (reprint author), Portland VA Med Ctr, Dept Surg, P3SURG,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM robert.goldman@va.gov FU National Heart, Lung, and Blood Institute [HL-088552]; American Heart Association [0750172Z]; Medical Research Foundation of Oregon FX This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-088552 and American Heart Association Grant 0750172Z, as well as a grant from the Medical Research Foundation of Oregon. NR 54 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD FEB PY 2010 VL 298 IS 2 BP R419 EP R426 DI 10.1152/ajpregu.00441.2009 PG 8 WC Physiology SC Physiology GA 547CI UT WOS:000273862700023 PM 19939977 ER PT J AU Acierno, R Hernandez, MA Amstadter, AB Resnick, HS Steve, K Muzzy, W Kilpatrick, DG AF Acierno, Ron Hernandez, Melba A. Amstadter, Ananda B. Resnick, Heidi S. Steve, Kenneth Muzzy, Wendy Kilpatrick, Dean G. TI Prevalence and Correlates of Emotional, Physical, Sexual, and Financial Abuse and Potential Neglect in the United States: The National Elder Mistreatment Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIOLENCE; ADULTS; RISK AB Objectives. We estimated prevalence and assessed correlates of emotional, physical, sexual, and financial mistreatment and potential neglect (defined as an identified need for assistance that no one was actively addressing) of adults aged 60 years or older in a randomly selected national sample. Methods. We compiled a representative sample by random digit dialing across geographic strata. We used computer-assisted telephone interviewing to standardize collection of demographic, risk factor, and mistreatment data. We subjected prevalence estimates and mistreatment correlates to logistic regression. Results. We analyzed data from 5777 respondents. One-year prevalence was 4.6% for emotional abuse, 1.6% for physical abuse, 0.6% for sexual abuse, 5.1% for potential neglect, and 5.2% for current financial abuse by a family member. One in 10 respondents reported emotional, physical, or sexual mistreatment or potential neglect in the past year. The most consistent correlates of mistreatment across abuse types were low social support and previous traumatic event exposure. Conclusions. Our data showed that abuse of the elderly is prevalent. Addressing low social support with preventive interventions could have significant public health implications. (Am J Public Health. 2010;100:292-297. doi:10.2105/AJPH.2009.163089) C1 [Acierno, Ron; Amstadter, Ananda B.; Resnick, Heidi S.; Muzzy, Wendy; Kilpatrick, Dean G.] Med Univ S Carolina, Charleston, SC USA. [Acierno, Ron] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Hernandez, Melba A.] Univ Simon Bolivar, Caracas, Venezuela. [Steve, Kenneth] Abt SRBI, New York, NY USA. RP Acierno, R (reprint author), Natl Crime Victims Res & Treatment Ctr, 67 President St,MUSC 861,2nd Floor,1OP S, Charleston, SC 29425 USA. EM acierno@musc.edu FU National Institute of Justice [2007-WG-BX-0009]; National Institute on Aging [R21AG030667] FX This study was supported primarily by the National Institute of Justice (grant 2007-WG-BX-0009) and by the National Institute on Aging (grant R21AG030667). NR 20 TC 214 Z9 228 U1 4 U2 55 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 FEB PY 2010 VL 100 IS 2 BP 292 EP 297 DI 10.2105/AJPH.2009.163089 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 554DF UT WOS:000274415000025 PM 20019303 ER PT J AU Iyer, VR Lee, SI AF Iyer, Veena R. Lee, Susanna I. TI MRI, CT, and PET/CT for Ovarian Cancer Detection and Adnexal Lesion Characterization SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE borderline tumor; endometriosis; gynecology; Krukenberg tumor; screening; staging ID POSITRON-EMISSION-TOMOGRAPHY; CORPUS LUTEAL CYST; COLOR DOPPLER; PATHOLOGICAL CORRELATION; IMAGING FINDINGS; HISTOPATHOLOGIC FINDINGS; COMPUTED-TOMOGRAPHY; SEROUS CARCINOMA; F-18-FDG UPTAKE; PREGNANT-WOMAN AB OBJECTIVE. The purpose of this article is to describe the role of MR, CT, and PET/CT in the detection of ovarian cancer and the evaluation of adnexal lesions. CONCLUSION. The goal of imaging in ovarian cancer detection is to expeditiously distinguish benign adnexal lesions from those requiring further pathologic evaluation for malignancy. For lesions indeterminate on ultrasound, MRI increases the specificity of imaging evaluation, thus decreasing benign resections. CT is useful in diagnosis and treatment planning of advanced cancer. Although (18)F-FDG-avid ovarian lesions in postmenopausal women are considered suspicious for malignancy, PET/CT is not recommended for primary cancer detection because of high false-positive rates. C1 [Iyer, Veena R.; Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Iyer, VR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM viyer@partners.org RI 李, 海明/I-2405-2012 NR 76 TC 46 Z9 49 U1 0 U2 7 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 FEB PY 2010 VL 194 IS 2 BP 311 EP 321 DI 10.2214/AJR.09.3522 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 548HU UT WOS:000273951900007 PM 20093590 ER PT J AU Abujudeh, HH Kosaraju, VK Kaewlai, R AF Abujudeh, Hani H. Kosaraju, Vijaya K. Kaewlai, Rathachai TI Acute Adverse Reactions to Gadopentetate Dimeglumine and Gadobenate Dimeglumine: Experience With 32,659 Injections SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE acute adverse reaction; gadobenate dimeglumine; gadolinium-based contrast agents; gadopentetate dimeglumine ID NEPHROGENIC SYSTEMIC FIBROSIS; CONTRAST-MEDIA; CLINICAL-EXPERIENCE; SAFETY; ADMINISTRATIONS; AGENT; RISK AB OBJECTIVE. The purpose of this study was to retrospectively assess the frequency, manifestations, and severity of acute adverse reactions associated with administration of two gadolinium-based contrast agents to patients who underwent MRI at a single large academic institution. MATERIALS AND METHODS. Data from continuous quality assurance records on the number of administrations of and acute adverse reactions to gadopentetate dimeglumine and gadobenate dimeglumine at our institution October 2007 to December 2008 were tabulated and analyzed. During the investigation period, 32,659 administrations of gadolinium-based contrast agents were performed for MRI examinations. Of these, 27,956 administrations were gadopentetate dimeglumine, and 4,703 administrations were gadobenate dimeglumine. Data were collected on the frequency and severity of acute adverse reactions. RESULTS. A total of 51 acute adverse reactions occurred in 50 patients (16 men, 34 women; mean age, 48 years), accounting for 0.16% of all administrations (51/32,659). Thirty-eight reactions (38/27,956, 0.14%) were associated with gadopentetate dimeglumine, and 13 (13/4,703, 0.28%) were associated with gadobenate dimeglumine. Forty-three reactions were mild, six were moderate, and two were severe. The severe reactions occurred with the use of gadobenate dimeglumine. CONCLUSION. The rates of acute adverse reactions to gadopentetate dimeglumine and gadobenate dimeglumine were 0.14% and 0.28%, respectively. The overall adverse reaction rate was 0.16% in our patient sample. Direct comparison of adverse reaction rates of the two agents was not possible because of the retrospective uncontrolled study design. C1 [Abujudeh, Hani H.; Kosaraju, Vijaya K.; Kaewlai, Rathachai] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abujudeh, Hani H.; Kosaraju, Vijaya K.; Kaewlai, Rathachai] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 213D, Boston, MA 02114 USA. EM habujudeh@partners.org OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 19 TC 41 Z9 43 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2010 VL 194 IS 2 BP 430 EP 434 DI 10.2214/AJR.09.3099 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 548HU UT WOS:000273951900023 PM 20093606 ER PT J AU Rabban, JT McAlhany, S Lerwill, MF Grenert, JP Zaloudek, CJ AF Rabban, Joseph T. McAlhany, Stephanie Lerwill, Melinda F. Grenert, James P. Zaloudek, Charles J. TI PAX2 Distinguishes Benign Mesonephric and Mullerian Glandular Lesions of the Cervix From Endocervical Adenocarcinoma, Including Minimal Deviation Adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE mesonephric remnants; mesonephric hyperplasia; PAX2; endocervical adenocarcinoma; adenoma malignum; minimal deviation adenocarcinoma ID UTERINE CERVIX; IMMUNOHISTOCHEMICAL ANALYSIS; ADENOMA MALIGNUM; CD10 EXPRESSION; USEFUL MARKER; HYPERPLASIA; CARCINOMAS; PROTEIN; CANCER; CORPUS AB Mesonephric remnants of the cervix are vestiges of the embryonic mesonephric system which typically regresses during female development. Uncommonly, hyperplasia of the mesonephric remnants may occur. The differential diagnosis of exuberant mesonephric hyperplasia includes minimal deviation adenocarcinoma of the cervix, a tumor with deceptively bland morphology for which no reliable diagnostic biomarkers currently exist. PAX2 encodes a transcription factor necessary in the development of the Wolffian duct system.. and the protein is expressed in several tumors of mesonephric origin, including renal cell carcinoma, Wilm tumor, and nephrogenic adenoma. We hypothesized that PAX2 may also be expressed in mesonephric lesions of the cervix and may distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma of the cervix. We demonstrated that PAX2 was strongly and diffusely expressed in mesonephric remnants (6 of 6) and in mesonephric hyperplasia (18 of 18),however, no expression was noted in mesonephric adenocarcinoma (0 of 1). PAX2 was expressed in normal endocervical glands (including tunnel clusters and Nabothian cysts) (86 of 86), lobular endocervical glandular hyperplasia (5 of 5), tubal/tuboendometrioid metaplasia (8 of 8), and cervical endometriosis (13 of 14). In contrast, only 2 cases of endocervical adenocarcinoma were positive for PAX2 [invasive adenocarcinoma of the minimal deviation type (0 of 5), usual type (I of 22), and endometrioid type (1 of 1)]. Adjacent adenocarcinoma in Situ, as well as cases of pure adenocarcinoma in situ (0 of 6), were also PAX2 negative. PAX2 expression in the 2 positive endocervical adenocarcinomas was patchy and weak. Most (11 of 15) stage II endometrial endometrioid adenocarcinomas lacked PAX2 expression but I of 10 grade I tumors and 3 of 5 grade 2 tumors did express PAX2. These results suggest that PAX2 immunoreactivity may be useful to (1) distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma, (2) to distinguish lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma, and (3) to distinguish endocervical tubal metaplasia or cervical endometriosis from endocervical adenocarcinoma in situ. Overall, a strong, diffuse nuclear PAX2 expression pattern in a cervical glandular proliferation predicts a benign diagnosis (positive predictive value 90%, negative predictive value 98%; P < 0.001); however, PAX2 should not be interpreted in isolation from the architectural and cytologic features of the lesion as it may be expressed in some stage II endometrial adenocarcinomas involving the cervix. C1 [Rabban, Joseph T.; McAlhany, Stephanie; Grenert, James P.; Zaloudek, Charles J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Lerwill, Melinda F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rabban, JT (reprint author), Univ Calif San Francisco, Dept Pathol, 505 Parnassus Ave,M-551, San Francisco, CA 94143 USA. EM joseph.rabban@ucsf.edu NR 24 TC 31 Z9 36 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2010 VL 34 IS 2 BP 137 EP 146 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 551OV UT WOS:000274219800001 PM 20061933 ER PT J AU Geyer, JT Ferry, JA Harris, NL Young, RH Longtine, JA Zukerberg, LR AF Geyer, Julia Turbiner Ferry, Judith A. Harris, Nancy L. Young, Robert H. Longtine, Janina A. Zukerberg, Lawrence R. TI Florid Reactive Lymphoid Hyperplasia of the Lower Female Genital Tract (Lymphoma-like Lesion): A Benign Condition That Frequently Harbors Clonal Immunoglobulin Heavy Chain Gene Rearrangements SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoma-like lesion; cervix; endometrium; clonality ID B-CELL CLONALITY; UTERINE CERVIX; CLINICOPATHOLOGICAL ANALYSIS; GASTRITIS; PRIMERS; UTERUS; VAGINA AB Lymphoma-like lesions (LLL) of the lower female genital tract are florid reactive inflammatory processes that mainly occur in women in their reproductive years. Histologically, they are characterized by a dense lymphoid infiltrate with admixed large cells that is Often Suspicious for lymphoma. In contrast to lymphoma, however, they are superficial lesions that typically show surface erosion and a mixed lymphoid infiltrate and do not have evidence of a mass, deep invasion, or prominent sclerosis. With the advent of widespread molecular genetic testing, it would seem that LLLs should be polyclonal helping make the correct diagnosis. However, we have found cases with morphologic and immunophenotypic features of LLLs and evidence of clonal rearrangement of the immunoglobulin heavy chain (IGH) gene, potentially leading to misdiagnosis. We examined the clinicopathologic features and outcome of 12 patients with LLL (9 in the cervix and 3 in the endometrium). The patients ranged in age from 18 to 54 (median 37) years and came to medical attention because of squamous dysplasia (8 patients), vaginal bleeding (3), or adnexal mass (1). One patient had an endocervical polyp, but otherwise none had a discrete mass. The specimens contained a dense, polymorphous inflammatory infiltrate, commonly associated with mucosal erosion. Immunohistochemical studies showed a mixture of B and T cells without immunoglobulin light chain restriction. Four cases (all cervical) had a clonal IGH gene rearrangement by PCR. There was no evidence of lymphoma on staging or on follow-up in any patient, including the 4 patients with clonal IGH rearrangement, after a mean follow-up of 3.5 years (range: 4 mo to 13 y). In summary, we describe 12 patients with LLL of the lower female genital tract. Four of the 9 cases (44%) analyzed by PCR had a clonal IGH gene rearrangement. The clinical and pathologic features of these cases Suggest that a clonal IGH rearrangement in this setting does not warrant a diagnosis of lymphoma. Careful correlation of clinical, histologic, immunophenotypic, and genetic features is required to avoid misdiagnosis and inappropriate treatment. Routine microscopic findings and detailed clinical information remain paramount in establishing the correct diagnosis. C1 [Geyer, Julia Turbiner; Ferry, Judith A.; Harris, Nancy L.; Young, Robert H.; Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Longtine, Janina A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zukerberg, LR (reprint author), Massachusetts Gen Hosp, Dept Pathol Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM lzukerberg@partners.org NR 25 TC 14 Z9 14 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 FEB PY 2010 VL 34 IS 2 BP 161 EP 168 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 551OV UT WOS:000274219800003 PM 20087162 ER PT J AU Geyer, JT Ferry, JA Harris, NL Stone, JH Zukerberg, LR Lauwers, GY Pilch, BZ Deshpande, V AF Geyer, Julia Turbiner Ferry, Judith A. Harris, Nancy L. Stone, John H. Zukerberg, Lawrence R. Lauwers, Gregory Y. Pilch, Ben Z. Deshpande, Vikram TI Chronic Sclerosing Sialadenitis (Kuttner Tumor) Is an IgG4-associated Disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Kuttner tumor; chronic sclerosing sialadenitis; Sjogren syndrome; lymphoepithelial sialadenitis; IgG4; plasma cells ID AUTOIMMUNE PANCREATITIS; SJOGRENS-SYNDROME; SALIVARY-GLAND; CHOLANGITIS; LYMPHADENOPATHY AB Background: Chronic sclerosing sialadenitis is a fibroinflammatory disease of the salivary glands, characteristically of the submandibular gland. One prior Asian study proposed that chronic sclerosing sialadenitis is a part of the spectrum of IgG4-associated disease. This association has not been confirmed in Western populations. We therefore, investigated the relationship between IgG4 and chronic sclerosing sialadenitis, and compared the histomorphologic features of this condition with those of chronic sialadenitis not otherwise specified, Sjogren syndrome, and lymphoepithelial sialadenitis. Materials and Methods: We evaluated 13 cases of chronic sclerosing sialadenitis and compared them with 15 cases of chronic sialadenitis-not otherwise specified, 8 lip biopsies from individuals with Sjogren syndrome, and 4 cases of lymphoepithelial sialadenitis. immunohistochemistry for IgG, and IgG4 was carried out. IgG4-positive plasma cells were quantified and the IgG4/IgG ratio was calculated. Results: Seven patients with chronic sclerosing sialadenitis were female and 6 were male. Their mean age was 61 years (range: 27 to 80). Twelve chronic sclerosing sialadenitis cases involved the submandibular gland (bilaterally in 3) and in I there was a parotid lesion. Three of these 12 cases had manifestations of IgG4-associated systemic disease. Morphologically these specimens had preservation of lobular architecture, hypercellular interlobular fibrosis, florid lymphoid hyperplasia, and numerous plasma cells. Obliterative phlebitis was observed in 6 cases. The histologic features of chronic sclerosing sialadenitis were reminiscent of autoimmune pancreatitis, and were either not observed or were present only focally in cases of chronic sialadenitis, Sjogren syndrome, and lymphoepithelial sialadenitis. Eleven of 12 evaluable cases showed an increased number of IgG4 plasma cells with a mean of 229/high-power field (HPF) (range 75 to 608) and an overall IgG4/IgG ratio of 0.86 (range 0.5 to 1). The only patient whose biopsy lacked IgG4-positive plasma cells had pathologic evidence of cytomegalovirus infection. Chronic sclerosing sialadenitis cases, in comparison with the other 3 groups studied, showed a significantly higher number of IgG4 positive plasma cells (P < 0.05). Patients with chronic sialadenitis-not otherwise specified had a median number of only 16 IgG4-positive plasma cells/HPF (range 2 to 44), with an IgG4/IgG ratio of 0.14 (range 0.02 to 0.28). The Sjogren syndrome patients had a median of 1 IgG4-positive plasma cell/HPF (range 0 to 3), with an IgG4/IgG ratio of 0.02 (range 0 to 0.07). Patients with lymphoepithelial sialadenitis had a median of 0 IgG4-positive plasma cells per HPF. Conclusion: Chronic sclerosing sialadenitis has a characteristic morphologic appearance. This morphologic appearance, in conjunction with the elevated IgG4 expression, distinguishes chrome sclerosing sialadenitis from other inflammatory diseases of the salivary glands. Chronic sclerosing sialadenitis belongs to the spectrum of IgG4-related diseases. C1 [Geyer, Julia Turbiner; Ferry, Judith A.; Harris, Nancy L.; Zukerberg, Lawrence R.; Lauwers, Gregory Y.; Pilch, Ben Z.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Rheumatol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Pathol Dept Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 32 TC 112 Z9 125 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2010 VL 34 IS 2 BP 202 EP 210 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 551OV UT WOS:000274219800007 PM 20061932 ER PT J AU Solt, K Kelly, EW Cotten, JF Raines, DE AF Solt, Ken Kelly, Elizabeth W. Cotten, Joseph F. Raines, Douglas E. TI Inhibition of Human alpha(4)beta(2) Neuronal Nicotinic Acetylcholine Receptors by Volatile Aromatic Anesthetics Depends on Drug Hydrophobicity SO ANESTHESIA AND ANALGESIA LA English DT Article ID GENERAL-ANESTHETICS; INHALED ANESTHETICS; XENOPUS OOCYTES; SPINAL-CORD; ISOFLURANE; MODULATION; BRAIN; MECHANISMS; CHANNELS; POTENCY AB BACKGROUND: Volatile aromatic compounds such as benzene are general anesthetics that cause amnesia, hypnosis, and immobility in response to noxious stimuli when inhaled. Although these compounds are not used clinically, they are frequently found in commercial items such as solvents and household cleaning products and are abused as inhalant drugs. Volatile aromatic anesthetics are useful pharmacological tools for probing the relationship between chemical structure and drug activity at putative general anesthetic targets. Neuronal nicotinic acetylcholine (nACh) receptors are ligand-gated ion channels widely expressed in the brain, which are thought to play important roles in learning and memory. In this study, we tested the hypothesis that aromatic anesthetics reversibly inhibit alpha(4)beta(2), neuronal nACh receptor function and sought to determine the structural correlates of receptor inhibition. METHODS: Electrophysiological techniques were used to quantify the effects of 8 volatile aromatic anesthetics on currents elicited by 1 mM ACh and mediated by human alpha(4)beta(2) nACh receptors expressed in Xenopus oocytes. RESULTS: All of the volatile aromatic anesthetics used in this study reversibly inhibited alpha(4)beta(2) nACh receptors with IC(50) values ranging from 0.00091. atm for 1,2-difluorobenzene to 0.045 atm for hexafluorobenzene. With the exception of hexafluorobenzene, all of the compounds had IC(50) values less than minimum alveolar concentration. Inhibitory potency correlated poorly with the cation-pi binding energies of the Compounds (r(2) = 0.48, P = 0.059). However, there was a good correlation between inhibitory potency and the octanol/gas partition coefficient (r(2) = 0.87, P = 0.0008). CONCLUSIONS: Volatile aromatic anesthetics potently and reversibly inhibit human alpha(4)beta(2) neuronal nACh receptors. This inhibition may play a role in producing amnesia. In contrast to N-methyl-D-aspartate receptors, the inhibitory potencies of aromatic anesthetics for alpha(4)beta(2) neuronal nACh receptors seem to be dependent on drug hydrophobicity rather than electrostatic properties. This implies that the volatile aromatic anesthetic binding site in the alpha(4)beta(2) neuronal nACh receptor is hydrophobic in character and differs from the nature of the binding site in N-methyl-D-aspartate receptors. (Anesth Analg 2010;110:455-60) C1 [Solt, Ken; Cotten, Joseph F.; Raines, Douglas E.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Solt, Ken; Kelly, Elizabeth W.; Cotten, Joseph F.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health [P01-GM58448]; The Foundation for Anesthesia Education and Research; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA FX Supported by National Institutes of Health Grant P01-GM58448, The Foundation for Anesthesia Education and Research, and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA NR 29 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 2010 VL 110 IS 2 BP 455 EP 460 DI 10.1213/ANE.0b013e3181c5f689 PG 6 WC Anesthesiology SC Anesthesiology GA 547XC UT WOS:000273922100034 PM 19917625 ER PT J AU Butterworth, JF Rathmell, JP AF Butterworth, John F. Rathmell, James P. TI Standard Care, Standards for Care, or Standard of Care? SO ANESTHESIOLOGY LA English DT Editorial Material ID PRACTICE GUIDELINES; RISKS C1 [Butterworth, John F.] Indiana Univ, Sch Med, Dept Anesthesia, Indianapolis, IN 46202 USA. [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Div Pain Med, Boston, MA USA. RP Butterworth, JF (reprint author), Indiana Univ, Sch Med, Dept Anesthesia, Indianapolis, IN 46202 USA. EM jfbutter@iupui.edu NR 10 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2010 VL 112 IS 2 BP 277 EP 278 PG 2 WC Anesthesiology SC Anesthesiology GA 549KD UT WOS:000274046400005 PM 20098125 ER PT J AU Musch, G Wiener-Kronish, JP AF Musch, Guido Wiener-Kronish, Jeanine P. TI Effect of Ventilator-induced Lung Injury on Skeletal Muscle Oxidative Balance SO ANESTHESIOLOGY LA English DT Editorial Material ID PROTEIN-TYROSINE NITRATION; STRESS C1 [Musch, Guido] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM guido.musch@gmail.com NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 2010 VL 112 IS 2 BP 279 EP 281 PG 3 WC Anesthesiology SC Anesthesiology GA 549KD UT WOS:000274046400006 PM 20098126 ER PT J AU Henderson, DC Sharma, B Fan, XD Copeland, PM Borba, CP Freudenreich, O Cather, C Evins, AE Goff, DC AF Henderson, David C. Sharma, Bikash Fan, Xiaoduo Copeland, Paul M. Borba, Christina P. Freudenreich, Oliver Cather, Corinne Evins, A. Eden Goff, Donald C. TI Dietary saturated fat intake and glucose metabolism impairments in nondiabetic, nonobese patients with schizophrenia on clozapine or risperidone SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE schizophrenia; clozapine; risperidone; insulin resistance; saturated fat ID CORONARY-ARTERY-DISEASE; INSULIN SENSITIVITY; DIABETES-MELLITUS; INTRAVENOUS GLUCOSE; HEART-DISEASE; BETA-CELL; ATYPICAL ANTIPSYCHOTICS; CARDIOVASCULAR-DISEASE; FRAMINGHAM NUTRITION; PRIMARY-PREVENTION AB BACKGROUND: High dietary saturated fat (SF) intake is strongly linked to metabolic disturbances. The goal of this study was to understand the relationship between clozapine and risperidone with glucose and lipid metabolism and dietary fat intake in patients with schizophrenia. METHODS: Thirty-one clozapine-treated patients and 15 risperidone-treated patients were assessed using a 4-day dietary record, an IV glucose tolerance test, and lipid profiles. RESULTS: Clozapine-treated patients consumed a significantly higher percentage of SF than did risperidone-treated patients (13.7% +/- 3.4% vs 10.6% +/- 3.0% of total energy; P = .007). Compared with the risperidone group, the clozapine group also had a significantly higher percentage of total fat in their diet (36% +/- 6.7% vs 30.9% +/- 5.7% of total energy; P = .007). Similarly, the clozapine group had a significant impairment in insulin sensitivity index (SI), glucose effectiveness (SG), and disposition index (DI) compared with the risperidone group (P < .05). Pearson correlation analysis of both groups showed that dietary SF was significantly correlated with impairment in glucose homeostasis (SG: r = -0.43; P = .004; DI: r = -0.35; P = .02). CONCLUSION: Abnormal glucose homeostasis in atypical clozapine-treated patients with schizophrenia may be associated with or aggravated by high dietary SF consumption. C1 [Henderson, David C.; Fan, Xiaoduo; Copeland, Paul M.; Freudenreich, Oliver; Cather, Corinne; Evins, A. Eden; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA USA. [Henderson, David C.; Sharma, Bikash; Fan, Xiaoduo; Borba, Christina P.; Freudenreich, Oliver; Cather, Corinne; Evins, A. Eden; Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU Stanley Foundation; National Institutes of Health National Center for Research Resources [5MO1RR01066-24]; NARSAD; Bristol-Myers Squibb; Covance; Janssen, L.P.; Pfizer Inc; PriMedia; Reed Medical Education; Solvay Pharmaceuticals; Takeda; Cephalon; Dainippon Sumitomo Pharma; Forest Laboratories; Genactics; MedReviews, LLC; Organon; Proteus; Solvay/Wyeth; Vanda Pharmaceuticals; XenoPort; Xytis; Eli Lilly and Company; Merck; sanofi-aventis; Consortium of Developmental Disabilities Councils (CDDC); GlaxoSmithKline; National Institute on Drug Abuse (NIDA) FX Stanley Foundation, National Institutes of Health National Center for Research Resources Grant 5MO1RR01066-24 (General Clinical Research Center), and a NARSAD New Investigator Award (D.C.H.).; Dr. Henderson receives research support and/or honoraria from Bristol-Myers Squibb, Covance, Janssen, L.P., Pfizer Inc, PriMedia, Reed Medical Education, Solvay Pharmaceuticals, and Takeda. Dr. Goff receives research support and/or honoraria from Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo Pharma, Forest Laboratories, Genactics, Janssen, L.P., MedReviews, LLC, Organon, Pfizer Inc, PriMedia, Proteus, Reed Medical Education, Solvay/Wyeth, Vanda Pharmaceuticals, XenoPort, and Xytis. Dr. Copeland receives research support and/or honoraria from Eli Lilly and Company, Merck, Takeda, and sanofi-aventis. Dr. Fan receives research support and honoraria from Eli Lilly and Company. Dr. Freudenreich receives research support and/or honoraria from Cephalon, PriMedia, and Reed Medical Education. Dr. Evins receives research support from the Consortium of Developmental Disabilities Councils (CDDC), GlaxoSmithKline, the National Institute on Drug Abuse (NIDA), and Pfizer Inc. Dr. Gather, Dr. Sharma, and Ms. Borba report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products. NR 87 TC 13 Z9 14 U1 4 U2 4 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD FEB PY 2010 VL 22 IS 1 BP 33 EP 42 PG 10 WC Psychiatry SC Psychiatry GA 752BT UT WOS:000289663700006 PM 20196981 ER PT J AU Daly, EJ Trivedi, MH Wisniewski, SR Nierenberg, AA Gaynes, BN Warden, D Morris, DW Luther, JF Farabaugh, A Cook, I Rush, AJ AF Daly, Ella J. Trivedi, Madhukar H. Wisniewski, Stephen R. Nierenberg, Andrew A. Gaynes, Bradley N. Warden, Diane Morris, David W. Luther, James F. Farabaugh, Amy Cook, Ian Rush, A. John TI Health-related quality of life in depression: A STAR*D report SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE Health-related quality of life; major depressive disorder; domains of quality of life ID SEQUENCED TREATMENT ALTERNATIVES; NATIONAL COMORBIDITY SURVEY; ILLNESS RATING-SCALE; MENTAL-DISORDERS; MAJOR DEPRESSION; MEDICAL ILLNESS; SYMPTOMATOLOGY IDS; ITEM SELECTION; DISABILITY; INVENTORY AB BACKGROUND: Although major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQOL), few studies have evaluated HRQOL dysfunction in multiple domains. This report examined the psychological, physical, and social domains in a large sample of outpatients who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHODS: The relationship of HRQOL, and baseline sociodemographic and clinical features, including depressive severity, was evaluated. We assessed HRQOL with the 12-item Short Form Health Survey, the 5-item Work and Social Adjustment Scale, and the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Among 2307 participants, greater depressive symptom severity was associated with poorer HRQOL. After controlling for age and depression severity, lower HRQOL was related independently to being African American or Hispanic, less educated, unemployed, divorced or separated, having public medical insurance, and to having more general medical disorders. We found impairments across all 3 domains, with low correlations between the 3 measures of HRQOL chosen, suggesting that they evaluate different and nonoverlapping aspects of function. CONCLUSION: Sociodemographically disadvantaged patients with greater general medical and depressive illness burden are at greatest risk for poorer quality of life. Distinct impairments are seen in the 3 domains of HRQOL. C1 [Daly, Ella J.] Univ Texas SW Med Ctr Dallas, Mood Disorders Program, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Nierenberg, Andrew A.; Farabaugh, Amy] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Cook, Ian] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Behav Sci, Los Angeles, CA USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Mood Disorders Program, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health [N01MH90003, K23]; Agency for Healthcare Research and Quality; National Institute on Drug Abuse; Targacept; PamLab; Pfizer Inc; Shire; AstraZeneca; Bristol-Myers Squibb; Eli Lilly and Company; M-3 Information; National Alliance for Research in Schizophrenia and Depression (NARSAD); Aspect Medical Systems; National Institutes of Health; Neuronetics; Sepracor FX This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (PI: A.J. Rush). The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.; Madhukar H. Trivedi, MD, is a consultant for Astra-Zeneca; Bristol-Myers Squibb; Cephalon; Eli Lilly and Company; Evotec; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals; GlaxoSmithKline; Janssen, L.P.; Johnson & Johnson PRD; Medtronic; Neuronetics; Otsuka Pharmaceuticals; Pfizer Inc; Shire Development Inc.; and Wyeth-Ayerst Laboratories. He serves on speakers bureaus for AstraZeneca; Bristol-Myers Squibb; Forest Pharmaceuticals; and Otsuka Pharmaceuticals. He receives grant support from the Agency for Healthcare Research and Quality; the National Institute of Mental Health; the National Institute on Drug Abuse; and Targacept.; Andrew A. Nierenberg, MD, is a full-time employee of the Massachusetts General Hospital (MGH). He has received grant/research support through MGH from the National Institute of Mental Health, PamLab, Pfizer Inc, and Shire. He received honoraria from American Drug Utilization Review, the American Society for Clinical Psychopharmacology, Baystate Medical Center, Belvoir Publications, Columbia University, Hillside Hospital, Imedex, MBL Publishing, MJ Consulting, New York State, Physicians Postgraduate Press, SUNY Buffalo, the University of Pisa, the University of Texas Southwestern Medical Center at Dallas, and the University of Wisconsin. Dr. Nierenberg is a presenter for the MGH Psychiatry Academy (MGHPA), whose education programs were supported through independent medical education (IME) grants from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company in 2009. He provides advisory/consulting services to the American Psychiatric Association (only travel expenses paid), Appliance Computing, Inc. (Mindsite), Brain Cells Inc., Brandeis University, Eli Lilly and Company, Novartis, PGxHealth, Schering-Plough, Shire, Takeda, and Targacept. Dr. Nierenberg owns stock options in Appliance Computing, Inc., and BrainCells Inc. Through MGH, he is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Also through MGH, Dr. Nierenberg has a patent extension application for the combination of buspirone, bupropion, and melatonin for the treatment of depression.; Bradley N. Gaynes, MD, MPH, receives grant/research support from the Agency for Healthcare Research and Quality, M-3 Information, and the National Institute of Mental Health.; Amy Farabaugh, PhD, receives grant/research support from the National Alliance for Research in Schizophrenia and Depression (NARSAD) and the National Institute of Mental Health (K23).; Ian Cook, MD, receives research support from Aspect Medical Systems, the National Institutes of Health, Neuronetics, and Sepracor. He provides advisory/consulting services to Bristol-Myers Squibb, Neuronetics, Scale Venture Partners, and USDOJ, and serves on speakers bureaus for the Medical Education Speakers Network, Neuronetics, and Wyeth Pharmaceuticals. Patents on biomedical inventions are assigned to and owned by the University of California. NR 44 TC 44 Z9 47 U1 5 U2 15 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD FEB PY 2010 VL 22 IS 1 BP 43 EP 55 PG 13 WC Psychiatry SC Psychiatry GA 752BT UT WOS:000289663700007 PM 20196982 ER PT J AU Nozari, A Dilekoz, E Sukhotinsky, I Stein, T Eikermann-Haerter, K Liu, C Wang, YM Frosch, MP Waeber, C Ayata, C Moskowitz, MA AF Nozari, Ala Dilekoz, Ergin Sukhotinsky, Inna Stein, Thor Eikermann-Haerter, Katharina Liu, Christina Wang, Yumei Frosch, Matthew P. Waeber, Christian Ayata, Cenk Moskowitz, Michael A. TI Microemboli May Link Spreading Depression, Migraine Aura, and Patent Foramen Ovale SO ANNALS OF NEUROLOGY LA English DT Article ID TO-LEFT SHUNT; ISCHEMIC-STROKE; TRANSCRANIAL DOPPLER; HEMIPLEGIC MIGRAINE; IMAGING FINDINGS; CONTROLLED TRIAL; CLOSURE; BRAIN; PREVALENCE; HEADACHE AB Objective: Patent foramen ovale and pulmonary arteriovenous shunts are associated with serious complications such as cerebral emboli, stroke, and migraine with aura. The pathophysiological mechanisms that link these conditions are unknown. We aimed to establish a mechanism linking microembolization to migraine aura in an experimental animal model. Methods: We introduced particulate or air microemboli into the carotid circulation in mice to determine whether transient microvascular occlusion, insufficient to cause infarcts, triggered cortical spreading depression (CSD), a propagating slow depolarization that underlies migraine aura. Results: Air microemboli reliably triggered CSD without causing infarction. Polystyrene microspheres (10 km) or cholesterol crystals (<70 mu m) triggered CSD in 16 of 28 mice, with 60% of the mice (40% of those with CSD) showing no infarcts or inflammation on detailed histological analysis of serial brain sections. No evidence of injury was detected on magnetic resonance imaging examination (9.4T; T2 weighted) in 14 of 15 selected animals. The occurrence of CSD appeared to be related to the magnitude and duration of flow reduction, with a triggering mechanism that depended on decreased brain perfusion but not sustained tissue damage. Interpretation: In a mouse model, microemboli triggered CSD, often without causing microinfarction. Paradoxical embolization then may link cardiac and extracardiac right-to-left shunts to migraine aura. If translatable to humans, a subset of migraine auras may belong to a spectrum of hypoperfusion disorders along with transient ischemic attacks and silent infarcts. ANN NEUROL 2010;67:221-229 C1 [Nozari, Ala; Dilekoz, Ergin; Sukhotinsky, Inna; Eikermann-Haerter, Katharina; Wang, Yumei; Waeber, Christian; Ayata, Cenk; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA. [Nozari, Ala] Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Charlestown, MA 02129 USA. [Stein, Thor; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Liu, Christina] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM moskowitz@helix.mgh.harvard.edu RI Waeber, Christian/A-8333-2009; OI Waeber, Christian/0000-0001-6078-0027; Stein, Thor/0000-0001-6954-4477; Liu, Christina/0000-0002-5723-177X FU National Institute of Neurological Disorders and Stroke [NS061505, NS35611]; General Hospital Department of Anesthesia; NIH National Research Service [GM07592] FX This project was supported by the National Institute of Neurological Disorders and Stroke (grant NS061505, CA.; grant NS35611, M.A.M.), Massachusetts; General Hospital Department of Anesthesia, and NIH National Research Service (grant GM07592, A.N.). NR 45 TC 104 Z9 111 U1 1 U2 13 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 FEB PY 2010 VL 67 IS 2 BP 221 EP 229 DI 10.1002/ana.21871 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 569SI UT WOS:000275620500009 PM 20225282 ER PT J AU Drzezga, A AF Drzezga, Alexander TI Amyloid-plaque imaging in early and differential diagnosis of dementia SO ANNALS OF NUCLEAR MEDICINE LA English DT Review DE Amyloid-plaque imaging; [(11)C]PIB-PET; Alzheimer's disease; Dementia; Neurodegeneration ID MILD COGNITIVE IMPAIRMENT; FRONTOTEMPORAL LOBAR DEGENERATION; PITTSBURGH-COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; PRECLINICAL ALZHEIMERS-DISEASE; LEWY BODIES; NONDEMENTED INDIVIDUALS; GLUCOSE-METABOLISM; SEMANTIC DEMENTIA; VASCULAR DEMENTIA AB The increasing life expectancy in our society results in a continuously growing number of patients suffering from neurodegenerative disorders, particularly Alzheimer's disease (AD). Apart from the deleterious consequences for patients and their relatives, this issue has also alarming effects on our social systems. These facts have justified increased scientific efforts regarding the identification of basic pathomechanisms of dementia and the development of new treatment options. Increased production of specific proteins and their pathologic aggregation in the brain appears to be a pathomechanism which occurs early in the course of many different neurodegenerative diseases. Among the most well-known of these protein aggregations are amyloid plaques, which arise from the aggregation of the beta-amyloid protein. Currently, this amyloid-aggregation pathology is regarded as a key pathology, playing a causal role in the development of AD. Consequently, modern therapy approaches are directed towards this target. Limited access to brain tissue has so far restricted the definite diagnosis of AD to postmortem histopathological assessment of brain tissue. For the same reason, a clear association between extent of amyloid deposition pathology and clinical course of AD has not been established so far. However, particularly with regard to new therapeutic options, a reliable in vivo diagnosis is required. Modern molecular imaging tracers such as [(11)C]PIB do now open the possibility to visualize amyloid depositions in vivo, using positron emission tomography. This type of "in vivo histopathology" approach allows the characterization of neurodegenerative disorders on the basis of the underlying pathology rather than on their symptomatic appearance. In this manuscript, we will discuss the options of amyloid-plaque imaging regarding early and differential diagnosis of different forms of dementia as well as for patient selection for therapy trials and for objective therapy monitoring. C1 [Drzezga, Alexander] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Drzezga, Alexander] Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin, D-8000 Munich, Germany. RP Drzezga, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM adrzezga@nmr.mgh.harvard.edu FU DFG grants (Deutsche Forschungsgemeinschaft) [DR 445/3-1, DR 445/4-1] FX This work has been supported in part by DFG grants (Deutsche Forschungsgemeinschaft) Project Numbers: DR 445/3-1, DR 445/4-1 (Drzezga). The author thanks Nicola Karina for the careful review of the manuscript. NR 91 TC 15 Z9 15 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0914-7187 J9 ANN NUCL MED JI Ann. Nucl. Med. PD FEB PY 2010 VL 24 IS 2 BP 55 EP 66 DI 10.1007/s12149-009-0330-9 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 555HH UT WOS:000274499200001 PM 20082230 ER PT J AU Viale, G Giobbie-Hurder, A Gusterson, BA Maiorano, E Mastropasqua, MG Sonzogni, A Mallon, E Colleoni, M Castiglione-Gertsch, M Regan, MM Price, KN Brown, RW Golouh, R Crivellari, D Karlsson, P Ohlschlegel, C Gelber, RD Goldhirsch, A Coates, AS AF Viale, G. Giobbie-Hurder, A. Gusterson, B. A. Maiorano, E. Mastropasqua, M. G. Sonzogni, A. Mallon, E. Colleoni, M. Castiglione-Gertsch, M. Regan, M. M. Price, K. N. Brown, R. W. Golouh, R. Crivellari, D. Karlsson, P. Oehlschlegel, C. Gelber, R. D. Goldhirsch, A. Coates, A. S. TI Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; breast cancer; endocrine responsiveness; metastasis; prognosis; vascular invasion ID BLOOD-VESSEL INVASION; LYMPHOVASCULAR INVASION; FOLLOW-UP; CARCINOMA; ESTROGEN; RESPONSIVENESS; IDENTIFICATION; CHEMOTHERAPY; RECURRENCE; INDICATOR AB Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up > 9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. C1 [Viale, G.] Univ Milan, Dept Pathol, European Inst Oncol, Div Pathol & Lab Med, I-20141 Milan, Italy. [Gusterson, B. A.; Mallon, E.] Univ Glasgow, Div Canc Sci & Mol Pathol, Fac Med, Glasgow, Lanark, Scotland. [Maiorano, E.] Univ Bari, Dept Pathol Anat, Bari, Italy. [Colleoni, M.] European Inst Oncol, Dept Med, Res Unit Med Senol, Milan, Italy. [Castiglione-Gertsch, M.] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Brown, R. W.] Melbourne Pathol, Collingwood, Vic, Australia. [Golouh, R.] Inst Oncol, Dept Pathol, Ljubljana, Slovenia. [Crivellari, D.] Ctr Riferimento Oncol, Dept Med Oncol, I-33081 Aviano, Italy. [Karlsson, P.] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Oehlschlegel, C.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Dana Farber Canc Inst,Stat Ctr,Int Breast Canc St, Boston, MA 02115 USA. [Goldhirsch, A.] Oncol Inst So Switzerland, Dept Med, Bellinzona, Switzerland. [Coates, A. S.] Int Breast Canc Study Grp, Sci Comm, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. RP Viale, G (reprint author), Univ Milan, Dept Pathol, European Inst Oncol, Div Pathol & Lab Med, Via Ripamonti 435, I-20141 Milan, Italy. EM giuseppe.viale@ieo.it RI Maiorano, Eugenio/F-1382-2015; Sonzogni, Angelica/C-1193-2017; OI Sonzogni, Angelica/0000-0002-4769-4316; Maiorano, Eugenio/0000-0002-0472-5338 FU NCI NIH HHS [CA-75362, U24 CA075362] NR 32 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2010 VL 21 IS 2 BP 245 EP 254 DI 10.1093/annonc/mdp317 PG 10 WC Oncology SC Oncology GA 549XK UT WOS:000274087600010 PM 19633051 ER PT J AU Regan, MM O'Donnell, EK Kelly, WK Halabi, S Berry, W Urakami, S Kikuno, N Oh, WK AF Regan, M. M. O'Donnell, E. K. Kelly, W. K. Halabi, S. Berry, W. Urakami, S. Kikuno, N. Oh, W. K. TI Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials SO ANNALS OF ONCOLOGY LA English DT Article DE carboplatin; estramustine; prostate cancer; taxanes ID PHASE-II; ESTRAMUSTINE PHOSPHATE; DOCETAXEL; PACLITAXEL; PREDNISONE; CHEMOTHERAPY; MITOXANTRONE; EXPERIENCE; TUMORS; MEN AB Background: Docetaxel is associated with prolonged survival in castration-resistant prostate cancer (CRPC). Platinum compounds have modest but distinct single-agent activity. Carboplatin may have greatest potential for benefit when combined with taxanes. We investigated whether there is a subset of patients with CRPC for whom the efficacy of combination taxane-estramustine-carboplatin (TEC) chemotherapy may be greatest. Patients and methods: Individual patient data (n = 310) were obtained from seven trials using TEC chemotherapy. Prostate-specific antigen (PSA) response was defined as 50% post-therapy decline from baseline. Overall survival was defined from baseline to death from any cause. Logistic and Cox regression were used to investigate heterogeneity in outcome to TEC by patient and disease characteristics. Predicted survival probabilities were calculated from the Halabi Cancer and Leukemia Group B (CALGB) nomogram. Results: The pooled PSA response proportion was 69% [95% confidence interval (CI) 56% to 80%]. There was no evidence of differential PSA response by disease characteristics. Established prognostic factors were associated with survival. The pooled 12-month survival estimate of 79% (95% CI 71% to 84%) was higher than the median 59% 12-month nomogram-predicted survival. Conclusions: TEC chemotherapy has significant clinical activity in CRPC. A randomized, controlled trial evaluating the addition of carboplatin to taxane-based chemotherapy is needed to elucidate the value of carboplatin in CRPC. C1 [Regan, M. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [O'Donnell, E. K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kelly, W. K.] Yale Univ, Dept Med & Surg, New Haven, CT USA. [Halabi, S.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Berry, W.] US Oncol Inc, Houston, TX USA. [Berry, W.] Canc Ctr N Carolina, Cary, NC USA. [Urakami, S.; Kikuno, N.] Shimane Univ, Sch Med, Dept Urol, Izumo, Shimane, Japan. [Oh, W. K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Regan, MM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM mregan@jimmy.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Bing Sound Wong Fund for Prostate Cancer Research; Louis DiGiovanni Fund for Prostate Cancer Research; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE [NCI 5P50CA90381]; CALGB Statistical Center [CA33601, CA32291, 99813]; U.S. National Cancer Institute [CA31946]; Sanofi-Aventis, USA; Dana-Farber Cancer Institute, Boston, MA [CA32291]; Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH [CA04326]; Memorial Sloan-Kettering Cancer Center, New York, NY [CA77651]; The Ohio State University Medical Center, Columbus, OH [CA77658]; University of California at San Francisco, San Francisco, CA [CA60138]; University of Chicago, Chicago, IL [CA41287]; University of North Carolina [CA47559]; Washington University School of Medicine, St Louis, MO FX Bing Sound Wong Fund for Prostate Cancer Research to W.K.O.; Louis DiGiovanni Fund for Prostate Cancer Research to W.K.O.; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (NCI 5P50CA90381); CALGB Statistical Center to S. H. (CA33601); CALGB Participating Center to W.K.O. (CA32291).; The research for CALGB 99813 was supported, in part, by grants from the U.S. National Cancer Institute to the CALGB (Richard L. Schilsky, CA31946) and to the CALGB Statistical Center (Stephen George, CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Funding for CALGB 99813 was provided, in part, by Sanofi-Aventis, USA. The following CALGB institutions participated in CALGB 99813: Dana-Farber Cancer Institute, Boston, MA (Eric P. Winer, CA32291); Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH (Marc S. Ernstoff, CA04326); Memorial Sloan-Kettering Cancer Center, New York, NY (Clifford A. Hudis, CA77651); The Ohio State University Medical Center, Columbus, OH (Clara D. Bloomfield, CA77658); University of California at San Francisco, San Francisco, CA (Alan P. Venook, CA60138); University of Chicago, Chicago, IL (Gini Fleming, CA41287); University of North Carolina at Chapel Hill, Chapel Hill, NC (Thomas C. Shea, CA47559); Washington University School of Medicine, St Louis, MO (Nancy Bartlett, CA77440). NR 26 TC 11 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2010 VL 21 IS 2 BP 312 EP 318 DI 10.1093/annonc/mdp308 PG 7 WC Oncology SC Oncology GA 549XK UT WOS:000274087600019 PM 19633053 ER PT J AU Wirth, LJ Allen, AM Posner, MR Haddad, RI Li, Y Clark, JR Busse, PM Chan, AW Goguen, LA Norris, CM Annino, DJ Tishler, RB AF Wirth, L. J. Allen, A. M. Posner, M. R. Haddad, R. I. Li, Y. Clark, J. R. Busse, P. M. Chan, A. W. Goguen, L. A. Norris, C. M. Annino, D. J. Tishler, R. B. TI Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck SO ANNALS OF ONCOLOGY LA English DT Article DE chemoradiotherapy; locoregionally advanced head and neck cancer; panitumumab ID GROWTH-FACTOR RECEPTOR; CONCURRENT CETUXIMAB; MONOCLONAL-ANTIBODY; RADIATION-THERAPY; ABX-EGF; III TRIAL; CARCINOMA; CHEMOTHERAPY; STANDARD; SURVIVAL AB Background: Panitumumab has the potential to improve the therapeutic ratio of concurrent chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This phase I dose-finding study investigated escalating doses of paclitaxel (Taxol) given concurrently with panitumumab, carboplatin and intensity-modulated radiotherapy (IMRT) for stage III-IVB SCCHN. Untreated patients with oral cavity, oropharynx, larynx, hypopharynx or unknown primaries were eligible. Additional eligibility criteria included measurable disease, good performance status and no contraindication to therapy. Patients received weekly fixed doses of panitumumab and carboplatin plus escalating doses of paclitaxel with IMRT. Results: Nineteen patients were enrolled on to two dose levels (DLs): weekly paclitaxel 15 mg/m(2) (n = 3) and 30 mg/m(2) (n = 16). One dose-limiting toxicity occurred in DL 2, which was declared the maximum tolerated dose. All patients experienced mucositis, primarily grade 3 or more. Oral pain, xerostomia, dysphagia, weight loss, dermatitis, nausea and acneiform rash were frequent. All patients had partial response according to RECIST, whereas the overall complete clinical response rate was 95%. At median follow-up of 21 months, 18 of 19 patients (95%) remained disease free. Conclusions: Panitumumab, carboplatin, paclitaxel and IMRT are well tolerated and appear highly active in the treatment of SCCHN. Further study of this regimen in SCCHN is warranted. C1 [Wirth, L. J.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Allen, A. M.; Tishler, R. B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Posner, M. R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Y.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Busse, P. M.; Chan, A. W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Goguen, L. A.; Norris, C. M.; Annino, D. J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Wirth, LJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM lwirth@partners.org FU Amgen FX funding Amgen. NR 33 TC 36 Z9 39 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2010 VL 21 IS 2 BP 342 EP 347 DI 10.1093/annonc/mdp477 PG 6 WC Oncology SC Oncology GA 549XK UT WOS:000274087600024 PM 19892746 ER PT J AU Anaya, DA Lahat, G Wang, X Xiao, L Pisters, PW Cormier, JN Hunt, KK Feig, W Lev, DC Pollock, RE AF Anaya, D. A. Lahat, G. Wang, X. Xiao, L. Pisters, P. W. Cormier, J. N. Hunt, K. K. Feig, W. Lev, D. C. Pollock, R. E. TI Postoperative nomogram for survival of patients with retroperitoneal sarcoma treated with curative intent SO ANNALS OF ONCOLOGY LA English DT Article DE postoperative nomogram; prognosis; retroperitoneal sarcoma; staging ID SOFT-TISSUE SARCOMA; RESECTION PREDICT PATTERN; PROGNOSTIC NOMOGRAM; HISTOLOGIC SUBTYPE; SINGLE INSTITUTION; LIPOSARCOMA; RECURRENCE; CLASSIFICATION; CARCINOMA; EXTREMITY AB Background: Current American Joint Committee on Cancer retroperitoneal sarcoma (RPS) staging is not representative of patients with RPS specifically and has limited discriminative power. Our objective was to develop a RPS disease-specific nomogram capable of stratifying patients based on probability of overall survival (OS) after resection. Patients and methods: In all, 1118 RPS patients were evaluated at our institution (1996-2006). Patients with resectable, nonmetastatic disease were selected (n = 343) and baseline, treatment and outcome variables were retrieved. A nomogram was created and its performance was evaluated by calculating its discrimination (concordance index) and calibration and by subsequent internal validation. Results: Median follow-up and OS were 50 and 59 months, respectively. Independent predictors of OS were included in the nomogram: age (>= 65), tumor size (>= 15 cm), type of presentation (primary versus recurrent), multifocality, completeness of resection and histology. The concordance index was 0.73 [95% confidence interval (CI) 0.71-0.75] and the calibration was excellent, with all observed outcomes within the 95% CI of each predicted survival probability. Conclusions: A RPS-specific postoperative nomogram was developed. It improves RPS staging by allowing a more dynamic and robust disease-specific risk stratification. This prognostic tool can help in patient counseling and for selection of high-risk patients that may benefit from adjuvant therapies or inclusion into clinical trials. C1 [Pollock, R. E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, U444, Houston, TX 77030 USA. [Wang, X.; Xiao, L.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Lev, D. C.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Anaya, D. A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA. RP Pollock, RE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, U444, 1400 Holcombe Blvd,POB 301402, Houston, TX 77030 USA. EM rpollock@mdanderson.org NR 32 TC 34 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2010 VL 21 IS 2 BP 397 EP 402 DI 10.1093/annonc/mdp298 PG 6 WC Oncology SC Oncology GA 549XK UT WOS:000274087600032 PM 19622598 ER PT J AU Rattner, DW Jakcson, TD AF Rattner, David W. Jakcson, Timothy D. TI Don't Stop Thinking About Tomorrow-Yesterday's Gone SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Rattner, David W.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Dept Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2010 VL 251 IS 2 BP 215 EP 216 DI 10.1097/SLA.0b013e3181cd9500 PG 2 WC Surgery SC Surgery GA 549KC UT WOS:000274046300006 PM 20040842 ER PT J AU Kakkar, AK Cohen, AT Tapson, VF Bergmann, JF Goldhaber, S Deslandes, B Huang, W Anderson, FA Cherfi, L Ammour, D Bentakouk, C Bourenane, R Grainat, N Maarouf, A Sissaoui, A Gallus, A Ayyar, V Crimmins, D Gan, E McRae, S Seldon, M Singh, B Siddiqui, FM Moula, K Nawaz, T Nazimuddin, K Rahman, S Sarker, S Rocha, A Brandao, C Costa, J Macedo, A Marino, R Menezes, P Oigman, W Paiva, M Pantoja, J Schramm, E Tandeitnik, L Timi, J Benov, H Borisov, SD Lalov, A Mirazchijski, B Postadziyan, A Sokolov, K Statelov, E Stefanov, C Stoykova, A Tadzher, S Todorov, R Dennis, R Duran, FRM Posada, A Restrepo, H Roa, J Villadiego, J Maly, J Brabec, T Gumulec, J Jochymek, R Kellnerova, I Kvasnicka, J Penka, M Skarkova, J Slezak, P Vit, P Vojtisek, P Gobran, H El Rahman, AMA El Haddad, A Gorgy, GS Rizk-Allah, M Sholkamy, S Bergmann, JF Abinader, M Abou Khoudir, F Boyer, JF Brun, N Canet, B Collard, C Cordier, C Durroux, C Emmerich, J Friocourt, P Genay, P Ibouanga, F Moumen, A Philippe, P Planchon, P Protin, Y Quere, I Rizcallah, MJ Zotz, R Bensch, K Bensmann, K Dropmann, A Gerold, D Gussmann, A Kortmann, B Kube, L Kuster, S Leupolz, W Neuhaus, T Nobel, W Pfiel, S Pleger, E Trautmann, H Voigt, I Wolf, S Antoniadis, P Arvanitis, D Bakatsglos, S Christakis, C Gerassimidis, T Kostakis, A Liovpis, A Manolis, A Matsagas, M Pappas, S Alsayegh, F Losonczy, H Bernath, B Domjan, G Gyani, E Kecskes, G Lakatos, J Ledniczki, I Mayer, K Nyuzo, B Zeher, M Pinjala, R Agnihotri, V Balraj, A Chakraborty, A Desai, S Elangovan, A Goswami, P Rupert, E Toraskar, K Venkatesh, K Gaine, S Connaughton, J Costello, R Liston, R Zubieta, RM Fematt, FMA Esponda, JAB Maldonado, DRB Serrano, ME Perez, FEG Montalvo, CL Marquez, SL Sanchez, AQ Diaz, SR Serrano, AT de la Vega, MIV Faridi, S Javaid, M Khan, F Malik, AZ Sadiq, M Yusaf-Shah, M Musial, J Biedziuk, B Gellert, R Klonowski, W Kosiniau-Kamysz, A Kuta, M Prajs, Z Sell, M Tadeusz, K Witkiewicz, W Wysota, J Franca, A Abreu, R Campello, MDC Cartucho, D Lohmann, C Moreira, P Paulino, A Reis, A de Morais, MLR de Abreu, TT Tulbure, D Andrei, M Christian, P Ciurea, M Constantin, P Enachescu, M Gostian, O Grintescu, IM Mimor, O Natalia, H Puiac, C Valerica, S Sulimov, VA Belentsov, S Dubrovnaya, N Eliseeva, E Fridman, I Kazantchian, P Mashtacov, B Redkin, A Rodoman, G Shershnev, V Zhidkov, K Gaspa, L Barta, P Benova, K Duris, T Fecik, J Hajas, J Herman, O Lehotsky, J Macek, V Pradova, V Arcelus, J Carrascosa, M Luque, RC Gil, JD de Souza, PD Enfedaque, MA Gonzalo, FE Sanchez, FG Garcia, MG Lobo-Beristain, JL Lopez, L Rodriguez, JAN Paredes, RM Rodriguez, JLR Cantero, AR Lorenzo, PR Legarre, ALS Sanchez, AC Cardenas, MJS Bernad, RV Moreno, JRV Doerffler, J Beer, J Brunner, B Chopard, P Doerffler, J Fischer, J Ludwig, C Peter, J Rime, F Salomon, F Ulrich, M Angchaisuksiri, P Chetanachan, M Chuamuangphan, N Insiripong, S Nawarawong, W Ben Salah, A Ghedira, H Houman, MH Mohamed, M Samir, K Zouheir, J Ongen, G Altintas, F Cirak, AK Demirtas, N Dokucu, A Erden, F Guven, H Halezeroglu, S Karaoglan, H Kaynar, L Tereci, H Yildirim, C Cohen, A Calvey, T Gallegos, N Gaminara, E James, A Jeffreys, M Jowett, N Keaney, N Kesteven, P Khan, Z Mackie, P Mallick, A Marval, P Parapia, L Picozzi, N Praveen, B Satchi, G Valerio, D Tapson, V Anderson, F Antonacci, A Baker, G Beaver, R Becker, W Beckett, C Borchardt, C Briggs, M Bruckman, J Buck, L Caushaj, P Chausow, A Chowdary, M Christopulos, D Cica, P Cody, J Condit, B Cronin, S Cysyk, B Diefendorf, A Driggers, S Ellis, P Elvenia, J Feinbloom, D Feldman, M Fischer, M Froehlich, J Frost, C Gaffey, J Galster, R Geldmeier, R George, J Glielmi, V Goodwin, J Gottlieb, A Gray, B Harrington, D Henry, E Hernandez, C Hill, D Hutchinson, M Johnson, J Johnson, R Kapre, S Kowaloff, H Krodel, J Lehman, J Marney, T Marshall, I McDaniels, M Middleton, R Mitchell, P Nelson, C Netherland, S Ogden, M Packard, K Pieske, M Poole, L Radford, M Rathbun, S Roberts, C Robinson, M Rollins, D Rubinate, D Schmidt, C Scott, J Shutt, S Slone, B Spyropoulos, A Subramanian, S Sullivan, J Timmerman, C Wheeler, C White, D White, N Whitehead, A Wright, J Young, D AF Kakkar, Ajay K. Cohen, Alexander T. Tapson, Victor F. Bergmann, Jean-Francois Goldhaber, Samuel Deslandes, Bruno Huang, Wei Anderson, Frederick A., Jr. Cherfi, Lyes Ammour, Dehbia Bentakouk, Cherif Bourenane, Razika Grainat, Nadia Maarouf, Abderahmane Sissaoui, Abdelhak Gallus, Alexander Ayyar, Venkatraman Crimmins, Denis Gan, Eng McRae, Simon Seldon, Michael Singh, Bhuwan Siddiqui, F. M. Moula, Kaniz Nawaz, Taimor Nazimuddin, Khwaja Rahman, Saiyeedur Sarker, Shyamal Rocha, Ana Brandao, Carlos Costa, Jose Macedo, Alex Marino, Roberto Menezes, Paulo Oigman, Wille Paiva, Marcelo Pantoja, Joao Schramm, Edgar Tandeitnik, Liane Timi, Jorge Benov, Haralambi Borisov, Stefan Dimitrov Lalov, Anton Mirazchijski, Boyko Postadziyan, Arman Sokolov, Krassimir Statelov, Evgenii Stefanov, Chavdar Stoykova, Antoaneta Tadzher, Sheri Todorov, Radostin Dennis, Rodolfo Duran, Freddy Rafael Mendez Posada, Alfredo Restrepo, Hector Roa, Jairo Villadiego, Juan Maly, Jaroslav Brabec, Tomas Gumulec, Jaromir Jochymek, Roman Kellnerova, Ivana Kvasnicka, Jan Penka, Miroslav Skarkova, Jindra Slezak, Premysl Vit, Patrik Vojtisek, Petr Gobran, Hadi El Rahman, Alaa Mahmaud Aba El Haddad, Alaa Gorgy, George Sobhy Rizk-Allah, Mounir Sholkamy, Sherif Bergmann, Jean Francois Abinader, Marid Abou Khoudir, Falah Boyer, Jean-Francois Brun, Natacha Canet, Bernard Collard, Catherine Cordier, Christophe Durroux, Claire Emmerich, Joseph Friocourt, Patrick Genay, Patrick Ibouanga, Florent Moumen, Abdelrhani Philippe, Pierre Planchon, Pierre Protin, Yves Quere, Isabelle Rizcallah, Marie-Jeanne Zotz, Rainer Bensch, Kristina Bensmann, Klaus Dropmann, Axl Gerold, Dieter Gussmann, Andreas Kortmann, Bernd Kube, Lutz Kuster, Stefan Leupolz, Werner Neuhaus, Thomas Nobel, Wolfgang Pfiel, Sascha Pleger, Eberhard Trautmann, Harald Voigt, Ingo Wolf, Stefan Antoniadis, Pavlos Arvanitis, Dimitrios Bakatsglos, Spyridon Christakis, Christos Gerassimidis, Thomas Kostakis, Alkiviadis Liovpis, Anthanasios Manolis, Anastasakis Matsagas, Miltiadis Pappas, Stavros Alsayegh, Faisal Losonczy, Hajna Bernath, Bela Domjan, Gyula Gyani, Eva Kecskes, Gabor Lakatos, Jozsef Ledniczki, Istvan Mayer, Klara Nyuzo, Balint Zeher, Margit Pinjala, Ramakrishna Agnihotri, Vinod Balraj, A. Chakraborty, Amiya Desai, Sanjay Elangovan, Antony Goswami, Partha Rupert, Emmanuel Toraskar, Kedar Venkatesh, Kakollu Gaine, Sean Connaughton, John Costello, Richard Liston, Richard Zubieta, Ricardo Martinez Avila Fematt, Flor Mario Baeza Esponda, Juan Alejandro Benitez Maldonado, Daniel R. Escarela Serrano, Maricela Garcia Perez, Fernando Elias Lavalle Montalvo, Carlos Lopez Marquez, Santa Quesada Sanchez, Alejandro Ramirez Diaz, Santiago Tovar Serrano, Alejandro Villa de la Vega, Maria Isabel Faridi, Salman Javaid, Mansur Khan, Farrukh Malik, Asif Zafar Sadiq, Muzafaruddin Yusaf-Shah, Muhammad Musial, Jacek Biedziuk, Bartlomiej Gellert, Ryszard Klonowski, Wlodzimierz Kosiniau-Kamysz, Andrzey Kuta, Marcin Prajs, Zozislav Sell, Marek Tadeusz, Kalbarczyk Witkiewicz, Wojciech Wysota, Janusz Franca, Ana Abreu, Rui Cabral Campello, Maria da Gloria Cartucho, Daniel Lohmann, Corinna Moreira, Pedro Paulino, Aida Reis, Abilio Rojao de Morais, Maria Luisa de Abreu, Tiago Tribolet Tulbure, Dan Andrei, Muresan Christian, Pricop Ciurea, Mircea Constantin, Palivan Enachescu, Mihaela Gostian, Ovidiu Grintescu, Ioana Marina Mimor, Ovidiu Natalia, Hagau Puiac, Claudiu Valerica, Stan Sulimov, Vitalyi Andreevich Belentsov, Sergey Dubrovnaya, Nina Eliseeva, Ekaterina Fridman, Irina Kazantchian, Perch Mashtacov, Boris Redkin, Alexander Rodoman, Grigory Shershnev, Vladislav Zhidkov, Konstantin Gaspa, L'udovit Barta, Peter Benova, Katarina Duris, Tibor Fecik, Juraj Hajas, Jan Herman, Oto Lehotsky, Jan Macek, Vladimir Pradova, Viera Arcelus, Juan Carrascosa, Miguel Cuenca Luque, Rafael del Val Gil, Jose Diaz de Souza, Pedro Alvaro Enfedaque, Muriel Epelde Gonzalo, Francesc Garcia Sanchez, Florentino Guil Garcia, M. Luis Lobo-Beristain, Jose Lopez, Luciano Nieto Rodriguez, Jose Antonio Mateo Paredes, Ramon Ramos Rodriguez, Jose Luis Ruiz Cantero, Alberto Ruiz Lorenzo, Pedro Samperiz Legarre, Angel Luis Clavo Sanchez, Antonio Soto Cardenas, Maria Jose Valle Bernad, Reina Vela Moreno, Jeronimo Ramon Doerffler, Janine Beer, Jurg Brunner, Brigitte Chopard, Pierre Doerffler, Janine Fischer, Joseph Ludwig, Christian Peter, Jurg Rime, Francis Salomon, Franco Ulrich, Munch Angchaisuksiri, Pantep Chetanachan, Mariam Chuamuangphan, Nonlawan Insiripong, Somchai Nawarawong, Weerasak Ben Salah, Afif Ghedira, Habib Houman, Mohamed Habib Mohamed, Mnif Samir, Kammoun Zouheir, Jerbi Ongen, Gul Altintas, Faik Cirak, Ali Kadri Demirtas, Nazmi Dokucu, Ali Erden, Faruk Guven, Hulya Halezeroglu, Semih Karaoglan, Halim Kaynar, Leylagul Tereci, Hikmet Yildirim, Cuma Cohen, Alexander Calvey, Thomas Gallegos, Nick Gaminara, Elizabeth James, Anthony Jeffreys, Mike Jowett, Nigel Keaney, Niall Kesteven, Patrick Khan, Zafar Mackie, Peter Mallick, Abhiram Marval, Paul Parapia, L. Picozzi, Natalie Praveen, Bandipalyam Satchi, Gnanam Valerio, David Tapson, Victor Anderson, Fred Antonacci, Anthony Baker, Gennfer Beaver, Richard Becker, William Beckett, Cynthia Borchardt, Carla Briggs, Michael Bruckman, Joseph Buck, Lisa Caushaj, Philip Chausow, Alan Chowdary, Madhu Christopulos, Danielle Cica, Paula Cody, Jean Condit, Bruce Cronin, Sherill Cysyk, Barbara Diefendorf, Anne Driggers, Steven Ellis, Paula Elvenia, Jaeda Feinbloom, David Feldman, Mark Fischer, Marian Froehlich, James Frost, Christopher Gaffey, Joseph Galster, Ruth Geldmeier, Richard George, Joyce Glielmi, Vincent Goodwin, James Gottlieb, Anita Gray, Bruce Harrington, Darrell Henry, Edwina Hernandez, Cecilia Hill, David Hutchinson, Melissa Johnson, Juanita Johnson, Roberta Kapre, Sheela Kowaloff, Harvey Krodel, John Lehman, James Marney, Terri Marshall, Ingeborg McDaniels, Mary Middleton, Robert, III Mitchell, Phillip Nelson, Carrie Netherland, Susan Ogden, Maureen Packard, Keith Pieske, Marlys Poole, Lorie Radford, Martha Rathbun, Suman Roberts, Cathy Robinson, Margaret Rollins, David Rubinate, Donna Schmidt, Cheryl Scott, Julia Shutt, Sandra Slone, Betty Spyropoulos, Alex Subramanian, Seshan Sullivan, Jacqueline Timmerman, Carman Wheeler, Connie White, Diane White, Nancy Whitehead, Alva Wright, Joyce Young, Dereck CA ENDORSE Investigators TI Venous Thromboembolism Risk and Prophylaxis in the Acute Care Hospital Setting (ENDORSE Survey) Findings in Surgical Patients SO ANNALS OF SURGERY LA English DT Article ID FATAL PULMONARY-EMBOLISM; PREVENTION; SURGERY; HEPARIN; THROMBOSIS AB Objective: To evaluate venous thromboembolism (VTE) risk in patients who underwent a major operation, including the use of, and factors influencing, American College of Chest Physicians-recommended types of VTE prophylaxis. Summary Background Data: The Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) survey, conducted in 358 hospitals in 3 2 countries, reported that globally, more than 40% of at-risk patients do not receive VTE prophylaxis. Limited data are available regarding VTE prophylaxis practices according to surgery type and patient characteristics. Methods: Patients aged >= 18 years undergoing major surgery were included in this prespecified subanalysis. VTE risk and use of prophylaxis were determined from hospital medical records according to the 2004 American College of Chest Physicians guidelines. Multivariable analyses were performed to identify factors associated with VTE prophylaxis use. Results: Of the 18,461 patients in ENDORSE who had undergone major surgery, 17,084 (92.5%) were at-risk for VTE and 10,638 (62,3%) received prophylaxis. Use of prophylaxis varied according to major surgery type from 86.0% for orthopedic surgery to 53.8% in urologic/gynecologic and 53.6% in other procedures. Major orthopedic surgery was most strongly associated with prophylaxis use (hip replacement: odds ratio 6.2, 95% confidence interval [CI] 5.0-7.6; knee replacement: odds ratio 5.9, 95% CI 4.6-7.8). Conclusions: The majority of surgical patients are at high-risk for VTE Despite long-standing recognition of the high-risk for VTE in surgical patients, thromboprophylaxis remains underutilized. C1 [Kakkar, Ajay K.] Barts & London Queen Marys Sch Med & Dent, London SW3 6LR, England. [Kakkar, Ajay K.] Thrombosis Res Inst, London SW3 6LR, England. [Cohen, Alexander T.] Kings Coll Hosp London, London, England. [Tapson, Victor F.] Duke Univ, Med Ctr, Durham, NC USA. [Bergmann, Jean-Francois] Univ Paris 07, Hop Lariboisiere, Paris, France. [Goldhaber, Samuel] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. 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[Chetanachan, Mariam] Prapokkloa Hosp, Ampur Muang, Thailand. [Chuamuangphan, Nonlawan] Chiangrai Prachanukroh Hosp, Chiangrai, Thailand. [Insiripong, Somchai] Maharat Nakornratchasima Hosp, Korat, Thailand. [Nawarawong, Weerasak] Chiang Mai Med Sch, Chiang Mai, Thailand. [Ghedira, Habib] Hop Abderrahmane MAMI Ariana, Ariana, Tunisia. [Houman, Mohamed Habib] Hosp La Rabta, Tunis, Tunisia. [Mohamed, Mnif] Reg Hosp Mahares, Mahares, Tunisia. [Samir, Kammoun] Hedi Chaker Hosp, Sfax, Tunisia. [Zouheir, Jerbi] Hosp Habib Thameur, Tunis, Tunisia. [Altintas, Faik] Goztepe Training Hosp, Istanbul, Turkey. [Cirak, Ali Kadri] Dr Suat Seren Gogus Hastaliklari & Cerrahisi EAH, Izmir, Turkey. [Demirtas, Nazmi] Ozel Anadolu Cinar Hosp, Istanbul, Turkey. [Dokucu, Ali] Sisli Etfal Educ & Res Hosp, Istanbul, Turkey. [Erden, Faruk] Kacaeli Univ, Fac Med Hosp, Kacaeli, Turkey. [Guven, Hulya] Esrefpaza Hosp Izmir Metropolitan Municipal, Izmir, Turkey. [Halezeroglu, Semih] Sureyyapasa Thorac & Cardio Vasc Dis Teaching Hos, Istanbul, Turkey. [Karaoglan, Halim] Ozel Hatay Hosp, Antakya, Turkey. [Kaynar, Leylagul] MKD Oncol Hosp, Kayseri, Turkey. [Tereci, Hikmet] Vezirkopru Devlet Hastanesi, Samsun, Turkey. [Yildirim, Cuma] Gaziantep Univ, Sahinbey Hosp, Gaziantep, Turkey. [Calvey, Thomas] Royal Lancaster Infirm, Lancaster, Lancs, England. [Gallegos, Nick] Weston Gen Hosp, Weston Super Mare, N Somerset, England. [Gaminara, Elizabeth] West Herts Hosp NHS Trust, Hemel Hempstead, Herts, England. [James, Anthony] Neath Port Talbot Hosp, Bridgend, Mid Glam, Wales. [James, Anthony] Princess Wales Hosp, Bridgend, Mid Glam, Wales. [Jeffreys, Mike] Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England. [Jowett, Nigel] Withybush Gen Hosp, Haverfordwest, Pembroke, Wales. [Keaney, Niall] Sunderland Royal Hosp, Sunderland, Tyne & Wear, England. [Kesteven, Patrick] Newcastle Upon Tyne NHS Hosp Trust, Newcastle Upon Tyne, Tyne & Wear, England. [Khan, Zafar] Pilgrim Hosp, Boston, Lincs, England. [Mackie, Peter] Heatherwood & Wexham Pk Hosp NHS Trust, Slough, Berks, England. [Mallick, Abhiram] Leeds Gen Infirm, Leeds, W Yorkshire, England. [Mallick, Abhiram] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. [Marval, Paul] Derby Hosp NHS Fdn Trust, Derby, Derby, England. [Parapia, L.] Bradford Royal Infirm Univ Hosp, Bradford, Mid Glam, Wales. [Picozzi, Natalie] W Suffolk Hosp, Bury St Edmunds, Suffolk, England. [Praveen, Bandipalyam] Southend Hosp NHS Trust, Westcliff On Sea, Essex, England. [Satchi, Gnanam] Whiston Hosp, Prescot, England. [Valerio, David] Grantham Dist Hosp, Grantham, England. [Anderson, Fred] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Anderson, Fred] Univ Massachusetts Mem Hlth Care, Worcester, MA USA. [Antonacci, Anthony] Christ Hosp, Jersey City, NJ USA. [Baker, Gennfer] Cullman Reg Med Ctr, Cullman, AL USA. [Beaver, Richard] Sewickley Valley Hosp, Sewickley, PA USA. [Beaver, Richard] Med Ctr, Sewickley, PA USA. [Becker, William] VAMC Fargo, Fargo, ND USA. [Beckett, Cynthia] Flagstaff Med Ctr, Flagstaff, AZ USA. [Borchardt, Carla] Avera McKennan, Sioux Falls, SD USA. [Briggs, Michael] Innovis Hlth, Fargo, ND USA. [Bruckman, Joseph] Floyd Mem Hosp & Hlth Serv, New Albany, IN USA. [Buck, Lisa] Wadley Reg Med Ctr, Texarkana, TX USA. [Caushaj, Philip] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Chausow, Alan] El Camino Hosp, Sunnyvale, CA USA. [Chowdary, Madhu] Jeanes Hosp, Philadelphia, PA USA. [Christopulos, Danielle] Ogden Reg Med Ctr, Ogden, UT USA. [Cica, Paula] UPMC Horizon, Greenville, PA USA. [Cody, Jean] Southwestern Vermont Med Ctr, Bennington, VT USA. [Condit, Bruce] Cent Maine Med Ctr, Lewiston, ME USA. [Cronin, Sherill] Jewish Hosp, Louisville, KY USA. [Cysyk, Barbara] Upper Chesapeake Hlth Syst, Bel Air, MD USA. [Diefendorf, Anne] Concord Hosp, Concord, NH USA. [Driggers, Steven] Holy Family Mem, Manitowoc, WI USA. [Ellis, Paula] St Francis Hlth Ctr, Topeka, KS USA. [Elvenia, Jaeda] Wilcox Mem Hosp, Lihue, HI USA. [Feinbloom, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Feldman, Mark] Presbyterian Med Ctr, Dallas, TX USA. [Fischer, Marian] FF Thompson Hosp, Canandaigua, NY USA. [Froehlich, James] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Frost, Christopher] Methodist Med Ctr Oak Ridge, Oak Ridge, TN USA. [Gaffey, Joseph] McAllen Med Ctr, Mcallen, TX USA. [Galster, Ruth] Mercy Med Ctr, Roseburg, OR USA. [Geldmeier, Richard] Watauga Med Ctr, Boone, NC USA. [George, Joyce] St Johns Hosp, Tulsa, OK USA. [Glielmi, Vincent] Ephrata Community Hosp, Ephrata, PA USA. [Goodwin, James] Harrington Mem Hosp, Southbridge, MA USA. [Gottlieb, Anita] St Josephs Mercy Hlth Ctr, Hot Springs, AR USA. [Gray, Bruce] Greenville Hosp Syst Greenville Mem, Greenville, SC USA. [Harrington, Darrell] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Henry, Edwina] Med Ctr Terrell, Terrell, TX USA. [Hernandez, Cecilia] Sutter Med Ctr Sacramento SMG SMH, Sacramento, CA USA. [Hill, David] Waterbury Hosp & Hlth Ctr, Ctr Hlth, Waterbury, CT USA. [Hutchinson, Melissa] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Johnson, Juanita] Albemarle Hosp, Elizabeth City, NC USA. [Johnson, Roberta] John C Lincoln Hosp NM, Phoenix, AZ USA. [Kapre, Sheela] San Joaquin Gen Hosp, Stockton, CA USA. [Kowaloff, Harvey] Jordan Hosp Inc, Plymouth, MA USA. [Krodel, John] Norman Reg Hosp, Norman, OK USA. [Lehman, James] Genesis Med Ctr Davenport, Davenport, IA USA. [Marney, Terri] Plains Reg Med Ctr, Clovis, NM USA. [Marshall, Ingeborg] Gulf Hlth Hosp Inc DBA Thomas Hosp, Fairhope, AL USA. [McDaniels, Mary] Catawba Valley Med Ctr, Hickory, NC USA. [Middleton, Robert, III] Southwest Mississippi Reg Med Ctr, Mccomb, MS USA. [Mitchell, Phillip] Ft Sanders Reg Med Ctr, Knoxville, TN USA. [Nelson, Carrie] Rush Copley Med Ctr, Aurora, IL USA. [Netherland, Susan] Morehead Mem Hosp, Eden, NC USA. [Ogden, Maureen] Tampa Gen Hosp, Tampa, FL 33606 USA. [Packard, Keith] Alta Vista Reg Hosp, Las Vegas, NM USA. [Pieske, Marlys] Jamestown Hosp, Jamestown, ND USA. [Poole, Lorie] Thomasville Med Ctr, Thomasville, NC USA. [Radford, Martha] New York Univ Hosp Syst, New York, NY USA. [Rathbun, Suman] VAMC Oklahoma City, Oklahoma City, OK USA. [Roberts, Cathy] St Marys Hosp, Grand Junction, CO USA. [Robinson, Margaret] Midland Mem Hosp, Midland, TX USA. [Rollins, David] Lake Hosp Syst Inc, Willoughby, OH USA. [Rubinate, Donna] St Annes Hosp, Fall River, MA USA. [Schmidt, Cheryl] St Elizabeth Hosp, Appleton, WI USA. [Scott, Julia] Northern Nevada Med Ctr, Sparks, NV USA. [Shutt, Sandra] Blanchard Valley Reg Hlth Ctr, Findlay, OH USA. [Slone, Betty] Three Rivers Med Ctr, Louisa, KY USA. [Spyropoulos, Alex] Lovelace Med Ctr, Albuquerque, NM USA. [Subramanian, Seshan] Mercy Hosp & Med Ctr, Chicago, IL USA. [Sullivan, Jacqueline] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Timmerman, Carman] Rapid City Reg Hosp, Rapid City, SD USA. [Wheeler, Connie] Jordan Valley Hosp, W Jordan, UT USA. [White, Diane] Exeter Hosp, Exeter, NH USA. [White, Nancy] Mary Black Mem Hosp, Spartanburg, SC USA. [Whitehead, Alva] McLeod Reg Med Ctr, Florence, SC USA. [Wright, Joyce] Armstrong Cty Mem Hosp, Kittanning, PA USA. [Young, Dereck] North Mississippi Med Ctr, Tupelo, MS USA. RP Kakkar, AK (reprint author), Barts & London Queen Marys Sch Med & Dent, London SW3 6LR, England. EM akkakkar@tri-london.ac.uk RI Kaynar, Leylagul/F-6991-2013; Hagau, Natalia/B-7787-2012 OI Kaynar, Leylagul/0000-0002-2035-9462; FU sanofi-aventis (Paris, France) FX Sponsored by sanofi-aventis (Paris, France). Statistical analyses were performed by the Center for Outcomes Research (University of Massachusetts Medical School, Worcester, USA), which receives research funding from sanofi-aventis. NR 13 TC 52 Z9 56 U1 8 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2010 VL 251 IS 2 BP 330 EP 338 DI 10.1097/SLA.0b013e3181c0c58f PG 9 WC Surgery SC Surgery GA 549KC UT WOS:000274046300024 PM 20054273 ER PT J AU Raut, CP Wang, Q Manola, J Morgan, JA George, S Wagner, AJ Butrynski, JE Fletcher, CDM Demetri, GD Bertagnolli, MM AF Raut, Chandrajit P. Wang, Qian Manola, Judith Morgan, Jeffrey A. George, Suzanne Wagner, Andrew J. Butrynski, James E. Fletcher, Christopher D. M. Demetri, George D. Bertagnolli, Monica M. TI Cytoreductive Surgery in Patients with Metastatic Gastrointestinal Stromal Tumor Treated with Sunitinib Malate SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID IMATINIB MESYLATE; SURGICAL RESECTION; TYROSINE-KINASE; PHASE-III; THERAPY; GIST AB Background. In patients with metastatic gastrointestinal stromal tumor (GIST) on first-line imatinib (IM) undergoing cytoreductive surgery, response to IM at time of surgery correlates with completeness of resection and progression-free and overall survival (PFS, OS). Impact of surgery in IM-resistant patients on second-line sunitinib (SU) is unknown. Methods. Patients on SU undergoing surgery for metastatic GIST at our institution were reviewed. Response to SU at time of surgery was categorized as responsive disease (RD), limited progression (LP) or generalized progression (GP). Results. Fifty patients underwent surgery after a median 6.7 months of SU. Forty patients (80%) had prior surgery at initial presentation of GIST; 16 (32%) underwent prior surgery on IM. At time of surgery on SU, 10 patients (20%) had RD, 22 (44%) had LP, and 18 (36%) had GP. Resections were macroscopically complete in 25 patients (50%); completeness of resection did not correlate with response to SU. Complication rate was 54%; reoperations were required in 16%. Median PFS after surgery and start of SU was 5.8 and 15.6 months, respectively (median follow-up 15.2 months). Corresponding median OS was 16.4 and 26.0 months, respectively. Differences in PFS and OS based on response to SU were not significant. Younger age was prognostic of survival. Conclusion. Surgery is feasible in patients with metastatic GIST on SU, but incomplete resections are frequent and complication rates are high. Relevance of survival rates is difficult to assess given the selection bias. Benefits of surgery should be weighed against symptoms and alternative treatments. C1 [Raut, Chandrajit P.; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Raut, Chandrajit P.; Wang, Qian; Manola, Judith; Morgan, Jeffrey A.; George, Suzanne; Wagner, Andrew J.; Butrynski, James E.; Fletcher, Christopher D. M.; Demetri, George D.; Bertagnolli, Monica M.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Qian; Manola, Judith] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. [Morgan, Jeffrey A.; George, Suzanne; Wagner, Andrew J.; Butrynski, James E.; Demetri, George D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. EM craut@partners.org NR 12 TC 32 Z9 35 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 IS 2 BP 407 EP 415 DI 10.1245/s10434-009-0784-y PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 557SR UT WOS:000274690900012 PM 19898902 ER PT J AU Barkley, C Bellon, J Smith, B Wong, J Gadd, M Taghian, A Winer, E Iglehart, J Harris, J Golshan, M AF Barkley, C. Bellon, J. Smith, B. Wong, J. Gadd, M. Taghian, A. Winer, E. Iglehart, J. Harris, J. Golshan, M. TI Can Axillary Node Dissection Be Omitted in a Subset of Patients with Low Local and Regional Failure? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Barkley, C.; Bellon, J.; Wong, J.; Iglehart, J.; Golshan, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Winer, E.; Harris, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, B.; Gadd, M.; Taghian, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S53 EP S54 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700146 ER PT J AU Kim, E Sharko, J Drohan, B Roche, C Zhou, Y Specht, M Gadd, M Smith, BL Hughes, KS AF Kim, E. Sharko, J. Drohan, B. Roche, C. Zhou, Y. Specht, M. Gadd, M. Smith, B. L. Hughes, K. S. TI The Utility of Natural Language Processing (NLP) in determining the Incidence of High Risk Breast Disease and the Subsequent Development of Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Kim, E.; Sharko, J.; Drohan, B.; Roche, C.; Zhou, Y.; Specht, M.; Gadd, M.; Smith, B. L.; Hughes, K. S.] Massachusetts Gen Hosp, Dept Surg Oncol, 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S58 EP S58 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700163 ER PT J AU Liu, R Wade, JE Wolinsky, JB Winer, JH Catalano, PJ Wagner, AJ Grinstaff, MW Colson, YL Raut, CP AF Liu, R. Wade, J. E. Wolinsky, J. B. Winer, J. H. Catalano, P. J. Wagner, A. J. Grinstaff, M. W. Colson, Y. L. Raut, C. P. TI Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence in Mouse Model of Sarcoma: A Novel Investigational Therapy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Liu, R.; Wade, J. E.; Winer, J. H.; Colson, Y. L.; Raut, C. P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wolinsky, J. B.; Grinstaff, M. W.] Boston Univ, Boston, MA 02215 USA. [Catalano, P. J.; Wagner, A. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S31 EP S32 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700080 ER PT J AU Pandalai, PK Dominguez, FJ Michaelson, J Tanabe, KK AF Pandalai, P. K. Dominguez, F. J. Michaelson, J. Tanabe, K. K. TI Clinical value of radiographic staging inpatients diagnosed with AJCC stage III melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Pandalai, P. K.; Tanabe, K. K.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Michaelson, J.] Massachusetts Gen Hosp, Dept Pathol, Div Surg Oncol, Boston, MA 02114 USA. [Dominguez, F. J.] Pontificia Univ Catolica Chili, Sch Med, Dept Surg Oncol, Santiago, Chile. 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S110 EP S110 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700333 ER PT J AU Pandalai, PK Patel, D Chung, DC Lauwers, GY Yoon, SS AF Pandalai, P. K. Patel, D. Chung, D. C. Lauwers, G. Y. Yoon, S. S. TI Prophylactic total gastrectomy for hereditary diffuse gastric cancer: surgical and pathological results SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Pandalai, P. K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chung, D. C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Patel, D.] Massachusetts Gen Hosp, Ctr Risk Anal, Boston, MA 02114 USA. [Yoon, S. S.] Univ Penn, Div Endocrine, Philadelphia, PA 19104 USA. [Yoon, S. S.] Univ Penn, Oncol Surg Hosp, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S70 EP S70 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700202 ER PT J AU Saund, MS Al Natour, RH Huang, Q Boosalis, VA Gold, JS AF Saund, M. S. Al Natour, R. H. Huang, Q. Boosalis, V. A. Gold, J. S. TI Tumor Size and Depth Predict Rate of Lymph Node Metastasis and Utilization of Lymph Node Sampling in Surgically Managed Gastric Carcinoids SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Saund, M. S.; Al Natour, R. H.; Huang, Q.; Gold, J. S.] Brigham & Womens Hosp, VA Boston Healthcare Syst, W Roxbury, MA USA. [Boosalis, V. A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. RI Gold, Jason/O-5112-2014 OI Gold, Jason/0000-0002-2925-4755 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S66 EP S66 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700192 ER PT J AU Stucky, CH Pockaj, BA Novotny, PA Sloan, JA Sargent, DJ O'Connell, MJ Beart, RW Skibber, J Nelson, H Weeks, JC AF Stucky, C. H. Pockaj, B. A. Novotny, P. A. Sloan, J. A. Sargent, D. J. O'Connell, M. J. Beart, R. W. Skibber, J. Nelson, H. Weeks, J. C. TI Individual Item Analysis of Quality of Life Assessments Related to Laparoscopic-assisted Colectomy in the COST Trial 93-46-53 (INT 0146) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Stucky, C. H.; Pockaj, B. A.] Mayo Clin Arizona, Phoenix, AZ USA. [Novotny, P. A.; Sloan, J. A.; Sargent, D. J.; Nelson, H.] Mayo Clin, Rochester, MN USA. [O'Connell, M. J.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Beart, R. W.] Univ So Calif, Los Angeles, CA USA. [Skibber, J.] MD Anderson, Houston, TX USA. [Weeks, J. C.] Dana Farber Canc Inst, 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S36 EP S36 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700094 ER PT J AU Wasif, N Ko, CY Farrell, J Wainberg, Z Hines, OJ Reber, H Tomlinson, JS AF Wasif, N. Ko, C. Y. Farrell, J. Wainberg, Z. Hines, O. J. Reber, H. Tomlinson, J. S. TI Impact of Tumor Grade on Prognosis in Pancreatic Cancer: Should We Include Grade in AJCC Staging? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 63rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-07, 2010 CL St Louis, MO SP Soc Surg Oncol C1 [Wasif, N.] John Wayne Canc Inst, Santa Monica, CA USA. [Ko, C. Y.; Farrell, J.; Wainberg, Z.; Hines, O. J.; Reber, H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Tomlinson, J. S.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2010 VL 17 SU 1 BP S91 EP S91 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 560KY UT WOS:000274902700269 ER PT J AU Koyama, S Eden, UT Brown, EN Kass, RE AF Koyama, Shinsuke Eden, Uri T. Brown, Emery N. Kass, Robert E. TI Bayesian decoding of neural spike trains SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS LA English DT Article DE Point process; State-space model; Recursive Bayesian filter; Sequential Gaussian approximation; Neural decoding ID RECEPTIVE-FIELD PLASTICITY; MAXIMUM-LIKELIHOOD-ESTIMATION; MOTOR CORTEX; NEURONAL POPULATION; POINT-PROCESSES; HUMAN BRAIN; MODELS; ENSEMBLE; PATTERNS; POSITION AB Perception, memory, learning, and decision making are processes carried out in the brain. The performance of such intelligent tasks is made possible by the communication of neurons through sequences of voltage pulses called spike trains. It is of great interest to have methods of extracting information from spike trains in order to learn about their relationship to behavior. In this article, we review a Bayesian approach to this problem based on state-space representations of point processes. We discuss some of the theory and we describe the way these methods are used in decoding motor cortical activity, in which the hand motion is reconstructed from neural spike trains. C1 [Koyama, Shinsuke; Kass, Robert E.] Carnegie Mellon Univ, Dept Stat, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kass, Robert E.] Carnegie Mellon Univ, Ctr Neural Basis Cognit, Dept Machine Learning, Pittsburgh, PA 15213 USA. RP Koyama, S (reprint author), Carnegie Mellon Univ, Dept Stat, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. EM koyama@stat.cmu.edu; tzvi@bu.edu; brown@neurostat.mgh.harvard.edu; kass@stat.cmu.edu FU [RO1 MH064537]; [RO1 EB005847]; [RO1 NS050256] FX This work was supported by grants RO1 MH064537, RO1 EB005847 and RO1 NS050256. NR 68 TC 17 Z9 17 U1 1 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0020-3157 EI 1572-9052 J9 ANN I STAT MATH JI Ann. Inst. Stat. Math. PD FEB PY 2010 VL 62 IS 1 BP 37 EP 59 DI 10.1007/s10463-009-0249-x PG 23 WC Statistics & Probability SC Mathematics GA 536FS UT WOS:000273030900004 ER PT J AU Bakaeen, FG Chu, D Ratcliffe, M Gopaldas, RR Blaustein, AS Venkat, R Huh, J LeMaire, SA Coselli, JS Carabello, BA AF Bakaeen, Faisal G. Chu, Danny Ratcliffe, Mark Gopaldas, Raja R. Blaustein, Alvin S. Venkat, Raghunandan Huh, Joseph LeMaire, Scott A. Coselli, Joseph S. Carabello, Blase A. TI Severe Aortic Stenosis in a Veteran Population: Treatment Considerations and Survival SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVE-REPLACEMENT; ELDERLY-PATIENTS; DECISION-MAKING; IMPLANTATION; SURGERY; OCTOGENARIANS; ASSOCIATION; OUTCOMES AB Background. We examined factors affecting the choice of surgical versus medical treatment of severe aortic stenosis and evaluated associated patient survival. Methods. We retrospectively reviewed data from all patients diagnosed with severe aortic stenosis at a Veterans Affairs medical facility between January 1997 and April 2008. Results. Of 345 patients with severe aortic stenosis, 260 (75%) underwent surgical evaluation, and 205 (59%) underwent aortic valve replacement (AVR). The patient's decision to decline surgical referral or AVR (n = 47) and severe comorbidities (n = 34) were the top two reasons for medical treatment rather than AVR. The AVR group was younger (69.5 +/- 9.6 years versus 75.7 +/- 8.6 years; p < 0.001) and had a higher prevalence of symptoms (96% versus 71%; p < 0.001) than the medical group. The medical group had a lower cardiac ejection fraction (0.42 +/- 0.15 versus 0.50 +/- 0.12; p < 0.001) and was less likely to be independent in activities of daily living (64% versus 74%). The AVR group had higher survival rates than the medical patients at 1 year (92% versus 65%), 3 years (85% versus 29%), and 5 years (73% versus 16%; log-rank test p < 0.0001). Valve replacement was independently associated with decreased mortality (hazard ratio, 0.17; 95% confidence interval, 0.10 to 0.27; p < 0.0001). Conclusions. The management of severe aortic stenosis in veterans is sometimes limited to medical evaluation and treatment. Surgeons should be involved in the complex process of risk assessment, to select patients with severe aortic stenosis who would benefit from the survival advantage associated with AVR. (Ann Thorac Surg 2010;89:453-8) (C) 2010 by The Society of Thoracic Surgeons C1 [Bakaeen, Faisal G.] Michael E DeBakey VAMC, Dept Cardiothorac Surg, Houston, TX 77030 USA. Michael E DeBakey VAMC, Div Cardiol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Sect Adult Cardiac Surg, Houston, TX USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bakaeen, FG (reprint author), Michael E DeBakey VAMC, Dept Cardiothorac Surg, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 22 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2010 VL 89 IS 2 BP 453 EP 458 DI 10.1016/j.athoracsur.2009.10.033 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 547BV UT WOS:000273861100020 PM 20103320 ER PT J AU Bacharach, JM Slovut, DP Ricotta, J Sullivan, TM AF Bacharach, J. Michael Slovut, David P. Ricotta, Joseph Sullivan, Timothy M. TI Octogenarians are not at Increased Risk for Periprocedural Stroke following Carotid Artery Stenting SO ANNALS OF VASCULAR SURGERY LA English DT Article ID CHRONIC RENAL-INSUFFICIENCY; EMBOLIC PROTECTION; ELDERLY-PATIENTS; ENDARTERECTOMY; ANGIOPLASTY; STENOSIS; DEATH; COMPLICATIONS; AGE; REVASCULARIZATION AB Background: We analyzed the risk of adverse events following carotid angioplasty and stenting (CAS) in patients <80 years (group I) compared with those >= 80 years of age (group II). Methods: Prospective data from 224 patients who underwent 235 consecutive CAS procedures at three participating institutions were reviewed retrospectively. All subjects were enrolled in Food and Drug Administration-approved clinical trials of CAS in high-risk patients or in institutional protocols. Procedural details and angiographic morphology were reviewed in all cases. All patients underwent independent neurological evaluation at 24 hr and 30 days following CAS. Results: Mean age was 69.9 years in the younger cohort and 83.5 years in the older group. Embolic protection devices were successfully deployed in 97.5% of cases in group I compared with 98.7% in group II (p=nonsignificant [NS]). Procedural success, defined as <30% residual stenosis after CAS, was achieved in all cases. Mean hospital stay was similar in the two groups. Transient ischemia attacks occurred in 1.9% in group I and 1.3% in group II (p=NS). Within 30 days of CAS, the risk of minor or major stroke (p=NS) as well as the composite risk of stroke (minor or major) and death was 2.5% in group I and 3.8% in group II (p=NS). Multivariate logistic regression analysis showed that absence of hypertension (odds ratioi [OR]=0.38, p=0.0352) and chronic renal insufficiency (OR=2.62, p=0.0238) were significant predictors of the composite end point of stroke and all-cause mortality. Kaplan-Meier analysis revealed that survival and freedom from the combined end point of stroke and all-cause mortality were similar for patients in groups I and II. Conclusion: Octogenarians are not at increased risk of periprocedural adverse events following CAS compared to younger patients. Exclusion of high-risk patients from CAS based on age alone is unjustified. C1 [Bacharach, J. Michael] Heart Hosp S Dakota, Dept Cardiol, Sioux Falls, SD 57108 USA. [Bacharach, J. Michael] Univ S Dakota, Dept Med, Sioux Falls, SD USA. [Slovut, David P.] N Shore Med Ctr, Dept Cardiol, Salem, MA USA. [Slovut, David P.] N Shore Med Ctr, Dept Vasc Med, Salem, MA USA. [Slovut, David P.] Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. [Ricotta, Joseph] Mayo Clin, Dept Surg, Rochester, MN USA. [Sullivan, Timothy M.] Minneapolis Heart Inst, Dept Vasc & Endovasc Surg, Minneapolis, MN USA. RP Bacharach, JM (reprint author), Heart Hosp S Dakota, Dept Cardiol, 4500 W 69th St, Sioux Falls, SD 57108 USA. EM jhatch@ncheart.com NR 29 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD FEB PY 2010 VL 24 IS 2 BP 153 EP 159 DI 10.1016/j.avsg.2009.05.010 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 549US UT WOS:000274080400001 PM 19748765 ER PT J AU Sanchez, LA Illig, K Levy, M Jaff, M Trachiotis, G Shanley, C Irwin, E Jim, J Rossing, M Kieval, R AF Sanchez, Luis A. Illig, Karl Levy, Mark Jaff, Michael Trachiotis, Gregory Shanley, Charles Irwin, Eric Jim, Jeffrey Rossing, Martin Kieval, Robert TI Implantable Carotid Sinus Stimulator for the Treatment of Resistant Hypertension: Local Effects on Carotid Artery Morphology SO ANNALS OF VASCULAR SURGERY LA English DT Article ID SURGICAL TECHNIQUE; FEASIBILITY TRIAL; UNITED-STATES; BAROREFLEX; PREVALENCE; ACTIVATION; PRESSURE; SYSTEM AB Background: The Rheos (TM) System is a chronically implanted carotid sinus baroreflex activating system with a pulse generator and bilateral perivascular carotid sinus leads (CSLs) that is being evaluated in prospective clinical trials for the treatment of drug-resistant hypertension. We evaluated carotid artery structural integrity after implantation of the CSLs. Methods: To assess the effect of chronic CSL attachment, 29 CSLs were implanted on the common carotid arteries of eight sheep. The studies were terminated at 3 and 6 months postimplantation to assess anatomic and histologic changes. Additionally, 10 patients with resistant hypertension were enrolled in the Rheos Multicenter Feasibility Trial. Duplex ultrasound (DUS) was performed before device implantation and at 1 and 4 months postimplantation in this patient cohort. An independent core laboratory assessed all DUSs. Results: Ovine carotid angiography revealed no significant stenoses, while anatomic and histologic evaluations demonstrated electrode encapsulation in a thin layer of connective tissue with no evidence of stenosis, erosion, or inflammation. DUS evaluation revealed no significant increase in peak systolic velocities of the common and internal carotid arteries 1 and 4 months after initial implantation, indicating a lack of injury, remodeling, or stenosis. Conclusion: The current data suggest that the CSLs used with the Rheos System are not associated with the development of carotid stenosis or injury. These short-term data support the concept of CSL placement and merit long-term investigation in a larger multicenter prospective trial. C1 [Sanchez, Luis A.; Jim, Jeffrey] Washington Univ, Sch Med, Dept Surg, Div Vasc Surg, St Louis, MO 63110 USA. [Illig, Karl] Univ Rochester, Rochester, NY USA. [Levy, Mark] Virginia Commonwealth Univ, Richmond, VA USA. [Jaff, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Trachiotis, Gregory] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Shanley, Charles] Wayne State Univ, Detroit, MI USA. [Irwin, Eric] N Mem Med Ctr, Minneapolis, MN USA. [Rossing, Martin; Kieval, Robert] CVRx Inc, Maple Grove, MN USA. RP Sanchez, LA (reprint author), Washington Univ, Sch Med, Dept Surg, Div Vasc Surg, Campus Box 8109 Surg,660 S Euclid, St Louis, MO 63110 USA. EM sanchezl@wustl.edu NR 17 TC 10 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD FEB PY 2010 VL 24 IS 2 BP 178 EP 184 DI 10.1016/j.avsg.2009.10.003 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 549US UT WOS:000274080400004 PM 20036504 ER PT J AU Abularrage, CJ Patel, VI Crawford, RS Kwolek, CJ AF Abularrage, Christopher J. Patel, Virendra I. Crawford, Robert S. Kwolek, Christopher J. TI Carotid Stent Fracture with Recurrent High-Grade Stenosis SO ANNALS OF VASCULAR SURGERY LA English DT Article ID HEAD MOVEMENTS; ARTERY STENT; ANGIOPLASTY; SURVEILLANCE; RESTENOSIS; CORONARY; IMPACT AB Stent fracture is a rare complication after carotid angioplasty and stenting. Patient anatomy, stent design, and external forces may all be contributing risk factors. Treatment options include continued observation or reintervention by both endovascular and open techniques since patients are typically asymptomatic. We present a case of a 66-year-old male with carotid stent fracture who developed recurrent, high-grade, asymptomatic carotid artery stenosis that was treated with repeat carotid angioplasty and stenting. C1 [Abularrage, Christopher J.; Patel, Virendra I.; Crawford, Robert S.; Kwolek, Christopher J.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Abularrage, CJ (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM cacabularrage@partners.org NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD FEB PY 2010 VL 24 IS 2 AR 254.e11 DI 10.1016/j.avsg.2009.05.009 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 549US UT WOS:000274080400016 PM 19748762 ER PT J AU Bin Kim, H Wang, MH Ahmed, S Park, CH LaRocque, RC Faruque, ASG Salam, MA Khan, WA Qadri, F Calderwood, SB Jacoby, GA Hooper, DC AF Bin Kim, Hong Wang, Minghua Ahmed, Sabeena Park, Chi Hye LaRocque, Regina C. Faruque, Abu S. G. Salam, Mohammed A. Khan, Wasif A. Qadri, Firdausi Calderwood, Stephen B. Jacoby, George A. Hooper, David C. TI Transferable Quinolone Resistance in Vibrio cholerae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIDRUG EFFLUX PUMP; SINGLE-DOSE CIPROFLOXACIN; ESCHERICHIA-COLI; DNA GYRASE; DETERMINING REGION; GENE; DETERMINANTS; BANGLADESH; NON-O1; QNR AB Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera. C1 [Bin Kim, Hong; Wang, Minghua; Park, Chi Hye; LaRocque, Regina C.; Calderwood, Stephen B.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bin Kim, Hong] Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Songnam, South Korea. [Bin Kim, Hong] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Ahmed, Sabeena; Faruque, Abu S. G.; Salam, Mohammed A.; Khan, Wasif A.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Wang, Minghua] Fudan Univ, Inst Antibiot, Huashan Hosp, Shanghai 200433, Peoples R China. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org RI Kim, Hong Bin/J-5452-2012 OI Kim, Hong Bin/0000-0001-6262-372X FU United States Public Health Service [R01 AI57576, R01 AI43312, U01 AI058935, K01 TW07144]; National Institutes of Health; Ministry of Science and Technology; National Basic Research Program of China [2005CB0523101] FX This work was supported in part by grants R01 AI57576 (to D. C. H.), R01 AI43312 (to G. A. J.), U01 AI058935 (to S. B. C.), and K01 TW07144 (to R. C. L.) from United States Public Health Service, National Institutes of Health, and by a grant from the Ministry of Science and Technology, National Basic Research Program of China, 2005CB0523101 (to M. W.). NR 29 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2010 VL 54 IS 2 BP 799 EP 803 DI 10.1128/AAC.01045-09 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 547BR UT WOS:000273860600030 ER PT J AU Lat, A Thompson, GR Rinaldi, MG Dorsey, SA Pennick, G Lewis, JS AF Lat, Asma Thompson, George R., III Rinaldi, Michael G. Dorsey, Sheryl A. Pennick, Gennethel Lewis, James S., II TI Micafungin Concentrations from Brain Tissue and Pancreatic Pseudocyst Fluid SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PRACTICE GUIDELINES; PHARMACOKINETICS; CANDIDIASIS; FK463; ECHINOCANDIN; CASPOFUNGIN; INFECTIONS; RABBITS AB We report the attainment of micafungin concentrations from brain tissue and pancreatic pseudocyst fluid from two patients with invasive candidiasis. Micafungin was present in low levels at both body sites, indicating limited penetration into central nervous system (CNS) tissue and pancreatic fluid. Further studies are needed to fully characterize its pharmacokinetics at these locations, as micafungin may potentially serve as an alternative antifungal therapy for CNS or pancreatic candidal infections for which the currently recommended first-line therapy fails. C1 [Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX 78229 USA. [Lat, Asma; Thompson, George R., III] S Texas Vet Affairs Hlth Care Syst, San Antonio, TX 78229 USA. [Lat, Asma; Thompson, George R., III; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Dept Internal Med, Div Infect Dis, San Antonio, TX 78229 USA. [Rinaldi, Michael G.; Dorsey, Sheryl A.; Pennick, Gennethel] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. RP Lewis, JS (reprint author), Univ Hlth Syst, Dept Pharm, 4502 Med Dr, San Antonio, TX 78229 USA. EM james.lewis@uhs-sa.com NR 13 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2010 VL 54 IS 2 BP 943 EP 944 DI 10.1128/AAC.01294-09 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 547BR UT WOS:000273860600054 PM 19933794 ER PT J AU Kim, MS Boone, KB Victor, T Marion, SD Amano, S Cottingham, ME Ziegler, EA Zeller, MA AF Kim, Michelle S. Boone, Kyle B. Victor, Tara Marion, Sarah D. Amano, Stacy Cottingham, Maria E. Ziegler, Elizabeth A. Zeller, Michelle A. TI The Warrington Recognition Memory Test for Words as a Measure of Response Bias: Total Score and Response Time Cutoffs Developed on "Real World" Credible and Noncredible Subjects SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Malingering; symptom validity testing; Forensic neuropsychology; Head injury; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; MILD HEAD-INJURY; SUSPECT EFFORT; TEST-PERFORMANCE; SENSITIVITY; SPECIFICITY; IMPAIRMENT; DEFICITS; DYSFUNCTION; SYMPTOMS AB Several studies have examined the usefulness of the Warrington Recognition Memory Test-Words as a measure to detect suspect effort, although samples have generally been small and/or comprised of simulators rather than "real world" credible and noncredible patients. The current study examined the Warrington Recognition Memory Test-Words total score and response time of "real world" noncredible patients (as determined by motive to feign, failure on >= 2 independent measures of response bias, low cognitive scores inconsistent with normal ADLs; n = 190) versus credible patients (as determined by no motive to feign, failure of < 1 measure of response bias; n = 124) derived from an archival database of individuals from the Harbor-UCLA Medical Center, Department of Psychiatry, Outpatient Neuropsychology Service, and the private practice of the second author. Noncredible patients obtained significantly lower total scores and longer times to complete the task. A total correct cutoff of < 42 was found to have excellent specificity (91.9%) and sensitivity (88.9%), whereas a time cutoff of >= 207 ' was associated with 65.5% sensitivity at 90.7% specificity, and when the time cut-score was used in combination with the total score cutoff, an additional 5% of the noncredible participants were captured, raising overall sensitivity to 93.7% (at 87.1% specificity). Thus, the Warrington Recognition Memory Test-Words, although not originally created for the purposes of measuring suspect effort, appears to be an excellent measure for detecting response bias on neuropsychological testing. C1 [Kim, Michelle S.; Marion, Sarah D.; Amano, Stacy] Fuller Grad Sch Psychol, Pasadena, CA USA. [Boone, Kyle B.] Alliant Int Univ, Calif Sch Forens Studies, Ctr Forens Studies, Los Angeles, CA USA. [Victor, Tara] Calif State Univ Dominguez Hills, Dept Psychol, Carson, CA USA. [Cottingham, Maria E.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Ziegler, Elizabeth A.] Spokane VA Med Ctr, Spokane, WA USA. [Zeller, Michelle A.] W Los Angeles VA Med Ctr, Dept Psychol, Los Angeles, CA USA. RP Boone, KB (reprint author), 24564 Hawthorne Blvd,Suite 208, Torrance, CA 90505 USA. EM kboone@labiomed.org NR 35 TC 26 Z9 26 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD FEB PY 2010 VL 25 IS 1 BP 60 EP 70 DI 10.1093/arclin/acp088 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA 547DI UT WOS:000273865400007 PM 19906738 ER PT J AU Yu, CE Bird, TD Bekris, LM Montine, TJ Leverenz, JB Steinbart, E Galloway, NM Feldman, H Woltjer, R Miller, CA Wood, EM Grossman, M McCluskey, L Clark, CM Neumann, M Danek, A Galasko, DR Arnold, SE Chen-Plotkin, A Karydas, A Miller, BL Trojanowski, JQ Lee, VMY Schellenberg, GD Van Deerlin, VM AF Yu, Chang-En Bird, Thomas D. Bekris, Lynn M. Montine, Thomas J. Leverenz, James B. Steinbart, Ellen Galloway, Nichole M. Feldman, Howard Woltjer, Randall Miller, Carol A. Wood, Elisabeth McCarty Grossman, Murray McCluskey, Leo Clark, Christopher M. Neumann, Manuela Danek, Adrian Galasko, Douglas R. Arnold, Steven E. Chen-Plotkin, Alice Karydas, Anna Miller, Bruce L. Trojanowski, John Q. Lee, Virginia M. -Y. Schellenberg, Gerard D. Van Deerlin, Vivianna M. TI The Spectrum of Mutations in Progranulin A Collaborative Study Screening 545 Cases of Neurodegeneration SO ARCHIVES OF NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; AMYOTROPHIC-LATERAL-SCLEROSIS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MESSENGER-RNA; DEMENTIA; GENE; DISEASE; TDP-43; TAU; INCLUSIONS AB Background: Mutation in the progranulin gene (GRN) can cause frontotemporal dementia (FTD). However, it is unclear whether some rare FTD-related GRN variants are pathogenic and whether neurodegenerative disorders other than FTD can also be caused by GRN mutations. Objectives: To delineate the range of clinical presentations associated with GRN mutations and to define pathogenic candidacy of rare GRN variants. Design: Case-control study. Setting: Clinical and neuropathology dementia research studies at 8 academic centers. Participants: Four hundred thirty-four patients with FTD, including primary progressive aphasia, semantic dementia, FTD/amyotrophic lateral sclerosis (ALS), FTD/motor neuron disease, corticobasal syndrome/corticobasal degeneration, progressive supranuclear palsy, Pick disease, dementia lacking distinctive histopathology, and pathologically confirmed cases of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U); and 111 non-FTD cases (controls) in which TDP-43 deposits were a prominent neuropathological feature, including subjects with ALS, Guam ALS and/or parkinsonism dementia complex, Guam dementia, Alzheimer disease, multiple system atrophy, and argyrophilic grain disease. Main Outcome Measures: Variants detected on sequencing of all 13 GRN exons and at least 80 base pairs of flanking introns, and their pathogenic candidacy determined by in silico and ex vivo splicing assays. Results: We identified 58 genetic variants that included 26 previously unknown changes. Twenty-four variants appeared to be pathogenic, including 8 novel mutations. The frequency of GRN mutations was 6.9% (30 of 434) of all FTD-spectrum cases, 21.4% (9 of 42) of cases with a pathological diagnosis of FTLD-U, 16.0% ( 28 of 175) of FTD-spectrum cases with a family history of a similar neurodegenerative disease, and 56.2% (9 of 16) of cases of FTLD-U with a family history. Conclusions: Pathogenic mutations were found only in FTD-spectrum cases and not in other related neurodegenerative diseases. Haploinsufficiency of GRN is the predominant mechanism leading to FTD. C1 [Yu, Chang-En; Bird, Thomas D.; Bekris, Lynn M.; Steinbart, Ellen; Galloway, Nichole M.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr, Res Educ & Clin Ctr, Seattle, WA USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness, Res Educ & Clin Ctr, Seattle, WA USA. [Yu, Chang-En; Bekris, Lynn M.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Bird, Thomas D.; Leverenz, James B.; Steinbart, Ellen] Univ Washington, Sch Med, Dept Med, Div Neurol, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Med, Div Pathol, Seattle, WA 98195 USA. [Feldman, Howard] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Woltjer, Randall] Oregon Hlth & Sci Univ, Dept Neuropathol, Portland, OR 97201 USA. [Miller, Carol A.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Wood, Elisabeth McCarty; Chen-Plotkin, Alice; Trojanowski, John Q.; Lee, Virginia M. -Y.; Van Deerlin, Vivianna M.] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Trojanowski, John Q.; Lee, Virginia M. -Y.; Schellenberg, Gerard D.; Van Deerlin, Vivianna M.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Grossman, Murray; McCluskey, Leo; Clark, Christopher M.; Arnold, Steven E.; Chen-Plotkin, Alice] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Arnold, Steven E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Clark, Christopher M.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M. -Y.; Schellenberg, Gerard D.; Van Deerlin, Vivianna M.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Neumann, Manuela] Univ Munich, Ctr Neuropathol & Prion Res, Munich, Germany. [Danek, Adrian] Univ Munich, Neurol Klin, Munich, Germany. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Galasko, Douglas R.] Vet Affairs Med Ctr, San Diego, CA 92161 USA. [Karydas, Anna; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. RP Bird, TD (reprint author), 1660 S Columbian Way,GRECC, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu RI Neumann, Manuela/F-6558-2011; Arnold, Steven/J-7546-2012; Danek, Adrian/G-7339-2011; OI Danek, Adrian/0000-0001-8857-5383; Feldman, Howard/0000-0002-9258-4538 FU Veterans Affairs Biomedical Laboratory Research Development Merit Review; National Institutes of Health [AG10124, AG17586, AG005136-22, AG14382, AG008017]; German Federal Ministry of Education and Research [01GI0704] FX This work was funded by Veterans Affairs Biomedical Laboratory Research Development Merit Review, the National Institutes of Health (grants AG10124, AG17586, AG005136-22, AG14382, and AG008017), and the German Federal Ministry of Education and Research (grant 01GI0704). NR 54 TC 85 Z9 85 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2010 VL 67 IS 2 BP 161 EP 170 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 553NR UT WOS:000274374600005 PM 20142524 ER PT J AU Jakobiec, FA Bhat, P Colby, KA AF Jakobiec, Frederick A. Bhat, Pooja Colby, Kathryn A. TI Immunohistochemical Studies of Conjunctival Nevi and Melanomas SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PRIMARY ACQUIRED MELANOSIS; MALIGNANT MELANOCYTIC LESIONS; PROLIFERATIVE ACTIVITY; DYSPLASTIC NEVI; S100 PROTEIN; SPITZ NEVI; EXPRESSION; KI-67; ANTIBODY; BENIGN AB Objective: To evaluate the role of immunohistochemical methods in the diagnosis of benign and malignant conjunctival melanocytic proliferations. Design: Retrospective immunohistopathologic study. Methods: Paraffin-embedded tissue sections from 20 conjunctival nevi and 15 invasive melanomas were immunoreacted with antibodies against cellular antigens S-100 protein, MART-1, HMB-45, CD-45, and Ki-67 nuclear proliferation protein. Results: All nevi immunostained moderately to strongly for S-100 protein and MART-1. Results for HMB-45 were negative in the middle and lower subepithelial portions of 18 of 20 lesions; it was usually only weakly positive within the superficial junctional zone. Only 1 melanoma did not stain positively for S-100; MART-1 and HMB-45 were positive in all lesions at some level of intensity. Ki-67 positivity was restricted to the junctional zone of nevi and was diffuse in melanomas. The mean Ki-67 proliferation indices were 1.89% for the nevi and 17.3% for the melanomas. CD-45 can help to highlight lymphocytes that immunostain with Ki-67. Melanomas in situ and atypical primary acquired melanoses had more than twice the Ki-67 proliferation counts of intraepithelial junctional nevocytes (P < .001) and more intense HMB-45 cytoplasmic staining than junctional zone nevocytes. Conclusions: S-100 and MART-1 were not useful in separating benign from malignant lesions. Results for nevus cells beneath the junctional zone were overwhelmingly negative for HMB-45 and Ki-67. Two nevi and all melanomatous nodules were positive for HMB-45 (P < .001). A higher Ki-67 proliferation index convincingly separated melanomas from nevi (P <. 001). Immunostaining for HMB-45 and Ki-67 are valuable adjuncts to careful histopathologic evaluation in assessing benign and malignant conjunctival melanocytic tumors. C1 [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, David D Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Colby, Kathryn A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David D Cogan Lab Ophthalm Pathol, 243 Charles St,Ste 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 47 TC 27 Z9 27 U1 0 U2 3 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 FEB PY 2010 VL 128 IS 2 BP 174 EP 183 PG 10 WC Ophthalmology SC Ophthalmology GA 553OC UT WOS:000274375700002 PM 20142539 ER PT J AU Fay, A Nguyen, J Jakobiec, FA Meyer-Junghaenel, L Waner, M AF Fay, Aaron Nguyen, John Jakobiec, Frederick A. Meyer-Junghaenel, Lutz Waner, Milton TI Propranolol for Isolated Orbital Infantile Hemangioma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 [Fay, Aaron; Nguyen, John] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Div, Boston, MA 02114 USA. [Jakobiec, Frederick A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Meyer-Junghaenel, Lutz] St Joseph Hosp, Ctr Vasc Malformat Children, Berlin, Germany. [Waner, Milton] St Lukes Roosevelt Hosp, Vasc Birthmark Inst New York, New York, NY USA. RP Fay, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Div, 243 Charles St, Boston, MA 02114 USA. EM aaron_fay@meei.harvard.edu NR 3 TC 26 Z9 28 U1 0 U2 1 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 FEB PY 2010 VL 128 IS 2 BP 256 EP 258 PG 4 WC Ophthalmology SC Ophthalmology GA 553OC UT WOS:000274375700019 PM 20142556 ER PT J AU Rubin, BP Blanke, CD Demetri, GD DeMatteo, RP Fletcher, CDM Goldblum, JR Lasota, J Lazar, A Maki, RG Miettinen, M Noffsinger, A Washington, MK Krausz, T AF Rubin, Brian P. Blanke, Charles D. Demetri, George D. DeMatteo, Ronald P. Fletcher, Christopher D. M. Goldblum, John R. Lasota, Jerzy Lazar, Alexander Maki, Robert G. Miettinen, Markku Noffsinger, Amy Washington, Mary Kay Krausz, Thomas CA Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Gastrointestinal Stromal Tumor SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID TERM-FOLLOW-UP; DIFFERENTIAL-DIAGNOSIS; INTRAMURAL LEIOMYOMAS; DIFFERENT SITES; IMATINIB; KIT; MUTATIONS; CD117; LEIOMYOSARCOMAS; SPECTRUM C1 [Rubin, Brian P.; Goldblum, John R.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44195 USA. [Blanke, Charles D.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Blanke, Charles D.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr Canc Res, Boston, MA USA. [DeMatteo, Ronald P.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Melanoma Sarcoma Program, New York, NY 10021 USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Surg Pathol, Boston, MA 02115 USA. [Lasota, Jerzy; Miettinen, Markku] Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USA. [Lazar, Alexander] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Noffsinger, Amy; Krausz, Thomas] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. RP Rubin, BP (reprint author), Cleveland Clin, Dept Anat Pathol, L25,9500 Euclid Ave, Cleveland, OH 44195 USA. EM rubinb2@ccf.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 NR 22 TC 17 Z9 17 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2010 VL 134 IS 2 BP 165 EP 170 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 554SB UT WOS:000274453600006 PM 20121601 ER PT J AU Kind, AJH Smith, MA Liou, JI Pandhi, N Frytak, JR Finch, MD AF Kind, Amy J. H. Smith, Maureen A. Liou, Jinn-Ing Pandhi, Nancy Frytak, Jennifer R. Finch, Michael D. TI Discharge Destination's Effect on Bounce-Back Risk in Black, White, and Hispanic Acute Ischemic Stroke Patients SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Ethnic groups; Hospitalization; Rehabilitation; Skilled nursing facilities; Stroke ID LONG-TERM-CARE; NURSING-HOME RESIDENTS; RACIAL DISPARITIES; INTERNATIONAL-CLASSIFICATION; ADMINISTRATIVE DATA; POSTHOSPITAL CARE; MEDICARE; HOSPITALIZATION; COMMUNITY; REHOSPITALIZATION AB Kind AJH, Smith MA, Liou J-I, Pandhi N, Frytak JR, Finch MD. Discharge destination's effect on bounce-back risk in black, white, and Hispanic acute ischemic stroke patients. Arch Phys Med Rehabil 2010;91:189-95. Objective: To determine whether racial and ethnic effects on bounce-back risk (ie, movement to settings of higher care intensity within 30d of hospital discharge) in acute stroke patients vary depending on initial posthospital discharge destination. Design: Retrospective analysis of administrative data. Setting: Four hundred twenty-two hospitals, southern/eastern United States. Participants: All Medicare beneficiaries 65 years or more with hospitalization for acute ischemic stroke within one of the 422 target hospitals during the years 1999 or 2000 (N=63,679). Interventions: Not applicable. Main Outcome Measures: Adjusted predicted probabilities for discharge to and for bouncing back from each initial discharge site (ie, home, home with home health care, skilled nursing facility [SNF], or rehabilitation center) by race (ie, black, white, and Hispanic). Models included sociodemographics, comorbidities, stroke severity, and length of stay. Results: Blacks and Hispanics were significantly more likely to be discharged to home health care (blacks=21% [95% confidence interval (CI), 19.9-22.81, Hispanic=19% [17.1-21.7] vs whites=16% [15.5-16.8]) and less likely to be discharged to SNFs (blacks=26% [95% CI, 23.6-29.3], Hispanics=28% [25.4-31.6] vs whites=33% [31.8-35.1]) than whites. However, blacks and Hispanics were significantly more likely to bounce back when discharged to SNFs than whites (blacks=26% [95% CI, 24.2-28.6], Hispanics=28% [24-32.6] vs whites=21% [20.3-21.9]). Hispanics had a lower risk of bouncing back when discharged home than either blacks or whites (Hispanics=14% [95% CI, 11.3-17] vs blacks=20% [18.4-22.2], whites=18% [16.8-18.3]). Patients discharged to home health care or rehabilitation centers demonstrated no significant differences ill bounce-back risk. Conclusions: Racial/ethnic bounce-back risk differs depending on initial discharge destination. Additional research is needed to fully understand this variation in effect. C1 [Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Geriatr Sect, Madison, WI USA. [Kind, Amy J. H.; Smith, Maureen A.; Liou, Jinn-Ing; Pandhi, Nancy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Pandhi, Nancy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Kind, Amy J. H.] William S Middleton Hosp, GRECC, US Dept Vet Affairs, Madison, WI USA. [Frytak, Jennifer R.] I3 Innovus, Eden Prairie, MN USA. [Finch, Michael D.] Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Kind, AJH (reprint author), William S Middleton VA Hosp, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ajk@medicine.wisc.edu FU National Institute of Aging [R01-AG19747]; University of Wisconsin's John A. Hartford Center of Excellence in Geriatrics Medicine and Education; National Institutes of Health [1KL2RR025012-01, KL2]; National Center for Research Resources, National Institutes of Health [1UL1RR025011] FX Supported by the National Institute of Aging (grant no. R01-AG19747); the University of Wisconsin's John A. Hartford Center of Excellence in Geriatrics Medicine and Education; National Institutes of Health (grant no. 1KL2RR025012-01) (Institutional Clinical and Translational Science Award [UW-Madison] [KL2]); the Health Innovation Program and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (grant no. 1UL1RR025011) from the Clinical and Translational Science Award program of the National Center for Research Resources, National Institutes of Health. NR 40 TC 6 Z9 6 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2010 VL 91 IS 2 BP 189 EP 195 DI 10.1016/j.apmr.2009.10.015 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592YJ UT WOS:000277417600005 PM 20159120 ER PT J AU Stone, JH Papaliodis, GN Costello, DJ AF Stone, John H. Papaliodis, George N. Costello, Daniel J. TI A 29-Year-Old Woman With Headache, Fever, Right Leg Numbness, and Dysphagia SO ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID NEURO-BEHCETS-DISEASE; NEUROLOGICAL INVOLVEMENT; OROGENITAL ULCERATION; NERVOUS-SYSTEM; MRI; MANAGEMENT; RECOMMENDATIONS; PATTERNS; THERAPY; UVEITIS C1 [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, 55 Fruit St Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org NR 28 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD FEB PY 2010 VL 62 IS 2 BP 283 EP 290 DI 10.1002/acr.20080 PG 8 WC Rheumatology SC Rheumatology GA 639MM UT WOS:000280978900020 PM 20191530 ER PT J AU Cho, I Min, HS Chun, EJ Park, SK Choi, Y Blumenthal, RS Rivera, JJ Nasir, K Kim, YJ Sohn, DW Oh, BH Park, YB Chang, HJ AF Cho, Iksung Min, Hee-Suk Chun, Eun Ju Park, Sue K. Choi, Yunhee Blumenthal, Roger S. Rivera, Juan J. Nasir, Khurram Kim, Yong-Jin Sohn, Dae-Won Oh, Byung-Hee Park, Young-Bae Chang, Hyuk-Jae TI Coronary atherosclerosis detected by coronary CT angiography in asymptomatic subjects with early chronic kidney disease SO ATHEROSCLEROSIS LA English DT Article DE Coronary atherosclerosis; Chronic kidney disease; Proteinuria; Coronary CT angiography; Coronary artery calcium score ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; STAGE RENAL-DISEASE; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; CAROTID ATHEROSCLEROSIS; MORTALITY; INSUFFICIENCY; HEMODIALYSIS; INDIVIDUALS AB Objectives: The purpose of this study is to assess the independent association between early CKD (stages 1-3a) with coronary atherosclerosis and the feasibility of risk stratification of coronary atherosclerosis according to The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines using non-invasive coronary angiography. Methods: We consecutively enrolled 4297 asymptomatic subjects who underwent coronary CT angiography as part of a general health evaluation and had estimated glomerular filtration rates (eGFR) over 45 ml/min/1.73m(2). Subjects were categorized from no CKD to stage 3a CKD, and multiple regression analyses for coronary atherosclerosis were performed. Results: Early CKD was an independent risk factor for coronary artery disease (CAD) and obstructive CAD. However, neither the risk of CAD nor CACS > 100 increased as stage of CKD advanced. The reason for unsuccessful stratification of coronary atherosclerosis risk was that the presence of proteinuria, which was used to define stages 1 and 2 CKD, was an independent risk factor for coronary atherosclerosis, but eGFR of 45-89 ml/min/1.73m(2) was not associated with coronary atherosclerosis. Conclusions: Early CKD was an independent risk factor for coronary atherosclerosis, and the risk stratification for coronary atherosclerosis should be based on the presence of proteinuria rather than decreased eGFR within early CKD. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Chang, Hyuk-Jae] Seoul Natl Univ, Bundang Hosp, Div Cardiol, Ctr Cardiovasc, Songnam, Gyeonggi Do, South Korea. [Cho, Iksung; Min, Hee-Suk; Kim, Yong-Jin; Sohn, Dae-Won; Oh, Byung-Hee; Park, Young-Bae] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul Natl Univ Hosp,Cardiovasc Ctr, Seoul 151, South Korea. [Chun, Eun Ju] Seoul Natl Univ, Bundang Hosp, Div Radiol, Songnam, Gyeonggi Do, South Korea. [Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Choi, Yunhee] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Med Res Collaborating Ctr, Seoul, South Korea. [Blumenthal, Roger S.; Rivera, Juan J.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MRI, PET, CT Program, Boston, MA 02114 USA. RP Chang, HJ (reprint author), Seoul Natl Univ, Bundang Hosp, Div Cardiol, Ctr Cardiovasc, Songnam, Gyeonggi Do, South Korea. EM ross1042@gmail.com RI Sohn, Dae Won/J-5516-2012; Park, Young-Bae/J-5490-2012; Kim, Yong-Jin/J-2745-2012; Oh, Byung-Hee/G-9875-2011 NR 29 TC 24 Z9 25 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2010 VL 208 IS 2 BP 406 EP 411 DI 10.1016/j.atherosclerosis.2009.08.040 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 548TK UT WOS:000273989200020 PM 19781704 ER PT J AU Heid, IM Henneman, P Hicks, A Coassin, S Winkler, T Aulchenko, YS Fuchsberger, C Song, K Hivert, MF Waterworth, DM Timpson, NJ Richards, JB Perry, JRB Tanaka, T Amin, N Kollerits, B Pichler, I Oostra, BA Thorand, B Frants, RR Illig, T Dupuis, J Glaser, B Spector, T Guralnik, J Egan, JM Florez, JC Evans, DM Soranzo, N Bandinelli, S Carlson, OD Frayling, TM Burling, K Smith, GD Mooser, V Ferrucci, L Meigs, JB Vollenweider, P van Dijk, KW Pramstaller, P Kronenberg, F van Duijn, CM AF Heid, Iris M. Henneman, Peter Hicks, Andrew Coassin, Stefan Winkler, Thomas Aulchenko, Yurii S. Fuchsberger, Christian Song, Kijoung Hivert, Marie-France Waterworth, Dawn M. Timpson, Nicholas J. Richards, J. Brent Perry, John R. B. Tanaka, Toshiko Amin, Najaf Kollerits, Barbara Pichler, Irene Oostra, Ben A. Thorand, Barbara Frants, Rune R. Illig, Thomas Dupuis, Josee Glaser, Beate Spector, Tim Guralnik, Jack Egan, Josephine M. Florez, Jose C. Evans, David M. Soranzo, Nicole Bandinelli, Stefania Carlson, Olga D. Frayling, Timothy M. Burling, Keith Smith, George Davey Mooser, Vincent Ferrucci, Luigi Meigs, James B. Vollenweider, Peter van Dijk, Ko Willems Pramstaller, Peter Kronenberg, Florian van Duijn, Cornelia M. TI Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: Results of genome-wide association analyses including 4659 European individuals SO ATHEROSCLEROSIS LA English DT Article DE Adiponectin; Genome-wide association study; Polymorphism; Cardiovascular disease; Metabolic syndrome ID METABOLIC SYNDROME; INSULIN-RESISTANCE; APM1 GENE; RISK; PROMOTER; DISEASE; OBESITY; PREVALENCE; CAUCASIANS; CONTRIBUTE AB Objective: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods: Wecombined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men-and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results: The ADIPOQ locus showed genome-wide significant p-values in the combined (p = 4.3 x 10(-24)) as well as in both women-and men-specific analyses (p = 8.7 x 10(-17) and p = 2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci e x hibited association with plasma adiponectin (p > 0.01). Conclusions: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which e x plains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci e x plained the se x differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Coassin, Stefan; Kollerits, Barbara; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. [Heid, Iris M.; Winkler, Thomas] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. [Heid, Iris M.; Thorand, Barbara; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany. [Henneman, Peter; Amin, Najaf; Frants, Rune R.; van Dijk, Ko Willems; van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Hicks, Andrew; Fuchsberger, Christian; Pichler, Irene; Pramstaller, Peter] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Aulchenko, Yurii S.; Oostra, Ben A.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Song, Kijoung; Waterworth, Dawn M.; Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA. [Hivert, Marie-France] Univ Sherbrooke, Serv Endocrinol, Dept Med, Quebec City, PQ, Canada. [Timpson, Nicholas J.; Glaser, Beate; Evans, David M.; Smith, George Davey] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England. [Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. [Richards, J. Brent; Spector, Tim; Soranzo, Nicole] Kings Coll London, London SE1 7EH, England. [Perry, John R. B.; Frayling, Timothy M.] Peninsula Med Sch, Exeter, Devon, England. [Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Egan, Josephine M.; Carlson, Olga D.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Soranzo, Nicole] Wellcome Trust Sanger Inst, Hinxton, England. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, Florence, Italy. [Burling, Keith] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands. [Pramstaller, Peter] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Kronenberg, F (reprint author), Innsbruck Med Univ, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, Innsbruck, Austria. EM Florian.Kronenberg@i-med.ac.at RI Kronenberg, Florian/B-1736-2008; Willems van Dijk, Ko/A-1798-2008; Fuchsberger, Christian/C-9646-2010; Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Pramstaller, Peter/C-2357-2008; Thorand, Barbara/B-5349-2014; Fox, Laura /C-6249-2016; Davey Smith, George/A-7407-2013; OI Pichler, Irene/0000-0001-8251-0757; Monsalve, Beatriz Elena/0000-0002-5994-866X; Dupuis, Josee/0000-0003-2871-3603; St Pourcain, Beate/0000-0002-4680-3517; Evans, David/0000-0003-0663-4621; Kronenberg, Florian/0000-0003-2229-1120; Willems van Dijk, Ko/0000-0002-2172-7394; Aulchenko, Yurii/0000-0002-7899-1575; Thorand, Barbara/0000-0002-8416-6440; Davey Smith, George/0000-0002-1407-8314; Fuchsberger, Christian/0000-0002-5918-8947; Soranzo, Nicole/0000-0003-1095-3852 FU Medical Research Council [G0600705, G0800582, G9815508]; NHLBI NIH HHS [N01 HC025195]; NIDDK NIH HHS [R01 DK075787, R01 DK075787-01A1] NR 34 TC 88 Z9 90 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2010 VL 208 IS 2 BP 412 EP 420 DI 10.1016/j.atherosclerosis.2009.11.035 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 548TK UT WOS:000273989200021 PM 20018283 ER PT J AU Oates, JC AF Oates, Jim C. TI The biology of reactive intermediates in systemic lupus erythematosus SO AUTOIMMUNITY LA English DT Article DE Nitric oxide; systemic lupus erythematosus; reactive oxygen species; free radicals; oxidative stress ID NITRIC-OXIDE SYNTHASE; MRL-LPR/LPR MICE; SMOOTH-MUSCLE-CELLS; MRL/LPR MICE; MITOCHONDRIAL HYPERPOLARIZATION; ENDOTHELIAL-CELLS; 3-NITROTYROSINE LEVELS; MYCOPHENOLATE-MOFETIL; AUTOIMMUNE-DISEASE; SIGNALING PATHWAYS AB Systemic lupus erythematosus (SLE) is an autoimmune syndrome marked by autoantibody production. Innate immunity is essential to transform humoral autoimmunity into the clinical lupus phenotype. Nitric oxide (NO) is a membrane-permeable signaling molecule involved in a broad array of biologic processes through its ability to modify proteins, lipids, and DNA and alter their function and immunogenicity. The literature regarding mechanisms through which NO regulates inflammation and cell survival is filled with contradictory findings. However, the effects of NO on cellular processes depend on its concentration and its interaction with reactive oxygen. Understanding this interaction will be essential to determine mechanisms through which reactive intermediates induce cellular autoimmunity and contribute to a sustained innate immune response and organ damage in SLE. C1 [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Med Serv, Charleston, SC USA. [Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. RP Oates, JC (reprint author), 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA. EM oatesjc@musc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR045476]; GCRC [M01RR001070]; VA Research Enhancement; Arthritis Foundation; Alliance for Lupus Research FX This publication was made possible by Grant AR045476 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, GCRC Grant M01RR001070, an award from the VA Research Enhancement Award Program, a VA Merit Award funding from the Arthritis Foundation, and the Alliance for Lupus Research. Special thanks go to Gary Gilkeson, MD, for reviewing the manuscript before submission. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 60 TC 18 Z9 18 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD FEB PY 2010 VL 43 IS 1 BP 56 EP 63 DI 10.3109/08916930903374683 PG 8 WC Immunology SC Immunology GA 545GU UT WOS:000273721300007 PM 20001422 ER PT J AU Haapasalo, A Viswanathan, J Bertram, L Soininen, H Tanzi, RE Hiltunen, M AF Haapasalo, Annakaisa Viswanathan, Jayashree Bertram, Lars Soininen, Hilkka Tanzi, Rudolph E. Hiltunen, Mikko TI Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 4th Intracellular Proteolysis Meeting CY MAY 27-29, 2009 CL Inst Estudis Catalans, Barcelona, SPAIN HO Inst Estudis Catalans DE aggresome; Alzheimer's disease (AD); presenilin; proteasome; protein aggregation; ubiquilin-1 ID AMYLOID PRECURSOR PROTEIN; ENDOPLASMIC-RETICULUM; GENETIC ASSOCIATION; DISULFIDE ISOMERASE; AGGRESOME FORMATION; UBIQUITIN; PROTEASOME; CELL; PRESENILIN-1; DEGRADATION AB Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of A beta (amyloid beta-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration. C1 [Haapasalo, Annakaisa; Viswanathan, Jayashree; Soininen, Hilkka; Hiltunen, Mikko] Univ Kuopio, Dept Neurol, Kuopio, Finland. [Haapasalo, Annakaisa; Viswanathan, Jayashree; Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany. [Bertram, Lars; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Hiltunen, M (reprint author), Univ Kuopio, Dept Neurol, Kuopio, Finland. EM mikko.hiltunen@uku.fi RI Bertram, Lars/K-3889-2015; OI Bertram, Lars/0000-0002-0108-124X; Chadchankar, Jayashree/0000-0002-0189-569X NR 55 TC 26 Z9 27 U1 1 U2 7 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 FEB PY 2010 VL 38 BP 150 EP 155 DI 10.1042/BST0380150 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 558RT UT WOS:000274763800025 PM 20074050 ER PT J AU Ellis, BC Gattoni-Celli, S Kindy, MS AF Ellis, Blake C. Gattoni-Celli, Sebastiano Kindy, Mark S. TI The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells SO BIOLOGICAL CHEMISTRY LA English DT Article DE cell signaling; dolphin; gene expression; keratinocyte; toxicity; transcription factors; vitamin D ID BOTTLE-NOSED-DOLPHIN; VITAMIN-D-RECEPTOR; ANTIMICROBIAL PROTEIN HCAP18; TURSIOPS-TRUNCATUS; METHYL-MERCURY; GLUCOCORTICOID-RECEPTOR; MOLECULAR CHAPERONES; STEROID-RECEPTORS; STRESS-PROTEINS; CALCITROIC ACID AB The Atlantic bottlenose dolphin has been the focus of much attention owing to the considerable impact of environmental stress on its health and the associated implications for human health. Here, we used skin cells from the dolphin to investigate the protective role of the vitamin D pathway against environmental stressors. We previously reported that dolphin skin cells respond to 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive metabolite of vitamin D3, by upregulation of the vitamin D receptor (VDR) and expression of several genes. Methylmercury is a highly bioaccumulative environmental stressor of relevance to the dolphin. We currently report that in dolphin cells sublethal concentrations of methylmercury compromise the ability of 1,25D3 to upregulate VDR, to transactivate a vitamin D-sensitive promoter, and to express specific target genes. These results help elucidate the effects of vitamin D and methylmercury on innate immunity in dolphin skin and potentially in human skin as well, considering similarities in the vitamin D pathway between the two species. C1 [Ellis, Blake C.; Gattoni-Celli, Sebastiano; Kindy, Mark S.] Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, Charleston, SC 29412 USA. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano; Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark S.] Med Univ S Carolina, Inst Neurosci, Charleston, SC 29425 USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Marine Biomed & Environm Sci Ctr, 331 Ft Johnson Rd, Charleston, SC 29412 USA. EM kindyms@musc.edu NR 99 TC 1 Z9 1 U1 1 U2 9 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD FEB-MAR PY 2010 VL 391 IS 2-3 BP 245 EP 258 DI 10.1515/BC.2010.014 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 564DU UT WOS:000275194300014 PM 20030593 ER PT J AU Coppell, JA Richardson, PG Soiffer, R Martin, PL Kernan, NA Chen, A Guinan, E Vogelsang, G Krishnan, A Giralt, S Revta, C Carreau, NA Iacobelli, M Carreras, E Ruutu, T Barbui, T Antin, JH Niederwieser, D AF Coppell, Jason A. Richardson, Paul G. Soiffer, Robert Martin, Paul L. Kernan, Nancy A. Chen, Allen Guinan, Eva Vogelsang, Georgia Krishnan, Amrita Giralt, Sergio Revta, Carolyn Carreau, Nicole A. Iacobelli, Massimo Carreras, Enric Ruutu, Tapani Barbui, Tiziano Antin, Joseph H. Niederwieser, Dietger TI Hepatic Veno-Occlusive Disease following Stem Cell Transplantation: Incidence, Clinical Course, and Outcome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Veno-occlusive disease; Stem cell transplantation; Incidence; Outcome; Severity; Multiorgan failure ID BONE-MARROW-TRANSPLANTATION; ACUTE-RENAL-FAILURE; VENO-OCCLUSIVE DISEASE; SINUSOIDAL OBSTRUCTION SYNDROME; TISSUE-PLASMINOGEN ACTIVATOR; ORGAN DYSFUNCTION SYNDROME; DAILY INTRAVENOUS BUSULFAN; HIGH-DOSE CHEMOTHERAPY; INTENSIVE-CARE-UNIT; VERSUS-HOST-DISEASE AB The occurrence of hepatic veno-occlusive disease (VOD) has been reported in up to 60% of patients following stem cell transplantation (SCT), with incidence varying widely between studies depending on the type of transplant, conditioning regimen, and criteria used to make the diagnosis. Severe VOD is characterized by high mortality and progression to multiorgan failure (MOF); however, there is no consensus on how to evaluate severity. This review and analysis of published reports attempts to clarify these issues by calculating the overall mean incidence of VOD and mortality from severe VOD, examining the effect of changes in SCT practice on the incidence of VOD over time, and discussing the methods used to evaluate severity. Across 135 studies performed between 1979 and October 2007, the overall mean incidence of VOD was 13.7% (95% confidence interval [Cl] = 13.3%-14.1%). The mean incidence of VOD was significantly lower between 1979-1994 than between 1994-2007 (11.5% [95% Cl, 10.9%-12.1%] vs 14.6% [95% Cl, 14.0%-15.2%]; P<.05). The mortality rate from severe VOD was 84.3% (95% Cl, 79.6%-88.9%); most of these patients had MOF, which also was the most frequent cause of death. Thus, VOD is less common than early reports suggested, but the current incidence appears to be relatively stable despite recent advances in SCT, including the advent of reduced-intensity conditioning. The evolution of MOF in the setting of VOD after SCT can be considered a reliable indication of severity and a predictor of poor outcome. Biol Blood Marrow Transplant 16: 157-168 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Coppell, Jason A.] Royal Devon & Exeter Hosp, Haematol Ctr, Dept Haematol, Exeter EX2 5DW, Devon, England. [Richardson, Paul G.; Soiffer, Robert; Guinan, Eva; Revta, Carolyn; Carreau, Nicole A.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, Paul L.] Duke Univ, Med Ctr, Durham, NC USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chen, Allen; Vogelsang, Georgia] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Krishnan, Amrita] City Hope Canc Ctr, Duarte, CA USA. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Iacobelli, Massimo] Gentium SpA, Villa Guardia, Italy. [Carreras, Enric] Hosp Clin Barcelona, Barcelona, Spain. [Ruutu, Tapani] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Barbui, Tiziano] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Niederwieser, Dietger] Univ Leipzig, Leipzig, Germany. RP Coppell, JA (reprint author), Royal Devon & Exeter Hosp, Haematol Ctr, Dept Haematol, Level 1 Area B,Barrack Rd, Exeter EX2 5DW, Devon, England. EM jason.coppell@rdeft.nhs.uk; paul_richardson@dfci.harvard.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NCI NIH HHS [P01 CA142106, P01 CA142106-07] NR 142 TC 108 Z9 116 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2010 VL 16 IS 2 BP 157 EP 168 DI 10.1016/j.bbmt.2009.08.024 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DN UT WOS:000276730700002 PM 19766729 ER PT J AU Alyea, EP AF Alyea, Edwin P. TI Falling Chimerism after Reduced Intensity Conditioning Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID HEMATOPOIETIC-CELL TRANSPLANTATION; LEUKEMIA; IMPACT C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2010 VL 16 IS 2 BP 292 EP 293 DI 10.1016/j.bbmt.2008.05.012 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DN UT WOS:000276730700017 PM 20142046 ER PT J AU Tanwar, PS Kaneko-Tarui, T Zhang, LH Rani, P Taketo, MM Teixeira, J AF Tanwar, Pradeep S. Kaneko-Tarui, Tomoko Zhang, LiHua Rani, Poonam Taketo, Makoto M. Teixeira, Jose TI Constitutive WNT/Beta-Catenin Signaling in Murine Sertoli Cells Disrupts Their Differentiation and Ability to Support Spermatogenesis SO BIOLOGY OF REPRODUCTION LA English DT Article DE anti-Mullerian hormone; apoptosis; glial cell-derived neurotrophic factor; gonocyte; Mullerian-inhibiting substance; Sertoli cells; spermatogenesis; testis ID MULLERIAN-INHIBITING SUBSTANCE; SPERMATOGONIAL STEM-CELLS; SEXUAL DEVELOPMENT; C-KIT; MOUSE SPERMATOGENESIS; II RECEPTOR; INFERTILE MICE; SELF-RENEWAL; BETA-CATENIN; EXPRESSION AB Sertoli and germ cell interactions are essential for spermatogenesis and, thus, male fertility. Sertoli cells provide a specialized microenvironment for spermatogonial stem cells to divide, allowing both self-renewal and spermatogenesis. In the present study, we used mice with a conditional activated allele of the beta-catenin gene (Ctnnb1(tm1Mmt/+)) in Sertoli cells expressing Cre recombinase driven by the anti-Mullerian hormone (AMH; also known as Mullerian-inhibiting substance) type II receptor promoter (Amhr2(tm3(cre)Bhr/+)) to show that constitutively activated beta-catenin leads to their continuous proliferation and compromised differentiation. Compared to controls, Sertoli cells in mature mutant mice continue to express high levels of both AMH and glial cell-derived neurotrophic factor (GDNF), which normally are expressed only in immature Sertoli cells. We also show evidence that LiCl treatment, which activates endogenous nuclear beta-catenin activity, regulates both AMH and GDNF expression at the transcriptional level. The epididymides were devoid of sperm in the Amhr2(tm3(cre)Bhr/+); Ctnnb1(tm1Mmt/+) mice at all ages examined. We show that the mutant mice are infertile because of defective differentiation of germ cells and increased apoptosis, both of which are characteristic of GDNF overexpression in Sertoli cells. Constitutive activation of beta-catenin in Amhr2-null mice showed the same histology, suggesting that the phenotype was the result of persistent overexpression of GDNF. These results show that dysregulated wingless-related MMTV integration site/beta-catenin signaling in Sertoli cells inhibits their postnatal differentiation, resulting in increased germ cell apoptosis and infertility. C1 [Tanwar, Pradeep S.; Kaneko-Tarui, Tomoko; Zhang, LiHua; Rani, Poonam; Teixeira, Jose] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Tanwar, Pradeep S.; Kaneko-Tarui, Tomoko; Zhang, LiHua; Rani, Poonam; Teixeira, Jose] Harvard Univ, Sch Med, Boston, MA USA. [Taketo, Makoto M.] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto, Japan. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Thier 931,55 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.ed RI Kaneko-Tarui, Tomoko/E-3319-2010; OI Teixeira, Jose/0000-0002-6438-5064 FU NICHD [HD052701] FX Supported in part by a grant from the NICHD (HD052701). NR 58 TC 60 Z9 64 U1 0 U2 1 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 FEB PY 2010 VL 82 IS 2 BP 422 EP 432 DI 10.1095/biolreprod.109.079335 PG 11 WC Reproductive Biology SC Reproductive Biology GA 546AL UT WOS:000273779300022 PM 19794154 ER PT J AU Aichmayer, B Wiedemann-Bidlack, FB Gilow, C Simmer, JP Yamakoshi, Y Emmerling, F Margolis, HC Fratzl, P AF Aichmayer, Barbara Wiedemann-Bidlack, Felicitas B. Gilow, Christoph Simmer, James P. Yamakoshi, Yasuo Emmerling, Franziska Margolis, Henry C. Fratzl, Peter TI Amelogenin Nanoparticles in Suspension: Deviations from Spherical Shape and pH-Dependent Aggregation SO BIOMACROMOLECULES LA English DT Article ID DYNAMIC LIGHT-SCATTERING; ATOMIC-FORCE MICROSCOPY; ENAMEL MATRIX PROTEINS; SMALL-ANGLE; RECOMBINANT AMELOGENIN; OCTACALCIUM PHOSPHATE; MOUSE AMELOGENINS; SECRETORY-STAGE; CRYSTAL-GROWTH; IN-VITRO AB It is well-known that amelogenin self-assembles to form nanoparticles, usually referred to Lis amelogenin nanospheres, despite the fact that not much is known about their actual shape in solution In the Current paper, we combine SAXS and DLS to Study the three-dimensional shape of the recombinant amelogenins rP172 and rM179 Our results show for the first time that amelogenins build oblate nanoparticles in suspension using experimental approaches that do not require the proteins to be in contact with it support material surface. The SAXS studies give evidence for the existence of isolated amelogenin nano-oblates with aspect ratios in the range of 0 45-0 5 at pH values higher than pH 7 2 and show in aggregation of these nano-oblates at lower pH values. The role of the observed oblale shape in the formation of chain-like structures at physiological conditions is discussed its a key factor in the biomineralization of dental enamel C1 [Aichmayer, Barbara; Gilow, Christoph; Fratzl, Peter] Max Planck Inst Colloids & Interfaces, Dept Biomat, D-14424 Potsdam, Germany. [Simmer, James P.; Yamakoshi, Yasuo] Univ Michigan, Dent Res Lab, Ann Arbor, MI 48109 USA. [Wiedemann-Bidlack, Felicitas B.; Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. [Emmerling, Franziska] BAM Fed Inst Mat Res & Testing, D-12489 Berlin, Germany. RP Aichmayer, B (reprint author), Max Planck Inst Colloids & Interfaces, Dept Biomat, D-14424 Potsdam, Germany. EM aichmayer@mpikg.mpgde; hmargolis@forsyth.org RI Emmerling, Franziska/G-3011-2010 OI Emmerling, Franziska/0000-0001-8528-0301 FU National Institute of Dental and Craniofacial Research (NIDCR) [DE-016376, T32 DE-007327] FX We are grateful to Ingrid Zenke, Stefan Siegel, and Chenghao Li for file Support during the lab SAXS experiments and the synchrotron SAXS experiments that were performed at the mu-spot beamline at BESSY II (Berlin, Germany). This work was supported by Grant DE-016376 (HCM) from the National Institute of Dental and Craniofacial Research (NIDCR). F.B.W-B was also partially supported by Grant T32 DE-007327 from the NIDCR. NR 45 TC 19 Z9 20 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD FEB PY 2010 VL 11 IS 2 BP 369 EP 376 DI 10.1021/bm900983b PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 551MZ UT WOS:000274215000008 PM 20038137 ER PT J AU Ramaswamy, S Gottlieb, D Engelmayr, GC Aikawa, E Schmidt, DE Gaitan-Leon, DM Sales, VL Mayer, JE Sacks, MS AF Ramaswamy, Sharan Gottlieb, Danielle Engelmayr, George C., Jr. Aikawa, Elena Schmidt, David E. Gaitan-Leon, Diana M. Sales, Virna L. Mayer, John E., Jr. Sacks, Michael S. TI The role of organ level conditioning on the promotion of engineered heart valve tissue development in-vitro using mesenchymal stem cells SO BIOMATERIALS LA English DT Article DE Heart valves; Tissue engineering; Mechanical stimulation; Mesenchymal stem cells; Organ level conditioning; Engineered tissue development ID PULSATILE BIOREACTOR; CYCLIC FLEXURE; FLOW; SCAFFOLDS; COLLAGEN; MARROW; STRAIN; DIFFERENTIATION; CONSTRUCTS; LEAFLET AB We have previously shown that combined flexure and flow (CFF) augment engineered heart valve tissue formation using bone marrow-derived mesenchymal stem cells (MSC) seeded on polyglycolic acid (PGA)/poly-L-lactic acid (PLLA) blend nonwoven fibrous scaffolds (Engelmayr, et al., Biomaterials 2006; vol. 27 pp. 6083-95). In the present study, we sought to determine if these phenomena were reproducible at the organ level in a functional tri-leaflet valve. Tissue engineered valve constructs (TEVC) were fabricated using PGA/PLLA nonwoven fibrous scaffolds then seeded with MSCs. Tissue formation rates using both standard and augmented (using basic fibroblast growth factor [bFGF] and ascorbic acid-2-phosphate [AA2P]) media to enhance the overall production of collagen were evaluated, along with their relation to the local fluid flow fields. The resulting TEVCs were statically cultured for 3 weeks, followed by a 3 week dynamic culture period using our organ level bioreactor (Hildebrand et al., ABME, Vol. 32, pp. 1039-49, 2004) under approximated pulmonary artery conditions. Results indicated that supplemented media accelerated collagen formation (similar to 185% increase in collagen mass/MSC compared to standard media), as well as increasing collagen mass production from 3.90 to 4.43 pg/cell/week from 3 to 6 weeks. Using augmented media, dynamic conditioning increased collagen mass production rate from 7.23 to 13.65 pg/cell/week (88.8%) during the dynamic culture period, along with greater preservation of net DNA. Moreover, when compared to our previous CFF study, organ level conditioning increased the collagen production rate from 4.76 to 6.42 pg/cell/week (35%). Newly conducted CFD studies of the CFF specimen flow patterns suggested that oscillatory surface shear stresses were surprisingly similar to a tri-leaflet valve. Overall, we found that the use of simulated pulmonary artery conditions resulted in substantially larger collagen mass production levels and rates found in our earlier CFF study. Moreover, given the fact that the scaffolds underwent modest strains (similar to 7% max) during either CFF or physiological conditioning, the oscillatory surface shear stresses estimated in both studies may play a substantial role in eliciting MSC collagen production in the highly dynamic engineered heart valve fluid mechanical environment. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ramaswamy, Sharan; Schmidt, David E.; Gaitan-Leon, Diana M.; Sacks, Michael S.] Univ Pittsburgh, Dept Bioengn, Swanson Sch Engn, Cardiovasc Biomech Lab,McGowan Inst,Sch Med, Pittsburgh, PA 15219 USA. [Gottlieb, Danielle; Sales, Virna L.; Mayer, John E., Jr.] Harvard Univ, Sch Med, Dept Cardiac Surg, Childrens Hosp Boston, Boston, MA USA. [Engelmayr, George C., Jr.] Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA. [Aikawa, Elena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Sacks, MS (reprint author), Univ Pittsburgh, Dept Bioengn, Swanson Sch Engn, Cardiovasc Biomech Lab,McGowan Inst,Sch Med, 300 Technol Dr, Pittsburgh, PA 15219 USA. EM msacks@pitt.edu RI Sacks, Michael/F-3703-2011; Engelmayr, George/I-4368-2012 FU NIH [R01s HL-68816, HL-089750]; American Heart Association Scientist Development [0830061N, 0635620T] FX Funding for this work was provided by NIH R01s HL-68816 and HL-089750, and American Heart Association Scientist Development Grants 0830061N (Ramaswamy) and 0635620T (Sales). The authors would like to thank Mr. Steven M. Boronyak for his assistance with the custom-built index-matching chamber and performing the digitization of leaflet images. Finally, the authors also thank Mr. Chad Eckert for conducting the three-point bending tests. NR 50 TC 44 Z9 46 U1 0 U2 21 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 FEB PY 2010 VL 31 IS 6 BP 1114 EP 1125 DI 10.1016/j.biomaterials.2009.10.019 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 548RY UT WOS:000273985100011 PM 19944458 ER PT J AU Baum, L Chan, IHS Cheung, SKK Goggins, WB Mok, V Lam, L Leung, V Hui, E Ng, C Woo, J Chiu, HFK Zee, BCY Cheng, W Chan, MH Szeto, S Lui, V Tsoh, J Bush, AI Lam, CWK Kwok, T AF Baum, Larry Chan, Iris Hiu Shuen Cheung, Stanley Kwok-Kuen Goggins, William B. Mok, Vincent Lam, Linda Leung, Vivian Hui, Elsie Ng, Chelsia Woo, Jean Chiu, Helen Fung Kum Zee, Benny Chung-Ying Cheng, William Chan, Ming-Houng Szeto, Samuel Lui, Victor Tsoh, Joshua Bush, Ashley I. Lam, Christopher Wai Kei Kwok, Timothy TI Serum zinc is decreased in Alzheimer's disease and serum arsenic correlates positively with cognitive ability SO BIOMETALS LA English DT Article DE Alzheimer's disease; Aluminum; Arsenic; Metals; MMSE; Serum; Zinc ID AGE-AT-ONSET; TRACE-ELEMENTS; ALUMINUM; COPPER; BRAIN; IRON; IMBALANCES; ABSORPTION; DEMENTIA; RISK AB Zinc, copper, and iron aggregate A beta and accumulate in Alzheimer's disease (AD) plaques. Some metals are increased in AD vs. control serum. The authors examined levels of 12 metals in serum of 44 AD and 41 control subjects. Zinc decreased from 12.3 to 10.9 mu mol/L (means, p = 0.0007). Arsenic positively correlated with Mini-Mental State Examination score (p < 0.0001). Zinc deposition in brain amyloid might deplete zinc from other body compartments, such as serum. The arsenic correlation might be caused by the major contribution of seafood consumption to intake of both arsenic and docosahexaenoic acid, of which the latter may delay AD. C1 [Baum, Larry] Chinese Univ Hong Kong, Sch Pharm, Shatin, Hong Kong, Peoples R China. [Chan, Iris Hiu Shuen; Lam, Christopher Wai Kei] Chinese Univ Hong Kong, Dept Chem Pathol, Shatin, Hong Kong, Peoples R China. [Cheung, Stanley Kwok-Kuen; Mok, Vincent; Hui, Elsie; Ng, Chelsia; Woo, Jean; Kwok, Timothy] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China. [Goggins, William B.] Chinese Univ Hong Kong, Sch Publ Hlth, Shatin, Hong Kong, Peoples R China. [Lam, Linda; Leung, Vivian; Chiu, Helen Fung Kum; Lui, Victor; Tsoh, Joshua] Chinese Univ Hong Kong, Dept Psychiat, Shatin, Hong Kong, Peoples R China. [Zee, Benny Chung-Ying] Chinese Univ Hong Kong, Ctr Clin Trials, Shatin, Hong Kong, Peoples R China. [Cheng, William] Chinese Univ Hong Kong, Inst Chinese Med, Clin Trials Sect, Shatin, Hong Kong, Peoples R China. [Chan, Ming-Houng; Szeto, Samuel] Kwong Wah Hosp, Dept Med & Geriatr, Kowloon, Hong Kong, Peoples R China. [Bush, Ashley I.] Univ Melbourne, Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Bush, Ashley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Baum, L (reprint author), Chinese Univ Hong Kong, Sch Pharm, Shatin, Hong Kong, Peoples R China. EM lwbaum@cuhk.edu.hk RI Kwok, Timothy/C-3725-2008; Hossain, Sarah /C-7332-2009; Baum, Lawrence/B-1005-2013; Bush, Ashley/A-1186-2007; Woo, Jean/K-2625-2014; Mok, Vincent /N-6421-2015; OI Kwok, Timothy/0000-0001-9253-3549; Hossain, Sarah /0000-0003-1355-0979; Baum, Lawrence/0000-0002-5345-9355; Bush, Ashley/0000-0001-8259-9069; Woo, Jean/0000-0001-7593-3081; Zee, Benny Chung-Ying/0000-0002-7238-845X FU Chinese University of Hong Kong Institute of Chinese Medicine; Chinese University of Hong Kong; BUPA Foundation FX Supported by a grant from The Chinese University of Hong Kong Institute of Chinese Medicine, by a Chinese University of Hong Kong Direct Grant for Research, and by a BUPA Foundation medical research grant. NR 31 TC 58 Z9 59 U1 1 U2 17 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD FEB PY 2010 VL 23 IS 1 BP 173 EP 179 DI 10.1007/s10534-009-9277-5 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 536ZX UT WOS:000273083600016 PM 19911117 ER PT J AU Lloyd, JC Banez, LL Aronson, WJ Terris, MK Presti, JC Amling, CL Kane, CJ Freedland, SJ AF Lloyd, Jessica C. Banez, Lionel L. Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. Amling, Christopher L. Kane, Christopher J. Freedland, Stephen J. TI Estimated blood loss as a predictor of PSA recurrence after radical prostatectomy: results from the SEARCH database SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; radical prostatectomy; blood loss ID RETROPUBIC PROSTATECTOMY; CANCER RECURRENCE; LEARNING-CURVE; TRANSFUSION; SURVIVAL; SURGERY; RISK; METAANALYSIS; EXPERIENCE; CARCINOMA AB OBJECTIVE To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control. PATIENTS AND METHODS In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses. RESULTS Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of < 1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500-3499 mL, before decreasing again for patients with an EBL of >= 3500 mL. Men with an EBL of 2500-3499 mL had more than twice the risk of recurrence than men with an EBL of < 1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status. CONCLUSIONS There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion-related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study. C1 [Lloyd, Jessica C.; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol Surg, Dept Surg, Durham, NC 27710 USA. [Lloyd, Jessica C.; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC 27710 USA. [Lloyd, Jessica C.; Banez, Lionel L.; Freedland, Stephen J.] Duke Univ, Sch Med, Vet Affairs Med Ctr, Urol Sect, Durham, NC 27710 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Urol Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Vet Affairs Med Ctr, Augusta, GA 30912 USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Amling, Christopher L.] Univ Alabama, Div Urol, Birmingham, AL USA. [Kane, Christopher J.] Univ Calif San Diego, Sch Med, Urol Sect, Vet Affairs Med Ctr, San Diego, CA 92103 USA. [Kane, Christopher J.] Univ Calif San Diego, Sch Med, Div Urol, San Diego, CA 92103 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Box 2626 DUMC, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs; National Institute of Health [RR024126]; NIH [R01CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition; Department of Defense, Prostate Cancer Research Program; American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF) FX Supported by the Department of Veterans Affairs, National Institute of Health Training Grant TLq RR024126 (JCL), NIH R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (WJA), the Georgia Cancer Coalition (MKT), the Department of Defense, Prostate Cancer Research Program (LLB/SJF), and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. NR 21 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2010 VL 105 IS 3 BP 347 EP 351 DI 10.1111/j.1464-410X.2009.08792.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 544KW UT WOS:000273656600011 PM 19709073 ER PT J AU Azadzoi, KM Golabek, T Radisavljevic, ZM Yalla, SV Siroky, MB AF Azadzoi, Kazem M. Golabek, Tomasz Radisavljevic, Ziv M. Yalla, Subbarao V. Siroky, Mike B. TI Oxidative stress and neurodegeneration in penile ischaemia SO BJU INTERNATIONAL LA English DT Article DE erectile dysfunction; ischaemia; oxidative stress; neurodegeneration ID OXIDE SYNTHASE EXPRESSION; ERECTILE DYSFUNCTION; NITRIC-OXIDE; ACTIVATION; DISEASE; RAT; PATHOGENESIS; RELAXATION; DISRUPTION; AFFERENTS AB To seek markers of oxidative stress and examine neural structural integrity in chronic penile ischaemia using a rabbit model of arteriogenic erectile dysfunction (ED), as the role of ischaemia in penile neuropathy and the oxidative mechanism of neurodegeneration in ED remains unknown. A rabbit model of atherosclerosis-induced ED was developed by partial balloon de-endothelialization of the iliac arteries. After 10 weeks, intracavernosal blood flow and erectile function in the arteriogenic ED group were compared with age-matched controls. Erectile tissues were processed for analysis of oxidative stress markers and nerve fibre density using enzyme immunoassay and immunohistochemical staining, respectively. Oxidative stress-sensitive genes were determined with quantitative real-time polymerase chain reaction. Tissue ultrastructure was examined by transmission electron microscopy. Significant erectile tissue ischaemia, erectile dysfunction, increased levels of oxidative products, and marked nitrotyrosine immunoreactivity was evident in the ED group. Oxidative stress-sensitive genes encoding hypoxia inducible factor-1 alpha (HIF-1 alpha), superoxide dismutase (SOD), aldose reductase (AR) and nerve growth factor (NGF) were up-regulated in the ischaemic erectile tissue. These changes were associated with collapsed axonal and Schwann cell profiles, neurodegeneration, mitochondrial structural damage, increased caveolae, loss of endothelium, and sporadic vacuolization. Neuropathy appears to follow the vascular insult in arteriogenic ED. Neural injury in penile ischaemia involves a neurovascular phenomenon mediated by oxidative free radicals. Mitochondrial structural damage and increased HIF-1 alpha gene expression may be early signals of oxidative stress and neurodegeneration in ED. Up-regulation of SOD, AR and NGF may be a coordinated defensive reaction to oxidative radicals that seems to fail to prevent neural injury in the ischaemic penis. Our study introduces the concept of oxidative neurodegeneration in the pathophysiology of arteriogenic ED. Therapeutic strategies to protect penile nerves from free radical incursion may enhance the efficacy of surgical and pharmacological interventions in arteriogenic ED. C1 [Azadzoi, Kazem M.; Golabek, Tomasz; Yalla, Subbarao V.; Siroky, Mike B.] VA Boston Healthcare Syst, Boston, MA USA. [Azadzoi, Kazem M.; Golabek, Tomasz; Yalla, Subbarao V.; Siroky, Mike B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Radisavljevic, Ziv M.] Harvard Univ, Dept Urol, Sch Med, Boston, MA 02115 USA. RP Azadzoi, KM (reprint author), Surg Urol 151,150 S Huntington Ave, Boston, MA 02130 USA. EM kazadzoi@bu.edu FU United States Department of Veterans Affairs FX This study was supported by a Merit Review Grant from the United States Department of Veterans Affairs. NR 30 TC 11 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2010 VL 105 IS 3 BP 404 EP 410 DI 10.1111/j.1464-410X.2009.08717.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 544KW UT WOS:000273656600019 PM 19549113 ER PT J AU Turan, S Aydin, C Bereket, A Akcay, T Guran, T Yaralioglu, BA Bastepe, M Juppner, H AF Turan, Serap Aydin, Cumhur Bereket, Abdullah Akcay, Teoman Gueran, Tuelay Yaralioglu, Betul Akmen Bastepe, Murat Jueppner, Harald TI Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia SO BONE LA English DT Article DE Dentin matrix protein-1; Fibroblast growth factor-23 (FGF-23); Hypophosphatemia; Rickets; Tooth ID D-RESISTANT RICKETS; BONE MINERALIZATION; HYP MICE; IN-VIVO; PHOSPHATE; DEFECTS; MOUSE; DIFFERENTIATION; MANIFESTATIONS; DENTINOGENESIS AB An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we describe a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowing of his legs and showed hypophosphatemia due to insufficient renal phosphate retention. Serum alkaline phosphatase activity was elevated, with initially normal PTH. FGF23 was inappropriately normal at an older age while being treated with oral phosphate and 1,25(OH)(2)D. Similar clinical and biochemical findings, except for elevated FGF23 levels, were present in his 16-month-old brother and his 12.5-year-old female cousin; the parents of the three affected children are first-degree cousins. Nucleotide sequence analysis was performed on PCR-amplified exons encoding DMP-1 and flanking intronic regions. A novel homozygous frame-shift mutation (c.485Tdel; p.GLu163ArgfsX53) in exon 6 resulting in a premature stop codon was identified in all effected individuals. The parents and available unaffected siblings were heterozygous for c.485Tdel. Tooth growth and shape were normal for the index case, his affected brother and cousin, but their permanent and deciduous teeth displayed enlarged pulp chambers. The identified genetic mutation underscores the importance of DMP-1 mutations in the pathogenesis of ARHP. Furthermore, DMP-1 mutations appear to contribute, through yet unknown mechanisms, to tooth development. (C) 2009 Elsevier Inc. All rights reserved. C1 [Turan, Serap; Aydin, Cumhur; Bastepe, Murat; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Turan, Serap; Aydin, Cumhur; Bastepe, Murat; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Turan, Serap; Bereket, Abdullah; Akcay, Teoman; Gueran, Tuelay] Marmara Univ, Istanbul, Turkey. [Yaralioglu, Betul Akmen] Dentaura Dent Clin, Istanbul, Turkey. [Aydin, Cumhur] Gulhane Mil Med Acad, Ctr Dent Sci, Ankara, Turkey. RP Turan, S (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM serap.turan@marmara.edu.tr FU National Institutes of Health [R21 DK075856-01]; Scientific and Technical Research Council of Turkey (Tubitak); Scientific Human Resources Development (BAYG) FX This work was supported by the National Institutes of Health (R21 DK075856-01 to H.J.). Serap Turan is recipient of a fellowship from the Scientific and Technical Research Council of Turkey (Tubitak), Scientific Human Resources Development (BAYG) within the framework of Postdoctoral Research Fellowship program. Cumhur Aydin is a recipient of a fellowship from the Gulhane Military Medical Academy. The authors would like to thank Stephelynn DeLuca, D.D.S., Harvard School of Dental Medicine, for critically reviewing the dental findings. NR 36 TC 21 Z9 23 U1 0 U2 8 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 FEB PY 2010 VL 46 IS 2 BP 402 EP 409 DI 10.1016/j.bone.2009.09.016 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557XG UT WOS:000274702800022 PM 19796717 ER PT J AU Monfoulet, L Malaval, L Aubin, JE Rittling, SR Gadeau, AP Fricain, JC Chassande, O AF Monfoulet, Laurent Malaval, Luc Aubin, Jane E. Rittling, Susan R. Gadeau, Alain P. Fricain, Jean-Christophe Chassande, Olivier TI Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing SO BONE LA English DT Article DE Osteopontin; Bone sialoprotein; Cortical defect; Mineralization; Bone healing ID DRILL-HOLE INJURY; MESSENGER-RNA; IN-VITRO; OSTEOBLAST DIFFERENTIATION; HYDROXYAPATITE FORMATION; MATRIX PROTEINS; FRACTURE REPAIR; EXPRESSION; MICE; RESORPTION AB Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing. (C) 2009 Elsevier Inc. All rights reserved. C1 [Chassande, Olivier] Univ Bordeaux 2, INSERM, U577, F-33076 Bordeaux, France. [Malaval, Luc] INSERM, U890, F-42023 St Etienne, France. [Malaval, Luc] Univ Lyon, F-42023 St Etienne, France. [Aubin, Jane E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Rittling, Susan R.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Gadeau, Alain P.] INSERM, U828, F-33604 Pessac, France. [Chassande, Olivier] Univ Bordeaux 2, CHU Bordeaux, F-33604 Pessac, France. RP Chassande, O (reprint author), Univ Bordeaux 2, INSERM, U577, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM Olivier.Chassande@inserm.fr RI Malaval, Luc/D-2206-2011; Monfoulet, Laurent-Emmanuel/O-6508-2016; OI Malaval, Luc/0000-0002-8640-2646; Monfoulet, Laurent-Emmanuel/0000-0001-9836-0255; Aubin, Jane E./0000-0002-7268-5235 FU Canadian Institutes of Health Research [FRN83704] FX We thank Jerome Guignard from INSERM 0828 for technical assistance in the OPN-deficient mice facility and Pierre Costet from University of Bordeaux 2 transgenic animal facility for BSP-deficient animals. This work was supported by the Canadian Institutes of Health Research (FRN83704 to J.E. Aubin). NR 30 TC 31 Z9 31 U1 0 U2 4 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 FEB PY 2010 VL 46 IS 2 BP 447 EP 452 DI 10.1016/j.bone.2009.09.007 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557XG UT WOS:000274702800028 PM 19761880 ER PT J AU Lawson, EA Miller, KK Bredella, MA Phan, C Misra, M Meenaghan, E Rosenblum, L Donoho, D Gupta, R Klibanski, A AF Lawson, Elizabeth A. Miller, Karen K. Bredella, Miriam A. Phan, Catherine Misra, Madhusmita Meenaghan, Erinne Rosenblum, Lauren Donoho, Daniel Gupta, Rajiv Klibanski, Anne TI Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa SO BONE LA English DT Article DE Anorexia nervosa; IGF-I; Leptin; Androgens; Flat-panel volume CT ID GROWTH-FACTOR-I; PANEL VOLUME CT; 3-DIMENSIONAL MICROCOMPUTED TOMOGRAPHY; TRABECULAR ARCHITECTURE; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; DISTAL RADIUS; COMPUTED-TOMOGRAPHY; EATING-DISORDERS; ADOLESCENT GIRLS AB Osteopenia is a complication of anorexia nervosa (AN) associated with a two- to three-fold increase in fractures. Nutritional deficits and hormonal abnormalities are thought to mediate AN-induced bone loss. Alterations in bone microarchitecture may explain fracture risk independent of bone mineral density (BMD). Advances in CT imaging now allow for noninvasive evaluation of trabecular microstructure at peripheral sites in vivo. Few data are available regarding bone microarchitecture in AN. We therefore performed a cross-sectional study of 23 women (12 with AN and 11 healthy controls) to determine hormonal predictors of trabecular bone microarchitecture. Outcome measures included bone microarchitectural parameters at the ultradistal radius by flat-panel volume CT (fpVCT); BMD at the PA and lateral spine, total hip, femoral neck, and ultradistal radius by dual energy X-ray absorptiometry (DXA); and IGF-I, leptin, estradiol, testosterone, and free testosterone levels. Bone microarchitectural measures, including apparent (app.) bone volume fraction, app. trabecular thickness, and app. trabecular number, were reduced (p<0.03) and app. trabecular spacing was increased (p=0.02) in AN versus controls. Decreased structural integrity at the ultradistal radius was associated with decreased BMD at all sires (p <= 0.05) except for total hip. IGF-I, leptin, testosterone, and free testosterone levels predicted bone microarchitecture. All associations between both IGF-I and leptin levels and bone microarchitectural parameters and most associations between androgen levels and microarchitecture remained significant after controlling for body mass index. We concluded that bone microarchitecture is abnormal in women with AN. Endogenous IGF-I, leptin, and androgen levels predict bone microarchitecture independent of BMI. (C) 2009 Elsevier Inc. All rights reserved. C1 [Lawson, Elizabeth A.; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Rosenblum, Lauren; Donoho, Daniel; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lawson, Elizabeth A.; Miller, Karen K.; Bredella, Miriam A.; Phan, Catherine; Misra, Madhusmita; Meenaghan, Erinne; Rosenblum, Lauren; Donoho, Daniel; Gupta, Rajiv; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bredella, Miriam A.; Phan, Catherine; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM ealawson@partners.org FU National Institutes of Health [RO1 DK052625, MO1 RR01066, UL1 RR02575801]; Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center; Pfizer Inc.; Merck and Co FX We thank the nurses and bionutritionists in the Massachusetts General Hospital Clinical Research Center and the patients who participated in the study.; This work was supported in part by the following grants from the National Institutes of Health: RO1 DK052625, MO1 RR01066, UL1 RR02575801.; We also acknowledge the support of the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology-Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck and Co. NR 53 TC 45 Z9 45 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 EI 1873-2763 J9 BONE JI Bone PD FEB PY 2010 VL 46 IS 2 BP 458 EP 463 DI 10.1016/j.bone.2009.09.005 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557XG UT WOS:000274702800030 PM 19747572 ER PT J AU Maeda, Y Schipani, E Densmore, MJ Lanske, B AF Maeda, Yukiko Schipani, Ernestina Densmore, Michael J. Lanske, Beate TI Partial rescue of postnatal growth plate abnormalities in Ihh mutants by expression of a constitutively active PTH/PTHrP receptor SO BONE LA English DT Article DE Ihh; Bone; Growth plate; Jansen; PTHrP; Chondrocytes; Rescue ID ENDOCHONDRAL BONE-DEVELOPMENT; HORMONE-RELATED PEPTIDE; INDIAN-HEDGEHOG; PARATHYROID-HORMONE; TARGETED EXPRESSION; MICE; DIFFERENTIATION; PTHRP; CHONDROCYTES; SKELETON AB Indian hedgehog (Ihh) is essential for chondrocyte proliferation/differentiation and osteoblast differentiation during prenatal endochondral bone formation. Ihh expression in postnatal chondrocytes has a non-redundant role in maintaining a growth plate and sustaining trabecular bone after birth. Loss of Ihh in postnatal chondrocytes results in fusion of the growth plate and a decrease in trabecular bone. In order to normalize this abnormal chondrocyte phenotype and to investigate whether a putative rescue of the growth plate anomalies is sufficient to correct the severe alterations in the bone, we expressed a constitutively active PTH/PTHrP receptor (an Ihh downstream target) in the chondrocytes of Col2 alpha 1-Cre ER*: Ihh(dld) mice by mating Col2 alpha 1-Cre ER*; Ihh(fl/fl) mice with Col2 alpha 1-constitutively active PTH/PTHrP receptor transgenic mice (Jansen, J). Col2 alpha 1-Cre ER*; Ihh(f/f); J mice were then injected with tamoxifen at P0 to generate Col2 alpha 1-Cre ER*; Ihh(d/d); J mice. In contrast with the previously reported growth plate phenotype of Col2 alpha 1-Cre ER*; Ihh(d/d) mice that displayed ectopic chondrocyte hypertrophy at P7, growth plates of Col2 alpha 1-Cre ER*; Ihh(d/d); J double mutants were well organized, and exhibited a gene expression pattern similar to the one of control mice. However, expression of osteoblast markers and Dkk1, a Wnt signaling target, remains decreased in the bone collar of Col2 alpha 1-Cre ER*; Ihh(d/d); J mice when compared to control mice despite the rescue of abnormal chondrocyte differentiation. Moreover, proliferation of chondrocytes was still significantly impaired in Col2 alpha 1-Cre ER*; Ihh(d/d); J mice, and this eventually led to the fusion of the growth plate at P14. In summary, we have demonstrated that expression of a Jansen receptor in chondrocytes was able to rescue abnormal chondrocyte differentiation but not impaired chondrocyte proliferation and the bone anomalies in mice lacking the Ihh gene in chondrocytes after birth. Taken together, our findings suggest that Ihh has both PTHrP-dependent and -independent functions during postnatal endochondral bone development. (C) 2009 Elsevier Inc. All rights reserved. C1 [Maeda, Yukiko; Densmore, Michael J.; Lanske, Beate] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Schipani, Ernestina] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, Ernestina] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM beate_lanske@hsdm.harvard.edu FU NIH/NIAMS [AR050560] FX We thank Drs. T Sato and T Kobayashi for helpful suggestions. This work was supported by NIH/NIAMS AR050560 funding (BL). NR 23 TC 12 Z9 13 U1 1 U2 3 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 FEB PY 2010 VL 46 IS 2 BP 472 EP 478 DI 10.1016/j.bone.2009.09.009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557XG UT WOS:000274702800032 PM 19761883 ER PT J AU Tu, P Buckner, RL Zollei, L Dyckman, KA Goff, DC Manoach, DS AF Tu, Peichi Buckner, Randy L. Zollei, Lilla Dyckman, Kara A. Goff, Donald C. Manoach, Dara S. TI Reduced functional connectivity in a right-hemisphere network for volitional ocular motor control in schizophrenia SO BRAIN LA English DT Article DE saccadic eye movements; schizophrenia; anterior cingulate cortex; fMRI; executive control ID ANTERIOR CINGULATE CORTEX; MATTER DIFFUSION ANISOTROPY; COVERT SPATIAL ATTENTION; CONSCIOUS RESTING STATE; EVENT-RELATED FMRI; WHITE-MATTER; DEFAULT-MODE; CEREBRAL-CORTEX; BRAIN ACTIVITY; 1ST-EPISODE SCHIZOPHRENIA AB Patients with schizophrenia consistently show deficient performance on tasks requiring volitional saccades. We previously reported reduced fractional anisotropy in the white matter underlying right dorsal anterior cingulate cortex in schizophrenia, which, along with lower fractional anisotropy in the right frontal eye field and posterior parietal cortex, predicted longer latencies of volitional saccades. This suggests that reduced microstructural integrity of dorsal anterior cingulate cortex white matter disrupts connectivity in the right hemisphere-dominant network for spatial attention and volitional ocular motor control. To test this hypothesis, we examined functional connectivity of the cingulate eye field component of this network, which is located in dorsal anterior cingulate cortex, during a task comprising volitional prosaccades and antisaccades. In patients with schizophrenia, we expected to find reduced functional connectivity, specifically in the right hemisphere, which predicted prolonged saccadic latency. Twenty-seven medicated schizophrenia outpatients and 21 demographically matched healthy controls performed volitional saccades during functional magnetic resonance imaging. Based on task-related activation, seed regions in the right and left cingulate eye field were defined. In both groups, the right and left cingulate eye field showed positive correlations with the ocular motor network and negative correlations with the default network. Patients showed reduced positive functional connectivity of the cingulate eye field, specifically in the right hemisphere. Negative functional connectivity of the right cingulate eye field predicted faster saccades, but these relations differed by group, and were only present in controls. This pattern of relations suggests that the coordination of activity between ocular motor and default networks is important for efficient task performance and is disrupted in schizophrenia. Along with prior observations of reduced white matter microstructural integrity (fractional anisotropy) in schizophrenia, the present finding of reduced functional connectivity suggests that functional and structural abnormalities of the right cingulate eye field disrupt connectivity in the network for spatial attention and volitional ocular motor control. These abnormalities may contribute to deficits in overcoming prepotency in the service of directing eye gaze and attention to the parts of the environment that are the most behaviourally relevant. C1 [Tu, Peichi; Buckner, Randy L.; Dyckman, Kara A.; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Tu, Peichi; Buckner, Randy L.; Zollei, Lilla; Dyckman, Kara A.; Goff, Donald C.; Manoach, Dara S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Tu, Peichi] Natl Yang Ming Univ, Sch Life Sci, Inst Neurosci, Taipei 112, Taiwan. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.; Zollei, Lilla] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Buckner, Randy L.; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu FU Advanced Multimodal Neuroimaging Training Program [R90 DA023427-02]; National Institute for Mental Health [R01 MH67720, F32 MH082514]; National Alliance for Research on Schizophrenia and Depression; Mental Illness and Neuroscience Discovery (MIND) Institute; Howard Hughes Medical Institute; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Ellison Medical Foundation; National Center for Research Resources [P41RR14075] FX Advanced Multimodal Neuroimaging Training Program (R90 DA023427-02); National Institute for Mental Health (R01 MH67720, F32 MH082514); National Alliance for Research on Schizophrenia and Depression; Mental Illness and Neuroscience Discovery (MIND) Institute; Howard Hughes Medical Institute; National Institute for Biomedical Imaging and Bioengineering (R01EB006758); National Institute for Neurological Disorders and Stroke (R01 NS052585-01); Ellison Medical Foundation; National Center for Research Resources (P41RR14075). NR 103 TC 22 Z9 22 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 2010 VL 133 BP 625 EP 637 DI 10.1093/brain/awp317 PN 2 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 558VY UT WOS:000274777700025 PM 20159769 ER PT J AU Myung, JY Blumstein, SE Yee, E Sedivy, JC Thompson-Schill, SL Buxbaum, LJ AF Myung, Jong-yoon Blumstein, Sheila E. Yee, Eiling Sedivy, Julie C. Thompson-Schill, Sharon L. Buxbaum, Laurel J. TI Impaired access to manipulation features in Apraxia: Evidence from eyetracking and semantic judgment tasks SO BRAIN AND LANGUAGE LA English DT Article DE Apraxia; Manipulation knowledge; Perceptuomotor experiences; Implicit vs. explicit tasks; Lexical-semantic representation ID CONCEPTUAL KNOWLEDGE; LEXICAL DECISION; OBJECTS; APHASIA; REPRESENTATIONS; ACTIVATION; LANGUAGE; SYSTEMS AB Apraxic patients are known for deficits in producing and comprehending skilled movements. Two experiments tested their implicit and explicit knowledge about manipulable objects in order to examine whether such deficits accompany impairment in the conceptual representation of manipulation features. An eyetracking method was used to test implicit knowledge (Experiment 1): participants viewed a visual display on a computer screen and touched the corresponding object in response to an auditory input. Manipulation relationship among objects was not task-relevant, and thus the assessment of manipulation knowledge was implicit. Like the non-apraxic control patients, apraxic patients fixated on an object picture (e.g., "typewriter") that was manipulation-related to a target word (e.g., 'piano') significantly more often than an unrelated object picture (e.g., "bucket") as well as a visual control (e.g., "couch"). However, this effect emerged later than in the non-apraxic control group, suggesting impaired access to manipulation features in the apraxic group. In the semantic judgment task (Experiment 2), participants were asked to make an explicit judgment about the relationship of picture triplets of manipulable objects by choosing the pair with similar manipulation features. Apraxic patients performed significantly worse on this task than the non-apraxic control group. Both implicit and explicit measures of manipulation knowledge show that apraxia is not merely a perceptuomotor deficit of skilled movements, but results in a concomitant impairment in representing manipulation features and accessing them for cognitive processing. (C) 2009 Elsevier Inc. All rights reserved. C1 [Myung, Jong-yoon; Blumstein, Sheila E.; Sedivy, Julie C.] Brown Univ, Dept Cognit & Linguist Sci, Providence, RI 02912 USA. [Yee, Eiling; Thompson-Schill, Sharon L.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. [Thompson-Schill, Sharon L.; Buxbaum, Laurel J.] Moss Rehabil Res Inst, Philadelphia, PA USA. [Buxbaum, Laurel J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Blumstein, Sheila E.] Res Serv, Dept Vet Affairs Med Ctr, Providence, RI 02908 USA. [Blumstein, Sheila E.] Boston Univ, Harold Goodglass Aphasia Res Ctr, VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. RP Myung, JY (reprint author), 12569 Royal Wolf PL, Fairfax, VA 22030 USA. EM gklimt@alumni.brown.edu RI Yee, Eiling/F-2161-2010; Thompson-Schill, Sharon/M-1788-2013 FU NIH [NIDCD00314, NIDCD0081, MH62566, MH070850, NS36387, HD050836] FX This research was supported in part by NIH Grants NIDCD00314 to Brown University, NIDCD0081 to the Boston University School of Medicine, NIH Grant MH62566 to Julie Sedivy, NIH Grant MH070850 to Sharon L. Thompson-Schill, and NIH Grants NS36387 and HD050836 to Laurel Buxbaum. This material is the result of work supported by resources and the use of facilities at the Department of Veterans Affairs Medical Centers in Boston, MA and Providence, Rl. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. We thank Kathleen M. Kurowski, Audrey Kittredge, and Kathleen Kyle for their generou help with testing patients. NR 27 TC 23 Z9 23 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD FEB PY 2010 VL 112 IS 2 BP 101 EP 112 DI 10.1016/j.bandl.2009.12.003 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 566CP UT WOS:000275348000002 PM 20064657 ER PT J AU Moulder, S Li, HL Wang, ML Gradishar, WJ Perez, EA Sparano, JA Pins, M Yang, XM Sledge, GW AF Moulder, Stacy Li, Hailun Wang, Molin Gradishar, William J. Perez, Edith A. Sparano, Joseph A. Pins, Michael Yang, Ximing Sledge, George W. TI A phase II trial of trastuzumab plus weekly ixabepilone and carboplatin in patients with HER2-positive metastatic breast cancer: an Eastern Cooperative Oncology Group Trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Weekly ixabepilone; Carboplatin; Trastuzumab; Breast cancer ID EPOTHILONE-B ANALOG; WEEKLY PACLITAXEL; CLINICAL-TRIAL; SOLID TUMORS; BMS-247550; DOCETAXEL; ANTHRACYCLINE; CHEMOTHERAPY; RESISTANT; EFFICACY AB The epothilone B analogue, ixabepilone, binds to beta-tubulin, is effective for taxane-refractory metastatic breast cancer (MBC), and may be given every 3 weeks or weekly. We evaluated the efficacy of weekly ixabepilone (I) plus trastuzumab (T) and carboplatin (C) as first line therapy in HER2 + MBC. Patients with HER2+ (3+ by IHC or FISH amplified) MBC received I (15 mg/m(2) IV) and C (area under the curve, AUC = 2 IV) on days 1, 8, and 15 of a 28-day cycle for a maximum of 6 cycles, plus weekly T (4 mg/kg loading dose then 2 mg/kg IV) during chemotherapy then every 3 weeks (6 mg/kg IV) until disease progression. The primary objective was to determine whether the combination was associated with a response rate (RR) of at least 75%. Fifty-nine patients were treated, and 39 had HER2 overexpression confirmed in a central lab (cHER2+). For all treated patients, objective response occurred in 26 patients (44%; 95% CI 31-58%), median time to progression was 8.2 months (95% CI 6.3-9.9), and median overall survival was 34.7 months (95% CI 25.7 to [not reached]). Results were comparable for cHer2+ cancers. Grade 3-4 adverse events included neutropenia (49%), thrombocytopenia (14%), fatigue (12%), nausea (7%), diarrhea (7%), and neuropathy (7%). One patient died from treatment complications during cycle 1. Weekly ixabepilone and carboplatin plus trastuzumab have an acceptable toxicity profile, but are not likely to be associated with an RR of 75% in HER2+ MBC. Efficacy appears comparable to paclitaxel, carboplatin, and trastuzumab. C1 [Moulder, Stacy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Li, Hailun; Wang, Molin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gradishar, William J.; Pins, Michael; Yang, Ximing] Northwestern Univ, Evanston, IL USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Sparano, Joseph A.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Sledge, George W.] Indiana Univ, Med Ctr, Indianapolis, IN USA. RP Moulder, S (reprint author), Univ Texas MD Anderson Canc Ctr, 1155 Pressler St,Unit 1354,POB 301438, Houston, TX 77030 USA. EM smoulder@mdanderson.org FU Department of Health and Human Services; National Institutes of Health [CA23318, CA66636, CA21115, CA25224] FX This study was supported in part by grants from the Department of Health and Human Services and the National Institutes of Health (CA23318 to the ECOG statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center, CA25224 to NCCTG). NR 30 TC 27 Z9 27 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2010 VL 119 IS 3 BP 663 EP 671 DI 10.1007/s10549-009-0658-9 PG 9 WC Oncology SC Oncology GA 544AZ UT WOS:000273624900015 PM 20012354 ER PT J AU Shcherbina, A Cooley, J Lutskiy, MI Benarafa, C Gilbert, GE Remold-O'Donnell, E AF Shcherbina, Anna Cooley, Jessica Lutskiy, Maxim I. Benarafa, Charaf Gilbert, Gary E. Remold-O'Donnell, Eileen TI WASP plays a novel role in regulating platelet responses dependent on alpha IIb beta 3 integrin outside-in signalling SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Wiskott-Aldrich syndrome; platelet disorder; integrins; fibrin clot retraction; phosphatidylserine exposure ID WISKOTT-ALDRICH-SYNDROME; GLYCOPROTEIN-IIB-IIIA; SYNDROME PROTEIN; MEMBRANE SKELETON; CYTOPLASMIC DOMAIN; ARP2/3 COMPLEX; ACTIVATION; RECEPTOR; CYTOSKELETON; ADHESION AB P>The most consistent feature of Wiskott Aldrich syndrome (WAS) is profound thrombocytopenia with small platelets. The responsible gene encodes WAS protein (WASP), which functions in leucocytes as an actin filament nucleating agent -yet- actin filament nucleation proceeds normally in patient platelets regarding shape change, filopodia and lamellipodia generation. Because WASP localizes in the platelet membrane skeleton and is mobilized by alpha IIb beta 3 integrin outside-in signalling, we questioned whether its function might be linked to integrin. Agonist-induced alpha IIb beta 3 activation (PAC-1 binding) was normal for patient platelets, indicating normal integrin inside-out signalling. Inside-out signalling (fibrinogen, JON/A binding) was also normal for wasp-deficient murine platelets. However, adherence/spreading on immobilized fibrinogen was decreased for patient platelets and wasp-deficient murine platelets, indicating decreased integrin outside-in responses. Another integrin outside-in dependent response, fibrin clot retraction, involving contraction of the post-aggregation actin cytoskeleton, was also decreased for patient platelets and wasp-deficient murine platelets. Rebleeding from tail cuts was more frequent for wasp-deficient mice, suggesting decreased stabilisation of the primary platelet plug. In contrast, phosphatidylserine exposure, a pro-coagulant response, was enhanced for WASP-deficient patient and murine platelets. The collective results reveal a novel function for WASP in regulating pro-aggregatory and pro-coagulant responses downstream of integrin outside-in signalling. C1 [Shcherbina, Anna; Cooley, Jessica; Lutskiy, Maxim I.; Benarafa, Charaf; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Shcherbina, Anna] Res Inst Paediat Haematol, Moscow, Russia. [Gilbert, Gary E.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@idi.harvard.edu OI Benarafa, Charaf/0000-0002-2049-7769 FU National Institutes of Health [AI039574, HL59561, HL081407]; Jeffrey Modell Foundation FX We thank Drs John Cunningham and Arthur Nienhuis (St Jude Children's Research Hospital, Memphis, TN, USA) for wasp- mice, Dr Susanna Remold for advice on statistical analysis and Tessa LeCuyer and Michael Stolley for animal husbandry. We are grateful to the patients and control blood donors and to Drs Diana Beardsley, Francisco Bonilla, Raif Geha, Erwin Gelfand and the late Fred S. Rosen for procuring blood specimens. This work was supported by National Institutes of Health grants AI039574, HL59561, HL081407 and the Jeffrey Modell Foundation. NR 46 TC 12 Z9 13 U1 0 U2 1 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 FEB PY 2010 VL 148 IS 3 BP 416 EP 427 DI 10.1111/j.1365-2141.2009.07959.x PG 12 WC Hematology SC Hematology GA 543CH UT WOS:000273547000008 PM 19863535 ER PT J AU Souza, FF Fennessy, FM Yang, Q van den Abbeele, AD AF Souza, F. F. Fennessy, F. M. Yang, Q. van den Abbeele, A. D. TI PET/CT appearance of desmoid tumour of the chest wall SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID PATHOLOGICAL CORRELATION; RADIOLOGIC FINDINGS; SARCOMA; CT AB Desmoid tumours are rare, poorly circumscribed tumours that have a firm consistency and, although benign, have a remarkable tendency to infiltrate into surrounding structures. Extra-abdominal desmoid tumours involve mainly the extremities or the chest wall and are usually managed by wide radical resection. Moreover, desmoid tumours involving the chest wall are locally aggressive tumours with a high recurrence rate. We report a case of a pathologically proven desmoid tumour of the chest wall in a patient with a history of bilateral breast cancer and oesophageal cancer. We discuss the imaging appearances of this tumour on positron emission tomography combined with computed tomography (PET/CT) and magnetic resonance imaging. C1 [Souza, F. F.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Souza, F. F.; Fennessy, F. M.; Yang, Q.; van den Abbeele, A. D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Souza, FF (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM ffsouza@partners.org NR 14 TC 11 Z9 12 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD FEB PY 2010 VL 83 IS 986 BP E39 EP E42 DI 10.1259/bjr/18648939 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 568DT UT WOS:000275503000004 PM 20139256 ER PT J AU Nguyen, PL Chen, MH Beard, CJ Suh, WW Choueiri, TK Efstathiou, JA Hoffman, KE Loffredo, M Kantoff, PW D'Amico, AV AF Nguyen, Paul L. Chen, Ming-Hui Beard, Clair J. Suh, W. Warren Choueiri, Toni K. Efstathiou, Jason A. Hoffman, Karen E. Loffredo, Marian Kantoff, Philip W. D'Amico, Anthony V. TI Comorbidity, Body Mass Index, and Age and the Risk of Nonprostate-Cancer-Specific Mortality After a Postradiation Prostate-Specific Antigen Recurrence SO CANCER LA English DT Article DE salvage hormone therapy; prostate cancer; noncancer mortality; body-mass index; comorbidity; ACE-27 ID ANDROGEN DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; BIOCHEMICAL FAILURE; CUMULATIVE INCIDENCE; RADIATION-THERAPY; COMPETING RISK; RADIOTHERAPY; MEN; PROGRESSION; KINETICS AB BACKGROUND: Some men with a postradiation therapy (RT) prostate-specific antigen (PSA) recurrence will die of noncancer causes before developing metastases. Therefore, our ability to determine who would benefit from salvage hormonotherapy (HT) would be enhanced if an individual's risk of non prostate-cancer-specific mortality were known. METHODS: Among 206 men with unfavorable-risk localized prostate cancer initially randomized to RT+/-HT, 87 men who experienced PSA recurrence were studied. Fine and Gray's competing risks regression was used to assess whether body mass index (BMI) and the Adult Comorbidity Evaluation-27 comorbidity level at randomization were associated with the risk of nonprostate-cancer-specific mortality after PSA recurrence, adjusting for age at recurrence. RESULTS: After a median postrecurrence follow-up of 4.4 years, moderate/severe comorbidity (adjusted hazard ratio [HR] = 3.15; P = .02), BMI >= median (27.4 kg/m(2); adjusted HR=2.98; p=.04), and increasing age at recurrence (adjusted HR = 1.17; P = .03) were significantly associated with an increased risk of nonprostate-cancer-specific mortality. Five-year cumulative incidence estimates of nonprostate-cancer-specific mortality were as follows: 0% (95% confidence interval [CI] [0,0]) for low-risk patients (mild/no comorbidity and age= median or BMI >= median); and 37.9% (95% Cl, 6.8-68.9) for high-risk patients (moderate/severe comorbidity; P =.03 overall). CONCLUSIONS: After a post-RT PSA recurrence, men with moderate/severe comorbiclity and those who are obese or older face a substantial risk of nonprostate-cancer-specific mortality, and they could be considered for surveillance protocols with a plan to initiate salvage HT if the PSA rises rapidly (eg, PSA doubling time <6 months) or the patient develops clinically or radiographically evident disease. Cancer 2010;116:610-5. (D 2009 American Cancer Society. C1 [Nguyen, Paul L.; Beard, Clair J.; Suh, W. Warren; Loffredo, Marian; D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.; Beard, Clair J.; Suh, W. Warren; Choueiri, Toni K.; Loffredo, Marian; Kantoff, Philip W.; D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nguyen, Paul L.; Beard, Clair J.; Suh, W. Warren; Choueiri, Toni K.; Efstathiou, Jason A.; Kantoff, Philip W.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Choueiri, Toni K.; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 22 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2010 VL 116 IS 3 BP 610 EP 615 DI 10.1002/cncr.24818 PG 6 WC Oncology SC Oncology GA 550YA UT WOS:000274169200007 PM 19957321 ER PT J AU Barletta, JA Yeap, BY Chirieac, LR AF Barletta, Justine A. Yeap, Beow Y. Chirieac, Lucian R. TI Prognostic Significance of Grading in Lung Adenocarcinoma SO CANCER LA English DT Article DE lung adenocarcinoma; grading; survival; prognosis ID RENAL-CELL CARCINOMA; CANCER; STAGE; PARAMETERS; RECURRENCE; MUTATIONS; PAPILLARY; HISTOLOGY; DIAMETER; SUBTYPE AB BACKGROUND: Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma. METHODS: The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count. RESULTS: In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern >= 90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002). CONCLUSIONS: The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma. Cancer 2010;116:659-69. (C) 2009 American Cancer Society. C1 [Barletta, Justine A.; Chirieac, Lucian R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Chirieac, LR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM lchirieac@partners.org FU National Cancer Institute [CA090578]; Department of Defense [W81X-WH06-1-0303] FX Supported by Specialized Programs of Research Excellence (SPORE) grant in Lung Cancer CA090578 from the National Cancer Institute and by W81X-WH06-1-0303 from the Department of Defense. NR 29 TC 59 Z9 61 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2010 VL 116 IS 3 BP 659 EP 669 DI 10.1002/cncr.24831 PG 11 WC Oncology SC Oncology GA 550YA UT WOS:000274169200013 PM 20014400 ER PT J AU Mulligan, JK Young, MRI AF Mulligan, Jennifer Konopa Young, M. Rita I. TI Tumors induce the formation of suppressor endothelial cells in vivo SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Endothelial cell; Tumor; Immune suppression; Lewis lung carcinoma ID REGULATORY T-CELLS; NECK-CANCER; DIFFERENTIATION; HEAD; MACROPHAGES; PROGRESSION; INFLAMMATION; ACTIVATION; MECHANISMS; SECRETION AB Patients with solid tumors have defects in immune effector cells, which have been associated with a poorer prognosis. Previous studies by our laboratory have shown that exposure to Lewis lung carcinoma (LLC)-secreted products induces the formation of suppressor endothelial cells in vitro. The current studies examined if tumors could induce the formation of suppressor endothelial cells in vivo. Endothelial cells were immunomagnetically isolated from the lungs of tumor-bearing mice or normal controls and examined for their ability to modulate NK cell, T-cell and macrophage functions. Compared to normal controls, supernatants from endothelial cells isolated from tumor-bearing lungs had elevated secretion of PGE(2), IL-6, IL-10 and VEGF. Conditioned media from endothelial cells isolated from normal lungs increased CD8(+) T-cell IFN-gamma and CD4(+) T-cell IL-2 production in response to anti-CD3 stimulation, while media conditioned by endothelial cells from tumor-bearing lungs had a diminished stimulatory capacity. Examination of NK cell functions showed that supernatants from endothelial cells isolated from normal lungs were potent activators of NK cells, as indicated by their secretion of TNF-alpha and IFN-gamma. Endothelial cells isolated from tumor-bearing lungs had a significantly diminished capacity to activate NK cells. Finally, supernatants from endothelial cells of tumor-bearing lungs diminished macrophage phagocytosis compared to either treatment with supernatants of normal endothelial cells or treatment with media alone. The results of these studies demonstrate that tumors induce the formation of suppressor endothelial cells in vivo and provide support for the role of endothelial cells in tumor-induced immune suppression. C1 [Mulligan, Jennifer Konopa; Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. [Mulligan, Jennifer Konopa; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv, 109 Bee St, Charleston, SC 29401 USA. EM konopa@musc.edu; rita.young@va.gov FU Research Services of the Department of Veterans Affairs; National Institutes of Health [R01CA85266, R01CA97813, R01DE018168, 1R01CA128837] FX This work was supported by Research Services of the Department of Veterans Affairs and by grants R01CA85266, R01CA97813, R01DE018168 and 1R01CA128837 from the National Institutes of Health to MRIY. NR 28 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2010 VL 59 IS 2 BP 267 EP 277 DI 10.1007/s00262-009-0747-y PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 519EU UT WOS:000271748600009 PM 19669642 ER PT J AU Katiyar, SK Vaid, M van Steeg, H Meeran, SM AF Katiyar, Santosh K. Vaid, Mudit van Steeg, Harry Meeran, Syed M. TI Green Tea Polyphenols Prevent UV-Induced Immunosuppression by Rapid Repair of DNA Damage and Enhancement of Nucleotide Excision Repair Genes SO CANCER PREVENTION RESEARCH LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; INDUCED IMMUNE SUPPRESSION; SKIN-CANCER; ULTRAVIOLET-RADIATION; CONTACT HYPERSENSITIVITY; XERODERMA-PIGMENTOSUM; IRRADIATED MICE; INHIBITION; INDUCTION; CELLS AB UV radiation-induced immunosuppression has been implicated in the development of skin cancers. Green tea polyphenols (GTP) in drinking water prevent photocarcinogenesis in the skin of mice. We studied whether GTPs in drinking water (0.1-0.5%, w/v) prevent UV-induced immunosuppression and (if so) potential mechanisms of this effect in mice. GTPs (0.2% and 0.5%, w/v) reduced UV-induced suppression of contact hypersensitivity (CHS) in response to a contact sensitizer in local (58-62% reductions; P < 0.001) and systemic (51-55% reductions; P < 0.005) models of CHS. Compared with untreated mice, GTP-treated mice (0.2%, w/v) had a reduced number of cyclobutane pyrimidine dimer-positive (CPD(+)) cells (59%; P < 0.001) in the skin, showing faster repair of UV-induced DNA damage, and had a reduced (2-fold) migration of CPD(+) cells from the skin to draining lymph nodes, which was associated with elevated levels of nucleotide excision repair (NER) genes. GTPs did not prevent UV-induced immunosuppression in NER-deficient mice but significantly prevented it in NER-proficient mice (P < 0.001); immunohistochemical analysis of CPD(+) cells indicated that GTPs reduced the numbers of UV-induced CPD(+) cells in NER-proficient mice (P < 0.001) but not in NER-deficient mice. Southwestern dot-blot analysis revealed that GTPs repaired UV-induced CPDs in xeroderma pigmentosum complementation group A (XPA)-proficient cells of a healthy person but did not in XPA-deficient cells obtained from XPA patients, indicating that a NER mechanism is involved in DNA repair. This study is the first to show a novel NER mechanism by which drinking GTPs prevents UV-induced immunosuppression and that inhibiting UV-induced immunosuppression may underlie the chemopreventive activity of GTPs against photocarcinogenesis. Cancer Prev Res; 3(2); 179-89. (C) 2010 AACR. C1 [Katiyar, Santosh K.; Vaid, Mudit; Meeran, Syed M.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [van Steeg, Harry] Natl Inst Publ Hlth & Environm, Hlth Effects Res Lab, NL-3720 BA Bilthoven, Netherlands. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Center for Complementary and Alternative Medicine/NIH [R01 AT002536]; Veterans Administration Merit Review Award FX National Center for Complementary and Alternative Medicine/NIH grant R01 AT002536 (S. K. Katiyar) and Veterans Administration Merit Review Award (S. K. Katiyar). NR 27 TC 31 Z9 33 U1 3 U2 8 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 FEB PY 2010 VL 3 IS 2 BP 179 EP 189 DI 10.1158/1940-6207.CAPR-09-0044 PG 11 WC Oncology SC Oncology GA 551XP UT WOS:000274247000009 PM 20103727 ER PT J AU Vecchiarelli-Federico, LM Cervi, D Haeri, M Li, YM Nagy, A Ben-David, Y AF Vecchiarelli-Federico, Laura M. Cervi, David Haeri, Mehran Li, Yanmei Nagy, Andras Ben-David, Yaacov TI Vascular Endothelial Growth Factor-A Positive and Negative Regulator of Tumor Growth SO CANCER RESEARCH LA English DT Article ID METASTATIC COLORECTAL-CANCER; HYPOXIA INDUCIBLE FACTOR; NITRIC-OXIDE; TERM TREATMENT; MYELOID CELLS; VEGF; ANGIOGENESIS; BEVACIZUMAB; MICE; NEOVASCULARIZATION AB Over the past decade, the well-documented role of vascular endothelial growth factor (VEGF) in tumor angiogenesis has led it to become one of the leading therapeutic targets for the treatment of cancer. Emerging evidence from genetically modified animal models, however, suggests that elevated levels of VEGF, or a proangiogenic phenotype, may impede, rather than promote, early tumor development and progression. For example, hypermorph VEGF transgenic mice display delayed progression of a retroviral-induced murine leukemia, and knockdown of VEGF expression within the myeloid compartment accelerates tumor progression. Several mechanisms have been proposed to explain this paradox, whereby VEGF induces changes within the hematopoietic compartment and tumor microenvironment through recruitment of tumor inhibitory monocytic cells and the negative regulation of tumor angiogenesis. Thus, it is apparent that the levels of VEGF expression in both tumor and nontumor tissues, as well as the context and timing of its modulation relative to cancer induction, play an important role in determining the effects of VEGF expression on tumorigenicity. In light of these recent findings, the various mechanisms underlying the negative role of VEGF during early tumor development, progression, and metastasis will be discussed. Cancer Res; 70(3); 863-7. (C)2010 AACR. C1 [Vecchiarelli-Federico, Laura M.; Haeri, Mehran; Li, Yanmei; Ben-David, Yaacov] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Div Mol & Cellular Biol, Toronto, ON M4N 3M5, Canada. [Nagy, Andras] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Mol Genet, Toronto, ON M4N 3M5, Canada. [Cervi, David] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Cervi, David] Harvard Univ, Sch Med, Boston, MA USA. RP Ben-David, Y (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Div Mol & Cellular Biol, Room S-216,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM bendavid@sri.utoronto.ca RI Nagy, Andras/G-6465-2013 FU Canadian Institutes of Health Research [MOP84460] FX The Ben-David lab is supported by Canadian Institutes of Health Research grant MOP84460. NR 29 TC 20 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 863 EP 867 DI 10.1158/0008-5472.CAN-09-3592 PG 5 WC Oncology SC Oncology GA 607FX UT WOS:000278485600003 PM 20103650 ER PT J AU Sos, ML Rode, HB Heynck, S Peifer, M Fischer, F Kluter, S Pawar, VG Reuter, C Heuckmann, JM Weiss, J Ruddigkeit, L Rabiller, M Koker, M Simard, JR Getlik, M Yuza, Y Chen, TH Greulich, H Thomas, RK Rauh, D AF Sos, Martin L. Rode, Haridas B. Heynck, Stefanie Peifer, Martin Fischer, Florian Klueter, Sabine Pawar, Vijaykumar G. Reuter, Cecile Heuckmann, Johannes M. Weiss, Jonathan Ruddigkeit, Lars Rabiller, Matthias Koker, Mirjam Simard, Jeffrey R. Getlik, Matthaeus Yuza, Yuki Chen, Tzu-Hsiu Greulich, Heidi Thomas, Roman K. Rauh, Daniel TI Chemogenomic Profiling Provides Insights into the Limited Activity of Irreversible EGFR Inhibitors in Tumor Cells Expressing the T790M EGFR Resistance Mutation SO CANCER RESEARCH LA English DT Article ID LUNG-CANCER; DRUG SUSCEPTIBILITY; TYROSINE KINASE; GEFITINIB; SENSITIVITY; ACTIVATION; ERLOTINIB; THERAPY AB Reversible epidermal growth factor receptor (EGFR) inhibitors are the first class of small molecules to improve progression-free survival of patients with EGFR-mutated lung cancers. Second-generation EGFR inhibitors introduced to overcome acquired resistance by the T790M resistance mutation of EGFR have thus far shown limited clinical activity in patients with T790M-mutant tumors. In this study, we systematically analyzed the determinants of the activity and selectivity of the second-generation EGFR inhibitors. A focused library of irreversible as well as structurally corresponding reversible EGFR-inhibitors was synthesized for chemogenomic profiling involving over 79 genetically defined NSCLC and 19 EGFR-dependent cell lines. Overall, our results show that the growth-inhibitory potency of all irreversible inhibitors against the EGFR(T790M) resistance mutation was limited by reduced target inhibition, linked to decreased binding velocity to the mutant kinase. Combined treatment of T790M-mutant tumor cells with BIBW-2992 and the phosphoinositide3-kinase/mammalian target of rapamycin inhibitor PI-103 led to synergistic induction of apoptosis. Our findings offer a mechanistic explanation for the limited efficacy of irreversible EGFR inhibitors in EGFRT790M gatekeeper-mutant tumors, and they prompt combination treatment strategies involving inhibitors that target signaling downstream of the EGFR. Cancer Res; 70(3): 868-74. (C)2010 AACR. C1 [Rode, Haridas B.; Klueter, Sabine; Pawar, Vijaykumar G.; Ruddigkeit, Lars; Rabiller, Matthias; Simard, Jeffrey R.; Getlik, Matthaeus; Thomas, Roman K.; Rauh, Daniel] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany. [Sos, Martin L.; Heynck, Stefanie; Peifer, Martin; Fischer, Florian; Reuter, Cecile; Heuckmann, Johannes M.; Weiss, Jonathan; Koker, Mirjam; Thomas, Roman K.] Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, Cologne, Germany. [Sos, Martin L.; Heynck, Stefanie; Peifer, Martin; Fischer, Florian; Reuter, Cecile; Heuckmann, Johannes M.; Weiss, Jonathan; Koker, Mirjam; Thomas, Roman K.] Univ Cologne, Fac Med, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, Cologne, Germany. [Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, Cologne, Germany. [Yuza, Yuki] Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan. [Chen, Tzu-Hsiu; Greulich, Heidi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Greulich, Heidi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Chen, Tzu-Hsiu; Greulich, Heidi] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Rauh, D (reprint author), Max Planck Soc, Chem Genom Ctr, Otto Hahn Str 15, D-44227 Dortmund, Germany. EM nini@nf.mpg.de; daniel.rauh@cgc.mpg.de RI Rauh, Daniel/G-1595-2013; OI Rauh, Daniel/0000-0002-1970-7642 FU Deutsche Krebshilfe [107954]; Fritz-Thyssen-Stiftung [10.08.2.175]; German Ministry of Education and Research BMBF [01GS08100, 01GS08102]; Alexander von Humboldt Foundation; Schering Plough; Bayer-Schering Pharma; Merck-Serono; Bayer CropScience FX Deutsche Krebshilfe grant 107954, the Fritz-Thyssen-Stiftung grant 10.08.2.175, and the NGFNplus program of the German Ministry of Education and Research BMBF, grant 01GS08100 (R.K. Thomas); the Alexander von Humboldt Foundation (J.R. Simard); the German Ministry of Education and Research BMBF, grant 01GS08102 (D. Rauh); Schering Plough, Bayer-Schering Pharma, Merck-Serono, and Bayer CropScience. NR 20 TC 82 Z9 89 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 868 EP 874 DI 10.1158/0008-5472.CAN-09-3106 PG 7 WC Oncology SC Oncology GA 607FX UT WOS:000278485600004 PM 20103621 ER PT J AU Biernacki, MA Marina, O Zhang, WD Liu, FL Bruns, I Cai, A Neuberg, D Canning, CM Alyea, EP Soiffer, RJ Brusic, V Ritz, J Wu, CJ AF Biernacki, Melinda A. Marina, Ovidiu Zhang, Wandi Liu, Fenglong Bruns, Ingmar Cai, Ann Neuberg, Donna Canning, Christine M. Alyea, Edwin P. Soiffer, Robert J. Brusic, Vladimir Ritz, Jerome Wu, Catherine J. TI Efficacious Immune Therapy in Chronic Myelogenous Leukemia (CML) Recognizes Antigens That Are Expressed on CML Progenitor Cells SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; HEMATOPOIETIC STEM; ANTIBODY-RESPONSES; MELANOMA PATIENTS; NY-ESO-1 PROTEIN; GENE-EXPRESSION; DENDRITIC CELLS; CHRONIC PHASE; DIFFERENTIATION; CANCER AB Curative effects of graft-versus-leukemia-based therapies such as donor lymphocyte infusion (DLI) for chronic myelogenous leukemia (CML) may result from immunologic ablation of self-renewing CML progenitor cells. Patients who achieved durable remissions after DLI developed a significant B-cell lymphocytosis after treatment, which did not occur in patients who were unresponsive to DLI. In this study, we identified antigen targets of this B-cell response by probing two immunoproteomic platforms with plasma immunoglobulins from seven CML patients with clinically apparent graft-versus-leukemia responses after DLI. In total, 62 antigens elicited greater reactivity from post-DLI versus pre-DLI plasma. Microarray analysis revealed that > 70% of the antigens were expressed in CML CD34(+) cells, suggesting that expression in malignant progenitor cells is a feature common to antibody targets of DLI. We confirmed elevated expression of three target antigens (RAB38, TBCE, and DUSP12) in CML that together consistently elicited antibody responses in 18 of 21 of an additional cohort of CML patients with therapeutic responses, but not in normal donors and rarely in non-CML patients. In summary, immunologic targets of curative DLI responses include multiple antigens on CML progenitor cells, identifying them as potential immunogens for vaccination and/or monitoring of immunotherapeutics designed to eliminate myeloid leukemia stem cells. Cancer Res; 70(3); 906-15. (C)2010 AACR. C1 [Wu, Catherine J.] Dana Farber Canc Inst, Harvard Inst Med, Canc Vaccine Ctr, Boston, MA 02115 USA. [Biernacki, Melinda A.; Marina, Ovidiu; Zhang, Wandi; Cai, Ann; Canning, Christine M.; Alyea, Edwin P.; Soiffer, Robert J.; Brusic, Vladimir; Ritz, Jerome; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liu, Fenglong; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Alyea, Edwin P.; Soiffer, Robert J.; Ritz, Jerome; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bruns, Ingmar] Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, Dusseldorf, Germany. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Harvard Inst Med, Canc Vaccine Ctr, Room 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU Howard Hughes Medical Institute Medical Research Training Fellowship; Department of Defense [W81XWH-07-10080]; Miles and Eleanor Shore Award; National Cancer Institute [5R21CA115043-2]; Howard Hughes Medical Institute; Damon-Runyon Clinical Investigator Award [CI-38-07] FX Howard Hughes Medical Institute Medical Research Training Fellowship (O. Marina and A. Cai) and Department of Defense grant W81XWH-07-10080, Miles and Eleanor Shore Award, National Cancer Institute grant 5R21CA115043-2, Howard Hughes Medical Institute Early Career Physician-Scientist Award, and Damon-Runyon Clinical Investigator Award CI-38-07 (C.J. Wu). NR 42 TC 31 Z9 32 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 906 EP 915 DI 10.1158/0008-5472.CAN-09-2303 PG 10 WC Oncology SC Oncology GA 607FX UT WOS:000278485600008 PM 20103624 ER PT J AU Lee, YJ Koch, M Karl, D Torres-Collado, AX Fernando, NT Rothrock, C Kuruppu, D Ryeom, S Iruela-Arispe, ML Yoon, SS AF Lee, Yoon-Jin Koch, Moritz Karl, Daniel Torres-Collado, Antoni X. Fernando, Namali T. Rothrock, Courtney Kuruppu, Darshini Ryeom, Sandra Iruela-Arispe, M. Luisa Yoon, Sam S. TI Variable Inhibition of Thrombospondin 1 against Liver and Lung Metastases through Differential Activation of Metalloproteinase ADAMTS1 SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; FACTOR-BETA; IN-VITRO; ANGIOGENESIS; CARCINOGENESIS; PROGRESSION; EXPRESSION; MICE AB Metastasis relies on angiogenesis for tumor expansion. Tumor angiogenesis is restrained by a variety of endogenous inhibitors, including thrombospondin 1 (TSP1). The principal antiangiogenic activity of TSP1 resides in a domain containing three TSP1 repeats (3TSR), and TSP1 cleavage is regulated, in part, by the metalloproteinase ADAMTS1. In this study, we examined the role of TSP1 and ADAMTS1 in controlling metastatic disease in the liver and lung. TSP1 overexpression inhibited metastatic growth of colon or renal carcinoma cells in liver but not lung. Metastatic melanoma in liver grew more rapidly in Tsp1-null mice compared with controls, whereas in lung grew similarly in Tsp1-null mice or controls. Recombinant TSP1 was cleaved more efficiently in lysates from liver than lung. ADAMTS1 inhibition by neutralizing antibody, small interfering RNA, or genetic deletion abrogated cleavage activity. To confirm that lack of cleavage of TSP1 ablated its antiangiogenic function in the lung, we generated colon cancer cells stably secreting only the 3TSR domain and found that they inhibited formation of both liver and lung metastases. Collectively, our results indicate that the antiangiogenic activity of TSP1 is differentially regulated by ADAMTS1 in the liver and lung, emphasizing the concept that regulation of angiogenesis is varied in different tissue environments. Cancer Res; 70(3); 948-56. (C)2010 AACR. C1 [Ryeom, Sandra; Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. [Yoon, Sam S.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Lee, Yoon-Jin; Koch, Moritz; Karl, Daniel; Fernando, Namali T.; Rothrock, Courtney; Kuruppu, Darshini] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, Yoon-Jin; Koch, Moritz; Karl, Daniel; Fernando, Namali T.; Rothrock, Courtney; Kuruppu, Darshini] Harvard Univ, Sch Med, Boston, MA USA. [Torres-Collado, Antoni X.; Iruela-Arispe, M. Luisa] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. RP Yoon, SS (reprint author), Univ Penn, Sch Med, Dept Canc Biol, 4 Silverstein,3400 Spruce St, Philadelphia, PA 19104 USA. EM sam.yoon@uphs.upenn.edu FU NIH [5 K12 CA 87723-03, 1 R21 CA117129-01]; Polsky Family MGH Junior Faculty; Jung Foundation for Science and Research (Hamburg, Germany) FX NIH grants 5 K12 CA 87723-03 (S.S. Yoon) and 1 R21 CA117129-01 (S.S. Yoon), Polsky Family MGH Junior Faculty (S.S. Yoon), and Jung Foundation for Science and Research (Hamburg, Germany; M. Koch). NR 29 TC 32 Z9 33 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 948 EP 956 DI 10.1158/0008-5472.CAN-09-3094 PG 9 WC Oncology SC Oncology GA 607FX UT WOS:000278485600012 PM 20103648 ER PT J AU Wolpin, BM Kraft, P Gross, M Helzlsouer, K Bueno-de-Mesquita, HB Steplowski, E Stolzenberg-Solomon, RZ Arslan, AA Jacobs, EJ LaCroix, A Petersen, G Zheng, W Albanes, D Allen, NE Amundadottir, L Anderson, G Boutron-Ruault, MC Buring, JE Canzian, F Chanock, SJ Clipp, S Gaziano, JM Giovannucci, EL Hallmans, G Hankinson, SE Hoover, RN Hunter, DJ Hutchinson, A Jacobs, K Kooperberg, C Lynch, SM Mendelsohn, JB Michaud, DS Overvad, K Patel, AV Rajkovic, A Sanchez, MJ Shu, XO Slimani, N Thomas, G Tobias, GS Trichopoulos, D Vineis, P Virtamo, J Wactawski-Wende, J Yu, K Zeleniuch-Jacquotte, A Hartge, P Fuchs, CS AF Wolpin, Brian M. Kraft, Peter Gross, Myron Helzlsouer, Kathy Bueno-de-Mesquita, H. Bas Steplowski, Emily Stolzenberg-Solomon, Rachael Z. Arslan, Alan A. Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Albanes, Demetrius Allen, Naomi E. Amundadottir, Laufey Anderson, Garnet Boutron-Ruault, Marie-Christine Buring, Julie E. Canzian, Federico Chanock, Stephen J. Clipp, Sandra Gaziano, John Michael Giovannucci, Edward L. Hallmans, Goeran Hankinson, Susan E. Hoover, Robert N. Hunter, David J. Hutchinson, Amy Jacobs, Kevin Kooperberg, Charles Lynch, Shannon M. Mendelsohn, Julie B. Michaud, Dominique S. Overvad, Kim Patel, Alpa V. Rajkovic, Aleksandar Sanchez, Maria-Jose Shu, Xiao-Ou Slimani, Nadia Thomas, Gilles Tobias, Geoffrey S. Trichopoulos, Dimitrios Vineis, Paolo Virtamo, Jarmo Wactawski-Wende, Jean Yu, Kai Zeleniuch-Jacquotte, Anne Hartge, Patricia Fuchs, Charles S. TI Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; GROUP ANTIGENS; GENETIC-BASIS; DISEASE; STRATIFICATION; VARIANTS; SYSTEM AB A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015-23. (C)2010 AACR. C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wolpin, Brian M.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Kraft, Peter; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Michaud, Dominique S.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Aging, Boston, MA 02115 USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, John Michael] Brigham & Womens Hosp, Dept Med, Phys Hlth Study, Div Prevent Med, Boston, MA 02115 USA. [Gaziano, John Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius; Amundadottir, Laufey; Chanock, Stephen J.; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin; Mendelsohn, Julie B.; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Amundadottir, Laufey; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lynch, Shannon M.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [LaCroix, Andrea; Anderson, Garnet; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hutchinson, Amy; Jacobs, Kevin] NCI, Core Genotyping Facil, Adv Technol Program, Sci Applicat Int Corp Frederick Inc,, Frederick, MD 21701 USA. [Jacobs, Kevin] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Michaud, Dominique S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, Aalborg, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Rajkovic, Aleksandar] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain. [Sanchez, Maria-Jose] CIBER Epidemiol & Salud Publ, Granada, Spain. [Slimani, Nadia] IARC, Lyon, France. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org RI Tobias, Geoffrey/M-4135-2016; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016 OI Tobias, Geoffrey/0000-0002-2878-8253; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Amundadottir, Laufey/0000-0003-1859-8971 FU NCI [R01CA034588, R01CA098661, P30CA016087, R01 CA82729, R01 CA70867]; National Institute of Environmental Health Sciences [ES000260]; National Heart, Lung, and Blood Institute; NIH; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NCI, NIH [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908] FX NYUWHS is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the NCI, and the center grant ES000260 from the National Institute of Environmental Health Sciences.; The WHI program is funded by the National Heart, Lung, and Blood Institute; NIH; and U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. We thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf.; PHS, NHS, HPFS, and WHS at Harvard were supported by NCI, NIH, grants P01 CA87969, P01 CA55075, P50 CA127003, and R01 CA124908.; The Shanghai Men's Health Study was supported by NCI extramural research grant R01 CA82729. The Shanghai Women's Health Study was supported by NCI extramural research grant R01 CA70867 and, partially for biological sample collection, by the Intramural Research Program of NCI (Division of Cancer Epidemiology and Genetics). NR 34 TC 87 Z9 91 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2010 VL 70 IS 3 BP 1015 EP 1023 DI 10.1158/0008-5472.CAN-09-2993 PG 9 WC Oncology SC Oncology GA 607FX UT WOS:000278485600019 PM 20103627 ER PT J AU Ma, CHE Taylor, JSH AF Ma, Chi Him Eddie Taylor, Jeremy S. H. TI Trophic responsiveness of purified postnatal and adult rat retinal ganglion cells SO CELL AND TISSUE RESEARCH LA English DT Review DE Retinal ganglion cell; Schwann cell; Secreted factors; Survival; Neuritogenesis; Signaling pathway; Rat (Lister Hooded) ID PERIPHERAL-NERVE GRAFTS; CILIARY NEUROTROPHIC FACTOR; POSTSYNAPTIC TARGET NEURONS; LATERAL GENICULATE-NUCLEUS; PRIMARY CULTURE TECHNIQUE; SCHWANN-CELLS; GROWTH-FACTOR; IN-VITRO; AXON REGENERATION; OPTIC-NERVE AB Central neurons lose the ability for axonal re-growth during development and typically do not regenerate their axons following axotomy once they become mature unless given a growth-permissive environment i.e. peripheral nerve graft. In the present study, the growth responsiveness of purified retinal ganglion cells (RGCs) at different ages to neurotrophic factors and Schwann cell (SC)-secreted factors were examined directly. The purity of adult RGCs was 97% as assessed by retrograde labelling with 4,6-diamidino-2-phenylindole. The stability of cultures were demonstrated by long-term survival (30 days) in medium contained brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and forskolin (F) (BCF). RGCs from postnatal (P) (P0, P4, P8, P21) and adult (P90) rats showed decreasing levels of survival and neuritogenesis when grown in BCF. In contrast, the opposite was observed in SC-conditioned medium (CM)-treated P0-P8 RGCs which were increasingly responsive. SCCM induced maximal neurite outgrowth in P8 RGCs via the activation of extracellular regulated kinase 1/2 (Erk1/2). Inhibition of mitogen-activated protein kinase-Erk1/2 signaling using an Erk1/2-specific inhibitor (UO126) abolished SCCM-induced Erk1/2 phosphorylation and neuritogenesis completely. Although both SCCM and BCF failed to sustain the same levels of growth in P21 or P90 cultures as observed in P8 cultures, SCCM promoted higher survival and neuritogenesis than BCF-treated adult RGCs. This study is the first report of adult rat RGC purification and demonstrates that mature RGCs need multiple factors for survival and neurite outgrowth. C1 [Ma, Chi Him Eddie; Taylor, Jeremy S. H.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. RP Ma, CHE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 Bldg,13th St,Room 4309, Charlestown, MA 02129 USA. EM chi.ma@mgh.harvard.edu OI MA, Chi Him Eddie/0000-0003-2054-0445 NR 104 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 2010 VL 339 IS 2 BP 297 EP 310 DI 10.1007/s00441-009-0897-4 PG 14 WC Cell Biology SC Cell Biology GA 552YK UT WOS:000274331000002 PM 19936794 ER PT J AU Bommi-Reddy, A Kaelin, WG AF Bommi-Reddy, Archana Kaelin, William G., Jr. TI Slaying RAS with a synthetic lethal weapon SO CELL RESEARCH LA English DT Editorial Material ID NF-KAPPA-B; RNA INTERFERENCE; CANCER; CELLS; THERAPY C1 [Bommi-Reddy, Archana; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bommi-Reddy, Archana; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kaelin, William G., Jr.] Howard Hughes Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM William_Kaelin@dfci.harvard.edu NR 15 TC 5 Z9 5 U1 0 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD FEB PY 2010 VL 20 IS 2 BP 119 EP 121 DI 10.1038/cr.2010.16 PG 3 WC Cell Biology SC Cell Biology GA 572GQ UT WOS:000275816100003 PM 20118966 ER PT J AU Ware, LB Koyama, T Billheimer, D Wu, W Bernard, GR Thompson, BT Brower, RG Standiford, TJ Martin, TR Matthay, MA AF Ware, Lorraine B. Koyama, Tatsuki Billheimer, Dean Wu, William Bernard, Gordon R. Thompson, B. Taylor Brower, Roy G. Standiford, Theodore J. Martin, Thomas R. Matthay, Michael A. CA NHLBI ARDS Clinical Trials Network TI Prognostic and Pathogenetic Value of Combining Clinical and Biochemical Indices in Patients With Acute Lung Injury SO CHEST LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; MYOCARDIAL-INFARCTION; HOSPITAL MORTALITY; OUTCOME PREDICTION; ACUTE PHYSIOLOGY; RABBITS; INTERLEUKIN-8; PROTEIN; INFLAMMATION; VENTILATION AB Background: No single clinical or biologic marker reliably predicts clinical outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of biologic and clinical markers would be superior to either biomarkers or clinical factors alone in predicting ALI/ARDS mortality and would provide insight into the pathogenesis of clinical ALI/ARDS. Methods: Eight biologic markers that reflect endothelial and epithelial injury, inflammation, and coagulation (von Willebrand factor antigen, surfactant protein D [SP-D]) tumor necrosis factor receptor-1, interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C, plasminogen activator inhibitor-1) were measured in baseline plasma from 549 patients in the ARDSNet trial of low vs high positive end-expiratory pressure. Mortality was modeled with multivariable logistic regression. Predictors were selected using backward elimination. Comparisons between candidate models were based on the receiver operating characteristics (ROC) and tests of integrated discrimination improvement. Results: Clinical predictors (Acute Physiology And Chronic Health Evaluation III [APACHE III], organ failures, age, underlying cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers and the clinical predictors had an AUC of 0.85. The best performing hiomarkers were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar type 2 cells, supporting the concept that acute inflammation and alveolar epithelial injury are important pathogenetic pathways in human ALI/ARDS. Conclusions: A combination of biomarkers and clinical predictors is superior to clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and may be useful for stratifying patients in clinical trials. From a pathogenesis perspective, the degree of acute inflammation and alveolar epithelial injury are highly associated with the outcome of human ALI/ARDS. CHEST 2010; 137(2):288-296 C1 [Ware, Lorraine B.; Bernard, Gordon R.] Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Dept Med, Sch Med, Nashville, TN 37232 USA. [Koyama, Tatsuki; Wu, William] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. [Billheimer, Dean] Univ Arizona, Dept Agr & Biosyst Engn, Tucson, AZ USA. [Billheimer, Dean] Univ Arizona, Arizona Stat Consulting Lab, Tucson, AZ USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brower, Roy G.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Standiford, Theodore J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Martin, Thomas R.] Univ Washington & Med Serv, VA Puget Sound Healthcare Syst, Seattle, WA USA. [Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Ware, LB (reprint author), Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Dept Med, Sch Med, T1218 MCN,1161 21st Ave S, Nashville, TN 37232 USA. EM lorraine.ware@vanderbilt.edu OI Murray, Susan/0000-0003-4387-7673 FU National institutes of Health [HL81332, HR46059, HL74005, HL73996, HL74024, HL73994] FX This study was supported by the National institutes of Health [Grants HL81332, HR46059, HL74005, HL73996, HL74024, HL73994]. NR 35 TC 129 Z9 142 U1 0 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2010 VL 137 IS 2 BP 288 EP 296 DI 10.1378/chest.09-1484 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 556SQ UT WOS:000274612600009 PM 19858233 ER PT J AU Longworth, MS Dyson, NJ AF Longworth, Michelle S. Dyson, Nicholas J. TI pRb, a local chromatin organizer with global possibilities SO CHROMOSOMA LA English DT Review ID HISTONE H1 PHOSPHORYLATION; CELL-CYCLE PROGRESSION; MYB-MUVB/DREAM COMPLEX; SKELETAL-MUSCLE CELLS; CONDENSIN-II SUBUNIT; E2F TARGET GENES; RETINOBLASTOMA PROTEIN; TRANSCRIPTIONAL REPRESSOR; CHROMOSOME CONDENSATION; IN-VITRO AB The retinoblastoma (pRb) family of proteins are well known for their tumor suppressor properties and for their ability to regulate transcription. The action of pRb family members correlates with the appearance of repressive chromatin marks at promoter regions of genes encoding key regulators of cell proliferation. Recent studies raise the possibility that pRb family members do not simply act by controlling the activity of individual promoters but that they may also function by promoting the more general organization of chromatin. In several contexts, pRb family members stimulate the compaction or condensation of chromatin and promote the formation of heterochromatin. In this review, we summarize studies that link pRb family members to the condensation or compaction of DNA. C1 [Longworth, Michelle S.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Longworth, Michelle S.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU Leukemia and Lymphoma Society; Charles A. King Trust; NIH [CA064402] FX We thank members of the Dyson laboratory for helpful discussions. M. L. was supported by fellowships from the Leukemia and Lymphoma Society and the Charles A. King Trust. This work was supported by a grant from the NIH to ND (CA064402). NR 127 TC 17 Z9 18 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD FEB PY 2010 VL 119 IS 1 BP 1 EP 11 DI 10.1007/s00412-009-0238-0 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 543FD UT WOS:000273555600001 PM 19714354 ER PT J AU Scheuner, MT Setodji, CM Pankow, JS Blumenthal, RS Keeler, E AF Scheuner, Maren T. Setodji, Claude Messan Pankow, James S. Blumenthal, Roger S. Keeler, Emmett TI General Cardiovascular Risk Profile Identifies Advanced Coronary Artery Calcium and Is Improved by Family History The Multiethnic Study of Atherosclerosis SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE cardiovascular diseases; imaging; coronary artery calcium; family history; risk factors; subclinical atherosclerosis ID BEAM COMPUTED-TOMOGRAPHY; C-REACTIVE PROTEIN; HEART-DISEASE; MYOCARDIAL-INFARCTION; TASK-FORCE; PREDICTION; SCORE; CALCIFICATION; ACCURACY; EVENTS AB Background -The General Cardiovascular Risk Profile is a multivariable model that predicts global cardiovascular disease risk. Our goal was to assess the ability of the General Cardiovascular Risk Profile to identify individuals with advanced coronary artery calcification (CAC) and determine whether identification is improved with family history. Methods and Results - Using data from the Multiethnic Study of Atherosclerosis, 3 sex-specific models were developed with ordinal logistic regressions to relate risk factors to CAC scores. Model 1 included covariates in the General Cardiovascular Risk Profile. Then family history was added, defined as having at least 1 first-degree relative with premature coronary heart disease (model 2) or as a weak, moderate, or strong family history based on number of relatives with coronary heart disease, age at onset, and the presence of stroke or diabetes in the family (model 3). For each model, we estimated mathematical CAC risk functions, derived CAC score sheets, evaluated the ability to discriminate persons having positive CAC scores, and assessed reclassification of individuals with low, intermediate, or high probability of CAC > 300. Model 1 worked well to identify women and men with positive CAC scores; c-statistics were 0.752 and 0.718 and chi(2) values were 821.2 (P < 0.0001) and 730.6 (P < 0.0001), respectively. Addition of family history improved discrimination and fit of model 1. However, reclassification of participants with advanced CAC was significantly improved with model 3 only. Conclusions -The General Cardiovascular Risk Profile identifies advanced CAC, an emerging indication for aggressive risk factor modification. Incorporation of family history, especially comprehensive familial risk stratification, provides incremental prognostic value. (Circ Cardiovasc Genet. 2010;3:97-105.) C1 [Scheuner, Maren T.; Keeler, Emmett] RAND Corp, Santa Monica, CA 90407 USA. [Scheuner, Maren T.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Scheuner, Maren T.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Setodji, Claude Messan] RAND Corp, Pittsburgh, PA USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Blumenthal, Roger S.] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. RP Scheuner, MT (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM Scheuner@rand.org FU National Heart, Lung, and Blood Institute [1 R21 HL081175-01A1, NO1-HC-95159, N01-HC-95165, N01-HC95169] FX This work was supported by National Heart, Lung, and Blood Institute grant 1 R21 HL081175-01A1. MESA was supported by contracts NO1-HC-95159 through N01-HC-95165 and N01-HC95169 from the National Heart, Lung, and Blood Institute. NR 37 TC 18 Z9 18 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 FEB PY 2010 VL 3 IS 1 BP 97 EP U302 DI 10.1161/CIRCGENETICS.109.894527 PG 17 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HJ UT WOS:000275979700014 PM 20160201 ER PT J AU Ellinor, PT Van Eyk, JE AF Ellinor, Patrick T. Van Eyk, Jennifer E. TI Top Advances in Functional Genomics and Translational Biology for 2009 SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE aorta; diagnosis; genetics; signal transduction ID GROWTH-FACTOR-BETA; MARFAN-SYNDROME C1 [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. [Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. [Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM pellinor@partners.org FU NCRR NIH HHS [1U54RR023561]; NHLBI NIH HHS [HL092577, N01-HV28180]; NIDA NIH HHS [R21 DA027021, DA027021] NR 8 TC 0 Z9 0 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 FEB PY 2010 VL 3 IS 1 BP 106 EP 108 DI 10.1161/CIRCGENETICS.110.937367 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 574HJ UT WOS:000275979700015 PM 20160202 ER PT J AU Sanborn, TA Ebrahimi, R Manoukian, SV McLaurin, BT Cox, DA Feit, F Hamon, M Mehran, R Stone, GW AF Sanborn, Timothy A. Ebrahimi, Ramin Manoukian, Steven V. McLaurin, Brent T. Cox, David A. Feit, Frederick Hamon, Martial Mehran, Roxana Stone, Gregg W. TI Impact of Femoral Vascular Closure Devices and Antithrombotic Therapy on Access Site Bleeding in Acute Coronary Syndromes The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; anticoagulants; myocardial infarction; stents; vascular closure devices ID CARDIAC-CATHETERIZATION; MANUAL COMPRESSION; RANDOMIZED-TRIAL; COMPLICATIONS; METAANALYSIS; BIVALIRUDIN; ANGIOPLASTY; HEMOSTASIS AB Background-The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial demonstrated that bivalirudin monotherapy significantly reduces major bleeding compared with heparin (unfractionated or enoxaparin) or bivalirudin plus a glycoprotein IIb/IIIa inhibitor in acute coronary syndromes. Whether vascular closure devices (VCD) impact these results is unknown. Therefore, this study sought to determine whether VCD impact major access site bleeding (ASB) in patients with acute coronary syndromes undergoing early invasive management by the femoral approach. Methods and Results-Major ASB in ACUITY was defined as ASB requiring interventional or surgical correction, hematoma >= 5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop >= 3 g/dL with ecchymosis or hematoma <5 cm, oozing blood, or prolonged bleeding (>30 minutes) at the access site. Stepwise logistical regression was performed to identify the independent determinants of ASB. Of 11 621 patients undergoing angiography with or without percutaneous coronary intervention by the femoral approach, 4307 (37.1%) received a VCD and 7314 (62.9%) did not. Rates of major ASB were lower with VCD compared with no VCD (2.5% versus 3.3%, relative risk, 0.76; 95% CI, 0.61 to 0.94; P = 0.01) and were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). Stepwise logistic regression revealed that a VCD (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P = 0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25 to 0.49; P < 0.0001) were both independent determinates of freedom from major ASB. Conclusion-In patients with acute coronary syndromes undergoing an early invasive management strategy by the femoral approach, the use of a VCD, bivalirudin monotherapy, or both minimizes rates of major ASB. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00093158. (Circ Cardiovasc Interv. 2010;3:57-62.) C1 [Sanborn, Timothy A.] Evanston NW Healthcare, Evanston, IL USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Los Angeles, CA USA. [Ebrahimi, Ramin] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [Manoukian, Steven V.] Sarah Cannon Res Inst, Nashville, TN USA. [Manoukian, Steven V.] Hosp Corp Amer, Nashville, TN USA. [McLaurin, Brent T.] AnMed Hlth, Anderson, SC USA. [Cox, David A.] Lehigh Valley Hosp, Allentown, PA USA. [Feit, Frederick] NYU, Sch Med, New York, NY USA. [Hamon, Martial] Univ Hosp Caen, Normandy, France. [Ebrahimi, Ramin; Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. [Ebrahimi, Ramin; Stone, Gregg W.] Cardiovasc Res Fdn, New York, NY USA. RP Sanborn, TA (reprint author), NorthShore Univ HealthSyst, Dept Med, Div Cardiol, 2650 Ridge Ave,Walgreen Bldg,3rd Floor, Evanston, IL 60201 USA. EM tsanborn@northshore.org FU Medicines Company (Parsippany, NJ); Boston Scientific; Abbott FX The ACUITY trial was sponsored by The Medicines Company (Parsippany, NJ).; Dr Sanborn received honoraria from and is a member of speaker's bureau of The Medicines Company and Merck. Dr Ebrahimi received honoraria from and is a member of speaker's bureau of The Medicines Company and Abbott. Dr Manoukian received honoraria from and is a member of speaker's bureau of The Medicines Company. Dr McLaurin has no financial support to disclose. Dr Cox received honoraria from and is a member of speaker's bureau of Abbott, The Medicines Company, and Boston Scientific and is a consultant and a member of the advisory board of Abbott and Boston Scientific. Dr Feit holds an ownership interest in Johnson & Johnson, Lilly, and The Medicines Company and received honoraria and is a member of the speaker's bureau of The Medicines Company. Dr Hamon received honoraria from and is a member of the speaker's bureau of The Medicines Company and is a consultant and a member of the advisory board of The Medicines Company. Dr Mehran received honoraria from and is a member of speaker's bureau of The Medicines Company, Boston Scientific, Regardo, Therox, Sanofi/Aventis/ BMS, Lilly, Gubert, Abiomed, Cordis, Medtronic, and Abbott; is a consultant and a member of the advisory board of The Medicines Company, Boston Scientific, Sanofi/Aventis/BMS, Cordis, Medtronic, BRACCO, and Abbott; and received other research support (receipt of drugs, supplies, equipment, or other in-kind support) and research grant (principal investigator, collaborator or consultant, and pending or already received grants) from Boston Scientific. Dr Stone received other research support (receipt of drugs, supplies, equipment, or other in-kind support) and research grant (principal investigator, collaborator or consultant, and pending or already received grants) from The Medicines Company, Boston Scientific, and Abbott and received honoraria from and is a member of speaker's bureau of St Jude and Lilly. NR 16 TC 67 Z9 70 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD FEB PY 2010 VL 3 IS 1 BP 57 EP 62 DI 10.1161/CIRCINTERVENTIONS.109.896704 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575LV UT WOS:000276069500009 PM 20118151 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Controversies in non-ST-elevation acute coronary syndromes and percutaneous coronary interventions SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID DRUG-ELUTING STENTS; RANDOMIZED CLINICAL-TRIALS; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; UNSTABLE ANGINA; CLOPIDOGREL; METAANALYSIS; STRATEGIES; THROMBOSIS; DISEASE AB Non-ST-elevation myocardial infarction (MI) and unstable angina represent the majority of acute coronary syndromes. Recent studies have helped clarify treatment strategies. Drug-eluting stents have reduced the problem of restenosis, but questions remain about the length of time patients need dual antiplatelet therapy. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. [Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 75 Francis St,PBB 146, Boston, MA 02115 USA. EM dlbhattmd@post.harvard.edu NR 39 TC 1 Z9 1 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD FEB PY 2010 VL 77 IS 2 BP 101 EP + DI 10.3949/ccjm.77gr.32009 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 556TA UT WOS:000274613900009 PM 20124267 ER PT J AU Depta, JP Bhatt, DL AF Depta, Jeremiah P. Bhatt, Deepak L. TI Omeprazole and clopidogrel: Should clinicians be worried? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID PROTON PUMP INHIBITORS; TRIAL; PANTOPRAZOLE; ASPIRIN; THERAPY; RISK AB The US Food and Drug Administration has issued a warning that omeprazole (Prilosec) reduces the antiplatelet activity of clopidogrel (Plavix) by about 50%. However, the warning is based largely on ex vivo data. Preliminary results from a randomized clinical trial revealed no effect on cardiovascular outcomes when omeprazole was given with clopidogrel. We recommend that physicians continue to prescribe a proton pump inhibitor for patients receiving dual antiplatelet therapy who are at risk of gastrointestinal bleeding or have an indication for use of a proton pump inhibitor. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Depta, Jeremiah P.] Cleveland Clin, Inst Med, Dept Internal Med, Cleveland, OH 44106 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlb-hattmd@post.harvard.edu NR 20 TC 21 Z9 23 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD FEB PY 2010 VL 77 IS 2 BP 113 EP 116 DI 10.3949/ccjm.77a.09173 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 556TA UT WOS:000274613900010 PM 20124268 ER PT J AU Jegede, AB Rosado-Rivera, D Bauman, WA Cardozo, CP Sano, M Moyer, JM Brooks, M Wecht, JM AF Jegede, Adejoke B. Rosado-Rivera, Dwindally Bauman, William A. Cardozo, Christopher P. Sano, Mary Moyer, Jeremy M. Brooks, Monifa Wecht, Jill Maria TI Cognitive performance in hypotensive persons with spinal cord injury SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Blood pressure; Tetraplegia; Paraplegia; Cognitive testing; Hypotension; Spinal cord injury ID CEREBRAL-BLOOD-FLOW; CONTINGENT NEGATIVE-VARIATION; 110 MM HG; ORTHOSTATIC HYPOTENSION; REDEFINING HYPOTENSION; MEMORY CONSOLIDATION; TETRAPLEGIC MAN; HEALTHY HUMANS; LOWER LIMIT; PRESSURE AB Due to sympathetic de-centralization, individuals with spinal cord injury (SCI), especially those with tetraplegia, often present with hypotension, worsened with upright posture. Several investigations in the non-SCI population have noted a relationship between chronic hypotension and deficits in memory, attention and processing speed and delayed reaction times. To determine cognitive function in persons with SCI who were normotensive or hypotensive over a 24-h observation period while maintaining their routine activities. Subjects included 20 individuals with chronic SCI (2-39 years), 13 with tetraplegia (C4-8) and 7 with paraplegia (T2-11). Individuals with hypotension were defined as having a mean 24-h systolic blood pressure (SBP) below 110 mmHg for males and 100 mmHg for females, and having spent a parts per thousand yen50% of the total time below these gender-specific thresholds. The cognitive battery used included assessment of memory (CVLT), attention and processing speed (Digit Span, Stroop word and color and Oral Trails A), language (COWAT) and executive function (Oral Trails B and Stroop color-word). Demographic parameters did not differ among the hypotensive and normotensive groups; the proportion of individuals with tetraplegia (82%) was higher in the hypotensive group. Memory was significantly impaired (P < 0.05) and there was a trend toward slowed attention and processing speed (P < 0.06) in the hypotensive compared to the normotensive group. These preliminary data suggest that chronic hypotension in persons with SCI is associated with deficits in memory and possibly attention and processing speed, as previously reported in the non-SCI population. C1 [Jegede, Adejoke B.; Rosado-Rivera, Dwindally; Bauman, William A.; Cardozo, Christopher P.; Moyer, Jeremy M.; Wecht, Jill Maria] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, VA Rehabil Res & Dev Serv, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.; Sano, Mary; Moyer, Jeremy M.] James J Peters VAMC, Med Serv, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.; Sano, Mary; Wecht, Jill Maria] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Cardozo, Christopher P.; Wecht, Jill Maria] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Moyer, Jeremy M.; Brooks, Monifa] Kessler Inst Rehabil, W Orange, NJ USA. [Sano, Mary] James J Peters VA Med Ctr, Dept Res & Dev, Bronx, NY 10468 USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, VA Rehabil Res & Dev Serv, Rm 1E-02 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service [B3346V, B4723H, B4162C]; National Institute of Health [P50AG005138] FX This research was supported by the Veterans Affairs Rehabilitation Research and Development Service (# B3346V, # B4723H and # B4162C), the National Institute of Health (# P50AG005138). NR 61 TC 18 Z9 18 U1 1 U2 5 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 2010 VL 20 IS 1 BP 3 EP 9 DI 10.1007/s10286-009-0036-z PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 555HY UT WOS:000274501000002 PM 19842013 ER PT J AU Overmoyer, BA AF Overmoyer, Beth A. TI Inflammatory Breast Cancer: Novel Preoperative Therapies SO CLINICAL BREAST CANCER LA English DT Review DE Bevacizumab; E-Cadherin; Lapatinib; RhoC; Trastuzumab ID END RESULTS PROGRAM; E-CADHERIN; PHASE-II; NEOADJUVANT TRASTUZUMAB; CARCINOMA INCIDENCE; P53 GENE; EXPRESSION; PHENOTYPE; TUMOR; SURVIVAL AB The treatment of inflammatory breast cancer (IBC) has been hampered by the diagnostic rarity of the disease and its consequent inclusion in clinical trials of preoperative treatment for the more indolent locally advanced breast cancer (LABC). Patients with IBC have a 2-fold greater probability of dying of their disease compared with patients diagnosed with LABC. The aggressive clinical portrait of IBC supports the recent investigative focus on determining molecular changes specific to IBC and developing novel systemic therapies that will favorably affect its poor disease prognosis. A significant amount of laboratory research has been involved in defining a specific "inflammatory signature" for IBC, denoting molecular changes consistently found in IBC. This work has involved human IBC tissue and cell lines and has demonstrated overexpression of several molecules governing metastatic dissemination, such as overexpression of E-cadherin concurrent with a dysfunctional mucin 1. An increased prevalence of mutant TP53, overexpression of RhoC, and vascular endothelial growth factor-A has been found to contribute to the dominant influence of angiogenesis in this disease. A greater understanding of the molecular mechanisms governing the pathophysiology of IBC has led to the development and clinical application of novel targeting agents for preoperative therapy. This study reviews the advances in molecular understanding of IBC and focuses on the efficacy of therapies that target the epidermal growth factor pathway and angiogenesis as well as early investigational therapies involving RhoC and TP53. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Overmoyer, BA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bovermoyer@partners.org NR 61 TC 6 Z9 8 U1 0 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2010 VL 10 IS 1 BP 27 EP 32 DI 10.3816/CBC.2010.n.003 PG 6 WC Oncology SC Oncology GA 550AU UT WOS:000274099100002 PM 20133255 ER PT J AU Park, SY Lee, HE Li, HL Shipitsin, M Gelman, R Polyak, K AF Park, So Yeon Lee, Hee Eun Li, Hailun Shipitsin, Michail Gelman, Rebecca Polyak, Kornelia TI Heterogeneity for Stem Cell-Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; METHYLATION PATTERNS; CLONAL EVOLUTION; CD24 EXPRESSION; MAMMARY-GLAND; DIFFERENTIATION; CD44(+)/CD24(-); METASTASIS; CARCINOMAS; PHENOTYPE AB Purpose: To evaluate the expression of stem cell-related markers at the cellular level in human breast tumors of different subtypes and histologic stage. Experimental Design: We performed immunohistochemical analyses of 12 proteins [CD44, CD24, ALDH1, vimentin, osteonectin, EPCR, caveolin 1, connexin 43, cytokeratin 18 (CK18), MUC1, claudin 7, and GATA3] selected based on their differential expression in breast cancer cells with more differentiated and stem cell-like characteristics in 47 cases of invasive ductal carcinoma (IDC) only, 135 cases of IDC with ductal carcinoma in situ (DCIS), 35 cases of DCIS with microinvasion, and 58 cases of pure DCIS. We also analyzed 73 IDCs with adjacent DCIS to determine the differences in the expression of markers by histology within individual tumors. CD44+/CD24- and CD24-/CD24+ cells were detected using double immunohistochemistry. Results: CD44 and EPCR expression was different among the four histologic groups and was lower in invasive compared with in situ tumors, especially in luminal A subtype. The expression of vimentin, osteonectin, connexin 43, ALDH1, CK18, GATA3, and MUC1 differed by tumor subtype in some histologic groups. ALDH1-positive cells were more frequent in basal-like and HER2+ than in luminal tumors. CD44+/CD24- cells were detected in 69% of all tumors with 100% of the basal-like and 52% of HER2+ tumors having some of these cells. Conclusions: Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell-like and more differentiated cell markers varies according to tumor subtype and histologic stage. Clin Cancer Res; 16(3); 876-87. (C) 2010 AACR. C1 [Park, So Yeon; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Hailun; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Hailun; Shipitsin, Michail; Gelman, Rebecca; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA USA. [Li, Hailun; Gelman, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Park, So Yeon] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul, South Korea. [Park, So Yeon; Lee, Hee Eun] Seoul Natl Univ Bundang Hosp, Dept Pathol, Songnam, Gyeonggi, South Korea. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu RI Lee, Hee Eun/G-6372-2011; Park, So Yeon/A-2621-2012; Seoul National University, Pathology/B-6702-2012 FU Dana-Farber/Harvard Cancer Center [CA89393, CA006516]; Breast Cancer Research Foundation [W81XWH-07-1-0294]; Department of Defense [W81XWH-07-1-0294]; Susan G. Komen Foundation; Novartis Pharmaceuticals, Inc. FX National Cancer Institute Specialized Programs of Research Excellence in Breast Cancer (CA89393) at Dana-Farber Harvard Cancer Center (CA89393) and the Dana-Farber/Harvard Cancer Center grant CA006516 (R. Gelman and K. Polyak), the Breast Cancer Research Foundation and Department of Defense grant W81XWH-07-1-0294 (K. Polyak), and the Susan G. Komen Foundation fellowship (M. Shipitsin).; K. P. receives research support from Novartis Pharmaceuticals, Inc. and is a consultant to Novartis Pharmaceuticals, Inc. and Xceed Molecular. NR 48 TC 187 Z9 200 U1 4 U2 23 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 FEB 1 PY 2010 VL 16 IS 3 BP 876 EP 887 DI 10.1158/1078-0432.CCR-09-1532 PG 12 WC Oncology SC Oncology GA 607ZF UT WOS:000278545100012 PM 20103682 ER PT J AU Ghobrial, IM Roccaro, A Hong, FX Weller, E Rubin, N Leduc, R Rourke, M Chuma, S Sacco, A Jia, XY Azab, F Azab, AK Rodig, S Warren, D Harris, B Varticovski, L Sportelli, P Leleu, X Anderson, KC Richardson, PG AF Ghobrial, Irene M. Roccaro, Aldo Hong, Fangxin Weller, Edie Rubin, Nancy Leduc, Renee Rourke, Meghan Chuma, Stacey Sacco, Antonio Jia, Xiaoying Azab, Feda Azab, Abdel Kareem Rodig, Scott Warren, Diane Harris, Brianna Varticovski, Lyuba Sportelli, Peter Leleu, Xavier Anderson, Kenneth C. Richardson, Paul G. TI Clinical and Translational Studies of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; MULTIPLE-MYELOMA; THERAPY; PATHWAY; BORTEZOMIB; CANCER; MANAGEMENT; APOPTOSIS; CRITERIA AB Background: Waldenstrom's macroglobulinemia (WM) is a rare, low-grade lymphoproliferative disorder. Based on preclinical studies, we conducted a phase II clinical trial testing the efficacy and safety of the Akt inhibitor perifosine in patients with relapsed/refractory WM. Patients and Methods: Thirty-seven patients were treated with oral perifosine (150 mg daily) for six cycles. Stable or responding patients were allowed to continue therapy until progression. Results: The median age was 65 years (range, 44-82). The median number of prior therapy lines was two (range, one to five). Of the 37 patients, 4 achieved partial response (11%), 9 minimal response (24%), and 20 showed stable disease (54%). The median progression-free survival was 12.6 months. Additionally, beta 2 microglobulin of >3.5 mg/dL was associated with poor event-free survival (P = 0.002). Perifosine was generally well tolerated; adverse events related to therapy were cytopenias (grade 3-4, 13%), gastrointestinal symptoms (grade 1-2, 81%), and arthritis flare (all grades, 11%). Translational studies using gene expression profiling and immunohistochemistry showed that perifosine inhibited pGSK activity downstream of Akt, and inhibited nuclear factor kappa B activity. Conclusion: Perifosine resulted in at least a minimal response in 35% of patients and a median progression-free survival of 12.6 months in patients with relapsed or relapsed/refractory WM, as well as in vivo inhibition of pGSK activity. The results of this study warrant further evaluation of perifosine in combination with rituximab or other active agents in patients with WM. Clin Cancer Res; 16(3); 1033-41. (C) 2010 AACR. C1 [Ghobrial, Irene M.; Roccaro, Aldo; Hong, Fangxin; Weller, Edie; Leduc, Renee; Rourke, Meghan; Chuma, Stacey; Sacco, Antonio; Jia, Xiaoying; Azab, Feda; Azab, Abdel Kareem; Warren, Diane; Harris, Brianna; Leleu, Xavier; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Rubin, Nancy] Community Hosp Monterey Peninsula, Monterey, CA USA. [Varticovski, Lyuba] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Sportelli, Peter] Keryx Biopharmaceut Inc, New York, NY USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Harris, Brianna/0000-0001-6229-9907 FU Keryx Biopharmaceuticals; Millenium; Novartis; Celgene; International Waldenstrom Macroglobulinemia Foundation; Michelle and Steven Kirsch lab for Waldenstrom macroglobulinemia; Keryx Biopharmaceuticals, Inc; [R21 CA126119-01] FX I. M. Ghobrial, member of speakers' bureau for Novartis, Millenium, and Celgene and received funding from Keryx Biopharmaceuticals, Millenium, and Novartis; P. Sportelli, employed by Keryx Biopharmaceuticals; K. Anderson, received research funding and member of speakers' bureau for Novartis, Millenium, and Celgene; P. Richardson, member of speakers' bureau for Millenium and Celgene.; Grant Support; R21 CA126119-01, International Waldenstrom Macroglobulinemia Foundation, the Michelle and Steven Kirsch lab for Waldenstrom macroglobulinemia, and Keryx Biopharmaceuticals, Inc. NR 33 TC 73 Z9 76 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2010 VL 16 IS 3 BP 1033 EP 1041 DI 10.1158/1078-0432.CCR-09-1837 PG 9 WC Oncology SC Oncology GA 607ZF UT WOS:000278545100027 PM 20103671 ER PT J AU Regnier, FE Skates, SJ Mesri, M Rodriguez, H Tezak, Z Kondratovich, MV Alterman, MA Levin, JD Roscoe, D Reilly, E Callaghan, J Kelm, K Brown, D Philip, R Carr, SA Liebler, DC Fisher, SJ Tempst, P Hiltke, T Kessler, LG Kinsinger, CR Ransohoff, DF Mansfield, E Anderson, NL AF Regnier, Fred E. Skates, Steven J. Mesri, Mehdi Rodriguez, Henry Tezak, Zivana Kondratovich, Marina V. Alterman, Michail A. Levin, Joshua D. Roscoe, Donna Reilly, Eugene Callaghan, James Kelm, Kellie Brown, David Philip, Reena Carr, Steven A. Liebler, Daniel C. Fisher, Susan J. Tempst, Paul Hiltke, Tara Kessler, Larry G. Kinsinger, Christopher R. Ransohoff, David F. Mansfield, Elizabeth Anderson, N. Leigh TI Protein-Based Multiplex Assays: Mock Presubmissions to the US Food and Drug Administration SO CLINICAL CHEMISTRY LA English DT Article AB As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomic Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and Drug Administration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays. (C) 2009 American Association for Clinical Chemistry C1 [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC 20009 USA. [Regnier, Fred E.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. [Mesri, Mehdi; Rodriguez, Henry; Hiltke, Tara; Kinsinger, Christopher R.] NCI, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. [Tezak, Zivana; Kondratovich, Marina V.; Levin, Joshua D.; Roscoe, Donna; Reilly, Eugene; Callaghan, James; Kelm, Kellie; Philip, Reena; Mansfield, Elizabeth] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Alterman, Michail A.] TVBB, Ctr Biol Evaluat & Res, OCTGT, DCGT, Bethesda, MD USA. [Brown, David] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Carr, Steven A.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Liebler, Daniel C.] Vanderbilt Univ, Med Ctr, Jim Ayers Inst Precancer Detect & Diag, Nashville, TN USA. [Fisher, Susan J.] Univ Calif San Francisco, Biomol Ctr, San Francisco, CA 94143 USA. [Fisher, Susan J.] Univ Calif San Francisco, Mass Spectrometry Ctr, San Francisco, CA 94143 USA. [Tempst, Paul] Mem Sloan Kettering Canc Ctr, Prot Ctr, New York, NY 10021 USA. [Kessler, Larry G.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Ransohoff, David F.] Univ N Carolina, Chapel Hill, NC USA. RP Anderson, NL (reprint author), Plasma Proteome Inst, POB 53450, Washington, DC 20009 USA. EM leighanderson@plasmaproteome.org OI Liebler, Daniel/0000-0002-7873-3031 FU National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; National Cancer Institute-NIH; Agilent Technologies FX Research Funding: F.E. Regnier, National Cancer Institute, Clinical Proteomic Technology Assessment for Cancer; P. Tempst, National Cancer Institute-NIH; L.G. Kessler, National Cancer Institute; N.L. Anderson, Agilent Technologies. NR 3 TC 37 Z9 37 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 2010 VL 56 IS 2 BP 165 EP 171 DI 10.1373/clinchem.2009.140087 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200005 PM 20007858 ER PT J AU Gerszten, RE Carr, SA Sabatine, M AF Gerszten, Robert E. Carr, Steven A. Sabatine, Marc TI Integration of Proteomic-Based Tools for Improved Biomarkers of Myocardial Injury SO CLINICAL CHEMISTRY LA English DT Review ID ACUTE CORONARY SYNDROMES; C-REACTIVE PROTEIN; TARGETED MASS-SPECTROMETRY; NATRIURETIC PEPTIDE; TROPONIN-I; CARDIOVASCULAR-DISEASE; PROGNOSTIC VALUE; HEART-DISEASE; PHOSPHOLIPASE A(2); MULTIPLEXED ASSAYS AB BACKGROUND: Given the mounting evidence in favor of early pharmacologic and catheter-based interventions for patients across the spectrum of acute coronary syndromes, discovering novel diagnostically sensitive and specific biomarkers that provide biochemical proof of early or reversible myocardial injury could have a substantial positive impact on patient care. CONTENT: To address unmet needs in disease biomarkers, investigators have turned to proteomics approaches. We describe advances in proteomics discovery technologies based on liquid chromatography-tandem mass spectrometry that facilitate the unbiased analysis of low-abundance blood proteins. We detail the development of emerging techniques to enhance the biomarker verification process, such as accurate inclusion mass screening, stable isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM-MS), and stable isotope standards with capture by antipeptide antibodies, which combines the advantages of specific immunoaffinity enrichment of a target peptide with the structural specificity and quantitative capabilities of SID-MRM-MS. We highlight new assays incorporating these techniques for troponin 1, a representative low-abundance cardiac biomarker, and interleukin-33, an emerging novel marker of myocardial stress for which no existing ELISA exists. We demonstrate that troponin I and interleukin-33 peptides have a linear, dynamic range spanning 4 orders of magnitude and limits of detection of approximately 0.5 mu g/L back-calculated to the protein concentration. CONCLUSIONS: There remain important unmet diagnostic and prognostic needs in cardiology. Advances in technology may allow proteomics to play a vital role in the discovery and validation of novel biomarkers to help fill those needs. (C) 2009 American Association for Clinical Chemistry C1 [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Gerszten, Robert E.; Carr, Steven A.; Sabatine, Marc] Harvard Univ, Sch Med, Boston, MA USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Carr, Steven A.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Sabatine, Marc] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp E 8307, Div Cardiol, 149 13th St, Charlestown, MA 02129 USA. EM rgerszten@partners.org; scarr@broad.mit.edu FU National Heart Lung and Blood Institute [R01 HL096738-01]; National Cancer Institute (NCI) [U24 CA126476]; Women's Cancer Research Fund of the Entertainment Industry Foundation FX Research Funding: M. Sabatine, diaDexus, Ortho Clinical Diagnostics, and Singulex. This work was supported in part by grants to R.E. Gerszten, S.A. Carr, and M. Sabatine from the National Heart Lung and Blood Institute R01 HL096738-01 and by grants to S.A. Carr from the National Cancer Institute's (NCI's) U24 CA126476 [as part of the Clinical Proteomic Technologies for Cancer (CPTAC) initiative] and from the Women's Cancer Research Fund of the Entertainment Industry Foundation. NR 40 TC 26 Z9 26 U1 2 U2 10 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 FEB PY 2010 VL 56 IS 2 BP 194 EP 201 DI 10.1373/clinchem.2009.127878 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 551QD UT WOS:000274223200009 PM 20022985 ER PT J AU Crippa, S Fernandez-del Castillo, C Salvia, R Finkelstein, D Bassi, C Dominguez, I Muzikansky, A Thayer, SP Falconi, M Mino-Kenudson, M Capelli, P Lauwers, GY Partelli, S Pederzoli, P Warshaw, AL AF Crippa, Stefano Fernandez-del Castillo, Carlos Salvia, Roberto Finkelstein, Dianne Bassi, Claudio Dominguez, Ismael Muzikansky, Alona Thayer, Sarah P. Falconi, Massimo Mino-Kenudson, Mari Capelli, Paola Lauwers, Gregory Y. Partelli, Stefano Pederzoli, Paolo Warshaw, Andrew L. TI Mucin-Producing Neoplasms of the Pancreas: An Analysis of Distinguishing Clinical and Epidemiologic Characteristics SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID NATURAL-HISTORY; DUCT; TUMORS; RESECTION; MANAGEMENT; MALIGNANCY; GUIDELINES; EXPERIENCE; PREDICTORS; ENTITY AB BACKGROUND & AIMS: Mucin-producing neoplasms (MPNs) of the pancreas include mucinous cystic neoplasms (MCNs) and main-duct, branch-duct, and combined intraductal papillary mucinous neoplasms (IPMNs). MCNs and branch-duct IPMNs are frequently confused; it is unclear whether main-duct, combined, and branch-duct IPMNs are a different spectrum of the same disease. We evaluated their clinical and epidemiologic characteristics. METHODS: Patients who underwent resection for histologically confirmed MPNs Were identified (N = 557); specimens were reviewed and eventually reclassified. RESULTS: One hundred sixty-eight patients (30%) had MCNs, 159 (28.5%) had branch-duct IPMNs, 149 (27%) had combined IPMNs, and 81 (14.5%) had main-duct IPMNs. Patients with MCNs were significantly younger and almost exclusively women; 44% of patients with main-duct or combined IPMNs and 57% of those with branch-duct IPMNs were women. MCNs were single lesions located in the distal pancreas (95%); 11% were invasive. IPMNs were more frequently found in the proximal pancreas; invasive cancer was found in 11%, 42%, and 48% of branch-duct, combined, and main-duct IPMNs, respectively (P = .001). Patients with invasive MCN and those with combined and main-duct IPMNs were older than those with noninvasive tumors. The 5-year disease-specific survival rare approached 100% for patients with noninvasive MPNs. The rates for those with invasive cancer were 58%, 56%, 51%, and 64% for invasive MCNs, branch-duct IPMNs, main-duct IPMNs, and combined IPMNs, respectively. CONCLUSIONS: MPNs comprise 3 different neoplasms: MCNs, branch-duct IPMNs, and main-duct IPMNs, including the combined type. These tumors have specific clinical, epidemiologic, and morphologic features that allow a reasonable degree of accuracy in preoperative diagnosis. C1 [Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. [Mino-Kenudson, Mari; Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Finkelstein, Dianne; Muzikansky, Alona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. [Crippa, Stefano; Salvia, Roberto; Bassi, Claudio; Falconi, Massimo; Partelli, Stefano; Pederzoli, Paolo] Univ Verona, Dept Surg, Policlin GB Rossi, I-37100 Verona, Italy. [Capelli, Paola] Univ Verona, Dept Pathol, Policlin GB Rossi, I-37100 Verona, Italy. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org OI Falconi, Massimo/0000-0001-9654-7243 FU International Hepato-Pancreato-Biliary Association; Fundacion Harvard en Mexico; Fondazione Italiana Malattie Pancreas FX This study was supported by the International Hepato-Pancreato-Biliary Association (Warren Fellowship Award to S.C.), Fundacion Harvard en Mexico (to I.D.), Fondazione Italiana Malattie Pancreas. NR 28 TC 110 Z9 111 U1 0 U2 2 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 FEB PY 2010 VL 8 IS 2 BP 213 EP 219 DI 10.1016/j.cgh.2009.10.001 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 592ZP UT WOS:000277421000023 PM 19835989 ER PT J AU Xia, JX Liu, WT Hu, BL Tian, ZG Yang, YG AF Xia, Jinxing Liu, Wentao Hu, Biliang Tian, Zhigang Yang, Yongguang TI IL-15 promotes regulatory T cell function and protects against diabetes development in NK-depleted NOD mice SO CLINICAL IMMUNOLOGY LA English DT Article DE Diabetes; Mice; IL-15; Natural killer cells ID IFN-GAMMA; IMMUNE DYSREGULATION; AUTOIMMUNE-DISEASE; MOUSE; ANTIGEN; SUPPRESSION; ACTIVATION; TOLERANCE; MELLITUS; ANTIBODY AB IL-15, an anti-apoptotic cytokine, has been reported to promote the survival and function of NK cells and T cells, including regulatory T cells (Tregs). Here we examined the effect of repeated injections of IL-15 on the development of diabetes in NOD mice. Injection of recombinant murine IL-15, once a day for 2 weeks, neither inhibited nor accelerated diabetes development in untreated NOD mice. However, treatment with IL-15 significantly reduced the incidence and delayed the onset of diabetes in NOD mice that were depleted of NK cells, white NK cell depletion alone had no protection against the disease development. The protective effect in IL-15-treated, NK cell-depleted NOD mice was associated with an increase in immunosuppressive activity of CD4(+)CD25(+) Tregs. IL-15 also enhanced Foxp3 expression in CD4(+)CD25(+) cells in an in vitro culture system, and such an effect of IL-15 was abrogated by IL-15-activated NK cells. Inhibition of IL-15-induced Foxp3 expression by IL-15-activated NK cells likely resulted from their IFN-gamma production, as recombinant IFN-gamma, or the culture supernatant of IL-15-activated wild-type mouse NK cells but not of IL-15-activated IFN-gamma-deficient NK cells, mediated a similar inhibition. IFN-gamma also diminished the stimulatory effect of IL-15 on Treg function in vitro. These results indicate that IL-15 has the potential to promote Treg function and protect against diabetes development in NOD mice, but such an activity can be eliminated by simultaneous activation of NK cells in IL-15-treated mice. (C) 2009 Elsevier Inc. All rights reserved. C1 [Yang, Yongguang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02129 USA. [Xia, Jinxing; Liu, Wentao; Hu, Biliang; Tian, Zhigang; Yang, Yongguang] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Inst Immunol, Hefei 230027, Peoples R China. [Xia, Jinxing; Liu, Wentao; Hu, Biliang; Tian, Zhigang; Yang, Yongguang] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02129 USA. EM ustclwt@ustc.edu.cn; yang@tbrc.mgh.harvard.edu RI Hu, Biliang/J-7564-2013; Xia, Jinxing/E-5658-2015; Tian, Zhigang/J-3512-2013 FU National Natural Science Foundation of China [30671910, 30671982] FX This work was supported by grants of National Natural Science Foundation of China (#30671910 and #30671982). NR 39 TC 15 Z9 16 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD FEB PY 2010 VL 134 IS 2 BP 130 EP 139 DI 10.1016/j.clim.2009.09.011 PG 10 WC Immunology SC Immunology GA 544ZW UT WOS:000273701800005 PM 19875339 ER PT J AU Perfect, JR Dismukes, WE Dromer, F Goldman, DL Graybill, JR Hamill, RJ Harrison, TS Larsen, RA Lortholary, O Nguyen, MH Pappas, PG Powderly, WG Singh, N Sobel, JD Sorrell, TC AF Perfect, John R. Dismukes, William E. Dromer, Francoise Goldman, David L. Graybill, John R. Hamill, Richard J. Harrison, Thomas S. Larsen, Robert A. Lortholary, Olivier Nguyen, Minh-Hong Pappas, Peter G. Powderly, William G. Singh, Nina Sobel, Jack D. Sorrell, Tania C. TI Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ORGAN TRANSPLANT RECIPIENTS; RECONSTITUTION INFLAMMATORY SYNDROME; LIPOSOMAL AMPHOTERICIN-B; HIGH-DOSE FLUCONAZOLE; PLACEBO-CONTROLLED TRIAL; NEOFORMANS VAR GATTII; HIGH HIV SEROPREVALENCE; SOUTH-AFRICAN PROVINCE AB Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients. C1 [Perfect, John R.] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. [Dismukes, William E.; Pappas, Peter G.] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL USA. [Goldman, David L.] Albert Einstein Coll Med, Dept Pediat Infect Dis, Bronx, NY 10467 USA. [Graybill, John R.] Univ Texas San Antonio, Div Infect Dis, Audie L Murphy Vet Affairs Hosp, San Antonio, TX USA. [Hamill, Richard J.] VA Med Ctr, Div Infect Dis, Houston, TX USA. [Larsen, Robert A.] Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Larsen, Robert A.] Univ So Calif, Sch Med, Dept Infect Dis, Los Angeles, CA USA. [Nguyen, Minh-Hong] Univ Pittsburgh, Div Infect Dis, Coll Med, Pittsburgh, PA USA. VA Med Ctr, Infect Dis Sect, Pittsburgh, PA USA. [Singh, Nina; Sobel, Jack D.] Wayne State Univ, Harper Hosp, Detroit, MI USA. [Dromer, Francoise; Lortholary, Olivier] Inst Pasteur, Ctr Natl Reference Mycol & Antifong, Unite Mycol Mol, Paris, France. [Lortholary, Olivier] Univ Paris 05, Serv Malad Infect & Trop, Hop Necker Enfants Malad, Ctr Infectiol Necker Pasteur, Paris, France. [Powderly, William G.] Univ Coll Dublin, Dublin 2, Ireland. [Harrison, Thomas S.] St George Hosp, Sch Med, Dept Infect Dis, London, England. [Sorrell, Tania C.] Univ Sydney Westmead, Ctr Infect Dis & Microbiol, Sydney, NSW, Australia. RP Perfect, JR (reprint author), Duke Univ, Med Ctr, Div Infect Dis, Hanes House,Rm 163,Box 102359, Durham, NC 27710 USA. EM perfe001@mc.duke.edu FU Infectious Diseases Society of America [AI73896] FX The Infectious Diseases Society of America (Public Health Service Grant AI73896 to J.R.P.). NR 194 TC 631 Z9 704 U1 6 U2 73 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2010 VL 50 IS 3 BP 291 EP 322 DI 10.1086/649858 PG 32 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 542NG UT WOS:000273500300001 PM 20047480 ER PT J AU Bender, MA Kumarasamy, N Mayer, KH Wang, BX Walensky, RP Flanigan, T Schackman, BR Scott, CA Lu, ZG Freedberg, KA AF Bender, Melissa A. Kumarasamy, Nagalingeswaran Mayer, Kenneth H. Wang, Bingxia Walensky, Rochelle P. Flanigan, Timothy Schackman, Bruce R. Scott, Callie A. Lu, Zhigang Freedberg, Kenneth A. CA Cost Effectiveness Preventing AIDS TI Cost-Effectiveness of Tenofovir as First-Line Antiretroviral Therapy in India SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MULTIPLE VIROLOGICAL FAILURES; HIV-INFECTED PATIENTS; DISOPROXIL FUMARATE; OBSERVATIONAL DATABASE; RENAL-FAILURE; ADHERENCE; SAFETY; ADULTS; LOPINAVIR/RITONAVIR; LIPODYSTROPHY AB Background. World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared with current practice using stavudine or zidovudine. Methods. We used a state-transition model of human immunodeficiency virus (HIV) disease to examine strategies using different nucleoside reverse-transcriptase inhibitors, combined with lamivudine and nevirapine, compared with no ART: (1) stavudine, (2) stavudine with substitution by zidovudine after 6 months, (3) zidovudine, and (4) tenofovir. Data were from the Y. R. Gaitonde Centre for AIDS Research and Education in Chennai, India, and published studies. Results. Discounted mean per person survival was 36.9 months (40.2 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.7 months (145.6) with stavudine and 6-month zidovudine substitution, 115.8 months (145.6) with zidovudine-containing ART, and 125.8 months (162.0) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5580 with stavudine-containing ART to $5720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670 per year of life saved, compared with no ART, and was more economically efficient than the other regimens. Results were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after treatment failure, and quality of life adjustment. Conclusions. Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India. C1 [Bender, Melissa A.; Wang, Bingxia; Walensky, Rochelle P.; Scott, Callie A.; Lu, Zhigang; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bender, Melissa A.; Wang, Bingxia; Walensky, Rochelle P.; Scott, Callie A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Bender, Melissa A.; Wang, Bingxia; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Mayer, Kenneth H.; Flanigan, Timothy] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. [Kumarasamy, Nagalingeswaran] YR Gaitronde Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India. RP Bender, MA (reprint author), 423 E 23rd St, New York, NY 10010 USA. EM melissa.bender@nyumc.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [K01 AI074495, T32 AI007433 to, K24AI062476, R01 AI058736]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute on Drug Abuse [K01 DA017179]; Doris Duke Charitable Foundation Operations Research on AIDS Care and Treatment in Africa (ORACTA) Award [2007015]; Harvard Medical School Eleanor; Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine Award; Lifespan/Tufts/Brown University Center for AIDS Research [P30AI042853] FX National Institute of Allergy and Infectious Diseases (K01 AI074495 and T32 AI007433 to M. A. B., K24AI062476 and R01 AI058736 to K. A. F.), Harvard University Center for AIDS Research (P30 AI060354 to M. A. B.), National Institute on Drug Abuse (K01 DA017179 to B. R. S.), Doris Duke Charitable Foundation Operations Research on AIDS Care and Treatment in Africa (ORACTA) Award (2007015 to K. A. F. and M. A. B.), Doris Duke Charitable Foundation Clinical Scientist Development Award (2005075 to R. P. W.), Harvard Medical School Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine Award (to M. A. B.), and the Lifespan/Tufts/Brown University Center for AIDS Research (P30AI042853 to T. F. and K. H. M.). NR 40 TC 37 Z9 38 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2010 VL 50 IS 3 BP 416 EP 425 DI 10.1086/649884 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 542NG UT WOS:000273500300018 PM 20043752 ER PT J AU Granda-Cameron, C DeMille, D Lynch, MP Huntzinger, C Alcorn, T Levicoff, J Roop, C Mintzer, D AF Granda-Cameron, Clara DeMille, Debra Lynch, Mary Pat Huntzinger, Christine Alcorn, Theresa Levicoff, Joan Roop, Carly Mintzer, David TI An Interdisciplinary Approach to Manage Cancer Cachexia SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID WEIGHT-LOSS; NUTRITIONAL ASSESSMENT; PALLIATIVE CARE; CHEMOTHERAPY; FATIGUE; MALABSORPTION; EXERCISE; ANOREXIA AB Cancer cachexia occurs in about 33% of newly diagnosed patients with cancer and may lead to delayed, missed, or decreased treatments. An interdisciplinary team approach to manage cancer cachexia may result in fewer missed treatments and improved outcomes. The palliative care program of an urban community cancer center developed an interdisciplinary clinic to treat cancer cachexia with the goal of using an interdisciplinary approach to improve symptom management, nutrition, function, and quality of life (QOL) for patients with cancer at high risk for malnutrition. The Cancer Appetite and Rehabilitation Clinic team completes medical, nutritional, speech, swallowing, and physical therapy evaluations and then develops an individualized program directed to meet patients' needs and improve overall QOL. Patient outcomes are measured by symptom management and nutritional and functional parameters. Early intervention and aggressive symptom management may improve performance status and overall QOL. Results from this project will be used to expand this innovative program. The process of developing and implementing this clinic may help oncology nurses and other healthcare professionals to improve management of cancer cachexia and overall cancer care. C1 [Granda-Cameron, Clara] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [DeMille, Debra; Lynch, Mary Pat; Alcorn, Theresa; Roop, Carly] Penn Hosp, Joan Karnell Canc Ctr, Philadelphia, PA 19107 USA. [Huntzinger, Christine] Good Shepherd Penn Partners, Inpatient Rehabil Serv, Philadelphia, PA USA. [Mintzer, David] Penn Hosp, Pain & Support Care Program, Philadelphia, PA 19107 USA. RP Granda-Cameron, C (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM claritacameron@gmail.com NR 45 TC 17 Z9 19 U1 3 U2 10 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 FEB PY 2010 VL 14 IS 1 BP 72 EP 80 DI 10.1188/10.CJON.72-80 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 556UI UT WOS:000274618000015 PM 20118029 ER PT J AU Doherty, L LaFrankie, DC AF Doherty, Lisa LaFrankie, Debra Conrad TI Patient Safety Concerns for Cognitively Impaired Patients With Brain Tumors SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID THERAPY AB Patients with malignant gliomas often have safety concerns not common in patients with other types of cancer. Neurologic and cognitive deficits make the care of such patients more complex, with much of the burden of care falling to the primary caretaker and family. C1 [Doherty, Lisa; LaFrankie, Debra Conrad] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Doherty, L (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. EM ldoherty1@partners.org NR 10 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2010 VL 14 IS 1 BP 101 EP 102 DI 10.1188/10.CJON.101-102 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 556UI UT WOS:000274618000019 PM 20118033 ER PT J AU Stojanovic, MP Sethee, J Mohiuddin, M Cheng, JG Barker, A Wang, J Palmer, W Huang, A Cohen, SP AF Stojanovic, Milan P. Sethee, Jai Mohiuddin, Meraj Cheng, Jianguo Barker, Amanda Wang, Jing Palmer, William Huang, Ambrose Cohen, Steven P. TI MRI Analysis of the Lumbar Spine: Can It Predict Response to Diagnostic and Therapeutic Facet Procedures? SO CLINICAL JOURNAL OF PAIN LA English DT Article DE facet; MRI; RF denervation; spinal stenosis; zygapophysial joint ID LOW-BACK-PAIN; ZYGAPOPHYSIAL JOINT PAIN; RADIOFREQUENCY DENERVATION; DOUBLE-BLIND; MULTICENTER ANALYSIS; INJECTION; NEUROTOMY; BLOCKS; TRIAL; OSTEOARTHRITIS AB Objectives: To determine the correlation between magnetic resonance imaging (MRI) pathology and the response to diagnostic facet medial branch block (MBB) and L5 dorsal ramus medial branch block and radiofrequency (RF) denervation of lumbar facet joints. Methods: The medical records of 127 consecutive patients who underwent MBB for suspected zygapophysial joint pain were reviewed. The lumbar spine MRI of these patients was systematically graded by 2 musculoskeletal radiologists for loss of disc height, spinal stenosis, facet joint degeneration, and other forms of spinal Pathology. Results: Patients with central or foraminal spinal stenosis had statistically significant correlation with positive outcome of RF (P = 0.02), but not with MBB (P = 0.08). The presence of facet joint degeneration or hypertrophy was positively correlated with response to M BB (71% vs. 51%; P = 0.04), but not R F. Loss of disc height did not correlate with outcome of MBB (P = 0.08) and RF (P = 0.29). For other spinal pathology, no significant differences were noted for either the response to diagnostic blocks or the RF denervation. Younger patients were more likely to fail MBB (P < 0.01) but not RE denervation (P = 0.38). Discussion: Whereas some relationships were noted between MRI findings and the response to lumbar facet joint interventions, many of these correlations tended to be weak. However, this study does suggest the possibility that patients with spinal stenosis, often considered an exclusion criterion for facet interventions, may respond to RE denervation of facet joints. Prospective studies are needed to confirm these observations. C1 [Stojanovic, Milan P.; Sethee, Jai; Mohiuddin, Meraj] Harvard Univ, Dept Anesthesia & Crit Care, Ctr Pain Med,Sch Med, Massachusetts Gen Hosp,Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Palmer, William; Huang, Ambrose] Harvard Univ, Dept Radiol, Spaulding Rehabil Hosp, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Barker, Amanda] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. [Cheng, Jianguo] Cleveland Clin, Dept Pain Management, Inst Anesthesiol, Cleveland, OH 44106 USA. [Wang, Jing; Cohen, Steven P.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Div Pain Med, Baltimore, MD 21205 USA. RP Stojanovic, MP (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Ctr Pain Med,Sch Med, Massachusetts Gen Hosp,Spaulding Rehabil Hosp, 15 Parkman St, Boston, MA 02114 USA. EM mpstojanovic@gmail.com NR 41 TC 12 Z9 12 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD FEB PY 2010 VL 26 IS 2 BP 110 EP 115 PG 6 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 550CK UT WOS:000274105600005 PM 20090436 ER PT J AU Doolittle, MH Peterfy, M AF Doolittle, Mark H. Peterfy, Miklos TI Mechanisms of lipase maturation SO CLINICAL LIPIDOLOGY LA English DT Review DE chaperone; endoplasmic reticulum; endothelial lipase; glycosylation; hepatic lipase; lipase maturation factor 1; lipoprotein lipase protein folding ID HIGH-DENSITY-LIPOPROTEIN; N-LINKED GLYCOSYLATION; HUMAN HEPATIC LIPASE; ER QUALITY-CONTROL; ENDOPLASMIC-RETICULUM; ENDOTHELIAL LIPASE; INSULIN-RESISTANCE; PANCREATIC LIPASE; SEVERE HYPERTRIGLYCERIDEMIA; TRIGLYCERIDE LIPASE AB Lipases are acyl hydrolases that represent a diverse-group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps, occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding and subunit assembly. This article identifies key factors that facilitate this process and discusses mechanisms that direct early and late events in lipase folding and assembly. Lipase maturation employs the two general chaperone systems operating in the endoplasmic reticulum, as well as a recently identified lipase-specific chaperone termed lipase maturation factor 1. We propose that the two general chaperone systems act in a coordinated manner early in lipase maturation in order to help create partially folded monomers; lipase maturation factor 1 then facilitates final monomer folding and subunit assembly into fully functional homodimers. Once maturation is complete, the lipases exit the endoplasmic reticulum and are secreted to extracellular sites, where they carry out a number of functions related and lipid metabolism. C1 [Doolittle, Mark H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Doolittle, Mark H.; Peterfy, Miklos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Peterfy, Miklos] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. RP Doolittle, MH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. EM markdool@ucla.edu FU David Geffen School of Medicine; University of California; Los Angeles; Cedars-Sinai Medical Center; National Institutes of Health [HL24841] FX We acknowledge the support of the David Geffen School of Medicine, University of California, Los Angeles, the Cedars-Sinai Medical Center, the Department of Veterans Affairs and grant HL24841 from the National Institutes of Health. We would also like to acknowledge Drs Howard Wong and Keith Munson for their generous contribution of the structural model of hepatic lipase presented in Figure 1. 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 114 TC 1 Z9 1 U1 2 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-4299 J9 CLIN LIPIDOL JI Clin. Lipidol. PD FEB PY 2010 VL 5 IS 1 BP 117 EP 130 DI 10.2217/CLP.09.84 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 555NW UT WOS:000274520200016 ER PT J AU Tsourounis, C Bent, S AF Tsourounis, C. Bent, S. TI Why Change Is Needed in Research Examining Dietary Supplements SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 [Tsourounis, C.] Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94143 USA. [Bent, S.] Univ Calif San Francisco, Dept Med, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Bent, S.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Tsourounis, C (reprint author), Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94143 USA. EM tsourounisc@pharmacy.ucsf.edu NR 7 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2010 VL 87 IS 2 BP 147 EP 149 DI 10.1038/clpt.2009.241 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 550PK UT WOS:000274140200006 PM 20107446 ER PT J AU Konig, A Bleie, O Rieber, J Jung, P Schiele, TM Sohn, HY Leibig, M Siebert, U Klauss, V AF Koenig, Andreas Bleie, Oyvind Rieber, Johannes Jung, Philip Schiele, Thomas M. Sohn, Hae-Young Leibig, Marcus Siebert, Uwe Klauss, Volker TI Intravascular ultrasound radiofrequency analysis of the lesion segment profile in ACS patients SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Acute coronary syndrome; Intravascular ultrasound; Radiofrequency analysis; Plaque composition; Lesion profile ID ACUTE CORONARY-SYNDROME; ACUTE MYOCARDIAL-INFARCTION; PLAQUE COMPOSITION; VIRTUAL HISTOLOGY; RUPTURED PLAQUES; ARTERY DISEASE; STABLE ANGINA; MORPHOLOGY; CLASSIFICATION; INTERVENTIONS AB Intravascular ultrasound radiofrequency analysis (IVUS-RF) characterizes plaque components as necrotic core (NC) and dense calcium (DC). The aim of this study was to perform an IVUS-RF derived analysis of the lesion segment profile in acute coronary syndrome (ACS) patients. Therefore, we compared the site of the minimum lumen area-cross sectional area (mla-CSA) with the worst lesion site-CSA (ws-CSA) defined by the maximum NC site. We performed IVUS-RF derived plaque composition and plaque-type classification analysis in 48 ACS patients with 48 culprit (CL) and 69 non-culprit lesions (NCL). The plaque dimension of the mla- and ws-CSA was significantly different regarding the lumen area (5.18 +/- A 2.09 mm(2) vs. 6.72 +/- A 2.73 mm(2), p = 0.0013) and the vessel area (14.80 +/- A 5.86 mm(2) vs. 17.15 +/- A 4.94 mm(2), p = 0.0142). The absolute plaque composition was also significantly different regarding the DC tissue (0.71 +/- A 0.57 mm(2) vs. 0.98 +/- A 0.54 mm(2), p = 0.0102) and the NC tissue (1.41 +/- A 1.28 mm(2) vs. 1.85 +/- A 1.37 mm(2), p = 0.0469). The plaque-type classification revealed significantly more thin cap fibroatheroma (TCFA) lesions at the ws-CSA compared to the mla-CSA (n = 53/89.8% vs. n = 26/44.1%, p < 0.0001). In the majority of the CL and NCL lesion segments the ws-CSA was located proximal to the mla-CSA compared to the distal location (n = 65/55.6% vs. n = 23/19.7%). In the majority of the lesion segments in ACS patients the ws-CSA is not identical with the mla-CSA. The ws-CSA compared to mla-CSA presented with significantly more NC and DC tissue resulting in a higher amount of TCFA lesions. C1 [Koenig, Andreas; Rieber, Johannes; Jung, Philip; Schiele, Thomas M.; Sohn, Hae-Young; Leibig, Marcus; Klauss, Volker] Univ Munich, Med Klin & Poliklin, Dept Med, Div Cardiol, D-80336 Munich, Germany. [Bleie, Oyvind] Haukeland Hosp, Dept Heart Dis, N-5021 Bergen, Norway. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Konig, A (reprint author), Univ Munich, Med Klin & Poliklin, Dept Med, Div Cardiol, Ziemssenstr 1,Campus Innenstadt, D-80336 Munich, Germany. EM Andreas.Koenig@med.uni-muenchen.de NR 37 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD FEB PY 2010 VL 99 IS 2 BP 83 EP 91 DI 10.1007/s00392-009-0077-2 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 552KE UT WOS:000274287900003 PM 19768480 ER PT J AU Frei, CR Attridge, RT Mortensen, EM Restrepo, MI Yu, YF Oramasionwu, CU Ruiz, JL Burgess, DS AF Frei, Christopher R. Attridge, Russell T. Mortensen, Eric M. Restrepo, Marcos I. Yu, Yifan Oramasionwu, Christine U. Ruiz, Jessica L. Burgess, David S. TI Guideline-Concordant Antibiotic Use and Survival Among Patients With Community-Acquired Pneumonia Admitted to the Intensive Care Unit SO CLINICAL THERAPEUTICS LA English DT Article DE bacterial pneumonia; community-acquired pneumonia; guidelines; antibiotics; health outcomes; mortality ID LENGTH-OF-STAY; ANTIMICROBIAL THERAPY; CONTROLLED-TRIAL; MORTALITY; IMPLEMENTATION; MANAGEMENT; OUTCOMES; STABILITY; CRITERIA; PATHWAY AB Objective: This study evaluated the survival benefit of US community-acquired pneumonia (CAP) practice guidelines in the intensive care unit (ICU) setting. Methods: We conducted a retrospective cohort study of adult patients with CAP who were admitted to 5 community hospital ICUs between November 1, 1999, and April 30, 2000. The guidelines for antibiotic prescriptions were the 2007 Infectious Diseases Society of America/American Thoracic Society guidelines. Guideline-concordant antimicrobial therapy was defined as a beta-lactam plus fluoroquinolone or macrolide, antipseudomonal beta-lactam plus fluoroquinolone, or antipseudomonal beta-lactam plus ammoglycoside plus fluoroquinolone or macrolide. Patients with a documented beta-lactam allergy were considered to have received guideline-concordant therapy if they received a fluoroquinolone with or without clindamycin, or aztreonam plus fluoroquinolone with or without aminoglycoside. All other antibiotic regimens were considered to be guideline discordant. Time to clinical stability, time to oral antibiotics, length of hospital stay, and in-hospital mortality were evaluated with regression models that included the outcome as the dependent variable, guideline-concordant antibiotic therapy as the independent variable, and the Pneumonia Severity Index (PSI) score and facility as covariates. Results: The median age of the 129 patients included in the study was 71 years (interquartile range, 60-79 years). Sixty-two of 129 patients (48%) were male. Comorbidities included liver dysfunction (7 pa-tients [5%]), heart failure (62 [48%]), renal dysfunction (39 [30%]), cerebrovascular disease (21 [16%]), and cancer (14 [11%]). The median (25th-75th percentile) PSI score was 119 (98-142), and overall mortality was 19% (25 patients). Patient demographics were similar between groups. Fifty-three patients (41%) received guideline-endorsed therapies. Guideline-discordant therapy was associated with an increase in inpatient mortality (25% vs 11%; odds ratio = 2.99 [95% CI, 1.08-9.54]). Receipt of guideline-concordant antibiotics was not associated with reductions in time to clinical stability, time to oral antibiotics, or length of hospital stay when patients who died were excluded from the analysis. Conclusion: Guideline-concordant empiric antibiotic therapy was associated with improved survival among these patients with CAP who were admitted to 5 ICUs. (Clin Ther. 2010;32:293-299) (C) 2010 Excerpta Medica Inc. C1 [Burgess, David S.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, San Antonio, TX 78229 USA. [Frei, Christopher R.; Attridge, Russell T.; Yu, Yifan; Oramasionwu, Christine U.; Ruiz, Jessica L.; Burgess, David S.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Mortensen, Eric M.; Restrepo, Marcos I.] Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX USA. [Mortensen, Eric M.; Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Burgess, DS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM burgessD@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU Department of Veterans Affairs Vertically Integrated Service Network; Howard Hughes Medical Institute FX Dr. Frei has received research grants from Ortho-McNeil Janssen, Elan, AstraZeneca, Abbott, Merck, Roche, and Wyeth, and has served as a consultant and advisory-board member for Ortho-McNeil Janssen. Dr. Restrepo has served on speakers' bureaus for Ortho-McNeil Janssen, Johnson & Johnson, and Pfizer, and on advisory boards for Ortho-McNeil Janssen and Johnson & Johnson. Dr. Mortensen's work was supported by grants from the Department of Veterans Affairs Vertically Integrated Service Network and Howard Hughes Medical Institute. Dr. Burgess has received honoraria, received research grants, served as a consultant, or served on speakers' bureaus for the following pharmaceutical companies: Abbott, AstraZeneca, Merck, Ortho-McNeil Janssen, Roche, sanofiaventis, and Wyeth. The authors have indicated that they have no other conflicts of interest regarding the content of this article.; The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.; The authors acknowledge the assistance of the following clinical pharmacists from the Baptist Health System, who assisted with data collection: Brian Barthol, PharmD; Renee Bellanger, PharmD; Donna Burgess, RPh; Paige Cuellar, PharmD; Julie Gilbert, PharmD; Jennifer Hammond, PharmD; Scott Hollis, RPh; Loretta Lemoine, RPh; Andi Lewis, PharmD; Jane Mondino, RPh; Jon Olson, PharmD; Nish Patel, PharmD; Liz Sanchez, RPh; Morris Sauter, PharmD; Thomas Shank, PharmD; Jacque Snow, PharmD; Paige Staudt, PharmD; and Mary Allyn Watson, PharmD. NR 22 TC 39 Z9 41 U1 0 U2 6 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2010 VL 32 IS 2 BP 293 EP 299 DI 10.1016/j.clinthera.2010.02.006 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 568AZ UT WOS:000275495200008 PM 20206787 ER PT J AU Cook, ED Arnold, KB Hermos, JA McCaskill-Stevens, W Moody-Thomas, S Probstfield, JL Hamilton, SJ Campbell, RD Anderson, KB Minasian, LM AF Cook, Elise D. Arnold, Kathryn B. Hermos, John A. McCaskill-Stevens, Worta Moody-Thomas, Sarah Probstfield, Jeffrey L. Hamilton, Sandra J. Campbell, Russell D. Anderson, Karen B. Minasian, Lori M. TI Impact of supplemental site grants to increase African American accrual for the Selenium and Vitamin E Cancer Prevention Trial SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; MINORITY RECRUITMENT; PCPT UPDATE; PARTICIPATION; ENROLLMENT; SELECT AB Background African American accrual to prevention trials at rates representative of the disease burden experienced by this population requires additional resources and focused efforts. Purpose To describe the rationale, context, and criteria for selection of sites that received Minority Recruitment Enhancement Grants (MREGs) to increase African American recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). To determine if African American accrual was higher among the 15 MREG sites when compared with similar nonawarded sites. Methods Changes in African American accrual at sites that received MREGs are compared with changes in a group of 15, frequency-matched, nonawarded sites using a quasi-experimental, post hoc analysis. Successful and unsuccessful recruitment strategies reported by the MREG sites are described. Results The increased number of African American participants accrued per month at MREG sites post-funding was higher than the change at comparison sites by a factor of 3.38 (p = 0.004, 95% CI: 1.51-7.57). An estimated 602 additional African American participants were recruited at MREG sites due to MREG funding, contributing to the overall 14.9% African American recruitment. Successful recruitment strategies most reported by MREG sites included increasing staff, transportation resources, recruiting through the media, mailings, and prostate cancer screening clinics during off-hours. Limitations Comparison sites were chosen retrospectively, not by randomization. Although comparison sites were selected to be similar to MREG sites with regard to potential confounding factors, it is possible that unknown factors could have biased results. Cost-effective analyses were not conducted. Conclusions MREG sites increased African American accrual in the post-funding period more than comparison sites, indicating MREG funding enhanced the sites' abilities to accrue African American participants. Targeted grants early in the accrual period may be a useful multi-site intervention to increase African American accrual for a prevention study where adequate African American representation is essential. Clinical Trials 2010; 7: 90-99. http://ctj.sagepub.com. C1 [Cook, Elise D.] Univ Texas MD Anderson Canc Ctr, Unit 1360, Houston, TX 77230 USA. [Arnold, Kathryn B.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Hermos, John A.] VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA USA. [McCaskill-Stevens, Worta; Minasian, Lori M.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Moody-Thomas, Sarah] Sch Publ Hlth, Hlth Sci Ctr, LSU, New Orleans, LA USA. [Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA. [Hamilton, Sandra J.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Campbell, Russell D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Anderson, Karen B.] Canc Res & Biostat, Seattle, WA USA. RP Cook, ED (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1360, POB 301439, Houston, TX 77230 USA. EM edcook@mdanderson.org FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [5-U10-CA-37429, P30-CA015704]; Office of Research on Minority Health, Department of Health and Human Services; NCI, DHHS [CA37429]; National Center for Complementary and Alternative Medicine FX This study is supported in part by grants 5-U10-CA-37429 and P30-CA015704 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and the Office of Research on Minority Health, Department of Health and Human Services. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00006392.; This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the NCI, DHHS: CA37429, and supported in part by the National Center for Complementary and Alternative Medicine. NR 20 TC 6 Z9 6 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD FEB PY 2010 VL 7 IS 1 BP 90 EP 99 DI 10.1177/1740774509357227 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 561VU UT WOS:000275008800009 PM 20156960 ER PT J AU Kanner, AM Cole, AJ AF Kanner, Andres M. Cole, Andrew J. TI Case in Point: Evidence-Based Insights For Epilepsy Managemen SO CNS SPECTRUMS LA English DT Review ID QUALITY-OF-LIFE; COMORBID DEPRESSION; MAJOR DEPRESSION; OLDER-ADULTS; SEIZURES; MOOD; LAMOTRIGINE; MULTICENTER; SYMPTOMS; RISK AB Epilepsy affects >2 million people in the United States, making it one of the most common neurobiological conditions. Typically, epilepsy is treated with one of several available antiepileptic drugs, and patients are able to experience freedom from seizures with minimal side effects. However, there are some patients who do not respond to treatment and require the use of multiple drug combinations or surgical intervention. Although there are few studies supporting its use, multidrug regimens have been known to be helpful for patients; however, clinicians should monitor patients for adverse side effects. Vagus nerve stimulation is the only US Food and Drug Administration-approved surgical neurostimulation therapy for epilepsy, and patients' conditions often progress for many years before epilepsy surgery options are considered. Lastly, due to the chronic nature of epilepsy, clinicians should be aware of the presence of comorbid psychiatric conditions as well. This supplement is Part Two in the "Case in Point: Evidence-Based Insights for Epilepsy Management" series. In this Expert Review Supplement, Andrew J. Cole, MD, FRCPC, outlines a case of a patient with epilepsy and comorbid depression, and Andres M. Kanner, MID, outlines current pharmacologic treatments available for epilepsy as well as treatment options for depression and their effect on the illness course in patients with epilepsy. C1 [Kanner, Andres M.] Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. [Kanner, Andres M.] Rush Univ, Med Ctr, Sect Epilepsy, Chicago, IL 60612 USA. [Kanner, Andres M.] Rush Univ, Med Ctr, Rush Epilepsy Ctr, Chicago, IL 60612 USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Univ, Sch Med, Boston, MA USA. RP Kanner, AM (reprint author), Rush Univ, Rush Med Coll, Chicago, IL 60612 USA. NR 34 TC 1 Z9 1 U1 1 U2 2 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 FEB PY 2010 VL 15 IS 2 SU 4 BP 1 EP 6 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 566UN UT WOS:000275398800001 ER PT J AU Reilly-Harrington, N AF Reilly-Harrington, Noreen TI PSYCHOSOCIAL TREATMENT FOR BIPOLAR DISORDER SO CNS SPECTRUMS LA English DT Article ID DEPRESSION C1 [Reilly-Harrington, Noreen] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Reilly-Harrington, Noreen] Res Program, Boston, MA USA. [Reilly-Harrington, Noreen] NIMH, Bipolar Trials Network, Boston, MA USA. [Reilly-Harrington, Noreen] Harvard Univ, Sch Med, Boston, MA USA. RP Reilly-Harrington, N (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2010 VL 15 IS 2 SU 3 BP 14 EP 16 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 563QL UT WOS:000275148100004 PM 20414161 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Hopes and Dreams: Healthcare Reform and Comparative Effectiveness Research for Personalized Treatment in Psychiatry and Neurology SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nierenberg, Andrew A.] Bipolar Clin, Boston, MA USA. [Nierenberg, Andrew A.] Res Program, Boston, MA USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 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 FEB PY 2010 VL 15 IS 2 BP 74 EP 75 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 563QI UT WOS:000275147800001 PM 20414153 ER PT J AU Sprich, SE Knouse, LE Cooper-Vince, C Burbridge, J Safren, SA AF Sprich, Susan E. Knouse, Laura E. Cooper-Vince, Christine Burbridge, Jennifer Safren, Steven A. TI Description and Demonstration of CBT for ADHD in Adults SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID CHILDREN; THERAPY AB ADHD in adulthood is a valid, prevalent, distressing and interfere-rag condition. Although medications hell) treat this disorder; there are often residual symptoms after medication treatment, and, for some patients, they are contraindicated. Compared to other disorders; such as snood and anxiety disorders, there are fern resources available for clinicians wishing to conduct cognitive-behavioral treatment for this problem. The present manuscript provides a description of our cognitive-behavioral approach to treat ADHD in adulthood, which rue have developed and tested in, our clinic (Safren, Otto, et al., 2005), and for which detailed, therapist and client guides exist (Safren, Perlman, Sprich, & Otto, 2005; Safren, Sprich, Perlman, & Otto, 2005). To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight emporia-rat aspects of this treatment. This description and the accompanying demonstrations are intended, (is a practical guide to assist therapists wishing to conduct such a treatment in the, outpatient setting. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Sprich, SE (reprint author), MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssprich@partners.org NR 16 TC 3 Z9 4 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2010 VL 17 IS 1 BP 9 EP 15 PG 7 WC Psychology, Clinical SC Psychology GA 567YE UT WOS:000275484300002 ER PT J AU Reese, HE Timpano, KR Siev, J Rowley, T Wilhelm, S AF Reese, Hannah E. Timpano, Kiara R. Siev, Jedidiah Rowley, Theresa Wilhelm, Sabine TI Behavior Therapy for Tourette's Syndrome and Chronic Tic Disorder: A Web-Based Video Illustration of Treatment Components SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HABIT REVERSAL TREATMENT; SUPPORTIVE PSYCHOTHERAPY; COMPETING RESPONSES; PREVALENCE; CHILDREN AB Tic. disorders have traditionally been conceptualized as neurobiological conditions and consequently within the purview of neurologists. In the last few decades, however; a number of psychosocial treatments have been developed and tested. To date, a behavioral treatment called Habit Reversal Training (HRT) has garnered the most empirical support as can efficacious treatment for tic disorders. HRT is a multicomponent, short-terra, behavioral intervention. The purpose of this paper is to provide a brief overview of the behavioral treatment of tic, disorders including a detailed description of the core components of HRT: awareness training and competing response, training. Me will also review function-based assessment and treatment strategies, which have been emphasized in snore recent behavioral approaches. The accompanying videos demonstrate aspects of these clinical techniques. C1 [Reese, Hannah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Reese, HE (reprint author), Massachusetts Gen Hosp, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM hreese@partners.org RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722 NR 32 TC 3 Z9 3 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2010 VL 17 IS 1 BP 16 EP 24 PG 9 WC Psychology, Clinical SC Psychology GA 567YE UT WOS:000275484300003 ER PT J AU Willoughby, BLB Doty, ND AF Willoughby, Brian L. B. Doty, Nathan D. TI Brief Cognitive Behavioral Family Therapy Following a Child's Coming Out: A Case Report SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID SAME-SEX ATTRACTIONS; BISEXUAL YOUTHS; GAY MEN; PARENTS; DISCLOSURE; LESBIANS; ADOLESCENTS; AIDS AB Fern interventions have been, proposed for the treatment of families following a child's disclosure. of nonheterosexuality. To address this gaff in the literature, the current paper outlines a brief cognitive behavioral family treatment (CBFT) for families negotiating the coming out process and illustrates this approach with a case example. Parents' attributions, beliefs, and expectations are explored and challenged. The family is exposed to increasingly salient topics and directed to increase the frequency of positive family experiences. Lastly, the family is taught specific listening and problem-solving skills to bolster adaptive family communication. This paper is among the first to apply an. empirically supported therapeutic framework to support family adjustment following a child's disclosure of sexual orientation. The potential usefulness and limitations of this CBFT application are discussed. C1 [Willoughby, Brian L. B.; Doty, Nathan D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Willoughby, Brian L. B.; Doty, Nathan D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Willoughby, BLB (reprint author), Massachusetts Gen Hosp, 15 Merrimac St,5th Floor, Boston, MA 02114 USA. EM bwilloughby@partners.org NR 34 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FEB PY 2010 VL 17 IS 1 BP 37 EP 44 PG 8 WC Psychology, Clinical SC Psychology GA 567YE UT WOS:000275484300006 ER PT J AU Petersen, TJ Pava, JA Buchin, J Matthews, JD Papakostas, GI Nierenberg, AA Holmes, AJ Bogdan, R Graves, LM Harley, RM Fava, M AF Petersen, Timothy J. Pava, Joel A. Buchin, Jacqueline Matthews, John D. Papakostas, George I. Nierenberg, Andrew A. Holmes, Avram J. Bogdan, Ryan Graves, Lesley M. Harley, Rebecca M. Fava, Maurizio TI The Role of Cognitive-Behavioral Therapy and Fluoxetine in Prevention of Recurrence of Major Depressive Disorder SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE CBT; Fluoxetine; Recurrence; Relapse; Major Depressive Disorder; Treatment; Prevention ID RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; MAINTENANCE THERAPIES; RESIDUAL SYMPTOMS; PHARMACOTHERAPY; PSYCHOTHERAPY; INVENTORY; EFFICACY; OUTCOMES; RELAPSE AB This study evaluated the role of cognitive-behavioral therapy (CBT) and fluoxetine in preventing recurrence of a depressive episode during maintenance phase treatment for patients with remitted major depressive disorder (MDD). Patients (n = 52) completed open acute fluoxetine treatment and sustained remission during a 28-week randomized continuation treatment (CBT + fluoxetine vs. fluoxetine only). They were assigned to one of four maintenance treatments: CBT + fluoxetine, CBT + placebo, fluoxetine only, and placebo only. There were no statistically significant differences in MDD recurrence between maintenance treatments, but continued antidepressant treatment (with or without CBT) provided an 18-21% lower MDD recurrence rate than placebo. These findings are consistent with those of recent antidepressant studies of chronic and recurrent MDD populations. Although sample sizes were small, CBT did not significantly lower rates of MDD recurrence. C1 [Petersen, Timothy J.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. [Pava, Joel A.; Buchin, Jacqueline; Matthews, John D.; Nierenberg, Andrew A.; Holmes, Avram J.; Bogdan, Ryan; Graves, Lesley M.; Harley, Rebecca M.; Fava, Maurizio] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Petersen, TJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM tpetersen@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Bogdan, Ryan/0000-0002-1430-1045 NR 35 TC 4 Z9 4 U1 3 U2 8 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 FEB PY 2010 VL 34 IS 1 BP 13 EP 23 DI 10.1007/s10608-007-9166-6 PG 11 WC Psychology, Clinical SC Psychology GA 546YF UT WOS:000273850600002 ER PT J AU Reilly-Harrington, NA Miklowitz, DJ Otto, MW Frank, E Wisniewski, SR Thase, ME Sachs, GS AF Reilly-Harrington, Noreen A. Miklowitz, David J. Otto, Michael W. Frank, Ellen Wisniewski, Stephen R. Thase, Michael E. Sachs, Gary S. TI Dysfunctional Attitudes, Attributional Styles, and Phase of Illness in Bipolar Disorder SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Bipolar disorder; Cognitive style; Mood; Dysfunctional attitudes; Attributional styles ID COGNITIVE-BEHAVIORAL THERAPY; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TREATMENT ENHANCEMENT PROGRAM; RANDOMIZED CONTROLLED-TRIAL; RELAPSE PREVENTION; RATING-SCALE; MIXED STATES; DSM-IV; DEPRESSION; MANIA AB Whereas an abundance of studies have been devoted to the study of cognitive vulnerability in unipolar depression, comparatively less is known regarding the cognitive styles of patients with bipolar disorder. This study examined the cognitive styles of 395 of the first 500 bipolar patients enrolled in the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder as a function of mood state at study entry. Patients completed diagnostic and mood assessments and two measures of cognitive style: The Dysfunctional Attitudes Scale (DAS) and the Attributional Style Questionnaire (ASQ). Patients in mixed episodes exhibited significantly more negative dysfunctional attitudes and negative attributional styles than euthymic patients and significantly more dysfunctional attitudes than manic/hypomanic patients. The implications of these findings are discussed in relation to episode vulnerability, mood-state dependency of cognitive style, and cognitive-behavioral treatment. C1 [Reilly-Harrington, Noreen A.; Sachs, Gary S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA 02114 USA. [Reilly-Harrington, Noreen A.; Sachs, Gary S.] Harvard Univ, Res Program, Sch Med, Boston, MA 02114 USA. [Miklowitz, David J.] Univ Colorado, Boulder, CO 80309 USA. [Otto, Michael W.] Boston Univ, Boston, MA 02215 USA. [Frank, Ellen; Wisniewski, Stephen R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Reilly-Harrington, NA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM nhreilly@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 NR 64 TC 10 Z9 10 U1 3 U2 6 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 FEB PY 2010 VL 34 IS 1 BP 24 EP 34 DI 10.1007/s10608-008-9218-6 PG 11 WC Psychology, Clinical SC Psychology GA 546YF UT WOS:000273850600003 ER PT J AU Stacy, RC Kenyon, KR Jakobiec, FA Colby, KA AF Stacy, Rebecca C. Kenyon, Kenneth R. Jakobiec, Frederick A. Colby, Kathryn A. TI Conjunctival Melanoma Arising From Primary Acquired Melanosis in a Patient With Neurofibromatosis Type I SO CORNEA LA English DT Article DE conjunctival melanoma; mitomycin C; primary acquired melanosis; neurofibromatosis; cryotherapy ID MALIGNANT-MELANOMA AB Purpose: To describe a case of conjunctival malignant melanoma (MM) arising from primary acquired melanosis in a patient with neurofibromatosis type 1(NF-1). Methods: Case report and literature review. Results: A 66-year-old woman with a history of NF-1 presented with extensive pigmentation of the left bulbar conjunctiva. Conjunctival biopsies demonstrated MM arising from primary acquired melanosis with atypia. Two excision and cryotherapy procedures did not completely eradicate the conjunctival pigment, which was then treated with topical mitomycin C. Subsequent biopsies and clinical examinations have revealed no remaining tumor. Conclusion: Conjunctival MM is uncommon in patients with NF-1 and can be successfully treated with excision, cryotherapy, and topical mitomycin C. C1 [Stacy, Rebecca C.; Kenyon, Kenneth R.; Jakobiec, Frederick A.; Colby, Kathryn A.] Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kenyon, Kenneth R.; Colby, Kathryn A.] Schepens Eye Res Inst, Boston, MA USA. [Kenyon, Kenneth R.] Cornea Consultants Int, Munich, Germany. [Kenyon, Kenneth R.] Eye Hlth Vis Ctr, N Dartmouth, MA USA. RP Colby, KA (reprint author), Harvard Univ, Dept Ophthalmol, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 16 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD FEB PY 2010 VL 29 IS 2 BP 232 EP 234 PG 3 WC Ophthalmology SC Ophthalmology GA 550HR UT WOS:000274119400025 PM 20023582 ER PT J AU Levy, MM Dellinger, RP Townsend, SR Linde-Zwirble, WT Marshall, JC Bion, J Schorr, C Artigas, A Ramsay, G Beale, R Parker, MM Gerlach, H Reinhart, K Silva, E Harvey, M Regan, S Angus, DC AF Levy, Mitchell M. Dellinger, R. Phillip Townsend, Sean R. Linde-Zwirble, Walter T. Marshall, John C. Bion, Julian Schorr, Christa Artigas, Antonio Ramsay, Graham Beale, Richard Parker, Margaret M. Gerlach, Herwig Reinhart, Konrad Silva, Eliezer Harvey, Maurene Regan, Susan Angus, Derek C. CA Surviving Sepsis Campaign TI The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE severe sepsis; septic shock; knowledge transfer; performance measures; Surviving Sepsis Campaign; performance improvement; sepsis bundles; quality improvement ID CRITICALLY-ILL PATIENTS; FACILITATING CLINICIAN ADHERENCE; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; MECHANICAL VENTILATION; IMPLEMENTATION; MORTALITY; THERAPY; EPIDEMIOLOGY; MULTICENTER AB Objective: The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations. Design and Setting: A multifaceted intervention to facilitate compliance with selected guideline recommendations in the intensive care unit emergency department, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the United States, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 hrs and within 24 hrs. An analysis was conducted on data submitted from January 2005 through March 2008. Subjects: A total of 15,022 subjects. Measurements and Main Results: Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 yrs (p = .008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p = .001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.40% over 2 yrs (95% confidence interval, 2.5-8.4). Conclusions: The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts. (Crit Care Med 2010; 38:367-374) C1 [Levy, Mitchell M.] Brown Univ, Rhode Isl Hosp, Sch Med, Div Pulm Sleep & Crit Care Med Care Med, Providence, RI 02903 USA. [Dellinger, R. Phillip; Schorr, Christa] Univ Med & Dent New Jersey, Cooper Univ Hosp, Dept Med, Camden, NJ USA. [Townsend, Sean R.] Inst Healthcare Improvement, Cambridge, MA USA. [Townsend, Sean R.] Univ Massachusetts, Sch Med, Div Pulm Sleep Allergy & Crit Care Med, Worcester, MA USA. [Linde-Zwirble, Walter T.] ZD Associates LLC, Perkasie, PA USA. [Marshall, John C.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Surg, Toronto, ON M5B 1W8, Canada. [Bion, Julian] Queen Elizabeth Hosp, Univ Dept Anaesthesia & Intens Care Med, Birmingham B15 2TH, W Midlands, England. [Artigas, Antonio] Autonomous Univ Barcelona, Crit Care Ctr, Sabadell Hosp, CIBER Enfermedades Respiratorias, Barcelona, Spain. [Ramsay, Graham] Mid Essex Hosp Serv NHS Trust, London, England. [Beale, Richard] St Thomas Hosp, Guys & St Thomas NHS Fdn Trust, London, England. [Parker, Margaret M.] SUNY Stony Brook, Dept Med, Stony Brook, NY USA. [Gerlach, Herwig] Vivantes Klinikum Neukoelln, Berlin, Germany. [Reinhart, Konrad] Clin Anesthesiol & Intens Care, Jena, Germany. [Silva, Eliezer] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. [Regan, Susan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Harvey, Maurene] Consultants Crit Care Inc, Glenbrook, NV USA. [Angus, Derek C.] Univ Pittsburgh, CRISMA Lab, Dept Crit Care Med, Pittsburgh, PA USA. RP Levy, MM (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Div Pulm Sleep & Crit Care Med Care Med, Providence, RI 02903 USA. EM Mitchell_Levy@brown.edu RI Beale, Richard/J-7831-2013; Angus, Derek/E-9671-2012 NR 38 TC 394 Z9 422 U1 4 U2 39 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 FEB PY 2010 VL 38 IS 2 BP 367 EP 374 DI 10.1097/CCM.0b013e3181cb0cdc PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 547ZF UT WOS:000273927700001 PM 20035219 ER PT J AU Qureshi, AI Tariq, N Divani, AA Novitzke, J Hussein, HH Palesch, YY Martin, R Dillon, C Kirmani, JF Ezzeddine, MA Mohammad, I Suri, MFK Harris-Lane, P Suarez, JI Feen, E Selman, W Murphy, C Mayer, SA Parra, A Lee, K Ostapkovich, N Papamitsakis, NIH Panezai, S Anyanwu, C Terry, J Dickerson, K Goldstein, J Wendell, L Mohammad, YM Jradi, H Cruz-Flores, S Holzemer, E Sung, G Thomson, V Ehtisham, A Brown, B AF Qureshi, Adnan I. Tariq, Nauman Divani, Afskin A. Novitzke, Jill Hussein, Haitham H. Palesch, Yuko Y. Martin, Renee' Dillon, Catherine Kirmani, Jawad F. Ezzeddine, Mustapha A. Mohammad, Ibrahim Suri, M. Fareed K. Harris-Lane, Pansy Suarez, Jose I. Feen, Eliahu Selman, Warren Murphy, Christopher Mayer, Stephan A. Parra, Augusto Lee, Kiwon Ostapkovich, Noeleen Papamitsakis, Nikolaos I. H. Panezai, Spozhmy Anyanwu, Chinekwu Terry, John Dickerson, Kelly Goldstein, Joshua Wendell, Lauren Mohammad, Yousef M. Jradi, Hoda Cruz-Flores, Salvador Holzemer, Eve Sung, Gene Thomson, Vangie Ehtisham, As'ad Brown, Betty CA Antihypertensive Treatment Acute C TI Antihypertensive treatment of acute cerebral hemorrhage SO CRITICAL CARE MEDICINE LA English DT Article DE intracerebral hemorrhage; hypertension; nicardipine; systolic blood pressure; hematoma expansion ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; AMERICAN-HEART-ASSOCIATION; BLOOD-PRESSURE; INTRAVENOUS NICARDIPINE; MONITORING-COMMITTEE; RANDOMIZED-TRIAL; CLINICAL-TRIALS; STROKE COUNCIL; MANAGEMENT AB Objective: To determine the feasibility and acute (i.e., within 72 hrs) safety of three levels of systolic blood pressure reduction in subjects with supratentorial intracerebral hemorrhage treated within 6 hrs after symptom onset. Design: A traditional phase 1, dose-escalation, multicenter prospective study. Settings: Emergency departments and intensive care units. Patients: Patients with intracerebral hemorrhage with elevated systolic blood pressure >= 170 mm Hg who present to the emergency department within 6 hrs of symptom onset. Intervention: Intravenous nicardipine to reduce systolic blood pressure to a target of: (1) 170 to 200 mm Hg in the first cohort of patients; (2) 140 to 170 mm Hg in the second cohort; and (3) 110 to 140 mm Hg in the third cohort. Measurements and Main Results: Primary outcomes of interest were: (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs); (2) neurologic deterioration within 24 hrs; and (3) serious adverse events within 72 hrs. Safety stopping rules based on neurologic deterioration and serious adverse events were prespecified and approved by an NIH-appointed Data and Safety Monitoring Board, which provided oversight on subject safety. Each subject was followed-up for 3 months to preliminarily assess mortality and the clinical outcomes. A total of 18, 20, and 22 patients were enrolled in the respective three tiers of systolic blood pressure treatment goals. Overall, 9 of 60 patients had treatment failures (all in the last tier). A total of seven subjects with neurologic deterioration were observed: one (6%), two (10%), and four (18%) in tier one, two, and three, respectively. Serious adverse events were observed in one subject (5%) in tier two and in three subjects (14%) in tier three. However, the safety stopping rule was not activated in any of the tiers. Three (17%), two (10%), and five (23%) subjects in tiers one, two, and three, respectively, died within 3 months. Conclusions: The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds, and the 3-month mortality rate was lower than expected in all systolic blood pressure tiers. The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage. (Crit Care Med 2010; 38:637-648) C1 Univ Minnesota, Zeenat Oureshi Stroke Res Ctr, Minneapolis, MN USA. [Antihypertensive Treatment Acute C] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Qureshi, Adnan I.; Tariq, Nauman; Divani, Afskin A.; Novitzke, Jill; Hussein, Haitham H.] Univ Minnesota, Clin Coordinating Ctr, Minneapolis, MN 55455 USA. [Palesch, Yuko Y.; Martin, Renee'; Dillon, Catherine] Med Univ S Carolina, Stat Coordinating Ctr, Charleston, SC 29425 USA. [Qureshi, Adnan I.; Kirmani, Jawad F.; Ezzeddine, Mustapha A.; Mohammad, Ibrahim; Suri, M. Fareed K.; Harris-Lane, Pansy] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Suarez, Jose I.; Feen, Eliahu; Selman, Warren; Murphy, Christopher] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Mayer, Stephan A.; Parra, Augusto; Lee, Kiwon; Ostapkovich, Noeleen] Columbia Univ Med Ctr, New York, NY USA. [Papamitsakis, Nikolaos I. H.; Panezai, Spozhmy; Anyanwu, Chinekwu] JFK Med Ctr, Edison, NJ USA. [Terry, John; Dickerson, Kelly] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Goldstein, Joshua; Wendell, Lauren] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mohammad, Yousef M.; Jradi, Hoda] Ohio State Univ, Columbus, OH 43210 USA. [Cruz-Flores, Salvador; Holzemer, Eve] St Louis Univ, St Louis, MO 63103 USA. [Sung, Gene; Thomson, Vangie] Univ So Calif, Los Angeles, CA USA. [Ehtisham, As'ad; Brown, Betty] Via Christi Reg Med Ctr, Wichita, KS USA. RP Qureshi, AI (reprint author), Univ Minnesota, Clin Coordinating Ctr, Minneapolis, MN 55455 USA. EM aiqureshi@hotmail.com FU National Institutes of Health [R0-1-NS44976-01A2]; American Heart Association [0840053N]; Minnesota Medical Foundation, Minneapolis, MN; NIH [U01 NS054630, U01 NS059041, R01 NS057127, R01 NS062778]; Boehringer-Ingelheim FX Dr. Qureshi has received funding from National Institutes of Health R0-1-NS44976-01A2 (medication provided by ESP Pharma), American Heart Association Established Investigator Award 0840053N, and Minnesota Medical Foundation, Minneapolis, MN. Dr. Palesch is funded by the NIH U01 NS054630, U01 NS059041, R01 NS057127, and R01 NS062778, and by Boehringer-Ingelheim. NR 44 TC 71 Z9 73 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2010 VL 38 IS 2 BP 637 EP 648 DI 10.1097/CCM.0b013e3181b9e1a5 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA 547ZF UT WOS:000273927700037 ER PT J AU Alam, HB AF Alam, Hasan B. TI Why not? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE hypothermia; cardiac arrest; protocols; guidelines ID HOSPITAL CARDIAC-ARREST; INDUCED HYPOTHERMIA; THERAPEUTIC HYPOTHERMIA; PHYSICIANS; RESUSCITATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2010 VL 38 IS 2 BP 711 EP 712 DI 10.1097/CCM.0b013e3181cab091 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 547ZF UT WOS:000273927700059 PM 20083939 ER PT J AU Zhang, C Browne, A Kim, DY Tanzi, RE AF Zhang, C. Browne, A. Kim, D. Y. Tanzi, R. E. TI Familial Alzheimer's Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-Protein Precursor Generated by beta-Secretase Cleavage SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; FAD mutation; APP; PSEN1; N-APP; sAPP beta ID GAMMA-SECRETASE; ENDOPLASMIC-RETICULUM; APP METABOLISM; CASPASE-3; COMPLEX; CELLS; ACTIVATION; HYPOTHESIS; NICASTRIN; PEN-2 AB Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than similar to 80% of all FAD mutations. All PSEN1 FAD mutations can increase the A beta 42:A beta 40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPP beta), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPP beta levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPP beta levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPP beta. C1 [Zhang, C.; Browne, A.; Kim, D. Y.; Tanzi, R. E.] Harvard Univ, Sch Med, Genet & Aging Res Unit, Massachusetts Gen Hosp,Dept Neurol,MIND, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Genet & Aging Res Unit, Massachusetts Gen Hosp,Dept Neurol,MIND, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU Cure Alzheimer Fund FX This work was supported by the Cure Alzheimer's Fund. NR 23 TC 4 Z9 5 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD FEB PY 2010 VL 7 IS 1 BP 21 EP 26 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 549DO UT WOS:000274023800004 PM 20205669 ER PT J AU Horton, ES AF Horton, Edward S. TI Challenges and Approaches to Managing Type 2 Diabetes Mellitus SO CURRENT DIABETES REPORTS LA English DT Editorial Material DE ADOPT; NHANES; UKPDS ID GLUCOSE CONTROL; DISEASE; THERAPY; ADULTS C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Horton, ES (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Edward.Horton@joslin.harvard.edu NR 13 TC 2 Z9 2 U1 1 U2 1 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 FEB PY 2010 VL 10 IS 1 BP 7 EP 9 DI 10.1007/s11892-009-0079-5 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 555IA UT WOS:000274501300001 PM 20425060 ER PT J AU Signorovitch, JE Duh, MS Sengupta, A Gu, A Grant, R Raut, M Mody, SH Schein, J Fisher, AC Ng, D AF Signorovitch, James E. Duh, Mei Sheng Sengupta, Anirban Gu, Anna Grant, Richard Raut, Monika Mody, Samir H. Schein, Jeff Fisher, Alan C. Ng, Daniel TI Hospital visits and costs following outpatient treatment of CAP with levofloxacin or moxifloxacin SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Community acquired pneumonia; Costs; Levofloxacin; Moxifloxacin ID COMMUNITY-ACQUIRED PNEUMONIA; MANAGEMENT; ADULTS; GUIDELINES; THERAPY; INFECTIONS; CARE AB Background: Hospital admissions (inpatient and emergency room) are a major source of medical costs for community-acquired pneumonia (CAP) initially treated in the outpatient setting. Current CAP treatment guidelines do not differentiate between outpatient treatment with levofloxacin and moxifloxacin. Objective: Compare health care resource use and medical costs to payers for CAP outpatients initiating treatment with levofloxacin or moxifloxacin. Research design and methods: CAP episodes were identified in the PharMetrics database between 2Q04 and 2Q07 based on: pneumonia diagnosis, chest X-ray and treatment with levofloxacin or moxifloxacin. Subsequent 30-day risk of pneumonia-related hospital visits and 30-day health care costs to payers for levofloxacin vs. moxifloxacin treatment were estimated after adjusting for pre-treatment demographics, health care resource use and pneumonia-specific risk factors using propensity score and exact factor matching. Results: A total of 15,472 levofloxacin- and 6474 moxifloxacin-initiated CAP patients were identified. Among 6352 matched pairs, levofloxacin treatment was associated with a 35% reduction in the odds of pneumonia-related hospital visits (odds ratio = 0.65, P = 0.004), lower per-patient costs for pneumonia-related hospital visits ($ 102 vs. $ 210, P = 0.001), lower pneumonia-related total costs (medical services and prescription drugs, $ 363 vs. $ 491, P<0.001) and lower total costs ($ 1308 vs. $ 1446, P<0.001) vs. moxifloxacin over the 30-day observation period. Limitations: Although observational analyses of claims data provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure that patient characteristics are well-balanced between treatment groups. In addition, data may be missing or miscoded. Conclusions: CAP outpatients initiated with levofloxacin generated substantially lower costs to payers compared to matched patients initiated with moxifloxacin. The cost savings for patients initiated with levofloxacin were largely attributable to reduced rates of pneumonia-related hospitalization or ER visits. C1 [Signorovitch, James E.; Duh, Mei Sheng; Sengupta, Anirban; Gu, Anna] Anal Grp Inc, Boston, MA 02199 USA. [Grant, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raut, Monika; Mody, Samir H.; Schein, Jeff; Fisher, Alan C.; Ng, Daniel] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. RP Signorovitch, JE (reprint author), Anal Grp Inc, 111 Huntington Ave,10th Floor, Boston, MA 02199 USA. EM jsignorovitch@analysisgroup.com FU Ortho-McNeil Janssen Scientific Affairs (OMJSA), LLC, Raritan, NJ, USA FX This study and manuscript preparation were funded by Ortho-McNeil Janssen Scientific Affairs (OMJSA), LLC, Raritan, NJ, USA. NR 23 TC 2 Z9 2 U1 0 U2 0 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 FEB PY 2010 VL 26 IS 2 BP 355 EP 363 DI 10.1185/03007990903482418 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 554PL UT WOS:000274446800012 PM 19995325 ER PT J AU Kwak, J Andrawes, M Garvin, S D'Ambra, MN AF Kwak, Jenny Andrawes, Michael Garvin, Sean D'Ambra, Michael N. TI 3D transesophageal echocardiography: a review of recent literature 2007-2009 SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Review DE 3D transesophageal echocardiography; cardiac surgery; live 3D TEE; real-time 3D; RT3D; TEE ID TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; CARDIAC MAGNETIC-RESONANCE; COLOR DOPPLER-ECHOCARDIOGRAPHY; VENTRICULAR OUTFLOW TRACT; MITRAL-VALVE-PROLAPSE; ATRIAL SEPTAL-DEFECT; 2-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; INITIAL-EXPERIENCE; ANNULOPLASTY RING AB Purpose of review The use of two-dimensional (2D) transesophageal echocardiography (TEE) is nearly universal in cardiac surgical operating rooms around the world. Cardiac anesthesiologists or cardiologists perform these examinations, facilitating significant advancements in surgical techniques by the immediacy and accuracy of intra-operative ultrasound imaging. Three-dimensional (3D) TEE capabilities have been available since the 1990s but penetration has been poor. With the advent of real-time 3D TEE, interest in this technology has increased dramatically. This is a comprehensive review of English language publications in the field from 2007 to 2009. Recent findings This review utilized Pubmed databases, with search strategy based on primary key words: 3D echocardiography, transesophageal echocardiography, cardiac surgery, and/or cardiopulmonary bypass. Three major areas of clinical practice are impacted by the findings of these studies: cardiac valve repair and replacement, assessment of ventricular function, and image guidance for percutaneous procedures. Summary The review resulted in the conclusion that 3D TEE provides unique and dynamic 3D spatial information that cannot be obtained by 2D TEE or fluoroscopy. In addition to technical and process advancements, future studies should address educational value in terms of acceleration of learning curves, and impact on surgical decision making. C1 [D'Ambra, Michael N.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Div Cardiac Anesthesiol, Boston, MA 02115 USA. [Kwak, Jenny] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Andrawes, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Garvin, Sean] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. RP D'Ambra, MN (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Div Cardiac Anesthesiol, 75 Francis St, Boston, MA 02115 USA. EM mdambra@partners.org NR 64 TC 13 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0952-7907 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD FEB PY 2010 VL 23 IS 1 BP 80 EP 88 DI 10.1097/ACO.0b013e328334a6b3 PG 9 WC Anesthesiology SC Anesthesiology GA 544WB UT WOS:000273689200013 PM 19949326 ER PT J AU Hilderbrand, SA Weissleder, R AF Hilderbrand, Scott A. Weissleder, Ralph TI Near-infrared fluorescence: application to in vivo molecular imaging SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID GROWTH-FACTOR RECEPTOR; QUANTUM DOTS; HYDROGEN-PEROXIDE; UP-CONVERSION; ATHEROSCLEROTIC PLAQUES; TUMOR RESPONSE; DRUG-DELIVERY; BREAST-CANCER; LIVING MICE; NANOPARTICLES AB Molecular imaging often relies on the use of targeted and activatable reporters to quantitate and visualize targets, biological processes, and cells in vivo. The use of optical probes with near-infrared fluorescence allows for improved photon penetration through tissue and minimizes the effects of tissue autofluorescence. There are several parameters that define the effectiveness of imaging agents in vivo. These factors include probe targeting, activation, pharmacokinetics, biocompatibility, and photophysics. Recent advances in our understanding of these variables as they pertain to the application of optical reporters for in vivo imaging are discussed in this review. C1 [Hilderbrand, Scott A.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Simches Res Ctr, Boston, MA 02114 USA. RP Hilderbrand, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Simches Res Ctr, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM Scott_Hilderbrand@hms.harvard.edu; RWeissleder@mgh.harvard.edu FU National Heart, Lung, and Blood Institute [U01-HL080731] FX This work was supported by the National Heart, Lung, and Blood Institute (U01-HL080731). NR 83 TC 407 Z9 417 U1 27 U2 291 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD FEB PY 2010 VL 14 IS 1 BP 71 EP 79 DI 10.1016/j.cbpa.2009.09.029 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 561AH UT WOS:000274946700012 PM 19879798 ER PT J AU Moskowitz, SM Wiener-Kronish, JR AF Moskowitz, Samuel M. Wiener-Kronish, Jeanine R. TI Mechanisms of bacterial virulence in pulmonary infections SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE antibiotic resistance; horizontal gene transfer; pathogen; Staphylococcus aureus; virulence ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; FRANCISELLA-TULARENSIS; MULTIDRUG-RESISTANT; PROTECTS MICE; CLONE USA300; PNEUMONIA; LUNG; PATHOGENESIS; TOXIN AB Purpose of review To consider the relevance to severe human lung infections of recently discovered virulence mechanisms of Staphylocaccus aureus and Francisella tularensis. Recent findings S. aureus has long been considered an opportunistic pathogen. However, due to the emergence of community-acquired methicillin-resistant S. aureus (CA-MRSA) strains that can readily infect and kill normal hosts, S. aureus must now be considered a potentially virulent pathogen. The evolution of S. aureus from an organism associated with asymptomatic nasopharyngeal colonization to one associated with community-acquired lethal infections may reflect horizontal acquisition of bacterial genes that enable efficient spread, aggressive host invasion, and effective immune evasion. Alleviating the burden of staphylococcal disease will require better understanding of host susceptibility and of staphylococcal virulence and antibiotic resistance. In contrast to the rapidly evolving staphylococcal virulence strategy, recent genomic analysis of F tularensis has revealed a small set of bacterial genes associated with the marked virulence of its North American subspecies. This suggests that a relatively stable strategy of immune evasion underlies this pathogen's ability to establish serious life-threatening lung infections from a very small inoculum. Summary Understanding bacterial pathogenesis will require additional research into both host susceptibility factors and bacterial virulence mechanisms, including horizontal gene transfer. Refinements in the molecular detection of bacteria in the clinical setting, as well as whole genome analysis of both pathogens and patients, are expected to aid in the understanding of bacterial-induced lung injury. C1 [Wiener-Kronish, Jeanine R.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.; Wiener-Kronish, Jeanine R.] Harvard Univ, Sch Med, Boston, MA USA. RP Wiener-Kronish, JR (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol, 15 Fruit St, Boston, MA 02114 USA. EM jwiener-kronish@partners.org FU National Institutes of Health [R01AI067653, R01GM 088416, UO1 AI075410]; Cystic Fibrosis Foundation [MOSKOW07Y3] FX S.M.M. is supported by grants from the National Institutes of Health (R01AI067653) and the Cystic Fibrosis Foundation (MOSKOW07Y3). J.P.W.-K. is supported by and consults on grants from the National Institutes of Health (R01GM 088416 and UO1 AI075410, respectively). NR 33 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD FEB PY 2010 VL 16 IS 1 BP 8 EP 12 DI 10.1097/MCC.0b013e3283354710 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 544ZJ UT WOS:000273700200002 PM 19956071 ER PT J AU Frank, AJ Thompson, BT AF Frank, Angela J. Thompson, B. Taylor TI Pharmacological treatments for acute respiratory distress syndrome SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE acute respiratory distress syndrome; alveolar clotting; corticosteroids; neutrophil elastase inhibitor; surfactant ID ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; RANDOMIZED CONTROLLED-TRIAL; FACTOR PATHWAY INHIBITOR; GLYCATION END-PRODUCTS; PROTEIN-C SURFACTANT; NEUTROPHIL ELASTASE; SEVERE SEPSIS; RECOMBINANT SURFACTANT; CLINICAL-TRIAL AB Purpose of review Studies of the pharmacologic management of acute respiratory distress syndrome (ARDS) have yielded conflicting results. The purpose of this review is to discuss recent pharmacologic trials in ARDS, using the conceptual framework of ARDS as a heterogeneous disease. Recent findings Whereas most drug trials in ARDS have been negative, some studies suggest that targeting therapies at subgroups of patients may be successful. Proposed subgroups include early versus late-phase ARDS, direct versus indirect lung injury, and patients with altered coagulation. Corticosteroids have beneficial short-term effects when given at low or moderate doses sooner than 2 weeks but appear to be harmful if initiated later and are of unclear benefit if lung protective ventilation is also used. Surfactant may be helpful in patients with direct lung injury. Anticoagulants and vasodilators may have a greater chance for success in the subset of patients with vascular disease and a high dead-space fraction may identify such a population. Summary ARDS is a heterogeneous syndrome. Failure to target subgroups more likely to benefit from specific therapies may be one explanation for largely disappointing trial results so far. C1 [Frank, Angela J.; Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM tthompson1@partners.org FU Lilly FX Dr Thompson is the Go-Principal Investigator of the Lilly funded PROWESS-SHOCK trial (DAA for persistent septic shock) and is a paid consultant for Eli Lilly and company. NR 85 TC 20 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-5295 EI 1531-7072 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD FEB PY 2010 VL 16 IS 1 BP 62 EP 68 DI 10.1097/MCC.0b013e328334b151 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 544ZJ UT WOS:000273700200010 PM 19952736 ER PT J AU Straussman, S Levitsky, LL AF Straussman, Sharon Levitsky, Lynne L. TI Neonatal hypoglycemia SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE central nervous system; energy deficiency; hyperinsulinism; hypoglycemia ID INTENSIVE-CARE-UNIT; HYPERINSULINEMIC HYPOGLYCEMIA; CONGENITAL HYPERINSULINISM; GLUCOSE MEASUREMENT; RELIABILITY ASSESSMENT; HEMOCUE ANALYZER; ABCC8 MUTATIONS; BRAIN-INJURY; BETA-CELL; GENE AB Purpose of review Hypoglycemia in the newborn may be associated with both acute decompensation and long-term neuronal loss. Studies of the cause of hypoglycemic brain damage and the relationship of hypoglycemia to disorders associated with hyperinsulinism have aided in our understanding of this common clinical finding. Recent findings A recent consensus workshop concluded that there has been little progress toward a precise numerical definition of neonatal hypoglycemia. Nonetheless, newer brain imaging modalities have provided insight into the relationship between neuronal energy deficiency and central nervous system damage. Laboratory studies have begun to reveal the mechanism of hypoglycemic damage. In addition, there is new information about hyperinsulinemic hypoglycemia of genetic, environmental, and iatrogenic origin. Summary The quantitative definition of hypoglycemia in the newborn remains elusive because it is a surrogate marker for central nervous system energy deficiency. Nonetheless, the recognition that hyperinsulinemic hypoglycemia, which produces profound central nervous system energy deficiency, is most likely to lead to long-term central nervous system damage, has altered management of children with hypoglycemia. In addition, imaging studies on neonates and laboratory evaluation in animal models have provided insight into the mechanism of neuronal damage. C1 [Straussman, Sharon; Levitsky, Lynne L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. EM llevitsky@partners.org NR 38 TC 16 Z9 17 U1 0 U2 9 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 FEB PY 2010 VL 17 IS 1 BP 20 EP 24 DI 10.1097/MED.0b013e328334f061 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691CS UT WOS:000285058500004 PM 19952738 ER PT J AU Mitchell, DM Juppner, H AF Mitchell, Deborah M. Jueppner, Harald TI Regulation of calcium homeostasis and bone metabolism in the fetus and neonate SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE calcium; parathyroid hormone; parathyroid hormone-related peptide; phosphorus; vitamin D ID VITAMIN-D DEFICIENCY; MATERNAL-FETAL CALCIUM; PARATHYROID-HORMONE; TARGETED DISRUPTION; PREGNANCY; TRANSPORT; CHILDREN; GENE; PLACENTA; SKELETAL AB Purpose of review Regulation of calcium and phosphorus levels in the fetus and neonate is critical for proper bone development and mineralization. Recent findings Parathyroid hormone-related peptide plays an important role in transferring calcium across the placenta into the fetal circulation. In contrast, the factors controlling placental phosphate transport have not yet been explored, and numerous studies have indicated that maternal and childhood vitamin D deficiency continues to be a significant clinical concern. Summary The molecular basis for mineral ion homeostasis in the fetus and child remains incompletely understood. More attention must be paid to identifying and treating maternal, neonatal, and childhood vitamin D deficiency. C1 [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hjueppner@partners.org NR 42 TC 26 Z9 28 U1 1 U2 6 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 FEB PY 2010 VL 17 IS 1 BP 25 EP 30 DI 10.1097/MED.0b013e328334f041 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691CS UT WOS:000285058500005 PM 19952739 ER PT J AU Wong, KK Engelman, JA Cantley, LC AF Wong, Kwok-Kin Engelman, Jeffrey A. Cantley, Lewis C. TI Targeting the PI3K signaling pathway in cancer SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; ANTITUMOR-ACTIVITY; PIK3CA MUTATIONS; LUNG-CANCER; CELLS; BREAST; GROWTH; AMPLIFICATION; MEK AB The phosphoinositide 3-kinase (PI3K) pathway is activated in a variety of different human cancers, and inhibitors of this pathway are under active development as anti-cancer therapeutics. In this review, we discuss the data supporting the use of PI3K pathway inhibitors in genetically and clinically defined cancers. This review focuses on their efficacy as single agents and in combination with other targeted therapies, specifically those targeting the MEK-ERK signaling pathway. C1 [Wong, Kwok-Kin; Engelman, Jeffrey A.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. [Engelman, Jeffrey A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM kwok-kin_wong@dfci.harvard.edu RI lv, xiaoqing/A-2591-2012; Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [R01 CA137008, K08 CA120060, K08 CA120060-04, P01 CA089021, P01 CA089021-05, R01 CA122794, R01 CA122794-04, R01 CA137008-01, R01 CA140594, R01 CA140594-01]; NIGMS NIH HHS [R01 GM036624, R01 GM036624-22, R01 GM041890, R01 GM056203, R01 GM056203-13] NR 32 TC 255 Z9 256 U1 3 U2 44 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2010 VL 20 IS 1 BP 87 EP 90 DI 10.1016/j.gde.2009.11.002 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 564TL UT WOS:000275240200012 PM 20006486 ER PT J AU Maheswaran, S Haber, DA AF Maheswaran, Shyamala Haber, Daniel A. TI Circulating tumor cells: a window into cancer biology and metastasis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID RESISTANT PROSTATE-CANCER; PERIPHERAL-BLOOD; BREAST-CANCER; LUNG-CANCER; MUTATIONS AB The presence of circulating tumor cells (CTCs) accompanies tumor invasion into the bloodstream. Detection, monitoring, and molecular analysis of these rare cancer cells shed into blood will provide a powerful and noninvasive approach for the detection of early disease, assessing prognosis and therapeutic response in established cancers, and targeting metastatic precursor cells. We review current and emerging technologies for CTC isolation, with a focus on capture efficiency, purity, and viability of CTCs, and their potential clinical applications. C1 [Haber, Daniel A.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU Howard Hughes Medical Institute NR 17 TC 125 Z9 138 U1 3 U2 48 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2010 VL 20 IS 1 BP 96 EP 99 DI 10.1016/j.gde.2009.12.002 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 564TL UT WOS:000275240200014 PM 20071161 ER PT J AU Sokol, CL Medzhitov, R AF Sokol, Caroline L. Medzhitov, Ruslan TI Role of basophils in the initiation of Th2 responses SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN IGE SYNTHESIS; ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; IL-4 PRODUCTION; IN-VIVO; B-CELLS; HELMINTH INFECTION; TYPE-2 IMMUNITY; MOUSE BASOPHIL; CUTTING EDGE AB Long appreciated for their role as Type-2 effector cells, basophils have recently come into the spotlight for their role in the initiation of Type-2 immunity. Via an assortment of different activation pathways, basophils produce cytokines such as IL-4 that promote Th2 differentiation. Furthermore, recent studies using different experimental systems have shown that basophils can act as antigen presenting cells both in vitro and in vivo. In addition, basophils shape the Type-2 immune response by guiding antibody production and the memory response. C1 [Sokol, Caroline L.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Medzhitov, Ruslan] Yale Univ, Sch Med, Dept Immunobiol, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Sokol, CL (reprint author), Massachusetts Gen Hosp, Dept Internal Med, 55 Fruit St, Boston, MA 02114 USA. EM clsokol@PARTNERS.ORG FU Howard Hughes Medical Institute; NIAID NIH HHS [R01 AI055502, R01 AI055502-07] NR 33 TC 43 Z9 50 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 2010 VL 22 IS 1 BP 73 EP 77 DI 10.1016/j.coi.2010.01.012 PG 5 WC Immunology SC Immunology GA 576BN UT WOS:000276118800011 PM 20144855 ER PT J AU Park, L Wexler, D AF Park, Lee Wexler, Deborah TI Update in diabetes and cardiovascular disease: synthesizing the evidence from recent trials of glycemic control to prevent cardiovascular disease SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE cardiovascular disease; diabetes mellitus; glucose control ID BLOOD-GLUCOSE CONTROL; CAUSE-SPECIFIC MORTALITY; MELLITUS; COMPLICATIONS; METAANALYSIS; ASSOCIATION; POPULATION; VETERANS; OUTCOMES; RISK AB Purpose of review To review the recent studies on intensive glucose control and the risk of cardiovascular disease (CVD) in type 2 diabetes, to discuss potential reasons for discordant results among recent trials, and to comment on implications for clinical practice. Recent findings Three large randomized controlled trials on the effect of tight glycemic control (TGC) on CVD in patients with type 2 diabetes have been published within the last year, along with the cardiovascular outcomes from the long-term follow-up of the United Kingdom Prospective Diabetes study. This narrative review of the methods and results of these trials reveals cardiovascular benefit from early institution of TGC, and lack of benefit or potential harm with intensification of glucose control late in the course of type 2 diabetes or after CVD has developed. Also, the benefits of TGC may be outweighed by weight gain and hypoglycemia. All trials had fewer cardiovascular events than anticipated, likely due to improvements in treatment of other cardiovascular risk factors. Summary In addition to controlling cardiovascular risk factors, patients with type 2 diabetes should aim for good glycemic control (HbA1c < 7%) soon after the diagnosis of diabetes to prevent macrovascular as well as microvascular complications. Glycemic targets should be individualized as diabetes progresses, comorbidities develop, and to avoid having the side-effects of therapy (hypoglycemia and weight gain) predominate. C1 [Park, Lee] Newton Wellesley Hosp, Newton, MA USA. [Wexler, Deborah] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Wexler, Deborah] Harvard Univ, Sch Med, Boston, MA USA. RP Wexler, D (reprint author), Massachusetts Hosp, Bulfinch 408, Boston, MA 02114 USA. EM dwexler@partners.org FU NIH [K23 DK 080 228] FX DJW is supported by NIH Career Development Award K23 DK 080 228. NR 25 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 EI 1473-6535 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD FEB PY 2010 VL 21 IS 1 BP 8 EP 14 DI 10.1097/MOL.0b013e328332dfaa PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 549GN UT WOS:000274035500002 PM 19829110 ER PT J AU Fader, AN Boruta, D Olawaiye, AB Gehrig, PA AF Fader, Amanda Nickles Boruta, David Olawaiye, Alexander B. Gehrig, Paola A. TI Uterine papillary serous carcinoma: epidemiology, pathogenesis and management SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE platinum/taxane-based chemotherapy; radiotherapy; surgical staging; targeted therapy; uterine papillary serous carcinoma ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; ADVANCED ENDOMETRIAL CARCINOMA; WHOLE-ABDOMINAL IRRADIATION; PLATINUM-BASED CHEMOTHERAPY; POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; CLEAR-CELL CARCINOMA; STAGE-I; HER-2/NEU OVEREXPRESSION AB Purpose of review Uterine papillary serous carcinoma (UPSC) is a rare but aggressive subtype of endometrial cancer. Although it represents only 10% of all endometrial cancer cases, UPSC accounts for up to 40% of all endometrial cancer-related recurrences and subsequent deaths. The present article reviews the literature concerning the epidemiology, molecular pathogenesis and recent updates on management of UPSC. Recent findings Women most often present with postmenopausal vaginal bleeding but may also be diagnosed by vaginal cytology. In women diagnosed with metastatic disease, ascites, omental implants or a pelvic mass may be present. Pelvic and extrapelvic recurrences some occur frequently, with extrapelvic relapses being observed most commonly. Although few prospective trials exist, several retrospective series have demonstrated that optimal cytoreduction and adjuvant platinum/taxane-based chemotherapy with or without radiotherapy appears to improve survival. In addition, another approach to UPSC management may lie in targeted therapy. Summary Women diagnosed with UPSC should undergo comprehensive surgical staging and an attempt at optimal cytoreduction. Platinum/taxane-based adjuvant chemotherapy should be considered in the treatment of both early and advanced-stage patients. Careful long-term surveillance is indicated as many of these women will recur. Prospective studies are needed to define the optimal treatment regimens and to study the role of targeted therapies in UPSC. C1 [Fader, Amanda Nickles] Greater Baltimore Med Ctr, Gynecol Oncol Sect, Baltimore, MD USA. [Fader, Amanda Nickles] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Boruta, David] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Gynecol Oncol Sect, Boston, MA 02114 USA. [Olawaiye, Alexander B.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Gynecol Oncol Sect, Pittsburgh, PA 15213 USA. [Gehrig, Paola A.] Univ N Carolina, Dept Obstet & Gynecol, Gynecol Oncol Sect, Chapel Hill, NC USA. RP Fader, AN (reprint author), 6569 N Charles St,Ste 206, Baltimore, MD 21204 USA. EM amandanfader@gmail.com NR 80 TC 40 Z9 43 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2010 VL 22 IS 1 BP 21 EP 29 DI 10.1097/GCO.0b013e328334d8a3 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 548BW UT WOS:000273934800005 PM 19952744 ER PT J AU Juhl, K Bonner-Weir, S Sharma, A AF Juhl, Kirstine Bonner-Weir, Susan Sharma, Arun TI Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE beta-cells; diabetes; in-vivo regeneration; neogenesis; transdifferentiation ID INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; PROGENITOR CELLS; ENDOCRINE PANCREAS; MOUSE PANCREAS; EPITHELIAL-CELLS; LIVER; DIFFERENTIATION; TRANSDIFFERENTIATION; EXPRESSION AB Purpose of review Diabetes results from inadequate functional mass of pancreatic beta-cells and therefore replenishing with new glucose-responsive beta-cells is an important therapeutic option. In addition to replication of pre-existing beta-cells, new beta-cells can be produced from differentiated adult cells using in-vitro or in-vivo approaches. This review will summarize recent advances in in-vivo generation of P-cells from cells that are not beta-cells (neogenesis) and discuss ways to overcome the limitations of this process. Recent findings Multiple groups have shown that adult pancreatic ducts, acinar and even endocrine cells exhibit cellular plasticity and can differentiate into beta-cells in vivo. Several different approaches, including misexpression of transcription factors and tissue injury, have induced neogenesis of insulin-expressing cells in vivo and ameliorated diabetes. Summary Recent breakthroughs demonstrating cellular plasticity of adult pancreatic cells to form new beta-cells are a positive first step towards developing in-vivo regeneration-based therapy for diabetes. Currently, neogenesis processes are inefficient and do not generate sufficient amounts of beta-cells required to normalize hyperglycemia. However, an improved understanding of mechanisms regulating neogenesis of beta-cells from adult pancreatic cells and of their maturation into functional glucose-responsive beta-cells can make therapies based on in-vivo regeneration a reality. C1 [Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM Arun.Sharma@joslin.harvard.edu FU Lundbeckfonden, Denmark [R7-A714-B576]; JDRF [3-2009-683]; National Institutes of Health (NIH/NIDDK); ADA FX K.J. is a recipient of Postdoctoral fellowships #R7-A714-B576 from Lundbeckfonden, Denmark and 3-2009-683 from JDRF. Research in Sharma and Bonner-Weir laboratories was supported by grants from National Institutes of Health (NIH/NIDDK), JDRF, and ADA. We thank members of our laboratories for their contribution to this research. NR 70 TC 35 Z9 37 U1 0 U2 4 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 FEB PY 2010 VL 15 IS 1 BP 79 EP 85 DI 10.1097/MOT.0b013e3283344932 PG 7 WC Transplantation SC Transplantation GA 548YW UT WOS:000274007500016 PM 19907327 ER PT J AU Carinci, AJ Mao, JR AF Carinci, Adam J. Mao, Jianren TI Pain and Opioid Addiction: What is the Connection? SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Opioids; Abuse; Addiction; Aberrant drug related behavior (ADRB); Chronic pain; Epidemiology; Neurobiology; Cellular mechanisms ID ACTIVATED PROTEIN-KINASE; CHRONIC NONCANCER PAIN; DRUG-ABUSE; THERAPY; MORPHINE; PREVALENCE; EXPRESSION; WITHDRAWAL; BEHAVIORS; TOLERANCE AB Addiction to opioid analgesics is an important and yet underinvestigated clinical issue, which has substantial implications in opioid therapy for chronic pain management. Problematic opioid use, including compulsive opioid seeking and addiction, arises in some fraction of opioid-treated chronic pain patients. The connection between chronic pain and opioid addiction is a complex interplay between psychological, epidemiological, and neurobiological factors. Herein, we explore this critical relationship. C1 [Carinci, Adam J.; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Div Pain Med, Boston, MA 02114 USA. RP Carinci, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Div Pain Med, 15 Parkman St, Boston, MA 02114 USA. EM acarinci@partners.org; jmao@partners.org NR 41 TC 4 Z9 4 U1 1 U2 8 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1531-3433 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD FEB PY 2010 VL 14 IS 1 BP 17 EP 21 DI 10.1007/s11916-009-0086-x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 559SC UT WOS:000274845900003 PM 20425210 ER PT J AU Swick, JM Grattan, EG Burges, GE AF Swick, Julie M. Grattan, Elizabeth G. Burges, Gene E. TI What Is Your Diagnosis? - The Diagnosis: Metastatic Adenocarcinoma SO CUTIS LA English DT Editorial Material ID CUTANEOUS METASTASES; CARCINOMA; SKIN C1 [Swick, Julie M.; Grattan, Elizabeth G.; Burges, Gene E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Burges, Gene E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Swick, JM (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 EI 2326-6929 J9 CUTIS JI Cutis PD FEB PY 2010 VL 85 IS 2 BP 64 EP + PG 2 WC Dermatology SC Dermatology GA 560NZ UT WOS:000274910700002 PM 20349678 ER PT J AU Cannizzo, E Bellio, E Ferry, JA Hasserjian, RP Sohani, AR Dorn, ME Sadowski, C Bucci, JJ Petrini, M Carulli, G Preffer, F AF Cannizzo, Elisa Bellio, Emanuele Ferry, Judith A. Hasserjian, Robert P. Sohani, Aliyah R. Dorn, Michelle E. Sadowski, Craig Bucci, Janessa J. Petrini, Mario Carulli, Giovanni Preffer, Frederic TI MULTIPARAMETER IMMUNOPHENOTYPING BY FLOW CYTOMETRY IN MULTIPLE MYELOMA: DEFINING RANGES OF NORMAL EXPRESSION AND THEIR DIAGNOSTIC UTILITY SO CYTOMETRY PART A LA English DT Meeting Abstract CT 27th National Conference of the Italian-Society-of-Cytometry-GIC CY OCT 14-17, 2009 CL Ferrara, ITALY SP Italian Soc Cytometry GIC C1 [Cannizzo, Elisa; Ferry, Judith A.; Hasserjian, Robert P.; Sohani, Aliyah R.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cannizzo, Elisa; Ferry, Judith A.; Hasserjian, Robert P.; Sohani, Aliyah R.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.] Harvard Univ, Sch Med, Boston, MA USA. [Cannizzo, Elisa; Bellio, Emanuele; Petrini, Mario; Carulli, Giovanni; Preffer, Frederic] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Adv Med, Pisa, Italy. EM elisacannizzo@libero.it NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2010 VL 77A IS 2 BP 165 EP 165 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 556EL UT WOS:000274572100055 ER PT J AU Cannizzo, E Bellio, E Sohani, AR Hasserjian, RP Ferry, JA Dorn, ME Sadowski, C Bucci, JJ Petrini, M Carulli, G Preffer, F AF Cannizzo, Elisa Bellio, Emanuele Sohani, Aliyah R. Hasserjian, Robert P. Ferry, Judith A. Dorn, Michelle E. Sadowski, Craig Bucci, Janessa J. Petrini, Mario Carulli, Giovanni Preffer, Frederic TI THE DIAGNOSTIC ROLE OF MULTIPARAMETER IMMUNOPHENOTYPING BY FLOW CYTOMETRY IN MULTIPLE MYELOMA: A NEW MODEL SO CYTOMETRY PART A LA English DT Meeting Abstract CT 27th National Conference of the Italian-Society-of-Cytometry-GIC CY OCT 14-17, 2009 CL Ferrara, ITALY SP Italian Soc Cytometry GIC C1 [Cannizzo, Elisa; Sohani, Aliyah R.; Hasserjian, Robert P.; Ferry, Judith A.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cannizzo, Elisa; Sohani, Aliyah R.; Hasserjian, Robert P.; Ferry, Judith A.; Dorn, Michelle E.; Sadowski, Craig; Bucci, Janessa J.; Preffer, Frederic] Harvard Univ, Sch Med, Boston, MA USA. [Cannizzo, Elisa; Bellio, Emanuele; Petrini, Mario; Carulli, Giovanni] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Adv Med, Pisa, Italy. EM elisacannizzo@libero.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD FEB PY 2010 VL 77A IS 2 BP 166 EP 166 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 556EL UT WOS:000274572100057 ER PT J AU Lewis-Fernandez, R Hinton, DE Laria, AJ Patterson, EH Hofmann, SG Craske, MG Stein, DJ Asnaani, A Liao, B AF Lewis-Fernandez, Roberto Hinton, Devon E. Laria, Amaro J. Patterson, Elissa H. Hofmann, Stefan G. Craske, Michelle G. Stein, Dan J. Asnaani, Ann Liao, Betty TI CULTURE AND THE ANXIETY DISORDERS: RECOMMENDATIONS FOR DSM-V SO DEPRESSION AND ANXIETY LA English DT Review DE DSM-V; culture; classification; anxiety disorders; diagnostic; criteria ID OBSESSIVE-COMPULSIVE DISORDER; COMORBIDITY SURVEY REPLICATION; MENTAL-HEALTH-SURVEY; NATIONAL EPIDEMIOLOGIC SURVEY; ATAQUES-DE-NERVIOS; PANIC DISORDER; SOCIAL ANXIETY; 12-MONTH PREVALENCE; PSYCHIATRIC-DISORDERS; TAIJIN-KYOFUSHO AB Background: The anxiety disorders specified in the fourth edition, text revision, of The Diagnostic and Statistical Manual (DSM-IV-TR) are identified universally in human societies, and also show substantial cultural particularities in prevalence and symptomatology. Possible explanations for the observed epidemiological variability include lack of measurement equivalence, true differences in prevalence, and limited validity or precision of diagnostic criteria. One central question is whether, through inadvertent "over-specification" of disorders, the post-DSM-III nosology has missed related but somewhat different presentations of the same disorder because the do not exactly fit specified criteria sets. This review canvases the mental health literature for evidence of cross-cultural limitations in DSM-IV-TR anxiety disorder criteria. Methods: Searches were conducted of the mental health literature, particularly since 1994, regarding cultural or race/ethnicity-related factors that might limit the universal applicability of the diagnostic criteria for six anxiety disorders. Results: Possible mismatches between the DSM criteria and the local phenomenology of the disorder in specific cultural contexts were found for three anxiety disorders in particular. These involve the unexpectedness and 10-minute crescendo criteria in Panic Disorder; the definition of social anxiety and social reference group in Social Anxiety Disorder; and the priority given to psychological symptoms of worry in Generalized Anxiety Disorder, Limited evidence was found throughout, particularly in terms of neurobiological markers, genetic risk factors, treatment response, and other DSM-V validators that could help clarify the cross-cultural applicability of criteria. Conclusions: On the basis of the available data, options and preliminary recommendations for DSM-V are put forth that should be further evaluated and tested. Depression and Anxiety 27:212-229, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Lewis-Fernandez, Roberto] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hinton, Devon E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Laria, Amaro J.; Patterson, Elissa H.] Massachusetts Sch Profess Psychol, Boston, MA USA. [Hofmann, Stefan G.; Asnaani, Ann] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Craske, Michelle G.; Liao, Betty] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Stein, Dan J.] Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. RP Lewis-Fernandez, R (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr,Suite 3200,Unit 69, New York, NY 10032 USA. EM rlewis@nyspi.cpmc.columbia.edu RI Hofmann, Stefan/B-8769-2014; Stein, Dan/A-1752-2008 OI Hofmann, Stefan/0000-0002-3548-9681; Stein, Dan/0000-0001-7218-7810 FU NIMH NIH HHS [R01 MH077226] NR 132 TC 62 Z9 63 U1 8 U2 25 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 FEB PY 2010 VL 27 IS 2 BP 212 EP 229 DI 10.1002/da.20647 PG 18 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 555LM UT WOS:000274512300008 PM 20037918 ER PT J AU Florez, JC AF Florez, Jose C. TI A Genome-Wide Association Study of Treated A1C A Genetic Needle in an Environmental Haystack? SO DIABETES LA English DT Editorial Material ID QUANTITATIVE TRAIT LOCUS; SORCS1; SCAN C1 [Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. [Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Res Ctr,Diabet Unit, Boston, MA USA. RP Florez, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. EM jcflorez@partners.org NR 11 TC 10 Z9 10 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2010 VL 59 IS 2 BP 332 EP 334 DI 10.2337/db09-1636 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 554LG UT WOS:000274435900003 PM 20103712 ER PT J AU Driver, JP Scheuplein, F Chen, YG Grier, AE Wilson, SB Serreze, DV AF Driver, John P. Scheuplein, Felix Chen, Yi-Guang Grier, Alexandra E. Wilson, S. Brian Serreze, David V. TI Invariant Natural Killer T-Cell Control of Type 1 Diabetes: A Dendritic Cell Genetic Decision of a Silver Bullet or Russian Roulette SO DIABETES LA English DT Article ID NKT CELLS; NOD MICE; EXPRESSION; IMMUNITY; ACTIVATION; INDUCTION; TOLERANCE; RESPONSES; PD-L1; CD4 AB OBJECTIVE-In part, activation of invariant natural killer T (iNKT)-cells with the superagonist a-galactosylceramide (alpha-Gal-Cer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotolerogenic state. However, in other systems iNKT-cell activation has an adjuvant-like effect that enhances rather than suppresses various immunological responses. Thus, we tested whether in some circumstances genetic variation would enable activated iNKT-cells to support rather than inhibit type 1. diabetes development. RESEARCH DESIGN AND METHODS-We tested whether iNKT-conditioned DCs in NOD mice and a major histocompatibility complex-matched C57BL/6 (B6) background congenic stock differed in capacity to inhibit type 1 diabetes induced by the adoptive transfer of pathogenic AI4 CD8 T-cells. RESULTS-Unlike those of NOD origin, iNKT-conditioned DCs in the 136 background stock matured to a state that actually supported rather than inhibited AI4 T-cell-induced type 1 diabetes. The induction of a differing activity pattern of T-cell costimulatory molecules varying in capacity to override programmed death-ligand-1 inhibitory effects contributes to the respective ability of iNKT-conditioned DCs in NOD and 136 background mice to inhibit or support type 1 diabetes development. Genetic differences inherent to both iNKT-cells and DCs contribute to their varying interactions in NOD and B6.H2(97) mice. CONCLUSIONS-This great variability in the interactions between iNKT-cells and DCs in two inbred mouse strains should raise a cautionary note about considering manipulation of this axis as a potential type 1 diabetes prevention therapy in genetically heterogeneous humans. Diabetes 59:423-432, 2010 C1 [Driver, John P.; Scheuplein, Felix; Chen, Yi-Guang; Grier, Alexandra E.; Serreze, David V.] Jackson Lab, Bar Harbor, ME 04609 USA. [Wilson, S. Brian] Massachusetts Gen Hosp, Diabet Res Labs, Cambridge, MA USA. RP Serreze, DV (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM dave.serreze@jax.org OI Scheuplein, Felix/0000-0002-2691-0796 FU National Institutes of Health [DK-46266, DK-51090]; Cancer Center Support [CA34196]; Juvenile Diabetes Research Foundation International FX This work was supported by National Institutes of Health Grants DK-46266 and DK-51090, Cancer Center Support Grant CA34196, and grants from the Juvenile Diabetes Research Foundation International. NR 41 TC 13 Z9 13 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2010 VL 59 IS 2 BP 423 EP 432 DI 10.2337/db09-1116 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 554LG UT WOS:000274435900013 PM 19903740 ER PT J AU Fioramonti, X Marsollier, N Song, ZT Fakira, KA Patel, RM Brown, S Duparc, T Pica-Mendez, A Sanders, NM Knauf, C Valet, P McCrimmon, RJ Beuve, A Magnan, C Routh, VH AF Fioramonti, Xavier Marsollier, Nicolas Song, Zhentao Fakira, Kurt A. Patel, Reema M. Brown, Stacey Duparc, Thibaut Pica-Mendez, Arnaldo Sanders, Nicole M. Knauf, Claude Valet, Philippe McCrimmon, Rory J. Beuve, Annie Magnan, Christophe Routh, Vanessa H. TI Ventromedial Hypothalamic Nitric Oxide Production Is Necessary for Hypoglycemia Detection and Counterregulation SO DIABETES LA English DT Article ID CEREBRAL-BLOOD-FLOW; GLUCOSE-INHIBITED NEURONS; INSULIN-INDUCED HYPOGLYCEMIA; DEPENDENT DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; ARCUATE NUCLEUS; HORMONE-RELEASE; EXCITED NEURONS; NEUROPEPTIDE-Y; HEART-RATE AB OBJECTIVE-The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR. RESEARCH DESIGN AND METHODS-The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed. RESULTS-Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebro-ventricular and VMH injection of the nonselective NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH L-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice. CONCLUSIONS-We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy. Diabetes 59:519-528, 2010 C1 [Fioramonti, Xavier; Song, Zhentao; Fakira, Kurt A.; Patel, Reema M.; Pica-Mendez, Arnaldo; Beuve, Annie; Routh, Vanessa H.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ 07103 USA. [Marsollier, Nicolas; Magnan, Christophe] Univ Paris Diderot, Natl Ctr Sci Res, Paris, France. [Brown, Stacey] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Duparc, Thibaut; Knauf, Claude; Valet, Philippe; McCrimmon, Rory J.] Univ Toulouse 3, INSERM, Inst Med Mol Rangueil, U858,IFR150, F-31062 Toulouse, France. [Sanders, Nicole M.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. RP Routh, VH (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, 185 S Orange Ave, Newark, NJ 07103 USA. EM routhvh@umdnj.edu OI McCrimmon, Rory/0000-0002-3957-1981 FU Juvenile Diabetes Research Foundation; National Institutes of Health [28O1-DK-55619, 1RO1-DK-64566]; Philippe Foundation FX This work was supported in part by the Juvenile Diabetes Research Foundation (X.F. and V.H.R.) and the National Institutes of Health (28O1-DK-55619 and 1RO1-DK-64566) (V.H.R.). X.F. was also supported in part by the Philippe Foundation. NR 44 TC 32 Z9 32 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2010 VL 59 IS 2 BP 519 EP 528 DI 10.2337/db09-0421 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 554LG UT WOS:000274435900024 PM 19934009 ER PT J AU Lin, EHB Rutter, CM Katon, W Heckbert, SR Ciechanowski, P Oliver, MM Ludman, EJ Young, BA Williams, LH McCulloch, DK Von Korff, M AF Lin, Elizabeth H. B. Rutter, Carolyn M. Katon, Wayne Heckbert, Susan R. Ciechanowski, Paul Oliver, Malia M. Ludman, Evette J. Young, Bessie A. Williams, Lisa H. McCulloch, David K. Von Korff, Michael TI Depression and Advanced Complications of Diabetes - A prospective cohort study SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR EVENTS; SELF-REPORT; SYMPTOMS; CARE; INDIVIDUALS; ASSOCIATION; ADHERENCE; APPRAISAL; RISK AB OBJECTIVE - To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000-2002 and followed through 2005-2007. Advanced microvascular complications included blindness, end-Stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes. RESULTS - After adjustment for prior complications and demographic, clinical and diabetes self-care variables, major depression was associated with significantly higher rises of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05-1.75]) and adverse macrovascular outcomes (1.24 [1.0-1.54]). CONCLUSIONS - Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these Findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to Lest Interventions to reduce the risk of diabetes complications among patients with comorbid depression. C1 [Lin, Elizabeth H. B.; Rutter, Carolyn M.; Oliver, Malia M.; Ludman, Evette J.; McCulloch, David K.; Von Korff, Michael] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Katon, Wayne; Ciechanowski, Paul] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Sch Med, Epidemiol Res & Informat Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Williams, Lisa H.] Univ Washington, Sch Med, Dept Med Dermatol, Seattle, WA 98195 USA. RP Lin, EHB (reprint author), Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. EM lin.e@ghc.org FU National Institutes of Health [MH 073686] FX This research was supported by grants from the National Institutes of Health (MH 073686). NR 24 TC 175 Z9 181 U1 6 U2 20 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 FEB PY 2010 VL 33 IS 2 BP 264 EP 269 DI 10.2337/dc09-1068 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563PA UT WOS:000275143700009 PM 19933989 ER PT J AU Weinger, K Beverly, EA AF Weinger, Katie Beverly, Elizabeth A. TI Barriers to Achieving Glycemic Targets: Who Omits Insulin and Why? SO DIABETES CARE LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; BETA-CELL FUNCTION; SELF-CARE; METABOLIC-CONTROL; EATING-DISORDERS; GLUCOSE CONTROL; DEPRESSION; ADHERENCE; COMPLICATIONS; ASSOCIATION C1 [Weinger, Katie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, Boston, MA 02215 USA. RP Weinger, K (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM katie.weinger@joslin.harvard.edu FU NIDDK NIH HHS [P30DK36836, P30 DK036836] NR 36 TC 8 Z9 8 U1 4 U2 4 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 FEB PY 2010 VL 33 IS 2 BP 450 EP 452 DI 10.2337/dc09-2132 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563PA UT WOS:000275143700047 PM 20103561 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Exodontia may improve glycemic control of diabetic patients with periodontitis SO DIABETES & METABOLISM LA English DT Letter C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Hosp Dent Serv, Med Ctr, Los Angeles, CA 90095 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD FEB PY 2010 VL 36 IS 1 BP 88 EP 88 DI 10.1016/j.diabet.2009.10.002 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 565IX UT WOS:000275285000013 PM 20080427 ER PT J AU Grasing, K Mathur, D Newton, TF DeSouza, C AF Grasing, Kenneth Mathur, Deepan Newton, Thomas F. DeSouza, Cherilyn TI Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Acetylcholine; Cholinesterase inhibitors; Cocaine; Cocaine-related disorders; Donepezil ID NUCLEUS-ACCUMBENS; ALZHEIMERS-DISEASE; RATS; ACETYLCHOLINE; METHAMPHETAMINE; STIMULATION; AMPHETAMINE; VOLUNTEERS; WITHDRAWAL; RESPONSES AB Acetylcholinesterase (ACNE) inhibitors increase synaptic levels of acetylcholine (ACh) by inhibiting its breakdown. Donepezil is a reversible ACNE inhibitor that is clinically available and relatively selective for inhibiting ACNE but not other cholinesterases. Because ACNE inhibitors have been shown to decrease the reinforcing effects of cocaine in animals, our hypothesis was that pretreatment with donepezil would attenuate the perceived value and other positive subjective effects of cocaine. We conducted a within-subject, double-blind, placebo-controlled, laboratory-based evaluation of the subjective effects produced by intravenous cocaine in human subjects receiving oral donepezil. Following three days of daily treatment with 5 mg of donepezil or oral placebo, participants received intravenous placebo or cocaine (0.18 and 0.36 mg/kg). After a three-clay washout period, participants were crossed over to the opposite oral treatment, which was followed by identical intravenous infusions. Donepezil was well-tolerated with only two drug-related adverse events reported that were mild and self-limiting. Treatment with donepezil increased ratings of 'any' and 'good' drug effect produced by low-dose cocaine, without modifying the response to high-close cocaine. When collapsed across intravenous close, treatment with donepezil decreased dysphoric effects and somatic symptoms, but did not modify the value of cocaine injections as determined by the Multiple Choice Questionnaire (MCQ). In summary, pretreatment with donepezil potentiated some measures for nonspecific and positive effects of low-dose cocaine. Across all intravenous treatments, participants receiving donepezil reported fewer somatic-dysphoric effects. Neither of these actions support the value of donepezil as a treatment for cocaine dependence. Published by Elsevier Ireland Ltd. C1 [Grasing, Kenneth; Mathur, Deepan; DeSouza, Cherilyn] Kansas City VA Med Ctr, Subst Abuse Res Lab, Kansas City, MO 64128 USA. [Grasing, Kenneth] Univ Kansas, Sch Med, Dept Med, Div Clin Pharmacol, Kansas City, KS 66160 USA. [DeSouza, Cherilyn] Univ Kansas, Sch Med, Dept Psychiat, Kansas City, KS 66160 USA. [Newton, Thomas F.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Newton, Thomas F.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Grasing, K (reprint author), Kansas City VA Med Ctr, Subst Abuse Res Lab, 151,4801 Linwood Blvd, Kansas City, MO 64128 USA. EM kenneth.grasing@med.va.gov; deepan.mathur@va.gov; tnewton@bcm.tmc.edu; cherilyn.desouza@med.va.gov OI newton, thomas/0000-0002-3198-5901 NR 44 TC 15 Z9 15 U1 4 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD FEB 1 PY 2010 VL 107 IS 1 BP 69 EP 75 DI 10.1016/j.drugalcdep.2009.09.010 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 566FI UT WOS:000275355100010 PM 19836169 ER PT J AU Huffman, JC Freudenreich, O Romeo, S Baer, L Sutton-Skinner, K Petersen, T Fromson, JA Birnbaum, RJ AF Huffman, Jeff C. Freudenreich, Oliver Romeo, Sarah Baer, Lee Sutton-Skinner, Kelly Petersen, Tim Fromson, John A. Birnbaum, Robert J. TI Assessing clinicians' management of first episode schizophrenia using clinical case vignettes SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE antipsychotics; educational measurement; needs assessment; psychotic disorders; schizophrenia ID UNTREATED PSYCHOSIS; 1ST-EPISODE SCHIZOPHRENIA; ONSET SCHIZOPHRENIA; RISPERIDONE; DURATION; TRIAL; HALOPERIDOL; OLANZAPINE; EFFICACY; DISORDER AB Background: Patients with first episode schizophrenia may present in a variety of clinical settings to providers who have a range of knowledge and skills. A thoughtful workup of patients with new-onset psychosis is critical, and the treatment of first episode schizophrenia differs from that of chronic psychotic disorders. Clinical case vignettes with free-form responses can be used to carefully assess whether front line practitioners provide guideline-adherent management of first episode psychosis. Methods: A clinical case vignette, presenting a patient with first episode schizophrenia, was created and administered to the attendees of a continuing medical education programme. Free-form responses to questions regarding differential diagnosis, workup, treatment and treatment duration were scored based on published practice guidelines. Response frequencies were tabulated and performance was compared among professional disciplines. Results: Sixty-two attendees comattendees typically considered a broad differential diagnosis and appropriately initiated treatment with antipsychotics, the respondents' proposed medical workup was limited, and they prescribed antipsychotics at higher doses and for a shorter duration than recommended in the literature. The prescribers outperformed the non-prescribers on treatment questions ( P = 0.006), but the two groups' performance did not signficantly differ on the assessment questions ( P = 0.08). Conclusions: The front line clinicians who encounter patients with first episode schizophrenia may have significant practice gaps in the initial and follow-up care of these patients. Given the preliminary nature of this study and the debate about the optimal care for first episode psychosis, further study is needed. If such gaps are confirmed, additional educational interventions are required to align clinical management with published practice guidelines. C1 [Huffman, Jeff C.; Freudenreich, Oliver; Romeo, Sarah; Baer, Lee; Sutton-Skinner, Kelly; Petersen, Tim; Fromson, John A.; Birnbaum, Robert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Huffman, Jeff C.; Freudenreich, Oliver; Baer, Lee; Petersen, Tim; Fromson, John A.; Birnbaum, Robert J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 55 Fruit St,Warren 1220C, Boston, MA 02114 USA. EM jhuffman@partners.org FU pharmaceutical companies; Cephalon FX Jeff Huffman, Oliver Freudenreich, John Fromson and Tim Petersen have received honoraria payments from Reed Medical Education related to the MGH Psychiatry Academy. The education programmes conducted by the MGH Psychiatry Academy and Reed Medical Education (a publicly traded company working as a logistics collaborator for the MGH Psychiatry Academy) are supported through independent medical education grants from pharmaceutical companies co-supporting various components of the overall programme along with participant tuition. Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website at www.mghcme.org. Dr Freudenreich also receives research support from Cephalon. No other authors have conflicts of interest to report related to this manuscript. NR 20 TC 3 Z9 3 U1 4 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD FEB PY 2010 VL 4 IS 1 BP 31 EP 38 DI 10.1111/j.1751-7893.2009.00152.x PG 8 WC Psychiatry SC Psychiatry GA 550XI UT WOS:000274166700004 PM 20199478 ER PT J AU Blake, KD Blendon, RJ Viswanath, K AF Blake, Kelly D. Blendon, Robert J. Viswanath, Kasisomayajula TI Employment and Compliance with Pandemic Influenza Mitigation Recommendations SO EMERGING INFECTIOUS DISEASES LA English DT Article ID BRITISH CIVIL-SERVANTS; TELEPHONE SURVEY; WHITEHALL-II; HEALTH; PREPAREDNESS; NONRESPONSE; EMERGENCY; ATTITUDES AB In the event of a serious pandemic influenza outbreak, businesses must play a key role in protecting employees' health and safety. With regard to pandemic influenza mitigation recommendations requiring social distancing, we examined whether some US employees would disproportionately fail to comply because of job insecurity and financial problems associated with missing work. We used the 2006 Harvard School of Public Health Pandemic Influenza Survey and multivariable logistic regression to determine whether employment characteristics such as inability to work from home, lack of pay when absent from work, and self-employment would be associated with less ability to comply with recommendations. We found that inability to work from home, lack of paid sick leave, and income are associated with working adults' ability to comply and should be major targets for workplace interventions in the event of a serious outbreak. C1 [Blake, Kelly D.; Blendon, Robert J.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Blake, Kelly D.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blake, KD (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St,MS LW703, Boston, MA 02115 USA. EM kellyblake@post.harvard.edu NR 23 TC 15 Z9 15 U1 0 U2 4 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 FEB PY 2010 VL 16 IS 2 BP 212 EP 218 DI 10.3201/eid1602.090638 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 553XO UT WOS:000274400300005 PM 20113549 ER PT J AU Adler, DC Zhou, C Tsai, TH Lee, HC Becker, L Schmitt, JM Huang, Q Fujimoto, JG Mashimo, H AF Adler, D. C. Zhou, C. Tsai, T. H. Lee, H. C. Becker, L. Schmitt, J. M. Huang, Q. Fujimoto, J. G. Mashimo, H. TI Biased assessment of 3D optical coherence tomography in a single post-radiofrequency ablation patient without histological correlation Reply SO ENDOSCOPY LA English DT Letter ID BARRETTS-ESOPHAGUS C1 [Mashimo, H.] VA Boston Healthcare, Boston, MA 02120 USA. [Fujimoto, J. G.] MIT, Cambridge, MA 02139 USA. EM jgfuji@mit.edu; hmashimo@hms.harvard.edu RI Zhou, Chao/A-1327-2007 NR 6 TC 2 Z9 2 U1 4 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD FEB PY 2010 VL 42 IS 2 BP 180 EP 181 DI 10.1055/s-0029-1243842 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 552XZ UT WOS:000274329800019 ER PT J AU Chiu, YH Hart, JE Spiegelman, D Garshick, E Smith, TJ Dockery, DW Hammond, SK Laden, F AF Chiu, Yueh-Hsiu Hart, Jaime E. Spiegelman, Donna Garshick, Eric Smith, Thomas J. Dockery, Douglas W. Hammond, S. Katharine Laden, Francine TI Workplace Secondhand Smoke Exposure in the US Trucking Industry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE personal sampling; secondhand smoke; self-reported exposure; smoking policy; trucking industry; vapor-phase nicotine; workplace exposure ID ENVIRONMENTAL TOBACCO-SMOKE; SERUM COTININE; CIGARETTE-SMOKING; PASSIVE SMOKING; RISK-FACTORS; NICOTINE; TRENDS; NONSMOKERS; OCCUPATION; ADULTS AB BACKGROUND: Although the smoking rate in the United States is declining because of an increase of smoke-free laws, among blue-collar workers it remains higher than that among many other occupational groups. OBJECTIVES: We evaluated the factors influencing workplace secondhand smoke (SHS) exposures in the U.S. unionized trucking industry. METHODS: Front 2003 through 2005, we measured workplace SHS exposure among 203 nonsmoking and 61 smoking workers in 25 trucking terminals. Workers in several job groups wore personal vapor-phase nicotine samplers oil their lapels for two consecutive work shifts and completed a workplace SHS exposure questionnaire at the end of the personal sampling. RESULTS: Median nicotine level was 0.87 mu g/m(3) for nonsmokers and 5.96 mu g/m(3) for smokers. As expected, smokers experienced higher SHS exposure duration and intensity than did nonsmokers. For nonsmokers, multiple regression analyses indicated that self-reported exposure duration combined with intensity, lack of a smoking policy as reported by workers, having a nondriver job, and lower educational level were independently associated with elevated personal nicotine levels (model R(2) = 0.52). Nondriver job and amount of active smoking were associated with elevated personal nicotine level in smokers, but self-reported exposure, lack of a smoking policy, and lower educational level were not. CONCLUSIONS: Despite movements toward smoke-free laws, this population of blue-collar workers was still exposed to workplace SHS as recently as 2005. The perceived (reported by the workers) rather than the official (reported by the terminal managers), smoking policy was associated with measured SHS exposure levels among the nonsmokers. job duties and educational level might also be important predictors of workplace SHS exposure. C1 [Chiu, Yueh-Hsiu; Hart, Jaime E.; Smith, Thomas J.; Dockery, Douglas W.; Laden, Francine] Harvard Univ, Sch Publ Hlth, EER Program, Dept Environm Hlth, Boston, MA 02215 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Spiegelman, Donna; Dockery, Douglas W.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Garshick, Eric] Vet Affairs Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Chiu, YH (reprint author), Harvard Univ, Sch Publ Hlth, EER Program, Dept Environm Hlth, 401 Pk Dr,Landmark 4th Floor, Boston, MA 02215 USA. EM yhchiu@hsph.harvard.edu RI Smith, Thomas/A-9640-2010 FU Flight Attendant Medical Research Institute; National Institutes of Health/National Cancer Institute [R01 CA90792] FX This study is supported by the Flight Attendant Medical Research Institute and by National Institutes of Health/National Cancer Institute grant R01 CA90792. NR 47 TC 7 Z9 7 U1 2 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2010 VL 118 IS 2 BP 216 EP 221 DI 10.1289/ehp.0900892 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 555BQ UT WOS:000274482400021 PM 20123606 ER PT J AU Thiele, EA AF Thiele, Elizabeth A. TI Managing and understanding epilepsy in tuberous sclerosis complex SO EPILEPSIA LA English DT Article; Proceedings Paper CT Symposium on Epilepsy at the Cutting Edge held in honor of Fred and Eva Andermann CY OCT 22-25, 2008 CL Montreal Neurol Inst, Montreal, CANADA HO Montreal Neurol Inst ID INFANTILE SPASMS; SURGERY; TSC2; BEHAVIOR; CHILDREN C1 Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr TSC, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr TSC, Boston, MA 02114 USA. EM ethiele@partners.org NR 18 TC 8 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2010 VL 51 SU 1 BP 90 EP 91 DI 10.1111/j.1528-1167.2009.02458.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 545WP UT WOS:000273768000028 PM 20331728 ER PT J AU Leon, C de Nijs, L Chanas, G Delgado-Escueta, AV Grisar, T Lakaye, B AF Leon, Christine de Nijs, Laurence Chanas, Grazyna Delgado-Escueta, Antonio V. Grisar, Thierry Lakaye, Bernard TI Distribution of EFHC1 or Myoclonin 1 in mouse neural structures SO EPILEPSY RESEARCH LA English DT Article DE Juvenile myoclonic epilepsy; Brain development; Ependymal cells; Radial glia; Motile cilia; Neural stem cells ID EPILEPSY; EXPRESSION; MIGRATION; BRAIN; CELLS; MICROTUBULES; MUTATIONS; SPINDLE; CILIA AB EFHC1, a gene mutated in juvenile myoclonic epilepsy, encodes EFHC1, a protein with three DM10 domains and one EF-hand motif. We recently demonstrated that this molecule is a microtubule-associated protein (MAP) implicated in neuronal. migration. Because some controversies persist about the precise localization in the CNS, we studied the neuroanatomical distribution of EFHC1 in mature and developing mouse brain. In the adult, low mRNA expression was detected in several brain structures such as cortex, striatum, hippocampus and cerebellum. At E16, EFHC1 mRNA was shown to be expressed in cortex and not only in cells lining ventricles. Using a purified polyclonal antibody, EFHC1 staining was observed in all cortical layers, in piriform cortex, in hippocampus and in Purkinje cells of cerebellum. In the cortex, the majority of EFHC1 positive cells correspond to neurons, however some glial. cells were also stained. In agreement with a previous study, we demonstrated strong EFHC1 expression in cilia of ependymal cells lining cerebral ventricles. Moreover, at Ell 6, the protein was observed at the borders of brain ventricles, in choroid plexus, but also, although to a lesser extent, in piriform and neocortex. In these latter structures, the pattern of expression seems to correspond to the extensions of the radial glia fibers as demonstrated by BLBP immunostaining. Finally, we confirmed that EFHC1 was also expressed and co-localized with the mitotic spindle of neural stem cells. These results confirm that EFHC1 is a protein with a likely low expression level, in mouse brain but detectable both in adult and embryonic brain supporting our previous data and hypothesis that EFHC1 could play an important role during brain development. As discussed, this opens the door to a new conceptual approach viewing some idiopathic generalized epilepsies as developmental diseases instead of classical channelopathies. (C) 2009 Elsevier B.V. All rights reserved. C1 [Leon, Christine; de Nijs, Laurence; Chanas, Grazyna; Grisar, Thierry; Lakaye, Bernard] Univ Liege, GIGA Neurosci, Liege, Belgium. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Epilepsy Genet Genom Labs, Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. [Delgado-Escueta, Antonio V.] VA GLAHS W Los Angeles Med Ctr, Los Angeles, CA 90073 USA. RP Grisar, T (reprint author), Univ Liege, GIGA Neurosci, Ave Hop 1, Liege, Belgium. EM tgrisar@ulg.ac.be OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU Fonds National de la Recherche Scientifique [FRSM 3.4565.03.F]; Leon Fredericq Foundation; Fonds pour la Recherche dans l'Industrie et l'Agriculture (FRIA) FX We thank the Dr. Ritsu Kamiya (University of Tokyo) for kindly providing the polyclonal anti-EFHC1 antibody used in this study. This work was supported by the Fonds National de la Recherche Scientifique (F.R.S.-FNRS; FRSM 3.4565.03.F to TG and BL) and the Leon Fredericq Foundation (to CL). CL is fellow of the Fonds pour la Recherche dans l'Industrie et l'Agriculture (FRIA). BL is a research associate at the F.R.S.-FNRS. NR 24 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 2010 VL 88 IS 2-3 BP 196 EP 207 DI 10.1016/j.eplepsyres.2009.11.009 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 568RF UT WOS:000275539500015 PM 20015616 ER PT J AU Ogunyemi, O Rojas, A Hematpour, K Rogers, D Head, C Bennett, C AF Ogunyemi, Ore Rojas, A. Hematpour, K. Rogers, D. Head, C. Bennett, C. TI Metastasis of genitourinary tumors to the head and neck region SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE Carcinoma of the prostate; Renal cell carcinoma; Transitional cell carcinoma; Genitourinary tumors ID RENAL-CELL CARCINOMA; UROGENITAL TRACT CARCINOMA; PROGNOSTIC FACTORS; PROSTATE-CANCER AB The objective of the present study is to characterize genitourinary tumors (GU) metastatic to the head and neck and to determine long-term prognoses. Using a retrospective chart review of 734 patients treated between January 1995 and May 2005 with an ICD-9 code pertaining to a metastatic head and neck cancer, we found 37 patients with primary GU tumors. There were 24 cases of prostate cancer, 10 cases of renal cell carcinoma, and 4 cases of transitional cell carcinoma. Sixteen of 24 patients (67%) with prostate cancer had a cranial metastasis while 6 of 9 (67%) patients with renal cell carcinoma had cerebral metastasis. We concluded that prolonged survival is possible in prostate cancer patients treated aggressively with radiation and chemotherapy, indicating that early detection and aggressive screening are important in these patients. C1 [Bennett, C.] Greater Los Angeles Healthcare Syst, Dept Urol, Los Angeles, CA 90073 USA. [Ogunyemi, Ore; Rojas, A.; Bennett, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hematpour, K.] Columbia Univ Coll Phys & Surg, Dept Internal Med, St Lukes Roosevelt Hosp, New York, NY 10032 USA. [Rogers, D.] Greater Los Angeles VA Med Ctr, Dept Pathol, Los Angeles, CA USA. [Head, C.] Greater Los Angeles VA Med Ctr, Dept Otolaryngol, Los Angeles, CA USA. [Bennett, C.] Greater Los Angeles VA Med Ctr, Dept Urol, Los Angeles, CA USA. RP Bennett, C (reprint author), Greater Los Angeles Healthcare Syst, Dept Urol, 11301 Wilshire Blvd 10H2, Los Angeles, CA 90073 USA. EM carol.bennett@med.va.gov FU Pfizer FX The authors declare that they have no stated conflicts of interest. Dr. Carol Bennett has a grant from Pfizer. NR 26 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD FEB PY 2010 VL 267 IS 2 BP 273 EP 279 DI 10.1007/s00405-009-1006-8 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 537HC UT WOS:000273102900018 PM 19536555 ER PT J AU Hammerness, P Geller, D Petty, C Lamb, A Bristol, E Biederman, J AF Hammerness, Paul Geller, Daniel Petty, Carter Lamb, Alexis Bristol, Elyssa Biederman, Joseph TI Does ADHD moderate the manifestation of anxiety disorders in children? SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Anxiety; ADHD; Pediatric ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; PSYCHIATRIC COMORBIDITY; METHYLPHENIDATE; ASSOCIATION; ADOLESCENTS; PREVALENCE AB The main aim of this study was to examine the moderating effects of attention deficit hyperactivity disorder (ADHD) on anxiety disorders in children. Data were analyzed from a large referred sample of children with anxiety disorder without comorbid ADHD (anxiety disorder, N = 253), anxiety disorder plus comorbid ADHD (anxiety disorder + ADHD, N = 704), and ADHD without comorbid anxiety disorder (ADHD, N = 511). Children were comprehensively assessed, including by structured diagnostic interview (K-SADS-E). Overall rates of individual anxiety disorders, as well as age of onset and severity of illness were not significantly different in the presence of comorbid ADHD. School functioning in children with anxiety disorders was negatively impacted by the presence of comorbid ADHD. Frequency of mental health treatment in children with anxiety disorders was significantly increased in the presence of comorbid ADHD. ADHD had a limited impact on the manifestation of anxiety disorder in children suggesting that ADHD and anxiety disorders are independently expressed. C1 [Hammerness, Paul; Geller, Daniel; Petty, Carter; Lamb, Alexis; Bristol, Elyssa; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Cambridge, MA 02138 USA. [Hammerness, Paul; Geller, Daniel; Petty, Carter; Lamb, Alexis; Bristol, Elyssa; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hammerness, P (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Norma Fine Fellowship in Pediatric Psychopharmacology FX Supported by the Norma Fine Fellowship in Pediatric Psychopharmacology. NR 20 TC 9 Z9 10 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD FEB PY 2010 VL 19 IS 2 BP 107 EP 112 DI 10.1007/s00787-009-0041-8 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 546KI UT WOS:000273809300002 PM 19543790 ER PT J AU Prati, F Regar, E Mintz, GS Arbustini, E Di Mario, C Jang, IK Akasaka, T Costa, M Guagliumi, G Grube, E Ozaki, Y Pinto, F Serruys, PWJ AF Prati, Francesco Regar, Evelyn Mintz, Gary S. Arbustini, Eloisa Di Mario, Carlo Jang, Ik-Kyung Akasaka, Takashi Costa, Marco Guagliumi, Giulio Grube, Eberhard Ozaki, Yukio Pinto, Fausto Serruys, Patrick W. J. CA Expert's OCT Review Document TI Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis SO EUROPEAN HEART JOURNAL LA English DT Review DE Atherosclerosis; OCT; Intravascular imaging; Angioplasty ID INTRAVASCULAR ULTRASOUND; IN-VIVO; PLAQUE CHARACTERISTICS; INTRACORONARY ULTRASOUND; FEASIBILITY; ANGIOGRAPHY; ANGIOSCOPY; CULPRIT; IVUS AB Optical coherence tomography (OCT) is a novel intravascular imaging modality, based on infrared light emission, that enables a high resolution arterial wall imaging, in the range of 10-20 microns. This feature of OCT allows the visualization of specific components of the atherosclerotic plaques. The aim of the present Expert Review Document is to address the methodology, terminology and clinical applications of OCT for qualitative and quantitative assessment of coronary arteries and atherosclerosis. C1 [Prati, Francesco] San Giovanni Hosp, I-00184 Rome, Italy. [Regar, Evelyn; Serruys, Patrick W. J.] Univ Rotterdam Hosp, Thoraxctr, Rotterdam, Netherlands. [Mintz, Gary S.] Washington Hosp Ctr, Washington, DC 20010 USA. [Arbustini, Eloisa] IRCCS Fdn Policlin San Matteo, Pavia, Italy. [Di Mario, Carlo] Royal Brompton Hosp, London SW3 6LY, England. [Di Mario, Carlo] Univ London Imperial Coll Sci Technol & Med, London, England. [Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Akasaka, Takashi] Wakayama Med Univ, Wakayama, Japan. [Costa, Marco] Med Ctr Cleveland, Cleveland, OH USA. [Guagliumi, Giulio] Spedali Riuniti, Bergamo, Italy. [Grube, Eberhard] Heart Ctr Siegburg, Siegburg, Germany. [Ozaki, Yukio] Fujita Hlth Univ, Fujita, Japan. [Pinto, Fausto] Univ Lisbon, P-1699 Lisbon, Portugal. RP Prati, F (reprint author), San Giovanni Hosp, Via Amba Aradam 8, I-00184 Rome, Italy. EM fprati@hsangiovanni.roma.it RI Pinto, Fausto/G-9363-2015; OI Pinto, Fausto/0000-0002-8034-4529; Arbustini, Eloisa/0000-0003-2948-7994 NR 37 TC 302 Z9 308 U1 2 U2 27 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 FEB PY 2010 VL 31 IS 4 BP 401 EP 415 DI 10.1093/eurheartj/ehp433 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 558ZB UT WOS:000274787100007 PM 19892716 ER PT J AU Lozner, AW Reisner, A Shear, ML Patel, S Connolly, J Shaltis, P Thomas, SH AF Lozner, Alison W. Reisner, Andrew Shear, Melissa L. Patel, Sagar Connolly, John Shaltis, Phillip Thomas, Stephen H. TI Pain severity is the key to emergency department patients' preferred frequency of pain assessment SO EUROPEAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency department; numeric rating scale; pain assessment ID ABDOMINAL-PAIN; ANALGESIA AB This study's objective was to ascertain emergency department (ED) patient preferences for pain assessment frequency. This was a prospective, convenience-sample trial of all-diagnosis adults with pain at least 3/10, in an academic ED (census 90000). Using a computer-based automated pain tracker, patients entered initial pain level and indicated how frequently they wanted pain assessed. Automated pain tracker prompted patients to update pain levels and pain assessment frequency preferences. Regression was used to assess relationships between patient factors and the endpoint 'frequency of preferred pain assessment' There was no association between initially suggested time interval (median, 15 min) and sex (P=0.455), race (P=0.976), age (P=0.391), or in-room visitors (P=0.956). Pain severity was associated with preference for more frequent pain assessment (P=0.009). ED patients' preference for pain assessment is approximately 15 min, with more frequent intervals preferred when pain is severe. European Journal of Emergency Medicine 17:30-32 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Thomas, Stephen H.] Univ Oklahoma, Dept Emergency Med, Sch Community Med, OU Schusterman Ctr, Tulsa, OK 74135 USA. [Lozner, Alison W.; Reisner, Andrew; Shear, Melissa L.; Patel, Sagar; Connolly, John; Shaltis, Phillip] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA USA. RP Thomas, SH (reprint author), Univ Oklahoma, Dept Emergency Med, Sch Community Med, OU Schusterman Ctr, 4502 E 41st St,Suite 2E14, Tulsa, OK 74135 USA. EM Stephen-Thomas@OUHSC.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0969-9546 EI 1473-5695 J9 EUR J EMERG MED JI Eur. J. Emerg. Med. PD FEB PY 2010 VL 17 IS 1 BP 30 EP 32 DI 10.1097/MEJ.0b013e32832cf724 PG 3 WC Emergency Medicine SC Emergency Medicine GA 547DZ UT WOS:000273867300010 PM 19641465 ER PT J AU van Kimmenade, RRJ Mohammed, AA Uthamalingam, S van der Meer, P Felker, GM Januzzi, JL AF van Kimmenade, Roland R. J. Mohammed, Asim A. Uthamalingam, Shanmugam van der Meer, Peter Felker, G. Michael Januzzi, James L., Jr. TI Red blood cell distribution width and 1-year mortality in acute heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Anaemia; Heart failure; Natriuretic peptides; Prognosis ID BRAIN NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT; ANEMIA; DYSPNEA; DISEASE; UTILITY; RISK; ERYTHROPOIETIN; PREDICTION; DEATH AB Red blood cell distribution width (RDW) predicts mortality in chronic heart failure (HF) and stable coronary artery disease. The prognostic value of RDW in more acute settings such as acute HF, and its relative prognostic value compared with more established measures such as N-terminal pro-brain natriuretic peptide (NT-proBNP), remains unknown. In a cohort of 205 patients with acute HF, independent predictors of RDW were identified using linear regression analysis. The association between RDW and 1-year survival in the context of other predictors was assessed using Cox's proportional hazards analysis. Red blood cell distribution width was elevated in 67 (32.7%) patients; RDW was independently associated with haematological variables such as haemoglobin (P < 0.001) as well as the use of loop diuretics (P = 0.006) and beta-blockers (P = 0.015) on presentation, but not with nutritional deficiencies, recent transfusion, or inflammatory variables. Log-transformed RDW values independently predicted mortality in multivariable Cox's proportional hazards analysis (hazards ratio, 1.03; 95% confidence interval, 1.00-1.06; P = 0.04); when stratified on the basis of RDW and NT-proBNP status, the combination provided additional prognostic information. Red blood cell distribution width is frequently elevated among patients with acute HF and does not appear to be associated with nutritional status, transfusion history, or inflammation. Red blood cell distribution width independently predicts 1-year mortality in acute HF. The value of RDW appears additive to other established prognostic variables such as NT-proBNP. C1 [van Kimmenade, Roland R. J.; Mohammed, Asim A.; Uthamalingam, Shanmugam; van der Meer, Peter; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.; Mohammed, Asim A.; Uthamalingam, Shanmugam; van der Meer, Peter; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Univ Hosp Maastricht, Maastricht, Netherlands. [van der Meer, Peter] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Felker, G. Michael] Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015 FU Interuniversity Cardiology Institute of the Netherlands (ICIN); Dennis and Marilyn Barry Fund for Cardiac Research; Netherlands Organization for Scientific Research; Balson Scholar Fund FX R.R.J.v.K. is sponsored by a research fellowship grant from the Interuniversity Cardiology Institute of the Netherlands (ICIN). A. A. M. is supported by the Dennis and Marilyn Barry Fund for Cardiac Research. P.v.d.M. is sponsored by the Netherlands Organization for Scientific Research (Rubicon Grant). J.L.J. is supported in part by the Balson Scholar Fund. NR 25 TC 111 Z9 112 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD FEB PY 2010 VL 12 IS 2 BP 129 EP 136 DI 10.1093/eurjhf/hfp179 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 547EN UT WOS:000273868800006 PM 20026456 ER PT J AU Vidan, MT Bueno, H Wang, YF Schreiner, G Ross, JS Chen, J Krumholz, HM AF Vidan, Maria T. Bueno, Hector Wang, Yongfei Schreiner, Geoffrey Ross, Joseph S. Chen, Jersey Krumholz, Harlan M. TI The relationship between systolic blood pressure on admission and mortality in older patients with heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Systolic blood pressure; Heart failure; Mortality; Prediction ID PRESERVED EJECTION FRACTION; IN-HOSPITAL MORTALITY; CLINICAL CHARACTERISTICS; RANDOMIZED-TRIAL; UNITED-STATES; RISK; HYPERTENSION; SURVIVAL; ASSOCIATION; PROGRESSION AB To determine the relationship between admission systolic blood pressure (SBP) and mortality in older patients hospitalized for heart failure (HF) and among various subgroups. We evaluated the independent association between initial SBP and 30-day and 1-year mortality, and potential interactions by age, gender, race, previous hypertension, and left ventricular dysfunction using multivariable logistic regression in the National Heart Failure Project, a database of Medicare patients > 65 years old recruited from 1998 through 2001. Among 56 942 patients, mean admission SBP was 147.0 +/- 92.3 mmHg, 15% presenting with SBP > 180 mmHg. Systolic blood pressure showed an inverse relationship with 30-day and 1-year mortality rates in all subgroups analysed. Using admission SBP of 120-149 mmHg as the reference, the adjusted odds ratios (95% confidence intervals) for 1-year mortality were 2.18 (1.77-2.69) for SBP < 90 mmHg, 1.57 (1.47-1.69) for SBP 90-119 mmHg, 0.71 (0.67-0.76) for SBP 150-179 mmHg, 0.63 (0.57-0.68) for SBP 180-209 mmHg, and 0.51 (0.44-0.59) for SBP >= 210 mmHg. Higher SBP on admission is associated with significant lower 30-day and 1-year mortality in patients hospitalized for HF. The relationship is strong, graded, independent of other clinical factors and consistent among subgroups. C1 [Vidan, Maria T.] Hosp Gen Univ Gregorio Maranon, Dept Geriatr Med, Madrid 28007, Spain. [Bueno, Hector] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid 28007, Spain. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev & Med, New York, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Wang, Yongfei; Chen, Jersey; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sch Publ Hlth, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA. [Schreiner, Geoffrey; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Vidan, MT (reprint author), Hosp Gen Univ Gregorio Maranon, Dept Geriatr Med, Dr Esquerdo 46, Madrid 28007, Spain. EM mvidan.hgugm@salud.madrid.org RI BUENO, HECTOR/I-3910-2015 OI BUENO, HECTOR/0000-0003-0277-7596 FU Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III, Spain [BA08/90012, BA08/90010]; National Institute on Aging [K08 AG032886]; American Federation of Aging Research FX M. T. V. and H. B. were supported in part by grants of the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III, Spain (BA08/90012 and BA08/90010, respectively) during their stay at the Centre for Outcomes Research and Evaluation, Yale-New Haven Hospital, where they participated in the development of this study. J.S.R. is supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. NR 29 TC 19 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD FEB PY 2010 VL 12 IS 2 BP 148 EP 155 DI 10.1093/eurjhf/hfp195 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 547EN UT WOS:000273868800008 PM 20083624 ER PT J AU Sembajwe, G Cifuentes, M Tak, SW Kriebel, D Gore, R Punnett, L AF Sembajwe, G. Cifuentes, M. Tak, S. W. Kriebel, D. Gore, R. Punnett, L. TI National income, self-reported wheezing and asthma diagnosis from the World Health Survey SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Asthma; income inequality; prevalence; wheezing; World Health Survey ID HYGIENE HYPOTHESIS; RESPIRATORY SYMPTOMS; ATOPIC ECZEMA; PREVALENCE; DISEASES; GUIDELINES; CHILDREN AB The aims of this study were to quantify and describe the variations in respiratory symptoms and diagnosis prevalence across regions of the world according to national income. In 2002 and 2003, the World Health Organization implemented the World Health Survey (WHS), which used a standardised survey instrument to compile comprehensive baseline information on health and healthcare expenditure. We analysed the WHS data to assess the global patterns of self-reported wheeze and doctor-diagnosed asthma, two commonly reported measures of respiratory health. In total there were 308,218 participants with complete records, from 64 countries. The weighted mean age of the survey population was 43 yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a U-shaped pattern with the largest prevalence reported in low- and high-income countries. The smallest prevalence was consistently found in middle-income countries. These WHS analyses have provided global prevalence estimates of wheeze and doctor-diagnosed asthma using data gathered simultaneously and consistently across six continents. These findings support the need for continued global respiratory illness surveillance for disease prevention, health policy and management. C1 [Sembajwe, G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sembajwe, G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sembajwe, G.; Cifuentes, M.; Tak, S. W.; Kriebel, D.; Gore, R.; Punnett, L.] Univ Massachusetts Lowell, Dept Work Environm, Lowell, MA USA. RP Sembajwe, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. EM grace_sembajwe@dfci.harvard.edu FU National Institute for Occupational Safety and Health (Washington, DC, USA) [GL GLO PHE 231 XD.04.Z.999.00, 200-2005-M-11506] FX This study was supported by World Health Organisation agreement No. GL GLO PHE 231 XD.04.Z.999.00 and contract No. 200-2005-M-11506 from the National Institute for Occupational Safety and Health (Washington, DC, USA). NR 51 TC 41 Z9 43 U1 2 U2 6 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD FEB PY 2010 VL 35 IS 2 BP 279 EP 286 DI 10.1183/09031936.00027509 PG 8 WC Respiratory System SC Respiratory System GA 556AW UT WOS:000274559900009 PM 19741032 ER PT J AU Casas, E Barron, C Francis, SA McCormack, JM McCarthy, KM Schneeberger, EE Lynch, RD AF Casas, Elizabeth Barron, Cory Francis, Stacy A. McCormack, Joanne M. McCarthy, Karin M. Schneeberger, Eveline E. Lynch, Robert D. TI Cholesterol efflux stimulates metalloproteinase-mediated cleavage of occludin and release of extracellular membrane particles containing its C-terminal fragments SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Tight junction; Occludin; Cholesterol; Methyl-beta-cyclodextrin ID TRANSEPITHELIAL ELECTRICAL-RESISTANCE; TYROSINE PHOSPHATASE INHIBITION; EPITHELIAL TIGHT JUNCTIONS; MDCK CELLS; CELLULAR CHOLESTEROL; LIPID RAFTS; FUNCTIONAL TARGET; PROTEIN OCCLUDIN; DEPLETION; ADAM17 AB That changes in membrane lipid composition alter the barrier function of tight junctions illustrates the importance of the interactions between tetraspan integral tight junction proteins and lipids of the plasma membrane. Application of methyl-beta-cyclodextrin to both apical and basolateral surfaces of MDCK cell monolayers for 2 h, results in an similar to 80% decrease in cell cholesterol, a fall in transepithelial electrical resistance, and a 30% reduction in cell content of occludin, with a smaller reduction in levels of claudins-2, -3, and -7. There were negligible changes in levels of actin and the two non-tight junction membrane proteins GP-135 and caveolin-1. While in untreated control cells breakdown of occludin, and probably other tight junction proteins, is mediated by intracellular proteolysis, our current data suggest an alternative pathway whereby in a cholesterol-depleted membrane, levels of tight junction proteins are decreased via direct release into the intercellular space as components of membrane-bound particles. Occludin, along with two of its degradation products and several claudins, increases in the basolateral medium after incubation with methyl-beta-cyclodextrin for 30 min. In contrast caveolin-1 is detected only in the apical medium after adding methyl-beta-cyclodextrin. Release of occludin and its proteolytic fragments continues even after removal of methyl-beta-cyclodextrin. Sedimentation and ultrastructural studies indicate that the extracellular tight junction proteins are associated with the membrane-bound particles that accumulate between adjacent cells. Disruption of the actin filament network by cytochalasin D did not diminish methyl-beta-cyclodextrin-induced release of tight junction proteins into the medium, suggesting that the mechanism underlying their formation is not actin-dependent. The 41- and 48-kDa C-terminal occludin fragments formed during cholesterol depletion result from the action of a GM6001-sensitive metalloproteinase(s) at some point in the path leading to release of the membrane particles. (C) 2009 Elsevier Inc. All rights reserved. C1 [Casas, Elizabeth; Barron, Cory; Lynch, Robert D.] Univ Massachusetts, Dept Biol Sci, Boston, MA 02125 USA. [Francis, Stacy A.; McCormack, Joanne M.; McCarthy, Karin M.; Schneeberger, Eveline E.; Lynch, Robert D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, 149 13th St,Bldg 149, Charlestown, MA 02129 USA. EM eschneeberger@partners.org FU NIH [HL25822, HL36781] FX This study was supported by NIH grants HL25822 and HL36781. NR 43 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 1 PY 2010 VL 316 IS 3 BP 353 EP 365 DI 10.1016/j.yexcr.2009.10.020 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 549YH UT WOS:000274090100005 PM 19854171 ER PT J AU Quinn, LS Anderson, BG Strait-Bodey, L Wolden-Hanson, T AF Quinn, LeBris S. Anderson, Barbara G. Strait-Bodey, Lena Wolden-Hanson, Tami TI Serum and muscle interleukin-15 levels decrease in aging mice: Correlation with declines in soluble interleukin-15 receptor alpha expression SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Aging; Cytokines; IL-15; Skeletal muscle; Sarcopenia; IL-15 receptors; Soluble IL-15 alpha receptor; Body composition ID TUMOR-BEARING RATS; SKELETAL-MUSCLE; BODY-COMPOSITION; FAT MASS; IL-15; AGE; ASSOCIATION; ADIPOCYTES; RESISTANCE; COMPLEXES AB Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15R alpha) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15R alpha (sIL-15R alpha) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15R alpha expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15R alpha gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15R alpha in determining body composition in aging mice, as a model for humans. (C) 2009 Elsevier Inc. All rights reserved. C1 [Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Amer Lake Div 151, Tacoma, WA 98493 USA. [Quinn, LeBris S.; Anderson, Barbara G.; Wolden-Hanson, Tami] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Strait-Bodey, Lena; Wolden-Hanson, Tami] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Amer Lake Div 151, Tacoma, WA 98493 USA. EM quinnL@u.washington.edu FU National Institute on Aging (LSQ) [1101AG024136] FX Supported by NIH Grant #1101AG024136 from the National Institute on Aging (LSQ), and use of resources and facilities at VA Puget Sound Health Care System. NR 36 TC 13 Z9 15 U1 0 U2 3 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 FEB PY 2010 VL 45 IS 2 BP 106 EP 112 DI 10.1016/j.exger.2009.10.012 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 561TW UT WOS:000275003100004 PM 19854259 ER PT J AU Yamuy, J Fung, SJ Xi, MC Chase, MH AF Yamuy, Jack Fung, Simon J. Xi, Mingchu Chase, Michael H. TI State-dependent control of lumbar motoneurons by the hypocretinergic system SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Brainstem; Reticular formation; Spinal cord; Neuropeptides; Narcolepsy; Presynaptic ID PONTINE RETICULAR-FORMATION; EYE-MOVEMENT SLEEP; MELANIN-CONCENTRATING HORMONE; INDUCED MOTOR INHIBITION; CAT MASSETER MOTONEURONS; AMINO-ACID ANTAGONISTS; INDUCED REM-SLEEP; ACTIVE SLEEP; BRAIN-STEM; PARADOXICAL SLEEP AB Neurons in the lateral hypothalamus (LH) that synthesize hypocretins (Hcrt-1 and Hcrt-2) are active during wakefulness and excite lumbar motoneurons. Because hypocretinergic cells also discharge during phasic periods of rapid eye movement (REM) sleep, we sought to examine their action on the activity of motoneurons during this state. Accordingly, cat lumbar motoneurons were intracellularly recorded, under alpha-chloralose anesthesia, prior to (control) and during the carbachol-induced REM sleep-like atonia (REMc). During control conditions, LH Stimulation induced excitatory postsynaptic potentials (composite EPSP) in motoneurons. In contrast, during REMc, identical LH stimulation induced inhibitory PSPs in motoneurons. We then tested the effects of LH stimulation on motoneuron responses following the stimulation of the nucleus reticularis gigantocellularis (NRGc) which is part of a brainstem-spinal cord system that controls motoneuron excitability in a state-dependent manner. LH stimulation facilitated NRGc stimulation-induced composite EPSP during control conditions whereas it enhanced NRGc stimulation-induced IPSPs during REMc. These intriguing data indicate that the LH exerts a state-dependent control of motor activity. As a first step to understand these results, we examined whether hypocretinergic synaptic mechanisms in the spinal cord were state dependent. We found that the juxtacellular application of Hcrt-1 induced motoneuron excitation during control conditions whereas motoneuron inhibition was enhanced during REMc. These data indicate that the hypocretinergic system acts on motoneurons in a state-dependent manner via spinal synaptic mechanisms. Thus, deficits in Hcrt-1 may cause the coexistence of incongruous motor signs in cataplectic patients, such as motor suppression during wakefulness and movement disorders during REM sleep. (C) 2009 Elsevier Inc. All rights reserved. C1 [Yamuy, Jack; Fung, Simon J.; Xi, Mingchu; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. RP Yamuy, J (reprint author), VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM jyamuy@ucla.edu FU USPHS [MH 43362, NS 09999, NS 23426, AGO 4307, HL 60296] FX The authors thank Oscar Ramos, Andrui Nazarian, and Matthew Fruzza for their valuable technical support and Trent Wenzel for his useful additions to the Axograph analysis package. Supported by USPHS grant nos. MH 43362, NS 09999, NS 23426, AGO 4307, and HL 60296. NR 117 TC 12 Z9 12 U1 1 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 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2010 VL 221 IS 2 BP 335 EP 345 DI 10.1016/j.expneurol.2009.11.020 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 556BD UT WOS:000274560800008 PM 19962375 ER PT J AU Abraham, JA Baldini, EH Butrynski, JE AF Abraham, John A. Baldini, Elizabeth H. Butrynski, James E. TI Management of adult soft-tissue sarcoma of the extremities and trunk SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE brachytherapy; doxorubicin; local recurrence; radiation therapy; sarcoma; soft tissue; wide resection ID LIMB-SPARING SURGERY; MALIGNANT FIBROUS HISTIOCYTOMA; PROSPECTIVE RANDOMIZED-TRIAL; RADIATION-INDUCED SARCOMA; REFRACTORY SOLID TUMORS; CORE NEEDLE-BIOPSY; PHASE-I TRIAL; PROGNOSTIC-FACTORS; LOCAL RECURRENCE; HIGH-GRADE AB Soft-tissue sarcomas are a heterogeneous group of tumors consisting of approximately 100 distinct diagnoses. Management requires a multimodality approach with the input of pathologists, surgeons, radiation oncologists, medical oncologists and radiologists. In localized disease, the primary modality of treatment is wide-resection surgery, and the use of radiation therapy has improved local control rates for high-grade tumors. Currently, most localized tumors can be managed with limb-sparing treatment, and local control rates of 80-90% can be seen with appropriate management. Improvements in classification and diagnosis of these tumors have led to the current idea that the specific histology is an important consideration when developing a treatment plan and may affect prognosis, although existing staging systems have not yet incorporated this parameter. Treatment of metastatic disease continues to be difficult, but current research focuses on clarifying molecular mechanisms of disease and identifying new potential targets for medical therapy. This review focuses on the current status of management of these tumors including a review of epidemiology, initial evaluation, and treatment including surgical, radiation, and medical aspects. C1 [Abraham, John A.; Baldini, Elizabeth H.; Butrynski, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Bone & Sarcoma Oncol, Boston, MA 02115 USA. RP Abraham, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Bone & Sarcoma Oncol, 44 Binney St, Boston, MA 02115 USA. EM jabraham1@partners.org; ebaldini@partners.org; jbutrynski@partners.org NR 144 TC 3 Z9 3 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD FEB PY 2010 VL 10 IS 2 BP 233 EP 248 DI 10.1586/ERA.09.193 PG 16 WC Oncology SC Oncology GA 557LO UT WOS:000274670800012 PM 20131999 ER PT J AU Nakao, S Maruyama, K Zandi, S Melhorn, MI Taher, M Noda, K Nusayr, E Doetschman, T Hafezi-Moghadam, A AF Nakao, Shintaro Maruyama, Kazuichi Zandi, Souska Melhorn, Mark I. Taher, Mahdi Noda, Kousuke Nusayr, Eyad Doetschman, Tom Hafezi-Moghadam, Ali TI Lymphangiogenesis and angiogenesis: concurrence and/or dependence? Studies in inbred mouse strains SO FASEB JOURNAL LA English DT Article DE cornea; conjunctiva; VEGF-A; FGF-2; VEGF-C; LYVE-1 ID FIBROBLAST-GROWTH-FACTOR; LYMPHATIC VESSELS; GENETIC-LOCI; FACTOR-C; NEOVASCULARIZATION; INFLAMMATION; HYPERPLASIA; MACROPHAGES; CORNEA; CELLS AB Genetic background significantly affects angiogenesis in mice. However, lymphangiogenic response to growth factors (GFs) in different strains has not been studied. We report constitutive expression of corneal lymphatics that extends beyond the limits of normal limbal vessels. In untreated corneas, the total number (P = 0.006), the number above blood vessels (P = 10(-8)), and the area of preexisting lymphatics (P = 0.007) were significantly higher in C57BL/6 than in BALB/c mice. Normal corneas of three other strains, the nu/nu, 129E, and Black Swiss mice, showed in most parameters intermediate phenotypes. FGF-2(-/-) mice showed significantly less preexisting lymphatics than control (P = 0.009), which suggests a role for this GF in lymphatic development. VEGF-A-induced corneal lymphangiogenic response was significantly higher in BALB/c mice (P = 0.03), but it did not differ significantly in C57BL/6 mice, when compared to PBS-implanted control. FGFR-3 expression was higher in C57BL/6 than BALB/c mice, which suggests GF-receptor heterogeneity as a possible explanation for strain-dependent differences. The heterogeneity of preexisting lymphatic vessels in the limbal area significantly correlated with the extent of corneal lymphangiogenesis (VEGF-A: r = 0.7, P = 0.01; FGF-2: r = 0.96, P = 10(-5)) in BALB/c but not in C57BL/6 mice. Removal of conjunctival lymphatics did not affect GF-induced lymphangiogenesis. This work introduces physiological expression of lymphatics without blood vessels, which indicates that angiogenesis and lymphangiogenesis, even though intricately related, may occur independently. Furthermore, we show strain-dependence of normal and GF-induced lymphangiogenesis. These differences may affect disease development in various strains.-Nakao, S., Maruyama, K., Zandi, S., Melhorn, M. I., Taher, M., Noda, K., Nusayr, E., Doetschman, T., Hafezi-Moghadam, A. Lymphangiogenesis and angiogenesis: concurrence and/or dependence? Studies in inbred mouse strains. FASEB J. 24, 504-513 (2010). www.fasebj.org C1 [Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Taher, Mahdi; Noda, Kousuke; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Taher, Mahdi; Noda, Kousuke; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Maruyama, Kazuichi] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan. [Nusayr, Eyad; Doetschman, Tom] Univ Arizona, Dept Cell Biol & Anat, Tucson, AZ USA. [Nusayr, Eyad; Doetschman, Tom] Univ Arizona, Inst BIO5, Tucson, AZ USA. RP Hafezi-Moghadam, A (reprint author), Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM ali_hafezi-moghadam@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NIH [AI050775, HL086933, HL070174]; American Health Assistance Foundation; Japan Eye Bank Association and Tear Film and Ocular Surface Society; Young Investigator Fellowship; Massachusetts Lions Eye Research Fund; Research to Prevent Blindness FX This work was supported by NIH grants AI050775 (A.H.-M.), HL086933 (Alan Cross, University of Maryland, principal investigator, and A. H.-M.), and HL070174 (T. D.), the American Health Assistance Foundation (A. H.-M.), an overseas research fellowship award from Bausch & Lomb, a fellowship award from the Japan Eye Bank Association and Tear Film and Ocular Surface Society, a Young Investigator Fellowship (to S.N. under the mentorship of A. H.-M.), the Massachusetts Lions Eye Research Fund, and Research to Prevent Blindness. The authors thank Alexander Schering and Eiichi Sekiyama for their help with the preparation of the manuscript and Dr. Patricia D'Amore for her critical view of the work and helpful suggestions. NR 29 TC 28 Z9 30 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 FEB PY 2010 VL 24 IS 2 BP 504 EP 513 DI 10.1096/fj.09-134056 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 549JS UT WOS:000274045000018 PM 19858096 ER PT J AU Xu, YZ Zhang, ZY Hu, J Stillman, IE Leopold, JA Handy, DE Loscalzo, J Stanton, RC AF Xu, Yizhen Zhang, Zhaoyun Hu, Ji Stillman, Isaac E. Leopold, Jane A. Handy, Diane E. Loscalzo, Joseph Stanton, Robert C. TI Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria SO FASEB JOURNAL LA English DT Article DE pentose phosphate pathway; inflammation; mouse kidney ID CHRONIC KIDNEY-DISEASE; ENDOTHELIAL DYSFUNCTION; DIABETES-MELLITUS; OXIDANT STRESS; NITRIC-OXIDE; ENZYME; G6PD; MUTATION; GROWTH AB Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway and the principal source of NADPH, a major cellular reductant, and is central to cell survival. Our previous work showed that diabetes and increased aldosterone are acquired forms of G6PD deficiency, leading to decreased G6PD activity and NADPH levels and damage to kidney tissue and endothelial cells. In this study, G6PD-deficient mice were studied to test the hypothesis that decreased G6PD activity per se can cause changes similar to those seen in the acquired conditions of G6PD deficiency. Results show that as compared with control mice, G6PD-deficient mice had increased oxidative stress, as manifested by decreased NADPH levels and decreased GSH levels, and increased markers of lipid peroxidation. G6PD-deficient mice had increased protein kinase C activity, increased nuclear factor-kappa B activity, and increased urinary albumin levels, all of which is similar to changes seen in diabetic mice. Changes persisted as the mice aged, as old G6PD-deficient mice (17-20 mo) had higher urine albumin levels and also had evidence for increased apoptosis in the renal cortex. These results show that decreased G6PD activity per se is sufficient to cause changes similar to those seen in diabetic mice.-Xu, Y., Zhang, Z., Hu, J., Stillman, I. E., Leopold, J. A., Handy, D. E., Loscalzo, J., Stanton, R. C. Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria. FASEB J. 24, 609-616 (2010). www.fasebj.org C1 [Xu, Yizhen; Zhang, Zhaoyun; Hu, Ji; Stanton, Robert C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Brigham & Womens Hosp,Res Div, Boston, MA 02115 USA. [Leopold, Jane A.; Handy, Diane E.; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. [Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Div Renal, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu FU National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK54380]; NIH/National Heart, Lung, and Blood Institute [R37HL61795, R01-HL58796, P01-HL81587, K02 HL081110, U54-HL70819] FX This work was supported by National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01-DK54380 to R. C. S.; NIH/National Heart, Lung, and Blood Institute grants R37HL61795, R01-HL58796, and P01-HL81587 to J. L.; and grants K02 HL081110 and U54-HL70819 to J. A. L. NR 32 TC 42 Z9 43 U1 1 U2 11 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 FEB PY 2010 VL 24 IS 2 BP 609 EP 616 DI 10.1096/fj.09-135731 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 549JS UT WOS:000274045000028 PM 19805580 ER PT J AU Johnson, EE Srikanth, CV Sandgren, A Harrington, L Trebicka, E Wang, LJ Borregaard, N Murray, M Cherayil, BJ AF Johnson, Erin E. Srikanth, Chittur V. Sandgren, Andreas Harrington, Lynne Trebicka, Estela Wang, Lijian Borregaard, Niels Murray, Megan Cherayil, Bobby J. TI Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE iron; infection; lipocalin 2; NGAL ID MEDIATED IRON ACQUISITION; ACUTE-PHASE PROTEIN; HUMAN NEUTROPHILS; LIPOCALIN; GROWTH; NGAL; HEMOCHROMATOSIS; INFECTION; HEPCIDIN; CELLS AB Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis. C1 [Srikanth, Chittur V.; Harrington, Lynne; Trebicka, Estela; Wang, Lijian; Cherayil, Bobby J.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Pediat Gastroenterol Unit, Charlestown, MA 02129 USA. [Johnson, Erin E.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Wang, Lijian] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sandgren, Andreas; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Borregaard, Niels] Univ Copenhagen, Dept Hematol, Copenhagen, Denmark. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Pediat Gastroenterol Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIH [R21 AI065619]; Milton Fund of Harvard University; Wyeth Nutrition FX The authors are grateful to Dr Michael Fischbach for providing the H9049 bacterial strain, and to Dr Marianne Wessling-Resnick for encouragement and advice. This work was supported by grants to B.J.C. from the NIH (R21 AI065619) and the Milton Fund of Harvard University. E.E.J. was supported by an NIH Roadmap Grant to Dr Marianne Wessling-Resnick and L.W. by an unrestricted grant from Wyeth Nutrition. NR 40 TC 16 Z9 16 U1 2 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD FEB PY 2010 VL 58 IS 1 BP 138 EP 145 DI 10.1111/j.1574-695X.2009.00622.x PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 543DB UT WOS:000273549200015 PM 19863663 ER PT J AU Toschi, L Cappuzzo, F AF Toschi, Luca Cappuzzo, Federico TI Clinical implications of MET gene copy number in lung cancer SO FUTURE ONCOLOGY LA English DT Review DE HGF; MET; non-small-cell lung cancer; NSCLC; tyrosine kinase inhibitors ID HEPATOCYTE GROWTH-FACTOR; SUPPRESSES TUMOR-GROWTH; FACTOR SCATTER FACTOR; FACTOR RECEPTOR GENE; C-MET; CELL-LINES; IN-VIVO; MONOCLONAL-ANTIBODIES; JUXTAMEMBRANE DOMAIN; PRIMARY RESISTANCE AB MET, the receptor for HGF, has recently been identified as a novel promising forget in several human malignancies, including non-small-cell lung cancer (NSCLC). Deregulation of the HGF/MET signaling pathway can occur via different mechanisms, including HGF and/or MET overexpression, MET gene amplification, mutations or rearrangements. While the role of MET mutations in NSCLC is not yet fully understood, MET amplification emerged as a critical event in driving cell survival, with preclinical data suggesting that MET-amplified cell lines are exquisitely sensitive to MET inhibition, True MET amplification, which has been associated with poor prognosis in different retrospective series, is a relatively uncommon event in NSCLC, occurring in 1-7% of unselected cases. Nevertheless, in highly selected cohorts of patients, such as those harboring somatic mutations of the EGF receptor (EGFR) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs), MET amplification can be observed in up to 20% of cases. Preclinical data suggested that a treatment approach including a combination of EGFR and MET TKIs could be an effective strategy in this setting and led to the clinical investigation of multiple MET TKIs in combination with erlotinib. Results from ongoing and future trials will clarify the role of MET TKIs for the treatment of NSCLC and will provide insights into the most appropriate timing for their use. C1 [Cappuzzo, Federico] Osped Livorno, I-57123 Livorno, Italy. [Toschi, Luca] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Cappuzzo, F (reprint author), Osped Livorno, Via Alfieri 36, I-57123 Livorno, Italy. EM luca_toschi@dfci.harvard.edu; cappuzzo@tim.eu.blackberry.com OI Cappuzzo, Federico/0000-0002-6295-6767 NR 71 TC 24 Z9 28 U1 0 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD FEB PY 2010 VL 6 IS 2 BP 239 EP 247 DI 10.2217/FON.09.164 PG 9 WC Oncology SC Oncology GA 561WR UT WOS:000275011300012 PM 20146583 ER PT J AU Walker, WA Sherman, P Shneider, BL Cohen, M Barnard, J AF Walker, W. Allan Sherman, Philip Shneider, Benjamin L. Cohen, Mitchell Barnard, John TI State of Research in Pediatric Gastroenterology, Hepatology, and Nutrition: 2010 and Beyond SO GASTROENTEROLOGY LA English DT Editorial Material ID SALT EXPORT PUMP; EXPERIMENTAL BILIARY ATRESIA; INFLAMMATORY-BOWEL-DISEASE; FAMILIAL INTRAHEPATIC CHOLESTASIS; FATTY LIVER-DISEASE; ANTI-IL-5 MEPOLIZUMAB THERAPY; SEVERE CROHNS-DISEASE; NONALCOHOLIC STEATOHEPATITIS; EOSINOPHILIC ESOPHAGITIS; INFLIXIMAB THERAPY C1 [Walker, W. Allan] Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Mucosal Immunol Lab, Boston, MA USA. [Sherman, Philip] Univ Toronto, Hosp Sick Children, Div Pediat Gastroenterol & Nutr, Toronto, ON M5G 1X8, Canada. [Shneider, Benjamin L.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr Pittsburgh, Pittsburgh, PA 15213 USA. [Cohen, Mitchell] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH 45267 USA. [Barnard, John] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 13th St 114-3503, Charlestown, MA 02129 USA. OI Sherman, Philip/0000-0002-4733-6690; Cohen, Mitchell/0000-0002-4412-350X NR 70 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 FEB PY 2010 VL 138 IS 2 BP 411 EP U24 DI 10.1053/j.gastro.2009.12.034 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900004 PM 20025876 ER PT J AU Mahmood, U AF Mahmood, Umar TI Optical Molecular Imaging Approaches in Colorectal Cancer SO GASTROENTEROLOGY LA English DT Editorial Material ID IN-VIVO; MICE; ENDOSCOPY; ANTIBODY C1 Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NCI NIH HHS [U01 CA143056, P50 CA127003-04, U01 CA143056-01, P50 CA127003, P50CA127003, U01CA143056] NR 12 TC 19 Z9 20 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2010 VL 138 IS 2 BP 419 EP 422 DI 10.1053/j.gastro.2009.12.014 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900006 PM 20026448 ER PT J AU Lok, AS Sterling, RK Everhart, JE Wright, EC Hoefs, JC Di Bisceglie, AM Morgan, TR Kim, HY Lee, WM Bonkovsky, HL Dienstag, JL AF Lok, Anna S. Sterling, Richard K. Everhart, James E. Wright, Elizabeth C. Hoefs, John C. Di Bisceglie, Adrian M. Morgan, Timothy R. Kim, Hae-Young Lee, William M. Bonkovsky, Herbert L. Dienstag, Jules L. CA HALT C Trial Grp TI Des-gamma-Carboxy Prothrombin and alpha-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma SO GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; VITAMIN-K ABSENCE; EARLY-DIAGNOSIS; LIVER-DISEASE; ABNORMAL PROTHROMBIN; CIRRHOTIC-PATIENTS; UNITED-STATES; RISK-FACTORS; SURVEILLANCE; TRIAL AB BACKGROUND & AIMS: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC. METHODS: Among 1031 patients randomized in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month - 12) to the time of HCC diagnosis (month 0). RESULTS: The sensitivity and specificity of DCP at month 0 was 74% and 86%, respectively, at a cutoff of 40 mAU/mL and 43% and 100%, respectively, at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month - 12, the sensitivity and specificity at the low cutoff was 43% and 94%, respectively, for DCP and 47% and 75%, respectively, for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12, but the specificity decreased to 74% and 71%, respectively. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5, and combination of tests in 5 patients. CONCLUSIONS: Biomarkers are needed to complement ultrasound in the detection of early HCC, but neither DCP nor AFP is optimal. C1 [Lok, Anna S.] Univ Michigan, Div Gastroenterol, Med Ctr, Ann Arbor, MI USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Everhart, James E.; Wright, Elizabeth C.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hoefs, John C.; Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Div Gastroenterol & Hepatol, Sch Med, St Louis, MO USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Lok, AS (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, Taubman Ctr 3912, SPC 5362, Ann Arbor, MI 48109 USA. EM aslok@umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources and National Institutes of Health FX Supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below); the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources and National Institutes of Health (grant numbers are listed below); by Eisai Co, Ltd, through a Materials Cooperative Research and Development Agreement (M-CRADA) with the National Institutes of Health for testing of des-gamma-carboxy prothrombin; and by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 39 TC 152 Z9 164 U1 3 U2 10 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 FEB PY 2010 VL 138 IS 2 BP 493 EP 502 DI 10.1053/j.gastro.2009.10.031 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900017 PM 19852963 ER PT J AU Davis, GL Alter, MJ El-Serag, H Poynard, T Jennings, LW AF Davis, Gary L. Alter, Miriam J. El-Serag, Hashem Poynard, Thierry Jennings, Linda W. TI Aging of Hepatitis C Virus (HCV)-Infected Persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression SO GASTROENTEROLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; NON-B-HEPATITIS; SUSTAINED VIROLOGICAL RESPONSE; HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; FIBROSIS PROGRESSION; FOLLOW-UP; NON-A; COMPENSATED CIRRHOSIS; CLINICAL-OUTCOMES AB BACKGROUND & AIMS: The prevalence of chronic hepatitis C (CH-C) remains high and the complications of infection are common. Our goal was to project the future prevalence of CH-C and its complications. METHODS: We developed a multicohort natural history model to overcome limitations of previous models for predicting disease outcomes and benefits of therapy. RESULTS: Prevalence of CH-C peaked in 2001 at 3.6 million. Fibrosis progression was inversely related to age at infection, so cirrhosis and its complications were most common after the age of 60 years, regardless of when infection occurred. The proportion of CH-C with cirrhosis is projected to reach 25% in 2010 and 45% in 2030, although the total number with cirrhosis will peak at 1.0 million (30.5% higher than the current level) in 2020 and then decline. Hepatic decompensation and liver cancer will continue to increase for another 10 to 13 years. Treatment of all infected patients in 2010 could reduce risk of cirrhosis, decompensation, cancer, and liver-related deaths by 16%, 42%, 31%, and 36% by 2020, given current response rates to antiviral therapy. CONCLUSIONS: Prevalence of hepatitis C cirrhosis and its complications will continue to increase through the next decade and will mostly affect those older than 60 years of age. Current treatment patterns will have little effect on these complications, but wider application of antiviral treatment and better responses with new agents could significantly reduce the impact of this disease in coming years. C1 [Davis, Gary L.; Jennings, Linda W.] Baylor Univ, Med Ctr, Div Hepatol, Dallas, TX 75246 USA. [Davis, Gary L.; Jennings, Linda W.] Baylor Reg Transplant Inst, Dallas, TX USA. Univ Texas Med Branch, Infect Dis Epidemiol Program, Galveston, TX USA. [El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [El-Serag, Hashem] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Poynard, Thierry] Univ Paris 06, Ctr Liver, AP HP, Paris, France. RP Davis, GL (reprint author), Baylor Univ, Med Ctr, Div Hepatol, 4 Roberts,3500 Gaston Ave, Dallas, TX 75246 USA. EM GaryDav@BaylorHealth.edu OI Poynard, Thierry/0000-0002-2050-640X FU Vertex Pharmaceutical Inc. FX Sponsored by an unrestricted grant from Vertex Pharmaceutical Inc. NR 67 TC 466 Z9 472 U1 5 U2 32 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 FEB PY 2010 VL 138 IS 2 BP 513 EP U141 DI 10.1053/j.gastro.2009.09.067 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900019 PM 19861128 ER PT J AU Weinberg, BM Spiegel, BMR Tomlinson, JS Farrell, JJ AF Weinberg, Benjamin M. Spiegel, Brennan M. R. Tomlinson, James S. Farrell, James J. TI Asymptomatic Pancreatic Cystic Neoplasms: Maximizing Survival and Quality of Life Using Markov-Based Clinical Nomograms SO GASTROENTEROLOGY LA English DT Article ID PAPILLARY MUCINOUS NEOPLASMS; BRANCH DUCT TYPE; PYLORUS-PRESERVING PANCREATICODUODENECTOMY; RANDOMIZED CONTROLLED-TRIAL; FINE-NEEDLE-ASPIRATION; LONG-TERM SURVIVAL; INTRADUCTAL PAPILLARY; FOLLOW-UP; SURGICAL RESECTION; WHIPPLE RESECTION AB BACKGROUND & AIMS: The natural history and management of pancreatic cysts, especially for branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), remain uncertain. We developed evidence-based nomograms to assist with clinical decision making. METHODS: We used decision analysis with Markov modeling to compare competing management strategies in a patient with a pancreatic head cyst radiographically suggestive of BD-IPMN, including the following: (1) initial pancreaticoduodenectomy (PD), (2) yearly noninvasive radiographic surveillance, (3) yearly invasive surveillance with endoscopic ultrasound, and (4) "do nothing." We derived probability estimates from a systematic literature review. The primary outcomes were overall and quality-adjusted survival. We depicted the results in a series of nomograms accounting for age, comorbidities, and cyst size. RESULTS: Initial PD was the dominant strategy to maximize overall survival for any cyst greater than 2 cm, regardless of age or comorbidities. In contrast, surveillance was the dominant strategy for any lesion less than 1 cm. However, when measuring quality-adjusted survival, the do-nothing approach maximized quality of life for all cysts less than 3 cm in patients younger than age 75. Once age exceeded 85 years, noninvasive surveillance dominated. Initial PD did not maximize quality of life in any age group or cyst size. CONCLUSIONS: Management of pancreatic cysts can be guided using novel Markov-based clinical nomograms, and depends on age, cyst size, comorbidities, and whether patients value overall survival vs quality-adjusted survival. For patients focused on overall survival, regardless of quality of life, surgery is optimal for lesions greater than 2 cm. For patients focused on quality-adjusted survival, a 3-cm threshold is more appropriate for surgery except for the extreme elderly. C1 [Spiegel, Brennan M. R.; Farrell, James J.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA 90073 USA. [Weinberg, Benjamin M.; Spiegel, Brennan M. R.; Farrell, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gastroenterol, Los Angeles, CA 90073 USA. [Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Weinberg, Benjamin M.; Spiegel, Brennan M. R.; Farrell, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. [Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90073 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90073 USA. RP Farrell, JJ (reprint author), Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu; JFarrell@mednet.ucla.edu FU Veteran's Affairs Health Services Research [RCD 03-179-2]; National Institutes of Health [2P30 DK 041301-17] FX Dr Spiegel is supported by a Veteran's Affairs Health Services Research and Development Career Development Transition Award (RCD 03-179-2), and by the CURE Digestive Disease Research Center (National Institutes of Health 2P30 DK 041301-17); Dr Farrell is supported by a National Institutes of Health K12 Career Development Award. NR 79 TC 45 Z9 46 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 FEB PY 2010 VL 138 IS 2 BP 531 EP 540 DI 10.1053/j.gastro.2009.10.001 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900021 PM 19818780 ER PT J AU Bao, Y Spiegelman, D Li, RF Giovannucci, E Fuchs, CS Michaud, DS AF Bao, Ying Spiegelman, Donna Li, Ruifeng Giovannucci, Edward Fuchs, Charles S. Michaud, Dominique S. TI History of Peptic Ulcer Disease and Pancreatic Cancer Risk in Men SO GASTROENTEROLOGY LA English DT Article ID PAST MEDICAL HISTORY; N-NITROSO COMPOUNDS; HELICOBACTER-PYLORI; GASTRIC-CANCER; CARCINOGENESIS; NITROSAMINES; TOBACCO; MODEL; INFLAMMATION; SURGERY AB BACKGROUND & AIMS: Peptic ulcer disease has been associated with an increased risk of pancreatic cancer, but findings on this topic are inconsistent. We investigated the association between pancreatic cancer and the occurrence of gastric or duodenal ulcer in a large US cohort. METHODS: We analyzed data collected from 51,529 male health professionals in a prospective cohort study. History of peptic ulcer disease was assessed at baseline in 1986 and updated biennially thereafter. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models adjusting for smoking, body mass index, diabetes, and physical activity. RESULTS: During 18 years of follow-up evaluation, we observed 274 incident pancreatic cancer cases. Compared with those with report of no peptic ulcer disease, men with gastric ulcer had an increased risk of pancreatic cancer (RR, 1.83; 95% CI, 1.13-2.97). Although the risk was highest for those with a diagnosis of gastric ulcer that was close in time to the cancer diagnosis (RR, 3.66; 95% CI, 1.45-9.24), the risk remained significantly increased 10-19 years after the gastric ulcer diagnosis (RR, 2.89; 95% CI, 1.26-6.64). In contrast, duodenal ulcer was not associated with pancreatic cancer risk (RR, 1.15; 95% CI, 0.78-1.71). CONCLUSIONS: Gastric ulcer increases the risk of pancreatic cancer, whereas there does not appear to be an association between duodenal ulcers and pancreatic cancer. C1 [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Bao, Ying; Spiegelman, Donna; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Bao, Ying; Spiegelman, Donna; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michaud, DS (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM d.michaud@imperial.ac.uk RI Michaud, Dominique/I-5231-2014 FU National Cancer Institute, National Institutes of Health, Bethesda, MD [CA124908] FX This study was supported by grants from the National Cancer Institute, National Institutes of Health, Bethesda, MD (grant number CA124908). NR 42 TC 12 Z9 12 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 FEB PY 2010 VL 138 IS 2 BP 541 EP 549 DI 10.1053/j.gastro.2009.09.059 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 552OB UT WOS:000274300900022 PM 19818786 ER PT J AU Suter, MJ Jillella, PA Vakoc, BJ Halpern, EF Mino-Kenudson, M Lauwers, GY Bouma, BE Nishioka, NS Tearney, GJ AF Suter, Melissa J. Jillella, Priyanka A. Vakoc, Benjamin J. Halpern, Elkan F. Mino-Kenudson, Mari Lauwers, Gregory Y. Bouma, Brett E. Nishioka, Norman S. Tearney, Guillermo J. TI Image-guided biopsy in the esophagus through comprehensive optical frequency domain imaging and laser marking: a study in living swine SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COHERENCE TOMOGRAPHY; INTESTINAL METAPLASIA; BARRETTS-ESOPHAGUS; MICROSCOPY; DYSPLASIA AB Background: Random biopsy esophageal Surveillance can be subject to sampling errors, resulting in diagnostic uncertainty Optical frequency domain imaging (OFDI) is a high-speed, 3-dimensional endoscopic microscopy technique. When deployed through a balloon-centering catheter, OFDI can automatically image the entire distal esophagus (6.0 cm length) in approximately 2 minutes. Objective: To test a new platform for guided biopsy that allows the operator to select target regions of interest on an OFDI dataset, and then use a laser to mark the esophagus at corresponding locations. The specific goals include determining the optimal laser Parameters, testing the accuracy of the laser marking process, evaluating the endoscopic visibility of the laser marks, and assessing the amount of mucosal damage produced by the laser. Design: Experimental study conducted in 5 swine in vivo. Setting: Massachusetts General Hospital. Main Outcome Measurements: Success rate, including endoscopic visibility of laser marks and accuracy of the laser marking process for selected target sites, and extent of the thermal damage caused by the laser marks. Results: All of the laser-induced marks were visible by endoscopy. Target locations were correctly marked with a success rate of 97.07% (95% confidence interval, 89.8%-99.7%). Thermal damage was limited to the superficial layers of the mucosa and was observed to partially heal within 2 days. Limitations: An animal study with artificially placed targets to Simulate pathology. Conclusions: The study demonstrates that laser marking of esophageal sites identified in comprehensive OFDI datasets is feasible and can be performed with sufficient accuracy, precision, and visibility to guide biopsy in vivo. (Gastrointest Endosc 2010;71:346-53.) C1 [Mino-Kenudson, Mari; Lauwers, Gregory Y.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Suter, Melissa J.; Jillella, Priyanka A.; Vakoc, Benjamin J.; Bouma, Brett E.; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.; Jillella, Priyanka A.; Vakoc, Benjamin J.; Bouma, Brett E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Nishioka, Norman S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 40 Blossom St,BAR 703, Boston, MA 02114 USA. EM msuter@partners.org FU National Institutes of Health [R01CA103769, K99CA134920]; Center for Integration of Medicine and Innovative Technology FX This work was Supported by the National Institutes of Health (grant nos. R01CA103769 and K99CA134920) and by the Center for Integration of Medicine and Innovative Technology (development of the imaging platform). The authors would like to thank William Puricelli, Joseph -Gardecki, and Alexander Chau for their assistance in this study NR 12 TC 25 Z9 25 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2010 VL 71 IS 2 BP 346 EP 353 DI 10.1016/j.gie.2009.07.007 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 558VT UT WOS:000274777200022 PM 19879573 ER PT J AU Chan, ED Iseman, MD AF Chan, Edward D. Iseman, Michael D. TI Slender, Older Women Appear to Be More Susceptible to Nontuberculous Mycobacterial Lung Disease SO GENDER MEDICINE LA English DT Editorial Material DE nontuberculous mycobacteria; leptin; estrogen; fat ID GROWTH-FACTOR-BETA; RAPIDLY GROWING MYCOBACTERIA; INTERFERON-GAMMA PRODUCTION; NECROSIS-FACTOR-ALPHA; AVIUM COMPLEX; PULMONARY TUBERCULOSIS; CYTOKINE PRODUCTION; TNF-ALPHA; TGF-BETA; MACROPHAGE APOPTOSIS AB Background: Nontuberculous mycobacteria (NTM) are environmental microbes that are associated with a variety of human diseases, particularly chronic lung infections. Over the past several decades, NTM lung disease has been increasingly seen in postmenopausal women with slender body habitus. Objective: This article reviewed the clinical and experimental evidence that supports the observation that thin older women (aged 50-80 years) are predisposed to NTM lung disease. We posited 3 potential pathways for this predisposition: relative estrogen deficiency, abnormal levels of adipokines that alter immune responses, and abnormal expression of transforming growth factor-beta (TGF-beta) related to fibrillin anomalies similar to Marfan syndrome (MFS). Methods: Using the PubMed database, a literature search was performed (all publications up to July 2009) by pairing the key phrase nontuberculous mycobacteria with weight, malnutrition, female gender, body habitus, leptin, adipokines, estrogen, menopause, postmenopausal, or body mass index. Non-English-language articles were included if their abstracts were in English. Relevant articles were also identified from the abstracts. Results: Published case reports and series indicate that in the past 20 years, NTM lung disease has been recognized in disproportionately increased numbers in postmenopausal women. Among these patients, slender body habitus and thoracic cage abnormalities, such as pectus excavatum and scoliosis, are commonly described. Notably, no long-term prospective clinical studies exist to corroborate that low weight is an independent risk factor for NTM lung disease. However, based on the findings of a limited number of experimental studies, we hypothesize that decreased leptin, increased adiponectin, and/or decreased estrogen in older women with slender body habitus may account for their increased susceptibility to NTM infections. We further speculate that in some patients with features mindful of MFS (slender, scoliosis, pectus excavatum, or mitral valve prolapse), there may be anomalies of fibrillin, similar to MFS, that lead to the expression of the immunosuppressive cytokine TGF-beta, further increasing their susceptibility to NTM. Conclusions: It is likely that both sufficient environmental exposure and host susceptibility are required for the establishment of NTM lung disease. The observation that NTM lung infections are more common in slender, older women without any overt immune defects suggests that abnormal expression of adipokines, sex hormones, and/or TGF-beta may play an important role in their susceptibility. (Gend Med. 2010;7:5-18) (C) 2010 Excerpta Medica Inc. C1 [Chan, Edward D.; Iseman, Michael D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Chan, Edward D.] Natl Jewish Hlth, Cell Biol Program, Denver, CO 80206 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.; Iseman, Michael D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Chan, Edward D.; Iseman, Michael D.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, K720 Goodman Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 74 TC 25 Z9 25 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1550-8579 J9 GENDER MED JI Gend. Med. PD FEB PY 2010 VL 7 IS 1 BP 5 EP 18 DI 10.1016/j.genm.2010.01.005 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 567VS UT WOS:000275475600003 PM 20189150 ER PT J AU Brooks, WW Shen, SS Conrad, CH Goldstein, RH Bing, OHL AF Brooks, Wesley W. Shen, Steven S. Conrad, Chester H. Goldstein, Ronald H. Bing, Oscar H. L. TI Transition from compensated hypertrophy to systolic heart failure in the spontaneously hypertensive rat: Structure, function, and transcript analysis SO GENOMICS LA English DT Article DE Heart failure; Hypertension; Cardiac hypertrophy; Gene expression microarray ID CARDIAC GENE-EXPRESSION; CONVERTING ENZYME-INHIBITION; LEFT-VENTRICULAR HYPERTROPHY; TUMOR-NECROSIS-FACTOR; UP-REGULATION; MYOCARDIAL FIBROSIS; MICROARRAY ANALYSIS; FAILING MYOCARDIUM; DOWN-REGULATION; PROFILES AB Gene expression, determined by micro-array analysis, and left ventricular (LV) remodeling associated with the transition to systolic heart failure (HF) were examined in the spontaneously hypertensive rat (SHR). By combining transcript and gene set enrichment analysis (GSEA) of the LV with assessment of function and structure in age-matched SHR with and without HF, we aimed to better understand the molecular events underlying the onset of hypertensive HF. Failing hearts demonstrated depressed LV ejection fraction, systolic blood pressure, and LV papillary muscle force while LV end-diastolic and systolic volume and ventricular mass increased. 1431 transcripts were differentially expressed between failing and non-failing animals. GSEA identified multiple enriched gene sets, including those involving inflammation, oxidative stress, cell degradation and cell death, as well as TGF-beta and insulin signaling pathways. Our findings support the concept that these pathways and mechanisms may contribute to deterioration of cardiac function and remodeling associated with hypertensive HF. Published by Elsevier Inc. C1 [Brooks, Wesley W.; Conrad, Chester H.; Goldstein, Ronald H.; Bing, Oscar H. L.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Brooks, Wesley W.; Conrad, Chester H.; Goldstein, Ronald H.; Bing, Oscar H. L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Shen, Steven S.] Boston Univ, Sch Med, Clin & Translat Sci Inst, Boston, MA 02118 USA. RP Brooks, WW (reprint author), VA Boston Hlth Care Syst 151, Res Bldg R-127,150 S Huntington Ave, Boston, MA 02130 USA. EM wesley.brooks@va.gov OI Shen, Steven/0000-0001-7725-1260 FU Department of Veterans Affairs FX This work was supported by Medical Research Funds provided to WWB from the Department of Veterans Affairs. We are particularly grateful to Dr. Marc Lenburg of the Genomics Department at Boston University School of Medicine for his help in carrying out the data acquisition and statistical analysis of the Affymetrix GeneChip data. NR 45 TC 14 Z9 17 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 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 2010 VL 95 IS 2 BP 84 EP 92 DI 10.1016/j.ygeno.2009.12.002 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 557MR UT WOS:000274673800002 PM 20006699 ER PT J AU Roche, MR Rudd, PJ Krasner, CN Matulonis, UA Berlin, ST Lee, H Silver, M Tran, CD Seiden, MV Penson, RT AF Roche, Maria R. Rudd, Pandora J. Krasner, Carolyn N. Matulonis, Ursula A. Berlin, Suzanne T. Lee, Hang Silver, Michael Tran, Chau D. Seiden, Michael V. Penson, Richard T. TI Phase II trial of GM-CSF in women with asymptomatic recurrent mullerian tumors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Immunotherapy ID COLONY-STIMULATING FACTOR; AUGMENTS ANTITUMOR IMMUNITY; EPITHELIAL OVARIAN-CANCER; PROSTATE-CANCER; T-CELLS; VACCINATION; CARCINOMA; PEPTIDE; MELANOMA; SURVIVAL AB Objective. GM-CSF is a recombinant human cytokine, which promotes the proliferation and differentiation of granulocytes and monocytes, and is associated with anti-tumor activity. The primary objective was to define the median time to treatment termination (M) with women With relapsed ovarian cancer treated with single agent GM-CSF delivered Subcutaneously (SC). Patients and methods. Open label phase II study in asymptomatic patients with recurrent mullerian malignancy Without all indication for immediate systemic chemotherapy. In the first cohort of 35 women, GM-CSF 250 mu g/m(2) was administered SC on days 1-14 of a 28-day cycle, the second cohort received Continuous GM-CSF 150 mu g/m(2) given with dose escalation. Results. Seventy-two women were enrolled. Best overall response included one complete response, and 20 patients with stable disease (23%), 4 of whom had stable disease for >6 months. Median TTT was 78 days. Toxicity in both cohorts was generally mild; however, four patients experienced excessive toxicity and withdrew consent. In the first Cohort, CA-125 dropped in 70% of women from their baseline on study value (median change -23%, range -48 to + 116%) after 14 days of GM-CSF. The magnitude of CA-125 drop during the first 2 weeks of therapy also showed a positive inverse Correlation with day 15 white cell count for the whole group (p = 0.038). Conclusion. GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT is modest, a Subset of women had prolonged stable disease, (C) 2009 Elsevier Inc. All rights reserved. C1 [Penson, Richard T.] Massachusetts Gen Hosp, Div Hematol Oncol, Dana Farber Harvard Canc Ctr, DF HCC Gynecol Oncol Res Grp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dana Farber Harvard Canc Ctr, DF HCC Gynecol Oncol Res Grp, Yawkey 9-064,32 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org FU Berlex Labs (Bayer HealthCare Pharmaceuticals) FX The study was supported by an investigator-initiated grant from Berlex Labs (Bayer HealthCare Pharmaceuticals). NR 23 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2010 VL 116 IS 2 SI SI BP 168 EP 172 DI 10.1016/j.ygyno.2009.10.075 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 555IV UT WOS:000274504200004 PM 19922985 ER PT J AU Minig, L Trimble, EL Birrer, MJ Kim, KY Takebe, N Abrams, JS AF Minig, Lucas Trimble, Edward L. Birrer, Michael J. Kim, Kelly Y. Takebe, Naoko Abrams, Jeffrey S. TI NIH and NCI support for development of novel therapeutics in gynecologic cancer: A user's guide SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Novel therapeutics; NIH and NCI resources; Grants AB The development of novel therapeutics is a lengthy and often tortuous process. it frequently spans the identification of new targets, preclinical validation, discovery and refinement of novel therapies, safety studies. phase 0, 1, 2, and 3 trials, and reverse translation. NIH and NCI provide via web sites a variety of resources and research tools of great value to investigators. NCI also provides tissue resources useful for discovery and validation, as well as extensive Support for preclinical drug development. The NCI's effective partnership with industry and academia, as well as the ongoing NCI-supported clinical trials network, facilitates clinical development of novel therapeutics. Specialized NCI programs focused on cancer imaging, radiation research, and complementary and alternative medicine, also assist the development of novel agents. Finally, the NIH and the NCI sponsor a variety of grant mechanisms, Supporting institutions, consortia, and individuals, which investigators seeking to develop novel therapeutics should make themselves familiar. Published by Elsevier Inc. C1 [Minig, Lucas; Trimble, Edward L.; Birrer, Michael J.; Kim, Kelly Y.; Takebe, Naoko; Abrams, Jeffrey S.] NCI, Bethesda, MD 20892 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trimble, EL (reprint author), NCI, 6130 Execut Blvd,Suite 7025, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2010 VL 116 IS 2 SI SI BP 177 EP 180 DI 10.1016/j.ygyno.2009.10.046 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 555IV UT WOS:000274504200006 PM 19889449 ER PT J AU Ilyas, AM Jupiter, JB AF Ilyas, Asif M. Jupiter, Jesse B. TI Distal Radius Fractures-Classification of Treatment and Indications for Surgery SO HAND CLINICS LA English DT Article DE Fracture; Distal radius; Classification ID COLLES FRACTURES; YOUNG-ADULTS; INTRAARTICULAR FRACTURES; INTERNAL-FIXATION; JOINT MECHANICS; OPEN REDUCTION; INSTABILITY; PREDICTION; DEFORMITY; END AB Distal radius fractures are common injuries. Multiple classification systems have highlighted the evolution of the understanding of distal radius fractures. Understanding the classifications of distal radius fractures is important in identifying the important aspects that affect their outcome. Surgical indications of distal radius fractures can be divided into the following categories: patient factors, fracture reduction, fracture stability, and the presence of associated injuries. C1 [Ilyas, Asif M.; Jupiter, Jesse B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 41 TC 5 Z9 7 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD FEB PY 2010 VL 26 IS 1 BP 37 EP 42 DI 10.1016/j.hcl.2009.08.003 PG 6 WC Orthopedics SC Orthopedics GA 621MZ UT WOS:000279584300004 PM 20006242 ER PT J AU Blaya, JA Fraser, HSF Holt, B AF Blaya, Joaquin A. Fraser, Hamish S. F. Holt, Brian TI E-Health Technologies Show Promise In Developing Countries SO HEALTH AFFAIRS LA English DT Article ID PHYSICIAN ORDER ENTRY; INFORMATION-SYSTEMS; PRIMARY-CARE; FOLLOW-UP; TELEMEDICINE; IMPACT; TUBERCULOSIS; FAILURE; SUCCESS; QUALITY AB Is there any evidence that e-health-using information technology to manage patient care-can have a positive impact in developing countries? Our systematic review of evaluations of e-health implementations in developing countries found that systems that improve communication between institutions, assist in ordering and managing medications, and help monitor and detect patients who might abandon care show promise. Evaluations of personal digital assistants and mobile devices convincingly demonstrate that such devices can be very effective in improving data collection time and quality. Donors and funders should require and sponsor outside evaluations to ensure that future e-health investments are well-targeted. C1 [Fraser, Hamish S. F.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Fraser, Hamish S. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Holt, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jblaya@hms.harvard.edu RI Fraser, Hamish/E-3773-2013 FU Rockefeller Foundation FX An initial version of this paper was requested by the Rockefeller Foundation for the Making the eHealth Connection conference held in Bellagio, Italy, in July 2008. This paper was funded by the Rockefeller Foundation. Joaquin A. Blaya is cofounder of eHealth Systems, a Chilean company that provides health informatics consulting and technology in Latin America. The authors acknowledge those who took the time to provide additional information: Holly Ladd and Berhane Gebru from AED-Satellife, Libby Levison, Heather Zornetzer, Veronica Rojas, Adesina Iluyemi, Mauricio Soto, Waldo Ortega, Chris Bailey, Patrick Whitaker, Gerry Douglas, Natasha Kanagat, Steve Yoon, Zach Landis Lewis, Joel Selanikio, and Neal Lesh. Finally, the authors thank Claire Mack for her invaluable editing. NR 39 TC 107 Z9 112 U1 7 U2 35 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD FEB PY 2010 VL 29 IS 2 BP 244 EP 251 DI 10.1377/hlthaff.2009.0894 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 550RN UT WOS:000274146400005 PM 20348068 ER PT J AU Goldman, DP Jena, AB Lakdawalla, DN Malin, JL Malkin, JD Sun, E AF Goldman, Dana P. Jena, Anupam B. Lakdawalla, Darius N. Malin, Jennifer L. Malkin, Jesse D. Sun, Eric TI The Value of Specialty Oncology Drugs SO HEALTH SERVICES RESEARCH LA English DT Article DE Willingness to pay; economic analysis; cost-benefit analysis; oncology ID COST-EFFECTIVENESS; BREAST-CANCER; PRICE; LIFE; DESIGN; HEALTH; CLAIMS AB Objective To estimate patients' elasticity of demand, willingness to pay, and consumer surplus for five high-cost specialty medications treating metastatic disease or hematologic malignancies. Data Source/Study Setting Claims data from 71 private health plans from 1997 to 2005. Study Design This is a revealed preference analysis of the demand for specialty drugs among cancer patients. We exploit differences in plan generosity to examine how utilization of specialty oncology drugs varies with patient out-of-pocket costs. Data Collection/Extraction Methods We extracted key variables from administrative health insurance claims records. Principal Findings A 25 percent reduction in out-of-pocket costs leads to a 5 percent increase in the probability that a patient initiates specialty cancer drug therapy. Among patients who initiate, a 25 percent reduction in out-of-pocket costs reduces the number of treatments (claims) by 1-3 percent, depending on the drug. On average, the value of these drugs to patients who use them is about four times the total cost paid by the patient and his or her insurer, although this ratio may be lower for oral specialty therapies. Conclusions The decision to initiate therapy with specialty oncology drugs is responsive to price, but not highly so. Among patients who initiate therapy, the amount of treatment is equally responsive. The drugs we examine are highly valued by patients in excess of their total costs, although oral agents warrant further scrutiny as copayments increase. C1 [Goldman, Dana P.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Sch Pharm, Los Angeles, CA 90089 USA. [Goldman, Dana P.; Lakdawalla, Darius N.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Sch Policy Planning & Dev, Los Angeles, CA 90089 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Malin, Jennifer L.] Greater Los Angeles, Dept Vet Affairs, Los Angeles, CA USA. [Malkin, Jesse D.] RAND Corp, Santa Monica, CA USA. RP Goldman, DP (reprint author), Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Sch Pharm, Ralph & Goldy Lewis Hall 214, Los Angeles, CA 90089 USA. EM dpgoldma@sppd.usc.edu RI Lakdawalla, Darius/B-4409-2011; OI Lakdawalla, Darius/0000-0001-5934-8042 FU Amgen Incorporated and the Bing Center for Health Economics at RAND FX Joint Acknowledgment/Disclosure Statement: This research was sponsored by Amgen Incorporated and the Bing Center for Health Economics at RAND. The opinions expressed here are solely those of the authors. Disclosures: None. Disclaimers: None. NR 27 TC 26 Z9 26 U1 1 U2 3 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 FEB PY 2010 VL 45 IS 1 BP 115 EP 132 DI 10.1111/j.1475-6773.2009.01059.x PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 541YC UT WOS:000273456400008 PM 19878344 ER PT J AU Rose, DE Tisnado, DM Malin, JL Tao, ML Maggard, MA Adams, J Ganz, PA Kahn, KL AF Rose, Danielle E. Tisnado, Diana M. Malin, Jennifer L. Tao, May L. Maggard, Melinda A. Adams, John Ganz, Patricia A. Kahn, Katherine L. TI Use of Interpreters by Physicians Treating Limited English Proficient Women with Breast Cancer: Results from the Provider Survey of the Los Angeles Women's Health Study SO HEALTH SERVICES RESEARCH LA English DT Article DE Physician survey; limited English proficient patients; interpreters; breast cancer care ID QUALITY-OF-CARE; LANGUAGE BARRIERS; UNITED-STATES; PATIENT CHARACTERISTICS; MEDICAL INTERPRETATION; SERVICES; IMPACT; COMMUNICATION; SATISFACTION; ACCESS AB Objective Little is known about how cancer physicians communicate with limited English proficient (LEP) patients. We studied physician-reported use and availability of interpreters. Data Sources A 2004 survey was fielded among physicians identified by a population-based sample of breast cancer patients. Three hundred and forty-eight physicians completed mailed surveys (response rate: 77 percent) regarding the structure and organization of care. Study Design and Settings We used logistic regression to analyze use and availability of interpreters. Principal Findings Most physicians reported treating LEP patients. Among physicians using interpreters within the last 12 months, 42 percent reported using trained medical interpreters, 21 percent telephone interpreter services, and 75 percent reported using untrained interpreters to communicate with LEP patients. Only one-third of physicians reported good availability of trained medical interpreters or telephone interpreter services when needed. Compared with HMO physicians, physicians in solo practice and single-specialty medical groups were less likely to report using trained medical interpreters or telephone interpreter services, and they were less likely to report good availability of these services. Conclusions There were important practice setting differences predicting use and availability of trained medical interpreters and telephone interpretation services. These findings may have troubling implications for effective physician-patient communication critically needed during cancer treatment. C1 [Rose, Danielle E.] VA Greater Los Angeles Healthcare Syst, VAHSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. [Tisnado, Diana M.; Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Tao, May L.] E Bay Partners Canc Care, Antioch, CA USA. [Maggard, Melinda A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Canc Prevent & Control Res,Sch Publ Hlth, Los Angeles, CA 90095 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Adams, John; Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. RP Rose, DE (reprint author), VA Greater Los Angeles Healthcare Syst, VAHSR&D Ctr Study Healthcare Provider Behav, 16111 Plummer St 152, Sepulveda, CA 91343 USA. EM droseash@gmail.com FU UCLA Cancer Education and Career Development Program; National Cancer Institute [R25 CA087949]; U.S. Department of Defense Breast Cancer Research Program Postdoctoral [DAMD17-03-1-0328]; University of California Los Angeles Resource Center for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) NIH/NIA [P30-AG021684]; California Breast Cancer Research [7PB-0126S]; National Cancer Institute and the Agency for Health Care Research and Quality [1-R01-CA81338-01A1] FX Joint Acknowledgment/Disclosure Statement: Dr. Rose received support from the UCLA Cancer Education and Career Development Program, National Cancer Institute grant R25 CA087949. Dr. Tisnado received support from a U.S. Department of Defense Breast Cancer Research Program Postdoctoral Award DAMD17-03-1-0328 and The University of California Los Angeles Resource Center for Minority Aging Research/Center for Health Improvement of Minority Elderly (RCMAR/CHIME) NIH/NIA grant P30-AG021684. This research was funded by the California Breast Cancer Research program grant 7PB-0126S and the National Cancer Institute and the Agency for Health Care Research and Quality grant 1-R01-CA81338-01A1. We thank the two anonymous referees for suggestions that significantly strengthened the analysis. Disclosure: None. Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. NR 53 TC 7 Z9 7 U1 3 U2 8 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 FEB PY 2010 VL 45 IS 1 BP 172 EP 194 DI 10.1111/j.1475-6773.2009.01057.x PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 541YC UT WOS:000273456400011 PM 19878346 ER PT J AU Larsen, E Liberman, MC AF Larsen, Erik Liberman, M. Charles TI Contralateral cochlear effects of ipsilateral damage: No evidence for interaural coupling SO HEARING RESEARCH LA English DT Article DE Hearing loss; Feedback; Acoustic injury ID CROSSED OLIVOCOCHLEAR BUNDLE; HEARING-LOSS; LOUD SOUND; EFFERENT INNERVATION; NEURONS; NOISE; EAR; REFLEX; STIMULATION; SENSITIVITY AB Lesion studies of the olivocochlear efferents have suggested that feedback via this neuronal pathway normally maintains an appropriate binaural balance in excitability of the two cochlear nerves (Darrow et al., 2006). If true, a decrease in cochlear nerve output from one ear, due to conductive or sensorineural hearing loss, should change cochlear nerve response in the opposite ear via modulation in olivocochlear feedback. To investigate this putative efferent-mediated interaural coupling, we measured cochlear responses repeatedly from both ears in groups of mice for several weeks before, and for up to 5 weeks after, a unilateral manipulation causing either conductive or sensorineural hearing loss. Response measures included amplitude vs. level functions for distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs), evoked at 7 log-spaced frequencies. Ipsilateral manipulations included either tympanic membrane removal or an acoustic overstimulation designed to produce a reversible or irreversible threshold shift over a restricted frequency range. None of these ipsilateral manipulations produced systematic changes in contralateral cochlear responses, either at threshold or suprathreshold levels, either in ABRs or DPOAEs. Thus, we find no evidence for compensatory contralateral changes following ipsilateral hearing loss. We did, however, find evidence for age-related increases in DPOAE amplitudes as animals mature from 6 to 12 weeks and evidence for a slow apical spread of noise-induced threshold shifts, which continues for several days post-exposure. (C) 2009 Elsevier B.V. All rights reserved. C1 [Larsen, Erik; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Larsen, Erik; Liberman, M. Charles] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02215 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu FU NIH [R01 DC00188, P30 DC005209] FX This work was supported by NIH Grants R01 DC00188 and P30 DC005209. E. Larsen was partly supported by NIH Training Grant T32 DC00038. This paper is based on a thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Speech and Hearing Bioscience and Technology Program of the Harvard-MIT Division of Health Sciences and Technology in September, 2008. NR 30 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD FEB PY 2010 VL 260 IS 1-2 BP 70 EP 80 DI 10.1016/j.heares.2009.11.011 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 559RR UT WOS:000274844400008 PM 19944141 ER PT J AU Donaldson, DM Shah, A Heist, EK Barrett, CD Holmvang, G Abbara, S Ruskin, J Mansour, M AF Donaldson, David M. Shah, Amar Heist, E. Kevin Barrett, Conor D. Holmvang, Godtfred Abbara, Suhny Ruskin, Jeremy Mansour, Moussa TI Relevance of imaging structures adjacent to the left atrium during catheter ablation for atrial fibrillation SO HEART RHYTHM LA English DT Review DE Atrial fibrillation; Left atrial mapping; Computed tomography; Magnetic resonance imaging; Transesophageal echocardiography; Ablation; Imaging ID SUPERIOR VENA-CAVA; RADIOFREQUENCY ABLATION; COMPUTED-TOMOGRAPHY; PULMONARY VEINS; ESOPHAGUS; ANATOMY; FISTULA; AORTA C1 [Donaldson, David M.; Heist, E. Kevin; Barrett, Conor D.; Holmvang, Godtfred; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Shah, Amar; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM mmansour@partners.org NR 22 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2010 VL 7 IS 2 BP 269 EP 275 DI 10.1016/j.hrthm.2009.09.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 576ZQ UT WOS:000276189400025 PM 19939740 ER PT J AU Everhart, JE Wright, EC Goodman, ZD Dienstag, JL Hoefs, JC Kleiner, DE Ghany, MG Mills, AS Nash, SR Govindarajan, S Rogers, TE Greenson, JK Brunt, EM Bonkovsky, HL Morishima, C Litman, HJ AF Everhart, James E. Wright, Elizabeth C. Goodman, Zachary D. Dienstag, Jules L. Hoefs, John C. Kleiner, David E. Ghany, Marc G. Mills, A. Scott Nash, S. Russell Govindarajan, Sugantha Rogers, Thomas E. Greenson, Joel K. Brunt, Elizabeth M. Bonkovsky, Herbert L. Morishima, Chihiro Litman, Heather J. CA HALT-C Trial Grp TI Prognostic Value of Ishak Fibrosis Stage: Findings from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial SO HEPATOLOGY LA English DT Article ID PERCUTANEOUS LIVER-BIOPSY; NATURAL-HISTORY; PROGRESSION; CLASSIFICATION; REVERSAL; THERAPY AB Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0 = no fibrosis to 6 = cirrhosis). Biopsy fiagmentation and length as well as number of portal tracts were recorded. We compared rates of prespecified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages. Of 1050 biopsy specimens, 25% were fragmented, 63% longer than 1.5 cm) 69% larger than 10 mm(2), and 75% had 10 or more portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (P < 0.0001). The 6-year cumulative incidence of first clinical outcome was 5.6% for stage 2, 16.1% for stage 3, 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6. Among nonfragmented biopsy specimens, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsy specimens because of high rates of outcomes for patients with noncirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome. Conclusion: Ishak fibrosis stage predicts clinical outcomes, need for liver transplantation, and liver-related death in patients with chronic hepatitis C. Patients with fragmented biopsy specimens with low Ishak stage may be understaged histologically. (HEPATOLOGY 2010;51:585-594.) C1 [Everhart, James E.] NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Div Hepat Pathol, Washington, DC 20306 USA. [Goodman, Zachary D.] Vet Adm, Special Reference Lab Pathol, Washington, DC USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Dept Med, Sch Med, Boston, MA USA. [Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mills, A. Scott] Virginia Commonwealth Univ, Med Ctr, Dept Pathol, Richmond, VA USA. [Nash, S. Russell] Colorado GI Pathol, Centennial, CO USA. [Govindarajan, Sugantha] Univ So Calif, Dept Pathol, Rancho Los Amigos Med Ctr, Doumey, CA USA. [Rogers, Thomas E.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Greenson, Joel K.] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA. [Brunt, Elizabeth M.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Litman, Heather J.] New England Res Inst, Watertown, MA 02172 USA. RP Everhart, JE (reprint author), NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, 2 Democracy Plaza,Room 655,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM JE17G@nih.gov OI Kleiner, David/0000-0003-3442-4453 FU National Institute of Diabetes and Digestive and Kidney Diseases; national Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources, National Institutes of Health FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below) Additional support was provided by the national Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Center for Research Resources or the National Institutes of Health Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 25 TC 40 Z9 41 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2010 VL 51 IS 2 BP 585 EP 594 DI 10.1002/hep.23315 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 550ME UT WOS:000274131200028 PM 20101752 ER PT J AU Justice, AC McGinnis, KA Skanderson, M Chang, CC Gibert, CL Goetz, MB Rimland, D Rodriguez-Barradas, MC Oursler, KK Brown, ST Braithwaite, RS May, M Covinsky, KE Roberts, MS Fultz, SL Bryant, KJ AF Justice, A. C. McGinnis, K. A. Skanderson, M. Chang, C. C. Gibert, C. L. Goetz, M. B. Rimland, D. Rodriguez-Barradas, M. C. Oursler, K. K. Brown, S. T. Braithwaite, R. S. May, M. Covinsky, K. E. Roberts, M. S. Fultz, S. L. Bryant, K. J. CA VACS Project Team TI Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers SO HIV MEDICINE LA English DT Article DE anaemia; CD4 cell count; hepatitis C coinfection; hepatology; injecting drug use; outcomes; renal; kidney; risk groups; viral load ID ACTIVE ANTIRETROVIRAL THERAPY; SURROGATE END-POINTS; INTENSIVE-CARE-UNIT; COLLABORATIVE ANALYSIS; HIV-1-INFECTED PATIENTS; PROSPECTIVE COHORT; CLINICAL-TRIALS; LIVER-DISEASE; MORTALITY; VETERANS AB Background As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). Methods Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. Results Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data. Conclusions When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research. C1 [Justice, A. C.] Yale Univ, Sch Med, Dept Internal Med, West Haven, CT 06516 USA. [Justice, A. C.; Braithwaite, R. S.] VA Connecticut Healthcare Syst, Gen Internal Med Sect, West Haven, CT USA. [McGinnis, K. A.] Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. [Skanderson, M.] Pittsburgh VA Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chang, C. C.; Roberts, M. S.] Univ Pittsburgh, Sch Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. [Gibert, C. L.] George Washington Univ, Med Ctr, VA Med Ctr, Washington, DC 20037 USA. [Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Rimland, D.] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, D.] VA Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, M. C.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Oursler, K. K.] Univ Maryland, Sch Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA. [Brown, S. T.] James J Peters VA Med Ctr, Bronx, NY USA. [Brown, S. T.] Mt Sinai Sch Med, New York, NY USA. [May, M.] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Covinsky, K. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Covinsky, K. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Fultz, S. L.] US Dept Vet Affairs, Vet Hlth Adm, Off Publ Hlth & Environm Hazards, Washington, DC USA. [Bryant, K. J.] NIAAA, Bethesda, MD USA. RP Justice, AC (reprint author), Yale Univ, Sch Med, Dept Internal Med, 950 Campbell Ave,11 ACSL,Bldg 35A,2nd Fl,Rm 212, West Haven, CT 06516 USA. EM amy.justice2@va.gov RI May, Margaret/E-8099-2013; Andrade, Hugo/M-6631-2013; OI May, Margaret/0000-0002-9733-1003; Andrade, Hugo/0000-0001-6781-6125; Goetz, Matthew/0000-0003-4542-992X FU National Institute on Alcohol Abuse and Alcoholism [2U10 AA 13566] FX This study was funded by the National Institute on Alcohol Abuse and Alcoholism (2U10 AA 13566). NR 52 TC 77 Z9 77 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD FEB PY 2010 VL 11 IS 2 BP 143 EP 151 DI 10.1111/j.1468-1293.2009.00757.x PG 9 WC Infectious Diseases SC Infectious Diseases GA 540CS UT WOS:000273309000007 PM 19751364 ER PT J AU Dillon, DG Bogdan, R Fagerness, J Holmes, AJ Perlis, RH Pizzagalli, DA AF Dillon, Daniel G. Bogdan, Ryan Fagerness, Jesen Holmes, Avram J. Perlis, Roy H. Pizzagalli, Diego A. TI Variation in TREK1 Gene Linked to Depression-Resistant Phenotype is Associated with Potentiated Neural Responses to Rewards in Humans SO HUMAN BRAIN MAPPING LA English DT Article DE anhedonia; basal ganglia; endophenotype; imaging genomics; magnetic resonance imaging ID CATECHOL-O-METHYLTRANSFERASE; DOPAMINE TRANSPORTER; POTASSIUM CHANNEL; MAJOR DEPRESSION; HUMAN BRAIN; ORBITOFRONTAL CORTEX; FMRI; POLYMORPHISM; EXPRESSION; SYSTEM AB The TREK1 gene has been linked to a depression-resistant phenotype in rodents and antidepressant response in humans, but the neural mechanisms underlying these links are unclear. Because TREK1 is expressed in reward-related basal ganglia regions, it has been hypothesized that TREK1 genetic variation may be associated with anhedonic symptoms of depression. To investigate whether TREK1 genetic variation influences reward processing, we genotyped healthy individuals (n = 31) who completed a monetary incentive delay task during functional magnetic resonance imaging (WRI). Three genotypes previously linked to positive antidepressant response were associated with potentiated basal ganglia activity to gains, but did not influence responses to penalties or no change feedback. TREK1 genetic variations did not affect basal ganglia volume, and WRI group differences were confirmed when accounting for self-report measures of anhedonia. In addition, the total number of "protective" TREK1. alleles was associated with stronger responses to gains in several other reward-related regions, including the dorsal anterior cingulate cortex, orbitofrontal. cortex, and mesial prefrontal cortex. In control analyses, associations between basal ganglia responses to gains and functional polymorphisms in the dopamine transporter (DAT1) and catechol-O-methyltransferase (COMT) genes were also explored. Results revealed that TREK1 and DAT/COMT genotypes were independently related to basal ganglia responses to gains. These findings indicate that TREK1 genotypes are associated with individual differences in reward-related brain activity. Future studies in depressed samples Should evaluate whether variation in neural responses to rewards may contribute to the association between TREK1 and antidepressant response in humans. Hum Brain Mapp 31:210-221, 2010. (C) 2009 Wiley-Liss. Inc. C1 [Dillon, Daniel G.; Bogdan, Ryan; Holmes, Avram J.; Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Fagerness, Jesen; Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. RP Pizzagalli, DA (reprint author), Harvard Univ, Dept Psychol, 1220 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. EM dap@wjh.harvard.edu OI Dillon, Daniel/0000-0002-1977-700X; Bogdan, Ryan/0000-0002-1430-1045 FU GlaxoSmithKline; Merck Co FX The authors declare that over the past three years Dr. Pizzagalli has received research Support from GlaxoSmithKline and Merck & Co. for studies unrelated to this project, and that Dr. Perlis has received honoraria, speaker's or consulting fees from AstraZeneca, Bristol Myers-Squibb, Eli Lilly & Co., Glaxo SmithKline, Pfizer, and Proteus. Dr. Perlis is a major stockholder in Concordant Rater Systems, LLC. Dr. Dillon, Mr. Bogdan, Mr. Fagerness, and Mr. Holmes report no competing interests. Finally, the authors declare that there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. NR 55 TC 20 Z9 24 U1 0 U2 5 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 FEB PY 2010 VL 31 IS 2 BP 210 EP 221 DI 10.1002/hbm.20858 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 554UO UT WOS:000274460900005 PM 19621370 ER PT J AU Castaldi, PJ Cho, MH Cohn, M Langerman, F Moran, S Tarragona, N Moukhachen, H Venugopal, R Hasimja, D Kao, E Wallace, B Hersh, CP Bagade, S Bertram, L Silverman, EK Trikalinos, TA AF Castaldi, Peter J. Cho, Michael H. Cohn, Matthew Langerman, Fawn Moran, Sienna Tarragona, Nestor Moukhachen, Hala Venugopal, Radhika Hasimja, Delvina Kao, Esther Wallace, Byron Hersh, Craig P. Bagade, Sachin Bertram, Lars Silverman, Edwin K. Trikalinos, Thomas A. TI The COPD genetic association compendium: a comprehensive online database of COPD genetic associations SO HUMAN MOLECULAR GENETICS LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; MICROSOMAL EPOXIDE HYDROLASE; HUMAN GENOME EPIDEMIOLOGY; SYSTEMATIC METAANALYSES; CHRONIC-BRONCHITIS; POLYMORPHISMS; DEFICIENCY AB Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. COPD is thought to arise from the interaction of environmental exposures and genetic susceptibility, and major research efforts are underway to identify genetic determinants of COPD susceptibility. With the exception of SERPINA1, genetic associations with COPD identified by candidate gene studies have been inconsistently replicated, and this literature is difficult to interpret. We conducted a systematic review and meta-analysis of all population-based, case-control candidate gene COPD studies indexed in PubMed before 16 July 2008. We stored our findings in an online database, which serves as an up-to-date compendium of COPD genetic associations and cumulative meta-analysis estimates. On the basis of our systematic review, the vast majority of COPD candidate gene era studies are underpowered to detect genetic effect odds ratios of 1.2-1.5. We identified 27 genetic variants with adequate data for quantitative meta-analysis. Of these variants, four were significantly associated with COPD susceptibility in random effects meta-analysis, the GSTM1 null variant (OR 1.45, CI 1.09-1.92), rs1800470 in TGFB1 (0.73, CI 0.64-0.83), rs1800629 in TNF (OR 1.19, CI 1.01-1.40) and rs1799896 in SOD3 (OR 1.97, CI 1.24-3.13). In summary, most COPD candidate gene era studies are underpowered to detect moderate-sized genetic effects. Quantitative meta-analysis identified four variants in GSTM1, TGFB1, TNF and SOD3 that show statistically significant evidence of association with COPD susceptibility. C1 [Castaldi, Peter J.; Cohn, Matthew; Langerman, Fawn; Moran, Sienna; Tarragona, Nestor; Moukhachen, Hala; Venugopal, Radhika; Hasimja, Delvina; Kao, Esther; Wallace, Byron; Trikalinos, Thomas A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Cho, Michael H.; Hersh, Craig P.; Silverman, Edwin K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Cho, Michael H.; Hersh, Craig P.; Silverman, Edwin K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Bagade, Sachin; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis MIND, Genet & Aging Unit, Charlestown, MA USA. [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany. RP Trikalinos, TA (reprint author), Tufts Med Ctr, Inst Clin Res, 800 Washington St, Boston, MA 02111 USA. EM ttrikalinos@tuftsmedicalcenter.org RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU National Institute of Health [T32 HS00060, F32 HL094035, T32HL007427, K12HL089990, UL1 RR025752, R01 HL075478, R01 HL084323] FX This work was supported by National Institute of Health Grants T32 HS00060 (P. J. C.), F32 HL094035 (P. J. C.), T32HL007427 (M. H. C.), K12HL089990 (M. H. C.), UL1 RR025752, R01 HL075478 (E. K. S.) and R01 HL084323 (E. K. S.). NR 25 TC 66 Z9 72 U1 2 U2 8 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 FEB 1 PY 2010 VL 19 IS 3 BP 526 EP 534 DI 10.1093/hmg/ddp519 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 539BA UT WOS:000273227200012 PM 19933216 ER PT J AU Thadhani, R AF Thadhani, Ravi TI Inching Towards A Targeted Therapy for Preeclampsia SO HYPERTENSION LA English DT Editorial Material ID HYPERTENSION; ISCHEMIA; KIDNEY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU NIDDK NIH HHS [DK67397, R01 DK067397] NR 10 TC 4 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB 1 PY 2010 VL 55 IS 2 BP 238 EP 240 DI 10.1161/HYPERTENSIONAHA.109.143933 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 546HS UT WOS:000273802500012 PM 20026761 ER PT J AU Daumerie, G Bridges, L Yancey, S Davis, W Huang, P Loscalzo, J Pointer, MA AF Daumerie, Geraldine Bridges, LaKeesha Yancey, Sadiqa Davis, Wendell Huang, Paul Loscalzo, Joseph Pointer, Mildred A. TI The effect of salt on renal damage in eNOS-deficient mice SO HYPERTENSION RESEARCH LA English DT Article DE blood pressure; kidney; nitric oxide synthase; renal fibrosis ID NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR HYPERTROPHY; DIETARY-SODIUM INTAKE; AFRICAN-AMERICANS; SENSITIVE HYPERTENSION; RACIAL-DIFFERENCES; KNOCKOUT MICE; NORMOTENSIVE RATS; BLOOD-PRESSURE; CARDIAC-HYPERTROPHY AB African Americans have an increased incidence of end-stage renal disease and are characterized as having reduced bioavailability of nitric oxide and salt-sensitivity. We propose that endothelial nitric oxide synthase (eNOS) knockout mice (eNOS(-/-)) are a suitable model of hypertension-associated renal injury as seen in African Americans. Therefore, the purpose of this study was to determine whether older eNOS(-/-) mice have hypertension-associated renal injury and if dietary salt modulates this injury. Six-month-old eNOS(-/-) mice were placed on 0.12%, 0.45% or 8% NaCl diet for 8 weeks and blood pressure measured weekly; kidneys were collected for pathology evaluation and scoring at the end of the 8-week period. Mice deficient of eNOS were hypertensive at baseline compared with control mice in all three groups (128 +/- 3 vs. 112 +/- 3, P<0.05). Blood pressure was significantly elevated from baseline in eNOS(-/-) on 0.45 and 8% salt diets (P<0.02). The composite renal pathology scores for eNOS(-/-) mice were significantly greater than wild-type mice, indicating high salt intake exacerbates the injury (P<0.001 vs. normal salt diet). eNOS(-/-) mice may be used as a model of salt-induced and hypertension-associated renal injury as seen in African Americans. Hypertension Research ( 2010) 33, 170-176; doi: 10.1038/hr.2009.197; published online 4 December 2009 C1 [Bridges, LaKeesha; Yancey, Sadiqa; Pointer, Mildred A.] N Carolina Cent Univ, Cardiovasc Program, JLC Biomed Biotechnol Res Inst, Durham, NC 27707 USA. [Daumerie, Geraldine] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Med, Boston, MA 02118 USA. [Davis, Wendell] Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NC USA. [Huang, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loscalzo, Joseph] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. RP Pointer, MA (reprint author), N Carolina Cent Univ, Cardiovasc Program, JLC Biomed Biotechnol Res Inst, Durham, NC 27707 USA. EM mpointer@nccu.edu FU National Heart, Lung and Blood Institute [P50 HL55993-01, UH1 HL59868] FX This work was supported in part by the National Heart, Lung and Blood Institute Grant P50 HL55993-01 (to JL, MP) and UH1 HL59868 (to LB, SY and MP). NR 55 TC 4 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD FEB PY 2010 VL 33 IS 2 BP 170 EP 176 DI 10.1038/hr.2009.197 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 553UR UT WOS:000274392800018 PM 19960018 ER PT J AU Fang, QQ Meaney, PM Paulsen, KD AF Fang, Qianqian Meaney, Paul M. Paulsen, Keith D. TI Viable Three-Dimensional Medical Microwave Tomography: Theory and Numerical Experiments SO IEEE TRANSACTIONS ON ANTENNAS AND PROPAGATION LA English DT Article DE Adjoint method; alternating-direction implicit finite-difference time-domain (ADI-FDTD); finite-difference time-domain (FDTD); microwave tomography ID BREAST-CANCER DETECTION; IMAGE-RECONSTRUCTION; INVERSE SCATTERING; DIELECTRIC-PROPERTIES; SYSTEM; DISPERSION; PROTOTYPE; TISSUES; TUMOR AB Three-dimensional microwave tomography represents a potentially very important advance over 2D techniques because it eliminates associated approximations which may lead to more accurate images. However, with the significant increase in problem size, computational efficiency is critical to making 3D microwave imaging viable in practice. In this paper, we present two 3D image reconstruction methods utilizing 3D scalar and vector field modeling strategies, respectively. Finite element (FE) and finite-difference time-domain (FDTD) algorithms are used to model the electromagnetic field interactions in human tissue in 3D. Image reconstruction techniques previously developed for the 2D problem, such as the dual-mesh scheme, iterative block solver, and adjoint Jacobian method are extended directly to 3D reconstructions. Speed improvements achieved by setting an initial field distribution and utilizing an alternating-direction implicit (ADI) FDTD are explored for 3D vector field modeling. The proposed algorithms are tested with simulated data and correctly recovered the position, size and electrical properties of the target. The adjoint formulation and the FDTD method utilizing initial field estimates are found to be significantly more effective in reducing the computation time. Finally, these results also demonstrate that cross-plane measurements are critical for reconstructing 3D profiles of the target. C1 [Fang, Qianqian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Fang, Qianqian] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Meaney, Paul M.; Paulsen, Keith D.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Paulsen, Keith D.] Dartmouth Hitchcock Med Ctr, Radiobiol & Bioengn Res Program, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM qianqian.fang.th05@alum.dartmouth.org; paul.m.meaney@dartmouth.edu; pkeith.d.paulsen@dartmouth.edu FU National Institutes of Health (NIH) through the National Cancer Institute [P01-CA80139] FX This work was supported in part by the National Institutes of Health (NIH) through the National Cancer Institute under Grant P01-CA80139. NR 37 TC 28 Z9 30 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-926X J9 IEEE T ANTENN PROPAG JI IEEE Trans. Antennas Propag. PD FEB PY 2010 VL 58 IS 2 BP 449 EP 458 DI 10.1109/TAP.2009.2037691 PG 10 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 551LL UT WOS:000274210700022 PM 20352084 ER PT J AU Milenkovic, O Alterovitz, G Battail, G Coleman, TP Hagenauer, J Meyn, SP Price, N Ramoni, MF Shmulevich, I Szpankowski, W AF Milenkovic, Olgica Alterovitz, Gil Battail, Gerard Coleman, Todd P. Hagenauer, Joachim Meyn, Sean P. Price, Nathan Ramoni, Marco F. Shmulevich, Ilya Szpankowski, Wojciech TI Introduction to the Special Issue on Information Theory in Molecular Biology and Neuroscience SO IEEE TRANSACTIONS ON INFORMATION THEORY LA English DT Editorial Material C1 [Milenkovic, Olgica; Meyn, Sean P.] Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. [Milenkovic, Olgica] Univ Colorado, Dept Elect & Comp Engn, Boulder, CO 80309 USA. [Alterovitz, Gil] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Alterovitz, Gil] IBM Corp, Armonk, NY USA. [Coleman, Todd P.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Coleman, Todd P.] Massachusetts Gen Hosp, Neurosci Stat Res Lab Computat Neurosci, Boston, MA 02114 USA. [Coleman, Todd P.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Coleman, Todd P.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. [Hagenauer, Joachim] IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Hagenauer, Joachim] German Aerosp Res Ctr DLR, Inst Commun Technol, Cologne, Germany. [Hagenauer, Joachim] Tech Univ Munich, Munich, Germany. [Hagenauer, Joachim] Bell Labs, Crawford Hill, NJ USA. [Meyn, Sean P.] Australian Natl Univ, Canberra, ACT, Australia. [Price, Nathan] Univ Illinois, Dept Chem & Biomol Engn, Inst Genom Biol, Urbana, IL 61801 USA. [Price, Nathan] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA. [Ramoni, Marco F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ramoni, Marco F.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Ramoni, Marco F.] Harvard Partners Ctr Genet & Genom, Biomed Cybernet Lab, Cambridge, MA USA. [Shmulevich, Ilya] Univ Nijmegen, Nijmegen Inst Cognit & Informat, Nijmegen, Netherlands. [Shmulevich, Ilya] Univ Amsterdam, Natl Res Inst Math & Comp Sci, NL-1012 WX Amsterdam, Netherlands. [Shmulevich, Ilya] Tampere Univ Technol, Signal Proc Lab, Tampere Int Ctr Signal Proc, FIN-33101 Tampere, Finland. [Shmulevich, Ilya] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Canc Genom Lab, Houston, TX USA. [Shmulevich, Ilya] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Szpankowski, Wojciech] Purdue Univ, W Lafayette, IN 47907 USA. [Ramoni, Marco F.] Childrens Hosp Boston, Boston, MA USA. [Shmulevich, Ilya] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Shmulevich, Ilya] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. [Shmulevich, Ilya] Tampere Univ Technol, Dept Signal Proc, FIN-33101 Tampere, Finland. [Shmulevich, Ilya] Univ Strathclyde, Dept Elect & Elect Engn, Glasgow G1 1XW, Lanark, Scotland. RP Milenkovic, O (reprint author), Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. NR 0 TC 11 Z9 11 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9448 J9 IEEE T INFORM THEORY JI IEEE Trans. Inf. Theory PD FEB PY 2010 VL 56 IS 2 BP 649 EP 652 DI 10.1109/TIT.2009.2036971 PG 4 WC Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 562EQ UT WOS:000275032900001 ER PT J AU Gurubhagavatula, I AF Gurubhagavatula, Indira TI Consequences of obstructive sleep apnoea SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Review DE Day time sleepiness; health care cost; obstructive sleep apnoea; quality of life; traffic accidents; vigilence ID HEALTH-CARE UTILIZATION; QUALITY-OF-LIFE; POSITIVE AIRWAYS PRESSURE; MOTOR-VEHICLE CRASHES; LATENCY TEST MSLT; AUTOMOBILE ACCIDENTS; COMMERCIAL DRIVERS; DAYTIME SLEEPINESS; COGNITIVE FUNCTION; WAKEFULNESS TEST AB A plethora of medical consequences have been associated with the syndrome of obstructive sleep apnoea (OSA). These are global, affecting nearly every body function, and have been related to two key pathophysiological findings in sleep apnoea: repetitive falls in oxyhaemoglobin saturation during sleep, and recurrent arousals from sleep which terminate apnoea episodes. Sufferers of OSA may experience daytime sleepiness, which has been measured both subjectively using the Epworth Sleepiness Scale and the Stanford Sleepiness Scale, but also objectively, using Multiple Sleep Latency Testing, Maintenance of Wakefulness testing, and the Oxford Sleep Resistance test. In addition to the loss of alertness, sleep apnoea contributes to memory deficits, reduced vigilance, impaired executive function, increased risk for automobile and occupational accidents, and decreased quality of life. Importantly, afflicted individuals experience improvements in these outcomes with treatment. Taken together, this evidence forms a compelling basis to identify and treat latent cases of sleep apnoea. Not only do patients have the opportunity to achieve improvements in these outcomes and health-related quality of life, but the enormous economic burden that untreated apnoea imposes on the health care system may be eased. C1 [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Div Sleep Med, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm & Crit Care & Sleep Sect, Philadelphia, PA USA. RP Gurubhagavatula, I (reprint author), Univ Penn, Med Ctr, Ctr Sleep & Resp Neurobiol, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM gurubhag@mail.med.upenn.edu NR 49 TC 11 Z9 12 U1 1 U2 3 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD FEB PY 2010 VL 131 IS 2 SI SI BP 188 EP 195 PG 8 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 569XD UT WOS:000275635200010 PM 20308744 ER PT J AU Reinisch, W de Villiers, W Bene, L Simon, L Racz, I Katz, S Altorjay, I Feagan, B Riff, D Bernstein, CN Hommes, D Rutgeerts, P Cortot, A Gaspari, M Cheng, M Pearce, T Sands, BE AF Reinisch, Walter de Villiers, Williem Bene, Laszlo Simon, Laszlo Racz, Istvan Katz, Seymour Altorjay, Istvan Feagan, Brian Riff, Dennis Bernstein, Charles N. Hommes, Daniel Rutgeerts, Paul Cortot, Antoine Gaspari, Michael Cheng, May Pearce, Tillman Sands, Bruce E. TI Fontolizumab in Moderate to Severe Crohn's Disease: A Phase 2, Randomized, Double-blind, Placebo-controlled, Multiple-dose Study SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE fontolizumab; inflammatory bowel disease; Crohn's disease; interferon gamma; clinical study ID ANTIINTERFERON-GAMMA ANTIBODY; INFLAMMATORY-BOWEL-DISEASE; INTERFERON-GAMMA; ACTIVITY INDEX; IFN-GAMMA; SAFETY AB Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CID, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. C1 Univ Vienna, Dept Gastroenterol & Hepatol, Clin Internal Med 3, Vienna, Austria. [de Villiers, Williem] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY USA. [Cheng, May; Pearce, Tillman] PDL BioPharma Inc, Redwood City, CA USA. [Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Sands, Bruce E.] Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Gaspari, Michael] Carolina Digest Hlth Associates, Charlotte, NC USA. [Bernstein, Charles N.] Univ Manitoba, John Buhler Res Ctr, Winnipeg, MB, Canada. [Feagan, Brian] Univ Western Ontario, London Hlth Sci Ctr, London, ON, Canada. [Rutgeerts, Paul] Univ Ziekenhuizen Gasthuisberg, Dept Gastroenterol, Louvain, Belgium. [Riff, Dennis] Adv Clin Res Inst, Anaheim, CA USA. [Hommes, Daniel] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. [Altorjay, Istvan] Univ Debrecen, H-4012 Debrecen, Hungary. [Cortot, Antoine] CHU Hop Claude Huriez, Serv Malad Appareil Digestif & Nutr, Lille, France. [Bene, Laszlo] Peterfy S Hosp, Budapest, Hungary. [Simon, Laszlo] Cty Hosp Szekszard, Dept Internal Med 2, Szekszard, Hungary. [Racz, Istvan] Petz Aladar Cty Hosp, Gyor, Hungary. [Katz, Seymour] Long Isl Clin Res Associates LLP, Great Neck, NY USA. RP Reinisch, W (reprint author), Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM walter.reinisch@meduniwien.ac.at RI CORTOT, Antoine/I-5796-2015; Feagan, Brian/M-4283-2015; CORTOT, ANTOINE/I-7739-2016; OI CORTOT, ANTOINE/0000-0002-1067-8996; katz, seymour/0000-0002-3492-9200 FU PDL BioPharma. Inc., Redwood City, CA FX Supported by PDL BioPharma. Inc., Redwood City, CA. NR 9 TC 78 Z9 80 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD FEB PY 2010 VL 16 IS 2 BP 233 EP 242 DI 10.1002/ibd.21038 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 560OE UT WOS:000274911200013 PM 19637334 ER PT J AU Windolf, M Schwieger, K Ockert, B Jupiter, JB Gradl, G AF Windolf, Markus Schwieger, Karsten Ockert, Ben Jupiter, Jesse B. Gradl, Georg TI A novel non-bridging external fixator construct versus volar angular stable plating for the fixation of intra-articular fractures of the distal radius-A biomechanical study SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Distal radial fracture; External fixation; Angular stable plate; Biomechanics ID FIXED-ANGLE PLATE; INTERNAL-FIXATION; LOCKING PLATES; EXTRAARTICULAR FRACTURES; UNSTABLE FRACTURES; DORSAL; MODEL; OSTEOSYNTHESIS; COMPLICATIONS; MANAGEMENT AB Non-bridging external fixation has recently been introduced as an alternative to volar angular stable plating for the fixation of unstable intra-articular distal radial fractures. The purpose of this study was to biomechanically compare a new non-bridging external fixator construct to volar angular stable plate fixation in a dorsally comminuted intra-articular fracture model of the distal radius. Materials and methods: Five pairs of fresh frozen human cadaveric radii were randomly supplied with either a non-bridging external fixator or a stainless steel volar locking plate. A three-fragmental AO 23-C2.1 fracture was created by removing a 15 degrees dorsal wedge with remaining volar cortical contact and by an intra-articular osteotomy lateral to the lister-tubercle. Physiological load transfer via the wrist was simulated by means of a custom-made seesaw. For biomechanical testing, the bones were loaded in cyclic axial compression. Starting at 100 N. the load was monotonically increased at 0.025 degrees N per cycle until failure of the construct. Motion of the lunate and scaphoid fragments with respect to the radial diaphysis was acquired by optical three-dimensional (3D) motion tracking. Plastic wedge deformation was determined after 2000, 4000 and 6000 cycles. Results: The amplitude of wedge motion at the beginning of the test as a measure for construct stiffness was significantly lower for the fixator group (P = 0.003, power = 0.99). Plastic wedge deformation after 2000, 4000 and 6000 cycles was found significantly lower for the external fixator (repeated measures analysis of variance (ANOVA), P = 0.009, power = 0.86). Displacement of the intra-articular gap was found below 0.6 mm (mean) for both groups (P > 0.05). Conclusion: The study revealed Superior biomechanical properties of the proposed non-bridging external fixation compared to volar locked plating in an unstable intra-articular fracture model with volar cortical support. However, both fixation techniques seem to apply sufficient stabilisation to restore and retain anatomy after fracture of the most distal part of the radius and should be individually chosen according to distinct criteria. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Windolf, Markus; Schwieger, Karsten; Ockert, Ben] AO Fdn, AO Res Inst, CH-7270 Davos, Switzerland. [Ockert, Ben] Univ Munich, Dept Traumatol & Orthopaed Surg, D-80539 Munich, Germany. [Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv, Boston, MA USA. [Gradl, Georg] Univ Rostock, Dept Trauma & Reconstruct Surg, D-2500 Rostock, Germany. RP Windolf, M (reprint author), AO Fdn, AO Res Inst, Clavadelerstr 8, CH-7270 Davos, Switzerland. EM markus.windolf@aofoundation.org NR 44 TC 11 Z9 12 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD FEB PY 2010 VL 41 IS 2 BP 204 EP 209 DI 10.1016/j.injury.2009.09.025 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 560KT UT WOS:000274902200017 PM 19818959 ER PT J AU Levy, MM Dellinger, RP Townsend, SR Linde-Zwirble, WT Marshall, JC Bion, J Schorr, C Artigas, A Ramsay, G Beale, R Parker, MM Gerlach, H Reinhart, K Silva, E Harvey, M Regan, S Angus, DC AF Levy, Mitchell M. Dellinger, R. Phillip Townsend, Sean R. Linde-Zwirble, Walter T. Marshall, John C. Bion, Julian Schorr, Christa Artigas, Antonio Ramsay, Graham Beale, Richard Parker, Margaret M. Gerlach, Herwig Reinhart, Konrad Silva, Eliezer Harvey, Maurene Regan, Susan Angus, Derek C. TI The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis SO INTENSIVE CARE MEDICINE LA English DT Article DE Severe sepsis; Septic shock; Knowledge transfer; Performance measures; Surviving sepsis campaign; Performance improvement; Sepsis bundles; Quality improvement ID CRITICALLY-ILL PATIENTS; FACILITATING CLINICIAN ADHERENCE; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; MECHANICAL VENTILATION; IMPLEMENTATION; MANAGEMENT; MORTALITY; THERAPY; EPIDEMIOLOGY AB The Surviving Sepsis Campaign (SSC or "the Campaign") developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes. A multifaceted intervention to facilitate compliance with selected guideline recommendations in the ICU, ED, and wards of individual hospitals and regional hospital networks was implemented voluntarily in the US, Europe, and South America. Elements of the guidelines were "bundled" into two sets of targets to be completed within 6 h and within 24 h. An analysis was conducted on data submitted from January 2005 through March 2008. Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mortality. Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P < 0.0001). Compliance with the entire management bundle started at 18.4% in the first quarter and increased to 36.1% by the end of 2 years (P = 0.008). Compliance with all bundle elements increased significantly, except for inspiratory plateau pressure, which was high at baseline. Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.5-8.4%). The Campaign was associated with sustained, continuous quality improvement in sepsis care. Although not necessarily cause and effect, a reduction in reported hospital mortality rates was associated with participation. The implications of this study may serve as an impetus for similar improvement efforts. C1 [Levy, Mitchell M.] Brown Univ, Rhode Isl Hosp, Sch Med, Div Pulm Sleep & Crit Care Med, Providence, RI 02903 USA. [Dellinger, R. Phillip; Schorr, Christa] Univ Med & Dent New Jersey, Cooper Univ Hosp, Dept Med, Camden, NJ USA. [Townsend, Sean R.] Univ Massachusetts, Sch Med, Div Pulm Allergy & Crit Care Med, Worcester, MA USA. [Townsend, Sean R.] Inst Healthcare Improvement, Cambridge, MA USA. [Linde-Zwirble, Walter T.] ZD Associates LLC, Perkasie, PA USA. [Marshall, John C.] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Surg, Toronto, ON M5B 1W8, Canada. [Bion, Julian] Queen Elizabeth Hosp, Univ Dept Anaesthesia & Intens Care Med, Birmingham B15 2TH, W Midlands, England. [Artigas, Antonio] Autonomous Univ Barcelona, CIBER Enfermedades Resp, Crit Care Ctr, Sabadell Hosp, Barcelona, Spain. [Ramsay, Graham] Mid Essex Hosp Serv NHS Trust, London, England. [Beale, Richard] St Thomas Hosp, Guys & St Thomas NHS Fdn Trust, London, England. [Parker, Margaret M.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Gerlach, Herwig] Vivantes Klinikum Neukoelln, Berlin, Germany. [Reinhart, Konrad] Clin Anesthesiol & Intens Care, Jena, Germany. [Silva, Eliezer] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. [Harvey, Maurene] Consultants Crit Care Inc, Glenbrook, NV USA. [Regan, Susan] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Regan, Susan] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Angus, Derek C.] Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA USA. RP Levy, MM (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Div Pulm Sleep & Crit Care Med, 593 Eddy St, Providence, RI 02903 USA. EM Mitchell_Levy@brown.edu RI Beale, Richard/J-7831-2013; Angus, Derek/E-9671-2012; OI Regan, Susan/0000-0003-0940-2017 FU Eli Lilly and Co.; Edwards Lifesciences; Philips Medical Systems; Society of Critical Care Medicine; European Society of Intensive Care Medicine FX The authors gratefully acknowledge the dedication and efforts of Deb McBride during the Campaign and in the development of this manuscript. We also acknowledge the individuals leading the effort at participating sites who made all of this happen as volunteers who believed in the Campaign and what we were trying to accomplish as their sole motivation. The work was supported by Eli Lilly and Co., Edwards Lifesciences, Philips Medical Systems, the Society of Critical Care Medicine, and European Society of Intensive Care Medicine.; Dr. Levy has received grants from Eli Lilly & Co and Philips Medical Systems. Dr. Marshall has consultancies with Eisai, Eli Lilly, Specter Diagnostics, Bayer, Artisan, and Leo Pharma. Dr. Artigas has received grants from Eli Lilly. Dr. Beale has disclosed payment from multiple sources that were paid to his department and institution (details on file with the editorial office). Drs. Reihart and Silva have consultancies with Eli Lilly. Dr. Angus has participation in DSMB, Prowess-Shock, and Eli Lilly. The remaining authors have not disclosed any potential conflicts of interest. NR 36 TC 343 Z9 389 U1 2 U2 21 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 FEB PY 2010 VL 36 IS 2 BP 222 EP 231 DI 10.1007/s00134-009-1738-3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 546KU UT WOS:000273810500007 PM 20069275 ER PT J AU Joshi, SB Chao, T Herzka, DA Zeman, PR Cooper, HA Lindsay, J Fuisz, AR AF Joshi, Subodh B. Chao, Tania Herzka, Daniel A. Zeman, Peter R. Cooper, Howard A. Lindsay, Joseph Fuisz, Anthon R. TI Cardiovascular magnetic resonance T2 signal abnormalities in left ventricular ballooning syndrome SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Takotsubo; Left ventricular ballooning syndrome; Stress cardiomyopathy; Magnetic resonance imaging ID TAKO-TSUBO CARDIOMYOPATHY; ELEVATION MYOCARDIAL-INFARCTION; TAKOTSUBO CARDIOMYOPATHY; DYSFUNCTION; REPERFUSION; EDEMA; ENHANCEMENT; INSIGHTS; STRESS; MIMICS AB Left ventricular ballooning syndrome (LVBS), also known as Takotsubo cardiomyopathy, is characterized by regional left ventricular dysfunction associated with severe psychological stress. T2 weighted cardiac magnetic resonance (CMR) can identify myocardial edema due to ischemia or other insults. A standard clinical CMR scan with double inversion recovery fast spin echo T2 weighted sequences was performed on consecutive patients with LVBS. T2 signal was compared in myocardial segments with normal and impaired function based on systolic wall thickening (SWT). Eight LVBS patients were identified, all female, with a median age of 61 years and median left ventricular ejection fraction of 52%. Four patients had apical ballooning and four had mid-wall or basal ballooning. In severely dysfunctional segments (those with SWT < 25%), the median percentage of high T2 signal was 85 compared with 35 in those with SWT > 25% (P < 0.001). When the segments were categorized into tertiles based on SWT, the percentage of high T2 signal was greatest in segments with the worst function (68% vs. 43% vs. 31%, P = 0.005). In the five patients who returned for follow up, there was a significant reduction in high T2 signal compared with baseline in those segments that were initially severely dysfunctional (85% vs. 35%, P < 0.001). In conclusion, we describe elevated T2 signal consistent with myocardial edema in patients with LVBS. The T2 signal is highest in myocardium with the most impaired function and resolves over time. C1 [Joshi, Subodh B.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Joshi, Subodh B.; Chao, Tania; Zeman, Peter R.; Cooper, Howard A.; Lindsay, Joseph; Fuisz, Anthon R.] Washington Hosp Ctr, Cardiol Sect, Dept Med, Washington, DC 20010 USA. [Herzka, Daniel A.] Philips Res N Amer, Clin Sites Res Program, Bethesda, MD USA. RP Joshi, SB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM sbjoshi@partners.org OI Herzka, Daniel/0000-0002-9400-7814 NR 28 TC 16 Z9 16 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD FEB PY 2010 VL 26 IS 2 BP 227 EP 232 DI 10.1007/s10554-009-9515-5 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 552ZS UT WOS:000274334400019 PM 19862639 ER PT J AU Aschner, P Horton, E Leiter, LA Munro, N Skyler, JS AF Aschner, P. Horton, E. Leiter, L. A. Munro, N. Skyler, J. S. CA Global Partnership Effective Diabe TI Practical steps to improving the management of type 1 diabetes: recommendations from the Global Partnership for Effective Diabetes Management SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article ID SUBCUTANEOUS INSULIN INFUSION; ENABLE DIETARY FREEDOM; POOR GLYCEMIC CONTROL; BETA-CELL FUNCTION; CARDIOVASCULAR-DISEASE; BLOOD-GLUCOSE; MICROVASCULAR COMPLICATIONS; SEVERE HYPOGLYCEMIA; INTENSIVE TREATMENT; METABOLIC SYNDROME AB P>The Diabetes Control and Complications Trial (DCCT) led to considerable improvements in the management of type 1 diabetes, with the wider adoption of intensive insulin therapy to reduce the risk of complications. However, a large gap between evidence and practice remains, as recently shown by the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, in which 30-year rates of microvascular complications in the 'real world' EDC patients were twice that of DCCT patients who received intensive insulin therapy. This gap may be attributed to the many challenges that patients and practitioners face in the day-to-day management of the disease. These barriers include reaching glycaemic goals, overcoming the reality and fear of hypoglycaemia, and appropriate insulin therapy and dose adjustment. As practitioners, the question remains: how do we help patients with type 1 diabetes manage glycaemia while overcoming barriers? In this article, the Global Partnership for Effective Diabetes Management provides practical recommendations to help improve the care of patients with type 1 diabetes. C1 [Skyler, J. S.] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33101 USA. [Aschner, P.] Javeriana Univ, Sch Med, Bogota, Colombia. [Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Leiter, L. A.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Leiter, L. A.] Univ Toronto, Toronto, ON, Canada. [Munro, N.] Chelsea & Westminster Hosp, Beta Cell Diabet Ctr, London, England. RP Skyler, JS (reprint author), Univ Miami, Miller Sch Med, Diabet Res Inst, 1450 NW 10th Ave,Suite 3054,POB 016960 D-110, Miami, FL 33101 USA. EM jskyler@miami.edu RI Skyler, Jay/F-4211-2016; Del Prato, Stefano/K-3405-2016 OI Del Prato, Stefano/0000-0002-5388-0270 NR 87 TC 20 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1368-5031 EI 1742-1241 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD FEB PY 2010 VL 64 IS 3 BP 305 EP 315 DI 10.1111/j.1742-1241.2009.02296.x PG 11 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 543DC UT WOS:000273549300008 PM 20456170 ER PT J AU Schorge, JO Wingo, SN Bhore, R Heffernan, TP Lea, JS AF Schorge, John O. Wingo, Shana N. Bhore, Rafia Heffernan, Thomas P. Lea, Jayanthi S. TI Secondary cytoreductive surgery for recurrent platinum-sensitive ovarian cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the New-England-Association-of-Gynecologic-Oncologists CY JUN, 2008 CL Chatham, MA SP New England Assoc Gynecol Oncol DE Recurrent ovarian cancer; Secondary cytoreductive surgery ID SURGICAL CYTOREDUCTION; PROGNOSTIC-FACTORS; CARCINOMA; SURVIVAL; METAANALYSIS; SELECTION AB Objective: To determine the risks and benefits of secondary cytoreductive surgery for recurrent platinum-sensitive ovarian cancer. Methods: Data were obtained retrospectively for all women with recurrent platinum-sensitive epithelial ovarian cancer who underwent a second debulking operation between 1998 and 2008 at the University of Texas Southwestern Medical Center. Survival analysis and comparisons were performed using the Kaplan-Meier method, log-rank test, and Cox multivariate proportional hazards model. Results: Optimal secondary cytoreductive surgery (<5 mm of residual disease) was achieved in 32 of 40 patients (80%). Nine women (23%) developed major complications. Two variables, residual disease of less than 5 mm vs 5 mm or greater (median 63 months vs 11 months: P = 0.003); and less than 5 vs 5 or more sites of disease relapse (median 63 months vs 22 months; P = 0.009), were independently associated with survival and retained prognostic significance on multivariate analysis. Conclusions: Optimal secondary cytoreductive surgery was associated with a survival advantage and acceptable risks. (C) 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Schorge, John O.] Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey Ctr 9E, Boston, MA 02114 USA. [Wingo, Shana N.; Heffernan, Thomas P.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Bhore, Rafia] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX 75390 USA. [Lea, Jayanthi S.] Carolinas Med Ctr, Div Gynecol Oncol, Charlotte, NC 28203 USA. RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey Ctr 9E, 55 Fruit St, Boston, MA 02114 USA. EM jschorge@partners.org NR 20 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD FEB PY 2010 VL 108 IS 2 BP 123 EP 127 DI 10.1016/j.ijgo.2009.08.034 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 557DA UT WOS:000274647700009 PM 19892337 ER PT J AU Spencer, TJ Bonab, AA Dougherty, DD Martin, J McDonnell, T Fischman, AJ AF Spencer, Thomas J. Bonab, Ali A. Dougherty, Darin D. Martin, Jessica McDonnell, Tara Fischman, Alan J. TI A PET study examining pharmacokinetics and dopamine transporter occupancy of two long-acting formulations of methylphenidate in adults SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE dopamine transporter; methylphenidate; attention deficit hyperactivity disorder; positron emission tomography; controlled-release; binding potential ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; ORAL METHYLPHENIDATE; RECEPTOR OCCUPANCY; DRUG AB The delivery systems of two long-acting formulations of methylphenidate (MPH) were designed for different durations. Diffucaps bead-delivery system (DBDS)-MPH was designed to last 8 h and osmotically control led-release oral delivery system (OROS)-MPH was designed to last 12 h. While the plasma pharmacokinetics and timing of efficacy have been studied, the corresponding central nervous system dopamine transporter (DAT) occupancies are unknown. In this study, 21 healthy volunteers underwent PET imaging with (11)C Altropane before and after administration of oral doses of DBDS-MPH and OROS-MPH. Each subject received 40 mg DBDS-MPH and 36 mg OROS-MPH on different days. PET imaging occurred at 10 h after dosing. Each subject was injected with 5 mCi of (11)C Altropane and serial images of the brain were acquired over 60 min with a Siemens HR(+) PET camera. Binding potentials (BP, k(3)/k(4)) were calculated from time-activity curves using the simplified reference region method with cerebellum as reference. Transporter occupancy was calculated by standard methods. At 10 h, plasma d-MPH levels were lower (3.8 +/- 1.2 vs. 5.2 +/- 2.0) and brain DAT occupancy was lower (34.8 +/- 12.9 vs. 44.3 +/- 11.8) for DBDS-MPH than OROS-MPH. Across the range of values, for each unit of change in plasma d-MPH level there was a larger change in DAT occupancy with the DBDS-MPH formulation than with the OROS-MPH formulation. As predicted from previous pharmacokinetic and efficacy data, the average plasma level and DAT occupancy of 36 mg OROS-MPH was >40 mg DBDS-MPH at 10 h. Moreover, a relatively small difference in plasma levels (1.4 ng/ml at 10 h) was associated with a more impressive difference in DAT occupancy (similar to 10% at 10 h). C1 [Spencer, Thomas J.; Martin, Jessica; McDonnell, Tara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Dept Psychiat, Boston, MA USA. [Spencer, Thomas J.; Dougherty, Darin D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Serv,Dept Psychiat, Boston, MA USA. [Bonab, Ali A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA USA. [Bonab, Ali A.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, 55 Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org FU McNeil Pharmaceuticals; Shire Laboratories, Inc.; Eli Lilly Company; GlaxoSmith Kline; Janssen Pharmaceutical; McNeil Pharmaceutical; Novartis Pharmaceuticals; Cephalon; Pfizer; National Institute of Mental Health FX This study was supported by funding from McNeil Pharmaceuticals. Dr Thomas Spencer receives research support from, is a speaker for or is on the Advisory Board of the following sources: Shire Laboratories, Inc., Eli Lilly & Company, GlaxoSmith Kline, Janssen Pharmaceutical, McNeil Pharmaceutical, Novartis Pharmaceuticals, Cephalon, Pfizer and the National Institute of Mental Health. NR 13 TC 6 Z9 6 U1 1 U2 4 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD FEB PY 2010 VL 25 IS 2 BP 261 EP 265 DI 10.3892/ijmm_00000339 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 547CE UT WOS:000273862300011 PM 20043136 ER PT J AU Stewart, JW McGrath, PJ Fava, M Wisniewski, SR Zisook, S Cook, I Nierenberg, AA Trivedi, MH Balasubramani, GK Warden, D Lesser, I Rush, AJ AF Stewart, Jonathan W. McGrath, Patrick J. Fava, Maurizio Wisniewski, Stephen R. Zisook, Sidney Cook, Ian Nierenberg, Andrew A. Trivedi, Madhukar H. Balasubramani, G. K. Warden, Diane Lesser, Ira Rush, A. John TI Do atypical features affect outcome in depressed outpatients treated with citalopram? SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Citalopram; depression with atypical features; STAR*D ID STAR-ASTERISK-D; DIAGNOSTIC SCREENING QUESTIONNAIRE; SEROTONIN REUPTAKE INHIBITORS; NATIONAL COMORBIDITY SURVEY; ILLNESS RATING-SCALE; REPORT QIDS-SR; MAJOR DEPRESSION; SELF-REPORT; SYMPTOMATIC VOLUNTEERS; PSYCHOMETRIC EVALUATION AB Depressed patients with atypical features have an earlier onset of depression, a more chronic course of illness, several distinctive biological and familial features, and a different treatment response than those without atypical features. The efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) have not been fully evaluated in depression with atypical features. This report evaluates data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to determine whether depressed outpatients with and without atypical features respond differently to the SSRI citalopram. Treatment-seeking participants with non-psychotic major depressive disorder were recruited from primary- and psychiatric-care settings. The presence/absence of atypical features was approximated using baseline ratings on the 30-item Inventory of Depressive Symptomatology - Clinician-rated. Following baseline assessments, participants received citalopram up to 60 mg/d for up to 14 wk. Baseline socio-demographic and clinical characteristics, and treatment outcomes, were compared between participants with and without atypical features. Of the 2876 evaluable STAR*D participants, 541 (19%) had atypical features. Participants with atypical features were significantly more likely to be female, Younger, unemployed, have greater physical impairment, a younger age of depression onset, a longer index episode, greater depressive severity, and more concurrent anxiety diagnoses. Those with atypical features had significantly lower remission rates, although this difference was no longer present after adjustment for baseline differences. Depressed patients with atypical features are less likely to remit with citalopram than those without atypical features. This finding is probably due to differences in baseline characteristics other than atypical symptom features. C1 [Stewart, Jonathan W.; McGrath, Patrick J.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. [Stewart, Jonathan W.; McGrath, Patrick J.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Fava, Maurizio; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Zisook, Sidney] San Diego VA Med Ctr, San Diego, CA USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cook, Ian] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Trivedi, Madhukar H.; Warden, Diane; Lesser, Ira] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. RP Stewart, JW (reprint author), 1051 Riverside Dr, New York, NY 10032 USA. EM jws6@columbia.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU National Institute of Mental Health, National Institutes of Health [N01MH90003]; Eli Lilly; GlaxoSmithKline; Organon; Pfizer; New York State Office of Mental Health; Research Foundation for Mental Hygiene (New York State); NARSAD; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Lipha Pharmaceuticals; Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb Company; Cephalon; Forest Pharmaceuticals Inc.; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; PamLab; LLC; Pfizer Inc; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals Inc.; Wyeth-Ayerst Laboratories; Cyberonics; National Institutes of Health; Sepracor; West Coast College of Biological Psychiatry; Cederroth; Cyberonics Inc.; Janssen Pharmaceutica; Lichtwer Pharma; National Alliance for Research in Schizophrenia and Depression; Stanley Foundation; Abbott Laboratories Inc.; Abdi Brahim; Agency for Healthcare Research and Quality (AHRQ); Akzo (Organon Pharmaceuticals Inc.); Bayer; Cephalon Inc.; Corcept Therapeutics Inc.; Fabre Kramer Pharmaceuticals Inc.; Forest Pharmaceuticals; LP; Johnson Johnson PRD; Meade Johnson; Merck; National Institute on Drug Abuse; Neuronetics; Parke-Davis Pharmaceuticals Inc.; Pharmacia Upjohn; Predix Pharmaceuticals; Targacept; VantagePoint FX This project was funded by the National Institute of Mental Health, National Institutes of Health, under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (PI: A. J. Rush). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We acknowledge the editorial support of Jon Kilner, M.S., M.A. (Pittsburgh, PA) and the secretarial support of Fast Word Information Processing Inc. (Dallas, TX). [ClinicalTrials.gov: NCT00021528]; Dr Stewart has received honoraria from Bristol-Myers Squibb, Forest Laboratories, Organon, Shire, and Somerset; consulting fees from Biovail, Merck, and Organon, Wyeth, research funding from Eli Lilly, GlaxoSmithKline, Organon, and Pfizer; study medication from GlaxoSmithKline and Forest Laboratories; has given speaking engagements paid for by Eli Lilly, GlaxoSmithKline, Organon, and Pfizer; has been informed lie will receive money from Biovail in consideration of their intent to file a patent based on work done by himself and colleagues; and has received other funding support from New York State Office of Mental Health, Research Foundation for Mental Hygiene (New York State), NARSAD, and the National Institute of Mental Health. In addition, Dr Stewart owns mutual funds and other managed accounts which own stock in pharmaceutical companies. Dr McGrath has received consulting fees from GlaxoSmithKline, Somerset Pharmaceuticals, Novartis Pharmaceuticals, Sanofi Aventis and Roche; and research support from the National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, the New York State Office of Mental Health, NARSAD, Research Foundation for Mental Hygiene (New York State), GlaxoSmithKline, Eli Lilly, Organon, Lipha Pharmaceuticals. Dr Fava has received Research Support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals Inc., and Wyeth-Ayerst Laboratories; consultation fees from Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management Inc., Biovail Pharmaceuticals Inc., Brain-Cells Inc. Bristol-Myers Squibb Company, Cephalon, Compellis, CNS Response, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre-Kramer Pharmaceuticals Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lundbeck, MedAvante Inc., Merck, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals Inc., Somaxon, Somerset Pharmaceuticals, Takeda, and Wyeth-Ayerst Laboratories; speaking fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Novartis, Organon Inc., Pfizer Inc, PharmaStar and Wyeth-Ayerst Laboratories; and has equity holdings in Compellis and MedAvante. Dr Wisniewski has received consulting fees from Cyberonics, ImaRx Therapeutics Inc., Bristol-Myers Squibb Company, Organon, and Case-Western University. Dr. Zisook has received research support from PamLab and Aspect and speaking honoraria from AstraZeneca and GlaxoSmithKline. Dr Cook has received research support from Aspect Medical Systems, Cyberonics, Eli Lilly & Company, National Institutes of Health, Novartis, Pfizer, Sepracor, West Coast College of Biological Psychiatry; consulting fees from Ascend Media, Bristol-Myers Squibb, Cyberonics, Janssen, Scale Venture Partners; and speaker's fees from Bristol-Myers Squibb, Medical Education Speakers Network, Pfizer and Wyeth-Ayerst;and is listed on patents owned by the University of California.; Dr Niereberg has received research support from Bristol-Myers Squibb Company, Cederroth, Cyberonics Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly & Company, PamLabs, Pfizer Inc., National Institute of Mental Health, National Alliance for Research in Schizophrenia and Depression, Stanley Foundation, and Wyeth-Ayerst Laboratories; consulting fees from AstraZeneca, Basilea Pharmaceutica, Brain Cells Inc., Bristol-Myers Squibb Company, Dainippon Sumitomo, Eli Lilly & Company, EpiQ, Genaissance, GlaxoSmithKline, jazz Pharmaceuticals, Innapharma, Merck, Neuronetics, Novartis, Pfizer Inc., PGx Health, Sepracor, Shire, Targacept, Takeda; speaking fees from Eli Lilly & Company, GlaxoSmithKline, Organon Inc., Wyeth-Ayerst Laboratories, Massachusetts General Psychiatry Academy [MGHPA talks are supported through Independent Medical Education (IME) grants from the following pharmaceutical companies in 2008: AstraZeneca, Eli Lilly, and Janssen Pharmaceuticals]; and has equity holdings in Appliance Computing Inc. Dr Trivedi has received research support from, served as a consultant to, or has been on the speakers' boards of: Abbott Laboratories Inc., Abdi Brahim, Agency for Healthcare Research and Quality (AHRQ), Akzo (Organon Pharmaceuticals Inc.), AstraZeneca, Bayer, Bristol-Myers Squibb Company, Cephalon Inc., Corcept Therapeutics Inc., Cyberonics Inc., Eli Lilly & Company, Fabre Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Meade Johnson, Merck, National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, Neuronetics, Novartis, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., Pharmacia & Upjohn, Predix Pharmaceuticals, Sepracor, Solvay Pharmaceuticals Inc., Targacept, VantagePoint, and Wyeth-Ayerst Laboratories. Dr Balasubramani reports no financial or other relationships relevant to this article. Dr Warden reports current equity ownership in Pfizer and prior equity ownership of Bristol-Myers Squibb. Dr Lesser has received grant support from National Institute of Mental Health and Aspect Medical Systems and has been on the speakers bureau for Medical Education Speakers Network. Dr Rush reports consulting fees from Advanced Neuromodulation Systrems, AstraZeneca, Best Practice Project Management, Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals, Gerson Lehrman Group, GlaxoSmithKline, jazz Pharmaceuticials, Magellan Health Services, Merck, Neuronetics, Novartis, Otsuka, Ono, Organon, Pamlab, Pfizer, Trancept Pharmaceuticals, Urban Institute and Wyeth-Ayerst; honoraria from Cyberonics, Forest and GlaxoSmithKline; royalties from Guilford Publications and Healthcare Technology Systems; a stipend from the Society of Biological Psychiatry, research support from the National Institute of Mental Health, and other income from Pfizer. NR 65 TC 28 Z9 28 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD FEB PY 2010 VL 13 IS 1 BP 15 EP 30 DI 10.1017/S1461145709000182 PG 16 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 560DX UT WOS:000274883300003 PM 19341509 ER PT J AU Wilfley, DE Haymond, M Anderson, B Gunn, S Holden, H Jones, M Hwu, K McGirk, S Mckay, S Schreiner, B Cuttler, L Abrams, E Casey, T Dahms, W Drotar, D Huestis, S Levers-Landis, C McGuigan, P Sundararajan, S Geffner, M Chang, N Dreimane, D Halvorson, M Hernandez, S Kaufman, F Mansilla, V Ortiz, R Ward, A Wexler, K Yasuda, P Katz, LL Berkowitz, R Boyd, S Carchidi, C Kaplan, J Keating, C Kneeshaw-Price, S Lassiter, C Lipman, T Magge, S McGinley, G Schwartzman, B Willi, S Arslanian, S Bacha, F Foster, S Galvin, B Hannon, T Kriska, A Libman, I Marcus, M Porter, K Songer, T Venditti, E Goland, R Cain, R Fennoy, I Gallagher, D Kringas, P Leibel, N Motaghedi, R Ng, D Ovalles, M Pellizzari, M Rapaport, R Robbins, K Seidman, D Siegel-Czarkowski, L Speiser, P Laffel, L Goebel-Fabbri, A Higgins, L Malloy, M Milaszewski, K Orkin, L Rodriguez-Ventura, A Nathan, D Bissett, L Blumenthal, K Delahanty, L Goldman, V Goseco, A Larkin, M Levitsky, L McEachern, R Milaszewski, K Norman, D Nwosu, B Park-Bennett, S Richards, D Sherry, N Steiner, B Tollefsen, S Carnes, S Dempsher, D Flomo, D Kociela, V Whelan, T Wolff, B Weinstock, R Bowerman, D Duncan, K Franklin, R Hartsig, J Izquierdo, R Kanaley, J Kearns, J Meyer, S Saletsky, R Trief, P Zeitler, P Bradhurst, A Celona-Jacobs, N Glazner, J Higgins, J Hoe, F Klingensmith, G Nadeau, K Strike, H Walders, N Witten, T Copeland, K Brown, R Chadwick, J Chalmers, L Macha, C Nordyke, A Poulsen, T Pratt, L Preske, J Schanuel, J Smith, J Sternlof, S Swisher, R Hale, D Amodei, N Barajas, R Cody, C Haffner, S Hernandez, J Lynch, J Morales, E Rivera, S Rupert, G Wauters, A White, N Arbelaez, A Jones, J Jones, T Sadler, M Tanner, M Welch, R Caprio, S Grey, M Guandalini, C Lavietes, S Rose, P Syme, A Tamborlane, W Hirst, K Coombs, L Edelstein, S Grover, N Long, C Pyle, L Linder, B Marcovina, S Chmielewski, J Ramirez, M Strylewicz, G Shepherd, J Fan, B Marquez, L Sherman, M Wang, J Mayer-Davis, E Liu, Y Nichols, M Aldrich-Rasche, D Franklin, K Massmann, C O'Brien, D Patterson, J Tibbs, T Van Buren, D Zhang, P Palmert, M Epstein, L Silverstein, J AF Wilfley, D. E. Haymond, M. Anderson, B. Gunn, S. Holden, H. Jones, M. Hwu, K. McGirk, S. Mckay, S. Schreiner, B. Cuttler, L. Abrams, E. Casey, T. Dahms, W. Drotar, D. Huestis, S. Levers-Landis, C. McGuigan, P. Sundararajan, S. Geffner, M. Chang, N. Dreimane, D. Halvorson, M. Hernandez, S. Kaufman, F. Mansilla, V. Ortiz, R. Ward, A. Wexler, K. Yasuda, P. Katz, L. Levitt Berkowitz, R. Boyd, S. Carchidi, C. Kaplan, J. Keating, C. Kneeshaw-Price, S. Lassiter, C. Lipman, T. Magge, S. McGinley, G. Schwartzman, B. Willi, S. Arslanian, S. Bacha, F. Foster, S. Galvin, B. Hannon, T. Kriska, A. Libman, I. Marcus, M. Porter, K. Songer, T. Venditti, E. Goland, R. Cain, R. Fennoy, I. Gallagher, D. Kringas, P. Leibel, N. Motaghedi, R. Ng, D. Ovalles, M. Pellizzari, M. Rapaport, R. Robbins, K. Seidman, D. Siegel-Czarkowski, L. Speiser, P. Laffel, L. Goebel-Fabbri, A. Higgins, L. Malloy, M. Milaszewski, K. Orkin, L. Rodriguez-Ventura, A. Nathan, D. Bissett, L. Blumenthal, K. Delahanty, L. Goldman, V. Goseco, A. Larkin, M. Levitsky, L. McEachern, R. Milaszewski, K. Norman, D. Nwosu, B. Park-Bennett, S. Richards, D. Sherry, N. Steiner, B. Tollefsen, S. Carnes, S. Dempsher, D. Flomo, D. Kociela, V. Whelan, T. Wolff, B. Weinstock, R. Bowerman, D. Duncan, K. Franklin, R. Hartsig, J. Izquierdo, R. Kanaley, J. Kearns, J. Meyer, S. Saletsky, R. Trief, P. Zeitler, P. Bradhurst, A. Celona-Jacobs, N. Glazner, J. Higgins, J. Hoe, F. Klingensmith, G. Nadeau, K. Strike, H. Walders, N. Witten, T. Copeland, K. Brown, R. Chadwick, J. Chalmers, L. Macha, C. Nordyke, A. Poulsen, T. Pratt, L. Preske, J. Schanuel, J. Smith, J. Sternlof, S. Swisher, R. Hale, D. Amodei, N. Barajas, R. Cody, C. Haffner, S. Hernandez, J. Lynch, J. Morales, E. Rivera, S. Rupert, G. Wauters, A. White, N. Arbelaez, A. Jones, J. Jones, T. Sadler, M. Tanner, M. Welch, R. Caprio, S. Grey, M. Guandalini, C. Lavietes, S. Rose, P. Syme, A. Tamborlane, W. Hirst, K. Coombs, L. Edelstein, S. Grover, N. Long, C. Pyle, L. Linder, B. Marcovina, S. Chmielewski, J. Ramirez, M. Strylewicz, G. Shepherd, J. Fan, B. Marquez, L. Sherman, M. Wang, J. Mayer-Davis, E. Liu, Y. Nichols, M. Aldrich-Rasche, D. Franklin, K. Massmann, C. O'Brien, D. Patterson, J. Tibbs, T. Van Buren, D. Zhang, P. Palmert, M. Epstein, L. Silverstein, J. CA Today Study Grp TI Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study The TODAY Study Group SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE pediatric; chronic illness; childhood obesity; adolescents ID IMPAIRED GLUCOSE-TOLERANCE; LONG-TERM MANAGEMENT; PEDIATRIC OBESITY; WEIGHT-LOSS; ADOLESCENT OVERWEIGHT; PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; BEHAVIOR-MODIFICATION; CHILDHOOD OVERWEIGHT; COST-EFFECTIVENESS AB Type 2 diabetes is associated with obesity and is increasing at an alarming rate in youth. Although weight loss through lifestyle change is one of the primary treatment recommendations for adults with type 2 diabetes, the efficacy of this approach has not been tested with youth. This paper provides a summary of the reviews and meta-analyses of pediatric weight-loss interventions that informed the design and implementation of an intensive, family-based lifestyle weight management program for adolescents with type 2 diabetes and their families developed for the Treatment Options for type 2 Diabetes in Adolescents and Youth ( TODAY) study. A total of 1092 youth have been screened, and 704 families have been randomized for inclusion in this 15-center clinical trial sponsored by the National Institutes of Health. The TODAY study is designed to test three approaches ( metformin, metformin plus rosiglitazone and metformin plus an intensive lifestyle intervention) to the treatment of a diverse cohort of youth, 10-17 years of age, within 2 years of their diagnosis. The principal goal of the TODAY Lifestyle Program (TLP) is to decrease baseline weight of youth by 7-10% ( or the equivalent for children who are growing in height) through changes in eating and physical activity habits, and to sustain these changes through ongoing treatment contact. The TLP is implemented by interventionists called Personal Activity and Nutrition Leaders (PALs) and delivered to youth with type 2 diabetes, and at least one family support person. The TLP provides a model for taking a comprehensive, continuous care approach to the treatment of severe overweight in youth with comorbid medical conditions such as type 2 diabetes. International Journal of Obesity (2010) 34, 217-226; doi: 10.1038/ijo.2009.195; published online 13 October 2009 C1 [Haymond, M.; Anderson, B.; Gunn, S.; Holden, H.; Jones, M.; Hwu, K.; McGirk, S.; Mckay, S.; Schreiner, B.] Baylor Coll Med, Ctr Clin, Houston, TX 77030 USA. [Cuttler, L.; Abrams, E.; Casey, T.; Dahms, W.; Drotar, D.; Huestis, S.; Levers-Landis, C.; McGuigan, P.; Sundararajan, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Geffner, M.; Chang, N.; Dreimane, D.; Halvorson, M.; Hernandez, S.; Kaufman, F.; Mansilla, V.; Ortiz, R.; Ward, A.; Wexler, K.; Yasuda, P.] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Katz, L. Levitt; Berkowitz, R.; Boyd, S.; Carchidi, C.; Kaplan, J.; Keating, C.; Kneeshaw-Price, S.; Lassiter, C.; Lipman, T.; Magge, S.; McGinley, G.; Schwartzman, B.; Willi, S.] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Arslanian, S.; Bacha, F.; Foster, S.; Galvin, B.; Hannon, T.; Kriska, A.; Libman, I.; Marcus, M.; Porter, K.; Songer, T.; Venditti, E.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Goland, R.; Cain, R.; Fennoy, I.; Gallagher, D.; Kringas, P.; Leibel, N.; Motaghedi, R.; Ng, D.; Ovalles, M.; Pellizzari, M.; Rapaport, R.; Robbins, K.; Seidman, D.; Siegel-Czarkowski, L.; Speiser, P.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Milaszewski, K.; Nathan, D.; Bissett, L.; Blumenthal, K.; Delahanty, L.; Goldman, V.; Goseco, A.; Larkin, M.; Levitsky, L.; McEachern, R.; Norman, D.; Nwosu, B.; Park-Bennett, S.; Richards, D.; Sherry, N.; Steiner, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tollefsen, S.; Carnes, S.; Dempsher, D.; Flomo, D.; Kociela, V.; Whelan, T.; Wolff, B.] St Louis Univ, St Louis, MO 63103 USA. [Weinstock, R.; Bowerman, D.; Duncan, K.; Franklin, R.; Hartsig, J.; Izquierdo, R.; Kanaley, J.; Kearns, J.; Meyer, S.; Saletsky, R.; Trief, P.] SUNY Upstate Med Univ, Syracuse, NY USA. [Zeitler, P.; Bradhurst, A.; Celona-Jacobs, N.; Glazner, J.; Higgins, J.; Hoe, F.; Klingensmith, G.; Nadeau, K.; Strike, H.; Walders, N.; Witten, T.] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. [Copeland, K.; Brown, R.; Chadwick, J.; Chalmers, L.; Macha, C.; Nordyke, A.; Poulsen, T.; Pratt, L.; Preske, J.; Schanuel, J.; Smith, J.; Sternlof, S.; Swisher, R.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Hale, D.; Amodei, N.; Barajas, R.; Cody, C.; Haffner, S.; Hernandez, J.; Lynch, J.; Morales, E.; Rivera, S.; Rupert, G.; Wauters, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [White, N.; Arbelaez, A.; Jones, J.; Jones, T.; Sadler, M.; Tanner, M.; Welch, R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Caprio, S.; Grey, M.; Guandalini, C.; Lavietes, S.; Rose, P.; Syme, A.; Tamborlane, W.] Yale Univ, New Haven, CT 06520 USA. [Hirst, K.; Coombs, L.; Edelstein, S.; Grover, N.; Long, C.; Pyle, L.] Washington Univ, Ctr Biostat, Coordinating Ctr George, St Louis, MO 63130 USA. [Linder, B.] NIDDK, Project Off, Bethesda, MD 20892 USA. [Marcovina, S.; Chmielewski, J.; Ramirez, M.; Strylewicz, G.] Univ Washington, NW Lipid Res Labs, Cent Units Cent Blood Lab, Seattle, WA 98195 USA. [Shepherd, J.; Fan, B.; Marquez, L.; Sherman, M.; Wang, J.] Univ Calif San Francisco, DEXA Reading Ctr, San Francisco, CA 94143 USA. [Mayer-Davis, E.; Liu, Y.; Nichols, M.] Univ S Carolina, Diet Assessment Ctr, Columbia, SC 29208 USA. [Wilfley, D. E.; Patterson, J.; Tibbs, T.; Van Buren, D.] Washington Univ, Lifestyle Program Core, St Louis, MO 63130 USA. [Zhang, P.] Ctr Dis Control, Atlanta, GA 30333 USA. [Palmert, M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Epstein, L.] SUNY Buffalo, Buffalo, NY 14260 USA. [Silverstein, J.] Univ Florida, Gainesville, FL 32611 USA. RP Wilfley, DE (reprint author), WUSM, Campus Box 8134,660 S Euclid, St Louis, MO 63110 USA. EM wilfleyd@psychiatry.wustl.edu FU NIDDK/NIH [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; NIMH [1K24MH070446-01]; National Center for Research Resources General Clinical Research Centers Program; Washington University School of Medicine [M01-RR00036]; Children's Hospital Los Angeles [M01-RR00043-45]; University of Colorado Health Sciences Center [M01-RR00069]; Children's Hospital of Pittsburgh [M01-RR00084]; Massachusetts General Hospital [M01-RR01066]; Yale University [M01-RR00125]; University of Oklahoma Health Sciences Center [M01-RR14467] FX This work was completed with funding from NIDDK/NIH grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254, from NIMH grant number 1K24MH070446-01 (Dr Wilfley) and from the National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069 (University of Colorado Health Sciences Center), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University) and M01-RR14467 (University of Oklahoma Health Sciences Center). Members of the writing group were D Wilfley (chair), B Berkowitz, L Epstein, K Hirst, A Kriska, L Laffel, M Marcus, T Tibbs and D Van Buren. NR 66 TC 12 Z9 12 U1 4 U2 17 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 FEB PY 2010 VL 34 IS 2 BP 217 EP 226 DI 10.1038/ijo.2009.195 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 555JZ UT WOS:000274508100001 ER PT J AU Righi, V Andronesi, OC Mintzopoulos, D Black, PM Tzika, AA AF Righi, Valeria Andronesi, Ovidiu C. Mintzopoulos, Dionyssios Black, Peter M. Tzika, A. Aria TI High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE brain/CNS cancers; tumor biomarkers; ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy ID SHORT ECHO-TIME; PROTON MR SPECTROSCOPY; NONKETOTIC HYPERGLYCINEMIA; GLIAL TUMORS; GRADE GLIOMA; H-1 MRS; SCHIZOPHRENIA; MYOINOSITOL; CELLS; CLASSIFICATION AB The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) (1)H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, NIT and GBM biopsies (P <= 0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification. C1 [Tzika, A. Aria] Massachusetts Gen Hosp, NMR Surg Lab, Dept Surg, Boston, MA 02114 USA. [Righi, Valeria; Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, NMR Surg Lab, Dept Surg, Sch Med, Boston, MA 02114 USA. [Righi, Valeria; Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Tzika, A. Aria] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Black, Peter M.] Harvard Univ, Dept Neurosurg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Tzika, AA (reprint author), Massachusetts Gen Hosp, NMR Surg Lab, Dept Surg, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu OI Righi, Valeria/0000-0003-2394-8462 FU National Institute Institutes of Health (NIH) [P50GM021700]; Shriners' Hospital [8893] FX This work was supported in part by a National Institute Institutes of Health (NIH) Center Grant (P50GM021700) to Ronald G. Tompkins (A. Aria Tzika, Director of the NMR core) and a Shriners' Hospital for Children research grant (no. 8893) to A. Aria Tzika. We also thank Dr Ann Power Smith of Write Science Right for editorial assistance. NR 38 TC 30 Z9 31 U1 1 U2 13 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 2010 VL 36 IS 2 BP 301 EP 306 DI 10.3892/ijo_00000500 PG 6 WC Oncology SC Oncology GA 547CB UT WOS:000273861900001 PM 20043062 ER PT J AU Lin, HW Kakarala, K Ostrower, ST Leonard, DS AF Lin, Harrison W. Kakarala, Kiran Ostrower, Samuel T. Leonard, David S. TI Laryngotracheobronchitis complicated by spontaneous pneumomediastinum SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Spontaneous pneumomediastinum; Croup; Laryngotracheobronchitis; Pediatric; Airway ID CHILDREN; EMPHYSEMA AB Spontaneous pneumomediastinum (SPM) is an unusual clinical entity that most frequently follows episodes of increased intrathoracic pressures. While typically a benign condition, potentially fatal complications of SPM must be considered and ruled out with each case. We aim to present the first case of croup-associated SPM in the otolaryngology literature and to discuss clinical, diagnostic and management principles. Days following the diagnosis of viral croup, a 7-year-old asthmatic girl presented with unstable vital signs and severe SPM. The patient was urgently taken to the operating room for an endoscopic airway evaluation, which revealed only a mild bacterial croup superinfection. Conservative treatment with inpatient monitoring and antibiotic therapy successfully resolved the episode. SPM should be immediately considered in the differential diagnosis of any patient presenting with cervical emphysema, especially in association with asthma, cough or strenuous activity. Following exclusion of other causes of SPM, conservative and supportive therapies are the mainstays of SPM management. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Lin, Harrison W.; Kakarala, Kiran] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Kakarala, Kiran; Ostrower, Samuel T.; Leonard, David S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Ostrower, Samuel T.; Leonard, David S.] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM harrison_lin@meei.harvard.edu OI Kakarala, Kiran/0000-0002-1003-8024 FU Royal College of Surgeons Ireland; Ethicon Foundation FX D.S.L. is supported by grants from the Royal College of Surgeons Ireland and the Ethicon Foundation. NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD FEB PY 2010 VL 74 IS 2 BP 221 EP 224 DI 10.1016/j.ijporl.2009.11.020 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 556NS UT WOS:000274598500022 PM 20018389 ER PT J AU Steinhauer, SR Condray, R AF Steinhauer, Stuart R. Condray, Ruth TI Psychophysiology of language processes in psychopathology: An overview of the special issue SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Editorial Material ID BRAIN POTENTIALS; RESPONSES; STIMULI C1 [Steinhauer, Stuart R.; Condray, Ruth] Univ Pittsburgh, Sch Med, Dept Psychiat, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. RP Steinhauer, SR (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. EM sthauer@pitt.edu FU NIMH NIH HHS [R01 MH050631, MH50631, R01 MH055762, R01 MH055762-11]; PHS HHS [55762] NR 13 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 63 EP 65 DI 10.1016/j.ijpsycho.2009.12.009 PG 3 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800001 PM 20034522 ER PT J AU Kuperberg, GR Kreher, DA Ditman, T AF Kuperberg, Gina R. Kreher, Donna A. Ditman, Tali TI What can Event-related Potentials tell us about language, and perhaps even thought, in schizophrenia? SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE ERP; N400; P600; Schizophrenia; Thought disorder; Language; Semantic; Delusions ID AUTOMATIC SPREADING ACTIVATION; WORKING-MEMORY CAPACITY; LEXICAL DECISION TASK; BRAIN POTENTIALS; ELECTROPHYSIOLOGICAL INSIGHTS; COMMUNICATION DISORDERS; SENTENCE COMPREHENSION; LINGUISTIC CONTEXT; SEMANTIC NETWORK; WORD RECOGNITION AB Disturbances of thought and language are fundamental to schizophrenia. Cognitive behavioral and electrophysiological research has implicated problems in two different neurocognitive mechanisms: abnormalities in the structure and function of semantic memory, and abnormalities in combining and integrating words together to build up sentence and discourse context. This review discusses recent electrophysiological evidence suggesting that these two deficits are not completely distinct, but rather that language impairment in schizophrenia results from a dysfunctional interaction between these systems in an effort to build up higher-order meaning. Moreover, although language abnormalities are more pronounced in patients with positive thought disorder, they manifest themselves in all patients when increased demands are placed on the comprehension system. Further investigation of language dysfunction may also provide insights into other aspects of psychotic thought. (C) 2009 Published by Elsevier B.V. C1 [Kuperberg, Gina R.; Kreher, Donna A.; Ditman, Tali] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.; Ditman, Tali] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Kuperberg, Gina R.; Ditman, Tali] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Mass Gen Hosp E, Bldg 149,13th St, Boston, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH [R01 MH071635]; NARSAD; Mass. General Hospital FX Gina Kuperberg, Tali Ditman and Donna Kreher were supported by NIMH (R01 MH071635). Gina Kuperberg was also supported by NARSAD (with the Sidney Baer Trust) and a Claflin Distinguished Scholars Award from Mass. General Hospital. NR 111 TC 28 Z9 29 U1 10 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 66 EP 76 DI 10.1016/j.ijpsycho.2009.09.005 PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800002 PM 19765622 ER PT J AU Sitnikova, T Perrone, C Goff, D Kuperberg, GR AF Sitnikova, Tatiana Perrone, Christopher Goff, Donald Kuperberg, Gina R. TI Neurocognitive mechanisms of conceptual processing in healthy adults and patients with schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE Real-world cognition; Schizophrenia; Comprehension of verbal and non-verbal information; Event-related potentials ID EVENT-RELATED POTENTIALS; REAL-WORLD EVENTS; BRAIN POTENTIALS; SENTENCE COMPREHENSION; PREFRONTAL CORTEX; WORKING-MEMORY; LANGUAGE COMPREHENSION; SEMANTIC INTEGRATION; THOUGHT-DISORDER; ELECTROPHYSIOLOGICAL INSIGHTS AB This overview outlines findings of cognitive and neurocognitive studies on comprehension of verbal, pictorial, and video stimuli in healthy participants and patients with schizophrenia. We present evidence for a distinction between two complementary neurocognitive streams of conceptual analysis during comprehension. In familiar situations, adequate understanding of events may be achieved by mapping the perceived information on the associative and similarity-based connections between concepts in semantic memory - a process reflected by an N400 waveform of event-related electrophysiological potentials (ERPs). However, in less conventional contexts, a more flexible mechanism may be needed. We suggest that this alternative processing stream, reflected by a P600 ERP waveform, may use discrete, rule-like goal-related requirements of real-world actions to comprehend relationships between perceived people, objects, and actions. This neurocognitive model of comprehension is used as a basis in discussing studies in schizophrenia. These studies suggest an imbalanced engagement of the two conceptual streams in schizophrenia, whereby patients may rely on the associative and similarity-based networks in semantic memory even when it would be more adaptive to recruit mechanisms that draw upon goal-related requirements. Finally, we consider the roles that these conceptual mechanisms may play in real-life behavior, and the consequences that their dysfunction may have for disorganized behavior and inability to plan actions to achieve behavioral goals in schizophrenia. (C) 2009 Elsevier B.V. All rights reserved. C1 [Sitnikova, Tatiana] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Charlestown, MA 02129 USA. [Sitnikova, Tatiana; Goff, Donald] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sitnikova, Tatiana; Perrone, Christopher; Goff, Donald; Kuperberg, Gina R.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Perrone, Christopher; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Sitnikova, T (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Bldg 149 2301,13th St, Charlestown, MA 02129 USA. EM tatiana@nmr.mgh.harvard.edu FU National Institute of Mental Health [MH085062, MH02034]; National Alliance for Research in Schizophrenia and Depression (NARSAD); MGH Fund; Mental Illness and Neuroscience Discovery (MIND) FX This work was funded by the National Institute of Mental Health (MH085062 to TS and MH02034 to GRK), the National Alliance for Research in Schizophrenia and Depression (NARSAD) with the Sidney J. Baer Trust (TS and GRK), the MGH Fund for Medical Discovery grant to TS, and the Institute for Mental Illness and Neuroscience Discovery (MIND). NR 175 TC 6 Z9 6 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 86 EP 99 DI 10.1016/j.ijpsycho.2009.12.002 PG 14 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800004 PM 20004221 ER PT J AU Siegle, GJ Condray, R Thase, ME Keshavan, M Steinhauer, SR AF Siegle, Greg J. Condray, Ruth Thase, Michael E. Keshavan, Matcheri Steinhauer, Stuart R. TI Sustained gamma-band EEG following negative words in depression and schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE Depression; Schizophrenia; Emotion; Gamma; EEG; Rumination ID FREQUENCY CORTICAL RESPONSES; AFFECTIVE REACTIVITY; EMOTIONAL INFORMATION; UNIPOLAR DEPRESSION; MOOD; STIMULI; FMRI; OSCILLATIONS; MEMORY; BRAIN AB Introduction: Sustained and elaborative emotional information processing in depression and decreased affective elaboration in schizophrenia are considered hallmarks of these disorders but have not been directly measured. Gamma-band (35-45 Hz) EEG has been associated with semantic functions such as feature binding and may index these elaborative processing. This study examined whether there were group differences in baseline and sustained gamma-band EEG following emotional stimuli in healthy adults as well as adults with depression and schizophrenia. Methods: 24 never-depressed healthy controls, 14 patients with DSM-IV unipolar major depressive disorder, and 15 patients with DSM-IV schizophrenia completed a lexical emotion identification task during EEG assessment. Gamma-band (35-45 Hz) EEG in response to negative words was the primary dependent measure. Results: As predicted, depressed individuals displayed sustained and increased gamma-band EEG throughout the task, and particularly in the seconds following negative words. Individuals with schizophrenia displayed decreased gamma-band activity throughout the task. Conclusions: These data suggest that gamma-band EEG, measured over several seconds, may serve as a useful index of sustained semantic information processing. Depressed individuals appear to engage in sustained elaboration following emotional stimuli, whereas individuals with schizophrenia are not as prone to this type of elaborative processing. (C) 2009 Published by Elsevier B.V. C1 [Siegle, Greg J.; Condray, Ruth; Thase, Michael E.; Keshavan, Matcheri; Steinhauer, Stuart R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Steinhauer, Stuart R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Siegle, GJ (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM gsiegle@pitt.edu FU NARSAD; Veteran's Research Foundation [MH30915, MH58356, MH60473]; [MH50631]; [MH64159] FX Supported by MH50631, NARSAD, MH64159, the Veteran's Research Foundation MH30915, MH58356, and MH60473. NR 57 TC 12 Z9 12 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 107 EP 118 DI 10.1016/j.ijpsycho.2008.04.008 PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800006 PM 20005267 ER PT J AU Condray, R Siegle, GJ Keshavan, MS Steinhauer, SR AF Condray, Ruth Siegle, Greg J. Keshavan, Matcheri S. Steinhauer, Stuart R. TI Effects of word frequency on semantic memory in schizophrenia: Electrophysiological evidence for a deficit in linguistic access SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE N400; Semantic relatedness; Word frequency; Schizophrenia; Atypical antipsychotics ID ACETYLCHOLINE-RECEPTOR AVAILABILITY; ALZHEIMERS-DISEASE; ATYPICAL ANTIPSYCHOTICS; PREFRONTAL CORTEX; BRAIN POTENTIALS; IMPAIRMENT; KNOWLEDGE; DISORDER; LANGUAGE; STORAGE AB Background: Abnormal storage and/or access are among the hypothesized causes of semantic memory deficit in schizophrenia. Neuropsychological and connectionist models have emphasized functional systems that serve the processing of word meaning and frequency: semantic storage disturbance is presumed to result from weak representations of word meaning; defective access is assumed to result from compromises to pathways that activate word frequency knowledge. Candidate biological systems include neuromodulatory pathways that normally function to enhance neural signals (e.g., cholinergic system). Electrophysiological responding may be informative regarding the storage-access distinction for schizophrenia. Methods: Visual event-related potentials were recorded for 14 schizophrenia outpatients receiving atypical antipsychotics, and 14 healthy controls group-matched to patients on age, gender, and demographics. N400 was elicited using an incidental semantic priming paradigm, in which semantic relatedness and word frequency were varied, and a letter probe task. Results: Compared to controls, patients showed reduced N400 (mu V) discrimination of semantic relatedness. Groups also showed different patterns of N400 to word frequency. Controls' N400 increased in negativity as words decreased in frequency of occurrence, while patients did not show a linear relationship between N400 and word frequency. Groups also differed for N400 to frequently occurring words. Patients exhibited increased negativity to high and very high frequency words, compared to controls. A subgroup of patients receiving antipsychotics with known affinity binding for muscarinic receptors (clozapine and olanzapine) showed significant albeit limited N400 priming, but their N400 to word frequency remained nonsignificant. Conclusions: Results suggest a deficit in semantic access for schizophrenia, as well as an influence of neuromodulators on the activation of connections among semantic representations. Cumulative findings indicating only limited N400 priming for patients receiving either typical or atypical antipsychotics support the hypothesis that semantic memory deficit represents a trait marker for schizophrenia. (C) 2009 Elsevier B.V. All rights reserved. C1 [Condray, Ruth; Siegle, Greg J.; Keshavan, Matcheri S.; Steinhauer, Stuart R.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Steinhauer, Stuart R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Keshavan, Matcheri S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Condray, R (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM condrayr@upmc.edu FU National Institute of Mental Health [MH50631, MH55762, MH64023] FX This research was supported by the National Institute of Mental Health (MH50631 (RC), MH55762 (SRS), and MH64023 (MSK)), and with resources and use of facilities at Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. We are grateful to the patients who served as study participants. We are also grateful to a number of individuals who made valuable contributions to the study, including Debra Montrose, Ph.D., and the clinical and nursing staff of Western Psychiatric Institute and Clinic. Sincere thanks to Gregory A. Miller, Ph.D., for providing software for correction of eye movement artifacts, and to Patricia Carpenter, Ph.D., Daniel P. van Kammen, M.D., Ph.D., and William P. Wallace, Ph.D., for their generosity during discussions with the first author (R.C.) regarding study design and analytic approaches. Technical support was provided by Elisa LaDonne, M.Ed., Vince Penkrot, M.S., Carole Turocy, M.S.W., and jean Turocy, B.S. NR 76 TC 15 Z9 15 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 141 EP 156 DI 10.1016/j.ijpsycho.2009.10.010 PG 16 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800010 PM 19896508 ER PT J AU Dale, CL Findlay, AM Adcock, RA Vertinski, M Fisher, M Genevsky, A Aldebot, S Subramaniam, K Luks, TL Simpson, GV Nagarajan, SS Vinogradov, S AF Dale, Corby L. Findlay, Anne M. Adcock, R. Alison Vertinski, Mary Fisher, Melissa Genevsky, Alexander Aldebot, Stephanie Subramaniam, Karuna Luks, Tracy L. Simpson, Gregory V. Nagarajan, Srikantan S. Vinogradov, Sophia TI Timing is everything: Neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Review DE Schizophrenia; MEG; Auditory processing; Linguistic perception; M100; Voice onset time; Place of articulation; Second syllable attenuation ID MISMATCH NEGATIVITY; LEARNING-PROBLEMS; SPEECH-PERCEPTION; LANGUAGE LATERALIZATION; AUDITORY DYSFUNCTION; EVOKED-POTENTIALS; MAGNETIC-FIELDS; VERBAL MEMORY; HUMAN-BRAIN; DEFICITS AB Successful linguistic processing requires efficient encoding of successively-occurring auditory input in a time-constrained manner, especially under noisy conditions. In this study we examined the early neural response dynamics to rapidly-presented successive syllables in schizophrenia participants and healthy comparison subjects, and investigated the effects of noise on these responses. We used magnetoencephalography (MEG) to reveal the time-course of stimulus-locked activity over bilateral auditory cortices during discrimination of syllable pairs that differed either in voice onset time (VOT) or place of articulation (POA), in the presence or absence of noise. We also examined the association of these early neural response patterns to higher-order cognitive functions. The M100 response, arising from auditory cortex and its immediate environs, showed less attenuation to the second syllable in patients with schizophrenia than healthy comparison subjects during VOT-based discrimination in noise. M100 response amplitudes were similar between groups for the first syllable during all three discrimination conditions, and for the second syllable during VOT-based discrimination in quiet and POA-based discrimination in noise. Across subjects, the lack of M100 attenuation to the second syllable during VOT-based discrimination in noise was associated with poorer task accuracy, lower education and IQ and lower scores on measures of Verbal Learning and Memory and Global Cognition. Because the neural response to the first syllable was not significantly different between groups, nor was a schizophrenia-related difference obtained in all discrimination tasks, early linguistic processing dysfunction in schizophrenia does not appear to be due to general sensory input problems. Rather, data suggest that faulty temporal integration occurs during successive syllable processing when the signal-to-noise ratio is low. Further, the neural mechanism by which the second syllable is suppressed during noise-challenged VOT discrimination appears to be important for higher-order cognition and provides a promising target for neuroscience-guided cognitive training approaches to schizophrenia. Published by Elsevier B.V. C1 [Vinogradov, Sophia] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Dale, Corby L.; Findlay, Anne M.; Luks, Tracy L.; Simpson, Gregory V.; Nagarajan, Srikantan S.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Adcock, R. Alison] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Adcock, R. Alison] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27706 USA. [Dale, Corby L.; Fisher, Melissa; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Vinogradov, S (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. EM Sophia.vinogradov@ucsf.edu FU NIH [MH068725, R01 DC4855, R01 DC6435] FX We would like to thank Leighton Hinkley, Alexander B. Herman, Kasra Khatibi, and Darren Weber for their help with the analysis and presentation of this research. This project was supported with resources and the use of facilities at the San Francisco VA Medical Center, San Francisco, CA, and by NIH RO1 grant MH068725 to SM. and NIH R01 DC4855 and DC6435 to S.S.N. NR 74 TC 23 Z9 23 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD FEB PY 2010 VL 75 IS 2 SI SI BP 183 EP 193 DI 10.1016/j.ijpsycho.2009.10.009 PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 570TK UT WOS:000275700800014 PM 19879305 ER PT J AU Nguyen, PL Chen, MH Renshaw, AA Loffredo, M Kantoff, PW D'Amico, AV AF Nguyen, Paul L. Chen, Ming-Hui Renshaw, Andrew A. Loffredo, Marian Kantoff, Philip W. D'Amico, Anthony V. TI SURVIVAL FOLLOWING RADIATION AND ANDROGEN SUPPRESSION THERAPY FOR PROSTATE CANCER IN HEALTHY OLDER MEN: IMPLICATIONS FOR SCREENING RECOMMENDATIONS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Elderly; Comorbidity; Androgen suppression therapy; Radiation; Screening ID COMORBIDITY; DEPRIVATION; IMPACT; TRIAL AB Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Among healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio 0.36 (95% CI = 0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity. (C) 2010 Elsevier Inc. C1 [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.; Loffredo, Marian; D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 12 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2010 VL 76 IS 2 BP 337 EP 341 DI 10.1016/j.ijrobp.2009.01.045 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 550IM UT WOS:000274121500004 PM 19395186 ER PT J AU Michalski, JM Lawton, C El Naqa, I Ritter, M O'Meara, E Seider, MJ Lee, WR Rosenthal, SA Pisansky, T Catton, C Valicenti, RK Zietman, AL Bosch, WR Sandler, H Buyyounouski, MK Menard, C AF Michalski, Jeff M. Lawton, Colleen El Naqa, Issam Ritter, Mark O'Meara, Elizabeth Seider, Michael J. Lee, W. Robert Rosenthal, Seth A. Pisansky, Thomas Catton, Charles Valicenti, Richard K. Zietman, Anthony L. Bosch, Walter R. Sandler, Howard Buyyounouski, Mark K. Menard, Cynthia TI DEVELOPMENT OF RTOG CONSENSUS GUIDELINES FOR THE DEFINITION OF THE CLINICAL TARGET VOLUME FOR POSTOPERATIVE CONFORMAL RADIATION THERAPY FOR PROSTATE CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Conformal radiation therapy; Target volumes; Postoperative ID RADICAL PROSTATECTOMY; LOCAL RECURRENCE; ADJUVANT RADIOTHERAPY; ALGORITHM; TRIAL; COIL; MEN AB Purpose: To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer. Methods and Materials: An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary "consensus" PF-CTV. Results: Starting from the model-derived CTV, consensus was reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8-12 nun interior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1-2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement. Conclusions: Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT. (C) 2010 Elsevier Inc. C1 [Michalski, Jeff M.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. [Lawton, Colleen] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Ritter, Mark] Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. [O'Meara, Elizabeth] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Seider, Michael J.] Akron City Hosp, Akron, OH USA. [Lee, W. Robert] Duke Univ, Med Ctr, Durham, NC USA. [Rosenthal, Seth A.] Radiol Associates Sacramento, Radiat Oncol Ctr, Sacramento, CA USA. [Pisansky, Thomas] Mayo Clin, Rochester, MN USA. [Catton, Charles; Menard, Cynthia] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Valicenti, Richard K.] Bodine Ctr Canc Treatment, Philadelphia, PA USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sandler, Howard] Univ Michigan, Ann Arbor, MI 48109 USA. [Buyyounouski, Mark K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Michalski, JM (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4921 Parkview Pl,Campus Box 8224, St Louis, MO 63110 USA. EM michalski@wustl.edu FU NCI NIH HHS [U10 CA021661, CA21661, CA32115, CA37422, U10 CA021661-32, U10 CA032115, U10 CA032115-26, U10 CA037422, U10 CA037422-22, U24 CA081647, U24 CA081647-11] NR 19 TC 100 Z9 103 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 FEB 1 PY 2010 VL 76 IS 2 BP 361 EP 368 DI 10.1016/j.ijrobp.2009.02.006 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 550IM UT WOS:000274121500008 PM 19394158 ER PT J AU Cormack, RA Sridhar, S Suh, WW D'Amico, AV Makrigiorgos, GM AF Cormack, Robert A. Sridhar, Srinivas Suh, W. Warren D'Amico, Anthony V. Makrigiorgos, G. Mike TI BIOLOGICAL IN SITU DOSE PAINTING FOR IMAGE-GUIDED RADIATION THERAPY USING DRUG-LOADED IMPLANTABLE DEVICES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Image-guided radiation therapy; Fiducials; Brachytherapy seeds; Lung SBRT treatment ID RATE IRRADIATION; PACLITAXEL; DELIVERY; TUMORS; PHARMACOKINETICS; RADIOTHERAPY; RELEASE; CANCER; BRAIN; CELLS AB Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ("eluters"), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate (125)I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters; versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for similar to 4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of "biologically equivalent doses" to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region Juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting. (C) 2010 Elsevier Inc. C1 [Cormack, Robert A.; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Sridhar, Srinivas] Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. [Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), DFCI BWH Hosp, Dept Radiat Oncol, Div Med Phys & Biophys, 75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu RI Sridhar, Srinivas/A-3688-2012; OI Cormack, Robert/0000-0001-5553-9984 FU Kayes Scholars FX This work was funded by a Kayes Scholars grant award. NR 27 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2010 VL 76 IS 2 BP 615 EP 623 DI 10.1016/j.ijrobp.2009.06.039 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 550IM UT WOS:000274121500042 PM 19879699 ER PT J AU Kooy, HM Clasie, BM Lu, HM Madden, TM Bentefour, H Depauw, N Adams, JA Trofimov, AV Demaret, D Delaney, TF Flanz, JB AF Kooy, Hanne M. Clasie, Benjamin M. Lu, Hsiao-Ming Madden, Thomas M. Bentefour, Hassan Depauw, Nicolas Adams, Judy A. Trofimov, Alexei V. Demaret, Denis Delaney, Thomas F. Flanz, Jacob B. TI A CASE STUDY IN PROTON PENCIL-BEAM SCANNING DELIVERY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Proton radiotherapy; Pencil-beam scanning; Optimization; Treatment planning ID INTENSITY-MODULATED PHOTON; PAUL-SCHERRER-INSTITUTE; THERAPY; ALGORITHM; SARCOMA AB Purpose: We completed an implementation of pencil-beam scanning (PBS), a technology whereby a focused beam of protons, of variable intensity and energy, is scanned over a plane perpendicular to the beam axis and in depth. The aim of radiotherapy is to improve the target to healthy tissue dose differential. We illustrate how PBS achieves this aim in a patient with a bulky tumor. Methods and Materials: Our first deployment of PBS uses "broad" pencil-beams ranging from 20 to 35 mm (full-width-half-maximum) over the range interval from 32 to 7 g/cm(2). Such beam-brushes offer a unique opportunity for treating bulky tumors. We present a case study of a large (4,295 cc clinical target volume) retroperitoneal sarcoma treated to 50.4 Gy relative biological effectiveness (RBE) (presurgery) using a course of photons and protons to the clinical target volume and a course of protons to the gross target volume. Results: We describe our system and present the dosimetry for all courses and provide an interdosimetric comparison. Discussion: The use of PBS for bulky targets reduces the complexity of treatment planning and delivery compared with collimated proton fields. In addition, PBS obviates, especially for cases as presented here, the significant cost incurred in the construction of field-specific hardware. PBS offers improved dose distributions, reduced treatment time, and reduced cost of treatment. (C) 2010 Elsevier Inc. C1 [Kooy, Hanne M.; Clasie, Benjamin M.; Lu, Hsiao-Ming; Madden, Thomas M.; Depauw, Nicolas; Adams, Judy A.; Trofimov, Alexei V.; Delaney, Thomas F.; Flanz, Jacob B.] Massachusetts Gen Hosp, Dept Radiat Oncol, FH Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Kooy, Hanne M.; Clasie, Benjamin M.; Lu, Hsiao-Ming; Madden, Thomas M.; Depauw, Nicolas; Adams, Judy A.; Trofimov, Alexei V.; Delaney, Thomas F.; Flanz, Jacob B.] Harvard Univ, Sch Med, Boston, MA USA. [Bentefour, Hassan; Demaret, Denis] IBA Ltd, Louvain, Belgium. RP Kooy, HM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, FH Burr Proton Therapy Ctr, Boston, MA 02114 USA. EM hkooy@partners.org FU National Cancer Institute [POI-CA21239] FX Supported in part by program project grant POI-CA21239 from the National Cancer Institute. NR 10 TC 38 Z9 38 U1 0 U2 11 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 FEB 1 PY 2010 VL 76 IS 2 BP 624 EP 630 DI 10.1016/j.ijrobp.2009.06.065 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 550IM UT WOS:000274121500043 PM 20117294 ER PT J AU Smith, BD Arthur, DW Todor, DA Buchholz, TA Haffty, BG Hahn, CA Hardenbergh, PH Julian, TB Marks, LB Vicini, FA Whelan, TJ White, J Wo, JY Harris, JR AF Smith, Benjamin D. Arthur, Douglas W. Todor, Dorin A. Buchholz, Thomas A. Haffty, Bruce G. Hahn, Carol A. Hardenbergh, Patricia H. Julian, Thomas B. Marks, Lawrence B. Vicini, Frank A. Whelan, Timothy J. White, Julia Wo, Jennifer Y. Harris, Jay R. TI CONSENSUS STATEMENT: APBI FROM ASTRO (INT J RADIA T ONCOL BIOL PHYS 2009;74:987-1001) Reply SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 [Smith, Benjamin D.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. [Smith, Benjamin D.; Buchholz, Thomas A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Arthur, Douglas W.; Todor, Dorin A.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. [Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ USA. [Hahn, Carol A.] Duke Univ, Sch Med, Dept Radiat Oncol, Durham, NC USA. [Hardenbergh, Patricia H.] Shaw Reg Canc Ctr, Vail, CO USA. [Julian, Thomas B.] Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. [Marks, Lawrence B.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. [Vicini, Frank A.] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. [Whelan, Timothy J.] Juravinski Canc Ctr, Dept Radiat Oncol, Hamilton, ON, Canada. [White, Julia] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Wo, Jennifer Y.] Harvard Univ, Sch Med, Radiat Oncol Residency Program, Boston, MA USA. [Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Smith, BD (reprint author), Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA. RI Whelan, Timothy/D-3185-2017; OI Smith, Benjamin/0000-0001-7866-1093 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2010 VL 76 IS 2 BP 638 EP 639 DI 10.1016/j.ijrobp.2009.09.013 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 550IM UT WOS:000274121500046 ER PT J AU Traynor, AM Lee, JW Bayer, GK Tate, JM Thomas, SP Mazurczak, M Graham, DL Kolesar, JM Schiller, JH AF Traynor, Anne M. Lee, Ju-Whei Bayer, Gerald K. Tate, John M. Thomas, Sachdev P. Mazurczak, Miroslaw Graham, David L. Kolesar, Jill M. Schiller, Joan H. TI A phase II trial of TriapineA (R) (NSC# 663249) and gemcitabine as second line treatment of advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Study 1503 SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Non-small cell lung cancer; Combination chemotherapy; Ribonucleotide reductase; Single nucleotide polymorphism; ATP binding cassette transporter ID 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; RIBONUCLEOTIDE REDUCTASE INHIBITOR; P-GLYCOPROTEIN; MDR1; ADENOCARCINOMA; RESISTANCE; RRM1; POLYMORPHISMS; SUPPRESSION; EXPRESSION AB Background: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. Methods: Triapine 105 mg/m(2) IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15, of a 28 day cycle. Results: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7-44%). Median overall survival: 5.4 months (95% CI 4.2-11.6 months); median time to progression: 1.8 months (95% CI 1.7-3.5 months). Five patients developed acute infusion reactions to TriapineA (R) related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). Conclusion: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating. C1 [Traynor, Anne M.; Kolesar, Jill M.] Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bayer, Gerald K.] St Vincent Hosp, Green Bay, WI USA. [Mazurczak, Miroslaw] Sanford Hosp, Sanford Clin Oncol, Sioux Falls, SD USA. [Graham, David L.] Carle Canc Assoc, Urbana, IL USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hematol & Oncol, Dallas, TX 75390 USA. [Tate, John M.] Merit Care Hosp CCOP, Roger Maris Canc Ctr, Fargo, ND USA. [Thomas, Sachdev P.] Illinois Canc Care, Peoria, IL USA. RP Traynor, AM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, K6-568 CSC,5669,600 Highland Ave, Madison, WI 53792 USA. EM amt@medicine.wisc.edu RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU University of Wisconsin Paul P. Carbone Comprehensive Cancer Center [K12 CA087716, 5 P30 CA014520-35]; Public Health Service [CA23318, CA66636, CA21115, CA21076]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX The authors thank the patients who participated in this trial, as well as the investigators who enrolled patients, and the data managers, and the clinical and research nurses who brought this trial to completion. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K12 CA087716 and 5 P30 CA014520-35, and by the Public Health Service Grants CA23318, CA66636, CA21115, CA21076, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 28 TC 45 Z9 47 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD FEB PY 2010 VL 28 IS 1 BP 91 EP 97 DI 10.1007/s10637-009-9230-z PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 540FW UT WOS:000273317700010 PM 19238328 ER PT J AU Jin, YP Chauhan, SK Saban, DR Dana, R AF Jin, Yiping Chauhan, Sunil K. Saban, Daniel R. Dana, Reza TI Role of CCR7 in Facilitating Direct Allosensitization and Regulatory T-Cell Function in High-Risk Corneal Transplantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DENDRITIC CELLS; ALLOGRAFT-REJECTION; LYMPH-NODES; BONE-MARROW; TOLERANCE; MICE; SKIN; ALLOANTIGENS; TRAFFICKING; EXPANSION AB PURPOSE. Chemokine receptor 7 (CCR7) is a key homing molecule for immune cell trafficking, including corneal antigen-presenting cell (APC) migration from the inflamed cornea to draining lymph nodes (LNs). Here, the authors investigated the effect of CCR7-facilitated donor APC trafficking on allosensitization, regulatory T-cell (Treg) function, and graft survival in corneal transplantation. METHODS. CCR7(-/-) or wild-type (WT) allogeneic corneal grafts were transplanted onto the neovascularized high-risk recipient beds. Two weeks later, the frequency of directly alloprimed host T cells was measured by the IFN-gamma ELISPOT assay. Treg function was tested by a coculture suppression assay and an IFN-gamma ELISPOT assay. Kaplan-Meier analysis was performed to evaluate graft survival. RESULTS. The recipients of CCR7(-/-) grafts had fewer migrated donor APCs and lower frequency of IFN-gamma-producing T cells in the draining LNs. However, there was no statistically significant difference in transplant survival between recipients of CCR7(-/-) and those of WT grafts. Tregs from the CCR7(-/-) graft recipient group showed reduced regulatory potential for the suppression of proliferation of naive T cells and direct alloprimed T cells and expressed lower Foxp3 levels. In vitro studies confirmed that mature CCR7(+) major histocompatibility complex class II(+) CD86(+) graft-derived dendritic cells were critical for Treg function. CONCLUSIONS. Not only is CCR7-mediated donor-derived APC trafficking to the draining LNs important in the initiation of host T-cell priming, it is crucial for Treg-mediated tolerance. (Invest Ophthalmol Vis Sci. 2010; 51: 816-821) DOI:10.1167/iovs.09-3952 C1 [Jin, Yiping; Chauhan, Sunil K.; Saban, Daniel R.; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Jin, Yiping; Chauhan, Sunil K.; Saban, Daniel R.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [R01-EY 12963] FX Supported by National Institutes of Health Grant R01-EY 12963 (RD). NR 29 TC 13 Z9 14 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2010 VL 51 IS 2 BP 816 EP 821 DI 10.1167/iovs.09-3952 PG 6 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700028 PM 19797201 ER PT J AU Sayegh, RR Diaz, LA Vargas-Martin, F Webb, RH Dohlman, CH Peli, E AF Sayegh, Rony R. Diaz, Linda Avena Vargas-Martin, Fernando Webb, Robert H. Dohlman, Claes H. Peli, Eli TI Optical Functional Properties of the Boston Keratoprosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GLARE; PROSTHESES; LENS AB PURPOSE. To evaluate the optical characteristics of the Boston Keratoprosthesis (KPro), identify glare sources, evaluate possible glare control, and examine the benefit of implantation when the fellow eye has normal vision. METHODS. Computed and optical-bench-measured point spread function (PSF) and glare sources were compared. A translucent plastic cornea was used to determine the impact of glare caused by scatter in the cornea and its control with a dark-iris tinted contact lens. The effect of glare in implanted eyes was measured with a brightness acuity test (BAT), with and without the dark-iris contact lens. Computed and measured visual fields were compared. Stereopsis was measured in patients with an intact fellow eye. RESULTS. Computed and measured modulation transfer functions for the KPro were found to be very close to the diffraction limit. Both the model-eye measurements and patients' BAT glare responses identified that the hazy corneal graft surrounding the KPro is the main source of glare and can be controlled with a dark-iris contact lens. The lid effectively blocks the light that would be scattered in the hazy cornea of patients in whom the type II KPro was implanted. An intact fellow eye remains the dominant eye, with better acuity, and the KPro eye supports only minimal stereo ability and does not expand the binocular visual field. CONCLUSIONS. Glare can be reduced significantly with the use of a contact lens with a dark iris. Implanting the KPro in a patient whose fellow eye has normal or near normal vision does not seem to improve visual function. (Invest Ophthalmol Vis Sci. 2010; 51: 857-863) DOI:10.1167/iovs.09-3372 C1 [Sayegh, Rony R.; Vargas-Martin, Fernando; Webb, Robert H.; Dohlman, Claes H.; Peli, Eli] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Sayegh, Rony R.; Diaz, Linda Avena; Dohlman, Claes H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Vargas-Martin, Fernando] Univ Murcia, Dept Fis, E-30071 Murcia, Spain. RP Peli, E (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM eli.peli@schepens.harvard.edu RI Sayegh, Rony/G-8777-2013 OI Sayegh, Rony/0000-0002-0119-4201 FU National Institutes of Health [EY12890]; Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary FX Supported in part by National Institutes of Health Grant EY12890 (EP) and by the Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary. NR 18 TC 16 Z9 17 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2010 VL 51 IS 2 BP 857 EP 863 DI 10.1167/iovs.09-3372 PG 7 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700034 PM 19815733 ER PT J AU Kang, JH Wiggs, JL Rosner, BA Hankinson, SE Abdrabou, W Fan, BJ Haines, J Pasquale, LR AF Kang, Jae Hee Wiggs, Janey L. Rosner, Bernard A. Hankinson, Susan E. Abdrabou, Wael Fan, Bao Jian Haines, Jonathan Pasquale, Louis R. TI Endothelial Nitric Oxide Synthase Gene Variants and Primary Open-Angle Glaucoma: Interactions with Sex and Postmenopausal Hormone Use SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2009 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID OCULAR BLOOD-FLOW; REPLACEMENT THERAPY; INTRAOCULAR-PRESSURE; BREAST-CANCER; POSTURE CHANGE; WOMEN; RISK; ESTROGEN; MENOPAUSE; REPRODUCIBILITY AB PURPOSE. To evaluate the association between the nitric oxide synthase gene (NOS3) variants and primary open-angle glaucoma (POAG). METHODS. Two functional single-nucleotide polymorphisms (SNPs) (T - 786C: rs2070744; Glu298Asp: rs1799983) and three tagging SNPs (rs7830, rs3918188, and rs1800779) were evaluated in a nested case-control study from the Nurses' Health Study (1980-2002) and the Health Professionals' Follow-up Study (1986-2002). Participants were aged >= 40 years and Caucasian. Included were 527 incident cases and 1543 controls, matched by cohort, age, and eye examination at the matched cases' diagnosis dates. Cohort-specific relative risks (RR) were estimated by using multivariable conditional logistic regression and were pooled with meta-analysis. RESULTS. No NOS3 polymorphism was significantly associated with overall POAG. For high-tension POAG (HTPOAG), rs3918188 was significantly inversely associated among the women (AA versus CC genotype: RR = 0.48; 95% CI, 0.28-0.82) but not among the men (P-heterogeneity by sex = 0.02). The minor alleles of T - 786C and rs1800779 showed positive association with high-tension POAG (P-trend < 0.02) in the women only, but P-heterogeneity was not significant. In the women, four of the five NOS3 SNPs showed significant interactions with postmenopausal hormone (PMH) use in relation to HTPOAG: for example, among the women with the TT genotype in T - 786C, PMH use was inversely associated (RR = 0.41; 95% CI, 0.22-0.76), but among carriers of the minor allele, use of PMH was not associated. CONCLUSIONS. Interactions were observed between NOS3 SNPs and female sex and postmenopausal hormone use in the women in relation to HTPOAG. These findings should be confirmed in different racial/ethnic groups. (Invest Ophthalmol Vis Sci. 2010; 51: 971-979) DOI:10.1167/iovs.09-4266 C1 [Wiggs, Janey L.; Abdrabou, Wael; Fan, Bao Jian; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Kang, Jae Hee; Rosner, Bernard A.; Hankinson, Susan E.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Kang, Jae Hee; Rosner, Bernard A.; Hankinson, Susan E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Haines, Jonathan] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM pasquale@meei.harvard.edu OI Fan, Baojian/0000-0002-6851-2737 FU NCI NIH HHS [P01 CA087969-01, P01 CA055075, P01 CA055075-17, P01 CA087969]; NEI NIH HHS [R01 EY009611, R01 EY009611-09, R01 EY015473, R01 EY015473-08]; NHLBI NIH HHS [R01 HL035464, R01 HL035464-22] NR 49 TC 53 Z9 54 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2010 VL 51 IS 2 BP 971 EP 979 DI 10.1167/iovs.09-4266 PG 9 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700049 PM 19815736 ER PT J AU Sandberg, MA Johnson, EJ Berson, EL AF Sandberg, Michael A. Johnson, Elizabeth J. Berson, Eliot L. TI The Relationship of Macular Pigment Optical Density to Serum Lutein in Retinitis Pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CENTRAL RETINAL THICKNESS; TISSUE CONCENTRATIONS; PRIMATE RETINAS; VISUAL-ACUITY; CAROTENOIDS; ZEAXANTHIN; DIETARY; DEGENERATION; ASSOCIATION; PREVALENCE AB PURPOSE. To determine whether macular pigment optical density (MPOD) is related to serum lutein or serum zeaxanthin in patients with retinitis pigmentosa. METHODS. The authors measured MPOD with heterochromatic flicker photometry, serum lutein and serum zeaxanthin by high performance liquid chromatography, and central foveal retinal thickness by optical coherence tomography (OCT) in 176 patients (age range, 18-68 years) with typical forms of retinitis pigmentosa; 37 (21%) of these patients had cystoid macular edema (CME) by OCT. The authors performed multiple regression analysis with MPOD as the dependent variable and with log e serum lutein and log e serum zeaxanthin as independent variables adjusting for age, sex, iris color, central foveal retinal thickness, and, in some analyses, serum total cholesterol. RESULTS. MPOD increased with increasing serum lutein (P = 0.0017) and decreased with increasing serum total cholesterol (P = 0.0025) but was unrelated to serum zeaxanthin. MPOD was higher in patients with brown irides than in patients with lighter irides (P = 0.014) and was nonmonotonically related to central foveal retinal thickness (P < 0.0001), being lower in eyes with more photoreceptor cell loss and in eyes with moderate to marked CME. CONCLUSIONS. MPOD is independently related to serum lutein, serum total cholesterol, iris color, and central foveal retinal thickness in patients with retinitis pigmentosa. (Invest Ophthalmol Vis Sci. 2010;51:1086-1091) DOI:10.1167/iovs.09-3396 C1 [Sandberg, Michael A.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Johnson, Elizabeth J.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM masandberg@aol.com FU National Eye Institute [EY00169]; United States Department of Agriculture [58-1950-7-707]; Foundation Fighting Blindness FX Supported by National Eye Institute Grant EY00169, the United States Department of Agriculture under agreement number 58-1950-7-707, and The Foundation Fighting Blindness. NR 42 TC 6 Z9 6 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 FEB PY 2010 VL 51 IS 2 BP 1086 EP 1091 DI 10.1167/iovs.09-3396 PG 6 WC Ophthalmology SC Ophthalmology GA 545AS UT WOS:000273704700064 PM 19797209 ER PT J AU Yin, MT Lu, DL Cremers, S Tien, PC Cohen, MH Shi, QH Shane, E Golub, ET Anastos, K AF Yin, Miehael T. Lu, Dalian Cremers, Serge Tien, Phyllis C. Cohen, Mardge H. Shi, Qiuhu Shane, Elizabeth Golub, Elizabeth T. Anastos, Kathryn TI Short-Term Bone Loss in HIV-Infected Premenopausal Women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE bone density; bone loss; bone turnover markers; HIV; osteoporosis; premenopausal women ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; KAPPA-B LIGAND; MINERAL DENSITY; RECEPTOR ACTIVATOR; OSTEOPROTEGERIN; ASSOCIATION; MARKERS; WEIGHT; SYSTEM AB Background: Low bone mineral density (BMD) has been reported in HIV+ women, but less is known about the longitudinal evolution of BMD and fracture incidence. Methods: In 100 HIV+ and 68 HIV- premenopausal women in the Women's Interagency HIV Study, BMD was measured by dual energy x-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) at index visit and after a median of 2.5 years. Results: In HIV+ women, BMD at index visit was normal but 5% lower at the LS and FN than in HIV- women. Annual percent decrease in BMD did not differ between HIV+ and HIV- women at the LS (-0.8% +/- 0.2% vs -0.4% +/- - 0.2%, P = 0.20) or FN (-0.8% +/- 0.3% vs -0.6% +/- 0.3%, P = 0.56) and remained similar after adjustment for age, weight, and BMD at index visit. Among HIV+ women, bone loss was associated with vitamin D deficiency and opiate use but not with use or class of antiretrovirals. Incidence of self-reported fracture was 0.74 per 100 person-years in HIV+ women and similar in HIV- women. Conclusions: in premenopausal HIV+ women, index BMD was lower than comparable HIV- women; however, rates of bone loss at the LS and FN were similar over 2.5 years of observation, irrespective of antiretroviral therapy. C1 [Yin, Miehael T.] Columbia Univ, Div Infect Dis, Med Ctr, Dept Med, New York, NY 10032 USA. [Lu, Dalian] Data Solut LLC, Bronx, NY USA. [Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Shi, Qiuhu] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. RP Yin, MT (reprint author), Columbia Univ, Div Infect Dis, Med Ctr, Dept Med, 630 W168th St,PH8 876, New York, NY 10032 USA. EM mty4@columbia.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131]; [A1059884]; [A11065200] FX The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834: UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Also supported by A1059884 (MY) and A11065200 (ES). NR 36 TC 43 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2010 VL 53 IS 2 BP 202 EP 208 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549EQ UT WOS:000274029000007 PM 19890216 ER PT J AU Fischer, MJ Wyatt, CM Gordon, K Gibert, CL Brown, ST Rimland, D Rodriguez-Barradas, MC Justice, AC Parikh, CR AF Fischer, Michael J. Wyatt, Christina M. Gordon, Kirsha Gibert, Cynthia L. Brown, Sheldon T. Rimland, David Rodriguez-Barradas, Maria C. Justice, Amy C. Parikh, Chirag R. CA VACS Project Team TI Hepatitis C and the Risk of Kidney Disease and Mortality in Veterans With HIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE death; HIV; hepatitis C; kidney failure; veterans ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; STAGE RENAL-DISEASE; INFECTED PATIENTS; COINFECTION; PROGRESSION; COHORT; IMPACT; ASSOCIATION; OUTCOMES AB Objectives: To examine the effect of hepatitis C virus (HCV) oil the prevalence of chronic kidney disease (CKD) among veterans with HIV and to evaluate independent associations of HCV and CKD with mortality. Methods: We studied a national cohort of HIV-infected patients receiving care through the Veterans Healthcare Administration from 1998 to 2004. CKD was defined as an estimated glomerular filtration rate [eGFR (mL/min/1.73 m(2))] < 60. Poisson regression was used to assess relationships between CKD, HCV, and mortality. Results: Among 23,155 HIV-infected veterans, 12% had CKD. Forty percent of the cohort was coinfected with HCV, and a higher proportion of coinfected subjects had CKD compared with monoinfected subjects (14% vs 11%, P < 0.001). During the median follow-up of 7.6 years, 37% of subjects died and a graduated increase in adjusted mortality rates occurred with lower levels of eGFR (P < 0.001). Adjusted mortality rates were consistently higher in HCV-coinfected subjects across all levels of eGFR (P < 0.001). HCV was independently associated with increased mortality (incidence rate ratio 1.23, 95% confidence interval 1.17-1.29). Conclusions: CKD is prevalent in HIV-infected veterans and associated with substantially higher mortality. Compared with their monoinfected counterparts, veterans coinfected with HCV have significantly higher rates of CKD and mortality. C1 [Fischer, Michael J.] Univ Illinois, Dept Med, Nephrol Sect, Jesse Brown VA Med Ctr, Chicago, IL 60612 USA. [Fischer, Michael J.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA. [Wyatt, Christina M.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY USA. [Gordon, Kirsha; Justice, Amy C.; Parikh, Chirag R.; VACS Project Team] W Haven VA Med Ctr, New Haven, CT USA. [Gibert, Cynthia L.] George Washington Univ, Div Infect Dis, Dept Med, VA Med Ctr,Med Ctr, Washington, DC 20037 USA. [Brown, Sheldon T.] Mt Sinai Sch Med, Dept Med, Infect Dis Sect, James J Peters VA Med Ctr, New York, NY USA. [Rimland, David] Atlanta VA Emory Univ, Dept Med, Div Infect Dis, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Infect Dis Sect, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Justice, Amy C.] Yale Univ, Dept Med, Sch Med, New Haven, CT 06520 USA. [Justice, Amy C.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Nephrol Sect, New Haven, CT 06520 USA. RP Fischer, MJ (reprint author), Univ Illinois, Sect Nephrol MC 793, 820 S Wood St, Chicago, IL 60612 USA. EM fischerm@uic.edu FU National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA Public Health Strategic Healthcare Group; Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service; National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases [IK23DK077568] FX The Veterans Aging Cohort Study is supported by National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566) and VHA Public Health Strategic Healthcare Group; Department of Veterans Affairs, Veterans Health Administration, Health Services Research, and Development Service (VA HSR&D Career Development Award to M.F); and the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (IK23DK077568 to CW). NR 37 TC 20 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2010 VL 53 IS 2 BP 222 EP 226 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549EQ UT WOS:000274029000010 PM 20104121 ER PT J AU Freiberg, M McGinnis, KA Kraemer, K Samet, JH Conigliaro, J Ellison, RC Bryant, K Kuller, LH Justice, AC AF Freiberg, Matthew McGinnis, Kathleen A. Kraemer, Kevin Samet, Jeffrey H. Conigliaro, Joseph Ellison, R. Curtis Bryant, Kendall Kuller, Lewis H. Justice, Amy C. CA VACS Project Team TI The Association Between Alcohol Consumption and Prevalent Cardiovascular Diseases Among HIV-Infected and HIV-Uninfected Men SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA DE alcohol consumption; alcohol abuse; alcohol dependence; cardiovascular disease; HIV infection; veterans ID IMMUNODEFICIENCY-VIRUS-INFECTION; CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; METABOLIC ABNORMALITIES; ANTIRETROVIRAL THERAPY; ISCHEMIC-STROKE; VETERANS; DRINKING; COHORT AB Objective: To determine whether alcohol consumption is associated with cardiovascular disease (CVD) among HIV-infected veterans. Methods: Using established thresholds for alcohol consumption, we analyzed cross-sectional data from 4743 men (51% HIV infected) from the Veterans Aging Cohort Study, a prospective cohort of HIV-infected veterans and demographically similar HIV-uninfected veterans. Using logistic regression, we estimated the odds ratio (OR) for the association between alcohol consumption and prevalent CVD. Results: Among HIV-infected and HIV-uninfected men, respectively, hazardous drinking (33.2% vs. 30.9%,), alcohol abuse and a dependence (20.9% vs. 26.2%), and CVD (14.6% vs. 19.8%) were common. Among HIV-infected men, hazardous drinking [OR = 1.43, 95% confidence interval (CI) = 1.05 to 1.94] and alcohol abuse and dependence (OR = 1.55, 95% CI = 1.07 to 2.23) were associated with a higher prevalence of CVD compared with infrequent and moderate drinking. Among HIV-uninfected men, past drinkers had a higher prevalence of CVD (OR = 1.30, 95% CI = 1.01 to 1.67). For HIV-infected and HIV-uninfected men, traditional risk factors and kidney disease were associated with CVD. Conclusions: Among HIV-infected men, hazardous drinking and alcohol abuse and dependence were associated with a higher prevalence of CVD compared with infrequent and moderate drinking even after adjusting for traditional CVD risk factors, antiretroviral therapy, and CD4 count. C1 [Freiberg, Matthew; Kraemer, Kevin] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sch Med, Pittsburgh, PA 15213 USA. [Freiberg, Matthew; Kuller, Lewis H.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [McGinnis, Kathleen A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Conigliaro, Joseph] Lexington Veteran Affairs Med Ctr, Div Gen Internal Med, Lexington, KY USA. [Conigliaro, Joseph] Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. [Ellison, R. Curtis] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Boston, MA 02118 USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Justice, Amy C.] Veteran Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. RP Freiberg, M (reprint author), Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sch Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM freibergms@upmc.edu FU NHLBI NIH HHS [R01 HL095136, R01 HL095136-01, R01HL095136]; NIAAA NIH HHS [K23 AA015914, K23 AA015914-05, K24 AA015674, R01 AA013304, R01 AA013304-05, 2U10AA13566, K24 AA0155674, K24 AA015674-04, U10 AA013566, U10 AA013566-09] NR 34 TC 26 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD FEB 1 PY 2010 VL 53 IS 2 BP 247 EP 253 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549EQ UT WOS:000274029000014 PM 20009766 ER PT J AU Harrington, KM Waldman, ID AF Harrington, Kelly M. Waldman, Irwin D. TI Evaluating the Utility of Sluggish Cognitive Tempo in Discriminating Among DSM-IV ADHD Subtypes SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Attention-Deficit/Hyperactivity Disorder (ADHD); Subtypes; Sluggish cognitive tempo (SCT); Validity; DSM-IV ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; PREDOMINANTLY INATTENTIVE TYPE; DIAGNOSTIC-CRITERIA; TEACHER RATINGS; FIELD TRIALS; CHILDREN; SAMPLE; SYMPTOMS; VALIDITY AB The objective of the current study was to evaluate how the inclusion of 3 Sluggish Cognitive Tempo (SCT) symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD) diagnostic criteria influences the external validity of the ADHD subtypes. The sample comprised 228 children (166 boys, 62 girls) ranging in age from 5-18 years who were referred to clinics for attentional, behavioral, and/or learning problems and diagnosed with DSM-IV ADHD (124 Combined type, 81 Inattentive type, 23 Hyperactive-Impulsive type). Parent ratings of ADHD symptoms were obtained using the Emory Combined Rating Scale (ECRS), which assesses symptoms of the common DSM-IV childhood psychiatric disorders. Regression analyses incorporating planned comparisons were conducted to examine how the inclusion of SCT symptoms affects differences among ADHD subtypes on several external validity indicators (i.e., gender, age-of-onset, and overlapping conditions). The regression analyses did not yield any significant differences in gender ratios, mean age-of-onset, or overlapping externalizing or internalizing problems when the ADHD Inattentive type was subdivided into high- versus low-SCT groups. In conclusion, the current results suggest that the inclusion of parent-reported SCT symptoms in the ADHD diagnostic criteria has limited utility for isolating diagnostically meaningful subgroups of the Inattentive type or for enhancing the external validity of the ADHD subtypes in clinic-referred samples. C1 [Harrington, Kelly M.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Harrington, Kelly M.] Boston Univ, Sch Med, Boston, MA 02130 USA. [Harrington, Kelly M.; Waldman, Irwin D.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. RP Harrington, KM (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. EM kmharrington08@gmail.com FU NIMH NIH HHS [T32MH019836, K01-MH01818] NR 41 TC 18 Z9 18 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 2010 VL 38 IS 2 BP 173 EP 184 DI 10.1007/s10802-009-9355-8 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 554KZ UT WOS:000274435200003 PM 19731006 ER PT J AU Horan, WP Wynn, JK Kring, AM Simons, RF Green, MF AF Horan, William P. Wynn, Jonathan K. Kring, Ann M. Simons, Robert F. Green, Michael F. TI Electrophysiological. Correlates of Emotional Responding in Schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; anhedonia; emotion; pleasure; event-related potentials (ERPs) ID LOVING-KINDNESS MEDITATION; PSYCHIATRIC RATING-SCALE; NEGATIVE SYMPTOMS; UNPLEASANT PICTURES; AFFECTIVE-DISORDERS; QUALITY-ASSURANCE; BRAIN POTENTIALS; NEURAL RESPONSE; AFFECTIVE STYLE; EXPERIENCE AB People with schizophrenia consistently report normal levels of pleasant emotion when exposed to evocative stimuli, suggesting intact consummatory pleasure. However, little is known about the neural correlates and time course of emotion in schizophrenia. This study used a well-validated affective picture viewing task that elicits a characteristic pattern of event-related potentials (ERPs) from early to later processing stages (i.e., P1, P2, P3, and late positive potentials [LPPs]). Thirty-eight stabilized outpatients with schizophrenia and 36 healthy controls viewed standardized pleasant, unpleasant, and neutral pictures while ERPs were recorded and subsequently rated their emotional responses to the stimuli. Patients and controls responded to the pictures similarly in terms of their valence ratings, as well as the initial ERP components (P I, P2, and P3). However, at the later LPP component (500-1,000 ms), patients displayed diminished electrophysiological discrimination between pleasant versus neutral stimuli. This pattern suggests that patients demonstrated normal self-reported emotional experience and intact initial sensory processing of and resource allocation to emotional stimuli. However, they showed a disruption in a later component associated with sustained attentional processing of emotional stimuli. C1 [Horan, William P.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Simons, Robert F.] Univ Delaware, Dept Psychol, Newark, DE 19716 USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. EM horan@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH65707, MH077141, MH43292, R01 MH043292, R01 MH065707, R03 MH077141, R03 MH077141-01, R29 MH043292] NR 72 TC 58 Z9 60 U1 5 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2010 VL 119 IS 1 BP 18 EP 30 DI 10.1037/a0017510 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 554OT UT WOS:000274445000002 PM 20141239 ER PT J AU Yee, CM Williams, TJ White, PM Nuechterlein, KH Ames, D Subotnik, KL AF Yee, Cindy M. Williams, Terrance J. White, Patricia M. Nuechterlein, Keith H. Ames, Donna Subotnik, Kenneth L. TI Attentional Modulation of the P50 Suppression Deficit in Recent-Onset and Chronic Schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; P50; sensory gating; attention; stage of illness ID SELECTIVE ATTENTION; SMOOTH-PURSUIT; EYE TRACKING; MANIPULATIONS; DYSFUNCTION; INDEXES; CORTEX AB Schizophrenia is associated with deficits in P50 suppression to the second stimulus in a pair, a process often conceptualized as a preattentive index of sensory gating. This study assessed the malleability c of the deficit by determining whether early attentional control can influence P50 gating across different pleases of schizophrenia. Participants included 28 patients in the recent-onset (n = 16) or chronic (n = 12) phase of illness and 28 healthy comparison subjects. During the standard paradigm, chronic schizophrenia patients exhibited impaired P50 suppression relative to healthy subjects, whereas recent-onset schizophrenia patients were intermediate. Directing voluntary attention toward the initial stimulus yielded substantial improvements in the P50 ratio; recent-onset schizophrenia patients achieved ratio stores comparable to those of healthy participants, whereas chronic patients also improved and could no second be distinguished clearly from the healthy comparison sample. Directing attention toward the second stimulus enhanced P50 amplitude to the second stimulus across groups, possibly because activation c of the inhibitory mechanism was overridden or circumvented by task demands. Thus, P50 suppression may be primarily preattentive under standard conditions, but manipulation of early attention can expert a modulatory influence on P50, indicating that the suppression deficit is malleable in schizophrenia without pharmacological agents. C1 [Yee, Cindy M.; Williams, Terrance J.; White, Patricia M.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Yee, Cindy M.; Williams, Terrance J.; Nuechterlein, Keith H.; Ames, Donna; Subotnik, Kenneth L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ames, Donna] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Yee, CM (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM yee@psych.ucla.edu FU NIMH NIH HHS [R01 MH057322-01A2, R01 MH037705, R01 MH057322, P50 MH066286, MH57322, MH37705] NR 39 TC 24 Z9 24 U1 3 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2010 VL 119 IS 1 BP 31 EP 39 DI 10.1037/a0018265 PG 9 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 554OT UT WOS:000274445000003 PM 20141240 ER PT J AU Yee, CM Mathis, KI Sun, JC Sholty, GL Lang, PJ Bachman, P Williams, TJ Bearden, CE Cannon, TD Green, MF Subotnik, KL Ventura, J Nuechterlein, KH AF Yee, Cindy M. Mathis, Kristopher Ian Sun, Jane C. Sholty, Gretchen L. Lang, Peter J. Bachman, Peter Williams, Terrance J. Bearden, Carrie E. Cannon, Tyrone D. Green, Michael F. Subotnik, Kenneth L. Ventura, Joseph Nuechterlein, Keith H. TI Integrity of Emotional and Motivational States During the Prodromal, First-Episode, and Chronic Phases of Schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; emotion; motivation; attention; startle reflex ID STARTLE REFLEX; NEURAL RESPONSE; MODULATION; REWARD; ATTENTION; SALIENCE; PICTURES; BEHAVIOR; MEMORY; BRAIN AB Emotional and motivational dysfunction is fundamental to schizophrenia, and yet, the nature an, I scope of associated deficits are not well understood. This study assessed the integrity of emotional responding from the perspective of its underlying motivational systems during different phases of schizophrenia. Evaluative, somatic, and autonomic responses were measured during viewing of pictures categorized by emotional content, including threat, mutilation, contamination, illness, pollution, mild erotica, further food, and nature. Participants were 13 patients at ultra high risk or prodromal for psychosis, 40 first-episode schizophrenia patients, 37 chronic schizophrenia patients, and 74 healthy comparison subjects. Irrespective of phase of illness, schizophrenia patients showed a robust and normal pattern of response across multiple systems, with differential engagement of the defensive and appetitive E systems as a function of the motivational significance assigned to specific emotional contexts. Although the integrity of core motivational states also appeared to be intact in prodromal patients, a less consistent pattern of response was observed. As continuing efforts are made to identify emotional and motivational abnormalities in schizophrenia, identified deficits will likely be independent of a fundamental dysfunction in basic emotion and motivation response systems and involve integration with higher order processes. C1 [Yee, Cindy M.; Mathis, Kristopher Ian; Sun, Jane C.; Sholty, Gretchen L.; Bachman, Peter; Williams, Terrance J.; Cannon, Tyrone D.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Yee, Cindy M.; Williams, Terrance J.; Bearden, Carrie E.; Cannon, Tyrone D.; Green, Michael F.; Subotnik, Kenneth L.; Ventura, Joseph; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lang, Peter J.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA. [Green, Michael F.] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Yee, CM (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM yee@psych.ucla.edu FU NIMH NIH HHS [R01 MH037705, P50 MH066286-01A10006, L30 MH081486, L30 MH081486-01, P50 MH066286, T32 MH014584] NR 39 TC 14 Z9 14 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2010 VL 119 IS 1 BP 71 EP 82 DI 10.1037/a0018475 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 554OT UT WOS:000274445000007 PM 20141244 ER PT J AU Lund, HG Reider, BD Whiting, AB Prichard, JR AF Lund, Hannah G. Reider, Brian D. Whiting, Annie B. Prichard, J. Roxanne TI Sleep Patterns and Predictors of Disturbed Sleep in a Large Population of College Students SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Sleep quality; Sleep disturbance; Adolescence; Stress; Mood; College students ID QUALITY-OF-LIFE; ADOLESCENT SLEEP; CHRONIC INSOMNIA; DAYTIME SLEEPINESS; SCHOOL-CHILDREN; SUBSTANCE-ABUSE; RISK-FACTOR; DISORDERS; DEPRESSION; FREQUENCY AB Purpose: To characterize sleep patterns and predictors of poor sleep quality in a large population of college students. This study extends the 2006 National Sleep Foundation examination of sleep in early adolescence by examining sleep in older adolescents. Method: One thousand one hundred twenty-five students aged 17 to 24 years from an urban Midwestern university completed a cross-sectional online survey about sleep habits that included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale, the Horne-Ostberg Morningness-Eveningness Scale, the Profile of Mood States, the Subjective Units of Distress Scale, and questions about academic performance, physical health, and psychoactive drug use. Results: Students reported disturbed sleep; over 60% were categorized as poor-quality sleepers by the PSQI, bedtimes and risetimes were delayed during weekends, and students reported frequently taking prescription, over the counter, and recreational psychoactive drugs to alter sleep/wakefulness. Students classified as poor-quality sleepers reported significantly more problems with physical and psychological health than did good-quality sleepers. Students overwhelmingly stated that emotional and academic stress negatively impacted sleep. Multiple regression analyses revealed that tension and stress accounted for 24% of the variance in the PSQI score, whereas exercise, alcohol and caffeine consumption, and consistency of sleep schedule were not significant predictors of sleep quality. Conclusions: These results demonstrate that insufficient sleep and irregular sleep-wake patterns, which have been extensively documented in younger adolescents, are also present at alarming levels in the college student population. Given the close relationships between sleep quality and physical and mental health, intervention programs for sleep disturbance in this population should be considered. (C) 2010 Society for Adolescent Medicine. All rights reserved. C1 [Reider, Brian D.; Prichard, J. Roxanne] Univ St Thomas, Dept Psychol, St Paul, MN 55105 USA. [Lund, Hannah G.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Whiting, Annie B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Prichard, JR (reprint author), Univ St Thomas, Dept Psychol, 2115 Summit Ave,JRC LL56, St Paul, MN 55105 USA. EM jrprichard@stthomas.edu RI Andrade, Rubian/Q-2938-2016 NR 40 TC 230 Z9 238 U1 54 U2 281 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2010 VL 46 IS 2 BP 124 EP 132 DI 10.1016/j.jadohealth.2009.06.016 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 548RH UT WOS:000273983400005 PM 20113918 ER PT J AU Baldessarini, RJ Bolzani, L Cruz, N Jones, PB Lai, M Lepri, B Perez, J Salvatore, P Tohen, M Tondo, L Vieta, E AF Baldessarini, R. J. Bolzani, L. Cruz, N. Jones, P. B. Lai, M. Lepri, B. Perez, J. Salvatore, P. Tohen, M. Tondo, L. Vieta, E. TI Onset-age of bipolar disorders at six international sites SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar I and II disorders; Onset-age ID CASE REGISTRY; OF-ONSET; ILLNESS; MANIA AB Background: Onset-age is a stable characteristic of bipolar disorder (BPD) patients of clinical and probable psychobiological importance, but large pooled clinical samples from multiple sites employing modern diagnostic criteria to quantify onset-age remain rare. Methods: We pooled diagnostic, demographic, and clinical data from 1566 BPD patients from six international sites (5 European, 1 US) to compare onset-ages in subgroups. Results: Median +/- IQR onset in 1090 BP-l patients was 5.8 years Younger than 476 BP-II cases (24.3 +/- 18.3 vs. 30.1 +/- 13.8 years: p<0.0001). Onset-age ranked: [a] BP-I men (23.0 +/- 12.8); [b] BP-I women ( 26.0 +/- 14.2); [c] BP-II men (29.7 +/- 19.1); and [d] BP-II women (30.1 +/- 17.5 years. juvenile-onset (<= age 20) was more common in Europe than the US (27% vs. 16%), as was childhood-onset (<13 years: 3.3% vs. 0%; both p<0.001 Proportion of all cases, and median onset for first episodes ranked: [a] BP-I psychotic (6.3%: 22.7 +/- 9.2); [b] BP-I manic (29.3%; 24.0 +/- 12.1): [c] BP-l depressed (25.1%: 24.5 +/- 14.9): [d) BP-I mixed (9.7%; 27.9 +/- 16.0); le) BP-II depressed (26.9%: 30.0 +/- 19.5): and [f] BP-II hypomanic (2.8%: 33.6 +/- 15.1 years; p<0.0001). Among BP-I patients, onset was similar for various forms of mania and major depression: in BP-II patients initial depression was 9.6-times more frequent and diagnosed earlier than hypomania. Limitations: There was some variance among sites and only 34.1% of patients were evaluated at onset. Conclusions: Type I BPD began much earlier than type II: its mainly psychotic presentations occurred earliest, but BP-I men were younger than women, especially at psychotic or mixed onsets. (C) 2009 Elsevier B.V. All rights reserved. C1 [Baldessarini, R. J.; Cruz, N.; Salvatore, P.; Tohen, M.; Tondo, L.] Harvard Univ, Sch Med, Dept Psychiat & Neurosci Program, Cambridge, MA 02138 USA. [Baldessarini, R. J.; Bolzani, L.; Cruz, N.; Jones, P. B.; Lai, M.; Perez, J.; Salvatore, P.; Tohen, M.; Vieta, E.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. [Bolzani, L.; Lai, M.; Lepri, B.; Tondo, L.] Viarnetto Psychiat Clin, Dept Psychiat, Lugano, Switzerland. [Bolzani, L.; Lai, M.; Lepri, B.; Tondo, L.] Univ Cagliari, Dept Psychiat, Lucia Bini Mood Disorder Ctr, Cagliari, Sardinia, Italy. [Cruz, N.; Jones, P. B.; Vieta, E.] Univ Barcelona, CIBERSAM, IDIBAPS, Bipolar Disorders Program,Inst Clin Neurosci,Hosp, E-08007 Barcelona, Spain. [Perez, J.] Univ Cambridge, Dept Psychiat, CAMEO Early Intervent Serv, Cambridge CB2 1TN, England. [Salvatore, P.] Univ Parma, Sect Psychiat, Dept Neurosci, I-43100 Parma, Italy. [Tohen, M.] Univ Texas San Antonio, Dept Psychiat, San Antonio, TX USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org RI Koffel, Jonathan/G-5709-2010; Vieta, Eduard/I-6330-2013; OI Vieta, Eduard/0000-0002-0548-0053; Jones, Peter/0000-0002-0387-880X FU Bruce J. Anderson Foundation; McLean Private Donors Research Fund for Bipolar Disorder Research; Instituto de Salud Carlos III and CIBERSAM; NARSAD; Atlas Foundation FX This work was supported in part by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Research Fund for Bipolar Disorder Research (to RJB), a Rio-Hortega Fellowship from the Instituto de Salud Carlos III and CIBERSAM (to NC), by a grant from NARSAD to (PS), and by the Atlas Foundation (to MT). NR 17 TC 35 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD FEB PY 2010 VL 121 IS 1-2 BP 143 EP 146 DI 10.1016/j.jad.2009.05.030 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 553IP UT WOS:000274360200019 PM 19560827 ER PT J AU Camargo, CA Gurner, DM Smithline, HA Chapela, R Fabbri, LM Green, SA Malice, MP Legrand, C Dass, SB Knorr, BA Reiss, TF AF Camargo, Carlos A., Jr. Gurner, Deborah M. Smithline, Howard A. Chapela, Rocio Fabbri, Leonardo M. Green, Stuart A. Malice, Marie-Pierre Legrand, Catherine Dass, S. Balachandra Knorr, Barbara A. Reiss, Theodore F. TI A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Intravenous montelukast; acute asthma; asthma exacerbation; FEV(1); hospitalization; leukotriene receptor antagonist; randomized trial ID CONTROLLED-TRIAL; DISCHARGE; MULTICENTER; ADMISSION AB Background: Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies. Objective: To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma. Methods: A total of 583 adults with acute asthma were treated with standard care during a <= 60-minute screening period. Patients with FEV(1) <= 50% predicted were randomly allocated to intravenous montelukast 7 mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind treatment period lasted until a decision for discharge, hospital admission, or discontinuation from the study. The primary efficacy endpoint was the time-weighted average change in FEV(1) during 60 minutes after drug administration. Secondary endpoints included the time-weighted average change in FEV(1) at various intervals (10-120 minutes) and percentage of patients with treatment failure (defined as hospitalization or lack of decision to discharge by 3 hours postadministration). Results: Montelukast significantly increased FEV(1) at 60 minutes postdose; the difference between change from baseline for placebo (least-squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI, 0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV(1)-related variables were seen at all time points (all P <.05). Although treatment failure did not differ between groups (OR 0.92; 95% CI, 0.63, 1.34), a prespecified subgroup analysis suggests likely benefit for intravenous montelukast at US sites. Conclusion: Intravenous montelukast added to standard care in adults with acute asthma produced significant relief of airway obstruction throughout the 2 hours after administration, with an onset of action as early as 10 minutes. (J Allergy Clin Immunol 2010;125:374-80.) C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Gurner, Deborah M.; Green, Stuart A.; Malice, Marie-Pierre; Legrand, Catherine; Dass, S. Balachandra; Knorr, Barbara A.; Reiss, Theodore F.] Merck Res Labs, Rahway, NJ USA. [Smithline, Howard A.] Tufts Univ, Sch Med, Dept Emergency Med, Baystate Med Ctr, Springfield, MA 01199 USA. [Chapela, Rocio] Inst Nacl Enfermedades Resp, Unidad Invest, Clin Asma, Mexico City, DF, Mexico. [Fabbri, Leonardo M.] Univ Modena & Reggio Emilia, Dept Resp Dis, Modena, Italy. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Fabbri, Leonardo/I-4055-2012 OI Fabbri, Leonardo/0000-0001-8894-1689 FU Merck Co, Inc.; AstraZeneca; Dev; GlaxoSmithKline; Merck; Novartis FX Supported by Merck & Co, Inc.; Disclosure of potential conflict of interest: C. A. Camargo has received financial support for consulting. lectures. advisory boards. and medical research for many groups, including AstraZeneca, Dev, GlaxoSmithKline. Merck. and Novartis. L. M. Fabbri receives fees for lecturing, consultancies. and advisory boards from Nycomed, AstraZeneca. Boehringer Ingelheim. Chiesi Farmaceutiei GlaxoSmithKline, Merck Sharp & Dohme, Novartis. Roche. and Pfizer. D. M. Gurner. S. A. Green, M.-P Malice. C. Legrand, S. B. Dass. B. A. Knorr. and T. F Reiss are employed by Merck and Co. Inc. The rest of the authors have declared that they have no conflict of interest. NR 29 TC 42 Z9 43 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 BP 374 EP 380 DI 10.1016/j.jaci.2009.11.015 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 558RU UT WOS:000274764000014 PM 20159247 ER PT J AU Amirzadeh, A Klaustermeyer, W AF Amirzadeh, A. Klaustermeyer, W. TI Epipen Demographics and Use in a VA Population SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Amirzadeh, A.; Klaustermeyer, W.] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB33 EP AB33 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100131 ER PT J AU Banerji, A AF Banerji, A. TI Clinical Efficacy and Safety of Icatibant: Results from the Controlled and Open-Label Extension Phases of the FAST-1 Trial SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Banerji, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB166 EP AB166 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100649 ER PT J AU Griscti, KD Kianifard, F Figliomeni, M Inhaber, N Brown, MA Camargo, CA Szefler, SJ Zeldin, RK AF Griscti, K. D. Kianifard, F. Figliomeni, M. Inhaber, N. Brown, M. A. Camargo, C. A., Jr. Szefler, S. J. Zeldin, R. K. TI Baseline Allergic Co-morbidities and Aeroallergen Sensitivities in an Observational Study of Children with Moderate-to-Severe Inadequately Controlled Allergic Asthma - The BUS Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Griscti, K. D.; Kianifard, F.; Figliomeni, M.; Inhaber, N.; Zeldin, R. K.] Novartis Pharmaceut, E Hanover, NJ USA. [Brown, M. A.] Univ Arizona, Coll Med, Tucson, AZ USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Szefler, S. J.] Natl Jewish Hlth, Denver, CO USA. NR 0 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB65 EP AB65 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100254 ER PT J AU Jartti, T Ruuskanen, O Mansbach, J Vuorinen, T Camargo, C AF Jartti, T. Ruuskanen, O. Mansbach, J. Vuorinen, T. Camargo, C., Jr. TI The Association between Serum 25-Hydroxyvitamin D Levels and Rhinovirus-associated Wheezing in Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Jartti, T.; Ruuskanen, O.] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland. [Mansbach, J.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Vuorinen, T.] Univ Turku, Dept Virol, Turku, Finland. [Camargo, C., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, C., Jr.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. NR 0 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB43 EP AB43 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100172 ER PT J AU Jones, SM Fleischer, DM Sicherer, SH Wood, RA Lindblad, R Stablein, D Liu, AH Shreffler, W Leung, DYM Sampson, HA Burks, AW AF Jones, S. M. Fleischer, D. M. Sicherer, S. H. Wood, R. A. Lindblad, R. Stablein, D. Liu, A. H. Shreffler, W. Leung, D. Y. M. Sampson, H. A. Burks, A. W. TI \ Egg Oral Immunotherapy (OIT) Induces Clinical Desensitization in a Double-Blind, Placebo-Controlled (DBPC) Trial in Egg Allergic Children from the Consortium of Food Allergy Research (CoFAR) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Jones, S. M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Res Inst, Little Rock, AR 72205 USA. [Fleischer, D. M.; Liu, A. H.; Leung, D. Y. M.] Natl Jewish Hlth, Denver, CO USA. [Sicherer, S. H.; Sampson, H. A.] Mt Sinai Sch Med, New York, NY USA. [Wood, R. A.] Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. [Lindblad, R.; Stablein, D.] EMMES Corp, Rockville, MD USA. [Shreffler, W.] Massachusetts Gen Hosp, Charlestown, MA USA. [Burks, A. W.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB357 EP AB357 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100936 ER PT J AU Rudders, SA Katzman, DP Banerji, A Clark, S Camargo, CA AF Rudders, S. A. Katzman, D. P. Banerji, A. Clark, S. Camargo, C. A., Jr. TI Repeat Epinephrine Treatments For Stinging Insect Hypersensitivity Reactions Presenting To The Emergency Department SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Rudders, S. A.] Childrens Hosp Boston, Boston, MA USA. [Katzman, D. P.; Banerji, A.; Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, S.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB30 EP AB30 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100117 ER PT J AU Vassallo, MF Banerji, A Rudders, SA Clark, S Mullins, RJ Camargo, CA AF Vassallo, M. F. Banerji, A. Rudders, S. A. Clark, S. Mullins, R. J. Camargo, C. A., Jr. TI Season of Birth is Associated with Risk of Food Allergy in Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 02, 2010 CL New Orleans, LA SP Amer Acad Allergy, Asthma & Immunol C1 [Vassallo, M. F.; Banerji, A.; Rudders, S. A.; Camargo, C. A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mullins, R. J.] Univ Pittsburgh, Pittsburgh, PA USA. [Camargo, C. A., Jr.] Univ Canberra, Canberra, ACT 2601, Australia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 1 BP AB217 EP AB217 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 629MS UT WOS:000280204100849 ER PT J AU Dykewicz, MS Hamilos, DL AF Dykewicz, Mark S. Hamilos, Daniel L. TI Rhinitis and sinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Rhinitis; sinusitis; rhinosinusitis; allergic; fungal sinusitis; nasal polyposis ID ALLERGIC FUNGAL SINUSITIS; UBIQUITOUS AIRBORNE FUNGI; CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; EOSINOPHILIA SYNDROME; NONALLERGIC RHINITIS; BRONCHIAL RESPONSIVENESS; COMPUTED-TOMOGRAPHY; MOMETASONE FUROATE; EPITHELIAL-CELLS AB Rhinitis and sinusitis are among the most common medical conditions and are frequently associated. In Western societies an estimated 10% to 25% of the population have allergic rhinitis, with 30 to 60 million persons being affected annually in the United States. It is estimated that sinusitis affects 31 million patients annually in the United States. Both rhinitis and sinusitis can significantly decrease quality of life, aggravate comorbid conditions, and require significant direct medical expenditures. Both conditions also create even greater indirect costs to society by causing lost work and school days and reduced workplace productivity and school learning. Management of allergic rhinitis involves avoidance, many pharmacologic options, and, in appropriately selected patients, allergen immunotherapy. Various types of nonallergic rhinitis are treated with avoidance measures and a more limited repertoire of medications. For purposes of this review, sinusitis and rhinosinusitis are synonymous terms. An acute upper respiratory illness of less than approximately 7 days' duration is most commonly caused by viral illness (viral rhinosinusitis), whereas acute bacterial sinusitis becomes more likely beyond 7 to 10 days. Although the mainstay of management of acute bacterial sinusitis is antibiotics, treatment of chronic sinusitis is less straightforward because only some chronic sinusitis cases have an infectious basis. Chronic rhinosinusitis (CRS) has been subdivided into 3 types, namely CRS without nasal polyps, CRS with nasal polyps, and allergic fungal rhinosinusitis. Depending on the type of CRS present, a variety of medical and surgical approaches might be required. (J Allergy Clin Immunol 2010;125:S103-15.) C1 [Dykewicz, Mark S.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom & Personalized Med Res,Dept Inter, Allergy & Immunol Unit,Sect Pulm Crit Care Allerg, Winston Salem, NC 27157 USA. [Hamilos, Daniel L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. RP Dykewicz, MS (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom & Personalized Med Res,Dept Inter, Allergy & Immunol Unit,Sect Pulm Crit Care Allerg, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dykewicz@wfubmc.edu FU Merck; Flight Attendant Medical Research Institute FX Disclosure of potential conflict of interest: M. S. Dykewicz is an advisor for Alcon, Boehringer Ingelheim, and Ista; is on the speakers' bureau for Merck and Sanofi-Aventis; is on the Board of Directors for the American Board of Allergy and Immunology; is on the Board of Directors and is a member of the Rhinitis Committee for the American Academy of Allergy, Asthma & Immunology; and is Vice Chair and on the Committee on Rhinitis and Sinusitis for the American College of Allergy, Asthma & Immunology. D. L. Hamilos has received research support from Merck and the Flight Attendant Medical Research Institute and has served an as expert witness on the topics of anaphylaxis and occupational asthma. NR 90 TC 114 Z9 119 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2010 VL 125 IS 2 SU 2 BP S103 EP S115 DI 10.1016/j.jaci.2009.12.989 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 629CC UT WOS:000280170600010 PM 20176255 ER PT J AU Samuelson, M Foret, M Baim, M Lerner, J Fricchione, G Benson, H Dusek, J Yeung, A AF Samuelson, Marlene Foret, Megan Baim, Margaret Lerner, Jonathan Fricchione, Gregory Benson, Herbert Dusek, Jeffery Yeung, Albert TI Exploring the Effectiveness of a Comprehensive Mind-Body Intervention for Medical Symptom Relief SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID HEALTH-CARE UTILIZATION; CARDIOVASCULAR-DISEASE; UNITED-STATES; STRESS; DISORDERS; PAIN; DEPRESSION; DISABILITY; REDUCTION; BURDEN AB Objective: The objective of this study was to describe possible changes in physical and psychologic symptoms among outpatients completing a 12-week mind-body medical symptom reduction program related to chronic medical conditions. Design: The cornerstone of the program is elicitation of the relaxation response, and the curriculum also incorporates trainings on mind-body interactions, cognitive restructuring, nutrition, and physical activity. The Medical Symptom Checklist (MSCL), Health Promoting Lifestyle Profile-II (HPLP-II) and Symptom Checklist-90R (SCL-90-R) were used to assess 331 patients' physical and psychologic symptoms before and after the intervention. Results: Significant post-treatment improvements in symptom frequency occurred for 12 individual symptoms on the MSCL, all 6 of the HPLP-II subscales, and 8 of the 9 SCL-90-R subscales from pre- to post-treatment. Conclusions: The results from this uncontrolled study suggest that a comprehensive mind-body intervention program might be useful as a complementary or adjunct therapy for treatment of chronic medical symptoms. C1 [Samuelson, Marlene; Foret, Megan; Baim, Margaret; Lerner, Jonathan; Fricchione, Gregory; Benson, Herbert; Dusek, Jeffery; Yeung, Albert] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Samuelson, Marlene] Curry Coll, Dept Nat Sci & Mathd, Milton, MA USA. RP Benson, H (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, 151 Merrimac St, Boston, MA 02114 USA. EM hbenson@partners.org OI Dusek, Jeffery/0000-0001-9581-0564 FU Centers for Disease Control and Prevention [5R01DP000339] FX This investigation was supported in part by funds supplied by the Centers for Disease Control and Prevention, grant number 5R01DP000339. NR 26 TC 16 Z9 16 U1 0 U2 5 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 FEB PY 2010 VL 16 IS 2 BP 187 EP 192 DI 10.1089/acm.2009.0142 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 560GZ UT WOS:000274891600010 PM 20180692 ER PT J AU Rosenfeld, L Rudd, R Chew, GL Emmons, K Acevedo-Garcia, D AF Rosenfeld, Lindsay Rudd, Rima Chew, Ginger L. Emmons, Karen Acevedo-Garcia, Dolores TI Are Neighborhood-Level Characteristics Associated with Indoor Allergens in the Household? SO JOURNAL OF ASTHMA LA English DT Article DE indoor allergens; dust mite; cat; cockroach; mouse; asthma; neighborhoods; community districts; housing code violations; policy; New York City; Puerto Rican ID INNER-CITY CHILDREN; NEW-YORK-CITY; ENVIRONMENTAL RISK-FACTORS; HEALTH IMPACT ASSESSMENT; PUERTO-RICAN CHILDREN; 1ST NATIONAL-SURVEY; COCKROACH ALLERGEN; AIR-POLLUTION; CHILDHOOD ASTHMA; LOW-INCOME AB Background: Individual home characteristics have been associated with indoor allergen exposure, however, the influence of neighborhood-level characteristics has not been well studied. We defined neighborhoods as community districts determined by the New York City Department of City Planning. Objective: We examined the relationship between neighborhood-level characteristics and the presence of dust mite (Der f 1), cat (Fel d 1). cockroach (Bla g 2), and mouse (MUP) allergens in the household. Methods: Using data from the Puerto Rican Asthma Project, a birth cohort of Puerto Rican children at risk of allergic sensitization (n = 261), we examined associations between neighborhood characteristics (percent tree canopy, asthma hospitalizations per 1,000 children, roadway length within 100 meters of buildings, serious housing code violations per 1000 rental units, poverty rates, and felony crime rates), and the presence of indoor allergens. Allergen cutpoints were used for categorical analyses and defined as follows: dust mite: >0.25 mu g/g; cat: > 1 mu g/g; cockroach: > 1 U/g; mouse: > 1.6 mu g/g. Results: Serious housing code violations were statistically significantly positively associated with dust mite, cat, and mouse allergens (continuous variables), adjusting for mother's income and education, and all neighborhood-level characteristics. In multivariable logistic regression analyses, medium levels of housing code violations were associated with higher dust mite and cat allergens (1.81, 95%CI: 1.08. 3.03 and 3.10, 95%CI: 1.22, 7.92, respectively). A high level of serious housing code violations was associated with higher mouse allergen (2.04, 95%CI: 1.15, 3.62). A medium level of housing code violations was associated with higher cockroach allergen (3.30. 95%CI: 1.11, 9.78). Conclusions: Neighborhood-level characteristics, specifically housing code violations, appear to be related to indoor allergens, which may have implications for future research explorations and policy decisions. C1 [Rosenfeld, Lindsay; Rudd, Rima; Acevedo-Garcia, Dolores] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02130 USA. [Rosenfeld, Lindsay; Acevedo-Garcia, Dolores] Northeastern Univ, Inst Urban Hlth Res, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chew, Ginger L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Rosenfeld, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge 7th Floor, Boston, MA 02130 USA. EM lrosenfe@hsph.harvard.edu FU NIEHS [R01 ES 10922, P30 ES 009089] FX The authors thank the Puerto Rican Asthma Project research participants and staff for their time and effort, especially Dr. Luis Acosta and Marianne Turner. They also thank Jeff Blossom for creating variables and maps in ArcGIS 9.2, and Amy Cohen for her SAS programming expertise. This work was supported by NIEHS grants R01 ES 10922 and P30 ES 009089. NR 113 TC 17 Z9 18 U1 5 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD FEB PY 2010 VL 47 IS 1 BP 66 EP 75 DI 10.3109/02770900903362676 PG 10 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 565EL UT WOS:000275271900012 PM 20100024 ER PT J AU Camargo, CA Boulet, LP Sutherland, ER Busse, WW Yancey, SW Emmett, AH Ortega, HG Ferro, TJ AF Camargo, Carlos A., Jr. Boulet, Louis-Philippe Sutherland, E. Rand Busse, William W. Yancey, Steven W. Emmett, Amanda H. Ortega, Hector G. Ferro, Thomas J. TI Body Mass Index and Response to Asthma Therapy: Fluticasone Propionate/Salmeterol versus Montelukast SO JOURNAL OF ASTHMA LA English DT Article DE asthma; fluticasone propionate/salmeterol; montelukast; obesity ID SMOOTH-MUSCLE-CELLS; PERSISTENT ASTHMA; COMBINATION THERAPY; MODERATE ASTHMA; OBESITY; WEIGHT; SALMETEROL; RECEPTOR; WOMEN; RISK AB We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 mu g twice daily and montelukast (MON) 10mg daily were compared. BMI was classified as underweight (less than 20 kg/m(2)), normal (20-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)) obese-1 (30-34.9 kg/m(2)), obese-2 (35-39.9 kg/m(2)), or obese-3 (at least 40 kg/m(2)). Outcomes assessed included forced expiratory volume in one second (FEV(1)), asthma symptom score, and albuterol use. FP/salmeterol produced greater improvements compared to MON in each of the asthma outcomes studied over the entire BMI range at the week-12 endpoint. with statistically significant differences noted among normal. overweight, obese-1, and obese-3 subjects. The within-treatment responses to FP/salmeterol across BMI ranges at the week-12 endpoint was statistically significantly greater in normal compared to obese-3 for FEV(1) and albuterol use. and in overweight compared to the obese-3 for each outcome studied. The within-treatment comparisons of MON across BMI ranges were significant for albuterol use in normal and underweight compared to obese-3 at the week-12 endpoint. Compared to subjects with normal BMI, the onset to peak FEV(1) may require longer treatment exposure in the very obese. Treatment responses to FP/salmeterol were consistently greater compared to MON and persisted at higher BMI. C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Boulet, Louis-Philippe] Univ Laval, Inst Univ Cardiol & Pneumol, Hop Laval, Quebec City, PQ, Canada. [Sutherland, E. Rand] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Sutherland, E. Rand] Univ Colorado, Dept Med, Denver, CO USA. [Busse, William W.] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. [Yancey, Steven W.; Emmett, Amanda H.; Ortega, Hector G.; Ferro, Thomas J.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Ferro, TJ (reprint author), Clin Dev Resp & Immunoinflammat Med Dev Ctr, Sanders Bldg 17-1326C-1C,GlaxoSmithKline 5 Moore, Res Triangle Pk, NC 27709 USA. EM Thomas.J.Ferro@GSK.com NR 38 TC 38 Z9 38 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD FEB PY 2010 VL 47 IS 1 BP 76 EP 82 DI 10.3109/02770900903338494 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 565EL UT WOS:000275271900013 PM 20100025 ER PT J AU Beckner, V Howard, I Vella, L Mohr, DC AF Beckner, Victoria Howard, Isa Vella, Lea Mohr, David C. TI Telephone-administered psychotherapy for depression in MS patients: moderating role of social support SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Social support; Depression; Multiple sclerosis; Cognitive Behavioral Therapy; Emotion-Focused Therapy; Treatment outcome ID PRIMARY-CARE PATIENTS; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SPINAL-CORD-INJURY; MULTIPLE-SCLEROSIS; MAJOR DEPRESSION; RATING-SCALE; CLINICAL PREDICTORS; BREAST-CANCER; OLDER-ADULTS AB Depression is common in individuals with multiple sclerosis (MS). While psychotherapy is an effective treatment for depression, not all individuals benefit. We examined whether baseline social support might differentially affect treatment outcome in 127 participants with MS and depression randomized to either Telephone-administered Cognitive-Behavioral Therapy (T-CBT) or Telephone-administered Emotion-Focused Therapy (T-EFT). We predicted that those with low social support would improve more in T-EFT, since this approach emphasizes the therapeutic relationship, while participants with strong social networks and presumably more emotional resources might fare better in the more structured and demanding T-CBT. We found that both level of received support and satisfaction with that support at baseline did moderate treatment outcome. Individuals with high social support showed a greater reduction in depressive symptoms in the T-CBT as predicted, but participants with low social support showed a similar reduction in both treatments. This suggests that for participants with high social support, CBT may be a more beneficial treatment for depression compared with EFT. C1 [Beckner, Victoria] San Francisco Grp Evidence Based Psychotherapy, San Francisco, CA 94123 USA. [Beckner, Victoria] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Howard, Isa] San Francisco VA Med Ctr, San Francisco, CA USA. [Vella, Lea] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. [Mohr, David C.] Northwestern Univ, Dept Prevent Med, Evanston, IL USA. RP Beckner, V (reprint author), San Francisco Grp Evidence Based Psychotherapy, 1777 Union St, San Francisco, CA 94123 USA. EM victoria.beckner@ucsf.edu FU NCRR NIH HHS [UL1 RR025741]; NIMH NIH HHS [R01 MH059708, R01 MH059708-06] NR 54 TC 16 Z9 16 U1 4 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD FEB PY 2010 VL 33 IS 1 BP 47 EP 59 DI 10.1007/s10865-009-9235-2 PG 13 WC Psychology, Clinical SC Psychology GA 549XP UT WOS:000274088100005 PM 19941048 ER PT J AU Belogrudov, GI AF Belogrudov, Grigory I. TI Coupling factor B affects the morphology of mitochondria SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Coupling factor B; Inner mitochondrial membrane; Mitochondrial crista; Mitochondrial morphology ID ATP SYNTHASE COMPLEX; OXIDATIVE-PHOSPHORYLATION; SUPRAMOLECULAR ORGANIZATION; SUBMITOCHONDRIAL PARTICLES; CRISTAE MORPHOLOGY; P-I; MEMBRANE; YEAST; TRANSLOCATION; SUBUNITS AB Ectopic expression of coupling factor B in animal cells resulted in altered mitochondrial morphology. Cells expressing factor B fused to green fluorescent protein (GFP) contained fragmented, balloon-shaped or thinned, filamentous mitochondria, terminating at one end with balloon-like structures. Ultrastructural analysis using transmission electron microscopy revealed changes in the organization of mitochondrial cristae in cells expressing factor B-GFP fusion protein. 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 [R01GM066085] FX I thank Dr. George Sachs for access to a laser scanning confocal microscope LSM 510, Dr. Olga Vagin for advice on confocal microscopy, Marianne Cilluffo for preparing specimens and for help with transmission electron microscopy, and Dr. William C. Claycomb for providing the HL-1 cells. This work was supported by NIH grant R01GM066085. I dedicate this article to Dr. Youssef Hatefi on the occasion of his 80th birthday. NR 42 TC 2 Z9 3 U1 0 U2 1 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 FEB PY 2010 VL 42 IS 1 BP 29 EP 35 DI 10.1007/s10863-009-9263-1 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 571UU UT WOS:000275782100004 PM 20069349 ER PT J AU Fayaz, HC Yaremchuk, M Jupiter, JB AF Fayaz, Hangama C. Yaremchuk, Michael Jupiter, Jesse B. TI Reconstruction of a Traumatic Transmetatarsal Amputation with Use of a Latissimus Dorsi Free Tissue Transfer and the Ilizarov Technique A Case Report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OPEN TIBIAL FRACTURES; LOWER-EXTREMITY; EXTERNAL FIXATION; FREE FLAPS; STUMP; COVERAGE; DEFECTS; WOUNDS; FOOT; LEG C1 [Fayaz, Hangama C.] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Plast Surg, Boston, MA 02114 USA. RP Fayaz, HC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed, Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 26 TC 1 Z9 1 U1 1 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 FEB PY 2010 VL 92A IS 2 BP 459 EP 464 DI 10.2106/JBJS.H.00505 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 550YS UT WOS:000274171600026 PM 20124075 ER PT J AU Kamiya, N Kobayashi, T Mochida, Y Yu, PB Yamauchi, M Kronenberg, HM Mishina, Y AF Kamiya, Nobuhiro Kobayashi, Tatsuya Mochida, Yoshiyuki Yu, Paul B. Yamauchi, Mitsuo Kronenberg, Henry M. Mishina, Yuji TI Wnt Inhibitors Dkk1 and Sost Are Downstream Targets of BMP Signaling Through the Type IA Receptor (BMPRIA) in Osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BMP RECEPTOR TYPE IA (BMPRIA); WNT; OSTEOBLASTS; SOST; DKK1 ID BONE MORPHOGENETIC PROTEINS; VAN-BUCHEM-DISEASE; BETA-CATENIN; CELL-DIFFERENTIATION; ALKALINE-PHOSPHATASE; SMAD PROTEINS; MASS; SCLEROSTIN; EXPRESSION; GENE AB The bone morphogenetic protein (BMP) and Wnt signaling pathways both contribute essential roles in regulating bone mass. However, the molecular interactions between these pathways in osteoblasts are poorly understood. We recently reported that osteoblast-targeted conditional knockout (cKO) of BMP receptor type IA (BMPRIA) resulted in increased bone mass during embryonic development, where diminished expression of Sost as a downstream effector of BMPRIA resulted in increased Wnt/beta-catenin signaling. Here, we report that Bmpr1a cKO mice exhibit increased bone mass during weanling stages, again with evidence of enhanced Wnt/beta-catenin signaling as assessed by Wnt reporter TOPGAL mice and TOPFLASH luciferase. Consistent with negative regulation of the Wnt pathway by BMPRIA signaling, treatment of osteoblasts with dorsomorphin, an inhibitor of Smad-dependent BMP signaling, enhanced Wnt signaling. In addition to Sost, Wnt inhibitor Dkk1 also was downregulated in cKO bone. Expression levels of Dkk1 and Sost were upregulated by BMP2 treatment and downregulated by Noggin. Moreover, expression of a constitutively active Bmpr1a transgene in mice resulted in the upregulation of both Dkk1 and Sost and partially rescued the Bmpr1a cKO bone phenotype. These effectors are differentially regulated by mitogen-activated protein kinase (MAPK) p38 because pretreatment of osteoblasts with SB202190 blocked BMP2-induced Dkk1 expression but not Sost. These results demonstrate that BMPRIA in osteoblasts negatively regulates endogenous bone mass and Wnt/beta-catenin signaling and that this regulation may be mediated by the activities of Sost and Dkk1. This study highlights several interactions between BMP and Wnt signaling cascades in osteoblasts that may be amenable to therapeutic intervention for the modification of bone mass density. (C) 2010 American Society for Bone and Mineral Research. C1 [Kamiya, Nobuhiro] Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA. [Kamiya, Nobuhiro; Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Yu, Paul B.; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. [Mochida, Yoshiyuki; Yamauchi, Mitsuo] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. [Yu, Paul B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Kamiya, N (reprint author), Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA. EM Nobby.Kamiya@tsrh.org OI Mochida, Yoshiyuki/0000-0002-2115-4303; Yu, Paul/0000-0003-2145-4944 FU National Institutes of Health (NIH) [P01 DK56246]; NIEHS/NIH [ES071003-11]; Lilly Fellowship Foundation FX We gratefully acknowledge Tomokazu Fukuda and Greg Scott for generation of the caBmpr1a mouse line and Laurie K McCauley and Donald J Lucas for critical reading of this manuscript. This work was Supported by National Institutes of Health (NIH) Grants P01 DK56246 (HK) and the Intramural Research Program of the NIEHS/NIH ES071003-11 (Y. Mi). The Lilly Fellowship Foundation supported NK. NR 74 TC 72 Z9 77 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2010 VL 25 IS 2 BP 200 EP 210 DI 10.1359/jbmr.090806 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564LJ UT WOS:000275215500004 PM 19874086 ER PT J AU Testa, A Mallamaci, F Benedetto, FA Pisano, A Tripepi, G Malatino, L Thadhani, R Zoccali, C AF Testa, Alessandra Mallamaci, Francesca Benedetto, Francesco A. Pisano, Anna Tripepi, Giovanni Malatino, Lorenzo Thadhani, Ravi Zoccali, Carmine TI Vitamin D Receptor (VDR) Gene Polymorphism Is Associated With Left Ventricular (LV) Mass and Predicts Left Ventricular Hypertrophy (LVH) Progression in End-Stage Renal Disease (ESRD) Patients SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE VITAMIN D; POLYMORPHISM; ASSOCIATION; LEFT VENTRICULAR HYPERTROPHY ID HEMODIALYSIS-PATIENTS; POTENTIAL ROLE; FOLLOW-UP; MORTALITY; IMPACT; DIMETHYLARGININE; DIALYSIS; RISK; SIZE AB Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end-stage renal disease (ESRD) patients. Vitamin D deficiency and/or disturbed vitamin D signaling has been implicated in LVH in experimental models. Because the Bsml vitamin D receptor VDR gene polymorphism may alter VDR function, we performed a cross-sectional and longitudinal study in a cohort of 182 dialysis patients to investigate (1) the relationship between Bsml VDR gene polymorphism and left ventricular mass index (LVMI) measured by echocardiography and (2) the predictive power of this polymorphism for progression in LVH over a 18 2 months of follow-up. As a reference group, we used 175 healthy subjects matched to the study population as for age and sex. The distribution of Bsml genotypes did not significantly deviate from Hardy-Weinberg equilibrium either in patients or in the control group of healthy subjects. The frequency of the B allele of Bsml polymorphism (40.4%) in dialysis patients was similar to that of healthy control subjects (38.6%), and the number of B alleles was directly related to LVMI (r = 0.20, P=.007). This relationship remained robust (beta=0.19, P=.006) in multivariate analysis adjusting for traditional and nontraditional risk factors and anti hypertensive and calcitriol treatment. In the longitudinal study, LVMI rose from 60.1 +/- 17.9 to 64.2 +/- 19.3 g/m(2.7) (p<.001), and again, the number of B alleles was associated with LVMI changes both in crude and in fully adjusted analyses. These cross-sectional and longitudinal observations coherently support the hypothesis that altered vitamin D signaling is implicated in LVH in ESRD patients. (C) 2010 American Society for Bone and Mineral Research. C1 [Zoccali, Carmine] Osped Riuniti Reggio Calabria, EUROLINE Ascrizzi Vincenzo, CNR & Nefrol,CNR IBIM, Res Unit Clin Epidemiol & Physiopathol Renal Dis, I-89124 Reggio Di Calabria, Italy. [Benedetto, Francesco A.] Morelli Hosp, Cardiol Unit, Reggio Di Calabria, Italy. [Thadhani, Ravi] Univ Catania, Osped Cannizzaro, Div Internal Med, Catania, Italy. [Malatino, Lorenzo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA USA. [Malatino, Lorenzo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr D Receptor Activat Res, Boston, MA USA. RP Zoccali, C (reprint author), Osped Riuniti Reggio Calabria, EUROLINE Ascrizzi Vincenzo, CNR & Nefrol,CNR IBIM, Res Unit Clin Epidemiol & Physiopathol Renal Dis, Via Vallone Petrara 55-57, I-89124 Reggio Di Calabria, Italy. EM carmine.zoccali@tin.it OI TESTA, ALESSANDRA/0000-0002-0529-6571; Zoccali, Carmine/0000-0002-6616-1996 FU NIEHS NIH HHS [P30 ES002109] NR 29 TC 34 Z9 34 U1 1 U2 3 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2010 VL 25 IS 2 BP 313 EP 319 DI 10.1359/jbmr.090717 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564LJ UT WOS:000275215500015 PM 20422622 ER PT J AU Stewart, GC Weintraub, JR Pratibhu, PP Semigran, MJ Camuso, JM Brooks, K Tsang, SW Anello, MS Nguyen, VT Lewis, EF Nohria, A Desai, AS Givertz, MM Stevenson, LW AF Stewart, Garrick C. Weintraub, Joanne R. Pratibhu, Parakash P. Semigran, Marc J. Camuso, Janice M. Brooks, Kimberly Tsang, Sui W. Anello, Mary Susan Nguyen, Viviane T. Lewis, Eldrin F. Nohria, Anju Desai, Akshay S. Givertz, Michael M. Stevenson, Lynne W. TI Patient Expectations From Implantable Defibrillators to Prevent Death in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Implantable defibrillators; heart failure; sudden death; cardiomyopathy ID QUALITY-OF-LIFE; SUDDEN CARDIAC DEATH; LEFT-VENTRICULAR DYSFUNCTION; CARDIOVERTER-DEFIBRILLATOR; NONISCHEMIC CARDIOMYOPATHY; COST-EFFECTIVENESS; MADIT-II; PROPHYLACTIC IMPLANTATION; MYOCARDIAL-INFARCTION; EJECTION FRACTION AB Background: Indications for implantable cardioverter-defibrillators (ICDs) in heart failure (HF) are expanding and may include more than 1 million patients. This study examined patient expectations from ICDs for primary prevention of sudden death in HF. Methods and Results: Study participants (n = 105) had an EF <35% and symptomatic HF, without history of ventricular tachycardia/fibrillation or syncope. Subjects completed a written survey about perceived ICD benefits, survival expectations, and circumstances under which they might deactivate defibrillation. Mean age was 58, LVEF 21%, 40% were New York Heart Association Class and 65% already had a primary prevention ICD. Most patients anticipated more than 10 years survival despite symptomatic HF. Nearly 54% expected an ICD to save >= 50 lives per 100 during 5 years. ICD recipients expressed more confidence that the device would save their own lives compared with those without an ICD (P < .001). Despite understanding the ease of deactivation, 70% of ICD recipients indicated they would keep the ICD on even if dying of cancer, 55% even if having daily shocks, and none would inactivate defibrillation even if suffering constant dyspnea at rest. Conclusions: HE patients anticipate long survival, overestimate survival benefits conferred by ICDs, and express reluctance to deactivate their devices even for end-stage disease. (J Cardiac Fail 2010:16:106-113) C1 [Stewart, Garrick C.; Weintraub, Joanne R.; Pratibhu, Parakash P.; Brooks, Kimberly; Anello, Mary Susan; Nguyen, Viviane T.; Lewis, Eldrin F.; Nohria, Anju; Desai, Akshay S.; Givertz, Michael M.; Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Semigran, Marc J.; Camuso, Janice M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tsang, Sui W.] Yale Univ, Sch Epidemiol & Publ Hlth, Dept Biostat, New Haven, CT USA. RP Stewart, GC (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM gcstewart@partners.org FU NHLBI NIH HHS [U01 HL084877, U01 HL084877-05] NR 51 TC 47 Z9 47 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2010 VL 16 IS 2 BP 106 EP 113 DI 10.1016/j.cardfail.2009.09.003 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594ZZ UT WOS:000277581800003 PM 20142021 ER PT J AU Ryu, K D'Avila, A Heist, EK Rosenberg, SP Chou, J Yang, M Singh, JP AF Ryu, Kyungmoo D'Avila, Andre Heist, E. Kevin Rosenberg, Stuart P. Chou, Jessie Yang, Michael Singh, Jagmeet P. TI Simultaneous Electrical and Mechanical Mapping Using 3D Cardiac Mapping System: Novel Approach for Optimal Cardiac Resynchronization Therapy SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE CRT; lead position; electroanatomic mapping; electromechanical activation ID VENTRICULAR LEAD POSITION; RESYNCHRONISATION THERAPY AB Electrical and Mechanical Mapping During CRT. Cardiac resynchronization therapy (CRT) restores synchrony in heart failure patients. However, a significant proportion of patients implanted with CRT devices do not realize any benefit from CRT. Placing a left ventricular (LV) lead at the sites of electrical or mechanical delay has been advocated to maximize response to CRT, but there is currently no technique described to measure mechanical delay in real-time. We describe a novel technique that can be used intraoperatively to assess mechanical and electrical activation of the coronary sinus for guidance of LV pacing site optimization during CRT implantation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 219-222, February 2010). C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ryu, Kyungmoo; Rosenberg, Stuart P.; Chou, Jessie; Yang, Michael] St Jude Med, Sylmar, CA USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. EM jsingh@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU St. Jude Medical FX K. Ryu, S. Rosenberg, J. Chou, and M. Yang are employed by St. Jude Medical. A. D'Avila reports participation as a speaker and on a research grant, J. Singh reports participation on a research grant, and E. Heist reports fees for serving on a steering committee for a CRT study, all supported by St. Jude Medical. NR 5 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2010 VL 21 IS 2 BP 219 EP 222 DI 10.1111/j.1540-8167.2009.01663.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 548XB UT WOS:000274002000020 PM 20021519 ER PT J AU Todani, A Al-Arfaj, K Melki, SA AF Todani, Amit Al-Arfaj, Khalid Melki, Samir A. TI Repositioning free laser in situ keratomileusis flaps SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID MANAGEMENT; COMPLICATIONS; LASIK; ASTIGMATISM; CAP AB We describe a protocol for adequate repositioning of free laser in situ keratomileusis (LASIK) corneal flaps created by a Mona M2 microkeratome even in the absence of fiduciary marks. In an enucleated porcine globe, a free flap was created by initially placing a longitudinal incision at the proposed hinge site followed by activating the forward pass of the automated microkeratome. A protocol was devised based on placement of a positioning dot on the free flap before the flap is retrieved from the microkeratome head. Prep laced surgical landmarks were used as a guide to determine the correct alignment of the free flap. Adequate orientation of the free flap to the stromal bed was achieved in 9 porcine eyes using the positioning dot method. The technique is applicable to the Mona M2 microkeratome only and must be validated for other types of keratomes. C1 [Todani, Amit; Melki, Samir A.] Boston Eye Grp, Boston, MA USA. [Todani, Amit; Al-Arfaj, Khalid; Melki, Samir A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Melki, SA (reprint author), Boston Eye Grp, 1101 Beacon St,6W, Brookline, MA 02446 USA. EM samir_melki@meei.harvard.edu NR 11 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD FEB PY 2010 VL 36 IS 2 BP 200 EP 202 DI 10.1016/j.jcrs.2009.09.028 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 592VY UT WOS:000277410900004 PM 20152597 ER PT J AU Ohishi, M Schipani, E AF Ohishi, Masanobu Schipani, Ernestina TI Bone Marrow Mesenchymal Stem Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE STEM CELLS; BONE MARROW; STROMA; PERICYTES ID STROMAL CELLS; REGENERATIVE MEDICINE; DIFFERENTIATION; REPAIR; OSTEOPROGENITORS; MICROENVIRONMENT; TRANSPLANTATION; IDENTIFICATION; THERAPY; ORIGIN AB Following the identification of bone marrow multipotent cells that could adhere to plastic and differentiate along numerous mesenchymal lineages in vitro, a considerable effort has been invested in characterizing and expanding these cells, which are flow called "mesenchymal stem cells" (MSCS), in vitro. Over the years, numerous lines of evidence have been provided in support of their plasticity, their extraordinary immunomodulatory properties, their potential use for tissue engineering purposes, as Well as their ability to be recruited 10 sites of injury, where they might contribute a "natural in Vivo system for tissue repair." Moreover, some studies have attempted the characterization of their cell-surface Specific antigens and of their anatomical location in vivo. Lastly, it has been shown that similar Cells could be also isolated Front organs other than the hone marrow. Despite this impressive body of investigations, numerous questions related to file developmental Origin of these cells, their proposed pluripotency, and their role in bone modeling and remodeling and tissue repair in vivo are still largely unanswered. In addition, both a systematic phenotypic in vivo characterization of the MSC population and file development of a reproducible and faithful in vivo assay that Would test the ability of MSCS to self-renew, proliferate, and differentiate in vivo arc just beginning. This brief review summarizes the current knowledge in the field of study of MSCs and file outstanding questions. J. Cell. Biochem. 109: 277-282, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Ohishi, Masanobu; Schipani, Ernestina] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Ohishi, Masanobu; Schipani, Ernestina] Harvard Univ, Sch Med, Boston, MA USA. [Schipani, Ernestina] Natl Hosp Org, Kyushu Med Ctr, Clin Res Inst, Dept Orthoped Surg & Rheumatol, Fukuoka, Japan. [Ohishi, Masanobu] Kyushu Univ, Grad Sch Med, Dept Orthopaed Surg, Fukuoka 812, Japan. RP Schipani, E (reprint author), Thier 11,50 Blossom St, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu NR 49 TC 58 Z9 67 U1 1 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 1 PY 2010 VL 109 IS 2 BP 277 EP 282 DI 10.1002/jcb.22399 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 554YB UT WOS:000274471400001 PM 19950205 ER PT J AU Roodman, GD AF Roodman, G. David TI Pathogenesis of Myeloma Bone Disease SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE MYELOMA; BONE DISEASE; METASTASIS ID TUMOR-NECROSIS-FACTOR; KAPPA-B LIGAND; OSTEOCLAST DIFFERENTIATION FACTOR; INTERACTING PROTEIN P62; MULTIPLE-MYELOMA; IN-VIVO; RECEPTOR ACTIVATOR; OSTEOBLAST DIFFERENTIATION; MARROW MICROENVIRONMENT; CELL-GROWTH AB Multiple myeloma (mm) is the most common cancer to involve bone with Up to 90% of patients developing bone lesions. The bone lesions are purely osteolytic in nature and do not heal in the vast majority of patients. Up to 60% of patients develop pathologic fractures over the course of their disease. Bone disease is a hallmark of MM, and myeloma bone disease differs front hone metastasis caused by other tumors. Although myeloma and other osteolytic metastases induce increased osteoclastic bone destruction, in contrast to other tumors, once myeloma tumor exceeds 50% in it local area, osteoblast activity is either severely depressed of absent. The basis For this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been the topic of intensive investigation over the last several years. These studies have helped to identify novel targets for treating myeloma bone disease and Will he discussed in this chapter. J. Cell. Biochem. 109: 283-29 1, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Roodman, G. David] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Dept Med Hematol Oncol, Res & Dev 151-U,Univ Dr C,Rm 2E113, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 86 TC 46 Z9 52 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 1 PY 2010 VL 109 IS 2 BP 283 EP 291 DI 10.1002/jcb.22403 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 554YB UT WOS:000274471400002 PM 20014067 ER PT J AU Tenzen, T Zembowicz, F Cowan, CA AF Tenzen, Toyoaki Zembowicz, Filip Cowan, Chad A. TI Genome Modification in Human Embryonic Stem Cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID ZINC-FINGER NUCLEASES; NONINTEGRATING LENTIVIRAL VECTORS; HUMAN SOMATIC-CELLS; IN-VITRO; REPROGRAMMING FACTORS; TRANSGENE EXPRESSION; GENETIC-MODIFICATION; HUMAN BLASTOCYSTS; DEFINED FACTORS; INTEGRASE AB Induced pluripotent stem cell (iPSC) technology has emerged as the most promising method for generating patient-specific human embryonic stem (ES) cells and adult stem cells (Takahashi et al., 2007, Cell 131:861-872; Wernig et al., 2007, Nature 448:318-324; Park et al., 2008, Nature 451:141-146). So far, most studies of direct reprogramming have been done by using lentiviruses/retroviruses encoding the reprogramming factors. This represents a major limitation to therapeutic applications since viral integration in the host genome increases the risk of tumorigenicity, and low-level residual expression of reprogramming factors may alter the differentiation potential of the human iPSCs (hiPSCs). As a result, more attention has been paid to developing new techniques to manipulate the human genome, with the goal of making safer hiPSCs that have fewer or no lesions or alterations in the genome. Additionally, the efficiency of reprogramming and of homologous recombination in gene therapy must be improved, if iPSC technology is to be a viable tool in regenerative medicine. Here, we summarize the recent developments in human genome manipulation for generating hiPSCs and advances in homologous recombination for gene targeting. J. Cell. Physiol. 222: 278-281, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Tenzen, Toyoaki; Zembowicz, Filip; Cowan, Chad A.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Cardiovasc Res Ctr, Stowers Med Inst,Ctr Regenerat Med, Boston, MA 02114 USA. RP Tenzen, T (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Cardiovasc Res Ctr, Stowers Med Inst,Ctr Regenerat Med, 185 Cambridge St,CPZN-4234, Boston, MA 02114 USA. EM totenzen@gmail.com; chadacowan@gmail.com FU Stowers Medical Institute; Harvard College Research Program FX We apologize to colleagues whose work could not be cited due to space limitations. We thank members of the Cowan Laboratory for their critical inputs and suggestions. This work is supported by the Stowers Medical Institute. F.Z. has been supported by Harvard College Research Program. NR 46 TC 20 Z9 20 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2010 VL 222 IS 2 BP 278 EP 281 DI 10.1002/jcp.21948 PG 4 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 544MV UT WOS:000273662300003 PM 19877154 ER PT J AU Curcio-Morelli, C Zhang, P Venugopal, B Charles, FA Browning, MF Cantiello, HF Slaugenhaupt, SA AF Curcio-Morelli, Cyntia Zhang, Peng Venugopal, Bhuvarahamurthy Charles, Florie A. Browning, Marsha F. Cantiello, Horacio F. Slaugenhaupt, Susan A. TI Functional Multimerization of Mucolipin Channel Proteins SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RECEPTOR POTENTIAL CHANNEL; CATION CHANNEL; IV; MUTATION; DEAFNESS; GENE; IDENTIFICATION; TRAFFICKING; PHENOTYPE; CLEAVAGE AB MCOLN I encodes mucolipin-I (TRPML1), a member of the transient receptor potential TRPML subfamily of channel proteins. Mutations in MCOLN I cause mucolipiclosis-type IV (MLIV), a lysosomal storage disorder characterized by severe neurologic, ophthalmologic, and gastrointestinal abnormalities. Along with TRPML1, there are two other TRPML family members, mucolipin-2 (TRPML2) and mucolipin-3 (TRPML3). In this study, we used immunocytochemical analysis to determine that TRPML1, TRPML2, and TRPML3 co-localize in cells. The multimerization of TRPML proteins was confirmed by co-immunoprecipitation and Western blot analysis, which demonstrated that TRPML1 homo-multimerizes as well as hetero-multimerizes with TRPML2 and TRPML3. MLIV-causing mutants of TRPML1 also interacted with wild-type TRPML1. Lipid bilayer re-constitution of in vitro translated TRPML2 and TRPML3 confirmed their cation channel properties with lower single channel conductance and higher partial permeability to anions as compared to TRPML1. We further analyzed the electrophysiological properties of single channel TRPML hetero-multimers, which displayed functional differences when compared to individual TRPMLs. Our data shows for the first time that TRPMLs form distinct functional channel complexes. Homo- and hetero-multimerization of TRPMLs may modulate channel function and biophysical properties, thereby increasing TRPML functional diversity. J. Cell. Physiol. 222: 328-335, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Curcio-Morelli, Cyntia; Venugopal, Bhuvarahamurthy; Charles, Florie A.; Browning, Marsha F.; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Curcio-Morelli, Cyntia; Venugopal, Bhuvarahamurthy; Charles, Florie A.; Browning, Marsha F.; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhang, Peng; Cantiello, Horacio F.] Massachusetts Gen Hosp East, Nephrol Div & Electrophysiol Core, Charlestown, MA 02129 USA. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM slaugenhaupt@chgr.mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke; MGH Fund for Medical Discovery [NS39995] FX Contract grant sponsor: National Institute of Neurological Disorders and Stroke. Contract grant sponsor: MGH Fund for Medical Discovery; Contract grant number: NS39995. NR 27 TC 26 Z9 27 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2010 VL 222 IS 2 BP 328 EP 335 DI 10.1002/jcp.21956 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 544MV UT WOS:000273662300010 PM 19885840 ER PT J AU Gandhi, CR Murase, N Starzl, TE AF Gandhi, Chandrashekhar R. Murase, Noriko Starzl, Thomas E. TI Cholera Toxin-Sensitive GTP-Binding Protein-Coupled Activation of Augmenter of Liver Regeneration (ALR) Receptor and Its Function in Rat Kupffer Cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HEPATIC STIMULATORY SUBSTANCE; NITRIC-OXIDE; PARTIAL-HEPATECTOMY; GROWTH-FACTORS; CULTURED-HEPATOCYTES; DNA-SYNTHESIS; GENE; MICE; EXPRESSION; APOPTOSIS AB Mitogenic effect of augmenter of liver regeneration (ALR), a protein produced and released by hepatocytes, on hepatocytes in vivo but not in vitro suggests that the effect is mediated by nonparenchymal cells. Since mediators produced by Kupffer cells are implicated in hepatic regeneration, we investigated receptor for ALR and its functions in rat Kupffer cells. Kupffer cells were isolated from rat liver by enzymatic digestion and centrifugal elutriation. Radioligand ([(125)I] ALR) receptor binding, ALR-induced GTP/G-protein association, and nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and interleukin-6 (IL-6) synthesis were determined. High-affinity receptor for ALR, belonging to the G-protein family, with K(d) of 1.25 +/- 0.18 nM and B(max) of 0.26 +/- 0.02 fmol/mu g DNA was identified. ALR stimulated NO, TNF-alpha, and IL-6 synthesis via cholera toxin-sensitive G-protein, as well as p38-MAPK activity and nuclear translocation of NF kappa B. While inhibitor of NF kappa B (MG132) inhibited ALR-induced NO synthesis, MG132 and p38-MAPK inhibitor (SB203580) abrogated ALR-induced TNF-alpha and IL-6 synthesis. ALR also prevented the release of mediator(s) from Kupffer cells that cause inhibition of DNA synthesis in hepatocytes. Administration of ALR to 40% partially hepatectomized rats increased expression of TNF-alpha, IL-6, and inducible nitric oxide synthase (iNOS) and caused augmentation of hepatic regeneration. These results demonstrate specific G-protein coupled binding of ALR and its function in Kupffer cells and suggest that mediators produced by ALR-stimulated Kupffer cells may elicit physiologically important effects on hepatocytes. J. Cell. Physiol. 222: 365-373, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Gandhi, Chandrashekhar R.; Murase, Noriko; Starzl, Thomas E.] Univ Pittsburgh, Thomas E Starzi Transplantat Inst, Dept Surg, Pittsburgh, PA 15213 USA. [Gandhi, Chandrashekhar R.] Univ Pittsburgh, Thomas E Starzi Transplantat Inst, Dept Pathol, Pittsburgh, PA 15213 USA. [Gandhi, Chandrashekhar R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Gandhi, CR (reprint author), Univ Pittsburgh, Thomas E Starzi Transplantat Inst, Dept Surg, E-1542 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. EM gandhics@msx.upmc.edu FU NIH [DK 54411] FX This work was supported by a VA Merit award and a grant from the NIH (DK 54411) to C.R.G. We thank Ms. Holly Grunebach, Ms. Kristin Anselmi, and Mr. Chao Huang for excellent technical assistance. NR 50 TC 15 Z9 18 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2010 VL 222 IS 2 BP 365 EP 373 DI 10.1002/jcp.21957 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 544MV UT WOS:000273662300014 PM 19859909 ER PT J AU Joshi, G Wozniak, J Mick, E Doyle, R Hammerness, P Georgiopoulos, A Kotarski, M Aleardi, M Williams, C Walls, S Biederman, J AF Joshi, Gagan Wozniak, Janet Mick, Eric Doyle, Robert Hammerness, Paul Georgiopoulos, Anna Kotarski, Meghan Aleardi, Megan Williams, Courtney Walls, Sarah Biederman, Joseph TI A Prospective Open-Label Trial of Extended-Release Carbamazepine Monotherapy in Children with Bipolar Disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIALS; DOUBLE-BLIND; RATING-SCALE; ATYPICAL ANTIPSYCHOTICS; DIVALPROEX SODIUM; MOOD STABILIZERS; MIXED EPISODES; ACUTE MANIA; ADOLESCENTS; MULTICENTER AB Objective: The aim of this study was to evaluate the safety and efficacy of extended release carbamazepine (CBZ-ER) monotherapy in the treatment of pediatric bipolar disorder ( BD). Method: This was an 8-week, open-label, prospective trial of CBZ-ER monotherapy (788 +/- 252 mg/day) to assess the effectiveness and tolerability of this compound in treating pediatric bipolar spectrum disorders. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale, Children's Depression Rating Scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Results: Of the 27 participating children with BD, 16 (59.%) completed the study. CBZ-ER treatment was associated with statistically significant, but modest, levels of improvement in mean YMRS scores (-10.1 +/- 10.2, p < 0.001) with end-point mean YMRS score (21.8 +/- 12.2) suggesting a lack of complete resolution of mania. CBZ-ER treatment also resulted in significant improvement in the severity of depressive, attention-deficit/hyperactivity disorder, and psychotic symptoms. With the exception of 2 participants who discontinued due to skin rash, CBZ-ER was well tolerated with marginal increase in body weight (0.8 +/- 2.5 kg, p = 0.04) and was not associated with any abnormal changes in laboratory parameters. Conclusions: Open-label CBZ-ER treatment was beneficial for the treatment of BD in children. Future controlled trials are warranted. C1 [Joshi, Gagan] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. [Joshi, Gagan; Wozniak, Janet; Mick, Eric; Doyle, Robert; Hammerness, Paul; Georgiopoulos, Anna; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Joshi, G (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Pediat Psychopharmacol Res Dept, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM Joshi.Gagan@mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU Shire Development, Inc.; Pediatric Psychopharmacology Council Fund; Norma Fine Pediatric Psychopharmacology Fellowship Fund FX This study was an investigator-initiated project funded by Shire Development, Inc. (with principal investigator Joseph Biederman, M.D.). Additional contributions were from the Pediatric Psychopharmacology Council Fund and the Norma Fine Pediatric Psychopharmacology Fellowship Fund. NR 57 TC 14 Z9 14 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2010 VL 20 IS 1 BP 7 EP 14 DI 10.1089/cap.2008.0162 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 556ZM UT WOS:000274636300002 PM 20166791 ER PT J AU Stevens, JR George, RA Fusillo, S Stern, TA Wilens, TE AF Stevens, Jonathan R. George, Robert A. Fusillo, Steven Stern, Theodore A. Wilens, Timothy E. TI Plasma Methylphenidate Concentrations in Youths Treated with High-Dose Osmotic Release Oral System Formulation SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; DAILY OROS METHYLPHENIDATE; TERM OPEN-LABEL; ONCE-A-DAY; CONTROLLED TRIAL; ADHD TREATMENT; CHILDREN; PHARMACOKINETICS; PHARMACOTHERAPY AB Background: Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. Objective: We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Methods: Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e. g., measures of blood pressure and heart rate) were also examined. Results: Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >= 50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. Conclusions: High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness. C1 [Stevens, Jonathan R.; Fusillo, Steven; Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [George, Robert A.] Oregon Hlth & Sci Univ, Dept Child & Adolescent Psychiat, Portland, OR 97201 USA. [Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Stevens, JR (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM jrstevens@partners.org NR 30 TC 9 Z9 10 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FEB PY 2010 VL 20 IS 1 BP 49 EP 54 DI 10.1089/cap.2008.0128 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 556ZM UT WOS:000274636300007 PM 20166796 ER PT J AU Zhang, XP Schmidt, U Wain, JC Bigatello, L AF Zhang, Xiaopeng Schmidt, Ulrich Wain, John C. Bigatello, Luca TI Bradycardia leading to asystole during dexmedetomidine infusion in an 18 year-old double-lung transplant recipient SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Asystole; Bradycardia; Dexmedetomidine infusion; Double lung transplantation ID INTENSIVE-CARE-UNIT; CARDIAC-ARREST; PROPOFOL; SEDATION; SURGERY; PHARMACOKINETICS; PHARMACODYNAMICS; VOLUNTEERS; FENTANYL; AGENT AB The case of an 18 year-old double-lung transplant recipient recovering from acute respiratory distress syndrome who developed repeated episodes of bradycardia and asystole (maximum duration: 10 sec) during dexmedetomidine administration is presented. Increased baseline vagal tone, paroxysmal coughing spells, and opioid administration were likely contributors to the episodes. Discontinuation of the drug restored regular sinus rhythm. Double-lung transplant recipients may be at especially increased risk for this phenomenon as a result of changes in the autonomic innervation of the heart. Published by Elsevier Inc. C1 [Zhang, Xiaopeng] Geisinger Med Ctr, Div Anesthesiol, Danville, PA 17821 USA. [Schmidt, Ulrich] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. [Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA 02114 USA. [Bigatello, Luca] VA Boston Healthcare Syst, Anesthesia & Crit Care Serv, Boston, MA 02132 USA. RP Bigatello, L (reprint author), VA Boston Healthcare Ctr, Dept Anesthesia & Crit Care Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Luca.Bigatello@va.gov NR 26 TC 17 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2010 VL 22 IS 1 BP 45 EP 49 DI 10.1016/j.jclinane.2009.06.002 PG 5 WC Anesthesiology SC Anesthesiology GA 584WH UT WOS:000276783800009 PM 20206851 ER PT J AU Alston, TA AF Alston, Theodore A. TI Early misconceptions about nitrous oxide, an "invigorating" asphyxiant SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Nitrous oxide; Allen F; Bigelow HJ; Goldman VA; Hypoxia; Lavoisier AL; Jackson CT; Seizures; Snow J AB Well into the twentieth century, nitrous oxide was often suspected to support life in the manner of oxygen. Authorities contributing to that life-threatening misimpression include Humphry Davy, Gardner Q. Colton, and George W. Crile. Concomitantly, deprivation of oxygen was long touted as a requisite for nitrous oxide anesthesia. (C) 2010 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM talston@partners.org NR 29 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2010 VL 22 IS 1 BP 59 EP 63 DI 10.1016/j.jclinane.2008.11.015 PG 5 WC Anesthesiology SC Anesthesiology GA 584WH UT WOS:000276783800013 PM 20206855 ER PT J AU Alston, TA AF Alston, Theodore A. TI Atracurium-like decomposition of remifentanil SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM talston@partners.org NR 5 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2010 VL 22 IS 1 BP 72 EP 73 DI 10.1016/j.jclinane.2009.04.003 PG 2 WC Anesthesiology SC Anesthesiology GA 584WH UT WOS:000276783800016 PM 20206858 ER PT J AU Miller, KK Wexler, T Fazeli, P Gunnell, L Graham, GJ Beauregard, C Hemphill, L Nachtigall, L Loeffler, J Swearingen, B Biller, BMK Klibanski, A AF Miller, Karen K. Wexler, Tamara Fazeli, Pouneh Gunnell, Lindsay Graham, Gwenda J. Beauregard, Catherine Hemphill, Linda Nachtigall, Lisa Loeffler, Jay Swearingen, Brooke Biller, Beverly M. K. Klibanski, Anne TI Growth Hormone Deficiency after Treatment of Acromegaly: A Randomized, Placebo-Controlled Study of Growth Hormone Replacement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID QUALITY-OF-LIFE; CARDIOVASCULAR RISK MARKERS; INTIMA-MEDIA THICKNESS; HOMEOSTASIS MODEL ASSESSMENT; MAJOR DEPRESSIVE DISORDER; ADULT GH DEFICIENCY; LONG-TERM CURE; BODY-COMPOSITION; INSULIN SENSITIVITY; CONTROLLED-TRIAL AB Context: The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study. Objective: The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly. Design: This was a 6-month, randomized, placebo-controlled study. Setting: The study was conducted at a clinical translational science center. Study Participants: Participants included 30 subjects with prior acromegaly and current GHD. Intervention: Interventions included GH or placebo. Main Outcome Measures: Body composition (dual-energy x-ray absorptiometry and cross-sectional computed tomography at L4), cardiovascular risk markers (high-sensitivity C-reactive protein (hsCRP), total, high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and carotid intimal-medial thickness), and quality of life were measured. Results: The mean GH dose at 6 months was 0.58 +/- 0.26 mg/d. Total fat mass, visceral adipose tissue (-15.3 +/- 18.6 vs. 1.3 +/- 12.5%, P = 0.01), and total abdominal fat decreased, and fat-free mass increased, in the GH vs. placebo group. Mean hsCRP levels decreased, but there was no GH effect on other cardiovascular risk markers. There was no change in glycosylated hemoglobin or homeostasis model assessment insulin resistance index. Quality of life improved with GH. Side effects were minimal. Conclusions: This is the first randomized, placebo-controlled study of the effects of GH replacement therapy on body composition and cardiovascular end points in patients who have developed GH deficiency after treatment for acromegaly, a disease complicated by metabolic and body composition alterations and increased cardiovascular risk. GH replacement decreased visceral adipose tissue, increased fat-free mass, decreased hsCRP, and improved quality of life in patients with GHD after cure of acromegaly, with minimal side effects and without an increase in insulin resistance. (J Clin Endocrinol Metab 95: 567-577, 2010) C1 [Miller, Karen K.; Wexler, Tamara; Fazeli, Pouneh; Gunnell, Lindsay; Graham, Gwenda J.; Beauregard, Catherine; Nachtigall, Lisa; Biller, Beverly M. K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Div Cardiol, Boston, MA 02114 USA. [Loeffler, Jay] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Div Cardiol, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU National Institutes of Health [MO1 RR01066, ULI RR0257801]; Pfizer Inc.; Guthart Family Foundation FX We thank the nurses and bionutritionists of the Massachusetts General Hospital General Clinical Research Center and the Harvard Catalyst Clinical Translational Science Center and the patients who participated in the study.; Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: kkmiller@partners.org.; This work was supported by National Institutes of Health Grants MO1 RR01066 and ULI RR0257801, an investigator-initiated grant from Pfizer Inc., and the Guthart Family Foundation.; Disclosure Summary: A. K. received funding for this investigator-initiated study from Pfizer Inc. B. M. K. B. consults for and has received research funding from Pfizer, Inc. No other authors have any conflicts to declare. NR 62 TC 28 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2010 VL 95 IS 2 BP 567 EP 577 DI 10.1210/jc.2009-1611 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200016 PM 20061426 ER PT J AU Shimada, T Urakawa, I Isakova, T Yamazaki, Y Epstein, M Wesseling-Perry, K Wolf, M Salusky, IB Juppner, H AF Shimada, Takashi Urakawa, Itaru Isakova, Tamara Yamazaki, Yuji Epstein, Michael Wesseling-Perry, Katherine Wolf, Myles Salusky, Isidro B. Jueppner, Harald TI Circulating Fibroblast Growth Factor 23 in Patients with End-Stage Renal Disease Treated by Peritoneal Dialysis Is Intact and Biologically Active SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAMILIAL TUMORAL CALCINOSIS; CHRONIC KIDNEY-DISEASE; DOMINANT HYPOPHOSPHATEMIC RICKETS; LEFT-VENTRICULAR HYPERTROPHY; VITAMIN-D METABOLISM; PHOSPHATE HOMEOSTASIS; INDUCED OSTEOMALACIA; PARATHYROID-HORMONE; MINERAL METABOLISM; FGF-23 AB Context: Fibroblast growth factor 23 (FGF23) regulates phosphorus homeostasis and vitamin D metabolism. Circulating FGF23 levels are elevated in inherited and acquired hypophosphatemic disorders that can cause rickets or osteomalacia. Particularly increased concentrations of FGF23 are observed in patients with chronic kidney disease (CKD), in which increased FGF23 is associated with more rapid disease progression, improved bone mineralization, the development of left ventricular hypertrophy, and increased mortality. Objective: Our objective was to determine whether the markedly elevated levels of immunoreactive FGF23 in CKD represent accumulation of intact, biologically active hormone, C-terminal cleavage fragments, or both. Design: Biologically active FGF23 in plasma from CKD patients treated by peritoneal dialysis was quantified using a cell-based Egr-1 reporter assay; bioactive FGF23 levels were compared with those measured with immunometric FGF23 assays detecting either intact hormone alone or intact hormone and C-terminal fragments. Setting and Patients: Adult and pediatric patients with end-stage renal disease treated with peritoneal dialysis participated in the study at a tertiary referral center. Results: Serially diluted patient samples revealed levels of bioactive FGF23 that ran in parallel to CHO cell-derived recombinant human FGF23. FGF23 bioactivity was inhibited by an anti-FGF23 antibody. Levels of bioactive and immunoreactive FGF23 were tightly correlated, and Western blot analysis of FGF23 immunoprecipitated with anti-FGF23 antibodies from plasma of dialysis patients revealed only a single prominent protein band, which was indistinguishable from recombinant intact FGF23, without clear evidence for FGF23 fragments. Conclusions: Our results provide strong evidence for the conclusion that virtually all circulating FGF23 in dialysis patients is intact and biologically active. ( J Clin Endocrinol Metab 95: 578-585, 2010) C1 [Shimada, Takashi; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Med, Boston, MA 02114 USA. [Isakova, Tamara; Epstein, Michael] Massachusetts Gen Hosp, Nephrol Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shimada, Takashi; Urakawa, Itaru; Yamazaki, Yuji] Kyowa Hakko Kirin Co Ltd, Innovat Drug Discovery Labs, Gunma 3701295, Japan. [Wesseling-Perry, Katherine; Salusky, Isidro B.] Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Thier 10,50 Blossum St, Boston, MA 02114 USA. EM hjueppner@partners.org FU National Institutes of Health [PO1 DK11794, DK67563, RO1DK076116] FX Address all correspondence and requests for reprints to: Harald Juppner, M. D., Endocrine Unit, Thier 10, 50 Blossum Street, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: hjueppner@partners.org.; This work was supported by the National Institutes of Health (PO1 DK11794, DK67563, and RO1DK076116).; Disclosure Summary: T. I., M. E., K. W.-P., M. W., and I. B. S. have nothing to declare. T. S., I. U., and Y.Y. are employed by Kyowa Hakko Kirin Co., Ltd., Japan. H.J. is named as a coinventor on the patent describing the cFGF23 assay described in this report ( U. S. Patent 7,094,551). NR 50 TC 103 Z9 108 U1 0 U2 11 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 FEB PY 2010 VL 95 IS 2 BP 578 EP 585 DI 10.1210/jc.2009-1603 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200017 PM 19965919 ER PT J AU Valassi, E Biller, BMK Swearingen, B Giraldi, FP Losa, M Mortini, P Hayden, D Cavagnini, F Klibanski, A AF Valassi, Elena Biller, Beverly M. K. Swearingen, Brooke Giraldi, Francesca Pecori Losa, Marco Mortini, Pietro Hayden, Douglas Cavagnini, Francesco Klibanski, Anne TI Delayed Remission after Transsphenoidal Surgery in Patients with Cushing's Disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM REMISSION; PITUITARY SURGERY; SERUM CORTISOL; FOLLOW-UP; CURE; MICROSURGERY; IMMEDIATE; DIAGNOSIS; RELAPSE; RISK AB Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease ( CD). Postoperative hypercortisolemia mandates further therapy. Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy. Design and Setting: A retrospective case series was conducted at three tertiary care centers. Patients and Intervention: We reviewed the records of 620 patients ( 512 females, 108 males; mean age, 38 +/- 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007. Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC ( immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC ( no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC ( delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 +/- 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC ( 43 vs. 14%; P = 0.02). Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined. (J Clin Endocrinol Metab 95: 601-610, 2010) C1 [Valassi, Elena; Biller, Beverly M. K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Valassi, Elena; Giraldi, Francesca Pecori; Cavagnini, Francesco] Univ Milan, Ist Auxol Italiano, Ist Ricovero & Cura Carattere Sci, Osped San Luca,Chair Endocrinol, I-20149 Milan, Italy. [Losa, Marco; Mortini, Pietro] Univ Vita Salute, Dept Neurosurg, Ist Sci San Raffaele, I-20132 Milan, Italy. [Hayden, Douglas] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org RI Pecori Giraldi, Francesca/F-5081-2011 OI Pecori Giraldi, Francesca/0000-0001-6065-7803 FU National Institute of Health (NIH) [UL1 RR025758]; L'OREAL Italia Per le Donne e la Scienza FX Dalia Batista, MD is acknowledged for her dedicated effort and contributions to the manuscript.; Address all correspondence and requests for reprints to: Anne Klibanski, M. D., Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 457B, Boston, Massachusetts 02114. E-mail: aklibanski@partners.org.; This work was supported by Grant UL1 RR025758 from National Institute of Health (NIH). E. V. was supported in part by the "L'OREAL Italia Per le Donne e la Scienza" Award 2008.; Disclosure Summary: The authors have nothing to disclose. NR 32 TC 48 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2010 VL 95 IS 2 BP 601 EP 610 DI 10.1210/jc.2009-1672 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200020 PM 20080848 ER PT J AU Fernandez-Rebollo, E Garcia-Cuartero, B Garin, I Largo, C Martinez, F Garcia-Lacalle, C Castano, L Bastepe, M de Nanclares, GP AF Fernandez-Rebollo, Eduardo Garcia-Cuartero, Beatriz Garin, Intza Largo, Cristina Martinez, Francisco Garcia-Lacalle, Concepcion Castano, Luis Bastepe, Murat Perez de Nanclares, Guiomar TI Intragenic GNAS Deletion Involving Exon A/B in Pseudohypoparathyroidism Type 1A Resulting in an Apparent Loss of Exon A/B Methylation: Potential for Misdiagnosis of Pseudohypoparathyroidism Type 1B SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; IMPRINTING CONTROL ELEMENT; STIMULATORY G-PROTEIN; GS-ALPHA GENE; MOLECULAR-MECHANISMS; HUMAN-DISEASE; IB; MUTATIONS; REARRANGEMENTS; MICRODELETION AB Context: Several endocrine diseases that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia show additional hormone resistance, defective erythrocyte G(s)alpha activity, and dysmorphic features termed Albright's hereditary osteodystrophy (AHO). Patients with PHP-Ib show less diverse hormone resistance and normal G(s)alpha activity; AHO features are typically absent in PHP-Ib. Mutations affecting G(s)alpha coding exons of GNAS and epigenetic alterations in the same gene are associated with PHP-Ia and -Ib, respectively. The epigenetic GNAS changes in familial PHP-Ib are caused by microdeletions near or within GNAS but without involving G(s)alpha coding exons. Objective: We sought to identify the molecular defect in a patient who was diagnosed with PHP-Ia based on clinical presentation (hormone resistance and AHO) but displayed the molecular features typically associated with PHP-Ib (loss of methylation at exon A/B) without previously described genetic mutations. Methods: Microsatellite typing, comparative genome hybridization, and allelic dosage were performed for proband and her parents. Results: Comparative genome hybridization revealed a deletion of 30,431 bp extending from the intronic region between exons XL and A/B to intron 5. The same mutation was also demonstrated, by PCR, in the patient's mother, but polymorphism and allele dosage analyses indicated that she had this mutation in a mosaic manner. Conclusion: We discovered a novel multiexonic GNAS deletion transmitted to our patient from her mother who is mosaic for this mutation. The deletion led to different phenotypic manifestations in the two generation and appeared, in the patient, as loss of GNAS imprinting. (J Clin Endocrinol Metab 95: 765-771, 2010) C1 [Fernandez-Rebollo, Eduardo; Garin, Intza; Castano, Luis; Perez de Nanclares, Guiomar] Hosp Cruces, Endocrinol & Diabet Res Grp, Baracaldo 48903, Basque Country, Spain. [Garcia-Cuartero, Beatriz; Garcia-Lacalle, Concepcion] Hosp Leganes, Madrid 28911, Spain. [Garin, Intza; Castano, Luis; Perez de Nanclares, Guiomar] Ctr Invest Biomed Red Enfermedades Raras, Baracaldo 48903, Bizkaia, Spain. [Largo, Cristina] Parque Tecnol Bizkaia, Genetadi Biotech, Derio 48160, Spain. [Martinez, Francisco] Hosp Univ La Fe, Unidad Genet & Diagnost Prenatal, Valencia 46009, Spain. [Castano, Luis] Univ Basque Country, Sch Med, Bilbao 48940, Spain. [Fernandez-Rebollo, Eduardo; Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Fernandez-Rebollo, Eduardo; Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP de Nanclares, GP (reprint author), Hosp Cruces, Endocrinol & Diabet Res Grp, Baracaldo 48903, Bizkaia, Spain. EM gnanclares@osakidetza.net RI Martinez, Francisco/A-2543-2009; OI Martinez, Francisco/0000-0002-0589-2584; FERNANDEZ-REBOLLO, EDUARDO/0000-0002-4378-7590; Perez de Nanclares, Guiomar/0000-0002-2424-5294; Castano, Luis/0000-0003-0437-9401 FU Instituto de Salud Carlos III of the Spanish Ministry of Health [CP03/0064]; Basque Department of Education [BFI06.266]; Basque Department of Health [GV2008/111035]; Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK073911]; [BIO08/ER/001] FX G. P. d. N. is a Fondo de Investigacion Sanitaria researcher supported by the Instituto de Salud Carlos III of the Spanish Ministry of Health (Grant CP03/0064). I. G. has received a grant from the Basque Department of Education (BFI06.266). This work was partially supported by Grant GV2008/111035 from the Basque Department of Health and BIO08/ER/001. This group is founded by the Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III. This work was also funded, in part, by Grant R01DK073911 from the National Institute of Diabetes and Digestive and Kidney Diseases (to M. B.). NR 28 TC 20 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2010 VL 95 IS 2 BP 765 EP 771 DI 10.1210/jc.2009-1581 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200039 PM 20008020 ER PT J AU Belfort, R Berria, R Cornell, J Cusi, K AF Belfort, Renata Berria, Rachele Cornell, John Cusi, Kenneth TI Fenofibrate Reduces Systemic Inflammation Markers Independent of Its Effects on Lipid and Glucose Metabolism in Patients with the Metabolic Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE RISK; ALPHA AGONIST FENOFIBRATE; CORONARY-HEART-DISEASE; PPAR-ALPHA; INSULIN SENSITIVITY; NONALCOHOLIC STEATOHEPATITIS; PRIMARY-PREVENTION; DIABETES-MELLITUS; CONTROLLED-TRIAL AB Context: Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist widely used in clinical practice, but its mechanism of action is incompletely understood. Objective: The aim of the study was to assess whether improvement in subclinical inflammation or glucose metabolism contributes to its antiatherogenic effects in insulin-resistant subjects with the metabolic syndrome (MetS). Design and Setting: We conducted a randomized, double-blind, placebo-controlled study in the research unit at an academic center. Patients: We studied 25 nondiabetic insulin-resistant MetS subjects. Intervention(s): We administered fenofibrate (200 mg/d) and placebo for 12 wk. Main Outcome Measures: Before and after treatment, we measured plasma lipids/apolipoproteins, inflammatory markers (high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule/vascular cell adhesion molecule), adipocytokines (adiponectin, TNF alpha, leptin), and insulin secretion (oral glucose tolerance test). We also assessed adipose tissue, hepatic and peripheral (muscle) insulin resistance fasting and during a euglycemic insulin clamp with (3)H glucose and (14)C palmitate infusion combined with indirect calorimetry. Results: Subjects displayed severe insulin resistance and systemic inflammation. Fenofibrate significantly reduced plasma triglyceride, apolipoprotein (apo) CII, apo CIII, and apo E (all P < 0.01), with a modest increase in high-density lipoprotein-cholesterol (+ 12%; P = 0.06). Fenofibrate markedly decreased plasma high-sensitivity C-reactive protein by 49.5 +/- 8% (P = 0.005) and IL-6 by 29.8 +/- 7% (P = 0.03) vs. placebo. However, neither insulin secretion nor adipose tissue, hepatic or muscle insulin sensitivity or glucose/lipid oxidation improved with treatment. Adiponectin and TNF-alpha levels were also unchanged. Improvement in plasma markers of vascular/systemic inflammation was dissociated from changes in triglyceride/high-density lipoprotein-cholesterol, apo CII/CIII, or free fatty acid concentrations or insulin secretion/insulin sensitivity. Conclusions: In subjects with the MetS, fenofibrate reduces systemic inflammation independent of improvements in lipoprotein metabolism and without changing insulin sensitivity. This suggests a direct peroxisome proliferator-activated receptor alpha-mediated effect of fenofibrate on inflammatory pathways, which may be important for the prevention of CVD in high-risk patients. (J Clin Endocrinol Metab 95: 829-836, 2010) C1 [Belfort, Renata; Berria, Rachele; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, San Antonio, TX 78229 USA. [Cornell, John] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Epidemiol, San Antonio, TX 78229 USA. [Cornell, John; Cusi, Kenneth] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, Dept Med, Room 3-380S,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cusi@uthscsa.edu FU Veterans Administration; Howard Hughes Medical Institute; Veterans Affairs Medical Research Fund; National Center for Research Resources [1RR025767] FX This work was supported by a Veterans Administration Research Career Development Award (to K. C.), a Howard Hughes Medical Institute Grant (to K. C.), the Veterans Affairs Medical Research Fund, and Award no. UL 1RR025767 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources of the National Institutes of Health. NR 34 TC 73 Z9 74 U1 0 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 FEB PY 2010 VL 95 IS 2 BP 829 EP 836 DI 10.1210/jc.2009-1487 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552NH UT WOS:000274298200046 PM 20061429 ER PT J AU Smith, MW Ma, J Stafford, RS AF Smith, Mark W. Ma, Jun Stafford, Randall S. TI Bar charts enhance Bland-Altman plots when value ranges are limited SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Statistics, nonparametric; Survey methods; Health services/utilization; Biometry; Reproducibility of results; Humans ID AGREEMENT AB Objective: A common form of validation study compares alternative methods for collecting data. The Bland-Altman plot pairs observations across methods and plots their mean values vs. their difference. This method provides only limited information, however, when the range of observed values is small relative to the number of observations. This brief report shows how adding a simple barchart to a Bland-Altman plot adds essential additional information. Study Design and Setting: The methodological approach is illustrated using data from a randomized controlled clinical trial of patients in a U.S. county health system. Results: When the number of unique values is small, a Bland-Altman plot alone may provide inadequate information. Adding a bar chart yields new and essential information about agreement, bias, and heteroscedasticity. Conclusion: Studies validating one data-collection method against another can be performed successfully even when the number of unique values is small. (C) 2010 Elsevier Inc. All rights reserved. C1 [Smith, Mark W.] VA Palo Alto HCS, Hlth Econ Resource Ctr, US Dept Vet Affairs, Menlo Pk, CA 94025 USA. [Ma, Jun] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Ma, Jun] Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. [Stafford, Randall S.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Program Prevent Outcomes & Practices, Stanford, CA 94305 USA. [Stafford, Randall S.] Stanford Univ, Sch Med, Dept Internal Med, Stanford, CA 94305 USA. RP Smith, MW (reprint author), VA Palo Alto HCS, Hlth Econ Resource Ctr, US Dept Vet Affairs, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM mark.smith9@va.gov RI Smith, Mark/G-1522-2012 OI Smith, Mark/0000-0002-4582-9088 FU National Heart, Lung, and Blood Institute [R01 HL070781]; U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service FX This research was supported by a grant from the National Heart, Lung, and Blood Institute (R01 HL070781). Additional support was provided by the U.S. Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service. NR 11 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2010 VL 63 IS 2 BP 180 EP 184 DI 10.1016/j.jclinepi.2009.06.001 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 549OG UT WOS:000274062400013 PM 19716265 ER PT J AU Lyubimova, A Garber, JJ Upadhyay, G Sharov, A Anastasoaie, F Yajnik, V Cotsarelis, G Dotto, GP Botchkarev, V Snapper, SB AF Lyubimova, Anna Garber, John J. Upadhyay, Geeta Sharov, Andrey Anastasoaie, Florentina Yajnik, Vijay Cotsarelis, George Dotto, Gian Paolo Botchkarev, Vladimir Snapper, Scott B. TI Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELL-CELL ADHESION; STEM-CELLS; N-WASP; ACTIN DYNAMICS; BETA-CATENIN; KERATINOCYTE GROWTH; SELF-RENEWAL; RHO-GTPASES; SKIN; DIFFERENTIATION AB The Rho family GTPases Cdc42 and Rac1 are critical regulators of the actin cytoskeleton and are essential for skin and hair function. Wiskott-Aldrich syndrome family proteins act downstream of these GTPases, controlling actin assembly and cytoskeletal reorganization, but their role in epithelial cells has not been characterized in vivo. Here, we used a conditional knockout approach to assess the role of neural Wiskott-Aldrich syndrome protein (N-WASP), the ubiquitously expressed Wiskott-Aldrich syndrome-like (WASL) protein, in mouse skin. We found that N-WASP deficiency in mouse skin led to severe alopecia, epidermal hyperproliferation, and ulceration, without obvious effects on epidermal differentiation and wound healing. Further analysis revealed that the observed alopecia was likely the result of a progressive and ultimately nearly complete block in hair follicle (HF) cycling by 5 months of age. N-WASP deficiency also led to abnormal proliferation of skin progenitor cells, resulting in their depletion over time. Furthermore, N-WASP deficiency in vitro and in vivo correlated with decreased GSK-3 beta phosphorylation, decreased nuclear localization of beta-catenin in follicular keratinocytes, and decreased Wnt-dependent transcription. Our results indicate a critical role for N-WASP in skin function and HF cycling and identify a link between N-WASP and Wnt signaling. We therefore propose that N-WASP acts as a positive regulator of beta-catenin-dependent transcription, modulating differentiation of HF progenitor cells. C1 [Lyubimova, Anna; Garber, John J.; Upadhyay, Geeta; Anastasoaie, Florentina; Yajnik, Vijay; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lyubimova, Anna; Garber, John J.; Upadhyay, Geeta; Anastasoaie, Florentina; Yajnik, Vijay; Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. [Lyubimova, Anna; Garber, John J.; Upadhyay, Geeta; Yajnik, Vijay; Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sharov, Andrey; Botchkarev, Vladimir] Boston Univ, Med Ctr, Dept Dermatol, Boston, MA USA. [Cotsarelis, George] Univ Penn, Sch Med, Dept Dermatol, Kligman Labs, Philadelphia, PA 19104 USA. [Dotto, Gian Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Dotto, Gian Paolo] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Dotto, Gian Paolo] Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. [Botchkarev, Vladimir] Univ Bradford, Cutaneous Biol Grp, Bradford BD7 1DP, W Yorkshire, England. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, SS Fruit St,Jackson 825C, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu FU NIH [5 P01 HLS9S61] FX We thank Alexander van Oudenaarden and members of the Snapper laboratory for critical reading of this manuscript. This work was funded in part by NIH grant 5 P01 HLS9S61 to S.B. Snapper. NR 55 TC 13 Z9 14 U1 1 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 FEB PY 2010 VL 120 IS 2 BP 446 EP 456 DI 10.1172/JCI36478 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 549IA UT WOS:000274040000007 PM 20071778 ER PT J AU Park, SY Gonen, M Kim, HJ Michor, F Polyak, K AF Park, So Yeon Goenen, Mithat Kim, Hee Jung Michor, Franziska Polyak, Kornelia TI Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR HETEROGENEITY; DUCTAL CARCINOMA; CANCER; MUTATIONS; PATTERNS; ORIGINS; CELLS AB Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal. evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments. C1 [Park, So Yeon; Kim, Hee Jung; Polyak, Kornelia] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Sch Med,Dept Med, Boston, MA 02115 USA. [Park, So Yeon] Seoul Natl Univ, Coll Med, Dept Pathol, Songnam, Gyeonggi, South Korea. [Park, So Yeon] Bundang Hosp, Songnam, Gyeonggi, South Korea. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Michor, Franziska] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10021 USA. RP Polyak, K (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol,Sch Med,Dept Med, 44 Binney St D740C, Boston, MA 02115 USA. EM michorf@mskcc.org; Korne-lia_Polyak@dfci.harvard.edu RI Park, So Yeon/A-2621-2012; Seoul National University, Pathology/B-6702-2012; Gonen, Mithat/E-4826-2012 FU Breast Cancer Research Foundation FX We greatly appreciate the help of Stanislawa Weremowicz (Brigham and Women's Hospital, Boston, Massachusetts, USA) with the optimization of FISH protocols and the evaluation of metaphase FISH analyses. We thank Ian Krop, Massimo Loda, William Kaelin, William Hahn, and members of the Polyak laboratory for their critical reading of the manuscript and stimulating discussions. This work was supported by the Breast Cancer Research Foundation (F. Michor). K. Polyak is a Leon Levy Foundation Young Investigator. NR 37 TC 169 Z9 174 U1 3 U2 17 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 FEB PY 2010 VL 120 IS 2 BP 636 EP 644 DI 10.1172/JCI40724 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 549IA UT WOS:000274040000022 PM 20101094 ER PT J AU Robinson, JG Wallace, R Safford, MM Pettinger, M Cochrane, B Ko, MG O'Sullivan, MJ Masaki, K Petrovich, H AF Robinson, Jennifer G. Wallace, Robert Safford, Monika M. Pettinger, Mary Cochrane, Barbara Ko, Marcia G. O'Sullivan, Mary Jo Masaki, Kamal Petrovich, Helen TI Another treatment gap: Restarting secondary prevention medications: The Women's Health Initiative SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Adherence; Coronary heart disease; Secondary prevention; Statins; Women ID ACUTE MYOCARDIAL-INFARCTION; DIETARY MODIFICATION TRIAL; BASE-LINE CHARACTERISTICS; CORONARY-ARTERY-DISEASE; LONG-TERM MORTALITY; MEDICARE BENEFICIARIES; CARDIOVASCULAR DRUGS; ADHERENCE; DISCHARGE; PARTICIPANTS AB BACKGROUND: Women's long-term patterns of evidence-based preventive medication use after a diagnosis of coronary heart disease have not been sufficiently studied. METHODS: Postmenopausal women ages 50 to 79 years were eligible for randomization in the Women's Health Initiative's hormone trials if they met inclusion and exclusion criteria and were >80% adherent during a placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20% fat diet. Those with adjudicated myocardial infarction or coronary revascularization after the baseline visit were included in the analysis (n = 2627). Baseline visits occurred between 1993 and 1998, then annually until the trials ended in 2002 through 2005; medication inventories were obtained at baseline and years 1, 3, 6, and 9. RESULTS: Use at the first Women's Health Initiative visit after a coronary heart disease diagnosis increased over time for statins (49% to 72%; P < .0001), beta-blockers (49% to 62%; P =.003), and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEI/ARBs; 26%-43%; P <.0001). Aspirin use remained stable at 76% (P = .09). Once women reported using a statin, aspirin, or beta-blocker, 84% to 89% reported use at 1 or more subsequent visits, with slightly lower rates for ACEI/ARBS (76%). Statin, aspirin, beta-blocker, or ACEI/ARB use was reported at 2 or more consecutive visits by 57%, 66%, 48%, and 28%, respectively. These drugs were initiated or resumed at a later visit by 24%, 17%, 15%, and 17%, respectively, and were never used during the period of follow-up by 19%, 10%, 33%, and 49% respectively. CONCLUSIONS: Efforts to improve secondary prevention medication use should target both drug initiation and restarting drugs in patients who have discontinued them. (C) 2010 National Lipid Association. All rights reserved. C1 [Robinson, Jennifer G.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Robinson, Jennifer G.; Wallace, Robert] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. [Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. [Safford, Monika M.] Univ Alabama, Birmingham, AL USA. [Pettinger, Mary] Fred Hutchinson Canc Ctr, Seattle, WA USA. [Cochrane, Barbara] Univ Washington, Seattle, WA 98195 USA. [Ko, Marcia G.] Mayo Clin, Div Womens Hlth, Scottsdale, AZ USA. [O'Sullivan, Mary Jo] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Masaki, Kamal] Univ Hawaii, Dept Geriatr Med, Manoa, HI USA. [Masaki, Kamal; Petrovich, Helen] Univ Hawaii, John A Burns Sch Med, Manoa, HI USA. [Masaki, Kamal; Petrovich, Helen] Univ Hawaii, Sch Publ Hlth, Manoa, HI USA. RP Robinson, JG (reprint author), Univ Iowa, Dept Med, 200 Hawkins Dr SE 21C GH, Iowa City, IA 52242 USA. EM jennifer-g-robinson@uiowa.edu FU Abbott; Bristol-Myers Squibb; Hoffman La Roche; Merck; Merck Schering-Plough; NIH; Pfizer; Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research [5 U18 HS016094] FX Dr. Robinson in the past year has received grants from Abbott, Bristol-Myers Squibb, Hoffman La Roche, Merck, and Merck Schering-Plough and was a consul tan tladvisory board for Astra-Zeneca and Wellmark. Dr. Wallace has received grants/research from NIH and Pfizer; was a consultant for Merck and Co.; and on the clinical trial monitoring board of Novartis. Dr. Masaki was on the speaker's bureau for Pfizer. This project was also supported (or supported in part) by an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement #5 U18 HS016094. NR 22 TC 2 Z9 2 U1 1 U2 1 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 FEB PY 2010 VL 4 IS 1 BP 36 EP 45 DI 10.1016/j.jacl.2009.12.006 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 561NL UT WOS:000274984300005 PM 20354566 ER PT J AU Lee, JW Tanaka, N Shiraishi, H Milligan, TA Dworetzky, BA Khoshbin, S Stufflebeam, SM Bromfield, EB AF Lee, Jong Woo Tanaka, Naoaki Shiraishi, Hideaki Milligan, Tracey A. Dworetzky, Barbara A. Khoshbin, Shahram Stufflebeam, Steven M. Bromfield, Edward B. TI Evaluation of Postoperative Sharp Waveforms Through EEG and Magnetoencephalography SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Breach rhythm; EEG; Magnetoencephalography; Interictal epileptiform discharges ID EPILEPSY; ELECTROENCEPHALOGRAPHY AB EEGs obtained after craniotomy are difficult to read because of a breach rhythm consisting of unfiltered sharply contoured physiologic wave-forms that can mimic interictal epileptiform discharges. Magnetoencephalography (MEG) is less affected by the skull breach. The postcraniotomy EEG and MEG scans of 20 patients were reviewed by two experienced electroencephalographers. Larger interrater variability was found for EEG as compared with MEG. Review of patients who had postoperative seizures suggested that EEG was more sensitive but less specific than MEG in detecting interictal epileptiform discharges. Furthermore, several instances of sharp waveforms that were difficult to evaluate on EEG were found to be more easily interpretable on MEG. MEG may also help determine whether asymmetries in physiologic rhythms on EEG result from the skull defect or are pathologic. MEG should be considered as an adjunctive study in patients with a breach rhythm for evaluation of interictal epileptiform discharges and cerebral dysfunction. C1 [Lee, Jong Woo; Milligan, Tracey A.; Dworetzky, Barbara A.; Khoshbin, Shahram; Bromfield, Edward B.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Tanaka, Naoaki; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Shiraishi, Hideaki] Hokkaido Univ, Dept Pediat, Sapporo, Hokkaido, Japan. RP Lee, JW (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM jlee38@partners.org RI Shiraishi, Hideaki/A-8427-2012; OI Dworetzky, Barbara/0000-0002-3364-2347 NR 15 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD FEB PY 2010 VL 27 IS 1 BP 7 EP 11 DI 10.1097/WNP.0b013e3181c9b283 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 562OB UT WOS:000275060600002 PM 20087209 ER PT J AU Recklitis, CJ Diller, LR Li, XC Najita, J Robison, LL Zeltzer, L AF Recklitis, Christopher J. Diller, Lisa R. Li, Xiaochun Najita, Julie Robison, Leslie L. Zeltzer, Lonnie TI Suicide Ideation in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID UNITED-STATES; RISK-FACTORS; CHRONIC PAIN; THOUGHTS; PREVALENCE; TRENDS; PLANS AB Purpose To evaluate risk of suicide ideation (SI) after childhood cancer, prevalence of SI in a cohort of adult survivors of pediatric cancers was compared with prevalence in a sibling comparison group. The relationship of SI to cancer treatment and current health was examined, and the hypothesis that poor physical health is significantly associated with suicidality, after adjusting for depression, was specifically tested. Methods Nine thousand one hundred twenty-six adult survivors of childhood cancer and 2,968 siblings enrolled onto the Childhood Cancer Survivor Study completed a survey describing their demographics and medical and psychological functioning, including SI in the prior week. Results Of survivors, 7.8% reported SI compared with 4.6% of controls (odds ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second malignancy. SI was associated with primary CNS cancer diagnosis, depression, and poor health outcomes including chronic conditions, pain, and poor global health rating. A logistic regression analysis showed that poor current physical health was significantly associated with SI even after adjusting for cancer diagnosis and depression. Conclusion Adult survivors of childhood cancers are at increased risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental and physical health, even many years after completion of therapy. The association of suicidal symptoms with physical health problems is important because these may be treatable conditions for which survivors seek follow-up care and underscores the need for a multidisciplinary approach to survivor care. C1 [Recklitis, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Calif Los Angeles, Sch Med, Mattel Childrens Hosp, Los Angeles, CA USA. RP Recklitis, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, 44 Binney St,SW330, Boston, MA 02115 USA. EM christopher_recklitis@dfci.harvard.edu FU National Cancer Institute [U24 CA55727]; American Foundation for Suicide Prevention; American Lebanese-Syrian Associated Charities FX Supported by Grant No. U24 CA55727 from the National Cancer Institute (L.L.R.) and a research grant from the American Foundation for Suicide Prevention (C.J.R.). St Jude Children's Research Hospital is supported by the American Lebanese-Syrian Associated Charities. NR 47 TC 62 Z9 63 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2010 VL 28 IS 4 BP 655 EP 661 DI 10.1200/JCO.2009.22.8635 PG 7 WC Oncology SC Oncology GA 550OX UT WOS:000274138800022 PM 19841325 ER PT J AU Schapira, L Butow, P Brown, R Boyle, F AF Schapira, Lidia Butow, Phyllis Brown, Richard Boyle, Frances TI Pessimism Is No Poison SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER-PATIENTS; INFORMATION NEEDS; BREAST-CANCER; OF-LIFE; HOPE; COMMUNICATION; PREFERENCES; DIAGNOSIS; PROGNOSIS; ISSUES C1 [Schapira, Lidia] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. Univ Sydney, Sch Psychol, Med Psychol Res Unit, Sydney, NSW 2006, Australia. Mater Hosp, Dept Canc Med, Sydney, NSW, Australia. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM lschapira@partners.org NR 24 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2010 VL 28 IS 4 BP 705 EP 707 DI 10.1200/JCO.2009.25.0027 PG 3 WC Oncology SC Oncology GA 550OX UT WOS:000274138800029 PM 19917853 ER PT J AU Smith, MR Kantoff, PW AF Smith, Matthew R. Kantoff, Philip W. TI Changes In PSA Kinetics After DNA Vaccine Therapy-Not So Fast! SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID PROSTATE-SPECIFIC ANTIGEN; AND/OR RADIATION-THERAPY; PLACEBO; MEN C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. FU NCI NIH HHS [K24 CA121990-04, K24 CA121990] NR 3 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2010 VL 28 IS 4 BP E58 EP E58 DI 10.1200/JCO.2009.26.3111 PG 1 WC Oncology SC Oncology GA 550OX UT WOS:000274138800040 PM 20008614 ER PT J AU Perlis, RH Ostacher, MJ Miklowitz, DJ Smoller, JW Dennehy, EB Cowperthwait, C Nierenberg, AA Thase, ME Sachs, GS AF Perlis, Roy H. Ostacher, Michael J. Miklowitz, David J. Smoller, Jordan W. Dennehy, Ellen B. Cowperthwait, Colleen Nierenberg, Andrew A. Thase, Michael E. Sachs, Gary S. TI Benzodiazepine Use and Risk of Recurrence in Bipolar Disorder: A STEP-BD Report SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; WEEKLY SYMPTOMATIC STATUS; ACUTE MANIA; FOLLOW-UP; COGNITIVE IMPAIRMENT; NATURAL-HISTORY; II DISORDER; DSM-IV; CLONAZEPAM AB Objective: Benzodiazepines are widely prescribed to patients with bipolar disorder, but their impact on relapse and recurrence has not been examined. Method: We examined prospective data from a cohort of DSM-IV bipolar I and II patients who achieved remission during evidence-guided naturalistic treatment in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study (conducted in the United States between 1999 and 2005). Risk for recurrence among individuals who did or did not receive benzodiazepine treatment was examined using survival analysis. Cox regression was used to adjust for clinical and sociodemographic covariates. Propensity score analysis was used in a confirmatory analysis to address the possible impact of confounding variables. Results: Of 1,365 subjects, 349 (25.6%) were prescribed a benzodiazepine at time of remission from a mood episode. After adjusting for potential confounding variables, the hazard ratio for mood episode recurrence among benzodiazepine-treated patients was 1.21 (95% Cl, 1.01-1.45). The effects of benzodiazepine treatment on relapse remained significant after excluding relapses occurring within 90 days of recovery, or stratifying the sample by propensity score, a summary measure of likelihood of receiving benzodiazepine treatment. In an independent cohort of 721 subjects already in remission at study entry, effects of similar magnitude were observed. Conclusion: Benzodiazepine use may be associated with greater risk for recurrence of a mood episode among patients with bipolar I and 11 disorder. The prescribing of benzodiazepines, at a minimum, appears to be a marker for a more severe course of illness. J Clin Psychiatry 2010;71(2):194-200 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Perlis, Roy H.; Ostacher, Michael J.; Cowperthwait, Colleen; Nierenberg, Andrew A.; Sachs, Gary S.] Bipolar Clin & Res Programs, Boston, MA 02114 USA. [Perlis, Roy H.; Ostacher, Michael J.; Smoller, Jordan W.; Cowperthwait, Colleen; Nierenberg, Andrew A.; Sachs, Gary S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Miklowitz, David J.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Perlis, RH (reprint author), Bipolar Clin & Res Programs, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM rperlis@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU NIMH K23 Career Development Award; NIMH, National Institutes of Health [N01MH80001] FX Funding/support: Dr Perlis was supported by an NIMH K23 Career Development Award. This project has been funded in whole or in part with Federal funds from NIMH, National Institutes of Health, under Contract N01MH80001. NR 39 TC 12 Z9 14 U1 1 U2 2 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 FEB PY 2010 VL 71 IS 2 BP 194 EP 200 DI 10.4088/JCP.09m05019yel PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 558RF UT WOS:000274762100010 PM 20193647 ER PT J AU Stewart, SE Jenike, EA Hezel, DM Stack, DE Dodman, NH Shuster, L Jenike, MA AF Stewart, S. Evelyn Jenike, Eric A. Hezel, Dianne M. Stack, Denise Egan Dodman, Nicholas H. Shuster, Louis Jenike, Michael A. TI A Single-Blinded Case-Control Study of Memantine in Severe Obsessive-Compulsive Disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE obsessive-compulsive disorder (OCD); memantine; glutamate; augmenting agents; anxiety disorders; treatment ID SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; INTENSIVE RESIDENTIAL-TREATMENT; DEFICIT HYPERACTIVITY DISORDER; TRANSPORTER GENE SLC1A1; PEDIATRIC OCD; WHITE-MATTER; AUGMENTATION; GLUTAMATE; ASSOCIATION AB Background: Obsessive-compulsive disorder (OCD) is a common debilitating psychiatric illness that typically improves but does not remit with first-line medication and behavioral treatments. Serotonergic agents including selective serotonin reuptake inhibitors and clomipramine have provided the mainstay of OCD medication management for decades. Combined dopamine/serotonergic agents such as atypical antipsychotics are presently the only OCD-augmenting strategies proven effective via randomized controlled trials. Despite increasing evidence for a pathogenic role of glutamate in OCD, no controlled trials of glutamatergic augmenting agents have been reported. Methods: An intent-to-treat sample included 44 subjects receiving standard treatment at the McLean/Massachusetts General Hospital Intensive Residential Treatment (IRT) program, 22 of whom also received memantine augmentation. Admission, monthly and discharge measures of OCD, depression, and psychosocial functioning were collected by raters blinded to augmentation status. Matched controls were selected based on sex, initial OCD severity, psychosocial functioning, and timing of admission. The Clinical Global Improvement Scale captured global clinical change. Results: Mean (SD) Yale-Brown Obsessive Compulsive Scale score decreases were 7.2 (6.4) among the cases and 4.6 (5.9) among the matched controls, reflecting mean clinical improvement among the cases (27.0% decrease) but not the controls (16.5% decrease). Mean (SD) depression severity score decreases were 5.8 (9.5) among the cases and 4.7 (9.9) among the controls. Initial intrusive obsessions were significantly more severe among marked responders compared with limited response or nonresponse cases (4.4 vs 2.9; t = 2.15; P = 0.048). Conclusions: This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted. C1 [Stewart, S. Evelyn; Jenike, Eric A.; Hezel, Dianne M.; Stack, Denise Egan; Jenike, Michael A.] McLean Hosp, Obsess Compuls Disorders Inst, Belmont, MA 02178 USA. [Stewart, S. Evelyn; Jenike, Eric A.; Hezel, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stewart, S. Evelyn; Jenike, Michael A.] Harvard Univ, Sch Med, Boston, MA USA. [Dodman, Nicholas H.; Shuster, Louis] Tufts Univ, Medford, MA 02155 USA. RP Stewart, SE (reprint author), PNGU, Ctr Human Genet Res, 6th Floor,185 Cambridge St, Boston, MA 02114 USA. EM stewart@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 NR 55 TC 66 Z9 68 U1 0 U2 7 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 FEB PY 2010 VL 30 IS 1 BP 34 EP 39 DI 10.1097/JCP.0b013e3181c856de PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 544FE UT WOS:000273637800006 PM 20075645 ER PT J AU Baldessarini, RJ Tondo, L Lepri, B AF Baldessarini, Ross J. Tondo, Leonardo Lepri, Beatrice TI Correlation of Initial Wellness With Long-Term Morbidity in Recurrent Major Affective Disorder Patients as a Test of Survival Analysis SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE assumptions; bipolar disorder; major depression; lithium; survival analysis; treatment ID BIPOLAR-I DISORDER; MAINTENANCE; DEPRESSION; DIVALPROEX; PREGNANCY; LITHIUM; TRIAL; WOMEN AB Because long-term monitoring of morbidity or wellness is often impractical, survival analysis is widely used in experimental therapeutics. In long-term applications, the method assumes that time-to-recurrence or time-to-intervention is a surrogate of long-term clinical status during sustained treatment. Because this plausible assumption has not been tested empirically, we evaluated prospectively and systematically acquired data from consenting adults with major affective disorders treated with lithium for an average of 5.4 years to compare, within-subjects, estimated long-term morbidity versus the first-wellness interval after clinical remission of a treated index episode. These measures were inversely correlated in all 450 subjects with mood disorder (r(s) = -0.65) and in those with bipolar I (n = 259; r(s) = -0.58), II (n = 150; r(s) = -0.65), or recurrent unipolar depression (n = 50; r(s) = -0.66). The wellness interval also predicted episodes per year (r(s) = -0.58, all P < 0.0001). These associations were sustained in multiple-regression modeling, in which a bipolar diagnosis (but not sex, age, or measures of preintake morbidity) was associated with greater long-term morbidity than in major depression. These findings provide moderate support for a basic assumption underlying the use of survival analysis for psychopharmacology research and suggest that clinical outcomes might be predictable from initial wellness intervals. C1 [Baldessarini, Ross J.; Tondo, Leonardo] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar & Psychot Disorder Res, Belmont, MA USA. [Baldessarini, Ross J.; Tondo, Leonardo] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tondo, Leonardo; Lepri, Beatrice] Lucio Bini Ctr Mood Disorder Res, Cagliari, Sardinia, Italy. [Tondo, Leonardo; Lepri, Beatrice] Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org FU Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund; Centro Bini Private Donors Research Fund FX Supported in part by a grant from the Bruce J. Anderson Foundation and by the McLean Private Donors Psychopharmacology Research Fund (to R.J.B.) and by the Centro Bini Private Donors Research Fund (to L.T.). NR 15 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2010 VL 30 IS 1 BP 72 EP 75 DI 10.1097/JCP.0b013e3181c9fdd3 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 544FE UT WOS:000273637800013 PM 20075652 ER PT J AU Bergman, J Logan, S Fink, A Ganz, DA Peterson, MA Litwin, MS AF Bergman, Jonathan Logan, Susan Fink, Arlene Ganz, David A. Peterson, Mark A. Litwin, Mark S. TI Caring for the Uninsured with Prostate Cancer: A Comparison of Four Policy Alternatives in California SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Prostate cancer; Medically uninsured; Vulnerable populations; Community health services ID QUALITY-OF-LIFE; MEDICAID MANAGED CARE; LOW-INCOME; UNITED-STATES; RADICAL PROSTATECTOMY; HEALTH-INSURANCE; SAFETY-NET; MEN; ACCESS; ISSUES AB The IMPACT Program seeks to improve access to prostate cancer care for low-income, uninsured men. The objective of the current study was to compare the cost-effectiveness of four policy alternatives in treating this population. We analyzed the cost-effectiveness of four policy alternatives for providing care to low-income, uninsured men with prostate cancer: (1) IMPACT as originally envisioned, (2) a version of IMPACT with reduced physician fees, (3) a hypothetical Medicaid prostate cancer treatment program, and (4) the existing county safety net. We calculated cost-effectiveness based on incremental cost-effectiveness ratios (ICERs) with the formula ICER = (Cost(alternative strategy) - Cost(baseline strategy)) / (QALY(alternative strategy) - QALY(baseline strategy)). We measured outcomes as quality-adjusted life years (QALYs). "Best-case" scenarios assumed timely access to care in 50% of cases in the county system and 70% of cases in any system that reimbursed providers at Medicaid fee-for-service rates. "Worst-case" scenarios assumed timely access in 35 and 50% of corresponding cases. In fiscal year 2004-2005, IMPACT allocated 11% of total expenditures to administrative functions and 23% to fixed clinical costs, with an overall budget of $5.9 million. The ICERs ($/QALY) assuming "best-case" scenarios for original IMPACT, modified IMPACT, and a hypothetical Medicaid program were $32,091; $64,663; and $10,376; respectively. ICERs assuming "worst-case" scenarios were $27,189; $84,236; and $10,714; respectively. County safety net was used as a baseline. In conclusion, IMPACT provides underserved Californians with prostate cancer care and value-added services with only 11% of funds allocated to administrative fixed costs. Both the original IMPACT program and the hypothetical Medicaid prostate cancer program were cost-effective compared to the county safety net, while the reduced-fees version of IMPACT was not. C1 [Bergman, Jonathan; Litwin, Mark S.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA. [Logan, Susan] Washington Univ, Dept Surg, St Louis, MO 63108 USA. [Fink, Arlene] Univ Calif Los Angeles, Dept Med, Pacific Palisades, CA 90272 USA. [Fink, Arlene; Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Pacific Palisades, CA 90272 USA. [Ganz, David A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Ganz, David A.] VA Greater LA Healthcare Sys 11G, VA Greater Los Angeles Healthcare Syst, Dept Geriatr Res, Educ & Clin Ctr, Los Angeles, CA 90095 USA. [Peterson, Mark A.] Univ Calif Los Angeles, Sch Publ Affairs, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Bergman, J (reprint author), Univ Calif Los Angeles, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jbergman@mednet.ucla.edu NR 42 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD FEB PY 2010 VL 35 IS 1 BP 18 EP 26 DI 10.1007/s10900-009-9199-8 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 552LN UT WOS:000274292300004 PM 19911260 ER PT J AU Martin-Ibanez, R Crespo, E Urban, N Sergent-Tanguy, S Herranz, C Jaumot, M Valiente, M Long, JE Pineda, JR Andreu, C Rubenstein, JLR Marin, O Georgopoulos, K Mengod, G Farinas, I Bachs, O Alberch, J Canals, JM AF Martin-Ibanez, Raquel Crespo, Empar Urban, Noelia Sergent-Tanguy, Solene Herranz, Cristina Jaumot, Montserrat Valiente, Manuel Long, Jason E. Pineda, Jose Ramon Andreu, Celia Rubenstein, John L. R. Marin, Oscar Georgopoulos, Katia Mengod, Guadalupe Farinas, Isabel Bachs, Oriol Alberch, Jordi Canals, Josep M. TI Ikaros-1 Couples Cell Cycle Arrest of Late Striatal Precursors With Neurogenesis of Enkephalinergic Neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE telencephalon; differentiation; striatum; P21; Dlx; Ebf-1 ID DNA-BINDING PROTEINS; NEURAL STEM-CELLS; NEUROTROPHIC FACTOR; TRANSCRIPTION FACTOR; SUBVENTRICULAR ZONE; OLFACTORY-BULB; HOMEOBOX GENES; MAMMALIAN TELENCEPHALON; GANGLIONIC EMINENCE; HUNTINGTONS-DISEASE AB During central nervous system development, several transcription factors regulate the differentiation of progenitor cells to postmitotic neurons. Here we describe a novel role for Ikaros-1 in the generation of late-born striatal neurons. Our results show that Ikaros-1 is expressed in the boundary of the striatal germinal zone (GZ)/mantle zone (MZ), where it induces cell cycle arrest of neural progenitors by up-regulation of the cyclin-dependent kinase inhibitor (CDKi) p21(Cip1/Waf1). This effect is coupled with the neuronal differentiation of late precursors, which in turn is critical for the second wave of striatal neurogenesis that gives rise to matrix neurons. Consistently, Ikaros(-/-) mice had fewer striatal projecting neurons and, in particular, enkephalin (ENK)-positive neurons. In addition, overexpression of Ikaros-1 in primary striatal cultures increases the number of calbindin- and ENK-positive neurons. Our results also show that Ikaros-1 acts downstream of the Dlx family of transcription factors, insofar as its expression is lost in Dlx1/2 double knockout mice. However, we demonstrate that Ikaros-1 and Ebf-1 independently regulate the final determination of the two populations of striatal projection neurons of the matrix compartment, ENK- and substance P-positive neurons. In conclusion, our findings identify Ikaros-1 as a modulator of cell cycle exit of neural progenitors that gives rise to the neurogenesis of ENK-positive striatal neurons. J. Comp. Neurol. 5 18:329-351, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Martin-Ibanez, Raquel; Crespo, Empar; Urban, Noelia; Sergent-Tanguy, Solene; Herranz, Cristina; Jaumot, Montserrat; Pineda, Jose Ramon; Bachs, Oriol; Alberch, Jordi; Canals, Josep M.] Univ Barcelona, Fac Med, Dept Biol Cellular Immunol & Neurociencies, IDIBAPS, E-08036 Barcelona, Spain. [Martin-Ibanez, Raquel; Crespo, Empar; Urban, Noelia; Herranz, Cristina; Andreu, Celia; Mengod, Guadalupe; Farinas, Isabel; Alberch, Jordi; Canals, Josep M.] CIBERNED, Seville 41013, Spain. [Valiente, Manuel; Marin, Oscar] CSIC, Inst Neurociencias Alicante, E-03550 Sant Joan dAlacant, Spain. [Valiente, Manuel; Marin, Oscar] Univ Miguel Hernandez, E-03550 Sant Joan dAlacant, Spain. [Long, Jason E.; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94143 USA. [Andreu, Celia; Farinas, Isabel] Univ Valencia, Dept Biol Celular, E-46010 Valencia, Spain. [Georgopoulos, Katia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02114 USA. [Mengod, Guadalupe] IDIBAPS, CSIC, Inst Invest Biomed Barcelona, Dept Neurochem & Neuropharmacol, E-08036 Barcelona, Spain. RP Canals, JM (reprint author), Univ Barcelona, Fac Med, Dept Biol Cellular Immunol & Neurociencies, IDIBAPS, C Casanova 143, E-08036 Barcelona, Spain. EM jmcanals@ub.edu RI Marin, Oscar/F-3856-2012; Farinas, Isabel/L-7118-2014; Valiente, Manuel/J-9523-2014; Canals, Josep/M-3846-2014; Pineda, Jose/F-9710-2015; OI Marin, Oscar/0000-0001-6264-7027; Farinas, Isabel/0000-0003-2903-4960; Valiente, Manuel/0000-0002-0647-7542; Canals, Josep/0000-0001-6829-7670; Pineda, Jose/0000-0002-0900-7466; Urban Avellaneda, Noelia/0000-0003-4813-9274; Mengod, Guadalupe/0000-0001-7223-7873; Alberch, Jordi/0000-0002-8684-2721 NR 90 TC 20 Z9 20 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD FEB 1 PY 2010 VL 518 IS 3 BP 329 EP 351 DI 10.1002/cne.22215 PG 23 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 531NB UT WOS:000272672500005 PM 19950118 ER PT J AU Mckay, JR Lynch, KG Coviello, D Morrison, R Cary, MS Skalina, L Plebani, J AF McKay, James R. Lynch, Kevin G. Coviello, Donna Morrison, Rebecca Cary, Mark S. Skalina, Lauren Plebani, Jennifer TI Randomized Trial of Continuing Care Enhancements for Cocaine-Dependent Patients Following Initial Engagement SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE cocaine dependence; treatment; contingency management; relapse prevention ID SUBSTANCE USE DISORDERS; ADDICTION SEVERITY INDEX; CONTINGENCY MANAGEMENT; RELAPSE PREVENTION; REINFORCEMENT THERAPY; ESTABLISHING SPECIFICITY; OUTPATIENT TREATMENT; DRINKING BEHAVIOR; SELF-REPORTS; ABSTINENCE AB Objective: The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline. Method: The participants were from intensive outpatient programs, which provide 10 hr per week of group counseling. The CM protocol provided gift certificates (maximum value $1,150; mean received = $740) for cocaine-free urines over 12 weeks on an escalating reinforcement schedule, and weekly individual RP sessions were offered for up to 20 weeks. Average number of RP sessions attended was 3 in RP and 13 in CM + RP. Results: Generalizing estimation equation analyses over 18 months postrandomization showed significant effects for CM (but not RP) on urine toxicology and self-reported cocaine use (p = .05), with no significant CM x RP interactions. Secondary analyses indicated CM + RP produced better cocaine urine toxicology outcomes at 6 months than treatment as usual, odds ratio [OR] = 3.96 (1.33, 11.80), p < .01, and RP, OR = 4.89 (1.51, 15.86), p < .01, and produced better cocaine urine toxicology outcomes at 9 months than treatment as usual, OR = 4.21 (1.37, 12.88), p < .01, and RP, OR = 4.24 (1.32, 13.65), p < .01. Trends also favored CM + RP over CM at 6 months, OR = 2.93 (0.94, 9.07), p = .06, and 9 months, OR = 2.93 (0.94, 9.10), p = .06. Differences between the conditions were not significant after 9 months. Conclusions: These results suggest CM can improve outcomes in cocaine-dependent patients in intensive outpatient programs who have achieved initial engagement, particularly when it is combined with RP. C1 [McKay, James R.] Univ Penn, Ctr Continuum Care Addict, Dept Psychol, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Lynch, Kevin G.; Coviello, Donna; Morrison, Rebecca; Skalina, Lauren; Plebani, Jennifer] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Cary, Mark S.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Mckay, JR (reprint author), Univ Penn, Ctr Continuum Care Addict, Dept Psychol, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM mckay_j@mail.trc.upenn.edu FU NIDA NIH HHS [K02 DA000361-02, K02 DA000361, R01 DA014059, R01 DA14059, R01 DA014059-01] NR 57 TC 19 Z9 19 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2010 VL 78 IS 1 BP 111 EP 120 DI 10.1037/a0018139 PG 10 WC Psychology, Clinical SC Psychology GA 548UO UT WOS:000273993600012 PM 20099956 ER PT J AU Rutkowski, L Vasterling, JJ Proctor, SP Anderson, CJ AF Rutkowski, Leslie Vasterling, Jennifer J. Proctor, Susan P. Anderson, Carolyn J. TI Posttraumatic Stress Disorder and Standardized Test-Taking Ability SO JOURNAL OF EDUCATIONAL PSYCHOLOGY LA English DT Article DE standardized testing; posttraumatic stress disorder; test taking ID MENTAL-HEALTH PROBLEMS; PSYCHOMETRIC PROPERTIES; INTELLECTUAL RESOURCES; VIOLENCE EXPOSURE; VIETNAM VETERANS; PTSD CHECKLIST; SYMPTOMS; SOLDIERS; MODELS; MEMORY AB Given the widespread use and high-stakes nature of educational standardized assessments. understanding factors that affect test-taking ability in young adults is vital. Although scholarly attention has often focused on demographic factors, (e.g., gender and race), sufficiently prevalent acquired characteristic,, may also help explain widespread individual differences on standardized tests. In particular, this article focuses on the role that posttraumatic stress symptoms (PSS) potentially play in standardized academic assessments. Using a military sample measured before and after exposure to war-zone stressors, the authors sought to explain test-taking ability differences with respect to symptoms of PTSD on two cognitive tasks that closely match standardized test constructs. The primary method for this analysis is based on an item response theory with covariates approach. Findings suggest that the effect for PSS is significant on both tasks, particularly for those who experience the highest levels of PSS following war-zone exposure. Findings provide potentially valuable information regarding the nature of the relationship between PSS and verbal and logical reasoning test performance. C1 [Rutkowski, Leslie; Anderson, Carolyn J.] Univ Illinois, Dept Educ Psychol, Urbana, IL 61801 USA. [Rutkowski, Leslie; Vasterling, Jennifer J.; Proctor, Susan P.] VA Boston Healthcare Syst, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Proctor, Susan P.] USA, Inst Environm Med, Natick, MA 01760 USA. RP Rutkowski, L (reprint author), Int Assoc Evaluat Educ Achievement, Data Proc & Res Ctr, Mexikoring 37, D-22297 Hamburg, Germany. EM leslie.rutkowski@iea-dpc.de NR 61 TC 2 Z9 2 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0663 J9 J EDUC PSYCHOL JI J. Educ. Psychol. PD FEB PY 2010 VL 102 IS 1 BP 223 EP 233 DI 10.1037/a0017287 PG 11 WC Psychology, Educational SC Psychology GA 551OF UT WOS:000274218200017 ER PT J AU Fischer, C Goldstein, J Edlow, J AF Fischer, Christopher Goldstein, Joshua Edlow, Jonathan TI CEREBRAL VENOUS SINUS THROMBOSIS IN THE EMERGENCY DEPARTMENT: RETROSPECTIVE ANALYSIS OF 17 CASES AND REVIEW OF THE LITERATURE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE cerebral venous sinus thrombosis; neurology ID RISK; VEIN; PUERPERIUM; PREGNANCY; CARRIERS; STROKE; USERS AB Background: Cerebral venous sinus thrombosis (CVST) is a rare but serious cause of neurologic impairment. Due to its relative rarity, there is limited research that describes the incidence and clinical features of CVST in the emergency department (ED). Objectives: To describe the demographic, clinical, and historical characteristics of patients with CVST who were initially seen in the ED. Methods: This is a retrospective analysis of all patients presenting to three urban, tertiary care hospitals between January 2001 and December 2005 who were diagnosed with CVST. Patients were excluded if they were transferred from other hospitals, or admitted directly to the hospital without evaluation in the ED. We use one representative case to describe the presentation, evaluation, and treatment of CVST. Results: Seventeen patients met the inclusion criteria. Patients had a mean age of 42 years. Presenting complaints included headache (70%), focal neurologic complaints (numbness, weakness, aphasia) (29%), seizure (24%), and head injury (12%). Ninety-four percent of patients had a focal neurologic finding in the ED. A likely contributing cause of thrombosis was identified in all but one patient. More than half of the patients had been evaluated in the ED in the previous 60 days. Two patients died, both as a result of their thrombosis and resulting cerebral infarctions and edema. Of the patients who survived, 80% had a good functional outcome. Conclusions: CVST is rare, but it can have significant associated morbidity and mortality. Whereas the clinical outcome and functional outcomes of treated patients can vary, prompt recognition of the disease is important. (C) 2010 Elsevier Inc. C1 [Fischer, Christopher; Edlow, Jonathan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Goldstein, Joshua] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Fischer, C (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 1 Deaconess Rd,W CC-2, Boston, MA 02215 USA. NR 31 TC 8 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2010 VL 38 IS 2 BP 140 EP 147 DI 10.1016/j.jemermed.2009.08.061 PG 8 WC Emergency Medicine SC Emergency Medicine GA 565NU UT WOS:000275301600004 PM 20031365 ER PT J AU Hasegawa, K Schofer, JM AF Hasegawa, Kohei Schofer, Joel M. TI RUPTURE OF THE PECTORALIS MAJOR: A CASE REPORT AND REVIEW SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE rupture of pectoralis major; weightlifting; anabolic steroid; magnetic resonance imaging; surgical therapy ID DELAYED REPAIR; MUSCLE; INJURIES; TENDON; AVULSION AB Background: Rupture of the pectoralis major muscle is a rare clinical entity that is becoming more common due to the increasing popularity of weightlifting and recreational sports. Due to the rarity of this condition, it may be missed at initial presentation and inappropriately treated, potentially leading to increased disability. Objectives: This case highlights the mechanism of injury, clinical features, diagnosis, and treatment of rupture of the pectoralis major. Case Report: The patient was a 31-year-old male bodybuilder who presented to the Emergency Department with acute pain and swelling in the left axilla after performing a bench press with a 400-pound barbell. The diagnosis of pectoralis major rupture was suspected and confirmed by magnetic resonance imaging, and early surgical repair was performed. Conclusion: The most common mechanism of injury is excessive tension on a maximally contracted pectoralis major muscle. Weightlifting, specifically bench pressing, is a common cause. The diagnosis can usually be made based on a patient's history and physical examination, but shortly after injury, the diagnosis may be obscured by severe pain and swelling. Magnetic resonance imaging is the imaging modality of choice when the diagnosis remains unclear, and can avoid surgical delays. Early diagnosis and treatment within 3 to 8 weeks after the injury has the advantage of avoiding adhesions and muscle atrophy, and can prevent a delayed return to normal activities. Given the trend toward improved results with early surgical repair of complete rupture, it is important to raise awareness about pectoralis major muscle injury among Emergency Physicians to prevent missed or delayed diagnosis and repair. (C) 2010 Elsevier Inc. C1 [Schofer, Joel M.] US Naval Hosp Okinawa, Dept Emergency Med, Okinawa, Japan. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, 75 Francis St,Neville House 236-A, Boston, MA 02115 USA. NR 34 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2010 VL 38 IS 2 BP 196 EP 200 DI 10.1016/j.jemermed.2008.01.025 PG 5 WC Emergency Medicine SC Emergency Medicine GA 565NU UT WOS:000275301600015 PM 18818044 ER PT J AU Ginde, AA Delaney, KE Pallin, DJ Camargo, CA AF Ginde, Adit A. Delaney, Kate E. Pallin, Daniel J. Camargo, Carlos A., Jr. TI MULTICENTER SURVEY OF EMERGENCY PHYSICIAN MANAGEMENT AND REFERRAL FOR HYPERGLYCEMIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE diabetes mellitus; hyperglycemia; survey; screening; emergency medicine ID DEPARTMENTS; GLUCOSE; HEALTH AB Background: The Emergency Department (ED), with its high-risk and often disenfranchised patient population, presents a novel opportunity to identify patients as having undiagnosed or uncontrolled diabetes. Objective: To evaluate Emergency Physician opinion on management and referral for incidental hyperglycemia and on ED-based diabetes screening. Methods: We conducted a web-based survey of all attending and resident Emergency Physicians at three academic EDs. We asked for glucose thresholds to treat and refer non-diabetic and diabetic ED patients for hyperglycemia, comparing physicians' ideal and actual practices. We also inquired about interest in and barriers for active ED-based diabetes screening compared to use of blood glucose values obtained during usual ED care. Results: We contacted 185 physicians, and 152 (85%) completed the survey; 75% of respondents reported routine outpatient referral of non-diabetic patients for random glucose values >= 200 mg/dL. However, a majority (71%) believed that they should use a lower threshold to refer than they currently use. Nearly all (92%) agreed that Emergency Physicians should inform non-diabetic patients of elevated glucose values; 53% supported and 21% opposed active ED-based screening of asymptomatic patients. The most commonly cited barriers were limited follow-up (69%), insufficient time/resources (51%), and outside scope of practice (36%). Conclusion: Emergency Physicians support improved recognition of and referral for hyperglycemia, based on glucose values collected during usual ED care. We plan to develop tools to interpret random ED glucose values in the context of undiagnosed and uncontrolled diabetes. (C) 2010 Elsevier Inc. C1 [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Ginde, Adit A.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Delaney, Kate E.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu RI Pallin, Daniel/H-6382-2013; Siry, Bonnie/D-7189-2017 OI Pallin, Daniel/0000-0002-8517-9702; FU Emergency Medicine Foundation Research Fellowship Grant FX Dr. Ginde was supported by the Emergency Medicine Foundation Research Fellowship Grant. NR 10 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD FEB PY 2010 VL 38 IS 2 BP 264 EP 270 DI 10.1016/j.jemermed.2007.11.088 PG 7 WC Emergency Medicine SC Emergency Medicine GA 565NU UT WOS:000275301600031 PM 18657930 ER PT J AU Pagonis, TC Chen, J Fontana, CR Devalapally, H Ruggiero, K Song, XQ Foschi, F Dunham, J Skobe, Z Yamazaki, H Kent, R Tanner, ACR Amiji, MM Soukos, NS AF Pagonis, Tom C. Chen, Judy Fontana, Carla Raquel Devalapally, Harikrishna Ruggiero, Karriann Song, Xiaoqing Foschi, Federico Dunham, Joshua Skobe, Ziedonis Yamazaki, Hajime Kent, Ralph Tanner, Anne C. R. Amiji, Mansoor M. Soukos, Nikolaos S. TI Nanoparticle-based Endodontic Antimicrobial Photodynamic Therapy SO JOURNAL OF ENDODONTICS LA English DT Article DE Endodontic disinfection; Enterococcus faecalis; methylene blue; photodynamic therapy; polymeric nanoparticles ID LIGHT-ACTIVATED DISINFECTION; POLY(BETA-AMINO ESTER) NANOPARTICLES; TUMOR-TARGETED DELIVERY; PH-SENSITIVE SYSTEM; IN-VITRO; ENTEROCOCCUS-FAECALIS; ROOT CANALS; POLY(DL-LACTIDE-CO-GLYCOLIDE) NANOPARTICLES; LETHAL PHOTOSENSITIZATION; ANTIBACTERIAL ACTIVITY AB Objective: To study the in vitro effects of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) and light against Enterococcus faecalis (ATCC 29212). Materials and Methods: The uptake and distribution of nanoparticles in E. faecalis in suspension was investigated by transmission electron microscopy (TEM) after incubation with PLGA complexed with colloidal gold particles for 2.5, 5, and 10 minutes. E. faecalis species were sensitized in planktonic phase and in experimentally infected root canals of human extracted teeth with MB-loaded nanoparticles for 10 minutes followed by exposure to red light at 665 nm. Results: The nanoparticles were found to be concentrated mainly on the cell walls of microorganisms at all three time points. The synergism of light and MB-loaded nanoparticles led to approximately 2 and 1 log(10) reduction of colony-forming units (CFUs) in planktonic phase and root canals, respectively. In both cases, mean log(10) CFU levels were significantly lower than controls and MB-loaded nanoparticles without light. Conclusion: The utilization of PLGA nanoparticles encapsulated with photoactive drugs may be a promising adjunct in antimicrobial endodontic treatment. (J Endod 2010;36:322-328) C1 [Fontana, Carla Raquel; Ruggiero, Karriann; Song, Xiaoqing; Foschi, Federico; Dunham, Joshua; Soukos, Nikolaos S.] Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. [Pagonis, Tom C.; Chen, Judy] Harvard Univ, Sch Dent Med, Div Endodont, Boston, MA 02115 USA. [Skobe, Ziedonis; Yamazaki, Hajime] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. [Tanner, Anne C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Kent, Ralph] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Devalapally, Harikrishna; Amiji, Mansoor M.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. EM nsoukos@forsyth.org RI Rastelli, Marcio/B-8034-2011; Foschi, Federico /E-7531-2012; Fontana, Carla/C-2033-2012; Amiji, Mansoor/A-4365-2014; OI Fontana, Carla/0000-0002-9135-3690; Amiji, Mansoor/0000-0001-6170-881X; Foschi, Federico/0000-0001-6901-0280 FU NIDCR [R01-DE-16922] FX Supported by NIDCR grant R01-DE-16922. NR 42 TC 73 Z9 78 U1 2 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD FEB PY 2010 VL 36 IS 2 BP 322 EP 328 DI 10.1016/j.joen.2009.10.011 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617KK UT WOS:000279279400029 PM 20113801 ER PT J AU Lauwers, GY Fujita, H Nagata, K Shimizu, M AF Lauwers, Gregory Y. Fujita, Hiroshi Nagata, Koji Shimizu, Michio TI Pathology of non-Helicobacter pylori gastritis: extending the histopathologic horizons SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Gastritis; Helicobacter pylori; Drug-induced; Acute; Chronic; Stomach ID SELECTIVE INTERNAL RADIATION; VERSUS-HOST-DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FOCALLY ENHANCED GASTRITIS; RUSSELL BODY GASTRITIS; ISOLATED GRANULOMATOUS GASTRITIS; ARTERIAL INFUSION CHEMOTHERAPY; UPPER GASTROINTESTINAL-TRACT; X-LINKED AGAMMAGLOBULINEMIA; BONE-MARROW TRANSPLANTATION AB The development of modern endoscopic techniques, easier and greater access to healthcare, and interest in Helicobacter pylori infection and its implications have all led to a significant increase in upper endoscopies. In turn, gastroenterologists and pathologists have been recognizing an ever-increasing number of patterns of mucosal injury. Consequently, there is now an interest in a wider aspect of non-neoplastic gastric pathology, namely, non-HP (H. pylori) gastritis. In this review, we present major clinico-pathological entities, based on either the salient morphological features or the underlying etiologies. C1 [Lauwers, Gregory Y.; Fujita, Hiroshi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Pathol Serv,Dept Pathol, Boston, MA 02114 USA. [Fujita, Hiroshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest Life Style Related Dis, Kagoshima 890, Japan. [Nagata, Koji; Shimizu, Michio] Saitama Med Univ, Saitama Int Med Ctr, Dept Pathol, Saitama, Japan. RP Lauwers, GY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Pathol Serv,Dept Pathol, 55 Fruit St WRN 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 133 TC 8 Z9 8 U1 1 U2 4 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0944-1174 EI 1435-5922 J9 J GASTROENTEROL JI J. Gastroenterol. PD FEB PY 2010 VL 45 IS 2 BP 131 EP 145 DI 10.1007/s00535-009-0146-3 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 555OF UT WOS:000274521100001 PM 19967418 ER PT J AU Konstantinidis, IT Deshpande, V Zheng, H Wargo, JA Fernandez-del Castillo, C Thayer, SP Androutsopoulos, V Lauwers, GY Warshaw, AL Ferrone, CR AF Konstantinidis, Ioannis T. Deshpande, Vikram Zheng, Hui Wargo, Jennifer A. Fernandez-del Castillo, Carlos Thayer, Sarah P. Androutsopoulos, Vasiliki Lauwers, Gregory Y. Warshaw, Andrew L. Ferrone, Cristina R. TI Does the Mechanism of Lymph Node Invasion Affect Survival in Patients with Pancreatic Ductal Adenocarcinoma? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 30-JUN 04, 2009 CL Chicago, IL SP Soc Surg Alimentary Tract DE Pancreatic ductal adenocarcinoma; Direct lymph node invasion; Lymph node ratio ID COMPARING STANDARD PANCREATICODUODENECTOMY; SINGLE-INSTITUTION EXPERIENCE; EXTENDED LYMPHADENECTOMY; PROGNOSTIC-SIGNIFICANCE; HEAD ADENOCARCINOMA; 5-YEAR SURVIVORS; CANCER SURVIVAL; RATIO; RESECTION; DATABASE AB Lymph node metastases are prognostically significant in pancreatic ductal adenocarcinoma. Little is known about the significance of direct lymph node invasion. The aim of this study is to find out whether direct lymph node invasion has the same prognostic significance as regional nodal metastases. Retrospective review of patients resected between 1/1/1993 and 7/31/2008. "Direct" was defined as tumor extension into adjacent nodes, and "regional" was defined as metastases to peripancreatic nodes. Overall, 517 patients underwent pancreatic resection for adenocarcinoma, of whom 89 had one positive node (direct 26, regional 63), and 79 had two positive nodes (direct 6, regional 68, both 5). Overall, survival of node-negative patients was improved compared to patients with positive nodes (N0 30.8 months vs. N1 16.4 months; p < 0.001). There was no survival difference for patients with direct vs. regional lymph node invasion (p = 0.67). Patients with one positive node had a better overall survival compared to patients with a parts per thousand yen2 positive nodes (22.3 and 15 months, respectively; p < 0.001). The lymph node ratio (+LN/total LN) was prognostically significant after Cox regression (p < 0.001). Isolated direct invasion occurs in 20% of patients with one to two positive nodes. Node involvement by metastasis or by direct invasion are equally significant predictors of reduced survival. Both the number of positive nodes and the lymph node ratio are significant prognostic factors. C1 [Konstantinidis, Ioannis T.; Wargo, Jennifer A.; Fernandez-del Castillo, Carlos; Thayer, Sarah P.; Androutsopoulos, Vasiliki; Warshaw, Andrew L.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Deshpande, Vikram; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Dept Biostat Ctr, Boston, MA 02114 USA. [Ferrone, Cristina R.] Wang Ambulatory Care Ctr 460, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Wang Ambulatory Care Ctr 460, 15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org FU NCI NIH HHS [L30 CA117696, L30 CA117696-02A1, P01 CA117969, P01 CA117969-02, P01 CA117969-03, P01 CA117969-04, P50 CA127003, P50 CA127003-02, P50 CA127003-03]; NIDDK NIH HHS [K08 DK071329, K08 DK071329-03, K08 DK071329-04, K08 DK071329-05] NR 24 TC 22 Z9 23 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2010 VL 14 IS 2 BP 261 EP 267 DI 10.1007/s11605-009-1096-z PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 546ZE UT WOS:000273853500014 PM 19937477 ER PT J AU Borrero, S Moore, CG Qin, L Schwarz, EB Akers, A Creinin, MD Ibrahim, SA AF Borrero, Sonya Moore, Charity G. Qin, Li Schwarz, Eleanor B. Akers, Aletha Creinin, Mitchell D. Ibrahim, Said A. TI Unintended Pregnancy Influences Racial Disparity in Tubal Sterilization Rates SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE unintended pregnancy; minority women; tubal sterilization ID FAMILY-PLANNING-SERVICES; UNITED-STATES; CONTRACEPTIVE USE; PHYSICIANS PERCEPTIONS; PRIVATE PROVIDERS; PUBLIC-HEALTH; NEW-ORLEANS; WOMEN; RACE; CARE AB BACKGROUND: Minority women are more likely than white women to choose tubal sterilization as a contraceptive method. Disparities in rates of unintended pregnancy may help explain observed racial/ethnic differences in sterilization, but this association has not been investigated. OBJECTIVE: To examine the associations among race/ethnicity, unintended pregnancy, and tubal sterilization. DESIGN AND PARTICIPANTS: Cross-sectional analysis of data from a nationally representative sample of women aged 15-44 years [65.7% white, 14.8% Hispanic, and 13.9% African American (AA)] who participated in the 2002 National Survey of Family Growth. MAIN MEASURES: race/ethnicity, history of unintended pregnancy, and tubal sterilization. A logistic regression model was used to estimate the effect of race/ethnicity on unintended pregnancy while adjusting for socio-demographic variables. A series of logistic regression models was then used to examine the role of unintended pregnancy as a confounder for the relationship between race/ethnicity and sterilization. KEY RESULTS: Overall, 40% of white. 48% of Hispanic, and 59% of AA women reported a history of unintended pregnancy. After adjusting for socio-demographic variables, AA women were more likely (OR: 2.0; 95% CI: 1.6-2.4) and Hispanic women as likely (OR: 1.0: 95% CI: 0.80-1.2) as white women to report unintended pregnancy. Sterilization was reported by 29% of women who had ever had an unintended pregnancy compared to 7% of women who reported never having an unintended pregnancy. In unadjusted analysis, AA and Hispanic women had significantly higher odds of undergoing sterilization (OR: 1.5; 95% CI: 1.3-1.9 and OR: 1.4: 95% CI: 1.2-1.7, respectively). After adjusting for unintended pregnancy, this relationship was attenuated and no longer significant (OR: 1.2: 95% CI: 0.95-1.4 for AA women and OR: 1.3:95% CI: 1.0-1.6 for Hispanic women). CONCLUSION: Minority women, who more frequently experience unintended pregnancy, may choose tubal sterilization in response to prior experiences with an unintended pregnancy. C1 [Borrero, Sonya; Moore, Charity G.; Qin, Li; Schwarz, Eleanor B.; Ibrahim, Said A.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Borrero, Sonya; Ibrahim, Said A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Schwarz, Eleanor B.; Akers, Aletha; Creinin, Mitchell D.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Schwarz, Eleanor B.; Akers, Aletha; Creinin, Mitchell D.] Magee Womens Res Inst, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Borrero, S (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu RI Potter, Joseph/A-3122-2008; OI Moore, Charity/0000-0002-0060-0124; Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU National Center for Research Resources (NCRR) [05 KL2 RR024154-04]; National Institutes of Health (NIH) FX This manuscript was made possible by Dr. Borrero's grant (05 KL2 RR024154-04) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The content of this publication is solely the responsibility of tire authors and does not necessarily represent the official view of NCRR or NIH. NR 50 TC 16 Z9 16 U1 2 U2 9 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 FEB PY 2010 VL 25 IS 2 BP 122 EP 128 DI 10.1007/s11606-009-1197-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 558LV UT WOS:000274744800007 PM 19967463 ER PT J AU Temel, JS Greer, JA Admane, S Solis, J Cashavelly, BJ Doherty, S Heist, R Pirl, WF AF Temel, Jennifer S. Greer, Joseph A. Admane, Sonal Solis, Jessica Cashavelly, Barbara J. Doherty, Stephen Heist, Rebecca Pirl, William F. TI Code Status Documentation in the Outpatient Electronic Medical Records of Patients with Metastatic Cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 29-JUN 02, 2009 CL Orlando, FL SP Amer Soc Clin Oncol DE resuscitation preferences; DNR/DNI; metastatic cancer ID NOT-RESUSCITATE ORDERS; ADVANCE DIRECTIVES; SERIOUSLY ILL; TREATMENT PREFERENCES; HOSPITALIZED-PATIENTS; TERMINAL ILLNESS; CARE; SUPPORT; DECISIONS; PROGNOSIS AB BACKGROUND: Advanced care planning (ACP) is considered an essential component of medical care in the United States, especially in patients with incurable diseases. However, little is known about clinical practices in outpatient oncology settings related to discussing end-of-life care and documenting code status preferences in ambulatory medical records. OBJECTIVE: To assess the rate of documentation of code status in the electronic longitudinal medical records (LMR) of patients with metastatic cancer. DESIGN: Retrospective review of 2.498 patients with metastatic solid tumors at an academic cancer center. An electronic patient database and the LMR were queried to identify demographic information, cancer type, number of clinic visits, and documentation of code status. PARTICIPANTS: The sample consisted of adult patients with metastatic prostate, breast, ovarian, bladder kidney, colorectal. non-colorectal gastrointestinal (GI). and lung cancers. MEASUREMENTS: Primary outcome was the percentage of documented code status in the LMR. MAIN RESULTS: Among the 2.498 patients. 20.3% had a documented code status. Code status was designated most frequently in patients with non-colorectal GI (193/609, 31.7%) and lung (179/583, 30.7%) cancers and least. frequently in patients with genitourinary malignancies [bladder/kidney (4/89, 4.5%), ovarian (4/93, 4.3%), and prostate (7/365, 1.9%) cancers]. Independent predictors of having documented code status included religious affiliation, cancer type, and a greater number of visits to the cancer center. Younger patients and black patients were less likely to be designated as DNR/DNI. CONCLUSIONS: Despite the incurable nature of metastatic cancer, only a minority of patients had a code status documented in the electronic medical record. C1 [Temel, Jennifer S.; Greer, Joseph A.; Admane, Sonal; Solis, Jessica; Cashavelly, Barbara J.; Doherty, Stephen; Heist, Rebecca; Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jtemel@partners.org NR 20 TC 28 Z9 28 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2010 VL 25 IS 2 BP 150 EP 153 DI 10.1007/s11606-009-1161-z PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 558LV UT WOS:000274744800012 PM 19894078 ER PT J AU Dhand, A Dhaliwal, G AF Dhand, Amar Dhaliwal, Gurpreet TI Examining Patient Conceptions: A Case of Metastatic Breast Cancer in an African American Male to Female Transgender Patient SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE transgender; breast cancer; estrogen; ethnography ID CARE; CULTURE; WOMEN AB An African American male to female transgender patient treated with estrogen detected a breast lump that was confirmed by her primary care provider. The patient refused mammography and 14 months later she was diagnosed with metastatic breast cancer with spinal cord compression. We used ethnographic interviews and observations to elicit the patient's conceptions of her illness and actions. The patient identified herself as biologically male and socially female; she thought that the former protected her against breast cancer: she had fears that excision would make a breast tumor spread; and she believed injectable estrogens were less likely than oral estrogens to cause cancer. Analysis suggests dissociation between the patient's social and biological identities, fear and fatalism around cancer screening, and legitimization of injectable hormones. This case emphasizes the importance of eliciting and interpreting a patient's conceptions of health and illness when discordant understandings develop between patient and physician. C1 [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv 1111, San Francisco, CA 94121 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Dhand, Amar] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, Med Serv 1111, 4150 Clement St, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@va.gov NR 16 TC 10 Z9 10 U1 2 U2 7 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 FEB PY 2010 VL 25 IS 2 BP 158 EP 161 DI 10.1007/s11606-009-1159-6 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 558LV UT WOS:000274744800014 PM 19898907 ER PT J AU Hammer, MJ Motzer, SA Voss, JG Berry, DL AF Hammer, Marilyn J. Motzer, Sandra Adams Voss, Joachim G. Berry, Donna L. TI Glycemic Control Among Older Adult Hematopoietic Cell Transplant Recipients SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID POSTTRANSPLANT DIABETES-MELLITUS; TOTAL PARENTERAL-NUTRITION; INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; CANCER-PATIENTS; INFECTIOUS-DISEASE; GLUCOSE CONTROL; IMMUNE-SYSTEM; HYPERGLYCEMIA; STRESS AB Adults age 55 and older with hematological malignancies who require hematopoietic cell transplantation (HCT) for survival are at risk for a number of nonmalignancy-related, potentially life-threatening outcomes, often due to suboptimal immune function. Evidence is emerging regarding how abnormal glycemic levels-newly termed malglycemia-impair cells of the immune system. Further, older adult HCT recipients appear highly susceptible to malglycemic states, particularly hyperglycemia, due to treatment regimens, nutritional imbalances, states of immobility, and stress, all coupled with the natural aging process. Patients with preexisting diabetes may be at further risk for malglycemic states. The growing number of older adults receiving HCT will substantially increase the likelihood nurses will have to provide care to HCT survivors. Therefore, it is important nurses in all practice settings have an understanding of the short- and long-term effects of glycemic status on immune function. C1 [Hammer, Marilyn J.] NYU, Coll Nursing, New York, NY 10003 USA. [Motzer, Sandra Adams; Voss, Joachim G.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Hammer, MJ (reprint author), NYU, Coll Nursing, 726 Broadway,10th Floor, New York, NY 10003 USA. EM marilyn.hammer@nyu.edu FU NINR NIH HHS [P30 NR011400] NR 77 TC 2 Z9 2 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD FEB PY 2010 VL 36 IS 2 BP 40 EP 50 DI 10.3928/00989134-20091207-99 PG 11 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 555GK UT WOS:000274496700005 PM 20047243 ER PT J AU Dohlman, CH Grosskreutz, CL Chen, TC Pasquale, LR Rubin, PAD Kim, EC Durand, M AF Dohlman, Claes H. Grosskreutz, Cynthia L. Chen, Teresa C. Pasquale, Louis R. Rubin, Peter A. D. Kim, Eva C. Durand, Marlene TI Shunts to Divert Aqueous Humor to Distant Epithelialized Cavities After Keratoprosthesis Surgery SO JOURNAL OF GLAUCOMA LA English DT Article DE glaucoma shunts; aqueous diversion; epithelialized cavities ID GLAUCOMA; MITOMYCIN AB Purpose: Glaucoma is a frequent and often severe problem in patients needing keratoprosthesis (KPro) surgery. Standard glaucoma shunts in these cases often develop a very dense capsule that obstructs flow and causes intraocular pressure elevation. Therefore, we developed shunts that deliver aqueous to distant epithelialized cavities where an obstructing capsule is less likely to form. In this retroactive study of such shunts, the risk of postoperative infection ( especially endophthalmitis) has been assessed. Methods: Ahmed shunts were connected with a tube to the lacrimal sac or ethmoid sinuses. In subsequent designs the polypropylene plate was eliminated, the valve was enclosed and a distal tube added ( New World Medical Inc, Rancho Cucamonga, CA). The latter shunts were connected to the maxillary sinus or lower lid fornix. Between 2001 and 2005 the devices were implanted in 34 patients with very severe ocular disease. ( 31 had KPro implanted). Thus, the distal tube was led to the lacrimal sac ( 2 cases), to the ethmoid sinuses ( 6), to the maxillary sinus ( 16 cases), and to the lower lid fornix ( 10 cases). The patients were followed for cumulatively 145 shunt years, with a mean follow-up of 4 years and 3 months. They were instructed to administer low-dose topical antibiotics indefinitely. Results: Only 1 case of acute bacterial endophthalmitis occurred, thus an incidence of 0.7% per shunt year. A slow-growing Mycobacterium was cultured in a disintegrating eye and 1 bacterial maxillary sinusitis occurred, both in autoimmune diseases. Three valves became exposed and had to be removed ( 1 replaced). Four eyes developed hypotony, probably from valve failure. Conclusions: The shunt arrangement, which connects the anterior chamber to potentially microbe-populated cavities or to the lower lid fornix and its flora, might be suspected to allow rapid retrograde invasion of infective agents, resulting in endophthalmitis. In this series of KPro patients, however, the incidence of severe infection was very low, in fact comparable to that after standard trabeculectomy. C1 [Dohlman, Claes H.; Grosskreutz, Cynthia L.; Chen, Teresa C.; Pasquale, Louis R.; Rubin, Peter A. D.; Kim, Eva C.; Durand, Marlene] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu NR 22 TC 15 Z9 16 U1 0 U2 0 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 FEB PY 2010 VL 19 IS 2 BP 111 EP 115 DI 10.1097/IJG.0b013e3181a2fbeb PG 5 WC Ophthalmology SC Ophthalmology GA 560PV UT WOS:000274915500007 PM 19373101 ER PT J AU Buijze, GA Ring, D AF Buijze, Geert A. Ring, David TI Clinical Impact of United Versus Nonunited Fractures of the Proximal Half of the Ulnar Styloid Following Volar Plate Fixation of the Distal Radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Distal radius fracture; nonunion; outcome; ulnar styloid base fracture ID TRIANGULAR FIBROCARTILAGE COMPLEX; RADIOULNAR JOINT INSTABILITY; COLLES FRACTURES; PERIPHERAL TEARS; STABILITY; SUPINATION; CHILDREN; FOREARM; WRIST AB Purpose Distal radius fractures are often associated with a fracture of the ulnar styloid at its base. This study tested the null hypothesis that there is no difference in outcome between patients with union and nonunion of a fracture of the proximal half of the ulnar styloid 6 months after volar plate fixation of a fracture of the distal radius. Methods A total of 36 consecutive patients with fractures of both distal radius and the proximal half of the ulnar styloid enrolled in 1 of 2 clinical trials evaluating volar plate fixation of the distal radius had no treatment of the ulnar styloid fracture. Six months after surgery, wrist function was assessed using the Mayo wrist score and the Gartland and Werley score system, and arm-specific health status was measured using the Disabilities of the Arm, Shoulder, and Hand questionnaire. Pain was assessed on a 10-point ordinal scale. Nonunion of the fracture of the proximal half of the ulnar styloid was defined as no signs of consolidation on 6-month postoperative radiographs. At the 6-month follow-up, patients were assessed for overall wrist function but not specifically for ulnar-sided wrist problems or stability. Results Sixteen ulnar styloid fractures had united, and 20 had not. There were no differences in demographic and injury characteristics. There were no significant differences in motion; strength; Gartland and Werley scores; Mayo scores; Disabilities of the Arm, Shoulder, and Hand scores; or pain scores 6 months after fracture. Conclusions Nonunion of a fracture of the proximal half of the ulnar styloid has no effect on wrist function, pain, and upper extremity specific health status 6 months after volar plate fixation of a fracture of the distal radius. (J Hand Slug 2010:35A:223-227. (C) 2010 Published by Elsevier hie. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, 55 Fruit St,YAW 2, Boston, MA 02114 USA. EM dring@partners.org NR 27 TC 23 Z9 29 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD FEB PY 2010 VL 35A IS 2 BP 223 EP 227 DI 10.1016/j.jhsa.2009.10.035 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 588SA UT WOS:000277092700007 PM 20079580 ER PT J AU Washington, DL Yano, EM McGuire, J Hines, V Lee, M Gelberg, L AF Washington, Donna L. Yano, Elizabeth M. McGuire, James Hines, Vivian Lee, Martin Gelberg, Lillian TI Risk Factors for Homelessness among Women Veterans SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Homeless people; women; hospitals; veterans/utilization; ambulatory care/utilization; health services accessibility; health services needs and demands ID AMBULATORY-CARE USE; HEALTH-CARE; LOGISTIC-REGRESSION; PATIENT POPULATION; FEMALE VETERANS; MEDICAL-CARE; NEEDS; VICTIMIZATION; RELIABILITY; DISORDER AB Background. Women veterans are three to four times more likely than non-veteran women to become homeless. However, their risk factors for homelessness have not been defined. Methods. Case-control study of non-institutionalized homeless women veterans (n=33) and age-matched housed women veterans (n=165). Health, health care, and factors associated with homelessness were assessed using multiple logistic regression with a Monte Carlo algorithm to estimate exact standard errors of the model coefficients and p-values. Results. Characteristics associated with homelessness were sexual assault during military service, being unemployed, being disabled, having worse overall health, and screening positive for an anxiety disorder or post-traumatic stress disorder. Protective factors were being a college graduate or married. Conclusions. Efforts to assess housed women veterans' risk factors for homelessness should be integrated into clinical care programs within and outside the Veterans Administration. Programs that work to ameliorate risk factors may prevent these women's living situations from deteriorating over time. C1 [Washington, Donna L.; Yano, Elizabeth M.; Lee, Martin] VA Greater Los Angeles HSR&D Ctr Excellence, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Hines, Vivian] VA Los Angeles Ambulatory Care Ctr VA Greater Los, Los Angeles, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Hlth Care Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov NR 37 TC 16 Z9 16 U1 2 U2 14 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2010 VL 21 IS 1 BP 81 EP 91 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 557WM UT WOS:000274700800007 ER PT J AU Parada, JP Yarnold, PR Uphold, CR Chmiel, JS DeHovitz, JA Goetz, MB Weinstein, RA McKoy, JM Chandler, KL Bennett, CL AF Parada, Jorge P. Yarnold, Paul R. Uphold, Constance R. Chmiel, Joan S. DeHovitz, Jack A. Goetz, Matthew B. Weinstein, Robert A. McKoy, June M. Chandler, Kevin L. Bennett, Charles L. TI Racial Variations in Care and Outcomes for Inpatient HIV-Related Pneumocystis Pneumonia SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE AIDS; HIV; Pneumocystis; PCP; race; ethnic; disparities; quality of care; outcomes ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AFFAIRS MEDICAL SYSTEM; CARINII-PNEUMONIA; UNITED-STATES; MYOCARDIAL-INFARCTION; REPERFUSION THERAPY; INFECTED ADULTS; PHYSICIANS; RACE; EXPERIENCE AB Racial disparities in HIV-care include the disproportionate impact of HIV/AIDS on African Americans. We conducted a retrospective review of 1,855 cases at 78 hospitals in nine cities to evaluate racial variations in inpatient care for AIDS-related Pneumocystis pneumonia (PCP) shortly after the introduction of highly active anti-retroviral therapies. While inpatient HIV-related PCP mortality was comparable between Whites and Hispanics (p=0.94), African Americans were less likely than Whites to die in-hospital (AOR 0.69, 95% CI 0.48, 0.99) and more likely to receive timely anti-PCP medications (AOR 1.67, 95% CI 1.21, 2.30) and timely corticosteroids (AOR 1.46, 95% CI 1.17, 1.82). Findings were compared with those from our study involving 1,547 patients at 82 hospitals in five cities over the first decade of the AIDS epidemic. In contrast to the first study, in the second decade African Americans were more likely to receive timely and appropriate therapy for HIV-related PCP, and resultantly were more likely to survive the hospitalization. C1 [Parada, Jorge P.] Hines VA Hosp, Midwest Ctr Hlth Serv Res & Policy, Hines, IL USA. [Parada, Jorge P.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Yarnold, Paul R.] Northwestern Univ, Feinberg Sch Med NW SOM, Dept Emergency Med, Chicago, IL 60611 USA. [Uphold, Constance R.] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [DeHovitz, Jack A.] SUNY Hlth Sci Ctr, Dept Preventat Med, Brooklyn, NY 11203 USA. [Goetz, Matthew B.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Goetz, Matthew B.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Weinstein, Robert A.] John H Stroger Jr Hosp Cook Cty, Rush Med Coll, Dept Med, Chicago, IL USA. [Bennett, Charles L.] Jesse Brown VA Med Ctr, Midwest Ctr Hlth Serv Res & Policy, Chicago, IL USA. [DeHovitz, Jack A.] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. RP McKoy, JM (reprint author), Northwestern Univ, 645 N Michigan Ave,Suite 630, Chicago, IL 60611 USA. EM jmmckoy@aol.com OI Goetz, Matthew/0000-0003-4542-992X NR 30 TC 0 Z9 0 U1 3 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD FEB PY 2010 VL 21 IS 1 BP 318 EP 333 PG 16 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 557WM UT WOS:000274700800022 PM 20173272 ER PT J AU Hiremath, J Thanikachalam, S Parikh, K Shanmugasundaram, S Bangera, S Shapiro, L Pott, GB Vnencak-Jones, CL Arneson, C Wade, M White, RJ AF Hiremath, Jagdish Thanikachalam, Sadagopa Parikh, Keyur Shanmugasundaram, Somasundaram Bangera, Sudhakar Shapiro, Leland Pott, Gregory B. Vnencak-Jones, Cindy L. Arneson, Carl Wade, Michael White, R. James CA TRUST Study Grp TI Exercise improvement and plasma biomarker changes with intravenous treprostinil therapy for pulmonary arterial hypertension: A placebo-controlled trial SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE pulmonary hypertension; prostacyclin; biomarkers; angiopoietin; six minute walk ID ENDOTHELIAL GROWTH-FACTOR; CONGESTIVE-HEART-FAILURE; EPOPROSTENOL PROSTACYCLIN; CELL GROWTH; ANGIOPOIETIN-2; SURVIVAL; GENE; INFUSION; MUTATION; DYSPNEA AB BACKGROUND: Pulmonary arterial hypertension (PAH) remains a poorly understood and frequently lethal disease with few treatment options. METHODS: We conducted a placebo-controlled trial of intravenous treprostinil, a prostacyclin analog, in treatment-naive PAH patients. During 12 weeks of treatment with treprostinil or placebo, we quantified 6-minute walk distance (6MW), clinical symptoms and 11 cytokines/growth factors. RESULTS: Forty-two of 44 study patients had idiopathic/familial PAH in New York Heart Association (NYHA) Class III. Treprostinil increased 6MW by a placebo-corrected median of 83 meters (p = 0.008; mean increase 93 +/- 42 meters), reduced Borg score by a median 2.0 units (p = 0.02), and improved NYHA class by a median of 1.0 (p = 0.02). There was a trend toward improved survival with treprostinil (p = 0.051). Baseline plasma angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and platelet-derived growth factor (PDGF) were elevated compared with reported normal ranges. Treatment with treprostinil was associated with decreased Ang-2 levels. Improvement in 6MW distance after treatment was associated with reductions in Ang-2 and MMP-9 levels. Most of the cytokines and growth factors studied were not abnormal with disease nor did they change with treatment. CONCLUSIONS: We conclude that treprostinil treatment significantly improved exercise capacity, dyspnea and functional class. Several plasma proteins that might track disease were abnormal at baseline, and changes were associated with improved exercise capacity. J Heart Lung Transplant 2010;29:137-49 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved. C1 [White, R. James] Univ Rochester, Div Pulm & Crit Care Med, Rochester, NY 14623 USA. [Hiremath, Jagdish] Ruby Hall Clin, Pune, Maharashtra, India. [Thanikachalam, Sadagopa] Sri Ramachandra Med Coll, Chennai, Tamil Nadu, India. [Parikh, Keyur] SAL Hosp & Med Inst, Ahmadabad, Gujarat, India. [Shanmugasundaram, Somasundaram] KS Hosp, Chennai, Tamil Nadu, India. [Bangera, Sudhakar] Asian Clin Trials Ltd, Hyderabad, Andhra Pradesh, India. [Shapiro, Leland; Pott, Gregory B.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Shapiro, Leland; Pott, Gregory B.] Univ Colorado, Denver, CO 80202 USA. [Vnencak-Jones, Cindy L.] Vanderbilt Univ, Med Ctr, Dept Pathol & Pediat, Nashville, TN USA. [Arneson, Carl; Wade, Michael] United Therapeut Corp, Res Triangle Pk, NC USA. RP White, RJ (reprint author), Univ Rochester, Div Pulm & Crit Care Med, 400 Red Creek Dr, Rochester, NY 14623 USA. EM jim_white@urmc.rochester.edu FU United Therapeutics Corporation; American Heart Association [073540N] FX Supported by United Therapeutics Corporation and by an American Heart Association National Scientist Development Grant (073540N) to R.J.W. NR 46 TC 77 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SI SI BP 137 EP 149 DI 10.1016/j.healun.2009.09.005 PG 13 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 558PC UT WOS:000274755700001 PM 20022264 ER PT J AU Murray, DR Osaki, S Jewel-Ripp, P Johnson, MR Lozonschi, L Edwards, NM Kohmoto, T AF Murray, D. R. Osaki, S. Jewel-Ripp, P. Johnson, M. R. Lozonschi, L. Edwards, N. M. Kohmoto, T. TI Heart Transplant Therapy in United States Veterans: 16-year Experience at A Single Center SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation CY APR 21-24, 2010 CL Chicago, IL SP Int Soc Heart & Lung Transplantat C1 [Murray, D. R.; Osaki, S.; Jewel-Ripp, P.; Johnson, M. R.; Lozonschi, L.; Edwards, N. M.; Kohmoto, T.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Murray, D. R.; Osaki, S.; Jewel-Ripp, P.; Johnson, M. R.; Lozonschi, L.; Edwards, N. M.; Kohmoto, T.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2010 VL 29 IS 2 SU S MA 456 BP S150 EP S151 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Transplantation GA 558PF UT WOS:000274756100454 ER PT J AU Silva, GK Gutierrez, FRS Guedes, PMM Horta, CV Cunha, LD Mineo, TWP Santiago-Silva, J Kobayashi, KS Flavell, RA Silva, JS Zamboni, DS AF Silva, Grace K. Gutierrez, Fredy R. S. Guedes, Paulo M. M. Horta, Catarina V. Cunha, Larissa D. Mineo, Tiago W. P. Santiago-Silva, Juliana Kobayashi, Koichi S. Flavell, Richard A. Silva, Joao S. Zamboni, Dario S. TI Cutting Edge: Nucleotide-Binding Oligomerization Domain 1-Dependent Responses Account for Murine Resistance against Trypanosoma cruzi Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; NITRIC-OXIDE; PROINFLAMMATORY CYTOKINES; NOD1; RECOGNITION; MACROPHAGES; PEPTIDOGLYCAN; PARASITEMIA; ACTIVATION; INDUCTION AB An effective innate immune recognition of the intracellular protozoan parasite Trypanosoma cruzi is critical for host resistance against Chagas disease, a severe and chronic illness that affects millions of people in Latin America. In this study, we evaluated the participation of nucleotide-binding oligomerization domain (Nod)like receptor proteins in host response to T cruzi infection and found that Nod1-dependent, but not Nod2-dependent, responses are required for host resistance against infection. Bone marrow-derived macrophages from Nod1(-/-) mice showed an impaired induction of NF-kappa B-dependent products in response to infection and failed to restrict T cruzi infection in presence of IFN-gamma. Despite normal cytokine production in the sera, Nod1(-/-) mice were highly susceptible to T cruzi infection, in a similar manner to MyD88(-/-) and NO synthase 2(-/-) mice. These studies indicate that Nod1-dependent responses account for host resistance against T cruzi infection by mechanisms independent of cytokine production. The Journal of Immunology, 2010, 184: 1148-1152. C1 [Zamboni, Dario S.] Univ Sao Paulo, Dept Cell Biol, Med Sch Ribeirao Preto, FMRP USP, BR-14049900 Ribeirao Preto, SP, Brazil. [Gutierrez, Fredy R. S.; Guedes, Paulo M. M.; Mineo, Tiago W. P.; Santiago-Silva, Juliana; Silva, Joao S.] Univ Sao Paulo, Dept Biochem & Immunol, Med Sch Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, Brazil. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Canc Immunol, Boston, MA 02115 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunol, New Haven, CT 06510 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Zamboni, DS (reprint author), Univ Sao Paulo, Dept Cell Biol, Med Sch Ribeirao Preto, FMRP USP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM dszamboni@fmrp.usp.br RI Mineo, Tiago/B-4153-2009; Silva, Joao/A-4484-2008; Gutierrez, Fredy RS/C-3911-2009; Silva, Grace/E-7673-2012; Cunha, Larissa/I-4204-2012; Vacinas, Inct/J-9431-2013; Zamboni, Dario/D-3024-2012 OI Mineo, Tiago/0000-0002-2339-2743; Gutierrez, Fredy RS/0000-0001-9873-8342; Silva, Grace/0000-0001-6417-4243; Zamboni, Dario/0000-0002-7856-7512 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [06/52867-4]; World Health Organization/TDR; Instituto Nacional de Ciencia e Tecnologia de Vacinas/ Conselho Nacional de Desenvolvimento Cientifico e Tecnolog'co FX lThis work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Grant 06/52867-4 to D.S.Z.), World Health Organization/TDR, and Instituto Nacional de Ciencia e Tecnologia de Vacinas/ Conselho Nacional de Desenvolvimento Cientifico e Tecnolog'co. R.A.F. is an Investigator of the Howard Hughes Medical Institute, and D.S.Z. and J.S.S. are research fellows from Conselho Nacional de Desenvolvimento Cientifico e Tehnologico. NR 23 TC 51 Z9 53 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1148 EP 1152 DI 10.4049/jimmunol.0902254 PG 5 WC Immunology SC Immunology GA 548JA UT WOS:000273956400005 PM 20042586 ER PT J AU Yang-Iott, KS Carpenter, AC Rowh, MAW Steinel, N Brady, BL Hochedlinger, K Jaenisch, R Bassing, CH AF Yang-Iott, Katherine S. Carpenter, Andrea C. Rowh, Marta A. W. Steinel, Natalie Brady, Brenna L. Hochedlinger, Konrad Jaenisch, Rudolf Bassing, Craig H. TI TCR beta Feedback Signals Inhibit the Coupling of Recombinationally Accessible V beta 14 Segments with DJ beta Complexes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-RECEPTOR-BETA; CHROMOSOMAL V(D)J RECOMBINATION; ALLELIC EXCLUSION; V-BETA; GERMLINE TRANSCRIPTION; TRANSGENIC MICE; DEFICIENT MICE; GENE SEGMENT; IMMATURE THYMOCYTES; ANTIGEN RECEPTOR AB Ag receptor allelic exclusion is thought to occur through monoallelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into V beta 14 (V beta 14(Rep)) indicated that V beta 14 chromatin accessibility is biallelic. To determine whether V beta 14 recombinational accessibility is subject to feedback inhibition, we analyzed TCR beta rearrangements in V beta 14(Rep) mice containing a preassembled in-frame transgenic V beta 8.2D beta 1J beta 1.1 or an endogenous V beta 14D beta 1J beta 1.4 rearrangement on the homologous chromosome. Expression of either preassembled V beta DJ beta C beta-chain accelerated thymocyte development because of enhanced cellular selection, demonstrating that the rate-limiting step in early alpha beta T cell development is the assembly of an in-frame V beta DJ beta rearrangement. Expression of these preassembled V beta DJ beta rearrangements inhibited endogenous V beta 14-to-DJ beta rearrangements as expected. However, in contrast to results predicted by the accepted model of TCR beta feedback inhibition, we found that expression of these preassembled TCR beta-chains did not down-regulate recombinational accessibility of V beta 14 chromatin. Our findings suggest that TCR beta-mediated feedback inhibition of V beta 14 rearrangements depends on inherent properties of V beta 14, D beta, and J beta recombination signal sequences. The Journal of Immunology, 2010,184:1369-1378. C1 [Yang-Iott, Katherine S.; Carpenter, Andrea C.; Rowh, Marta A. W.; Steinel, Natalie; Brady, Brenna L.; Bassing, Craig H.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Yang-Iott, Katherine S.; Carpenter, Andrea C.; Rowh, Marta A. W.; Steinel, Natalie; Brady, Brenna L.; Bassing, Craig H.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Yang-Iott, Katherine S.; Carpenter, Andrea C.; Rowh, Marta A. W.; Steinel, Natalie; Brady, Brenna L.; Bassing, Craig H.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Carpenter, Andrea C.; Rowh, Marta A. W.; Steinel, Natalie; Brady, Brenna L.; Bassing, Craig H.] Univ Penn, Sch Med, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02114 USA. [Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Bassing, CH (reprint author), Childrens Hosp Philadelphia, Ctr Childhood Canc Res, 4054 Colket Translat Res Bldg,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bassing@email.chop.edu FU Department of Pathology and Laboratory Medicine and Center for Childhood Cancer Research of the Children's Hospital of Philadelphia; Abramson Family Cancer Research Institute; University of Pennsylvania; University of Pennsylvania [5T32-AR007442-23, TG GM-0729] FX This work was supported by: the Department of Pathology and Laboratory Medicine and Center for Childhood Cancer Research of the Children's Hospital of Philadelphia (to C.H.B.) and the Abramson Family Cancer Research Institute (to C.H.B.) the Training Program in Immune System Development and Regulation of the University of Pennsylvania (to A.C.C.); the Training Program Rheumatic Disease of the University of Pennsylvania (5T32-AR007442-23 to M.A.W.R); and Training Grant TG GM-0729 from the University of Pennsylvania (to B.L.B). C.H.B. is a Pew Scholar in the Biomedical Sciences. NR 74 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1369 EP 1378 DI 10.4049/jimmunol.0900723 PG 10 WC Immunology SC Immunology GA 548JA UT WOS:000273956400029 PM 20042591 ER PT J AU Gosselin, A Monteiro, P Chomont, N Diaz-Griffero, F Said, EA Fonseca, S Wacleche, V El-Far, M Boulassel, MR Routy, JP Sekaly, RP Ancuta, P AF Gosselin, Annie Monteiro, Patricia Chomont, Nicolas Diaz-Griffero, Felipe Said, Elias A. Fonseca, Simone Wacleche, Vanessa El-Far, Mohamed Boulassel, Mohamed-Rachid Routy, Jean-Pierre Sekaly, Rafick-Pierre Ancuta, Petronela TI Peripheral Blood CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) CD4(+) T Cells Are Highly Permissive to HIV-1 Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; GASTROINTESTINAL-TRACT; CXCR4 EXPRESSION; CENTRAL MEMORY; INTERLEUKIN 22; IN-VIVO; RECEPTOR; REPLICATION; LYMPHOCYTES; DEPLETION AB There is limited knowledge on the identity of primary CD4(+) T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4(+) T cells. CCR4(+)CCR6(+), CCR4(+)CCR6(-), CXCR3(+)CCR6(+), and CXCR3(+)CCR6(-) T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells expressed the HIV coreceptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. CCR4(+)CCR6(-) T cells expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. CXCR3(+)CCR6(-) T cells expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro. Total CCR6(+) T cells compared with CCR6(-) T cells harbored higher levels of integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of total CCR6(+) T cells and those of CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells were diminished in chronically infected HIV-positive subjects, despite viral-suppressive therapy. A high-throughput analysis of cytokine profiles identified CXCR3(+)CCR6(+) T cells as a major source of TNF-alpha and CCL20 and demonstrated a decreased TNF-alpha/IL-10 ratio in CXCR3(+)CCR6(-) T cells. Finally, CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells exhibited gut- and lymph node-homing potential. Thus, we identified CCR4+CCR6+ and CXCR3(+)CCR6(+) T cells as highly permissive to HIV replication, with potential to infiltrate and recruit more CCR6(+) T cells into anatomic sites of viral replication. It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6(+) T cell subsets. The Journal of Immunology, 2010, 184: 1604-1616. C1 [Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Sekaly, Rafick-Pierre; Ancuta, Petronela] Ctr Hosp Univ Montreal, Ctr Rech, St Luc Hosp, Montreal, PQ H2X 1P1, Canada. [Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Sekaly, Rafick-Pierre; Ancuta, Petronela] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Montreal Chest Inst, Immunodeficiency Serv, Montreal, PQ, Canada. [Boulassel, Mohamed-Rachid; Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Montreal Chest Inst, Div Hematol, Montreal, PQ, Canada. [Diaz-Griffero, Felipe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ancuta, P (reprint author), Ctr Hosp Univ Montreal, Ctr Rech, St Luc Hosp, Pavillon Edouard Asselin,Room 411,264 Blvd Rene L, Montreal, PQ H2X 1P1, Canada. EM petronela.ancuta@umontreal.ca OI Said, Elias/0000-0003-4224-6351 FU Canadian Institutes of Health Research (CIHR) [MOP-82849]; Fondation du Centre Hospitalier de I'Universite de Montreal, Fonds de la Recherche en Sante Quebec (FRSQ); French National Institute of Health and Medical Research (INSERM); National Agency for AIDS Research (ANRS); Agence Nationale de Recherche sur le SIDA; Fondation de France FX This work was supported in part by grants to P.A. from the Canadian Institutes of Health Research (CIHR) (MOP-82849), Fondation du Centre Hospitalier de I'Universite de Montreal, Fonds de la Recherche en Sante Quebec (FRSQ), the French National Institute of Health and Medical Research (INSERM). National Agency for AIDS Research (ANRS), Agence Nationale de Recherche sur le SIDA, and Fondation de France. P.A. was supported by New Investigator awards from FRSQ and INSERM. P.M., N.C., E.A.S., and M.E.F. were supported by postdoctoral fellowships from ANRS, Fondation de France, FRSQ, The Foundation for AIDS Research, and CIHR, respectively. Core facilities were supported by the Fondation du Centre Hospitalier de l'Universite de Montreal and the FRSQ AIDS-Infectious Diseases Network. NR 71 TC 97 Z9 98 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2010 VL 184 IS 3 BP 1604 EP 1616 DI 10.4049/jimmunol.0903058 PG 13 WC Immunology SC Immunology GA 548JA UT WOS:000273956400055 PM 20042588 ER PT J AU Mulligan, JK Rosenzweig, SA Young, MRI AF Mulligan, Jennifer K. Rosenzweig, Steven A. Young, M. Rita I. TI Tumor Secretion of VEGF Induces Endothelial Cells to Suppress T cell Functions Through the Production of PGE(2) SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE endothelial cell; T cells; tumor immunity; lung; cytokines ID GROWTH-FACTOR VEGF; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAY; DENDRITIC CELLS; CANCER-PATIENTS; FACTOR-BETA; IN-VITRO; SU5416; ANGIOGENESIS; INHIBITION AB Endothelial cells are potent regulators of immune cell functions and have therefore been examined to determine their role in tumor-induced immune suppression. Previous studies by our laboratory showed that exposure to Lewis lung carcinoma (LLC)secreted products induced endothelial cells to suppress T-cell functions in vitro. The current studies examined in vitro and in vivo the mechanism by which tumors induce the formation of suppressor endothelial cells and the means by which suppressor endothelial cells disrupt T-cell functions. In vitro studies demonstrated that inhibition of tumor-derived VEGF with neutralizing antibodies or treatment of endothelial cells with the VEGF receptor tyrosine kinase inhibitor, SU5416, prevented endothelial cells from being induced to suppress T-cell functions. Treatment of tumor-bearing mice with SU5416 blocked the development of endothelial cells that are suppressive to CD4(+) and CD8(+) T-cell functions. We next examined the role of suppressor endothelial cell-derived PGE(2) in the inhibition of T-cell functions. Abrogation of endothelial cell PGE(2) production in vitro with indomethacin prevented tumor-conditioned media from stimulating endothelial cell production of immune inhibitory activity toward T-cell functions. Similar treatment of endothelial cells from lungs of tumor-bearing mice blocked their capacity to produce T-cell-inhibitory mediators. These studies demonstrate that tumor-derived VEGF induces endothelial cells to upregulate production of PGE(2) which, in turn, leads to suppression of T-cell functions. C1 [Mulligan, Jennifer K.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Rosenzweig, Steven A.] Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Rosenzweig, Steven A.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@va.gov FU Research Services of the Department of Veterans Affairs; National Institutes of Health [R01CA85266, R01DE018168, 1R01CA128837] FX Supported by Research Services of the Department of Veterans Affairs and by grants R01CA85266, R01DE018168, and 1R01CA128837 from the National Institutes of Health to MRIY. NR 50 TC 16 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2010 VL 33 IS 2 BP 126 EP 135 DI 10.1097/CJI.0b013e3181b91c9c PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 562NZ UT WOS:000275060300002 PM 20145550 ER PT J AU Rosenblatt, J Wu, ZK Vasir, B Zarwan, C Stone, R Mills, H Friedman, T Konstantinopoulos, PA Spentzos, D Ghebremichael, M Stevenson, K Neuberg, D Levine, JD Joyce, R Tzachanis, D Boussiotis, V Kufe, D Avigan, D AF Rosenblatt, Jacalyn Wu, Zekui Vasir, Baldev Zarwan, Corrine Stone, Richard Mills, Heidi Friedman, Thea Konstantinopoulos, Panagiotis A. Spentzos, Dimitrios Ghebremichael, Musie Stevenson, Kristen Neuberg, Donna Levine, James D. Joyce, Robin Tzachanis, Dimitrios Boussiotis, Vassiliki Kufe, Donald Avigan, David TI Generation of Tumor-specific T Lymphocytes Using Dendritic Cell/Tumor Fusions and Anti-CD3/CD28 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dendritic cell tumor fusion vaccine; adoptive immunotherapy; educated T cell ID KINASE-C-THETA; CELL TRANSFER THERAPY; KAPPA-B ACTIVATION; CARCINOMA-CELLS; IN-VIVO; CD3/CD28 COSTIMULATION; ANTITUMOR IMMUNITY; CANCER REGRESSION; EX-VIVO; BREAST AB Adoptive immunotherapy with tumor-specific T cells represents a promising treatment strategy for patients with malignancy. However, the efficacy of T-cell therapy has been limited by the ability to expand tumor-reactive cells with an activated phenotype that effectively target malignant cells. We have developed an anticancer vaccine in which patient-derived tumor cells are fused with autologous dendritic cells (DCs), such that a wide array of tumor antigens are presented in the context of DC-mediated costimulation. In this study, we demonstrate that DC/tumor fusions induce T cells that react with tumor and are dramatically expanded by subsequent ligation of the CD3/CD28 costimulatory complex. These T cells exhibit a predominantly activated phenotype as manifested by an increase in the percentage of cells expressing CD69 and interferon g. In addition, the T cells upregulate granzyme B expression and are highly effective in lysing autologous tumor targets. Targeting of tumor-specific antigen was demonstrated by the expansion of T cells with specificity for the MUC1 tetramer. Stimulation with anti-CD3/CD28 followed by DC/tumor fusions or either agent alone failed to result in a similar expansion of tumor-reactive T cells. Consistent with these findings, spectratyping analysis demonstrates selective expansion of T-cell clones as manifested by considerable skewing of the V beta repertoire following sequential stimulation with DC/tumor fusions and anti-CD3/CD28. Gene expression analysis was notable for the upregulation of inflammatory pathways. These findings indicate that stimulation with DC/tumor fusions provides a unique platform for subsequent expansion with anti-CD3/CD28 in adoptive T-cell therapy of cancer. C1 [Rosenblatt, Jacalyn; Zarwan, Corrine; Mills, Heidi; Konstantinopoulos, Panagiotis A.; Spentzos, Dimitrios; Levine, James D.; Joyce, Robin; Tzachanis, Dimitrios; Boussiotis, Vassiliki; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wu, Zekui; Vasir, Baldev; Stone, Richard; Ghebremichael, Musie; Stevenson, Kristen; Neuberg, Donna; Kufe, Donald] Dana Farber Canc Inst, Boston, MA USA. [Friedman, Thea] Hackensack Univ Med Ctr, Ctr Canc, Hackensack, NJ USA. RP Rosenblatt, J (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,KS-121, Boston, MA 02215 USA. EM jrosenb1@bidmc.harvard.edu FU NCI NIH HHS [P01 CA155258, P50 CA100707, P50 CA101942-06A18713, P01 CA078378, P50 CA101942-06A1] NR 35 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD FEB-MAR PY 2010 VL 33 IS 2 BP 155 EP 166 DI 10.1097/CJI.0b013e3181bed253 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 562NZ UT WOS:000275060300005 PM 20145548 ER PT J AU Rueda, AM Ormond, M Gore, M Matloobi, M Giordano, TP Musher, DM AF Rueda, Adriana M. Ormond, Mandy Gore, Meghana Matloobi, Mahsa Giordano, Thomas P. Musher, Daniel M. TI Hyperglycemia in diabetics and non-diabetics: Effect on the risk for and severity of pneumococcal pneumonia SO JOURNAL OF INFECTION LA English DT Article DE Pneumococcus; Pneumonia; Diabetes mellitus; Hyperglycemia; Severity of disease ID COMMUNITY-ACQUIRED PNEUMONIA; BACTERICIDAL FUNCTION; GLYCEMIC CONTROL; INFECTIONS; OUTCOMES; GLUCOSE; HOSPITALIZATION; NEUTROPHILS; INHIBITION; MELLITUS AB Objectives: We sought to determine whether poor glucose control among diabetics is associated with increased risk for pneumococcal pneumonia and whether elevated admitting plasma glucose (APG) levels are associated with increased severity of this infection in diabetic and non-diabetic patients. Methods: We compared hemoglobin A(1c) (HbA(1c)) in diabetics who had pneumococcal pneumonia with diabetic case-controls who did not have pneumonia. In patients with pneumococcal pneumonia, we related APG to disease severity as determined by SMART-COP score, need for ICU admission, and mortality at 7 and 30 days. Results: Fifty-three of 233 patients with pneumococcal pneumonia (22.7%) were diabetic. Diabetics with pneumonia had poorer glycemic control than diabetic case-controls (HbA(1c) 8.2% vs. 7.2%, respectively, P < 0.01). In pneumococcal pneumonia patients, SMART-COP scores, need for ICU admission, and mortality increased in proportion to the APG. These findings were attributable to the significant association between hyperglycemia and severity in non-diabetics. Conclusions: Poor glycemic control predisposes diabetics to pneumococcal pneumonia but, among diabetics, the degree of hyperglycemia at admission is not associated with increased disease severity. In contrast, among non-diabetics with pneumococcal pneumonia, hyperglycemia is a marker for severe disease and increased mortality, perhaps reflecting massive release of cytokines and glucocorticosteroids in overwhelming infection. (C) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved. C1 [Rueda, Adriana M.; Gore, Meghana; Matloobi, Mahsa; Musher, Daniel M.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. [Giordano, Thomas P.] Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Rueda, Adriana M.; Ormond, Mandy; Giordano, Thomas P.; Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Rueda, AM (reprint author), Michael E DeBakey VA Med Ctr, Infect Dis Sect, Med Serv, Room 4B-370, Houston, TX 77030 USA. EM adrianam.rueda@med.va.gov FU Department of Veterans Affairs; Houston VA HSR&D Center of Excellence [HFP90-020] FX Dr. Musher's research is supported by the Department of Veterans Affairs through the Merit Review Program. Dr. Giordano is supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020).; We gratefully acknowledge Christine Hartman and Louis Henderson for their assistance with the statistical analysis. NR 30 TC 20 Z9 20 U1 0 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD FEB PY 2010 VL 60 IS 2 BP 99 EP 105 DI 10.1016/j.jinf.2009.12.003 PG 7 WC Infectious Diseases SC Infectious Diseases GA 552IH UT WOS:000274282400002 PM 20005251 ER PT J AU Marucci, A Miscio, G Padovano, L Boonyasrisawat, W Doria, A Trischitta, V Di Paola, R AF Marucci, A. Miscio, G. Padovano, L. Boonyasrisawat, W. Doria, A. Trischitta, V. Di Paola, R. TI A functional variant in the gene 3 ' untranslated region regulates HSP70 expression and is a potential candidate for insulin resistance-related abnormalities SO JOURNAL OF INTERNAL MEDICINE LA English DT Letter ID ASSOCIATION; PROTEIN; OBESITY; STRESS; HEAT-SHOCK-PROTEIN-72; SITES; LOCI C1 [Marucci, A.; Miscio, G.; Padovano, L.; Trischitta, V.; Di Paola, R.] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Boonyasrisawat, W.; Doria, A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Boonyasrisawat, W.; Doria, A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Trischitta, V.] Univ Roma La Sapienza, Dept Med Pathophysiol, Rome, Italy. [Trischitta, V.] IRCCS Casa Sollievo della Sofferenza Mendel, Rome, Italy. RP Di Paola, R (reprint author), Sci Inst Casa Sollievo della Sofferenza, Res Unit Diabet & Endocrine Dis, Viale Padre Pio, I-71013 San Giovanni Rotondo, Italy. EM vincenzo.trischitta@uniroma1.it; r.dipaola@operapadrepio.it RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016; marucci, antonella/B-8722-2017 OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X; marucci, antonella/0000-0001-8131-8317 NR 16 TC 0 Z9 1 U1 0 U2 4 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 FEB PY 2010 VL 267 IS 2 BP 237 EP 240 DI 10.1111/j.1365-2796.2009.02132.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 545XV UT WOS:000273771200009 PM 19754858 ER PT J AU Humphreys, KL Sauder, CL Martin, EK Marx, BP AF Humphreys, Kathryn L. Sauder, Colin L. Martin, Elaine K. Marx, Brian P. TI Tonic Immobility in Childhood Sexual Abuse Survivors and Its Relationship to Posttraumatic Stress Symptomatology SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE sexual abuse; Hx of child abuse; mental health and violence ID ASSAULT SURVIVORS; PERITRAUMATIC DISSOCIATION; FEAR; SYMPTOMS; DISORDER; RAPE; REVICTIMIZATION; RESPONSES; WOMEN; SCALE AB Past research has shown that 37% to 52% of sexual assault survivors report experiencing a set of peritraumatic responses, which include gross motor inhibition, analgesia, and fixed or unfocused staring. This response set closely resembles a set of unconditioned responses, collectively known as Tonic Immobility (TI). This study examined TI among childhood sexual abuse (CSA) survivors and its relation to PTSD symptomatology. Participants were 131 female college undergraduates who completed questionnaires assessing sexual abuse history, TI, and PTSD symptom severity. Results showed that TI partially mediated the relation between peritraumatic fear and overall PTSD symptom severity and completely mediated the relation between fear and the PTSD reexperiencing symptoms. Although peritraumatic fear is associated with TI, the mediation findings provide evidence for the notion that these responses are separate from one another. These results suggest that TI during CSA may play an important role in the subsequent PTSD symptomatology in adulthood. C1 [Humphreys, Kathryn L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Sauder, Colin L.] Univ Washington, Seattle, WA 98195 USA. [Martin, Elaine K.] Univ Nebraska, Clin Psychol Training Program, Lincoln, NE 68583 USA. [Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Marx, Brian P.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Humphreys, KL (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 38 TC 18 Z9 18 U1 2 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD FEB PY 2010 VL 25 IS 2 BP 358 EP 373 DI 10.1177/0886260509334412 PG 16 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 535FF UT WOS:000272951900010 PM 19531633 ER PT J AU McLarry, JD Aljaroudi, W Venkataraman, R Faulkner, M Heo, J Iskandrian, AE Hage, FG AF McLarry, J. D. Aljaroudi, W. Venkataraman, R. Faulkner, M. Heo, J. Iskandrian, A. E. Hage, F. G. TI VIABILITY ASSESSMENT USING AUTOMATED QUANTITATIVE ANALYSIS OF THALLIUM-201 MYOCARDIAL PERFUSION IMAGING SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [McLarry, J. D.; Aljaroudi, W.; Venkataraman, R.; Faulkner, M.; Heo, J.; Iskandrian, A. E.; Hage, F. G.] Univ Alabama, Birmingham, AL USA. [Hage, F. G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 94 BP 382 EP 383 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600100 ER PT J AU Hage, FG Oparil, S Xing, D Chen, Y McCrory, M Szalai, AJ AF Hage, F. G. Oparil, S. Xing, D. Chen, Y. McCrory, M. Szalai, A. J. TI C-REACTIVE PROTEIN MEDIATED VASCULAR INJURY REQUIRES COMPLEMENT SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Hage, F. G.; Oparil, S.; Xing, D.; Chen, Y.; McCrory, M.; Szalai, A. J.] Univ Alabama, Birmingham, AL USA. [Hage, F. G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 287 BP 436 EP 437 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600293 ER PT J AU Ding, Y Wang, J Xie, S Li, H Mountz, JD AF Ding, Y. Wang, J. Xie, S. Li, H. Mountz, J. D. TI NUCLEAR EXPRESSION OF CXCR5 IN SPLEEN FOLLICULAR T HELPER CELLS IN AUTOIMMUNE BXD2 MICE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Ding, Y.; Wang, J.; Xie, S.; Li, H.; Mountz, J. D.] Univ Alabama, Birmingham, AL USA. [Mountz, J. D.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 304 BP 441 EP 442 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600310 ER PT J AU Martinez, DY Heudebert, G Henostroza, G Rodriguez, M Zamudio, C Centor, RM Gotuzzo, E Estrada, CA AF Martinez, D. Y. Heudebert, G. Henostroza, G. Rodriguez, M. Zamudio, C. Centor, R. M. Gotuzzo, E. Estrada, C. A. TI A NOVEL CLINICAL PREDICTION RULE FOR MULTIDRUG-RESISTANT TUBERCULOSIS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Martinez, D. Y.; Henostroza, G.; Zamudio, C.; Gotuzzo, E.] Univ Peruana Cayetano Heredia, Lima, Peru. [Martinez, D. Y.; Heudebert, G.; Henostroza, G.; Rodriguez, M.; Centor, R. M.; Estrada, C. A.] Univ Alabama, Birmingham, AL USA. [Heudebert, G.; Centor, R. M.; Estrada, C. A.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 461 BP 486 EP 486 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600467 ER PT J AU Snyder, ED Salanitro, A Castiglioni, A Estrada, C AF Snyder, E. D. Salanitro, A. Castiglioni, A. Estrada, C. TI PRACTICE MATTERS: RELATIONSHIP BETWEEN PREPARATION STYLE AND CHANGES MADE TO SCIENTIFIC PRESENTATIONS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Snyder, E. D.; Salanitro, A.; Castiglioni, A.; Estrada, C.] UAB, Birmingham, AL USA. [Snyder, E. D.; Salanitro, A.; Castiglioni, A.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 498 BP 497 EP 497 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600504 ER PT J AU Snyder, ED Salanitro, A Castiglioni, A Estrada, C AF Snyder, E. D. Salanitro, A. Castiglioni, A. Estrada, C. TI PREPARING FOR ORAL PRESENTATIONS: VARIATIONS IN PREPARATION BY LEVEL OF TRAINING SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Snyder, E. D.; Salanitro, A.; Castiglioni, A.; Estrada, C.] UAB, Birmingham, AL USA. [Snyder, E. D.; Salanitro, A.; Castiglioni, A.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 508 BP 500 EP 500 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600514 ER PT J AU Burton, M Charlton, K Estrada, C Ritchie, C AF Burton, M. Charlton, K. Estrada, C. Ritchie, C. TI RESIDENT INPATIENT HANDOFFS: A MULTI-METHOD QUALITY IMPROVEMENT INITIATIVE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Burton, M.; Charlton, K.; Estrada, C.; Ritchie, C.] UAB, Birmingham, AL USA. [Burton, M.; Estrada, C.; Ritchie, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 510 BP 501 EP 501 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600516 ER PT J AU Estrada, C Salanitro, A Safford, M Curry, W Williams, J Ovalle, F Payne-Foster, P Kim, Y Houston, T Allison, J AF Estrada, C. Salanitro, A. Safford, M. Curry, W. Williams, J. Ovalle, F. Payne-Foster, P. Kim, Y. Houston, T. Allison, J. TI A CLUSTER-RANDOMIZED TRIAL OF A WEB-BASED PHYSICIAN INTERVENTION TO IMPROVE DIABETES CARE SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Estrada, C.; Salanitro, A.; Curry, W.] Birmingham VA Med Ctr, Birmingham, AL USA. [Estrada, C.; Salanitro, A.; Safford, M.; Curry, W.; Williams, J.; Ovalle, F.; Kim, Y.] Univ Alabama, Birmingham, AL USA. [Payne-Foster, P.] Univ Alabama, Tuscaloosa, AL USA. [Houston, T.; Allison, J.] Univ Massachusetts, Boston, MA 02125 USA. RI Houston, Thomas/F-2469-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 512 BP 501 EP 501 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600518 ER PT J AU Conde, M Wathen, P Lawrence, V AF Conde, M. Wathen, P. Lawrence, V. TI USING STANDARDIZED PATIENTS TO TEACH ALCOHOL SCREENING SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Conde, M.; Lawrence, V.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Conde, M.; Wathen, P.; Lawrence, V.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 515 BP 502 EP 502 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600521 ER PT J AU Newson, J Willett, L Panisko, D Estrada, C AF Newson, J. Willett, L. Panisko, D. Estrada, C. TI SELECTING THE BEST CLINICAL VIGNETTES: SHOULD THE SCORING TOOL CRITERIA BE MODIFIED? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting 2010 CY FEB 25-27, 2010 CL New Orleans, LA SP SSCI, SAFMR, SSPR, SSGIM, APA C1 [Newson, J.; Willett, L.; Estrada, C.] Univ Alabama, Birmingham, AL USA. [Panisko, D.] Univ Toronto, Toronto, ON, Canada. [Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2010 VL 58 IS 2 MA 522 BP 504 EP 504 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 555HL UT WOS:000274499600528 ER PT J AU Papas, KK Colton, CK Qipo, A Wu, HY Nelson, RA Hering, BJ Weir, GC Koulmanda, M AF Papas, Klearchos K. Colton, Clark K. Qipo, Andi Wu, Haiyan Nelson, Rebecca A. Hering, Bernhard J. Weir, Gordon C. Koulmanda, Maria TI Prediction of Marginal Mass Required for Successful Islet Transplantation SO JOURNAL OF INVESTIGATIVE SURGERY LA English DT Article DE marginal graft; oxygen consumption rate; transplantation outcome; predictive assay; mouse bioassay; rat islets ID OXYGEN-CONSUMPTION RATE; ISOLATED PANCREATIC-ISLETS; LANGERHANS; SURVIVAL; QUALITY; MICE; FUNCTIONALITY; THERAPY; POTENCY; ASSAY AB Islet quality assessment methods for predicting diabetes reversal (DR) following transplantation are needed. We investigated two islet parameters, oxygen consumption rate (OCR) and OCR per DNA content, to predict transplantation outcome and explored the impact of islet quality on marginal islet mass for DR. Outcomes in immunosuppressed diabetic mice were evaluated by transplanting mixtures of healthy and purposely damaged rat islets for systematic variation of OCR/DNA over a wide range. The probability of DR increased with increasing transplanted OCR and OCR/DNA. On coordinates of OCR versus OCR/DNA, data fell into regions in which DR occurred in all, some, or none of the animals with a sharp threshold of around 150-nmol/min mg DNA. A model incorporating both parameters predicted transplantation outcome with sensitivity and specificity of 93% and 94%, respectively. Marginal mass was not constant, depended on OCR/DNA, and increased from 2,800 to over 100,000 islet equivalents/kg body weight as OCR/DNA decreased. We conclude that measurements of OCR and OCR/DNA are useful for predicting transplantation outcome in this model system, and OCR/DNA can be used to estimate the marginal mass required for reversing diabetes. Because human clinical islet preparations in a previous study had OCR/DNA. C1 [Papas, Klearchos K.; Colton, Clark K.; Wu, Haiyan] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Papas, Klearchos K.; Hering, Bernhard J.] Univ Minnesota, Dept Surg, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA. [Qipo, Andi; Koulmanda, Maria] Massachusetts Gen Hosp, Islet Transplantat Lab, Boston, MA 02114 USA. [Nelson, Rebecca A.] City Hope Natl Med Ctr, Adm & Bioinformat Coordinating Ctr, Duarte, CA 91010 USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Koulmanda, Maria] Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Boston, MA 02215 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,25 Ames St, Cambridge, MA 02139 USA. EM ckcolton@mit.edu RI Nelson, Rebecca/C-4438-2014 FU NCRR NIH HHS [U42 RR016606, U4Z RR 16606]; NIAID NIH HHS [P01 AI041521]; NIDDK NIH HHS [R01 DK063108, R01-DK063108] NR 32 TC 19 Z9 19 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0894-1939 J9 J INVEST SURG JI J. Invest. Surg. PD FEB PY 2010 VL 23 IS 1 BP 28 EP 34 DI 10.3109/08941930903410825 PG 7 WC Surgery SC Surgery GA 569GT UT WOS:000275585300005 PM 20233002 ER PT J AU del Rio, ML Lucas, CL Buhler, L Rayat, G Rodriguez-Barbosa, JI AF del Rio, M. L. Lucas, C. L. Buhler, L. Rayat, G. Rodriguez-Barbosa, J. I. TI HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE coinhibition; costimulation; transplantation; autoimmunity ID HERPESVIRUS ENTRY MEDIATOR; T-LYMPHOCYTE ATTENUATOR; VERSUS-HOST-DISEASE; NK-CELL ACTIVATION; FACTOR RECEPTOR SUPERFAMILY; LYMPHOTOXIN-BETA RECEPTOR; CHRONIC VIRAL-INFECTION; TNF FAMILY MEMBER; MHC CLASS-I; B-LYMPHOCYTE AB Immunosuppression is currently the treatment of choice to attenuate the chronic deterioration of tissue function as a result of the effector mechanisms of the immunological response in transplant rejection and autoimmune diseases. However, global immunosuppression greatly increases the risk of acquiring life-threatening infections and is associated with organ toxicity when used long-term. Thus, alternative approaches that inhibit only the unwanted immune responses and preserve general immunity are highly desirable. The receptor/ligand pairs involved in the cross-talk between DC and T cells have been the focus of intense and exciting research during the last decade. The HVEM/LIGHT/BTLA/CD160 costimulatory/coinhibitory pathway has emerged as a potential target for the development of immune therapeutic interventions. Herein, we will summarize and discuss how blockade of the costimulatory HVEM/LIGHT interaction or agonist signaling through the inhibitory BTLA and CD160 receptors could contribute to the control of deleterious immune responses. J. Leukoc. Biol. 87: 223-235; 2010. C1 [del Rio, M. L.; Rodriguez-Barbosa, J. I.] Inst Biomed, Immunobiol Lab, Leon, Spain. [Lucas, C. L.; Buhler, L.] Harvard Univ, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Buhler, L.] Univ Hosp Geneva, Dept Surg, Surg Res Unit, Geneva, Switzerland. [Rayat, G.] Univ Alberta, Fac Med & Dent, Alberta Diabet Inst, Edmonton, AB, Canada. RP Rodriguez-Barbosa, JI (reprint author), Univ Leon, Inst Biomed Immunobiol, Campus Vegazana S-N, E-24071 Leon, Spain. EM ignacio.barbosa@unileon.es RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; OI Rodriguez-Barbosa, Jose-Ignacio/0000-0001-7427-5654 FU Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) [FIS PI-050021]; Consejeria de Educacion, Junta de Castilla y Leon [LE012A08] FX This work has been supported by grant FIS PI-050021 of Fondo de Investigaciones Sanitarias (Ministerio de Sanidad y Consumo, Spanish Government, Spain) and grant LE012A08 of Consejeria de Educacion, Junta de Castilla y Leon to J. I. R-B. We thank Dr. David Sancho (London Research Institute, UK) and Dr. Yong Zhao (State Key Laboratory of Biomembrane and Membrane Biotechnology, China) for suggestions and critical reading of the manuscript. NR 95 TC 56 Z9 56 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 2010 VL 87 IS 2 BP 223 EP 235 DI 10.1189/jlb.0809590 PG 13 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 551KW UT WOS:000274208500006 PM 20007250 ER PT J AU Sun, PZ AF Sun, Phillip Zhe TI Simultaneous determination of labile proton concentration and exchange rate utilizing optimal RF power: Radio frequency power (RFP) dependence of chemical exchange saturation transfer (CEST) MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Amide proton transfer (APT); Chemical exchange saturation transfer (CEST); MRI ID CONTRAST AGENTS; PARACEST AGENTS; IN-VIVO; QUANTITATIVE DESCRIPTION; PH; RESONANCE; WATER; CELLS; SENSITIVITY; PARTICLES AB Chemical exchange saturation transfer (CEST) MRI is increasingly used to probe mobile proteins and microenvironment properties, and shows great promise for tumor and stroke diagnosis. However, CEST MRI contrast mechanism is complex, depending not only oil the CEST agent concentration, exchange and relaxation properties, but also varying with experimental conditions such as magnetic field strength and RF power. Hence, it remains somewhat difficult to quantify apparent CEST MRI contrast for properties Such as pH, temperature and protein content. In particular, CEST MRI is Susceptible to RF spillover effects in that RF irradiation may directly saturate the bulk water MR signal, leading to an optimal RF power at which the CEST contrast is maximal. Whereas RF spillover is generally considered an adverse effect, it is noted here that the optimal RF power strongly varies with exchange rate, although with negligible dependence on labile proton concentration. An empirical solution suggested that optimal RF power may serve as a sensitive parameter for simultaneously determining the labile proton content and exchange rate, hence, allowing improved characterization of the CEST system. The empirical solution was confirmed by numerical simulation, and experimental validation is needed to further evaluate the proposed technique. (C) 2009 Elsevier Inc. All rights reserved. C1 [Sun, Phillip Zhe] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU AHA/SDG [0835384N]; NIH/NINDS [R21NS061119-01]; NIH/NIBIB [K01EB 009771-01] FX This study was supported in part by grants from AHA/SDG 0835384N, NIH/NINDS R21NS061119-01 and NIH/NIBIB K01EB 009771-01. The author would like to thank Dr. Peter Caravan for stimulating discussions. NR 40 TC 30 Z9 30 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD FEB PY 2010 VL 202 IS 2 BP 155 EP 161 DI 10.1016/j.jmr.2009.10.012 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 545YT UT WOS:000273774000005 PM 19926319 ER PT J AU Georgopoulos, AP Tan, HRM Lewis, SM Leuthold, AC Winskowski, AM Lynch, JK Engdahl, B AF Georgopoulos, A. P. Tan, H-R M. Lewis, S. M. Leuthold, A. C. Winskowski, A. M. Lynch, J. K. Engdahl, B. TI The synchronous neural interactions test as a functional neuromarker for post-traumatic stress disorder (PTSD): a robust classification method based on the bootstrap SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID BIOMARKER AB Traumatic experiences can produce post-traumatic stress disorder (PTSD) which is a debilitating condition and for which no biomarker currently exists (Institute of Medicine ( US) 2006 Posttraumatic Stress Disorder: Diagnosis and Assessment (Washington, DC: National Academies)). Here we show that the synchronous neural interactions (SNI) test which assesses the functional interactions among neural populations derived from magnetoencephalographic (MEG) recordings (Georgopoulos A P et al 2007 J. Neural Eng. 4 349-55) can successfully differentiate PTSD patients from healthy control subjects. Externally cross-validated, bootstrap-based analyses yielded >90% overall accuracy of classification. In addition, all but one of 18 patients who were not receiving medications for their disease were correctly classified. Altogether, these findings document robust differences in brain function between the PTSD and control groups that can be used for differential diagnosis and which possess the potential for assessing and monitoring disease progression and effects of therapy. C1 [Georgopoulos, A. P.; Tan, H-R M.; Lewis, S. M.; Leuthold, A. C.; Winskowski, A. M.; Lynch, J. K.] US Dept Vet Affairs, Med Ctr 11B, Brain Sci Ctr, Minneapolis, MN 55417 USA. [Georgopoulos, A. P.; Tan, H-R M.; Leuthold, A. C.; Lynch, J. K.] Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. [Lewis, S. M.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. [Georgopoulos, A. P.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Georgopoulos, A. P.] Univ Minnesota, Ctr Cognit Sci, Minneapolis, MN 55455 USA. [Georgopoulos, A. P.; Winskowski, A. M.; Engdahl, B.] US Dept Vet Affairs, Med Ctr 11B, Psychol Sect, Minneapolis, MN 55417 USA. [Engdahl, B.] Univ Minnesota, Dept Psychol, Minneapolis, MN USA. [Tan, H-R M.] Univ Glasgow, Ctr Cognit Neuroimaging, Glasgow G12 8QB, Lanark, Scotland. RP Georgopoulos, AP (reprint author), US Dept Vet Affairs, Med Ctr 11B, Brain Sci Ctr, Minneapolis, MN 55417 USA. EM omega@umn.edu OI Tan, Heng-Ru May/0000-0003-2109-0781 FU United States Department of Veterans Affairs [VISN23]; American Legion Brain Sciences Chair FX We thank Nancy Tabaka and Cynthia Marceau for their help in patient consent and various aspects of database entry. This work was partially supported by a grant from the United States Department of Veterans Affairs VISN23 and the American Legion Brain Sciences Chair. A P Georgopoulos has a financial interest in the technology described in this publication. NR 13 TC 38 Z9 38 U1 1 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD FEB PY 2010 VL 7 IS 1 AR 016011 DI 10.1088/1741-2560/7/1/016011 PG 7 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 567WQ UT WOS:000275479000011 PM 20086271 ER PT J AU Maguire, CA Gianni, D Meijer, DH Shaket, LA Wakimoto, H Rabkin, SD Gao, GP Sena-Esteves, M AF Maguire, Casey A. Gianni, Davide Meijer, Dimphna H. Shaket, Lev A. Wakimoto, Hiroaki Rabkin, Samuel D. Gao, Guangping Sena-Esteves, Miguel TI Directed evolution of adeno-associated virus for glioma cell transduction SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Adeno-associated virus (AAV); Library; Brain tumor; Glioblastoma; Gene therapy; Gene transfer ID ENHANCED GENE-TRANSFER; MOUSE-BRAIN; IN-VITRO; GLIOBLASTOMA-MULTIFORME; DELIVERY VECTORS; VIRAL VECTORS; TROPISM; TYPE-2; TISSUE; SEROTYPES AB Glioblastoma multiforme (GBM) is a serious form of brain cancer for which there is currently no effective treatment. Alternative strategies such as adeno-associated virus (AAV) vector mediated-genetic modification of brain tumor cells with genes encoding anti-tumor proteins have shown promising results in preclinical models of GBM, although the transduction efficiency of these tumors is often low. As higher transduction efficiency of tumor cells should lead to enhanced therapeutic efficacy, a means to rapidly engineer AAV vectors with improved transduction efficiency for individual tumors is an attractive strategy. Here we tested the possibility of identifying high-efficiency AAV vectors for human U87 glioma cells by selection in culture of a newly constructed chimeric AAV capsid library generated by DNA shuffling of six different AAV cap genes (AAV1, AAV2, AAV5, AAVrh.8, AAV9, AAVrh.10). After seven rounds of selection, we obtained a chimeric AAV capsid that transduces U87 cells at high efficiency (97% at a dose of 10(4) genome copies/cell), and at low doses it was 1.45-1.6-fold better than AAV2, which proved to be the most efficient parental capsid. Interestingly, the new AAV capsid displayed robust gene delivery properties to all glioma cells tested (including primary glioma cells) with relative fluorescence indices ranging from 1- to 14-fold higher than AAV2. The selected vector should be useful for in vitro glioma research when efficient transduction of several cell lines is required, and provides proof-of-concept that an AAV library can be used to generate AAV vectors with enhanced transduction efficiency of glioma cells. C1 [Maguire, Casey A.; Gianni, Davide; Shaket, Lev A.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Gianni, Davide] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Meijer, Dimphna H.] UMC Utrecht, Dept Neurosci & Pharmacol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Wakimoto, Hiroaki; Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Maguire, Casey A.; Gianni, Davide; Shaket, Lev A.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gao, Guangping] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Gao, Guangping] Gene Therapy Ctr, Worcester, MA USA. RP Sena-Esteves, M (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 381 Plantat St,Suite 250, Worcester, MA 01605 USA. EM Miguel.Esteves@umassmed.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU Alliance for Cancer Gene Therapy (MSE); NIH [T32CA073479, P50CA86355]; MGH; NINDS [P30NS4577] FX This work was supported by a Young Investigator Award from the Alliance for Cancer Gene Therapy (MSE), NIH T32CA073479 (CM), and NIH P50CA86355 (MSE). We would like to acknowledge Dr. Rakesh Jain and the Edwin L. Steele Laboratory at MGH for support during this study. We would like to thank the MGH Nucleic Acid Quantitation Core facility supported by NINDS grant #P30NS4577 for the use of the thermal cyclers for quantitative PCR, and Drs. Johan Skog and Robert Carter for kindly providing the primary glioblastoma cells. We thank Johanna Niers for help with cell culture. We would like to thank Dr. Xandra O. Breakefield for advice and critical reading of the manuscript. NR 40 TC 18 Z9 19 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 FEB PY 2010 VL 96 IS 3 BP 337 EP 347 DI 10.1007/s11060-009-9972-7 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546DL UT WOS:000273788700005 PM 19618115 ER PT J AU Vincent, JL Kahn, I Van Essen, DC Buckner, RL AF Vincent, Justin L. Kahn, Itamar Van Essen, David C. Buckner, Randy L. TI Functional Connectivity of the Macaque Posterior Parahippocampal Cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DEFAULT-MODE NETWORK; MONKEY RETROSPLENIAL CORTEX; MEDIAL PREFRONTAL NETWORKS; EPISODIC MEMORY RETRIEVAL; CONSCIOUS RESTING STATE; PARIETAL CORTEX; RECOGNITION MEMORY; CORTICAL AFFERENTS; CEREBRAL-CORTEX; RHESUS-MONKEY AB Vincent JL, Kahn I, Van Essen DC, Buckner RL. Functional connectivity of the macaque posterior parahippocampal cortex. J Neurophysiol 103: 793-800, 2010. First published December 2, 2009; doi: 10.1152/jn.00546.2009. Neuroimaging experiments in humans suggest that regions in parietal cortex and along the posterior midline are functionally connected to the medial temporal lobe and are active during memory retrieval. It is unknown whether macaques have a similar network. We examined functional connectivity in isoflurane-anesthetized macaques to identify a network associated with posterior parahippocampal cortex (PPHC). Functional connectivity was observed between the PPHC and retrosplenial, posterior cingulate, superior temporal gyrus, and inferior parietal cortex. PPHC correlations were distinct from regions in parietal and temporal cortex activated by an oculomotor task. Comparison of macaque and human PPHC correlations revealed similarities that suggest the temporal-parietal region identified in the macaque may share a common lineage with human Brodmann area 39, a region thought to be involved in recollection. These results suggest that macaques and humans may have homologous PPHC-parietal pathways. By specifying the location of the putative macaque homologue in parietal cortex, we provide a target for future physiological exploration of this area's role in mnemonic or alternative processes. C1 [Vincent, Justin L.; Kahn, Itamar; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Vincent, Justin L.; Kahn, Itamar; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Vincent, Justin L.; Kahn, Itamar; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Van Essen, David C.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Buckner, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Vincent, JL (reprint author), Harvard Univ, Ctr Brain Sci, 52 Oxford St,Rm 280, Cambridge, MA 02138 USA. EM vincent@nmr.mgh.harvard.edu RI Vincent, Justin/B-5033-2012 FU National Institute of Mental Health [R01-MH-60974]; Howard Hughes Medical Institute FX This work was supported by National Institute of Mental Health Grant R01-MH-60974 and by the Howard Hughes Medical Institute. NR 73 TC 18 Z9 18 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2010 VL 103 IS 2 BP 793 EP 800 DI 10.1152/jn.00546.2009 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 552XK UT WOS:000274327900017 PM 19955295 ER PT J AU Lewis, RF Haburcakova, C Gong, WS Makary, C Merfeld, DM AF Lewis, Richard F. Haburcakova, Csilla Gong, Wangsong Makary, Chadi Merfeld, Daniel M. TI Vestibuloocular Reflex Adaptation Investigated With Chronic Motion-Modulated Electrical Stimulation of Semicircular Canal Afferents SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VESTIBULAR-NERVE AFFERENTS; ALERT GUINEA-PIG; SQUIRREL-MONKEY; UNILATERAL LABYRINTHECTOMY; NEURONAL-ACTIVITY; OCULAR REFLEX; PROSTHESIS; RECOVERY; COMPENSATION; PLASTICITY AB Lewis RF, Haburcakova C, Gong W, Makary C, Merfeld DM. Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents. J Neurophysiol 103: 1066-1079, 2010. First published December 16, 2009; doi:10.1152/jn.00241.2009. To investigate vestibuloocular reflex (VOR) adaptation produced by changes in peripheral vestibular afference, we developed and tested a vestibular "prosthesis" that senses yaw-axis angular head velocity and uses this information to modulate the rate of electrical pulses applied to the lateral canal ampullary nerve. The ability of the brain to adapt the different components of the VOR (gain, phase, axis, and symmetry) during chronic prosthetic electrical stimulation was studied in two squirrel monkeys. After characterizing the normal yaw-axis VOR, electrodes were implanted in both lateral canals and the canals were plugged. The VOR in the canal-plugged/instrumented state was measured and then unilateral stimulation was applied by the prosthesis. The VOR was repeatedly measured over several months while the prosthetic stimulation was cycled between off, low-sensitivity, and high-sensitivity stimulation states. The VOR response initially demonstrated a low gain, abnormal rotational axis, and substantial asymmetry. During chronic stimulation the gain increased, the rotational axis improved, and the VOR became more symmetric. Gain changes were augmented by cycling the stimulation between the off and both low-and high-sensitivity states every few weeks. The VOR time constant remained low throughout the period of chronic stimulation. These results demonstrate that the brain can adaptively modify the gain, axis, and symmetry of the VOR when provided with chronic motion-modulated electrical stimulation by a canal prosthesis. C1 [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Lewis, Richard F.; Haburcakova, Csilla; Gong, Wangsong; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Lewis, RF (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM richard_lewis@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [DC-6909, DC-8362, DC-8167] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants DC-6909 and DC-8362 to R. F. Lewis and DC-8167 to D. M. Merfeld. NR 45 TC 38 Z9 39 U1 3 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2010 VL 103 IS 2 BP 1066 EP 1079 DI 10.1152/jn.00241.2009 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 552XK UT WOS:000274327900040 PM 20018838 ER PT J AU Okada, DR Ghoshhajra, BB Blankstein, R Rocha, JA Shturman, LD Rogers, IS Bezerra, HG Sarwar, A Gewirtz, H Hoffmann, U Mamuya, WS Brady, TJ Cury, RC AF Okada, David R. Ghoshhajra, Brian B. Blankstein, Ron Rocha-Filho, Jose A. Shturman, Leonid D. Rogers, Ian S. Bezerra, Hiram G. Sarwar, Ammar Gewirtz, Henry Hoffmann, Udo Mamuya, Wilfred S. Brady, Thomas J. Cury, Ricardo C. TI Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Adenosine; computed tomography (CT); ischemia; myocardial; sestamibi; SPECT ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; INCREMENTAL PROGNOSTIC VALUE; ROTATIONAL TOMOGRAPHY; MAGNETIC-RESONANCE; TL-201; EXERCISE; INFARCTION; ISONITRILE; EXPERIENCE AB We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall gamma = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress. C1 [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, Miami, FL 33146 USA. [Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.] Harvard Univ, Sch Med, Boston, MA USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Bezerra, Hiram G.] Case Western Reserve Univ, Harrington McLaughlin Heart & Vasc Inst, Cleveland, OH 44106 USA. [Mamuya, Wilfred S.] Lown Cardiovasc Grp, Brookline, MA USA. [Sarwar, Ammar] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, Miami, FL USA. RP Cury, RC (reprint author), Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, 8900 N Kendall Dr, Miami, FL 33146 USA. EM rcury@baptisthealth.net RI Ghoshhajra, Brian/J-2114-2016 OI Ghoshhajra, Brian/0000-0002-3865-3432 FU Astellas Pharma, Inc; NIH [1T32 HL076136]; RSNA [213740] FX This study is supported in part by a grant from Astellas Pharma, Inc. Drs Blankstein, Ghoshhajra, Shturman, and Rogers have received support from NIH grant 1T32 HL076136. Dr Ghoshhajra has received support from RSNA 213740. Dr Cury reports receiving research grant support from Astellas, Pharma, Inc. NR 33 TC 52 Z9 57 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2010 VL 17 IS 1 BP 27 EP 37 DI 10.1007/s12350-009-9156-z PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 546ZF UT WOS:000273853600007 PM 19936863 ER PT J AU Subramanian, S Jaffer, FA Tawakol, A AF Subramanian, Sharath Jaffer, Farouc A. Tawakol, Ahmed TI Optical molecular imaging in atherosclerosis SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Atherosclerosis; inflammation; optical imaging; plaque; fluorescence imaging ID INFRARED FLUORESCENT-PROBES; FIBRONECTIN ED-B; EXTRA-DOMAIN-B; IN-VIVO; MATRIX METALLOPROTEINASES; MYOCARDIAL-INFARCTION; PLAQUE INSTABILITY; VULNERABLE PLAQUE; UNSTABLE ANGINA; BLOOD-VESSELS AB Current imaging techniques focus on evaluating the anatomical structure of blood vessel wall and atherosclerotic plaque. These techniques fail to evaluate the biological processes which take place in the vessel wall and inside the plaque. Novel imaging techniques like optical imaging can evaluate the biological and cellular processes inside the plaque and provide information which can be vital for better patient risk stratification. This review highlights the various optical imaging techniques and their application in assessing biological processes in atherosclerosis. C1 [Subramanian, Sharath; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, Boston, MA 02114 USA. [Jaffer, Farouc A.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02114 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM atawakol@partners.org OI Jaffer, Farouc/0000-0001-7980-384X FU Center for integration of Medicine and Innovative Technologies (CIMIT), Department of Defense [0830352N]; Howard Hughes Medical Institute Early Career Development FX Support Sources: Ahmed Tawakol, MD-Center for integration of Medicine and Innovative Technologies (CIMIT), Department of Defense Grant; Farouc A. Jaffer, MD, Phd-AHA Scientist Development Grant # 0830352N, Howard Hughes Medical Institute Early Career Development Award. NR 70 TC 2 Z9 2 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2010 VL 17 IS 1 BP 135 EP 144 DI 10.1007/s12350-009-9175-9 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 546ZF UT WOS:000273853600016 PM 20039152 ER PT J AU Aqel, RA Hage, FG Iskandrian, AE AF Aqel, Raed A. Hage, Fadi G. Iskandrian, Ami E. TI Improvement of myocardial perfusion with a percutaneously inserted left ventricular assist device SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID CARDIOGENIC-SHOCK; INFARCTION; SAFETY; LP2.5 C1 [Aqel, Raed A.; Hage, Fadi G.; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aqel, Raed A.; Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Aqel, RA (reprint author), Univ Alabama, Div Cardiovasc Dis, BDB 383,1530 3rd AVE S, Birmingham, AL 35294 USA. EM raed.aqel@med.va.gov OI Hage, Fadi/0000-0002-1397-4942 NR 10 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD FEB PY 2010 VL 17 IS 1 BP 158 EP 160 DI 10.1007/s12350-009-9127-4 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 546ZF UT WOS:000273853600019 PM 19685267 ER PT J AU Shick, M Banister AF Shick, Mulready Banister TI Enhancing Quality and Safety Competency Development at the Unit Level: An Initial Evaluation of Student Learning and Clinical Teaching on Dedicated Education Unites (vol 49, pg 716, 2009) SO JOURNAL OF NURSING EDUCATION LA English DT Correction C1 [Banister] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD FEB PY 2010 VL 49 IS 2 BP 107 EP 107 PG 1 WC Nursing SC Nursing GA 550XW UT WOS:000274168700009 ER PT J AU Nourhashemi, F Rikkert, MGO Burns, A Winblad, B Frisoni, GB Fitten, J Vellas, B AF Nourhashemi, F. Rikkert, M. G. Olde Burns, A. Winblad, B. Frisoni, G. B. Fitten, J. Vellas, B. TI FOLLOW-UP FOR ALZHEIMER PATIENTS: EUROPEAN ALZHEIMER DISEASE CONSORTIUM POSITION PAPER SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Alzheimer; follow-up; management; treatment; caregiver ID RANDOMIZED CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; MINI NUTRITIONAL ASSESSMENT; MILD COGNITIVE IMPAIRMENT; MENTAL-STATE-EXAMINATION; HIP FRACTURE PATIENTS; LOW BODY-WEIGHT; OF-LIFE CARE; RISK-FACTORS; ELDERLY-PATIENTS AB Background and purpose: Alzheimer disease (AD) is one of the leading causes of dependence in the elderly. Providing care for patients with AD is complex and the type of care required depends on the stage of the disease and varies over time. The aim of this article is to discuss available care strategies once the AD diagnosis has been made and to propose a follow-up plan as standard of care at a European level. Methods: The proposals developed in this article stem from the collaborative work of a panel of multidisciplinary experts involved in the care of AD patients (European Alzheimer Disease Consortium) based on the results of published scientific studies and on their experience from clinical practice. Conclusion: Suggestions for follow-up frequency and easily administered and scored assessment tools are provided, thereby increasing efficiency and quality of care for patients with Alzheimer disease. C1 [Nourhashemi, F.; Vellas, B.] Hop Toulouse, Toulouse, France. [Nourhashemi, F.; Vellas, B.] Fac Med Toulouse, INSERM, U558, F-31073 Toulouse, France. [Rikkert, M. G. Olde] Radboud Univ Nijmegen, Alzheimer Ctr Nijmegen, Dept Geriatr, Med Ctr, Nijmegen, Netherlands. [Burns, A.] Univ Manchester, Psychiat Res Grp, Manchester M13 9PL, Lancs, England. [Winblad, B.] Karolinska Inst, Alzheimer Dis Res Ctr, Stockholm, Sweden. [Frisoni, G. B.] IRCCS, Ctr San Giovanni Dio Fatebenefratelli, Brescia, Italy. [Fitten, J.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Nourhashemi, F (reprint author), Univ Hosp, Dept Internal Med & Clin Gerontol, Alzheimers Dis Res & Clin Ctr, 170 Chemin Casselardit, F-31059 Toulouse, France. EM nourhashemi.f@chu-toulouse.fr RI Olde Rikkert, Marcel/D-9773-2012; Olde Rikkert, M.G.M./H-8078-2014; Frisoni, Giovanni B/K-1360-2016; OI Olde Rikkert, M.G.M./0000-0003-1397-1677; Frisoni, Giovanni B/0000-0002-6419-1753; Burns, Alistair/0000-0002-9837-0645 NR 217 TC 3 Z9 3 U1 6 U2 7 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD FEB PY 2010 VL 14 IS 2 BP 121 EP 130 DI 10.1007/s12603-010-0023-z PG 10 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 581MG UT WOS:000276526800008 PM 20126960 ER PT J AU Harber, P Santiago, S Wu, S Bansal, S Liu, YH Yun, D AF Harber, Philip Santiago, Silverio Wu, Samantha Bansal, Siddharth Liu, Yihang Yun, David TI Subjective Response to Respirator Type: Effect of Disease Status and Gender SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NEW-ORLEANS; SIMULATED WORK; HEART-RATE; EXERCISE; PROTECTION; MASKS; ACCEPTABILITY; TEMPERATURE; PERFORMANCE; TOLERANCE AB Objective: To assess the effect of respirator type and user characteristics (eg, health status) on the subjective response to respirator use. Methods: The subjective responses for multiple domains were evaluated in 104 volunteers performing work tasks in a simulated work environment. Each used a dual cartridge half face mask and a filtering facepiece (N95) respirator. The study population was recruited to include four groups (normal respiratory status, mild asthma, chronic obstructive pulmonary disease, or chronic rhinitis). Mixed model regression analyses determined the effects of respirator type, disease, gender, and age. Results: Half face mask produced more adverse Subjective response than the N95 for most scales. There were significant interactions such that disease status modified the effect of respirator type. In general, women reported greater adverse ratings than did men. Conclusions: The effect of respirator type depends oil disease status. Respirator design evaluation panels should include persons with mild respiratory disease. C1 [Harber, Philip; Wu, Samantha; Bansal, Siddharth; Liu, Yihang; Yun, David] Univ Calif Los Angeles, David Geffen Sch Med, Occupat & Environm Med Div, Dept Family Med, Los Angeles, CA 90024 USA. [Santiago, Silverio] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Pulm Med, Los Angeles, CA USA. RP Harber, P (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Occupat & Environm Med Div, Dept Family Med, 10880 Wilshire,1800, Los Angeles, CA 90024 USA. EM pharber@mednet.ucla.edu FU CDC/NIOSH [R01 OH-8119] FX This work was supported by grant R01 OH-8119 from CDC/NIOSH NR 32 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2010 VL 52 IS 2 BP 150 EP 154 DI 10.1097/JOM.0b013e3181cfcf09 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 555ET UT WOS:000274491600006 PM 20134339 ER PT J AU Harber, P Santiago, S Bansal, S Liu, YH Yun, D Wu, S AF Harber, Philip Santiago, Silverio Bansal, Siddharth Liu, Yihang Yun, David Wu, Samantha TI Respirator Physiologic Impact in Persons With Mild Respiratory Disease SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CONTAINED BREATHING APPARATUS; INDUCTIVE PLETHYSMOGRAPHY; INSPIRATORY RESISTANCE; EXHALATION RESISTANCES; PHYSICAL PERFORMANCE; DEMAND RESPIRATOR; WORK PERFORMANCE; SIMULATED WORK; LUNG-DISEASE; FACE MASKS AB Objective: To assess whether mild respiratory disease affects physiologic adaptation to respirator use. Methods: The study compared the respiratory effects of dual cartridge half face mask and filtering facepeice (N95) respirators while performing simulated-work tasks. Subjects with mild chronic obstructive pulmonary disease (n = 14), asthma (n = 42), chronic rhinitis (n = 17), and normal respiratory status (n = 24) were studied. Mixed model regression analyses determined the effects of respirator type, disease status. and the respirator-disease interactions. Results: Respirator type significantly affected several physiologic measures. Respirator type effects differed among disease categories as shown by statistically significant interaction terms. Respiratory timing parameters were more affected than ventilatory volumes. In general, persons with asthma showed greater respirator-disease interactions than chronic obstructive pulmonary disease, rhinitis, or healthy Subjects. Conclusions: The effects of respirator type differ according to the category of respiratory disease. C1 [Harber, Philip; Bansal, Siddharth; Liu, Yihang; Yun, David; Wu, Samantha] Univ Calif Los Angeles, David Geffen Sch Med, Occupat & Environm Med Div, Dept Family Med, Los Angeles, CA 90095 USA. [Santiago, Silverio] VA Greater Los Angeles Healthcare Syst, Div Pulm Med, Dept Med, Los Angeles, CA USA. RP Harber, P (reprint author), UCLA Occupat & Environm Med, 10880 Wilshire,1800, Los Angeles, CA 90024 USA. EM pharber@mednet.ucla.edu FU CDC/NIOSH [R01 OH-8119] FX Supported by Grant R01 OH-8119 from CDC/NIOSH. NR 45 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2010 VL 52 IS 2 BP 155 EP 162 DI 10.1097/JOM.0b013e3181ca0ec9 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 555ET UT WOS:000274491600007 PM 20134350 ER PT J AU Abramson, Z Susarla, S August, M Troulis, M Kaban, L AF Abramson, Zachary Susarla, Srinivas August, Meredith Troulis, Maria Kaban, Leonard TI Three-Dimensional Computed Tomographic Analysis of Airway Anatomy in Patients With Obstructive Sleep Apnea SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MAXILLOMANDIBULAR ADVANCEMENT; SNORERS; LENGTH; PATHOGENESIS; DIMENSIONS; MORPHOLOGY; SEVERITY; PHARYNX; PATENCY; AGE AB Purpose: To identify abnormalities in airway size and shape that correlate with the presence and severity of obstructive sleep apnea (OSA). Materials and Methods: This was a retrospective case series of patients undergoing treatment of OSA who had preoperative computed tomographic (CT) scans of the upper airway available. Patients who had undergone CT scanning for nonairway pathologic features during the same period served as the controls. Digital 3D-CT reconstructions were made and 12 parameters of airway size and 4 of shape were analyzed. The posterior airway space, middle airway space, and hyoid to mandibular plane distance were measured on the lateral cephalograms of the patients with OSA. Bivariate analysis was used to identify the factors associated with the presence and severity of OSA as measured by the respiratory disturbance index (RDI). Multiple regression analysis identified the factors that correlated with the RDI. Results: Of the 44 patients with OSA, 15 (10 men and 5 women) had pre- and postoperative CT scans available. In addition, 17 patients (11 men and 6 women) were used as controls. The airway length was significantly increased in the patients with OSA (P<.01). On bivariate analysis, the length, lateral/retroglossal anteroposterior dimension ratio and genial tubercle to hyoid bone distance were associated with the RDI (P<.03). On multiple regression analysis, length (P<.01) had a positive correlation and the lateral/retroglOssal anteroposterior dimension ratio (P=.04) an inverse correlation with the RDI. Conclusions: The results of this study indicate that the presence of OSA is associated with an increase in airway length. Airways that were more elliptical in shape and mediolaterally oriented (greater lateral/retroglossal anteroposterior dimension ratio) had a decreased tendency toward obstruction. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxilloftic Surg 68.354-362, 2070 C1 [Abramson, Zachary; Susarla, Srinivas; August, Meredith; Troulis, Maria; Kaban, Leonard] Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02114 USA. RP Kaban, L (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 36 TC 47 Z9 50 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2010 VL 68 IS 2 BP 354 EP 362 DI 10.1016/j.joms.2009.09.087 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617KX UT WOS:000279280700020 PM 20116708 ER PT J AU Abramson, ZR Susarla, S Tagoni, JR Kaban, L AF Abramson, Zachary R. Susarla, Srinivas Tagoni, James R. Kaban, Leonard TI Three-Dimensional Computed Tomographic Analysis of Airway Anatomy SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; CONE-BEAM CT; MAXILLOMANDIBULAR ADVANCEMENT; SNORERS; RELIABILITY; AGE AB Purpose: To test the reliability of a 3-dimensional computed tomographic (3D-CT) analysis of airway size and shape and to correlate the 3D-CT findings with lateral cephalometric measurements. Materials and Methods: Fifteen pairs of preoperative maxillofacial 3D-CT scans and digital lateral cephalograms of patients treated for obstructive sleep apnea were used in the present study. Digital 3D-CT reconstructions were created and 12 measurements of airway size and 4 of shape were analyzed. The posterior airway space (PAS), middle airway space, and hyoid to mandibular plane distances were measured on the cephalograms. We then randomly selected 5 CT scans and 5 cephalograms which were analyzed blindly on 5 separate occasions by 2 investigators (Z.A., J.T.) to establish the intraclass correlation coefficients for inter- and intraexaminer reliability. All 15 pairs of images were used to compute the Pearson correlation coefficients to establish the relationship between the CT and cephalometric measurements. Results: The intra- and interexaminer reliabilities were high for all CT (0.86 to 1.0 and 0.89 to 1.0, respectively; P<.001) and cephalometric measurements (0.84 to 1.0 and 0.91 to 0.99, respectively; P<.001). The CT measurements retroglossal anteroposterior dimension and distance between the genial tubercle and hyoid exhibited a positive correlation with the PAS (r = .60, P = 02 and r = .54, P = .04, respectively), and the lateral/anteroposterior dimension demonstrated an inverse correlation (r = -.68, P = .01) with the PAS. Conclusion: The results of the present study indicate that the 3D-CT and lateral cephalometric measurements we selected are reliable and reproducible. The only cephalometric measurement that exhibited any correlation with the CT parameters was PAS. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:363-371, 2010 C1 [Abramson, Zachary R.; Susarla, Srinivas; Tagoni, James R.; Kaban, Leonard] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaban, L (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM LKaban@Partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Hanson Foundation FX The authors thank the Hanson Foundation for financial support; Thomas Dodson, MD, Associate Professor of Oral and Maxillofacial Surgery, Massachusetts General Hospital, for his input regarding the study design and statistical analysis; Ron Kikinis, MD and Raul San Jose, PhD, Harvard Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA, for their technical advice regarding the use of computer software; and former fellows Peter Everett and Krishna Yeshwant, Harvard Surgical Planning Laboratory, and Ed Seldin, MD, Associate Professor of Oral and Maxillofacial Surgery, Massachusetts General Hospital, who helped develop this method. NR 29 TC 43 Z9 43 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2010 VL 68 IS 2 BP 363 EP 371 DI 10.1016/j.joms.2009.09.086 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 617KX UT WOS:000279280700021 PM 20116709 ER PT J AU Morishita, Y Naito, M Miyazaki, M He, WB Wu, GZ Wei, F Sintuu, C Hymanson, H Brochmann, EJ Murray, SS Wang, JC AF Morishita, Yuichiro Naito, Masatoshi Miyazaki, Masashi He, Wubing Wu, Guizhong Wei, Feng Sintuu, Chananit Hymanson, Henry Brochmann, Elsa J. Murray, Samuel S. Wang, Jeffrey C. TI Enhanced Effects of BMP-Binding Peptide Combined with Recombinant Human BMP-2 on the Healing of a Rodent Segmental Femoral Defect SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE recombinant human bone morphogenetic protein-2 (rhBMP-2); BMP binding peptide (BBP); segmental femoral bone defect; osteogenic activity ID BONE MORPHOGENETIC PROTEIN; HUMAN OSTEOGENIC PROTEIN-1; FUSION; MODEL; REPAIR; RATS AB BMP-binding peptide (BBP) enhances the osteogenic activity of recombinant human bone morphogenetic protein-2 (rhBMP-2), but the mechanism underlying the enhancement remains unclear. We aimed to elucidate the potential enhanced efficacy of BBP using critical-sized segmental femoral bone defects in rats. Seventy defects in seven groups of rats were filled with various amounts (0, 2, 5, and 10 mu g) of rhBMP-2 with or without 1000 mu g BBP. Radiographs were obtained after 4 and 8 weeks. The animals were euthanized at 8 weeks, and femoral specimens were assessed manually, evaluated for bone volume using microcomputed tomography, and subjected to histological or biomechanical analysis. Although 10 mu g rhBMP-2 yielded consistent results in terms of bone healing and quality of bone repair across the segmental defect, lower doses of rhBMP-2 failed to induce satisfactory bone healing. However, the combined administration of lower doses of rhBMP-2 and BBP induced the formation of significantly large amounts of bone. Our results suggest that the combined administration of rhBMP-2 and BBP facilitates bone healing and has potential clinical applications. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:258-264, 2010 C1 [Miyazaki, Masashi; He, Wubing; Wu, Guizhong; Wei, Feng; Sintuu, Chananit; Hymanson, Henry; Wang, Jeffrey C.] Univ Calif Santa Monica, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, Santa Monica, CA 90404 USA. [Morishita, Yuichiro; Naito, Masatoshi] Fukuoka Univ, Dept Orthopaed Surg, Fukuoka 81401, Japan. [Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. RP Wang, JC (reprint author), Univ Calif Santa Monica, Dept Orthopaed Surg, UCLA Comprehens Spine Ctr, 1250 16th St,Suite 745, Santa Monica, CA 90404 USA. EM JWang@mednet.ucla.edu NR 20 TC 9 Z9 9 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD FEB PY 2010 VL 28 IS 2 BP 258 EP 264 DI 10.1002/jor.20970 PG 7 WC Orthopedics SC Orthopedics GA 544RD UT WOS:000273675700018 PM 19639633 ER PT J AU Sheahan, P Ahn, CN Harvey, RJ Wise, SK Mulligan, RM Lathers, DMR Schlosser, RJ AF Sheahan, Patrick Ahn, Chadwick N. Harvey, Richard J. Wise, Sarah K. Mulligan, Ryan M. Lathers, Deanne M. R. Schlosser, Rodney J. TI Local IgE Production in Nonatopic Nasal Polyposis SO JOURNAL OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article DE chronic rhinosinusitis; IgE; local production; nasal polyps; specific IgE ID ALLERGIC FUNGAL RHINOSINUSITIS; EOSINOPHILIC INFLAMMATION; DIAGNOSIS; PATHOPHYSIOLOGY; SINUSITIS; RHINITIS; TISSUE; ASTHMA AB Introduction: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. Methods: Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. Results: Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). Conclusions: Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy. C1 [Ahn, Chadwick N.; Harvey, Richard J.; Wise, Sarah K.; Mulligan, Ryan M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Sheahan, Patrick] S Infirm Victoria Univ Hosp, Dept Otolaryngol Head & Neck Surg, Cork, Ireland. [Wise, Sarah K.] Emory Univ, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30322 USA. [Lathers, Deanne M. R.] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Suite 1130,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu RI Sheahan, Patrick/H-6153-2013 FU American Academy of Otolaryngic Allergy (AAOA); Flight Attendant Medical Research Institute; XoranTech; NeilMed FX Financial disclosure of authors: This research was supported in part by a grant from the American Academy of Otolaryngic Allergy (AAOA) ROADS Scholarship program. Dr. Schlosser receives grant support from the Flight Attendant Medical Research Institute, XoranTech, and NeilMed. Dr. Schlosser is a consultant for BrainLAB, Medtronic Xomed, and Gyrus and serves on the speaker's bureau for GlaxoSmithKlein and Schering Plough. Dr. Wise has received grant support from XoranTech. Dr. Lathers is currently employed by Bristol Myers Squibb. NR 22 TC 14 Z9 15 U1 1 U2 3 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1916-0216 J9 J OTOLARYNGOL-HEAD N JI J. Otolaryngol-Head Neck Surg. PD FEB PY 2010 VL 39 IS 1 BP 45 EP 51 DI 10.2310/7070.2009.080280 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 678BP UT WOS:000284043400009 PM 20122344 ER PT J AU Claxton, RN Blackhall, L Weisbord, SD Holley, JL AF Claxton, Rene N. Blackhall, Leslie Weisbord, Steven D. Holley, Jean L. TI Undertreatment of Symptoms in Patients on Maintenance Hemodialysis SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Dialysis patients; quality of life; symptom burden; symptom management; symptom assessment ID QUALITY-OF-LIFE; CHRONIC DIALYSIS PATIENTS; STAGE RENAL-DISEASE; DEPRESSION; CARE; PAIN; PREVALENCE; MORTALITY; PATTERNS; DOPPS AB Context. Hemodialysis patients suffer a large symptom burden, and little is known about how effectively symptoms are treated. Objectives. To assess the management of treatable symptoms in hemodialysis patients, we administered a 30-item questionnaire on physical and emotional symptoms to patients receiving outpatient hemodialysis at the University of Virginia. Methods. We asked patients whether they were prescribed therapy for potentially treatable symptoms and assessed who prescribed the therapy. By means of chart review, we also documented whether medications were prescribed for these symptoms. Results. We approached 87 patients and enrolled 62 (71%). The most commonly reported, potentially treatable symptoms included bone/joint pain, insomnia, mood disturbance, sexual dysfunction, paresthesia, and nausea. Only 45% of patients with bone/joint pain reported receiving an analgesic medication. Twenty-three percent of patients with trouble falling asleep and 53% of patients with nausea reported receiving a medication to alleviate this symptom. Chart review revealed that 58% of patients who reported the presence of bone/joint pain were prescribed an analgesic, 23% of patients with trouble falling asleep were prescribed a sleep aid, and 42% of patients with nausea received an antiemetic. Primary care providers were more likely than nephrologists to provide for all symptoms except nausea and numbness or tingling in the feet, and this difference was significant for the treatment of worrying (3/3 vs. 0/3, P= 0.05) and nervousness (4/5 vs. 0/5, P= 0.02). Conclusion. Potentially treatable symptoms in hemodialysis are undertreated. Pharmacologic therapy, particularly for emotional symptoms, was more commonly prescribed by primary care providers than nephrologists. Additional study of the barriers to symptom treatment and interventions that increase nephrologist and primary care provider symptom management are needed. J Pain Symptom Manage 2010;39:211-218. 2010 (C) U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Claxton, Rene N.] Univ Pittsburgh, Sch Med, Dept Internal Med, Div Palliat Care & Eth, Pittsburgh, PA 15213 USA. [Weisbord, Steven D.] Univ Pittsburgh, Sch Med, Dept Internal Med, Div Nephrol, Pittsburgh, PA 15213 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Blackhall, Leslie] Univ Virginia Hlth Syst, Dept Internal Med, Div Gen Med Geriatr & Palliat Care, Charlottesville, VA USA. [Holley, Jean L.] Univ Illinois, Dept Internal Med, Div Nephrol, Urbana, IL 61801 USA. RP Claxton, RN (reprint author), Univ Pittsburgh, Sch Med, Dept Internal Med, Div Palliat Care & Eth, 200 Lothrop St,MUH G-100, Pittsburgh, PA 15213 USA. EM claxtonrn@upmc.edu NR 28 TC 38 Z9 42 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 211 EP 218 DI 10.1016/j.jpainsymman.2009.07.003 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400005 PM 19963337 ER PT J AU Blinderman, CD AF Blinderman, Craig D. TI Opioids, Iatrogenic Harm and Disclosure of Medical Error SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Opioids; adverse events; medical error; palliative care ID PHYSICIAN-ASSISTED SUICIDE; RESPIRATION; EUTHANASIA; SEDATION; THERAPY AB The safety of patients in U.S. hospitals is a serious problem, with adverse events because of medical error affecting a significant proportion, of hospitalized patients. Patients at the end of life are particularly vulnerable and are at risk of potential adverse events. This article presents a case in which opioids were rapidly titrated to neurotoxic doses in a patient who was terminally extubated. The patient was profoundly sedated and was noted to have Cheyne-Stokes breathing. The possibility of opioid-related iatrogenic harm is raised, and a discussion of what counts as medical error in these circumstances is explored. Palliative care specialists have a unique responsibility to provide guidance and establish a standard of care that clinicians should adhere to. Prevention of harm in dying patients should be a priority in the hospital setting. J Pain Symptom Manage 2010;39:309-313. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Blinderman, Craig D.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Blinderman, Craig D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Blinderman, CD (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Founders 600,55 Fruit St, Boston, MA 02114 USA. EM cblinderman@partners.org NR 16 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 309 EP 313 DI 10.1016/j.jpainsymman.2009.11.242 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400015 PM 20152593 ER PT J AU Ullrich, C Dussel, V Feudtner, C Hill, C Hinds, P Wolfe, J AF Ullrich, Christina Dussel, Veronica Feudtner, Chris Hill, Cherry Hinds, Pamela Wolfe, Joanne TI Research in Children with Advanced Illnesses: Advancing the Field Together (P5) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Ullrich, Christina; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ullrich, Christina; Dussel, Veronica] Childrens Hosp, Boston, MA 02115 USA. [Feudtner, Chris] Childrens Hosp Philadelphia, Cherry Hill, NJ USA. [Hinds, Pamela] Childrens Natl Med Ctr, Washington, DC 20010 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 322 EP 323 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400023 ER PT J AU Chrastek, J Duncan, J Eull, D AF Chrastek, Jody Duncan, Janet Eull, Donna TI "Yes of Course You can Care for Kids!-Just Need a Little Retooling!" (P16) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Chrastek, Jody; Eull, Donna] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Duncan, Janet] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400026 ER PT J AU Dahlin, C AF Dahlin, Constance TI Through the Looking Glass: Making Sense of APN Billing (P18) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Dahlin, Constance] Massachusetts Gen Hosp, Boston, MA 02114 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 325 EP 325 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400028 ER PT J AU Jackson, V Jacobsen, J DeLima-Thomas, J Seaver, M Block, S AF Jackson, Vicki Jacobsen, Juliet DeLima-Thomas, Jane Seaver, Margaret Block, Susan TI Understanding Normative Coping and Setting the Stage for Psychological Growth at the End-of-life (P10) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Jackson, Vicki] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [DeLima-Thomas, Jane] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Seaver, Margaret] Lahey Clin Fdn, Burlington, MA USA. [Block, Susan] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 326 EP 327 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400031 ER PT J AU Friedrichsdorf, SJ Foster-Barber, A Hauer, J Tremonti, N Ullrich, CK AF Friedrichsdorf, Stefan J. Foster-Barber, Audrey Hauer, Julie Tremonti, Nadia Ullrich, Christina K. TI Advanced Management of Distressing Non-Pain Symptoms in Pediatric Palliative Care (P13) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Friedrichsdorf, Stefan J.] Childrens Hosp, Minneapolis, MN USA. [Friedrichsdorf, Stefan J.] Clin Minnesota, Minneapolis, MN USA. [Foster-Barber, Audrey] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hauer, Julie] Univ Minnesota, Childrens Hosp, Natick, MA USA. [Hauer, Julie] Gillette Childrens Specialty Healthcare, Natick, MA USA. [Tremonti, Nadia] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Ullrich, Christina K.] Childrens Hosp, Boston, MA 02115 USA. [Ullrich, Christina K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 328 EP 329 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400034 ER PT J AU Coyne, PJ Dahlin, C McSteen, K AF Coyne, Patrick J. Dahlin, Constance McSteen, Kerstin TI Initiating and Maintaining a Palliative Care Service for APNs (P20) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Coyne, Patrick J.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Dahlin, Constance] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McSteen, Kerstin] Abbott NW Hosp, Minneapolis, MN 55407 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 329 EP 330 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400036 ER PT J AU Ullrich, C Dussel, V Hilden, J Sheaffer, J Lehmann, L Wolfe, J AF Ullrich, Christina Dussel, Veronica Hilden, Joanne Sheaffer, Jan Lehmann, Leslie Wolfe, Joanne TI End-of-Life Experience of Children Undergoing Hematopoietic Stem-Cell Transplantation: Parent and Provider Perspectives and Patterns of Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Ullrich, Christina; Dussel, Veronica; Lehmann, Leslie; Wolfe, Joanne] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hilden, Joanne] St Vincent Childrens Hosp, Indianapolis, IN USA. [Sheaffer, Jan] Childrens Hosp & Clin, Scandia, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 331 EP 332 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400040 ER PT J AU Walling, A Asch, S Lorenz, K Roth, C Monica, S Barry, T Wenger, N AF Walling, Anne Asch, Steven Lorenz, Karl Roth, Carol Monica, Santa Barry, Tod Wenger, Neil TI Quality of End-of-Life Care in the Hospital SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Walling, Anne; Monica, Santa; Barry, Tod; Wenger, Neil] Univ Calif Los Angeles, Los Angeles, CA USA. [Asch, Steven; Lorenz, Karl] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Roth, Carol] RAND Corp, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 332 EP 333 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400042 ER PT J AU Bernacki, R Ko, D AF Bernacki, Rachelle Ko, Danielle TI An Innovative Quality Improvement Initiative to Increase Palliative Care Consultation SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Bernacki, Rachelle] Dana Farber Canc Inst, Cambridge, MA USA. [Ko, Danielle] MGH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 339 EP 339 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400051 ER PT J AU Goebel, J Compton, P Lanto, A Asch, S Sherbourne, C Zubkoff, L Lorenz, K AF Goebel, Joy Compton, Peggy Lanto, Andy Asch, Steven Sherbourne, Cathy Zubkoff, Lisa Lorenz, Karl TI Is it Pseudoaddiction? Prescription Sharing, Alcohol, and Street Drug Use to Manage Pain among Veterans SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Goebel, Joy] Calif State Univ Long Beach, Long Beach, CA 90840 USA. [Compton, Peggy] Univ Calif Los Angeles, Los Angeles, CA USA. [Lanto, Andy] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven] W Angeles VA, Los Angeles, CA USA. [Sherbourne, Cathy] RAND, Santa Monica, CA USA. [Zubkoff, Lisa] Dept Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lorenz, Karl] Vet Adm Greater Los Angeles, Los Angeles, CA 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 340 EP 340 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400053 ER PT J AU Bernacki, R Sanchez-Reilly, S Carey, E Thomas, JD Kapo, J Morrison, L Periyakoil, VJ O'Neill, L AF Bernacki, Rachelle Sanchez-Reilly, Sandra Carey, Elise Thomas, Jane DeLima Kapo, Jen Morrison, Laura Periyakoil, V. J. O'Neill, Lynn TI Peer Mentoring: An Innovative Model for Professional Advancement in Hospice and Palliative Medicine (320) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Bernacki, Rachelle] Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. STVHCS, San Antonio, TX 78229 USA. [Carey, Elise] Mayo Clin, Rochester, MN USA. [Thomas, Jane DeLima] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kapo, Jen] Univ Penn, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. [Periyakoil, V. J.] Stanford Univ, Palo Alto, CA 94304 USA. [O'Neill, Lynn] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 357 EP 357 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400080 ER PT J AU Block, E AF Block, Eve TI IV Lidocaine: An Underutilized Therapy for Refractory Pain at the End of Life SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Block, Eve] Massachusetts Gen Hosp, Boston, MA 02114 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 368 EP 368 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400099 ER PT J AU Joselow, M Duncan, J Vesel, T AF Joselow, Marsha Duncan, Janet Vesel, Tamara TI An Interdisciplinary Model of Palliative Care Fellowship Training: From Application Through Graduation (405) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Joselow, Marsha; Vesel, Tamara] Childrens Hosp, Boston, MA 02115 USA. [Joselow, Marsha; Vesel, Tamara] Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 373 EP 374 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400109 ER PT J AU Selvaggi, K Jessell, S Miller, S Abrahm, J AF Selvaggi, Kathy Jessell, Susan Miller, Sarah Abrahm, Janet TI Palliative Care Partners with the Hematologic Malignancy (HM) Unit SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Selvaggi, Kathy; Jessell, Susan] W Penn Allegheny Hlth Syst, Pittsburgh, PA USA. [Abrahm, Janet] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 381 EP 382 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400122 ER PT J AU Bikson, K Lorenz, K Milch, M AF Bikson, Karra Lorenz, Karl Milch, Mario TI Organizational Challenges to Implementing Hospital-Based Palliative Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Bikson, Karra] NYU, New York, NY USA. [Lorenz, Karl] VA Greater Angeles, Los Angeles, CA USA. [Milch, Mario] Vitas, Encino, CA 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 386 EP 387 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400129 ER PT J AU Walling, A Lorenz, K Asch, S Malin, J Roth, C Wenger, N AF Walling, Anne Lorenz, Karl Asch, Steven Malin, Jennifer Roth, Carol Wenger, Neil TI Quality of Supportive Care among Inpatients Dying with Advanced Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Walling, Anne; Wenger, Neil] Univ Calif Los Angeles, Los Angeles, CA USA. [Lorenz, Karl] VA Greater Los Angeles, Los Angeles, CA USA. [Asch, Steven] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Roth, Carol] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 393 EP 393 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400139 ER PT J AU Hadid, T Sanchez-Reilly, S AF Hadid, Tank Sanchez-Reilly, Sandra TI Implications of Interdisciplinary Palliative Care when Caring for Older Adults with Advanced Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Hadid, Tank; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 394 EP 394 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400141 ER PT J AU Davila, A Garza, M Lee, S Ross, J Sanchez-Reilly, S AF Davila, Angelica Garza, Mary Lee, Shuko Ross, Jeanette Sanchez-Reilly, Sandra TI Effectiveness of a Geriatric Palliative Care Consult on Pain Management and Advance Directives among Older Adults SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Davila, Angelica; Ross, Jeanette; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Garza, Mary] Univ Texas San Antonio, San Antonio, TX USA. [Lee, Shuko] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 395 EP 395 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400142 ER PT J AU Morrison, L Otis-Green, S Fordham, P Carey, E Chittenden, E AF Morrison, Laura Otis-Green, Shirley Fordham, Pamela Carey, Elise Chittenden, Eva TI An Interactive Educational Exchange: Sharing Innovative Teaching Materials and Methods (425) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Morrison, Laura] Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. [Fordham, Pamela] Univ Alabama, Birmingham, AL USA. [Chittenden, Eva] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carey, Elise] Mayo Clin, Rochester, MN 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 400 EP 401 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400151 ER PT J AU Goldstein, NE Gabrielle, W AF Goldstein, Nathan E. Gabrielle, Wendy TI State of the Science: Update in Hospice and Palliative Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Goldstein, Nathan E.] Mt Sinai Sch Med, New York, NY USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, New York, NY USA. [Gabrielle, Wendy] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 405 EP 405 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400160 ER PT J AU Wolfe, J Eull, D AF Wolfe, Joanne Eull, Donna TI When East Meets West and West Meets East-Cultural Considerations in Pediatric Palliative Care (431) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolfe, Joanne] Childrens Hosp, Boston, MA 02115 USA. [Eull, Donna] Childrens Hosp & Clin, Minneapolis, MN 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 405 EP 405 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400159 ER PT J AU Fromme, E Lorenz, K Kutner, J AF Fromme, Erik Lorenz, Karl Kutner, Jean TI Palliative Care Research Issues and Methods: Pain Assessment, Prognostication, and CAM (518) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Fromme, Erik] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lorenz, Karl] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Kutner, Jean] Univ Colorado, Denver Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 414 EP 414 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400177 ER PT J AU Dy, S Lorenz, K Bull, J Abernethy, A AF Dy, Sydney Lorenz, Karl Bull, Janet Abernethy, Amy TI Update in Quality and How to Use New Resources for Quality Measurement in Palliative Care (521) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Dy, Sydney] Johns Hopkins Sch Publ Hlth, Linthicum, MD USA. [Lorenz, Karl] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Bull, Janet] Four Seasons, Flat Rock, NC USA. [Abernethy, Amy] Duke Univ, Sch Med, Durham, NC USA. OI Abernethy, Amy/0000-0001-6930-8722 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 415 EP 416 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400180 ER PT J AU Hultman, T Jackson, V Rinehart, T AF Hultman, Todd Jackson, Vicki Rinehart, Todd TI Working with Families in Crisis: A Strength-Based Approach (525) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Hultman, Todd; Jackson, Vicki; Rinehart, Todd] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 417 EP 418 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400184 ER PT J AU Lee, S Dahlin, C Carleton, P Coakley, E AF Lee, Susan Dahlin, Constance Carleton, Penny Coakley, Edward TI RN Residency: Transitioning to Geropalliative Care (526) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Lee, Susan; Dahlin, Constance; Coakley, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carleton, Penny] Ctr Integrat Med & Innovat Technol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 418 EP 419 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400185 ER PT J AU Prigerson, HG AF Prigerson, Holly G. TI End-of-Life Care as an Illusion-Wish-Fulfillment, but Whose Wishes and Why? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 420 EP 420 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400189 ER PT J AU Andrews, C Patel, J Sanchez-Reilly, S Ross, J AF Andrews, Cody Patel, Jignesh Sanchez-Reilly, Sandra Ross, Jeanette TI Do Older Adults with Completed Advance Directives Really Understand Them? (704) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Andrews, Cody; Patel, Jignesh; Sanchez-Reilly, Sandra; Ross, Jeanette] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez-Reilly, Sandra] S Texas Vet Hlth Care Syst, San Antonio, TX 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 423 EP 423 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400194 ER PT J AU Lannen, P Kreicbergs, U Wolfe, J Mack, J Onelov, E Nyberg, U AF Lannen, Patricia Kreicbergs, Ulrika Wolfe, Joanne Mack, Jennifer Onelov, Erik Nyberg, Ullakarin TI Absorbing Information about a Child's Incurable Cancer Prognosis (731) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Lannen, Patricia] Univ Bern, Bern, Switzerland. [Kreicbergs, Ulrika; Wolfe, Joanne; Mack, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Onelov, Erik; Nyberg, Ullakarin] MSc Karolinska Inst Stockholm, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 438 EP 439 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400219 ER PT J AU Lowery, A Lee, S Sanchez-Reilly, S Ross, J AF Lowery, Ashlei Lee, Shuko Sanchez-Reilly, Sandra Ross, Jeanette TI Effect of Prior Experience with a Dying Person on Medical Students' Communication Skill with Terminally Ill Patients (732) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 439 EP 440 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400220 ER PT J AU Patel, T Tabares, J Pugh, MJ AF Patel, Taral Tabares, Jeff Pugh, Mary Jo TI A Cause for Concern: Chronic Propoxyphene Use among Older Adults with Pain (740) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Patel, Taral; Tabares, Jeff] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo] S Texas Vet Hlth Care Syst, Helotes, TX USA. OI Pugh, Mary Jo/0000-0003-4196-7763 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 444 EP 444 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400228 ER PT J AU Schulman-Green, D Ercolano, E McCorkle, R Bradley, E Prigerson, H Knobf, T DiGiovanna, M Quinn, T Dixon, J AF Schulman-Green, Dena Ercolano, Elizabeth McCorkle, Ruth Bradley, Elizabeth Prigerson, Holly Knobf, Tish DiGiovanna, Michael Quinn, Thomas Dixon, Jane TI Initial Development and Content Validation of the Knowledge of Care Options (KOCO) Instrument (744) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract C1 [Ercolano, Elizabeth; Knobf, Tish; Dixon, Jane] Yale Univ, Sch Nursing, New Haven, CT USA. [Prigerson, Holly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Quinn, Thomas] Yale Canc Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2010 VL 39 IS 2 BP 446 EP 446 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 617KU UT WOS:000279280400232 ER PT J AU Anderson, WG Goldstein, NE AF Anderson, Wendy G. Goldstein, Nathan E. TI Update in Hospice and Palliative Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID ADVANCED CANCER; METHADONE; THERAPY; ILLNESS; QTC C1 [Anderson, Wendy G.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Anderson, Wendy G.] Univ Calif San Francisco, Palliat Care Program, San Francisco, CA 94143 USA. [Goldstein, Nathan E.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Bronx, NY USA. RP Anderson, WG (reprint author), Univ Calif San Francisco, Div Hosp Med, 521 Parnassus Ave,Box 0903, San Francisco, CA 94143 USA. EM anderson.wg@gmail.com FU National Institute of Aging [K23 AG025933] FX Dr. Anderson was supported by a Junior Faculty Career Development Award from the National Palliative Care Research Center. Dr. Goldstein was supported by a Mentored Patient-Oriented Research Career Development Award from the National Institute of Aging (K23 AG025933). Drs. Anderson and Goldstein presented these articles for the State of the Science Plenary Session at the Annual Assembly of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association on March 28, 2009 in Austin, Texas. NR 15 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2010 VL 13 IS 2 BP 197 EP 202 DI 10.1089/jpm.2009.0252 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 549VU UT WOS:000274083200021 PM 19929227 ER PT J AU Zhong, WW Xia, ZW Hinrichs, D Rosenbaum, JT Wegmann, KW Meyrowitz, J Zhang, ZL AF Zhong, Wenwei Xia, Zhenwei Hinrichs, David Rosenbaum, James T. Wegmann, Keith W. Meyrowitz, Jeffery Zhang, Zili TI Hemin Exerts Multiple Protective Mechanisms and Attenuates Dextran Sulfate Sodium-induced Colitis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE colitis; inflammatory bowel disease; interleukin-17; regulatory T cells ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; ROR-GAMMA-T; INTESTINAL INFLAMMATION; IL-17 PRODUCTION; MURINE COLITIS; OXYGENASE-1; DIFFERENTIATION; INTERLEUKIN-17; EXPRESSION AB Objective: Inflammatory bowel disease (IBD) is characterized by recurrent and severe gastrointestinal inflammation. Activation of inflammatory cells, such as T(H)17 lymphocytes, and/or deficiency of regulatory T cells (T(reg)) are responsible for the pathogenesis of 11313, As an acute phase reactant, heme oxygenase-1 (HO-1) has been shown to play an anti-inflammatory and immunomodulatory role in many disease processes. In this study, we used a dextran sulfate sodium (DSS)-induced murine colitis model to investigate the effect of upregulating HO-1 by hemin on the development of colonic inflammation. Materials and Methods: The mice were enterically challenged with 4% DSS. In addition, some mice were intraperitoneally administered with hemin or Sn-protoporphyrin (SnPP) on days 0, 1, and 6 after DSS treatment. The severity of colitis was evaluated by daily monitoring of weight change and diarrhea. At the end of the experiment, the colon, spleen, and mesenteric lymph nodes were harvested for histology and various immunological assays. Results: Compared to control groups, DSS challenge markedly induced HO-1 expression in the colon epithelium. Upregulation of HO-1 by hemin was further correlated with attenuation of DSS-induced colitis. In contrast, inhibition of endogenous HO-1 by SnPP aggravated the colitis. To further assess the anti-inflammatory mechanisms, we examined whether hemin enhanced the proliferation of T(reg) cells and suppressed the production of interleukin (IL)-17. Flow cytometry analysis revealed that hemin markedly expanded the CD4 + CD25 + Foxp3+ T(reg) population. Moreover, hemin attenuated IL-17 and T(H)17-related cytokines. This inhibition coincided with the attenuation of DSS-induced colitis. Finally, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling assay showed that hemin treatment markedly reduced programmed cell death of colonic epithelium, indicating that hemin exerts a modulatory effect on the induction of T(re)g, IL-17, and apoptosis. Conclusions: These results demonstrate that upregulation of HO-1 by hemin ameliorated experimental colitis. Moreover, our study suggests a broader protective mechanism of hemin. C1 [Zhang, Zili] Oregon Hlth & Sci Univ, Dept Pediat, CDRCP, Portland, OR 97239 USA. [Zhong, Wenwei; Xia, Zhenwei] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pediat, Shanghai 200030, Peoples R China. [Hinrichs, David; Wegmann, Keith W.] Portland VA Med Ctr, Dept Pediat, Portland, OR USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. RP Zhang, ZL (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, CDRCP, 707 SW Gaines St, Portland, OR 97239 USA. EM zhangzi@ohsu.edu FU National Natural Science Foundation of China [30871022, 30570798]; National Institutes of Health [EY016788]; CDHNF/CCFA FX This study was supported by National Natural Science Foundation of China Grants 30871022 and 30570798 (Z.W.), National Institutes of Health Grants EY016788 (Z.Z.), and CDHNF/CCFA Young Investigator Award (Z.Z.). NR 61 TC 34 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2010 VL 50 IS 2 BP 132 EP 139 DI 10.1097/MPG.0b013e3181c61591 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 548UQ UT WOS:000273994000006 PM 20081544 ER PT J AU Vacanti, J AF Vacanti, Joseph TI Tissue engineering and regenerative medicine: from first principles to state of the art SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Congress of the British-Association-of-Paediatric-Surgeons CY JUN 18-20, 2009 CL Graz, AUSTRIA SP British Assoc Paediat Surg DE Tissue engineering; Regenerative medicine; Stem cells; Organ shortage ID TRANSPLANTATION; LIVER AB This lecture updates pediatric surgeons on the state of the science of tissue engineering and regenerative medicine. (C) 2010 Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vacanti, J (reprint author), Massachusetts Gen Hosp, Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org NR 13 TC 15 Z9 15 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 2010 VL 45 IS 2 BP 291 EP 294 DI 10.1016/j.jpedsurg.2009.10.063 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 553VC UT WOS:000274393900001 PM 20152338 ER PT J AU Newburg, DS Woo, JG Morrow, AL AF Newburg, David S. Woo, Jessica G. Morrow, Ardythe L. TI Characteristics and Potential Functions of Human Milk Adiponectin SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Conference on Emerging Roles Functioning Proteins in Pediatric Nutrition CY OCT 29-31, 2008 CL San Francisco, CA ID INSULIN-RESISTANCE; GROWTH-FACTOR; OBESITY; PROTEOLYSIS; PLASMA; GLYCOSYLATION; CHILDREN; DECREASE; NEWBORN; BINDING AB Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions. (J Pediatr 2010;156:S41-6). C1 [Newburg, David S.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Newburg, David S.] Harvard Univ, Sch Med, Boston, MA USA. [Woo, Jessica G.; Morrow, Ardythe L.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Woo, Jessica G.; Morrow, Ardythe L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM dnewburg@partners.org FU NICHD NIH HHS [HD013021, P01 HD013021, P01 HD013021-31A16535] NR 30 TC 31 Z9 37 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2010 VL 156 IS 2 SU 1 BP S41 EP S46 DI 10.1016/j.jpeds.2009.11.020 PG 6 WC Pediatrics SC Pediatrics GA 549LV UT WOS:000274051400009 PM 20105665 ER PT J AU Walker, A AF Walker, Allan TI Breast Milk as the Gold Standard for Protective Nutrients SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Conference on Emerging Roles Functioning Proteins in Pediatric Nutrition CY OCT 29-31, 2008 CL San Francisco, CA ID FED INFANTS; KAPPA-B; INFLAMMATION; MODULATION; EPITHELIUM; TOLERANCE; INTESTINE; MOTHERS; SYSTEM; GROWTH AB In this introductory overview, I explore the observation that breast milk is the gold standard for protective nutrients fed to newborn infants and present clinical evidence of its strong protective effect against age-related infectious gastroenteritis. The composition of breast milk changes according to the newborn infant's needs for passive protection. In addition, substances in breast milk can actively stimulate development of the newborn's host defenses to provide continued mucosal protection after breastfeeding is terminated. Later I present several specific examples of the development of intestinal host defenses due to breastfeeding. An important function of early breastfeeding is its anti-inflammatory effect on the immature, excessive inflammatory response in newborns. Several components of breast milk can reduce the inflammatory response to stimuli in the newborn intestine. These include transforming growth factor (TGF)-beta, interleukin (IL)-10, erythropoietin, and lactoferrin. These components of breast milk can act individually or in concert to contain the neonatal immature anti-inflammatory response. (J Pediatr 2010;156:S3-7). C1 [Walker, Allan] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA. [Walker, Allan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Walker, Allan] Massachusetts Gen Hosp Children, Charlestown, MA USA. RP Walker, A (reprint author), Massachusetts Gen Hosp, Muscosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM allan_walker@hms.harvard.edu FU NICHD NIH HHS [R01-HD12437]; NIDDK NIH HHS [P01-DK33560, P30-DK405610, R01-DK70260] NR 33 TC 129 Z9 135 U1 7 U2 43 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2010 VL 156 IS 2 SU 1 BP S3 EP S7 DI 10.1016/j.jpeds.2009.11.021 PG 5 WC Pediatrics SC Pediatrics GA 549LV UT WOS:000274051400002 PM 20105662 ER PT J AU Walker, WA AF Walker, W. Allan TI Mead Johnson Symposium: Functional Proteins in Human Milk: Role in Infant Health and Development INTRODUCTION SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Walker, W. Allan] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA. [Walker, W. Allan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Walker, W. Allan] Massachusetts Gen Hosp Children, Charlestown, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp East, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-14] NR 4 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2010 VL 156 IS 2 SU 1 BP S1 EP S2 DI 10.1016/j.jpeds.2009.11.013 PG 2 WC Pediatrics SC Pediatrics GA 549LV UT WOS:000274051400001 PM 20105658 ER PT J AU Goodman, M New, AS Triebwasser, J Collins, KA Siever, L AF Goodman, Marianne New, Antonia S. Triebwasser, Joseph Collins, Katherine A. Siever, Larry TI PHENOTYPE, ENDOPHENOTYPE, AND GENOTYPE COMPARISONS BETWEEN BORDERLINE PERSONALITY DISORDER AND MAJOR DEPRESSIVE DISORDER SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID SEROTONIN TRANSPORTER GENE; DEXAMETHASONE-SUPPRESSION TEST; POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; HIPPOCAMPAL VOLUME REDUCTION; PITUITARY-ADRENAL AXIS; II COMPARISON SUBJECTS; OXIDASE-A GENE; FOLLOW-UP; MONOAMINE-OXIDASE AB Borderline personality disorders (BPD) and major depressive disorder (MDD) are distinct disorders with overlapping biological processes pertaining to emotional regulatory functions. However, while both disorders share affective symptomatology, the disturbance central to BPD is affective lability and its character is entirely different from the affective disturbance of MDD. This review highlights data from the last ten years and compares the two disorders' phenotypes, putative endophenotypes and genotypes, focusing heavily on neuroimaging findings. The familiality and phenotypic differences suggest that BPD differs in important ways with respect to symptomatology, prognosis, and heritability. The neurobiological findings in both MDD and BPD are still preliminary at present, and no coherent model for either disorder can be said to have emerged. Overlapping biological processes including amygdala hyperreactivity, volume changes in subgenual anterior cingulate cortex, and deficient serotonergic function appear to underlie emotional dysregulation in both disorders. However, the disorders seem to differ in their patterns of brain region involvement, neurohormonal indices, and sleep architecture. At present, the minimal data available for putative genotypes of BPD is still emerging. nonspecific to the disorder and demonstrates significant overlap with MDD. The ability to discern commonalities and differences in the neurobiology of these two disorders is limited by the differing methodologies applied in different studies. Definitive clarification of what MDD and BPD have in common and in what ways they are distinct will only be derived from studies that examine both illnesses using the same study design and methodology. C1 [Goodman, Marianne; New, Antonia S.; Triebwasser, Joseph; Siever, Larry] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Collins, Katherine A.] Mt Sinai Sch Med, New York, NY USA. RP Goodman, M (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Marianne.goodman@va.gov NR 137 TC 24 Z9 26 U1 5 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FEB PY 2010 VL 24 IS 1 BP 38 EP 59 PG 22 WC Psychiatry SC Psychiatry GA 563XW UT WOS:000275173700005 PM 20205498 ER PT J AU Koenigsberg, HW AF Koenigsberg, Harold W. TI AFFECTIVE INSTABILITY: TOWARD AN INTEGRATION OF NEUROSCIENCE AND PSYCHOLOGICAL PERSPECTIVES SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID BORDERLINE-PERSONALITY-DISORDER; TEMPORAL-LOBE EPILEPSY; POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; BIPOLAR SPECTRUM DISORDERS; MANIC-DEPRESSIVE PARENT; ATYPICAL DEPRESSION; INTERICTAL BEHAVIOR; AFFECTIVE LABILITY; EMOTION PERCEPTION AB Affective instability is a prominent feature of a wide variety of psychiatric and neurological disorders, yet it has not been systematically studied. It encompasses a number of distinct phenomena, including: (1) frequent affective category shifts, (2) disturbances in affect intensity, (3) excessively rapid emotion rise-times, (4) delayed return to emotional baseline, (5) excessive reactivity to psychosocial cues, (6) endogenously driven, random, chaotic or rapid-cycling changes, and (7) overdramatic expression. To further clarify the construct of affective instability, this article examines the manifestations of affective instability in a range of psychiatric and neurologic disorders, reviews relevant neurobiological and psychological emotion regulatory processes, and considers the psychology of affective instability. C1 [Koenigsberg, Harold W.] James J Peters VA Med Ctr, MHPCC, Bronx, NY 10468 USA. [Koenigsberg, Harold W.] Mt Sinai Sch Med, New York, NY USA. RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, MHPCC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM harold.w.koenigsberg@gmail.com NR 114 TC 45 Z9 46 U1 6 U2 13 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FEB PY 2010 VL 24 IS 1 BP 60 EP 82 PG 23 WC Psychiatry SC Psychiatry GA 563XW UT WOS:000275173700006 PM 20205499 ER PT J AU Tarica, DY Alvarado, VM Truong, ST AF Tarica, Diane Yoshinobu Alvarado, Veronica M. Truong, Samantha T. TI SURVEY OF UNITED STATES DENTAL SCHOOLS ON CEMENTATION PROTOCOLS FOR IMPLANT CROWN RESTORATIONS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the Pacific-Coast-Society-of-Prosthodontics CY JUN 21, 2008 CL Kona, HI SP Pacific Coast Soc Prosthodont ID PROVISIONAL LUTING AGENTS; SUPPORTED CROWNS; RETENTION; ABUTMENT; SYSTEM; CASTINGS; FORCES AB Statement of problem. With conflicting results in the literature and various manufacturer recommendations, it is not known what cementation protocols are currently being used for implant restorations in US dental schools. Purpose. The purpose of this survey was to determine what dental cementation protocols are taught and recommended by 62 US dental schools and postgraduate programs. Material and methods. From February to September 2008, 96 questionnaires consisting of 8 questions were sent to the chairperson or director of restorative departments, advanced prosthodontics programs, and implant programs. The questionnaire asked recipients which implant manufacturers provided the products used at their dental schools. Additionally, recipients were queried as to the choice of material and techniques for abutment and restoration preparations prior to definitive cementation. Data were analyzed with descriptive statistics. Results. A total of 68 (71%) surveys were returned, and 52 (84%) of the 62 predoctoral and postgraduate programs were represented. After deleting duplicate responses, 31 surveys were returned from restorative department chairpersons, 29 from advanced prosthodontic program directors, and 2 from implant program directors. Frequency of responses to each question was tabulated, and results are presented in 3 sections. For all 3 types of programs, Nobel Biocare was reported to be the most widely used implant system, followed by Biomet 3i, Straumann, Astra Tech, and Zimmer Dental systems. The most commonly used technique prior to definitive cementation is to airborne-particle abrade the intaglio surface of the restoration. Resin-modified glass ionomer is the most frequently used luting agent for cementing implant restorations. The 5 most commonly used materials to fill screw access openings are cotton pellets, composite resin, rubber-based material, gutta-percha, and light-polymerized provisional composite resin. Most predoctoral and postgraduate programs teach students to fill the screw access opening completely to the occlusal surface. Conclusions. There area wide range of implant cementation protocols and materials used; however, some common trends were identified among predoctoral and postgraduate programs. (J Prosthet Dent 2010;103:68-79) C1 [Tarica, Diane Yoshinobu] Vet Adm Greater Los Angeles Healthcare Syst, Dent Dept 160, Los Angeles, CA 90073 USA. RP Tarica, DY (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Dent Dept 160, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dctarica@earthlink.net NR 25 TC 25 Z9 26 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD FEB PY 2010 VL 103 IS 2 BP 68 EP 79 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 572KD UT WOS:000275829700001 PM 20141811 ER PT J AU Jin, W AF Jin, Wei TI Age-related increase of beta(1)-adrenergic receptor gene expression in rat liver: a potential mechanism contributing to increased beta-adrenergic receptor density and responsiveness during aging SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article DE beta AR; receptor density; aging; gene expression; liver ID C-MYC TRANSCRIPT; ADENYLATE-CYCLASE; MOLECULAR-CLONING; CYCLIC-AMP; TISSUE; GLYCOGENOLYSIS; STATE; RNA AB In this study we examined whether the levels of gene expressions of the three beta-adrenergic receptor (PAR) subtypes, beta(1), beta(2), and beta(3), contribute to age-related increase in beta AR density. Liver membranes and total RNA were prepared from young (4- to 6-month-old) and old (24-month-old) male Fischer 344 rats. beta AR density (B-max) in liver membranes was measured by a radioligand receptor binding assay using the receptor subtype nonselective beta AR antagonist I-125-pindolol as the radioligand. Steady-state levels of beta(2)AR mRNA in rat liver were measured by Northern blot analysis; because of the low abundance of beta(1)AR and beta(3)AR mRNA in rat liver, the expressions of these genes were measured by a semiquantitative RT-PCR or an RT-PCR. Scatchard analysis of saturation binding curves of the binding assay confirmed an age-related increase in B-max (young: 7.1 +/- 0.8 fmol/mg protein vs. old: 18.1 +/- 4.3 fmol/mg protein). No age-related differences were found in the levels of beta(2)AR mRNA. However, semiquantitative RT-PCR revealed an approximately twofold increase in beta(1)AR mRNA level between young and old rats (P < 0.05). beta(1)AR mRNA levels were also correlated with B-max for I-125-pindolol binding sites in individual rats (r = 0.67; P = 0.012). beta(3)AR mRNA, which was demonstrable in rat white adipose tissue by RT-PCR, was generally not detected in livers from young or old rats, with the exception of two old rats with the highest B-max. These results suggest that an age-related increase of beta(1)AR gene expression contributes to increased beta AR density and beta adrenergic responsiveness in rat liver during aging. C1 [Jin, Wei] Univ Texas Hlth Sci Ctr San Antonio, GRECC, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78229 USA. [Jin, Wei] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. RP Jin, W (reprint author), 2451-200-13-301 Zhong Shan Bei Rd, Shanghai 200063, Peoples R China. EM mazwang@fudan.edu.cn NR 23 TC 5 Z9 5 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PD FEB PY 2010 VL 30 IS 1 BP 24 EP 30 DI 10.3109/10799890903358206 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 572WG UT WOS:000275864200003 PM 19883205 ER PT J AU Dhikav, V Karmarkar, G Gupta, R Verma, M Gupta, R Gupta, S Anand, KS AF Dhikav, Vikas Karmarkar, Girish Gupta, Richa Verma, Myank Gupta, Ruchi Gupta, Supriya Anand, Kuljeet S. TI Yoga in Female Sexual Functions SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Yoga; Female Sexual Functions; Female Sexual Function Index; Female Sexual Dysfunctions; Female Sexuality ID POSTMENOPAUSAL WOMEN; DESIRE DISORDER; ALTERNATIVE THERAPIES; CLINICAL-APPLICATIONS; AROUSAL DISORDER; DYSFUNCTION; TESTOSTERONE; COMPLEMENTARY; INTERVENTION; MINDFULNESS AB Introduction. Yoga is a popular form of complementary and alternative therapy. It is practiced both in developing and developed countries. Female sexual dysfunctions are common and do not always get adequate clinical attention. Pharmacotherapies for treating female sexual dysfunctions are available but suffer from drawbacks such as poor compliance, low efficacy, and side effects. Many patients and yoga protagonists claim that it is useful in improving sexual functions and treating sexual disorders. Aim. To establish the effect yoga can have on female sexual functions. Methods. We recruited 40 females (age range 22-55 years, average age 34.7 +/- 8.49 years) who were enrolled in a yoga camp and were given a standardized questionnaire named Female Sexual Function Index (FSFI) before and after the 12 weeks session of yoga. Main Outcome Measures. FSFI scores. Results. It was found that after the completion of yoga sessions; the sexual functions scores were significantly improved (P < 0.0001). The improvement occurred in all six domains of FSFI (i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain). The improvement was more in older women (age > 45 years) compared with younger women (age < 45 years). Conclusions. Yoga appears to be an effective method of improving all domains of sexual functions in women as studied by FSFI. Dhikav V, Karmarkar G, Gupta R, Verma M, Gupta R, Gupta S, and Anand KS. Yoga in female sexual functions. J Sex Med 2010;7:964-970. C1 [Dhikav, Vikas; Anand, Kuljeet S.] GGS IP Univ, Dept Neurol, Dr Ram Manohar Lohia Hosp, New Delhi, India. [Karmarkar, Girish] DY Patil Med Coll, Bombay, Maharashtra, India. [Gupta, Ruchi] Postgrad Inst Med Sci, Rohtak, Haryana, India. [Gupta, Richa; Verma, Myank] Krishna Hosp, Gaziabad, UP, India. [Gupta, Supriya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Dhikav, V (reprint author), GGS IP Univ, Dept Neurol, Dr RML Hosp & PGIMER, E-3,Flat Number 280,Sector 18, Delhi 110085, Rohini, India. EM vikasdhikav@hotmail.com NR 45 TC 9 Z9 9 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD FEB PY 2010 VL 7 IS 2 BP 964 EP 970 DI 10.1111/j.1743-6109.2009.01580.x PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 551FH UT WOS:000274191700012 PM 19912493 ER PT J AU Rice, I Gagnon, D Gallagher, J Boninger, M AF Rice, Ian Gagnon, Dany Gallagher, Jere Boninger, Michael TI Hand Rim Wheelchair Propulsion Training Using Biomechanical Real-Time Visual Feedback Based on Motor Learning Theory Principles SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Wheelchair; Smart Wheel; Prevention; Motor skills; Rehabilitation; Paraplegia; Tetraplegia; Task performance and analysis; Upper extremity injuries; Carpal tunnel syndrome; Rotator cuff tendinopathy; Shoulder pain ID SPINAL-CORD-INJURY; BEARING UPPER EXTREMITY; CARPAL-TUNNEL SYNDROME; LONG-TERM PARAPLEGIA; MECHANICAL EFFICIENCY; CONTEXTUAL INTERFERENCE; PUSHRIM BIOMECHANICS; EXTERNAL-FOCUS; NERVE FUNCTION; SHOULDER PAIN AB Background/Objective: As considerable progress has been made in laboratory-based assessment of manual wheelchair propulsion biomechanics, the necessity to translate this knowledge into new clinical tools and treatment programs becomes imperative. The objective of this study was to describe the development of a manual wheelchair propulsion training program aimed to promote the development of an efficient propulsion technique among long-term manual wheelchair users. Methods: Motor learning theory principles were applied to the design of biomechanical feedback-based learning software, which allows for random discontinuous real-time visual presentation of key spatio-temporal and kinetic parameters. This software was used to train a long-term wheelchair user on a dynamometer during 3 low-intensity wheelchair propulsion training sessions over a 3-week period. Biomechanical measures were recorded with a Smart Wheel during over ground propulsion on a 50-m level tile surface at baseline and 3 months after baseline. Results: Training software was refined and administered to a participant who was able to improve his propulsion technique by increasing contact angle while simultaneously reducing stroke cadence, mean resultant force, peak and mean moment out of plane, and peak rate of rise of force applied to the pushrim after training. Conclusions: The proposed propulsion training protocol may lead to favorable changes in manual wheelchair propulsion technique. These changes could limit or prevent upper limb injuries among manual wheelchair users. In addition, many of the motor learning theory based techniques examined in this study could be applied to training individuals in various stages of rehabilitation to optimize propulsion early on. C1 [Rice, Ian; Gallagher, Jere; Boninger, Michael] Univ Pittsburgh, Pittsburgh, PA USA. [Gagnon, Dany] Univ Montreal, Ecole Readaptat, Montreal, PQ, Canada. RP Boninger, M (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R 1, 7180 Highland Dr,Bldg 4,2nd Floor E,151R-1, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 52 TC 14 Z9 14 U1 1 U2 7 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD FEB PY 2010 VL 33 IS 1 BP 33 EP 42 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 586IP UT WOS:000276900700006 PM 20397442 ER PT J AU Kolman, OK Spinelli, HM Magro, CM AF Kolman, Olga K. Spinelli, Henry M. Magro, Cynthia M. TI Juvenile temporal arteritis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE angiolymphoid hyperplasia with eosinophilia; juvenile temporal arteritis; Kimura disease; temporal arteritis ID T-CELL LYMPHOMA; OF-THE-LITERATURE; ANGIOLYMPHOID HYPERPLASIA; KIMURAS-DISEASE; NEPHROTIC SYNDROME; EPITHELIOID HEMANGIOMA; POLYMYALGIA-RHEUMATICA; RADIAL ARTERY; EOSINOPHILIA; CLONALITY AB Juvenile temporal arteritis (JTA) is a nongranulomatous inflammation of the temporal artery with fragmentation of the internal elastic lamina and no concurrent systemic manifestations. It is a rare clinicopathologic entity with fewer than 20 reported cases, most of which represent localized disease with no recurrence or systemic symptoms at follow-up of Lip to 2 years. Histopathologic features can include lymphoeosinophilic infiltrate and endothelial proliferation. As the histology may resemble angiolymphoid hyperplasia with eosinophilia or Kimura disease, whether JTA is a discrete localized disease or a manifestation of these systemic conditions has been debated. We present a case of a 36-year-old Jamaican woman with a painful forehead nodule that showed histologic features of JTA, including intimal hyperplasia, lymphoeosinophilic inflammation of the vessel wall, and disruption of the internal elastic lamina; distinctive signet ringlike cytomorphologic alterations of the endothelial cells were noted as well. The lesion also showed extensive subcutaneous lymphoeosinophilic infiltrates and neovascularization with extension into the underlying muscle consistent with angiolymphoid hyperplasia with eosinophilia oil Kimura disease, As the connection between JTA and angiolymphoid hyperplasia with eosinophilia and Kimura disease is currently debated and most reported cases of JTA have had only brief follow-up, the long-term sequelae of JTA are not known and careful patient monitoring may be necessary. (J Am Acad Dermatol 2010;62:308-14.) C1 [Magro, Cynthia M.] Cornell Univ, Weill Med Coll, Div Dermatopathol, Dept Pathol & Lab Med, New York, NY 10065 USA. [Kolman, Olga K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Spinelli, Henry M.] Cornell Univ, Weill Med Coll, Div Plast Surg, Dept Pathol & Lab Med, New York, NY 10065 USA. RP Magro, CM (reprint author), Cornell Univ, Weill Med Coll, Div Dermatol, Dept Pathol & Lab Med, 1300 York Ave,F-309, New York, NY 10065 USA. EM cym2003@med.cornell.edu NR 40 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2010 VL 62 IS 2 BP 308 EP 314 DI 10.1016/j.jaad.2009.04.013 PG 7 WC Dermatology SC Dermatology GA 558RM UT WOS:000274762900017 PM 19748701 ER PT J AU Thrall, JH AF Thrall, James H. TI Medical Value vs Cost and Risk: Redux SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,Room 216, Boston, MA 02114 USA. EM jthrall@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2010 VL 7 IS 2 BP 81 EP 82 DI 10.1016/j.jacr.2009.12.014 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SL UT WOS:000208362400001 PM 20142076 ER PT J AU Gunderman, RB Patti, JA Lexa, F Weinreb, J Hillman, BJ Thrall, JH Neiman, H AF Gunderman, Richard B. Patti, John A. Lexa, Frank Weinreb, Jeffrey Hillman, Bruce J. Thrall, James H. Neiman, Harvey TI The 2009 ACR Forum: Health Care Payment Models SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Health care; health policy; health care payment; radiology; radiologists AB The 2009 ACR Forum addressed health care payment models, the strengths and weaknesses of different models under consideration, their implications for radiology, and the role radiologists should play in the debate. C1 [Gunderman, Richard B.] Indiana Univ Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. [Patti, John A.] Commonwealth Radiol Associates, Brockton, MA USA. [Lexa, Frank] Univ Penn, Wharton Sch, Wynnewood, PA USA. [Weinreb, Jeffrey] Yale Univ, Sch Med, New Haven, CT USA. [Hillman, Bruce J.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Thrall, James H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neiman, Harvey] Amer Coll Radiol, Reston, VA USA. RP Gunderman, RB (reprint author), Indiana Univ Sch Med, Dept Radiol, 702 Barnhill Dr,Room 1053, Indianapolis, IN 46202 USA. EM rbgunder@iupui.edu NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD FEB PY 2010 VL 7 IS 2 BP 103 EP 108 DI 10.1016/j.jacr.2009.09.027 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SL UT WOS:000208362400008 PM 20142083 ER PT J AU Hamilton, BH Ko, CY Richards, K Hall, BL AF Hamilton, Barton H. Ko, Clifford Y. Richards, Karen Hall, Bruce Lee TI Missing Data in the American College of Surgeons National Surgical Quality Improvement Program Are Not Missing at Random: Implications and Potential Impact on Quality Assessments SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID VETERANS-AFFAIRS; PATIENT SAFETY; RISK-ADJUSTMENT; NONCARDIAC SURGERY; MORTALITY; CARE; HOSPITALS; PERFORMANCE; MORBIDITY; CANCER AB BACKGROUND: Studying risk-adjusted outcomes in health care relies on statistical approaches to handling missing data. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) provides risk-adjusted assessments of surgical programs, traditionally imputing certain missing data points using a single round of multivariable imputation. Such imputation assumes that data are missing at random-without systematic bias-and does not incorporate estimation uncertainty. Alternative approaches, including using multiple imputation to incorporate uncertainty or using an indicator of missingness, can enhance robustness of evaluations. STUDY DESIGN: One year of de-identified data from the ACS NSQIP, representing 117 institutions and 106,113 patients, was analyzed. Using albumin variables as the missing data modeled, several imputation/adjustment models were compared, including the traditional NSQIP imputation, a new single imputation, a multiple imputation, and use of a missing indicator. RESULTS: Coefficients for albumin values changed under new single imputation and multiple imputation approaches. Multiple imputation resulted in increased standard errors, as expected. An indicator of missingness was highly explanatory, disproving the missing-at-random assumption. The effects of changes in approach differed for different outcomes, such as mortality and morbidity, and effects were greatest in smaller datasets. However, ultimate changes in patient risk assessment and institutional assessment were minimal. CONCLUSIONS: Newer statistical approaches to modeling missing (albumin) values result in noticeable statistical distinctions, including improved incorporation of imputation uncertainty. In addition, the missing-at-random assumption is incorrect for albumin. Despite these findings, effects on institutional assessments are small. Although effects can be most important with smaller datasets, the current approach to imputing missing values in the ACS NSQIP appears reasonably robust. (J Am Coll Surg 2010;210:125-139. Published by Elsevier Inc. on behalf of the American College of Surgeons) C1 [Hall, Bruce Lee] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA. [Hamilton, Barton H.; Hall, Bruce Lee] Washington Univ, John M Olin Sch Business, St Louis, MO 63110 USA. [Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO 63110 USA. [Ko, Clifford Y.; Richards, Karen] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA. RP Hall, BL (reprint author), Washington Univ, Dept Surg, Sch Med, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM HallB@WUStL.edu RI Hamilton, Barton/P-5187-2015 FU Center for Health Policy; Center for Health Policy, under Washington University in St Louis, St Louis, MO FX Dr Hall was supported by the Center for Health Policy, under the direction of Dr William Peck, Washington University in St Louis, St Louis, MO. We thank Patrick Hosokawa, from the Colorado Health Outcomes program at the University of Colorado (Denver), for his assistance with supplemental information on missing variables within NSQIP. We also thank Dr Shukri Khuri and his staff, Dr William Henderson and his staff, all of the principals of the VA NSQIP and ACS NSQIP (Patient Safety in Surgery), and the staff of QCMetrix, Inc, for their critical roles in the conduct of the VA and ACS NSQIP and Patient Safety in Surgery programs. NR 38 TC 41 Z9 41 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2010 VL 210 IS 2 BP 125 EP 139 DI 10.1016/j.jamcollsurg.2009.10.021 PG 15 WC Surgery SC Surgery GA 617KP UT WOS:000279279900001 PM 20113932 ER PT J AU Ingraham, AM Cohen, ME Bilimoria, KY Feinglass, JM Richards, KE Hall, BL Ko, CY AF Ingraham, Angela M. Cohen, Mark E. Bilimoria, Karl Y. Feinglass, Joseph M. Richards, Karen E. Hall, Bruce Lee Ko, Clifford Y. TI Comparison of Hospital Performance in Nonemergency Versus Emergency Colorectal Operations at 142 Hospitals SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg ID QUALITY IMPROVEMENT PROGRAM; SEGMENTAL COLON RESECTION; ACUTE-CARE SURGERY; CARDIAC-SURGERY; THORACIC-SURGEONS; VETERANS-AFFAIRS; SURGICAL CARE; DECADES EXPERIENCE; PATIENT OUTCOMES; ADVERSE OUTCOMES AB BACKGROUND: Quality improvement efforts have demonstrated considerable hospital-to-hospital variation in surgical outcomes. However, information about the quality of emergency surgical care is lacking. The objective of this study was to assess whether hospitals have comparable outcomes for emergency and nonemergency operations. STUDY DESIGN: Patients undergoing colorectal resections were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) 2005 to 2007 dataset. Logistic regression models for 30-day morbidity and mortality after emergency and nonemergency colorectal resections were constructed. Hospital risk-adjusted outcomes as measured by observed to expected (O/E) ratios, outlier status, and rank-order differences were compared. RESULTS: Of 25,710 nonemergency colorectal resections performed at 142 ACS NSQIP hospitals, 6,138 (23.9%) patients experienced at least 1 complication, and 492 (1.9%) patients died. There were 5,083 emergency colorectal resections; 2,442 (48%) patients experienced at least 1 complication, and 780 (15.3%) patients died. Outcomes for nonemergency versus emergency operations were weakly correlated for morbidity and mortality (Pearson correlation coefficient: 0.28 versus 0.13). Median differences in hospital rankings based on O/E ratios between nonemergency and emergency performance were 30.5 ranks (interquartile range [IQR] 13 to 59) for morbidity and 34 ranks (interquartile ratio 17 to 61) for mortality. CONCLUSIONS: Hospitals with favorable outcomes after nonemergency colorectal resections do not necessarily have similar outcomes for emergency operations. Hospitals should specifically examine their performance on emergency surgical procedures to identify quality improvement opportunities and focus quality improvement efforts appropriately. (J Am Coll Surg 2010;210:155-165. (C) 2010 by the American College Of Surgeons) C1 [Ingraham, Angela M.; Cohen, Mark E.; Richards, Karen E.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Feinglass, Joseph M.] Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 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] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Ingraham, AM (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,Floor 22NE, Chicago, IL 60611 USA. NR 29 TC 52 Z9 52 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2010 VL 210 IS 2 BP 155 EP 165 DI 10.1016/j.jamcollsurg.2009.10.016 PG 11 WC Surgery SC Surgery GA 617KP UT WOS:000279279900004 PM 20113935 ER PT J AU Lin, JC Karno, MP Barry, KL Blow, FC Davis, JW Tang, LQ Moore, AA AF Lin, James C. Karno, Mitchell P. Barry, Kristen L. Blow, Frederic C. Davis, James W. Tang, Lingqi Moore, Alison A. TI Determinants of Early Reductions in Drinking in Older At-Risk Drinkers Participating in the Intervention Arm of a Trial to Reduce At-Risk Drinking in Primary Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE alcohol; physician advice; at-risk drinking ID ALCOHOL TREATMENT TRIAL; FOLLOW-UP INTERVIEWS; AGED 75; READINESS; CONSUMPTION; COMMUNITY; PEOPLE; ADULTS; MOTIVATION; BEHAVIORS AB OBJECTIVES: To describe differences between older at-risk drinkers, as determined using the Comorbidity Alcohol Risk Evaluation Tool, who reduced drinking and those who did not after an initial intervention and to determine factors associated with early reductions in drinking. DESIGN: Secondary analyses of data from a randomized controlled trial. SETTING: Seven primary care sites. PARTICIPANTS: Subjects randomized to the intervention group who completed the first health educator call approximately 2 weeks after enrollment (n = 239). INTERVENTION: Personalized risk reports, booklets on alcohol-associated risks, and advice from physicians, followed by a health educator call. MEASURMENTS: Reductions in number of alcoholic drinks. RESULTS: Thirty-nine percent of the sample had reduced drinking within 2 weeks of receiving the initial intervention. According to the final multiple logistic regression model, those who were concerned about alcohol-related risks (odds ratio (OR) = 2.03, 95% confidence interval (CI) = 1.01-4.07), read through the educational booklet (OR = 2.97, 95% CI = 1.48-5.95), or perceived that their physicians discussed risks and advised changing drinking behaviors (OR = 4.1, 95% CI = 2.02-8.32) had greater odds of reducing drinking by the first health educator call. CONCLUSION: Concern about risks, reading educational material, and perception of physicians providing advice to reduce drinking were associated with early reductions in alcohol use in older at-risk drinkers. Understanding these factors will enable development of better intervention strategies to reduce unhealthy alcohol use. J Am Geriatr Soc 58:227-233, 2010. C1 [Lin, James C.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lin, James C.] Cheng Ching Hosp, Dept Med, Taichung, Taiwan. [Karno, Mitchell P.; Moore, Alison A.] Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA USA. [Davis, James W.; Moore, Alison A.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Tang, Lingqi] Univ Calif Los Angeles, Hlth Serv Res Ctr, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Barry, Kristen L.; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Lin, JC (reprint author), 11301 Wilshire Ave,Bldg 220,Room 302, Los Angeles, CA 90073 USA. EM jlin1207@ucla.edu FU Veterans Affairs Greater Los Angeles Healthcare System; National Institutes of Health, National Institute on Alcoholism and Alcohol Abuse [AA013937, AA15957] FX The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.Special Fellowship in Advanced Geriatrics, Veterans Affairs Greater Los Angeles Healthcare System and National Institutes of Health, National Institute on Alcoholism and Alcohol Abuse (AA013937 and AA15957). NR 31 TC 8 Z9 8 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 FEB PY 2010 VL 58 IS 2 BP 227 EP 233 DI 10.1111/j.1532-5415.2009.02676.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 551CQ UT WOS:000274183800002 PM 20070414 ER PT J AU Griffith, HR Stewart, CC Stoeckel, LE Okonkwo, OC den Hollander, JA Martin, RC Belue, K Copeland, JN Harrell, LE Brockington, JC Clark, DG Marson, DC AF Griffith, H. Randall Stewart, Christopher C. Stoeckel, Luke E. Okonkwo, Ozioma C. den Hollander, Jan A. Martin, Roy C. Belue, Katherine Copeland, Jacquelynn N. Harrell, Lindy E. Brockington, John C. Clark, David G. Marson, Daniel C. TI Magnetic Resonance Imaging Volume of the Angular Gyri Predicts Financial Skill Deficits in People with Amnestic Mild Cognitive Impairment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE magnetic resonance imaging; mild cognitive impairment; financial capacity; angular gyrus; hippocampus; precuneus ID ALZHEIMERS-DISEASE; DEFAULT NETWORK; CLINICAL STATUS; DEMENTIA; BRAIN; HIPPOCAMPAL; ABILITIES; MRI; DYSCALCULIA; PERFORMANCE AB OBJECTIVES: To better understand how brain atrophy in amnestic mild cognitive impairment (MCI) as measured using magnetic resonance imaging (MRI) volumetrics could affect instrumental activities of daily living (IADLs) such as financial abilities. DESIGN: Controlled, matched-sample, cross-sectional analysis regressing MRI volumetrics with financial performance measures. SETTING: University medical and research center. PARTICIPANTS: Thirty-eight people with MCI and 28 older adult controls. MEASUREMENTS: MRI volumetric measurement of the hippocampi, angular gyri, precunei, and medial frontal lobes. Participants also completed neuropsychological tests and the Financial Capacity Instrument (FCI). RESULTS: Correlations were performed between FCI scores and MRI volumes in the group with MCI. People with MCI performed significantly below controls on the FCI and had significantly smaller hippocampi. Among people with MCI, performance on the FCI was moderately correlated with angular gyri and precunei volumes. Regression models demonstrated that angular gyrus volumes were predictive of FCI scores. Tests of mediation showed that measures of arithmetic and possibly attention partially mediated the relationship between angular gyrus volume and FCI score. CONCLUSION: Impaired financial abilities in amnestic MCI correspond with volume of the angular gyri as mediated by arithmetic knowledge. The findings suggest that early neuropathology within the lateral parietal region in MCI leads to a breakdown of cognitive abilities that affect everyday financial skills. The findings have implications for diagnosis and clinical care of people with MCI and AD. J Am Geriatr Soc 58:265-274, 2010. C1 [Griffith, H. Randall; Martin, Roy C.; Belue, Katherine; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Copeland, Jacquelynn N.] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [den Hollander, Jan A.] Univ Alabama, Dept Cardiol, Birmingham, AL 35294 USA. [Griffith, H. Randall; Stewart, Christopher C.; Stoeckel, Luke E.; den Hollander, Jan A.; Martin, Roy C.; Belue, Katherine; Harrell, Lindy E.; Brockington, John C.; Clark, David G.; Marson, Daniel C.] Univ Alabama, Alzheimers Dis Res Ctr, Birmingham, AL 35294 USA. [Stoeckel, Luke E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoeckel, Luke E.] Harvard Univ, Sch Med, Boston, MA USA. [Okonkwo, Ozioma C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Harrell, Lindy E.; Clark, David G.] Birmingham Reg Vet Affairs Med Ctr, Birmingham, AL USA. RP Griffith, HR (reprint author), ABPP CN, SC 650,1530 3rd Ave S, Birmingham, AL 35294 USA. EM rlgriffith@uabmc.edu FU National Institute on Aging [ADRC-1P50 AG16582-10, 1R01 AG021927-05]; Alzheimer's of Central Alabama FX This study was funded by grants from the National Institute on Aging (ADRC-1P50 AG16582-10, Marson, PI; 1R01 AG021927-05, Marson, PI) and Alzheimer's of Central Alabama (Griffith, PI). NR 61 TC 19 Z9 20 U1 1 U2 5 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 FEB PY 2010 VL 58 IS 2 BP 265 EP 274 DI 10.1111/j.1532-5415.2009.02679.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 551CQ UT WOS:000274183800007 PM 20374402 ER PT J AU Yaffe, K Ackerson, L Tamura, MK Le Blanc, P Kusek, JW Sehgal, AR Cohen, D Anderson, C Appel, L DeSalvo, K Ojo, A Seliger, S Robinson, N Makos, G Go, AS AF Yaffe, Kristine Ackerson, Lynn Tamura, Manjula Kurella Le Blanc, Patti Kusek, John W. Sehgal, Ashwini R. Cohen, Debbie Anderson, Cheryl Appel, Lawrence DeSalvo, Karen Ojo, Akinlolu Seliger, Stephen Robinson, Nancy Makos, Gail Go, Alan S. CA Chronic Renal Insufficiency Cohort TI Chronic Kidney Disease and Cognitive Function in Older Adults: Findings from the Chronic Renal Insufficiency Cohort Cognitive Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE chronic kidney disease; cognitive impairment; cognitive function ID CYSTATIN-C; ALZHEIMERS-DISEASE; CARDIOVASCULAR HEALTH; DEMENTIA; IMPAIRMENT; MEMORY; STROKE; WOMEN; RISK; PERFORMANCE AB OBJECTIVES: To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors. DESIGN: Cross-sectional. SETTING: Chronic Renal Insufficiency Cohort Study. PARTICIPANTS: Eight hundred twenty-five adults aged 55 and older with CKD. MEASUREMENTS: Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score <= 1 standard deviations from the mean). RESULTS: Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P < .05). In addition, participants with advanced CKD (eGFR < 30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI = 1.1-3.9), naming (AOR = 1.9, 95% CI = 1.0-3.3), attention (AOR = 2.4, 95% CI = 1.3-4.5), executive function (AOR = 2.5, 95% CI = 1.9-4.4), and delayed memory (AOR = 1.5, 95% CI = 0.9-2.6) but not on category fluency (AOR = 1.1, 95% CI = 0.6-2.0) than those with mild to moderate CKD (eGFR 45-59). CONCLUSION: In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment. J Am Geriatr Soc 58:338-345,2010. C1 [Yaffe, Kristine; Le Blanc, Patti] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ackerson, Lynn; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Tamura, Manjula Kurella] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Sehgal, Ashwini R.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Sehgal, Ashwini R.] Case Western Reserve Univ, Dept Biomed Eth, Cleveland, OH 44106 USA. [Sehgal, Ashwini R.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Cohen, Debbie; Robinson, Nancy] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Anderson, Cheryl; Appel, Lawrence] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Appel, Lawrence] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Appel, Lawrence] Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD USA. [DeSalvo, Karen] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Ojo, Akinlolu] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Ojo, Akinlolu] Univ Michigan, Sch Med, Div Nephrol, Ann Arbor, MI USA. [Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Makos, Gail] St Clair Specialty Phys PC, Chron Kidney Dis Clin, Detroit, MI USA. RP Yaffe, K (reprint author), 4150 Clement St,VAMC 181, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Health [U01-DK060990, U01 DK60980, U01 DK 60902, U01 DK61021, U01 DK60984, R01 DK069406]; [K24 AG 031155] FX This study was funded by National Institute of Health Grants U01-DK060990, U01 DK60980, U01 DK 60902, U01 DK61021, U01 DK60984, and R01 DK069406 (CRIC COG). Dr. Yaffe is also supported in part by K24 AG 031155 and an anonymous foundation. NR 35 TC 100 Z9 110 U1 2 U2 13 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 FEB PY 2010 VL 58 IS 2 BP 338 EP 345 DI 10.1111/j.1532-5415.2009.02670.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 551CQ UT WOS:000274183800017 PM 20374407 ER PT J AU Kottgen, A Hwang, SJ Larson, MG Van Eyk, JE Fu, Q Benjamin, EJ Dehghan, A Glazer, NL Kao, WHL Harris, TB Gudnason, V Shlipak, MG Yang, Q Coresh, J Levy, D Fox, CS AF Koettgen, Anna Hwang, Shih-Jen Larson, Martin G. Van Eyk, Jennifer E. Fu, Qin Benjamin, Emelia J. Dehghan, Abbas Glazer, Nicole L. Kao, W. H. Linda Harris, Tamara B. Gudnason, Vilmundur Shlipak, Michael G. Yang, Qiong Coresh, Josef Levy, Daniel Fox, Caroline S. TI Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; TAMM-HORSFALL GLYCOPROTEIN; JUVENILE HYPERURICAEMIC NEPHROPATHY; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; SERUM CREATININE; MUTATIONS; URINARY; PROTEIN; GENE AB Common variants in the region of the UMOD gene, which encodes uromodulin (Tamm-Horsfall protein), associate with chronic kidney disease (CKD) and estimated GFR (eGFR). Whether uromodulin levels associate with UMOD variants or with the risk for developing CKD is unknown. We conducted an age- and gender-matched case-control study (n = 200) of incident CKD (eGFR <60 ml/min per 1.73 m(2)) within the Framingham Heart Study (FHS). Baseline urinary uromodulin concentrations were related to case-control status 9.9 yr later and to genotype at rs4293393. As a replication set, we tested the genotype association with uromodulin concentration in the Atherosclerosis Risk in Communities (ARIC) Study (n = 42). Geometric means of uromodulin concentrations were 51% higher in case than in control subjects (P = 0.016). The adjusted odds ratio of CKD per 1-SD higher concentration of uromodulin was 1.72 (95% confidence interval 1.07 to 2.77; P = 0.03) after accounting for CKD risk factors and baseline eGFR. We observed lower urinary uromodulin concentrations per each copy of the C allele at rs4293393 in both cohorts. In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region. C1 [Koettgen, Anna; Kao, W. H. Linda; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hwang, Shih-Jen; Benjamin, Emelia J.; Levy, Daniel; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Larson, Martin G.; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Van Eyk, Jennifer E.; Fu, Qin] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Dehghan, Abbas] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Kottgen, Anna/D-2920-2012; Yang, Qiong/G-5438-2014; Gudnason, Vilmundur/K-6885-2015; OI Gudnason, Vilmundur/0000-0001-5696-0084; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336; Dehghan, Abbas/0000-0001-6403-016X FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Center for Population Studies; National Heart, Lung, and Blood Institute [N01-HC-55020, R01-DK076770-01, R01-HL087652, 5UL1 RR025005-3, 1U54RR023561-01A1]; NIH [N01-HV-28180, AG028321] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195), the Center for Population Studies, National Heart, Lung, and Blood Institute intramural program, N01-HC-55020, R01-DK076770-01, R01-HL087652, 5UL1 RR025005-3, 1U54RR023561-01A1 , NIH N01-HV-28180, AG028321, and HL092577-01A1 NR 30 TC 64 Z9 68 U1 0 U2 4 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 FEB PY 2010 VL 21 IS 2 BP 337 EP 344 DI 10.1681/ASN.2009070725 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 557PG UT WOS:000274680900019 PM 19959715 ER PT J AU Ayus, JC Achinger, SG Lee, S Sayegh, MH Go, AS AF Ayus, Juan Carlos Achinger, Steven G. Lee, Shuko Sayegh, Mohamed H. Go, Alan S. TI Transplant Nephrectomy Improves Survival following a Failed Renal Allograft SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID C-REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; FAILURE; MORTALITY; ERYTHROPOIETIN; MANAGEMENT; GRAFTS; IMPACT AB There is a growing number of patients returning to dialysis after a failed kidney transplant, and there is increasing evidence of higher mortality among this population. Whether removal of the failed renal allograft affects survival while receiving long-term dialysis is not well understood. We identified all adults who received a kidney transplant and returned to long-term dialysis after renal allograft failure between January 1994 and December 2004 from the US Renal Data System. Among 10,951 transplant recipients who returned to long-term dialysis, 3451 (31.5%) received an allograft nephrectomy during follow-up. Overall, 34.6% of these patients died during follow-up. Receiving an allograft nephrectomy associated with a 32% lower adjusted relative risk for all-cause death (adjusted hazard ratio 0.68; 95% confidence interval 0.63 to 0.74) after adjustment for sociodemographic characteristics, comorbidity burden, donor characteristics, interim clinical conditions associated with receiving allograft nephrectomy, and propensity to receive an allograft nephrectomy. In conclusion, within a large, nationally representative sample of high-risk patients returning to long-term dialysis after failed kidney transplant, receipt of allograft nephrectomy independently associated with improved survival. C1 [Ayus, Juan Carlos] Renal Consultants Houston, Dept Clin Res, Houston, TX USA. [Achinger, Steven G.] Phys Clin Res, San Antonio, TX USA. [Lee, Shuko] Vet Adm Hosp, San Antonio, TX USA. [Sayegh, Mohamed H.] Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. [Sayegh, Mohamed H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Ayus, JC (reprint author), Renal Consultants Houston, Dept Clin Res, 2412 Westgate St, Houston, TX USA. EM carlosayus@yahoo.com FU National Institutes of Health (NIH) [U01 DK066481, U01 DK60902, R01 DK067126, R01 DK58411] FX J.C.A. was Supported by National Institutes of Health (NIH) grant U01 DK066481, and S.G.A. was Supported by an NIH T32 Training Grant. A.S.G. has received research support from NIH grants U01 DK60902, R01 DK067126, and R01 DK58411. NR 26 TC 61 Z9 64 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2010 VL 21 IS 2 BP 374 EP 380 DI 10.1681/ASN.2009050480 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 557PG UT WOS:000274680900023 PM 19875809 ER PT J AU Saylor, PJ Smith, MR AF Saylor, Philip J. Smith, Matthew R. TI Adverse Effects of Androgen Deprivation Therapy: Defining the Problem and Promoting Health Among Men with Prostate Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Prostate cancer; survivorship; GnRH agonists; osteoporosis; diabetes; obesity; coronary heart disease ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; LEAN BODY-MASS; FRACTURE RISK; CARDIOVASCULAR MORTALITY; POSTMENOPAUSAL WOMEN; HORMONE AGONISTS; RADICAL PROSTATECTOMY AB Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population. (JNCCN 2010;8:211-223) C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Lawrence House,POB 2nd Floor,55 Fruit St, Boston, MA 02114 USA. EM psaylor@partners.org FU NCI NIH HHS [K24 CA121990-04, K24 CA121990, K24 CA121990-03] NR 94 TC 45 Z9 46 U1 0 U2 3 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 FEB PY 2010 VL 8 IS 2 BP 211 EP 223 PG 13 WC Oncology SC Oncology GA 555UO UT WOS:000274541700006 PM 20141678 ER PT J AU Richardson, PG Laubach, JP Schlossman, RL Mitsiades, C Anderson, K AF Richardson, Paul G. Laubach, Jacob P. Schlossman, Robert L. Mitsiades, Constantine Anderson, Kenneth TI Complications of Multiple Myeloma Therapy, Part 1: Risk Reduction and Management of Peripheral Neuropathy and Asthenia SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Fatigue; neurotoxicity; thalidomide; bortezomib ID CANCER-RELATED FATIGUE; LENALIDOMIDE PLUS DEXAMETHASONE; PHASE-III; PHARMACOLOGICAL MANAGEMENT; REFRACTORY MYELOMA; BORTEZOMIB; THALIDOMIDE; CHEMOTHERAPY; NEUROTOXICITY; REVERSIBILITY AB Peripheral neuropathy (PN) and asthenia (fatigue) occur as both disease- and treatment-related complications in patients with multiple myeloma (MM). Risk factors for treatment-related PN, which has an estimated incidence of 37% to 83% among patients with VIM, include therapy duration, dose intensity, cumulative dose, and the presence of preexisting neuropathy. Asthenia is the most common adverse effect of treatment, occurring in approximately 76% to 96% of patients receiving therapy. The severity of PN and asthenia can range from mild to potentially debilitating. These conditions can be dose limiting; they may interfere with optimizing duration of therapy and may also substantially affect patient quality of life. Regular screening and monitoring, combined with patient education and effective management strategies, can reduce the risk of these treatment-related complications, as well as their consequences. (JNCCN 2010;8[Suppl 1]:S4-S12) C1 [Richardson, Paul G.; Laubach, Jacob P.; Schlossman, Robert L.; Mitsiades, Constantine; Anderson, Kenneth] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Celgene Corporation and Millennium; OSI Pharmaceuticals, Inc.; Amgen, Inc.; AVEO Pharmaceuticals, Inc.; EMD Serono, Inc.; Sunesis Pharmaceuticals, Inc.; Millennium Pharmaceuticals, Inc.; Celgene Corporation; Novartis FX Dr. Richardson reports having participated in funded research for Celgene Corporation and Millennium and having participated as an advisory board member or consultant for Celgene Corporation; Millennium Pharmaceuticals, Inc.; and Johnson & Johnson. Dr. Laubach reports no potential conflicts of interest. Dr. Schlossman reports having served as a speakers' bureau member for Celgene Corporation and Millennium Pharmaceuticals, Inc. Dr. Mitsiacles reports having participated in funded research for OSI Pharmaceuticals, Inc.; Amgen, Inc.; AVEO Pharmaceuticals, Inc.; EMD Serono, Inc.; and Sunesis Pharmaceuticals, Inc., and having participated as an advisory board member for Millennium Pharmaceuticals, Inc.; Novartis International AG; Merck & Co.; and Pharmion Corporation. Dr. Anderson reports having received preclinical and clinical research support from Millennium Pharmaceuticals, Inc., Celgene Corporation, and Novartis, and having served as an advisory board member for Millennium Pharmaceuticals, Inc., Celgene Corporation, Novartis, and Merck & Co. NR 65 TC 18 Z9 18 U1 0 U2 1 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 FEB PY 2010 VL 8 SU 1 BP S4 EP S12 PG 9 WC Oncology SC Oncology GA 555VK UT WOS:000274544100002 PM 20141673 ER PT J AU Foster, PP Williams, JH Estrada, CA Higginbotham, JC Voltz, ML Safford, MM Allison, J AF Foster, Pamela Payne Williams, Jessica H. Estrada, Carlos A. Higginbotham, John C. Voltz, Mukesha L. Safford, Monika M. Allison, Jeroan TI Recruitment of Rural Physicians in a Diabetes Internet Intervention Study: Overcoming Challenges and Barriers SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE recruitment; physicians; diabetes; Internet intervention ID HEALTH-CARE; PARTICIPANTS; COMMUNITY; PROGRAM; TRIAL; LONG AB Purpose: This paper highlights a descriptive study of the challenges and lessons learned in the recruitment of rural primary care physicians into a randomized clinical trial using an Internet-based approach. Methods: A multidisciplinary/multi-institutional research team used a multilayered recruitment approach, including generalized mailings and personalized strategies such as personal office visits, letters, and faxes to specific contacts. Continuous assessment of recruitment strategies was used throughout study in order to readjust strategies that were not successful. Results: We recruited 205 primary care physicians from 11 states. The 205 lead physicians who enrolled in the study were randomized, and the overall recruitment yield was 1.8% (205/11231). in addition, 8 physicians from the some practices participated and 12 nonphysicians participated. The earlier participants logged on to the study Web site, the greater yield of participation. Most of the study participants had logged on within 10 weeks of the study. Conclusion: Despite successful recruitment, the 2 major challenges in recruitment in this study included defining a standardized definition of rurality and the high cost of chart abstractions. Because many of the patients of study recruits were African American, the potential implications of this study on the field of health disparities in diabetes are important. C1 [Foster, Pamela Payne; Higginbotham, John C.] Univ Alabama, Sch Med, Tuscaloosa, AL 35401 USA. [Foster, Pamela Payne; Higginbotham, John C.] Univ Alabama, Rural Hlth Inst Clin & Translat Sci, Tuscaloosa, AL 35401 USA. [Williams, Jessica H.; Estrada, Carlos A.; Safford, Monika M.] Univ Alabama, Birmingham, AL USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] VA Natl Qual Scholars Program, Birmingham, AL USA. [Allison, Jeroan] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. RP Foster, PP (reprint author), Univ Alabama, Sch Med, Tuscaloosa Campus, Tuscaloosa, AL 35401 USA. EM ppayne-foster@cchs.ua.edu OI Allison, Jeroan/0000-0003-4472-2112 FU National Institutes of Diabetes and Digestive and Kidney Diseases [X050111012, R18DK065001-01] FX Funding/Support: This work was supported by National Institutes of Diabetes and Digestive and Kidney Diseases X050111012 and R18DK065001-01 AZ (Drs Allison and Safford), and Clinical Trials registration NCT00403091, Internet Intervention to Improve Rural Diabetes Care (http://www.clinicaltdals.gov/). NR 26 TC 5 Z9 5 U1 2 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD FEB PY 2010 VL 102 IS 2 BP 101 EP 107 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 557VV UT WOS:000274699100003 PM 20191922 ER PT J AU Shahian, DM O'Brien, SM Normand, SLT Peterson, ED Edwards, FH AF Shahian, David M. O'Brien, Sean M. Normand, Sharon-Lise T. Peterson, Eric D. Edwards, Fred H. TI Association of hospital coronary artery bypass volume with processes of care, mortality, morbidity, and the Society of Thoracic Surgeons composite quality score SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 09-13, 2009 CL Boston, MA SP Amer Assoc Thorac Surg ID ADULT CARDIAC-SURGERY; GRAFT-SURGERY; OUTCOME RELATIONSHIP; OPERATIVE MORTALITY; PROCEDURAL VOLUME; SURGICAL VOLUME; CABG SURGERY; CANCER-SURGERY; HEART-FAILURE; PERFORMANCE AB Objective: This study examines the association of hospital coronary artery bypass procedural volume with mortality, morbidity, evidence-based care processes, and Society of Thoracic Surgeons composite score. Methods: The study population consisted of 144,526 patients from 733 hospitals that submitted data to the Society of Thoracic Surgeons Adult Cardiac Database in 2007. End points included use of National Quality Forum-endorsed process measures (internal thoracic artery graft; preoperative beta-blockade; and discharge beta-blockade, antiplatelet agents, and lipid drugs), operative mortality (in-hospital or 30-day), major morbidity (stroke, renal failure, reoperation, sternal infection, and prolonged ventilation), and Society of Thoracic Surgeons composite score. Procedural volume was analyzed as a continuous variable and by volume strata (<100, 100-149, 150-199, 200-299, 300-449, and >= 450). Analyses were performed with logistic and multivariate hierarchical regression modeling. Results: Unadjusted mortality decreased across volume categories from 2.6% (<100 cases) to 1.7% (>450 cases, P<.0001), and these differences persisted after risk factor adjustment (odds ratio for lowest-vs highest-volume group, 1.49). Care processes and morbidity end points were not associated with hospital procedural volume except for a trend (P=.0237) toward greater internal thoracic artery use in high-volume hospitals. The average composite score for the lowest volume (<100 cases) group was significantly lower than that of the 2 highest-volume groups, but only 1% of composite score variation was explained by volume. Conclusion: A volume-performance association exists for coronary artery bypass grafting but is weaker than that of other major complex procedures. There is considerable outcomes variability not explained by hospital volume, and low volume does not preclude excellent performance. Except for internal thoracic artery use, care processes and morbidity rates were not associated with volume. (J Thorac Cardiovasc Surg 2010; 139: 273-282) C1 [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA 02114 USA. [O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. [Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Gainesville, FL USA. RP Shahian, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org RI O'Brien, Sean/H-6268-2013 NR 47 TC 52 Z9 52 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2010 VL 139 IS 2 BP 273 EP 282 DI 10.1016/j.jtcvs.2009.09.007 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 549AX UT WOS:000274014300004 PM 20022608 ER PT J AU Amann, JM Lee, JW Roder, H Brahmer, J Gonzalez, A Schiller, JH Carbone, DP AF Amann, Joseph M. Lee, Ju-Whei Roder, Heinrich Brahmer, Julie Gonzalez, Adriana Schiller, Joan H. Carbone, David P. TI Genetic and Proteomic Features Associated with Survival after Treatment with Erlotinib in First-Line Therapy of Non-small Cell Lung Cancer in Eastern Cooperative Oncology Group 3503 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Proteomics; Erlotinib; KRAS; EGFR ID GROWTH-FACTOR-RECEPTOR; METASTATIC COLORECTAL-CANCER; PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; TYROSINE KINASE INHIBITORS; GROUP-STUDY BR.21; EGFR-INHIBITORS; PREDICT RESPONSE; GEFITINIB; MUTATIONS AB Introduction: Serum proteomics and imitations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study. Hypothesis: Pretreatment serum proteomics predicts Survival in Western advanced non-small cell lung cancer patients with wildtype EGFR and independent of KRAS mutation status. Methods: We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase 11 study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations. Results: Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes. A statistically significant correlation of VeriStrat status (P < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival. Conclusions: The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS. C1 [Carbone, David P.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Carbone, David P.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gonzalez, Adriana] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA. [Brahmer, Julie] Johns Hopkins Univ, Baltimore, MD USA. [Roder, Heinrich] BioDesix Corp, Steamboat Springs, CO USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Amann, Joseph M.; Carbone, David P.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA. RP Carbone, DP (reprint author), Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, 685 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA. EM d.carbone@vanderbilt.edu FU BioDesix; ECOG, NCI [CA23318]; [U01 CA114771-03]; [P50 CA90949] FX Supported by grants from U01 CA114771-03, P50 CA90949, BioDesix, and ECOG, NCI Grant CA23318. NR 35 TC 42 Z9 43 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 FEB PY 2010 VL 5 IS 2 BP 169 EP 178 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 548MF UT WOS:000273966500005 PM 20035238 ER PT J AU Mantha, S Bauer, KA Zwicker, JI AF Mantha, S. Bauer, K. A. Zwicker, J. I. TI Low molecular weight heparin to achieve live birth following unexplained pregnancy loss: a systematic review SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE anticoagulation; low molecular weight heparin; recurrent pregnancy loss ID LOW-DOSE ASPIRIN; RANDOMIZED CONTROLLED-TRIAL; PROTEIN-C RESISTANCE; FACTOR-V-LEIDEN; RECURRENT MISCARRIAGE; ANTIPHOSPHOLIPID ANTIBODIES; VENOUS THROMBOSIS; FETAL LOSS; WOMEN; THROMBOPHILIA AB Background: The management of recurrent pregnancy loss is uncertain. Some cohort studies have identified an association between inherited thrombophilias and recurrent or late non-recurrent pregnancy loss, which has prompted investigators to evaluate the benefit of low molecular weight heparin (LWMH) to achieve live birth. A similar benefit for LMWH has also been proposed independent of thrombophilia status. Objective and methods: We conducted a systematic review of randomized controlled trials to assess the benefit of LMWH in achieving live birth for women with a history of recurrent or late non-recurrent pregnancy loss in the absence of antiphospholipid antibodies. Results: For the five studies that satisfied the eligibility criteria, the risk ratio of live birth for women with a history of pregnancy loss treated with LWMH compared with control ranged from 0.95 to 3.00. There was considerable heterogeneity among studies in terms of treatment effect (Q-value was 41.7, P = 0.000, and I(2) = 90.4%) independent of thrombophilia status. There was also a wide variation among all studies in terms of definition of early or late pregnancy loss, thrombophilic risk factors, and number of prior pregnancy losses. Conclusion: There is a trend for increased live births when using LWMH for the prevention of recurrent pregnancy loss. Currently, there is insufficient evidence to support the routine use of LWMH to improve pregnancy outcomes in women with a history of pregnancy loss. Not only are additional studies necessary but standardized criteria for trials evaluating the benefit of an intervention in recurrent pregnancy loss should be established. C1 [Bauer, K. A.; Zwicker, J. I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. [Mantha, S.] Lahey Clin Fdn, Div Hematol Oncol, Burlington, MA USA. [Bauer, K. A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Zwicker, JI (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM jzwicker@bidmc.harvard.edu OI Zwicker, Jeffrey/0000-0001-5810-6893 FU Sanofi-Aventis; [K23 HL084052] FX Funding supported, in part by K23 HL084052 (J.I. Zwicker). J.I. Zwicker also reports research funding from Sanofi-Aventis for anticoagualant trials in cancer patients. The other authors state that they have no conflict of interest. NR 35 TC 15 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD FEB PY 2010 VL 8 IS 2 BP 263 EP 268 DI 10.1111/j.1538-7836.2009.03687.x PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 544VO UT WOS:000273687600008 PM 19912516 ER PT J AU Oertel, LB Libby, EN AF Oertel, Lynn B. Libby, Edward N. TI Is patient self-testing a good thing? SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article ID ORAL ANTICOAGULATION THERAPY; PROTHROMBIN TIME; HEALTH LITERACY; MANAGEMENT; KNOWLEDGE; CARE C1 [Oertel, Lynn B.] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. [Libby, Edward N.] Univ New Mexico, Ctr Canc, Div Hematol & Oncol, Albuquerque, NM 87131 USA. RP Oertel, LB (reprint author), Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA. EM loertel@partners.org NR 31 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2010 VL 29 IS 2 BP 214 EP 218 DI 10.1007/s11239-009-0414-3 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550AJ UT WOS:000274097500011 PM 19902148 ER PT J AU Moulaison, WJ Oertel, LB AF Moulaison, W. J. Oertel, L. B. TI Developing a Nursing Workload Measurement System in the Anticoagulation Management Service SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Moulaison, W. J.; Oertel, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2010 VL 29 IS 2 BP 242 EP 243 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550AJ UT WOS:000274097500016 ER PT J AU Lai, EH Dincher, KL Lee, T Andersen, M Abdelfattah, F AF Lai, Eunha Dincher, Kathryn L. Lee, Todd Andersen, Mara Abdelfattah, Faten TI A Retrospective Analysis of the Effects of a Pharmacist Managed Inpatient Anticoagulation Service at a VA Hospital SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Meeting Abstract C1 [Lai, Eunha; Dincher, Kathryn L.; Lee, Todd; Andersen, Mara; Abdelfattah, Faten] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2010 VL 29 IS 2 BP 244 EP 244 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550AJ UT WOS:000274097500019 ER PT J AU King, DR AF King, David R. TI Response to "The Utility of FAST as a Triage Tool" SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP King, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. OI King, David/0000-0003-1028-1478 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD FEB PY 2010 VL 68 IS 2 BP 508 EP 508 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 555FC UT WOS:000274492600057 ER PT J AU Schnurr, PP Kaloupek, D Sayer, N Weiss, DS Cohen, J Galea, S Weaver, TL AF Schnurr, Paula P. Kaloupek, Danny Sayer, Nina Weiss, Daniel S. Cohen, Judith Galea, Sandro Weaver, Terri L. TI Understanding the Impact of the Wars in Iraq and Afghanistan SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material C1 [Schnurr, Paula P.] Natl Ctr PTSD, Execut Div, White River Jct, VT USA. [Schnurr, Paula P.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Kaloupek, Danny] Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Kaloupek, Danny] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sayer, Nina] Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Sayer, Nina] Univ Minnesota, Minneapolis, MN USA. [Weiss, Daniel S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cohen, Judith] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Galea, Sandro] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Weaver, Terri L.] St Louis Univ, St Louis, MO 63103 USA. RP Schnurr, PP (reprint author), VA Med Ctr, Natl Ctr PTSD 116D, White River Jct, VT 05009 USA. EM paula.schnurr@dartmouth.edu RI Sayer, Nina/E-3249-2016 NR 8 TC 3 Z9 3 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 3 EP 4 DI 10.1002/jts.20502 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100002 PM 20135677 ER PT J AU Seal, KH Maguen, S Cohen, B Gima, KS Metzler, TJ Ren, L Bertenthal, D Marmar, CR AF Seal, Karen H. Maguen, Shira Cohen, Beth Gima, Kristian S. Metzler, Thomas J. Ren, Li Bertenthal, Daniel Marmar, Charles R. TI VA Mental Health Services Utilization in Iraq and Afghanistan Veterans in the First Year of Receiving New Mental Health Diagnoses SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; COMORBIDITY SURVEY REPLICATION; PRIMARY-CARE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; WAR; DEPRESSION; INTERVENTION; MANAGEMENT; SYMPTOMS AB Little is known about mental health services utilization among Iraq and Afghanistan veterans receiving care tit Department of Veterans Affairs (VA)facilities. Of 49,425 veterans with newly diagnosed Posttraumatic stress disorder (PTSD), only 9.5% attended 9 or more VA mental health sessions in 15 weeks or less in the first year of diagnosis. In addition, engagement in 9 or more VA treatment sessions for PTSD within 15 weeks varied by predisposing variables (age and gender), enabling variables (clinic of first mental health diagnosis and distance from VA facility), and need (type and complexity of mental health diagnoses). Thus, only a minority of Iraq and Afghanistan veterans with new PTSD diagnoses received a recommended number and intensity of VA menial health treatment sessions within the first year of diagnosis. C1 [Seal, Karen H.; Maguen, Shira; Bertenthal, Daniel] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA 94121 USA. [Seal, Karen H.; Cohen, Beth] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Seal, Karen H.; Maguen, Shira; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, 4150 Clement St,Box 111A-1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov FU NCRR NIH HHS [KL2 RR024130] NR 53 TC 187 Z9 188 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 5 EP 16 DI 10.1002/jts.20493 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100003 PM 20146392 ER PT J AU Vasterling, JJ Proctor, SP Friedman, MJ Hoge, CW Heeren, T King, LA King, DW AF Vasterling, Jennifer J. Proctor, Susan P. Friedman, Matthew J. Hoge, Charles W. Heeren, Timothy King, Lynda A. King, Daniel W. TI PTSD Symptom Increases in Iraq-Deployed Soldiers: Comparison With Nondeployed Soldiers and Associations With Baseline Symptoms, Deployment Experiences, and Postdeployment Stress SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID MENTAL-HEALTH PROBLEMS; GULF-WAR VETERANS; UK ARMED-FORCES; POSTTRAUMATIC-STRESS; RISK-FACTORS; MILITARY PERSONNEL; DISORDER; COMBAT; POPULATION; CHECKLIST AB This prospective study examined: (a) the effects of Iraq war deployment versus non-deployment on pre- to postdeployment change in PTSD symptoms and (b) among deployed soldiers, associations of deployment/postdeployment stress exposures and baseline PTSD symptoms with PTSD symptom change. Seven hundred seventy-four U.S. Army soldiers completed self-report measures of stress exposure and PTSD symptom severity before and after Iraq deployment and were compared with 309 soldiers who did not deploy. Deployed soldiers, compared with non-deployed soldiers, reported increased PTSD symptom severity from Time 1 to Time 2. After controlling for baseline symptoms, deployment-related stressors contributed to longitudinal increases in PTSD symptoms. Combat severity was more strongly associated with symptom increases among active duty soldiers with higher baseline PTSD symptoms. C1 [Vasterling, Jennifer J.; Proctor, Susan P.; King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Proctor, Susan P.] USA, Environm Med Res Inst, Natick, MA 01760 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Friedman, Matthew J.] VA Natl Ctr PTSD, White River Jct, VT USA. [Friedman, Matthew J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Friedman, Matthew J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03756 USA. [Hoge, Charles W.] USA, Med Res & Mat Command, Dept Psychiat & Behav Sci, Walter Reed Army Inst Res, Silver Spring, MD USA. [Heeren, Timothy] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov NR 34 TC 109 Z9 109 U1 1 U2 19 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 41 EP 51 DI 10.1002/jts.20487 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100007 PM 20135698 ER PT J AU Maguen, S Lucenko, BA Reger, MA Gahm, GA Litz, BT Seal, KH Knight, SJ Marmar, CR AF Maguen, Shira Lucenko, Barbara A. Reger, Mark A. Gahm, Gregory A. Litz, Brett T. Seal, Karen H. Knight, Sara J. Marmar, Charles R. TI The Impact of Reported Direct and Indirect Killing on Mental Health Symptoms in Iraq War Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT; PTSD; CARE; SCREEN; PHQ-9 AB This study examined the mental health impact of reported direct and indirect killing among 2,797 U.S. soldiers returning from Operation Iraqi Freedom. Data were collected as part of a postdeployment screening program at a large Army medical facility. Overall, 40% of soldiers reported killing or being responsible for killing during their deployment. Even after controlling for combat exposure, killing was a significant predictor of posttraumatic disorder (PTSD) symptoms, alcohol abuse, anger, and relationship problems. Military personnel returning from modern deployments are at risk of adverse mental health conditions and related psychosocial functioning related to killing in war. Mental health assessment and treatment should address reactions to killing to optimize readjustment following deployment. C1 [Maguen, Shira] San Francisco VA Med Ctr, PTSD Program 116 P, San Francisco, CA 94121 USA. [Maguen, Shira; Seal, Karen H.; Knight, Sara J.; Marmar, Charles R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lucenko, Barbara A.] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Reger, Mark A.; Gahm, Gregory A.] Def Ctr Excellence Psychol Hlth, Natl Ctr Telehlth & Technol, Tacoma, WA USA. [Reger, Mark A.; Gahm, Gregory A.] Def Ctr Traumat Brain Injury, Natl Ctr Telehlth & Technol, Tacoma, WA USA. [Litz, Brett T.] Boston Healthcare Syst, Dept Vet Affairs, Natl Ctr PTSD, Boston, MA USA. [Litz, Brett T.] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116 P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov NR 14 TC 98 Z9 98 U1 3 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 86 EP 90 DI 10.1002/jts.20434 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100012 PM 20104592 ER PT J AU Tuerk, PW Yoder, M Ruggiero, KJ Gros, DF Acierno, R AF Tuerk, Peter W. Yoder, Matthew Ruggiero, Kenneth J. Gros, Daniel F. Acierno, Ron TI A Pilot Study of Prolonged Exposure Therapy for Posttraumatic Stress Disorder Delivered via Telehealth Technology SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RURAL TELEPSYCHIATRY; RANDOMIZED-TRIAL; TELEMEDICINE; PTSD; CARE; SYMPTOMS; VETERANS; PROGRAM; IRAQ AB The authors present a study study of 12 veterans diagnosed with combat-related PTSD and treated with prolonged exposure therapy (PE) via telehealth technology. A reference sample of 35 combat veterans treated with in-person IT in the same clinic is also included for a comparison. Feasibility and clinical outcomes of interest include technical performance and practicality of the telehealth equipment, patient safety, treatment completion rates, number of sessions required for termination, and clinical outcomes. Results indicated large statistically significant decreases in self-reported pathology fir veterans treated with PE via telehealth technology. Preliminary results support the feasibility and safety of the modality Suggestions for the implementation of PE via telehealth technology are discussed. C1 Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Tuerk, PW (reprint author), 109 Bee St,Mental Hlth 116, Charleston, SC 29401 USA. EM Tuerk@musc.edu FU NCATS NIH HHS [UL1 TR000062]; NCRR NIH HHS [KL2 RR029880] NR 43 TC 96 Z9 97 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 116 EP 123 DI 10.1002/jts.20494 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100017 PM 20135675 ER PT J AU McCauley, JL Ruggiero, KJ Resnick, HS Kilpatrick, DG AF McCauley, Jenna L. Ruggiero, Kenneth J. Resnick, Heidi S. Kilpatrick, Dean G. TI Incapacitated, Forcible, and Drug/Alcohol-Facilitated Rape in Relation to Binge Drinking, Marijuana Use, and Illicit Drug Use: A National Survey SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID SEXUAL ASSAULT; SUBSTANCE USE; ALCOHOL-CONSUMPTION; SAMPLE; WOMEN; VICTIMIZATION; PREVALENCE; OUTCOMES; VICTIMS; VIOLENT AB This study examined the relation between rape and substance use problems as a function of three legally recognized firms of rape: forcible, incapacitated, and drug/alcohol facilitated rape. Data were collected via structured telephone interview within a national household sample of U.S. women aged 18-34 years (n = 1, 998). Lifetime experience of incapacitated rape was associated with increased odds of past-year binge drinking, marijuana use, and illicit drug use. Lifetime history of forcible rape and drug/alcohol facilitated rape were associated with increased odds of marijuana and illicit drug use. Findings highlight the importance of including incapacitated and drug/alcohol facilitated rape in trauma history assessments, particularly among substance abusing populations, and have implications for secondary prevention and treatment of women with victimization histories. C1 [McCauley, Jenna L.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP McCauley, JL (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Dept Psychiat & Behav Sci, 67 President St,MSC 861, Charleston, SC 29425 USA. EM mccaule@musc.edu NR 29 TC 17 Z9 17 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2010 VL 23 IS 1 BP 132 EP 140 DI 10.1002/jts.20489 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 571FW UT WOS:000275738100019 PM 20135676 ER PT J AU Makarov, DV AF Makarov, Danil V. TI Cost Analysis of Robotic Versus Open Radical Cystectomy for Bladder Cancer EDITORIAL COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Yale Univ, Sch Med, Dept Surg, US Dept Vet Affairs,Sect Urol, New Haven, CT 06510 USA. RP Makarov, DV (reprint author), Yale Univ, Sch Med, Dept Surg, US Dept Vet Affairs,Sect Urol, New Haven, CT 06510 USA. OI Makarov, Danil/0000-0002-0565-9272 NR 2 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2010 VL 183 IS 2 BP 509 EP 509 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 543AD UT WOS:000273540600028 PM 20006853 ER PT J AU Eisner, BH Porten, SP Bechis, SK Stoller, ML AF Eisner, Brian H. Porten, Sima P. Bechis, Seth K. Stoller, Marshall L. TI Hypertension is Associated With Increased Urinary Calcium Excretion in Patients With Nephrolithiasis SO JOURNAL OF UROLOGY LA English DT Article DE kidney; nephrolithiasis; hypertension; calcium; citric acid ID RISK-FACTORS; DISEASE; WOMEN; MEN AB Purpose: The epidemiological relationship between nephrolithiasis and hypertension is well-known. Patients with hypertension are at increased risk for nephrolithiasis and those with nephrolithiasis are at risk for hypertension. Urine calcium or urine citrate may be related to hypertension status. We examined the relationship between hypertension and 24-hour urine composition in patients with nephrolithiasis. Materials and Methods: We retrospectively reviewed the database on 462 stone forming patients to examine the relationship between hypertension and 24-hour urine composition. Multivariate linear regression models were adjusted for age, race, gender, body mass index, diabetes mellitus and 24-hour urine constituents. Nominal logistic regression was also done to examine the hypertension prevalence by quintile of calcium and citrate excretion. Results: On adjusted multivariate analysis compared with normotensive stone formers those with hypertension excreted 25.6 mg per day more urine calcium, corresponding to a 12% increase in urinary calcium excretion. The relative risk of hypertension was significantly associated with quintile of calcium excretion but not with quintile of citrate excretion (1.29, 95% CI 1.02 to 1.61 vs 0.94, 95% CI 0.78 to 1.14). Conclusions: In stone formers hypertension was associated only with significantly increased urine calcium. This association is important when treating patients with nephrolithiasis since those with hypertension may require unique dietary and medical therapy. C1 [Eisner, Brian H.] Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Eisner, Brian H.; Porten, Sima P.; Bechis, Seth K.; Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Eisner, BH (reprint author), Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org FU Boston Scientific and Ravine Group; Percsys and Ravine Group FX Financial interest and/or other relationship with Boston Scientific and Ravine Group.; Financial interest and/or other relationship with Percsys and Ravine Group. NR 19 TC 17 Z9 28 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 FEB PY 2010 VL 183 IS 2 BP 576 EP 579 DI 10.1016/j.juro.2009.10.011 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 543AD UT WOS:000273540600067 PM 20018328 ER PT J AU Kerfoot, BP AF Kerfoot, B. Price TI Adaptive Spaced Education Improves Learning Efficiency: A Randomized Controlled Trial SO JOURNAL OF UROLOGY LA English DT Article DE urology; medical education; educational technology learning; algorithms ID MEDICAL-STUDENTS; UROLOGY; RESIDENTS; RETENTION; KNOWLEDGE AB Purpose: Spaced education is a novel form of online education that harnesses the 2 psychology research findings of spacing and testing effects. Spaced education is delivered by daily emails containing clinically relevant multiple choice questions. To take advantage of the spacing effect the questions are repeated at fixed intervals for a fixed number of repetitions. An adaptive spaced education system was developed to customize spacing intervals and the number of repetitions based on learner knowledge level. To determine whether this system improves learning efficiency I performed a randomized trial to compare the learning efficiency of adaptive vs nonadaptive spaced education systems among surgery students at 2 medical schools. Materials and Methods: A total of 62 year 3 students were randomized to identical course content in adaptive or nonadaptive spaced education formats. The course consisted of 40 validated, spaced education items on the 4 urology topics benign prostatic hyperplasia, erectile dysfunction, prostate cancer and prostate specific antigen screening. The nonadaptive cohort received daily emails containing 2 questions with a linear review of the material 20 days after initial presentation. The adaptive cohort received daily emails via an adaptive algorithm that limited the repetition of mastered content. Each cohort completed a validated end of course test. Results: The adaptive cohort answered significantly fewer spaced education items than the nonadaptive cohort (p = 0.001) but achieved comparable end of course test scores (p = 0.37). The adaptive algorithm increased learning efficiency by 38%. Conclusions: Adaptive spaced education boosts learning efficiency. C1 [Kerfoot, B. Price] Vet Affairs Boston Healthcare Syst, Surg Serv, Jamaica Plain, MA 02130 USA. [Kerfoot, B. Price] Harvard Univ, Sch Med, Boston, MA USA. RP Kerfoot, BP (reprint author), Vet Affairs Boston Healthcare Syst, Surg Serv, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com FU United States Agency for Healthcare Research and Quality; American Urological Association Foundation; Astellas Pharma US, Inc FX Supported by the United States Agency for Healthcare Research and Quality, American Urological Association Foundation and Astellas Pharma US, Inc. NR 14 TC 18 Z9 18 U1 7 U2 12 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 FEB PY 2010 VL 183 IS 2 BP 678 EP 681 DI 10.1016/j.juro.2009.10.005 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 543AD UT WOS:000273540600115 PM 20022032 ER PT J AU Patel, R Conrad, MF Paruchuri, V Kwolek, CJ Cambria, RP AF Patel, Rajendra Conrad, Mark F. Paruchuri, Vikram Kwolek, Christopher J. Cambria, Richard P. TI Balloon expandable stents facilitate right renal artery reconstruction during complex open aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CONTEMPORARY EXPERIENCE; PREDICTIVE FACTORS; SURGERY; FAILURE; OPERATIONS; ISCHEMIA AB Objective: Patients undergoing repair of thoracoabdominal (TAA) or visceral aortic segment aneurysms typically require reconstruction of the renal arteries. The use of balloon expandable stents (BES) has been proposed as an alternative to endarterectomy or bypass for renal artery reconstruction (RAR) during open aortic aneurysm repair. We report technical aspects and long-term patency data for this method of right RAR during complex open aortic aneurysm repair. Methods: During the interval July 1, 2005 to December 31, 2007, a total of 67 patients underwent right RAR using a BES during concomitant TAA (type I: n = 2 [2.9%], type II: n = 8 [11.9%], type III: n = 13 [19.4%], and type IV: n = 22 [32.8%]), juxtarenal (n = 9 [13.4%]) or suprarenal (n = 13 [19.4%]) AAA repair. Indications for RAR were orificial stenosis (n = 21[31%]) and/or technical considerations referable to the proximal aortic suture line. Patency of the renal stent was evaluated in patients with computed tomography angiography using three-dimensional reconstruction or with abdominal duplex evaluation at follow-up. Results: The mean patient age was 75.1 years, 54.4% were male, and 18% of operations were in nonelective circumstances. Twenty-seven (39%) out of 67 patients had a preoperative creatinine level >= 1.4 mg/dL. Two patients (2.9%) developed permanent renal failure postoperatively (neither related to renal artery occlusion). Mean radiologic follow-up was 405 days (11-1281) with 98% stent patency noted. One patient had an early stent occlusion noted at I month. An additional patient was noted to have a nonflow-limiting dissection distal to the renal stent, and another was noted to have distal migration of the stent beyond the renal ostium; however, these findings were clinically silent. Conclusions: The use of BES during complex open aortic aneurysm repair affords a rapid and durable mode of RAR, obviating the need for endarterectomy and its associated technical complications. (J Vasc Surg 2010;51:310-6.) C1 [Patel, Rajendra; Conrad, Mark F.; Paruchuri, Vikram; Kwolek, Christopher J.; Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mconrad@partners.org NR 33 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2010 VL 51 IS 2 BP 310 EP 316 DI 10.1016/j.jvs.2009.04.079 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 556PG UT WOS:000274602800005 PM 19853403 ER PT J AU Crawford, RS Cambria, RP Abularrage, CJ Conrad, MF Lancaster, RT Watkins, MT LaMuraglia, GM AF Crawford, Robert S. Cambria, Richard P. Abularrage, Christopher J. Conrad, Mark F. Lancaster, Robert T. Watkins, Michael T. LaMuraglia, Glenn M. TI Preoperative functional status predicts perioperative outcomes after infrainguinal bypass surgery SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CRITICAL LIMB ISCHEMIA; PERIPHERAL ARTERIAL-DISEASE; QUALITY IMPROVEMENT PROGRAM; VEIN GRAFT FAILURE; POSTOPERATIVE OUTCOMES; SURGICAL REVASCULARIZATION; SALVAGE; RISK; MULTICENTER; MORBIDITY AB Objective: Infrainguinal surgical bypass (BPG) is a durable method for lower extremity revascularization, but is accompanied by significant 30-day morbidity and mortality (MM). The goal of this study is to relate preoperative functional status, a defined metric in the National Surgical Quality Improvement Program (NSQIP) database, to perioperative MM. Methods: Between January 1, 2005 and December 31, 2007, all patients who underwent BPG front the NSQIP private sector database were reviewed. The primary end-point was 30-day MM. Patients were stratified by preoperative functional status: independent (IND) vs dependent (DEP). Associated patient demographic/clinical data were analyzed using univariate and multivariate methods. Composite odds ratios were constructed with clusters of high-risk comorbidities. Results: There were 5639 BPG patients (4600 [81.6%] IND and 1039 [18.4%]) DEP. DEP patients were significantly older (71.6 +/- 11.8 vs 66.8 +/- 11.8 years; P < .0001), had more chronic obstructive pulmonary disease (COPD) (16.7% vs 11.4%; P < .0001), diabetes (54.2% vs 40.7%; P < .0001), dialysis dependence (16.4% vs 5.6%; P < .0001), and critical limb ischemia (64.6% vs 44.0%; P < .0001). DEP patients had a higher incidence of death (6.1% vs 1.5%; P < .0001) and major complications (30.3% vs 14.2%; P < .0001). DEP was an independent predictor of major complications (odds ratio [OR]: 2.0; 95% confidericc interval [Cl]: [1.7-2.4]; P < .0001) major systemic complications (2.5 [1.9-3.2]; P < .0001), major operative site complications (1.6 [1.4-1.9]; P < .0001) and death (2.3[1.6-3.4]; P < .0001). The combination of DEP with emergency surgery, Cr > 1.8, or rest pain increased the odds of major complications by five, seven, or 11-fold, respectively. The combination of DEP with hemodialysis, emergency surgery, or age >= 80 years increased the odds of death by 13, 38, or 87-fold, respectively. Conclusion: Preoperative DEP is significantly correlated with all adverse 30-day outcomes in BPG patients. Furthermore, when combined in high-risk composites with specific preoperative clinical variables, DEP is associated with prohibitive MM, thereby identifying patient cohorts that may be unsuitable for BPG. (J Vasc Surg 2010;51:351-9.) C1 [Crawford, Robert S.; Cambria, Richard P.; Abularrage, Christopher J.; Conrad, Mark F.; Watkins, Michael T.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Lancaster, Robert T.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP LaMuraglia, GM (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WC 440, Boston, MA 02114 USA. EM glamuraglia@partners.org FU Monte and Rita Goldman Foundation; John F. Murphy, and Bay State Federal Savings Foundation FX This study was supported in part by grants from the Monte and Rita Goldman Foundation, John F. Murphy, and Bay State Federal Savings Foundation. NR 40 TC 52 Z9 52 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2010 VL 51 IS 2 BP 351 EP 359 DI 10.1016/j.jvs.2009.08.065 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 556PG UT WOS:000274602800011 PM 20141958 ER PT J AU Rodriguez-Torres, M Sulkowski, MS Chung, RT Hamzeh, FM Jensen, DM AF Rodriguez-Torres, M. Sulkowski, M. S. Chung, R. T. Hamzeh, F. M. Jensen, D. M. TI Factors associated with rapid and early virologic response to peginterferon alfa-2a/ribavirin treatment in HCV genotype 1 patients representative of the general chronic hepatitis C population SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE chronic hepatitis C; on-treatment; pre-treatment; sustained virologic response ID ALPHA-2A (40 KD)/RIBAVIRIN; PLUS RIBAVIRIN; TREATMENT DURATION; RANDOMIZED-TRIAL; THERAPY; INTERFERON; EFFICACY; OUTCOMES; LATINO; 40KD AB Rapid virologic response (RVR) and complete early virologic response (cEVR) are associated with sustained virologic response to hepatitis C virus (HCV) therapy. We retrospectively examined baseline and on-treatment factors associated with RVR (HCV RNA undetectable at week 4) and cEVR (HCV RNA undetectable at week 12, regardless of week 4 response). The analysis comprised 1550 HCV genotype-1 patients from five clinical trials, including three enriched with difficult-to-treat populations, randomized to peginterferon alfa-2a 180 mu g/week plus ribavirin 1000-1200 mg/day. Overall, 15.6% achieved RVR and 54.0% achieved cEVR. Baseline factors predictive of RVR were serum HCV RNA <= 400 000 IU/mL (OR: 7.34; P < 0.0001), alanine aminotransferase >3 x ULN (OR: 2.01; P < 0.0001), non-cirrhotic status (OR: 1.92; P = 0.0087), age <= 40 years (OR: 1.56; P = 0.0085), white non-Latino ethnicity (OR: 1.41; P = 0.0666) and individual study (P < 0.0001). These factors plus body mass index <= 27 kg/m(2) were predictive of cEVR. After adjusting for these factors, mean on-treatment ribavirin dose >13 mg/kg/day was predictive of RVR (OR: 1.69; P = 0.005) and cEVR (OR: 1.24; P = 0.09), whereas peginterferon alfa-2a dose reduction was not. Greater decreases in haematologic parameters were observed in patients who achieved cEVR compared with patients who did not. In conclusion, several baseline and on-treatment factors were associated with RVR and cEVR to peginterferon alfa-2a plus ribavirin in difficult-to-treat HCV genotype-1 patients, providing important prognostic information on the antiviral response in a patient cohort that is reflective of the general chronic hepatitis C population. C1 [Rodriguez-Torres, M.] Fdn Invest Diego, San Juan, PR 00909 USA. [Sulkowski, M. S.] Johns Hopkins Univ, Baltimore, MD USA. [Chung, R. T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hamzeh, F. M.] Roche, Nutley, NJ USA. [Jensen, D. M.] Univ Chicago, Chicago, IL 60637 USA. RP Rodriguez-Torres, M (reprint author), Fdn Invest Diego, Ave Diego 359,Suite 302, San Juan, PR 00909 USA. EM rodztorres@coqui.net FU Roche; Vertex; Boehringer-Ingelheim; Schering-Plough FX D. Jensen has served as a consultant and an advisory board member for Roche, Vertex, Abbott and Boehringer-Ingelheim, and has received research funding from Roche, Vertex, Boehringer-Ingelheim and Schering-Plough. R. Chung has served as a consultant for Roche and has received research funding from Roche. M. Sulkowski has served as a speaker and a consultant for Roche and Schering, and has received research funding from John Hopkins University. M. Rodriguez-Torres has served as a speaker for Roche and an advisory board member for Roche, Pharmasset, Anadys, Vertex, Abbott and Merck, and has received research funding from Roche, Vertex, Bristol, HGS, Glaxo, Idera, Intarcia, Virochem Pharma, Novartis, Wyeth and Abbott, (ii) F. M. Hamzeh is an employee of Roche. NR 24 TC 19 Z9 19 U1 0 U2 0 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 FEB PY 2010 VL 17 IS 2 BP 139 EP 147 DI 10.1111/j.1365-2893.2009.01157.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 545KV UT WOS:000273731900008 PM 19674282 ER PT J AU Hessell, AJ Rakasz, EG Tehrani, DM Huber, M Weisgrau, KL Landucci, G Forthal, DN Koff, WC Poignard, P Watkins, DI Burton, DR AF Hessell, Ann J. Rakasz, Eva G. Tehrani, David M. Huber, Michael Weisgrau, Kimberly L. Landucci, Gary Forthal, Donald N. Koff, Wayne C. Poignard, Pascal Watkins, David I. Burton, Dennis R. TI Broadly Neutralizing Monoclonal Antibodies 2F5 and 4E10 Directed against the Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Protect against Mucosal Challenge by Simian-Human Immunodeficiency Virus SHIVBa-L SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1/SIV CHIMERIC VIRUS; T-CELL RESPONSES; CLASS-I ALLELES; PASSIVE TRANSFER; RHESUS MACAQUES; ENVELOPE GLYCOPROTEIN; LONG-TERM; INFECTION; EPITOPE; REPLICATION AB The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIV(Ba-L). In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41. C1 [Hessell, Ann J.; Tehrani, David M.; Huber, Michael; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Hessell, Ann J.; Tehrani, David M.; Huber, Michael; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat, Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Rakasz, Eva G.; Weisgrau, Kimberly L.; Watkins, David I.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53711 USA. [Landucci, Gary; Forthal, Donald N.] Univ Calif Irvine, Div Infect Dis, Dept Med, Irvine, CA 92697 USA. [Koff, Wayne C.; Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY USA. [Burton, Dennis R.] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu RI poignard, pascal/N-6678-2013; Huber, Michael/B-8509-2015 FU International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium; NIH [AI033292, 5R24RR16038-6] FX Support for this work was provided by the International AIDS Vaccine Initiative (IAVI) through the Neutralizing Antibody Consortium and by NIH grant AI033292 (to D. R. B.). MHC genotyping by sequence-specific PCR was performed by the University of Wisconsin Genotyping Core with support of NIH grant 5R24RR16038-6 awarded to David I. Watkins. NR 47 TC 183 Z9 184 U1 0 U2 3 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 FEB PY 2010 VL 84 IS 3 BP 1302 EP 1313 DI 10.1128/JVI.01272-09 PG 12 WC Virology SC Virology GA 542XC UT WOS:000273531600009 PM 19906907 ER PT J AU Kasprowicz, V Kang, YH Lucas, M zur Wiesch, JS Kuntzen, T Fleming, V Nolan, BE Longworth, S Berical, A Bengsch, B Thimme, R Lewis-Ximenez, L Allen, TM Kim, AY Klenerman, P Lauer, GM AF Kasprowicz, Victoria Kang, Yu-Hoi Lucas, Michaela zur Wiesch, Julian Schulze Kuntzen, Thomas Fleming, Vicki Nolan, Brian E. Longworth, Steven Berical, Andrew Bengsch, Bertram Thimme, Robert Lewis-Ximenez, Lia Allen, Todd M. Kim, Arthur Y. Klenerman, Paul Lauer, Georg M. TI Hepatitis C Virus (HCV) Sequence Variation Induces an HCV-Specific T-Cell Phenotype Analogous to Spontaneous Resolution SO JOURNAL OF VIROLOGY LA English DT Article ID IL-7 RECEPTOR; EXPRESSION; INFECTION; MEMORY; EPITOPE; EXHAUSTION; RESPONSES; SUBSETS; VARIANT; ESCAPE AB Hepatitis C virus (HCV)-specific CD8(+) T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127(+) T cells is driven by viral variation. C1 [Kasprowicz, Victoria; Kuntzen, Thomas; Berical, Andrew; Allen, Todd M.; Kim, Arthur Y.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [zur Wiesch, Julian Schulze; Nolan, Brian E.; Longworth, Steven; Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Kang, Yu-Hoi; Lucas, Michaela; Fleming, Vicki; Klenerman, Paul] Univ Oxford, Nuffield Dept Med, Oxford, England. [Bengsch, Bertram; Thimme, Robert] Univ Freiburg, Med Klin, D-7800 Freiburg, Germany. [Lewis-Ximenez, Lia] Fiocruz MS, Inst Oswaldo Cruz, Dept Virol, BR-21045900 Rio De Janeiro, Brazil. RP Kasprowicz, V (reprint author), MIT, Ragon Inst MGH, 149 13th St, Charlestown, MA 02129 USA. EM vkasprowicz@partners.org; glauer@helix.mgh.harvard.edu RI Allen, Todd/F-5473-2011 FU National Institutes of Health [U19-AI066345, RO1-AI067926-01]; Deutsche Forschungsgemeinschaft (DFG) [SCHU 2482/1-1] FX The work presented here was supported by the National Institutes of Health (U19-AI066345 to G. M. L., L. L.-X., T. M. A., and A. Y. K. and RO1-AI067926-01 to T. M. A.) and the Deutsche Forschungsgemeinschaft (DFG SCHU 2482/1-1 to J. S. Z. W.). NR 15 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2010 VL 84 IS 3 BP 1656 EP 1663 DI 10.1128/JVI.01499-09 PG 8 WC Virology SC Virology GA 542XC UT WOS:000273531600045 PM 19906915 ER PT J AU Tsaih, SW Pezzolesi, MG Yuan, R Warram, JH Krolewski, AS Korstanje, R AF Tsaih, Shirng-Wern Pezzolesi, Marcus G. Yuan, Rong Warram, James H. Krolewski, Andrzej S. Korstanje, Ron TI Genetic analysis of albuminuria in aging mice and concordance with loci for human diabetic nephropathy found in a genome-wide association scan SO KIDNEY INTERNATIONAL LA English DT Article DE albuminuria; diabetic nephropathy; genetic renal disease ID QUANTITATIVE TRAIT LOCI; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GLOMERULAR-FILTRATION-RATE; INBRED MOUSE STRAINS; RENAL-FUNCTION; FIBRONECTIN DEPOSITS; N-ACETYLASPARTATE; DISEASE; SUSCEPTIBILITY; LINKAGE AB Aging in the kidney can cause albuminuria, and discovering molecular mechanisms responsible for this might offer a new perspective on the etiology of this abnormality. Haplotype association mapping in the mouse is a novel approach which uses the haplotypes of the relatively closely related mouse inbred strains and the phenotypic variation among these strains to find associations between haplotypes and phenotype. The albumin-to-creatinine ratios, a measure of urinary albumin excretion, were determined in 30 inbred mouse strains at 12, 18, and 24 months of age. Mapping was performed for males and females separately at all three time points using a high density set of 63,222 single-nucleotide polymorphisms to determine genetic loci involved in albuminuria. One significant and eight suggestive loci were found, some of which map to previously identified loci for traits associated with kidney damage in the mouse, but with a much higher resolution thus narrowing their chromosomal location. These nine loci were then compared with genome-wide association scans for diabetic nephropathy (DN) in human type I diabetes. Our study found that two of the nine mouse loci for age-related albuminuria were significantly associated with DN and consistent across male and female strata. This suggests common underlying genes predispose to kidney disease in mice and humans. Kidney International (2010) 77, 201-210; doi:10.1038/ki.2009.434; published online 18 November 2009 C1 [Tsaih, Shirng-Wern; Yuan, Rong; Korstanje, Ron] Jackson Lab, Bar Harbor, ME 04609 USA. [Pezzolesi, Marcus G.; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Korstanje, R (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM ron.korstanje@jax.org FU NIDDK [DK77532, DK007260-31, DK069381]; FNIH [06GAIN0]; Nathan Shock Center, National Institute of Aging, NIH [AG 25707]; Ellison Medical Foundation [AG-NS-0421-07]; Glenn Foundation for Medical Research FX This work was funded by DK77532 (ASK), DK007260-31 (MGP), and DK069381 (RK) from the NIDDK, by 06GAIN0 (JHW) from the FNIH, the Nathan Shock Center Grant AG 25707 from the National Institute of Aging, NIH, by AG-NS-0421-07 (S-WT) from the Ellison Medical Foundation, and by a Glenn Award for Research in Biological Mechanisms of Aging (S-WT) from the Glenn Foundation for Medical Research. We thank David Schultz, Dana Godfrey, Milly So, Sue Grindle, Neeta Kumari, Yueming Ding, and Phyllis Magnani for excellent technical assistance; Joanne Currer for writing assistance; and Jesse Hammer for preparation of the figures. NR 41 TC 21 Z9 21 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2010 VL 77 IS 3 BP 201 EP 210 DI 10.1038/ki.2009.434 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 543JQ UT WOS:000273573000007 PM 19924099 ER PT J AU Isakova, T Gutierrez, OM Wolf, M AF Isakova, Tamara Gutierrez, Orlando M. Wolf, Myles TI Response to 'Targeting hyperphosphatemia: truth or dare' SO KIDNEY INTERNATIONAL LA English DT Letter C1 [Gutierrez, Orlando M.; Wolf, Myles] Univ Miami, Div Nephrol & Hypertens, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Isakova, Tamara] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Renal Unit, Boston, MA USA. RP Wolf, M (reprint author), Univ Miami, Div Nephrol & Hypertens, Miller Sch Med, Dept Med, 1120 NW 14th St, Miami, FL 33136 USA. EM mwolf2@med.miami.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2010 VL 77 IS 3 BP 257 EP 257 DI 10.1038/ki.2009.448 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 543JQ UT WOS:000273573000017 ER PT J AU Antonescu, CR Zhang, L Chang, NE Pawel, BR Travis, W Rosenberg, AE Nielsen, GP Dal Cin, P Fletcher, CD AF Antonescu, C. R. Zhang, L. Chang, N. E. Pawel, B. R. Travis, W. Rosenberg, A. E. Nielsen, G. P. Dal Cin, P. Fletcher, C. D. TI Novel EWSR1-POU5F1 Fusion in Soft Tissue Myoepithelial Tumors. A Molecular Analysis of 29 Cases, Including Soft Tissue, Bone and Visceral Locations Showing Common Involvement of EWSR1 Gene Rearrangement SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Pawel, Bruce/G-5466-2011 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 49 BP 14A EP 15A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300050 ER PT J AU Bridge, JA Streblow, R Frayer, RW Dal Cin, P Rosenberg, A Meloni-Ehrig, A Sumegi, J AF Bridge, J. A. Streblow, R. Frayer, R. W. Dal Cin, P. Rosenberg, A. Meloni-Ehrig, A. Sumegi, J. TI Recurrent (2;2) and (2;8) Translocations in Rhabdomyosarcoma without the Canonical PAX-FOXO1 Fuse PAX3 to Members of the Nuclear Receptor Transcriptional Coactivator (NCOA) Family SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Univ Nebraska Med Ctr, Omaha, NE USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Quest Diagnost Nichols Inst, Chantilly, VA 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 55 BP 16A EP 16A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300056 ER PT J AU Demicco, EG Rosenberg, AE Antonescu, CR Kobler, JB Nielsen, GP AF Demicco, E. G. Rosenberg, A. E. Antonescu, C. R. Kobler, J. B. Nielsen, G. P. TI Benign Notochordal Cell Proliferations in the Ferret: An Animal with a High Incidence of Chordoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 69 BP 19A EP 19A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300070 ER PT J AU Lee, AF Hayes, MM Rosenberg, AE Nielsen, TO Lee, CH AF Lee, A. F. Hayes, M. M. Rosenberg, A. E. Nielsen, T. O. Lee, C. H. TI FLI-1 Distinguishes Ewing Sarcoma from Small Cell Osteosarcoma and Mesenchymal Chondrosarcoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Vancouver Gen Hosp, Vancouver, BC, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 87 BP 22A EP 22A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300088 ER PT J AU Lee, CH Liebsch, NJ Nielsen, GP Ganguly, A Rosenberg, AE AF Lee, C. H. Liebsch, N. J. Nielsen, G. P. Ganguly, A. Rosenberg, A. E. TI Morphologic and Immunohistochemical Characterization of a Series of Clinically Atypical Skull Base Chordomas in the Paediatric Population SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Vancouver Gen Hosp, Vancouver, BC, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 89 BP 23A EP 23A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300090 ER PT J AU Romeo, S Duim, RAJ Bridge, JA Mertens, F De Jong, D Dal Cin, P Wijers-Koster, PM Debiec-Rychter, M Sciot, R Rosenberg, A Szuhai, K Hogendoorn, PCW AF Romeo, S. Duim, R. A. J. Bridge, J. A. Mertens, F. De Jong, D. Dal Cin, P. Wijers-Koster, P. M. Debiec-Rychter, M. Sciot, R. Rosenberg, A. Szuhai, K. Hogendoorn, P. C. W. TI Heterogeneous and Complex Rearragements of the Long Arm of Chromosome 6 in Chondromyxoid Fibroma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Treviso Reional Hosp, Treviso, Italy. Leiden Univ, Med Ctr, Leiden, Netherlands. Univ Nebraska Med Ctr, Omaha, NE USA. Univ Lund Hosp, S-22185 Lund, Sweden. Brigham & Womens Hosp, Boston, MA 02115 USA. Catholic Univ, Louvain, Belgium. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 107 BP 27A EP 27A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300108 ER PT J AU Imielinski, M Cha, S Richardson, EA Thakur, D Rejtar, T Wu, SL Karger, B Sgroi, D AF Imielinski, M. Cha, S. Richardson, E. A. Thakur, D. Rejtar, T. Wu, S-L Karger, B. Sgroi, D. TI Combined Proteomic-Transcriptomic Profiling of Laser Capture Microdissected Normal and Breast Cancer Epithelium Reveals Systematic Biochemical Network Alterations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northeastern Univ, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 225 BP 52A EP 53A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300225 ER PT J AU Johnson, MM Dialani, V Johnson, NB AF Johnson, M. M. Dialani, V. Johnson, N. B. TI Histologic Characteristics of Benign Breast Lesions Identified for Biopsy by Magnetic Resonance Imaging SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 231 BP 54A EP 54A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300231 ER PT J AU Kaplan, J Schnitt, S Collins, L Wang, Y Garber, J Montgomery, K West, R Tung, N AF Kaplan, J. Schnitt, S. Collins, L. Wang, Y. Garber, J. Montgomery, K. West, R. Tung, N. TI Histologic and Immunophenotypic Comparison of Estrogen Receptor (ER)-Positive Breast Cancers in BRCA1 Mutation Carriers and Sporadic ER-Positive Breast Cancers: A Case-Control Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Palo Alto, CA 94304 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 235 BP 55A EP 55A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300235 ER PT J AU Marotti, JD Collins, LC Gelber, S Ruddy, K Kereakoglow, S Brachtel, EF Winer, E Partridge, A AF Marotti, J. D. Collins, L. C. Gelber, S. Ruddy, K. Kereakoglow, S. Brachtel, E. F. Winer, E. Partridge, A. TI Pathologic Features and Distribution of Molecular Phenotype among Young Women with Breast Cancer: Results from the Young Women's Breast Cancer Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 266 BP 62A EP 62A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300266 ER PT J AU Stone, JR Khosroshahi, A Deshpande, V Stone, JH AF Stone, J. R. Khosroshahi, A. Deshpande, V. Stone, J. H. TI Thoracic Lymphoplasmacytic Aortitis Is Often Associated with IgG4-Related Systemic Disease SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Harvard Univ, Sch Med, Boston, MA USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 370 BP 84A EP 84A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300370 ER PT J AU Wang, H Smith, RN Stone, JR AF Wang, H. Smith, R. N. Stone, J. R. TI Ascending Giant Cell Aortitis without Systemic Symptoms Is Associated with an Increased Frequency of Subsequent Distal Aortic Events SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 375 BP 85A EP 85A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300375 ER PT J AU Chebib, I Yeager, K Mino-Kenudsen, M Brugge, W Pitman, MB AF Chebib, I. Yeager, K. Mino-Kenudsen, M. Brugge, W. Pitman, M. B. TI The Role of Cytopathology in the Diagnosis and Management of Pancreatic Cysts Greater Than 3 cm SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 [Chebib, I.; Yeager, K.; Mino-Kenudsen, M.; Brugge, W.; Pitman, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 394 BP 90A EP 90A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300394 ER PT J AU Moatamed, NA Apple, SK Moatamed, F AF Moatamed, N. A. Apple, S. K. Moatamed, F. TI Inclusion of the Uniform Tetraploid Cells Reduces the Specificity of the Urine FISH Assay SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. VA Greater LA Healthcare Syst, Los Angeles, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 447 BP 102A EP 102A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300447 ER PT J AU Baran, JL Laga, AC Duncan, LM Murphy, GF AF Baran, J. L. Laga, A. C. Duncan, L. M. Murphy, G. F. TI The Embryonic Stem Cell Transcription Factor SOX2 Is Expressed by Spitz Nevi SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 489 BP 111A EP 111A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300489 ER PT J AU Baran, JL Scott, K Muzikansky, A Chin, L Duncan, LM AF Baran, J. L. Scott, K. Muzikansky, A. Chin, L. Duncan, L. M. TI MITF Expression in Cutaneous Melanoma and Spitz Nevi: A Genomic and Immunohistochemical Study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 490 BP 111A EP 111A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300490 ER PT J AU Sepehr, A Chao, E Mihm, MC Tsao, H AF Sepehr, A. Chao, E. Mihm, M. C., Jr. Tsao, H. TI Comparative Analysis of Spitz Tumors: A Clinicopathologic Follow-Up of 163 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 536 BP 121A EP 121A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300536 ER PT J AU Ryan, R Brodsky, V Louissaint, A Gilbertson, J Yagi, Y AF Ryan, R. Brodsky, V. Louissaint, A. Gilbertson, J. Yagi, Y. TI Usage and Participation in a Resident-Built Virtual Slide-Based Atlas of Anatomic Pathology SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Weill Cornell Med Coll, New York, NY 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 552 BP 125A EP 125A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300552 ER PT J AU Kolman, OK Sadow, PM Hunt, JL AF Kolman, O. K. Sadow, P. M. Hunt, J. L. TI Sampling, Assessment, and Reporting of Thyroid Follicular Lesions: Survey of 165 Pathologists SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 567 BP 128A EP 129A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300567 ER PT J AU Agoston, AT Lauwers, GY Odze, RD AF Agoston, A. T. Lauwers, G. Y. Odze, R. D. TI Evidence That Dysplasia Begins in the Bases of the Pits in the Pathogenesis of Gastric Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 593 BP 134A EP 134A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300593 ER PT J AU Coco, D Goldblum, J Hornick, J Lauwers, GY Montgomery, E Srivastava, A Wang, H Odze, RD AF Coco, D. Goldblum, J. Hornick, J. Lauwers, G. Y. Montgomery, E. Srivastava, A. Wang, H. Odze, R. D. TI Interobserver Variability in the Diagnosis of Crypt Dysplasia in Barrett's Esophagus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Dartmouth Med Ctr, Lebanon, NH USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 621 BP 140A EP 140A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300621 ER PT J AU Courville, EL Srivastava, A Hong, TS Yilmaz, OH Calvo, LN Zaki, BI Mino-Kenudson, M AF Courville, E. L. Srivastava, A. Hong, T. S. Yilmaz, O. H. Calvo, L. N. Zaki, B. I. Mino-Kenudson, M. TI Lack of ERCC1 and Olfactomedin 4 (Olfm4) Protein Expression Predicts Neoadjuvant Therapy Sensitivity in GE Junction Adenocarcinoma (GEJAd) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 625 BP 141A EP 141A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300625 ER PT J AU Demicco, EG Farris, AB Iafrate, AK Gaissert, HA Fukuoka, J Cohen, C Zukerberg, LR Lauwers, GY Mino-Kenudson, M AF Demicco, E. G. Farris, A. B. Iafrate, A. K. Gaissert, H. A. Fukuoka, J. Cohen, C. Zukerberg, L. R. Lauwers, G. Y. Mino-Kenudson, M. TI Microsatellite Unstable Barrett's Esophagus-Associated Adenocarcinomas Are Rare, but Clinicopathologically Similar to the Colonic Counterpart SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Toyama Med Univ, Toyama, Japan. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 630 BP 142A EP 143A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300630 ER PT J AU Demicco, EG Farris, AB Agbor-Etang, B Fukuoka, J Davies, D Snimizu, M Gaissert, HA Mino-Kenudson, M AF Demicco, E. G. Farris, A. B. Agbor-Etang, B. Fukuoka, J. Davies, D. Snimizu, M. Gaissert, H. A. Mino-Kenudson, M. TI Validation of a Topographic-Anatomic Subclassification for Adenocarcinoma of the GE Junction (GEJ) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. Toyama Univ Hosp, Toyama, Japan. Saitama Med Univ, Saitama, Japan. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 631 BP 143A EP 143A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300631 ER PT J AU Golden, KL Baba, Y Fuchs, CS Ogino, S AF Golden, K. L. Baba, Y. Fuchs, C. S. Ogino, S. TI Loss of CDH1 Expression in Colorectal Cancer Is Independently Associated with Microsatellite Instability and Female Gender SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 645 BP 146A EP 146A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300645 ER PT J AU Kolman, OK Brown, I Moran, CJ Russell, GJ Mino-Kenudson, M AF Kolman, O. K. Brown, I. Moran, C. J. Russell, G. J. Mino-Kenudson, M. TI Neutrophilic Infiltration in Gluten Sensitive Enteropathy (GSE): A Series of 100 Pediatric Patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Sullivan Nicolaides Pathol, Taringa, Australia. RI Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 671 BP 152A EP 152A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300671 ER PT J AU Lennerz, JK Srivastava, A Batten, J Chen, JH Iafrate, AJ Lauwers, G AF Lennerz, J. K. Srivastava, A. Batten, J. Chen, J. H. Iafrate, A. J. Lauwers, G. TI Molecular Profile of Crohn's Colitis-Associated Colorectal Adenocarcinoma Is More Similar to the 'Sporadic' Rather Than Ulcerative Colitis-Associated Profile SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Indiana Univ, Indianapolis, IN 46204 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 678 BP 153A EP 153A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300678 ER PT J AU Ogino, S Nosho, K Glickman, JN Mino-Kenudson, M Fuchs, CS AF Ogino, S. Nosho, K. Glickman, J. N. Mino-Kenudson, M. Fuchs, C. S. TI Lymphoid Reaction to Colorectal Cancer Predicts Patient Survival Independent of Lymph Node Count and MSI, and Explains the Association between CIMP and Good Prognosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 701 BP 158A EP 159A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300701 ER PT J AU Ogino, S Nosho, K Tanaka, N Hornick, JL Fuchs, CS AF Ogino, S. Nosho, K. Tanaka, N. Hornick, J. L. Fuchs, C. S. TI Can We Predict Lymph Node Count in Colorectal Cancer Resection Specimen Using Clinical, Pathologic and Molecular Variables? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 703 BP 159A EP 160A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300703 ER PT J AU Ogino, S Nosho, K Mino-Kenudson, M Meyerhardt, JA Fuchs, CS AF Ogino, S. Nosho, K. Mino-Kenudson, M. Meyerhardt, J. A. Fuchs, C. S. TI Negative Lymph Node Count in Colorectal Cancer Resection Predicts Patient Survival, Independent of Positive Node Count, Tumoral Molecular Alterations and Lymphocytic Reaction SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 702 BP 159A EP 159A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300702 ER PT J AU Park, DY Kang, HJ Shin, DH Choi, KU Lee, CH Huh, GY Sol, MY Lauwers, GY AF Park, D. Y. Kang, H. J. Shin, D. H. Choi, K. U. Lee, C. H. Huh, G. Y. Sol, M. Y. Lauwers, G. Y. TI Gastric Foveolar Hyperplasia, Foveolar Dysplasia and Pit Dysplasia in 414 Gastric Cancers-Prevalence and Clinicopathological Significance SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Pusan Natl Univ Hosp, Pusan, South Korea. 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 NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 708 BP 160A EP 161A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300708 ER PT J AU Shima, K Nosho, K Chen, L Fuchs, CS Ogino, S AF Shima, K. Nosho, K. Chen, L. Fuchs, C. S. Ogino, S. TI Loss of PPARG Expression Is Common in CpG Island Methylator Phenotype-Low (CIMP-Low) Colorectal Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 738 BP 167A EP 168A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300738 ER PT J AU Yilmaz, OH Bhan, AK Lauwers, GY Deshpande, V AF Yilmaz, O. H. Bhan, A. K. Lauwers, G. Y. Deshpande, V. TI Olfactomedin-4, a Novel Marker of Intestinal Stem Cell Identity, Is Upregulated in Long-Standing Ulcerative Colitis and Accompanying Low Grade Dysplasia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 [Yilmaz, O. H.; Bhan, A. K.; Lauwers, G. Y.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 763 BP 173A EP 173A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300763 ER PT J AU Sangoi, AR Beck, AH Amin, MB Cheng, L Epstein, JI Hansel, DE Iczkowski, KA Ro, JY Lopez-Beltran, A Oliva, E Paner, GP Reuter, VE Shah, RB Shen, SS Tamboli, P McKenney, JK AF Sangoi, A. R. Beck, A. H. Amin, M. B. Cheng, L. Epstein, J. I. Hansel, D. E. Iczkowski, K. A. Ro, J. Y. Lopez-Beltran, A. Oliva, E. Paner, G. P. Reuter, V. E. Shah, R. B. Shen, S. S. Tamboli, P. McKenney, J. K. TI Interobserver Reproducibility (IOR) in the Diagnosis of Invasive Micropapillary Carcinoma (MPC) of the Genitourinary Tract among Expert Urologic Pathologists SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 U Indiana, Indianapolis, IN USA. Johns Hopkins, Baltimore, MD USA. Cleveland Clin, Cleveland, OH 44106 USA. U Colorado, Aurora, CO USA. Methodist, Houston, TX USA. Univ Cordoba, Fac Med, Anat Pathol Unit, E-14071 Cordoba, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering, New York, NY USA. U Michigan, Ann Arbor, MI USA. UT MD Anderson, Houston, TX 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 965 BP 216A EP 216A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337300964 ER PT J AU Chiang, S Fazlollahi, L Nguyen, A Roberts, DJ Iafrate, AJ AF Chiang, S. Fazlollahi, L. Nguyen, A. Roberts, D. J. Iafrate, A. J. TI In Situ Genetic Analysis of Hydatidiform Moles by Polymorphic Deletion Probe Fluorescence In Situ Hybridization SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 [Chiang, S.; Fazlollahi, L.; Nguyen, A.; Roberts, D. J.; Iafrate, A. J.] 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1061 BP 237A EP 237A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301077 ER PT J AU Han, G Soslow, RA Reuter, VE Oliva, E Gilks, CB Asad, H Tickoo, SK AF Han, G. Soslow, R. A. Reuter, V. E. Oliva, E. Gilks, C. B. Asad, H. Tickoo, S. K. TI Hypoxia-Inducible Factor (HIF) and Mammalian Target of Rapamycin (mTOR) Pathway Markers in Ovarian Clear Cell Carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1098 BP 246A EP 246A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301114 ER PT J AU Kindelberger, DW Matulonis, U AF Kindelberger, D. W. Matulonis, U. TI The Utility of Circulating Tumor Cells in Monitoring Patients with Recurrent Ovarian Cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1117 BP 250A EP 250A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301133 ER PT J AU Knoepp, SM Kuebler, DL Wilbur, DC AF Knoepp, S. M. Kuebler, D. L. Wilbur, D. C. TI Correlation of the Hybrid Capture II High-Risk HPV DNA Test Chemiluminescense Intensity from Cervical Samples with Follow-Up Histologic Results: A Cytologic/Histologic Review of 367 Cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1118 BP 250A EP 250A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301134 ER PT J AU Laury, AR Hornick, JL Corson, JM Krane, JF Drapkin, R Hirsch, MS AF Laury, A. R. Hornick, J. L. Corson, J. M. Krane, J. F. Drapkin, R. Hirsch, M. S. TI PAX8 Distinguishes Serous Ovarian Neoplasms from Malignant Mesothelioma with High Sensitivity and Specificity SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1125 BP 251A EP 252A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301141 ER PT J AU Mutter, GL Monte, NM Webster, KA Neuberg, D Dressler, GR AF Mutter, G. L. Monte, N. M. Webster, K. A. Neuberg, D. Dressler, G. R. TI Interaction of PAX2 and PTEN Drives Emergence of Endometrial Precancers from a Preclinical Latent Phase SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1146 BP 256A EP 256A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301162 ER PT J AU Schulte, S Roh, M Folkins, AK Jarboe, EA Garber, J Hecht, J Crum, CP AF Schulte, S. Roh, M. Folkins, A. K. Jarboe, E. A. Garber, J. Hecht, J. Crum, C. P. TI BRCA 1 or 2-Associated (BRCA+) Pelvic Serous Carcinomas Arise from Both the Ovaries and Fallopian Tubes: The Contrast between Symptomatic and Asymptomatic Women SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Utah, Med Ctr, Salt Lake City, UT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1171 BP 262A EP 262A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301187 ER PT J AU Van De Vijver, KK Castilla, MA Romero, L Biscuola, M Moreno-Bueno, G Palacios, J Oliva, E AF Van De Vijver, K. K. Castilla, M. A. Romero, L. Biscuola, M. Moreno-Bueno, G. Palacios, J. Oliva, E. TI Study of Epithelial-Mesenchymal Transition in 70 Endometrial Carcinosarcomas (ECS) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Maastricht Univ, Med Ctr, Maastricht, Netherlands. Hosp Univ Virgen Rocio, Seville, Spain. CSIC, Inst Invest Biomed, Madrid, Spain. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1199 BP 267A EP 267A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301215 ER PT J AU Xian, W Mehra, KK Vathipadiekal, V Tay, SW Birrer, M Crum, CP AF Xian, W. Mehra, K. K. Vathipadiekal, V. Tay, S. W. Birrer, M. Crum, C. P. TI Ovarian Cancer Risk Assessment Via Expression Profiling of the Distal Fallopian Tube Epithelium SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Mol Biol, Singapore, Singapore. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1207 BP 269A EP 269A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301223 ER PT J AU Xian, W Mehra, KK Miron, A Oliva, E Garber, J Roh, M Quade, BJ Crum, CP AF Xian, W. Mehra, K. K. Miron, A. Oliva, E. Garber, J. Roh, M. Quade, B. J. Crum, C. P. TI The Li Fraumeni Syndrome: A New Paradigm for p53 Signature Initiation in the Distal Fallopian Tube and In Vitro Modeling SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Inst Mol Biol, Singapore, Singapore. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1206 BP 269A EP 269A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301222 ER PT J AU Hafezi, S Seethala, RR Stelow, EB Mills, S Perez-Ordonez, B Leong, I Hunt, JL Weinreb, I AF Hafezi, S. Seethala, R. R. Stelow, E. B. Mills, S. Perez-Ordonez, B. Leong, I. hunt, J. L. Weinreb, I. TI Ewing Family of Tumors of the Sinonasal Tract SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Univ Hlth Network, Toronto, ON, Canada. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1229 BP 274A EP 274A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301245 ER PT J AU Adam, P Vela-Chavez, T Cremer, M Bink, K Ferry, JA Fend, F Jaffe, E Quintanilla-Martinez, L AF Adam, P. Vela-Chavez, T. Cremer, M. Bink, K. Ferry, J. A. Fend, F. Jaffe, E. Quintanilla-Martinez, L. TI Cyclin D1 Positive Diffuse Large B-Cell Lymphomas Feature a Post-Germinal Center - Immunophenotype and Lack Alterations in the CCND1 Gene Locus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Univ Tubingen, Tubingen, Germany. Tech Univ Munich, Munich, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1267 BP 282A EP 282A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301283 ER PT J AU Duong, A O'Malley, DP Barry, TS Chen, S Ferry, JA Hasserjian, RP Thompson, MA Richardson, MS Jaffe, R Sidhu, JS Banks, PM AF Duong, A. O'Malley, D. P. Barry, T. S. Chen, S. Ferry, J. A. Hasserjian, R. P. Thompson, M. A. Richardson, M. S. Jaffe, R. Sidhu, J. S. Banks, P. M. TI Coexistence of Langerhans Cell Histiocytosis and Rosai-Dorfman Disease: Related-Disorders? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acac Pathol C1 Med Univ S Carolina, Charleston, SC 29425 USA. Clarient Inc, Aliso Viejo, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt, Nashville, TN USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. UHS Hosp, Binghamton, NY USA. Carolinas Med Ctr, Charlotte, NC 28203 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1317 BP 294A EP 294A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301333 ER PT J AU Gibson, SE Swerdlow, SH Ferry, JA Surti, U Harris, NL Hasserjian, RP AF Gibson, S. E. Swerdlow, S. H. Ferry, J. A. Surti, U. Harris, N. L. Hasserjian, R. P. TI Reassessment of Small Lymphocytic Lymphoma (SLL) in the Era of Monoclonal B Lymphocytosis (MBL) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT 99th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 2010 CL Washington, DC SP US & Canadian Acad Pathol C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2010 VL 90 SU 1 MA 1328 BP 296A EP 297A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 553AR UT WOS:000274337301344 ER EF