FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mao, J Kim, BM Rajurkar, M Shivdasani, RA McMahon, AP AF Mao, Junhao Kim, Byeong-Moo Rajurkar, Mihir Shivdasani, Ramesh A. McMahon, Andrew P. TI Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract SO DEVELOPMENT LA English DT Article DE Hedgehog; Intestine; Stomach; Endoderm; Mesoderm; Mouse ID SONIC-HEDGEHOG; INDIAN HEDGEHOG; GASTROINTESTINAL DEVELOPMENT; REGULATES PROLIFERATION; MUTATIONS CAUSE; BONE-FORMATION; MOUSE MODEL; DIFFERENTIATION; GUT; STOMACH AB Homeostasis of the vertebrate digestive tract requires interactions between an endodermal epithelium and mesenchymal cells derived from the splanchnic mesoderm. Signaling between these two tissue layers is also crucial for patterning and growth of the developing gut. From early developmental stages, sonic hedgehog (Shh) and indian hedgehog (Ihh) are secreted by the endoderm of the mammalian gut, indicative of a developmental role. Further, misregulated hedgehog (Hh) signaling is implicated in both congenital defects and cancers arising from the gastrointestinal tract. In the mouse, only limited gastrointestinal anomalies arise following removal of either Shh or Ihh. However, given the considerable overlap in their endodermal expression domains, a functional redundancy between these signals might mask a more extensive role for Hh signaling in development of the mammalian gut. To address this possibility, we adopted a conditional approach to remove both Shh and Ihh functions from early mouse gut endoderm. Analysis of compound mutants indicates that continuous Hh signaling is dispensable for regional patterning of the gut tube, but is essential for growth of the underlying mesenchyme. Additional in vitro analysis, together with genetic gain-of-function studies, further demonstrate that Hh proteins act as paracrine mitogens to promote the expansion of adjacent mesenchymal progenitors, including those of the smooth muscle compartment. Together, these studies provide new insights into tissue interactions underlying mammalian gastrointestinal organogenesis and disease. C1 [Mao, Junhao; Rajurkar, Mihir] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [Mao, Junhao; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Kim, Byeong-Moo; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kim, Byeong-Moo; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Byeong-Moo; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [McMahon, Andrew P.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [McMahon, Andrew P.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Mao, J (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, 364 Plantat St,LRB 405, Worcester, MA 01605 USA. EM Junhao.mao@umassmed.edu; mcmahon@mcb.harvard.edu FU NINDS [R37 NS033642]; NIDDK [R01 DK081113]; Charles H. Hood Foundation; Diabetes Endocrinology Research Center [DK32520] FX This work was supported by an NIH Javits award (R37 NS033642) to A. P. M. from NINDS and R01 DK081113 to R. A. S. from NIDDK. Work in J.M.'s laboratory is supported by the Charles H. Hood Foundation and J.M. is a member of the UMass DERC (DK32520). Core resources supported by the Diabetes Endocrinology Research Center grant DK32520 were also used. We thank Dr Alex Joyner and Warren Zimmer for providing the Gli1-CreER and Bapx1-Cre mouse lines. Hydrophobically modified N-Shh protein was a generous gift from Dr R. Blake Pepinsky (Biogen). We also thank Jill McMahon and Julie Brooks for their technical support and members of the Mao, Shivdasani and McMahon groups for helpful discussions. J.M., B.-M. K. and M. R. performed the research; all authors designed and interpreted the studies, analyzed the data and drafted the manuscript. Deposited in PMC for release after 12 months. NR 62 TC 65 Z9 66 U1 2 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2010 VL 137 IS 10 BP 1721 EP 1729 DI 10.1242/dev.044586 PG 9 WC Developmental Biology SC Developmental Biology GA 588OI UT WOS:000277081100014 PM 20430747 ER PT J AU Gong, SP Lee, ST Lee, EJ Kim, DY Lee, G Chi, SG Ryu, BK Lee, CH Yum, KE Lee, HJ Han, JY Tilly, JL Lim, JM AF Gong, Seung Pyo Lee, Seung Tae Lee, Eun Ju Kim, Dae Yong Lee, Gene Chi, Sung Gil Ryu, Byung-Kyu Lee, Chae Hyun Yum, Kyung Eun Lee, Ho-Joon Han, Jae Yong Tilly, Jonathan L. Lim, Jeong Mook TI Embryonic stem cell-like cells established by culture of adult ovarian cells in mice SO FERTILITY AND STERILITY LA English DT Article DE Cell transformation; meiosis; ovary; stem cell; stroma cell ID PREANTRAL FOLLICLE CULTURE; OOCYTE PARTHENOGENESIS; MOUSE TESTIS; GENERATION; PLURIPOTENCY AB Objective: To suggest an alternative strategy for deriving histocompatible stems cells without undertaking genetic manipulation. Design: Prospective approach using an animal model. Setting: Stem cell and bioevaluation laboratory, Seoul National University. Animal(s): F1 (C57BL6 X DBA2) and outbred (ICR) mice. Intervention(s): Ovarian stroma cells of less than 40 mm in diameter were subcultured with fibroblast monolayer, and colony-forming cells were characterized. Main Outcome Measure(s): Stemness, genotype, and imprinted gene methylation. Result(s): Two-lines of colony-forming cells were established, which expressed markers specific for embryonic stem cells (ESC) and formed embryoid bodies and teratomas. Complete matching of microsatellite markers with the cell donor strain confirmed their establishment from ovarian tissue, and identification of both homozygotic and heterozygotic chromosomes raised the possibility of their derivation from parthenogenetic oocytes. However, the use of cells smaller than mature oocytes for primary culture, the difference in imprinted gene methylation compared with parthenogenetic ESCs, and failure to establish the ESC-like cells by primary follicle culture collectively suggested the irrelevancy to gametes. Conclusion(s): Coculture of adult ovarian cells with somatic fibroblasts can yield colony-forming cells having ESC-like activity, which may provide an alternative for establishing autologous stem cells from adults that can be obtained without genetic manipulation. (Fertil Steril (R) 2010; 93: 2594-601. (C) 2010 by American Society for Reproductive Medicine.) C1 [Gong, Seung Pyo; Lee, Chae Hyun; Yum, Kyung Eun; Han, Jae Yong; Lim, Jeong Mook] Seoul Natl Univ, WCU, Seoul 151921, South Korea. [Gong, Seung Pyo; Lee, Chae Hyun; Yum, Kyung Eun; Han, Jae Yong; Lim, Jeong Mook] Seoul Natl Univ, Dept Agr Biotechnol, Seoul 151921, South Korea. [Lee, Seung Tae] Swiss Fed Inst Technol, Dept Pharmacol & Regenerat Biol, CH-1015 Lausanne, Switzerland. [Lee, Eun Ju] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea. [Kim, Dae Yong] Seoul Natl Univ, Coll Vet Med, Seoul, South Korea. [Lee, Gene] Seoul Natl Univ, Sch Dent, Seoul, South Korea. [Chi, Sung Gil; Ryu, Byung-Kyu] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea. [Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. RP Lim, JM (reprint author), Seoul Natl Univ, WCU, Seoul 151921, South Korea. EM limjm@snu.ac.kr FU Ministry of Education, Science and Technology (MEST) [SC-5160, R31-10056]; Republic of Korea the National Institute on Aging [NIH R37-AG012279]; Henry and Vivian Rosenberg Philanthropic Fund; Vincent Memorial Research Funds FX Supported by a grant (SC-5160) from Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology (MEST), Republic of Korea the National Institute on Aging (NIH R37-AG012279), the National Institute of Child Health and Human Development (NIH R01-HD057873), the Henry and Vivian Rosenberg Philanthropic Fund, and Vincent Memorial Research Funds. This study was also supported by educational grants of Brain Korea 21 and WCU(World Class University) programs (R31-10056) through the National Research Foundation of Korea funded by MEST. NR 18 TC 33 Z9 34 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY 15 PY 2010 VL 93 IS 8 BP 2594 EP U153 DI 10.1016/j.fertnstert.2009.12.053 PG 17 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 595KH UT WOS:000277608700018 PM 20188358 ER PT J AU Jacobsen, JC Bawden, CS Rudiger, SR McLaughlan, CJ Reid, SJ Waldvogel, HJ MacDonald, ME Gusella, JF Walker, SK Kelly, JM Webb, GC Faull, RLM Rees, MI Snell, RG AF Jacobsen, Jessie C. Bawden, C. Simon Rudiger, Skye R. McLaughlan, Clive J. Reid, Suzanne J. Waldvogel, Henry J. MacDonald, Marcy E. Gusella, James F. Walker, Simon K. Kelly, Jennifer M. Webb, Graham C. Faull, Richard L. M. Rees, Mark I. Snell, Russell G. TI An ovine transgenic Huntington's disease model SO HUMAN MOLECULAR GENETICS LA English DT Article ID CAG REPEAT; SHEEP; MICE; EFFICIENCY; GENE; EXPRESSION; LAMBS AB Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene [Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell, 72, 971-983]. Despite identification of the gene in 1993, the underlying life-long disease process and effective treatments to prevent or delay it remain elusive. In an effort to fast-track treatment strategies for HD into clinical trials, we have developed a new large-animal HD transgenic ovine model. Sheep, Ovis aries L., were selected because the developmental pattern of the ovine basal ganglia and cortex (the regions primarily affected in HD) is similar to the analogous regions of the human brain. Microinjection of a full-length human HTT cDNA containing 73 polyglutamine repeats under the control of the human promotor resulted in six transgenic founders varying in copy number of the transgene. Analysis of offspring (at 1 and 7 months of age) from one of the founders showed robust expression of the full-length human HTT protein in both CNS and non-CNS tissue. Further, preliminary immunohistochemical analysis demonstrated the organization of the caudate nucleus and putamen and revealed decreased expression of medium size spiny neuron marker DARPP-32 at 7 months of age. It is anticipated that this novel transgenic animal will represent a practical model for drug/clinical trials and surgical interventions especially aimed at delaying or preventing HD initiation. New sequence accession number for ovine HTT mRNA: FJ457100. C1 [Reid, Suzanne J.; Snell, Russell G.] Univ Auckland, Sch Biol Sci, Neurogenet Grp, Auckland 1142, New Zealand. [Jacobsen, Jessie C.; Rees, Mark I.] Univ Auckland, Fac Med & Hlth Sci, Dept Mol Med & Pathol, Auckland 1142, New Zealand. [Jacobsen, Jessie C.; Waldvogel, Henry J.; Faull, Richard L. M.] Univ Auckland, Fac Med & Hlth Sci, Dept Anat Radiol, Auckland 1142, New Zealand. [Jacobsen, Jessie C.; Reid, Suzanne J.; Waldvogel, Henry J.; Faull, Richard L. M.; Snell, Russell G.] Univ Auckland, Fac Med & Hlth Sci, Ctr Brain Res, Auckland 1142, New Zealand. [Bawden, C. Simon; Rudiger, Skye R.; McLaughlan, Clive J.; Walker, Simon K.; Kelly, Jennifer M.] S Australian Res & Dev Inst, Livestock & Farming Syst Div, Mol Biol & Reprod Technol Labs, Glenside, SA, Australia. [MacDonald, Marcy E.; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Webb, Graham C.] Univ Adelaide, Livestock Syst Alliance, Adelaide, SA, Australia. [Rees, Mark I.] Swansea Univ, Sch Med, Inst Life Sci, Swansea, W Glam, Wales. [Rees, Mark I.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff, S Glam, Wales. RP Snell, RG (reprint author), Univ Auckland, Sch Biol Sci, Neurogenet Grp, Private Bag 92019, Auckland 1142, New Zealand. EM r.snell@auckland.ac.nz RI Reid, Suzanne/H-7082-2012; Rees, Mark/J-3129-2012; OI Reid, Suzanne/0000-0002-8068-6529 FU Freemasons of New Zealand; Neurological Foundation of New Zealand; Health Research Council of New Zealand; Wellcome Trust; Foundation of Research Science and Technology; National Institutes of Health NINDS [NS16367, NS32765] FX This work was supported by the Freemasons of New Zealand; the Neurological Foundation of New Zealand; the Health Research Council of New Zealand; Wellcome Trust; the Foundation of Research Science and Technology; and the National Institutes of Health NINDS grants (NS16367, NS32765). NR 16 TC 56 Z9 59 U1 2 U2 19 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 MAY 15 PY 2010 VL 19 IS 10 BP 1873 EP 1882 DI 10.1093/hmg/ddq063 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 590PD UT WOS:000277238200001 PM 20154343 ER PT J AU Truong-Bolduc, QC Hooper, DC AF Truong-Bolduc, Que Chi Hooper, David C. TI Phosphorylation of MgrA and Its Effect on Expression of the NorA and NorB Efflux Pumps of Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACILLUS-SUBTILIS; SIGB OPERON; HEAT-SHOCK; RESISTANCE; REGULATOR; VIRULENCE; SIGMA(B); ENDOCARDITIS; RSBU; TRANSCRIPTION AB MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrA(S110A-S113A) bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates. C1 [Truong-Bolduc, Que Chi; Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis & Med Serv, Bostonm, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU U.S. Public Health Service, National Institutes of Health [R37 AI23988] FX This work was supported in part by grant R37 AI23988 to D.C.H. from the U.S. Public Health Service, National Institutes of Health. NR 41 TC 35 Z9 37 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY 15 PY 2010 VL 192 IS 10 BP 2525 EP 2534 DI 10.1128/JB.00018-10 PG 10 WC Microbiology SC Microbiology GA 589OO UT WOS:000277161400006 PM 20233929 ER PT J AU Guo, CY Hirano, AA Stella, SL Bitzer, M Brecha, NC AF Guo, Chenying Hirano, Arlene A. Stella, Salvatore L., Jr. Bitzer, Michaela Brecha, Nicholas C. TI Guinea Pig Horizontal Cells Express GABA, the GABA-Synthesizing Enzyme GAD(65), and the GABA Vesicular Transporter SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GABA; GAD; GAT; VGAT; VIAAT; horizontal cells; retina; visual system ID GAMMA-AMINOBUTYRIC-ACID; PLASMA-MEMBRANE TRANSPORTER; OUTER PLEXIFORM LAYER; INTRACELLULAR CHLORIDE CONCENTRATION; MAMMALIAN CONE PHOTORECEPTORS; DECARBOXYLASE MESSENGER-RNA; CALCIUM-BINDING PROTEINS; CARRIER-MEDIATED RELEASE; IN-SITU HYBRIDIZATION; RAT RETINA AB gamma-Aminobutyric acid (GABA) is likely expressed in horizontal cells of all species, although conflicting physiological findings have led to considerable controversy regarding its role as a transmitter in the outer retina. This study has evaluated key components of the GABA system in the outer retina of guinea pig, an emerging retinal model system. The presence of GABA, its rate-limiting synthetic enzyme glutamic acid decarboxylase (GAD(65) and GAD(67) isoforms), the plasma membrane GABA transporters (GAT-1 and GAT-3), and the vesicular GABA transporter (VGAT) was evaluated by using immunohistochemistry with well-characterized antibodies. The presence of GAD(65) mRNA was also evaluated by using laser capture microdissection and reverse transcriptase-polymerase chain reaction. Specific GABA, GAD(65), and VGAT immunostaining was localized to horizontal cell bodies, as well as to their processes and tips in the outer plexiform layer. Furthermore, immunostaining of retinal whole mounts and acutely dissociated retinas showed GAD(65) and VGAT immunoreactivity. in both A-type and B-type horizontal cells. However, these cells did not contain GAD(67), GAT-1, or GAT-3 immunoreactivity. GAD(65) mRNA was detected in horizontal cells, and sequencing of the amplified GAD(65) fragment showed approximately 85% identity with other mammalian GAD(65) mRNAs. These studies demonstrate the presence of GABA, GAD(65), and VGAT in horizontal cells of the guinea pig retina, and support the idea that GABA is synthesized from GAD(65), taken up into synaptic vesicles by VGAT, and likely released by a vesicular mechanism from horizontal cells. J. Comp. Neurol. 518:1647-1669, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Guo, Chenying; Hirano, Arlene A.; Stella, Salvatore L., Jr.; Bitzer, Michaela; Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Brecha, Nicholas C.] Vet Adm Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Brecha, NC (reprint author), Univ Calif Los Angeles, Dept Neurobiol, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM nbrecha@ucla.edu OI Stella Jr., Salvatore/0000-0003-1971-2537 FU National Institutes of Health [EY 15573]; Veterans Administration FX Grant sponsor: National Institutes of Health; Grant number: EY 15573; Grant sponsor: Veterans Administration (Senior Career Research Scientist: N.C.B.). NR 161 TC 25 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 15 PY 2010 VL 518 IS 10 BP 1647 EP 1669 DI 10.1002/cne.22294 PG 23 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 581CX UT WOS:000276499800003 PM 20235161 ER PT J AU Jimenez, F Quinones, MP Martinez, HG Estrada, CA Clark, K Garavito, E Ibarra, J Melby, PC Ahuja, SS AF Jimenez, Fabio Quinones, Marlon P. Martinez, Hernan G. Estrada, Carlos A. Clark, Kassandra Garavito, Edgar Ibarra, Jessica Melby, Peter C. Ahuja, Seema S. TI CCR2 Plays a Critical Role in Dendritic Cell Maturation: Possible Role of CCL2 and NF-kappa B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEISHMANIA-MAJOR INFECTION; SECONDARY LYMPHOID ORGANS; REGULATORY T-CELLS; IN-VIVO; LANGERHANS CELLS; TNF-ALPHA; GENE-EXPRESSION; TRANSCRIPTION FACTORS; PROTEASOME INHIBITOR; ANTIGEN PRESENTATION AB We postulated that CCR2-driven activation of the transcription factor NF-kappa B plays a critical role in dendritic cell (DC) maturation (e.g., migration, costimulation, and IL-12p70 production), necessary for the generation of protective immune responses against the intracellular pathogen Leishmania major. Supporting this notion, we found that CCR2, its ligand CCL2, and NF-kappa B were required for CCL19 production and adequate Langerhans cell (LC) migration both ex vivo and in vivo. Furthermore, a role for CCR2 in upregulating costimulatory molecules was indicated by the reduced expression of CD80, CD86, and CD40 in Ccr2(-/-) bone marrow-derived dendritic cells (BMDCs) compared with wild-type (WT) BMDCs. Four lines of evidence suggested that CCR2 plays a critical role in the induction of protective immunity against L. major by regulating IL-12p70 production and migration of DC populations such as LCs. First, compared with WT, Ccr2(-/-) lymph node cells, splenocytes, BMDCs, and LCs produced lower levels of IL-12p70 following stimulation with LPS/IFN-gamma or L. major. Second, a reduced number of LCs carried L. major from the skin to the draining lymph nodes in Ccr2(-/-) mice compared with WT mice. Third, early treatment with exogenous IL-12 reversed the susceptibility to L major infection in Ccr2(-/-) mice. Finally, disruption of IL-12p70 in radioresistant cells, such as LCs, but not in BMDCs resulted in the inability to mount a fully protective immune response in bone marrow chimeric mice. Collectively, our data point to an important role for CCR2-driven activation of NF-kappa B in the regulation of DC/LC maturation processes that regulate protective immunity against intracellular pathogens. The Journal of Immunology, 2010, 184: 5571-5581. C1 [Jimenez, Fabio; Quinones, Marlon P.; Martinez, Hernan G.; Estrada, Carlos A.; Clark, Kassandra; Garavito, Edgar; Ibarra, Jessica; Melby, Peter C.; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Jimenez, Fabio; Quinones, Marlon P.; Martinez, Hernan G.; Clark, Kassandra; Melby, Peter C.; Ahuja, Seema S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Adm Ctr Res AIDS & HIV Infect 1, San Antonio, TX 78229 USA. RP Ahuja, SS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC 7870,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU National Institutes of Health [RO1-AR052755, RO1-AI48644]; Veterans Affairs FX This work was supported by National Institutes of Health Grants RO1-AR052755 and RO1-AI48644 and a Veterans Affairs merit grant. NR 76 TC 45 Z9 47 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2010 VL 184 IS 10 BP 5571 EP 5581 DI 10.4049/jimmunol.0803494 PG 11 WC Immunology SC Immunology GA 594IO UT WOS:000277530700018 PM 20404272 ER PT J AU Elboim, M Gazit, R Gur, C Ghadially, H Betser-Cohen, G Mandelboim, O AF Elboim, Moran Gazit, Roi Gur, Chamutal Ghadially, Hormas Betser-Cohen, Gili Mandelboim, Ofer TI Tumor Immunoediting by NKp46 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NK CELLS; ACTIVATING RECEPTOR; INFLUENZA INFECTION; IN-VIVO; RECOGNITION; NKG2D; NKP30; INHIBITION; IMMUNITY AB NK cells interact with a wide variety of hazardous cells including pathogen-infected and tumor cells. NKp46 is a specific NK killer receptor that recognizes various influenza hemagglutinins and unknown tumor ligands. It was recently shown that NKp46 plays a significant role in the in vivo eradication of tumor cells; however, the role played by NKp46 in vivo with regard to tumor development is still unclear. In this study, we used the 3-methylcholanthrene (MCA)-induced fibrosarcoma model in NKp46-deficient mice to test the NKp46 recognition of carcinogen-induced tumors. We show that although the rate of MCA-induced tumor formation was similar in the presence and in the absence of NKp46, the expression of its unknown ligands was NKp46 dependent. The unknown NKp46 ligands were nearly absent in tumors that originated in wild-type mice, whereas they were detected in tumors that originated in the NKp46-deficient mice. We demonstrate that the interactions between NKp46 and its MCA tumor-derived ligands lead to the secretion of IFN-gamma but not to the elimination of the MCA-derived tumor cells. In addition, we show that the in vivo growth of MCA-derived tumor cells expressing high levels of the NKp46 ligands is NKp46 and IFN-gamma dependent. Thus, we present in this study a novel NKp46-mediated mechanism of tumor editing. The Journal of Immunology, 2010, 184: 5637-5644. C1 [Elboim, Moran; Gur, Chamutal; Ghadially, Hormas; Betser-Cohen, Gili; Mandelboim, Ofer] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. [Gazit, Roi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Immune Dis Inst, Boston, MA 02115 USA. RP Mandelboim, O (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. EM oferm@ekmd.huji.ac.il OI Gazit, Roi/0000-0002-0548-2147 FU Israeli Science Foundation; Israeli Science Foundation (Morasha); Croatia Israel; MOST-DKFZ; European Consortium [MRTN-CT-2005]; Rosetrees Trust; Israel Cancer Association [20100003]; Association for International Cancer Research FX This work was supported by grants from the Israeli Science Foundation, the Israeli Science Foundation (Morasha), a Croatia Israel research grant, a MOST-DKFZ research grant, the European Consortium (Grant MRTN-CT-2005), the Rosetrees Trust, the Israel Cancer Association (Grant 20100003), and the Association for International Cancer Research (all to O.M). O.M is a Crown Professor of Molecular Immunology. NR 37 TC 41 Z9 42 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2010 VL 184 IS 10 BP 5637 EP 5644 DI 10.4049/jimmunol.0901644 PG 8 WC Immunology SC Immunology GA 594IO UT WOS:000277530700026 PM 20404273 ER PT J AU Haug, A Mahalingam, R Cohrs, RJ Schmid, DS Corboy, JR Gilden, D AF Haug, Aaron Mahalingam, Ravi Cohrs, Randall J. Schmid, D. Scott Corboy, John R. Gilden, Don TI Recurrent polymorphonuclear pleocytosis with increased red blood cells caused by varicella zoster virus infection of the central nervous system Case report and review of the literature SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE VZV; Recurrent vasculopathy; Myelitis; Polymorphonuclear cells; Red blood cells ID IMMUNE-DEFICIENCY-SYNDROME; CEREBROSPINAL-FLUID; TRANSVERSE MYELITIS; HERPES-ZOSTER; CYTOMEGALOVIRUS; MENINGITIS; PATIENT; ENCEPHALITIS; VASCULOPATHY; VASCULITIS AB We describe an immunocompetent 45-year-old woman who had four episodes of neurological disease (meningoencephalitis, multifocal vasculopathy, myelitis and inflammatory brain stem disease) produced by varicella zoster virus (VZV) over an 11-month period, all in the absence of rash. The cerebrospinal fluid (CSF) contained anti-VZV IgG antibody, but not VZV DNA throughout her illness, reaffirming the superiority of detection of anti-VZV IgG in CSF compared to VZV DNA in diagnosing VZV infection of the nervous system. Moreover, 3 of 7 CSF samples examined during the 11 months showed a VZV-induced pleocytosis consisting predominantly of polymorphonuclear cells (PMNs), and 4 of 7 samples also contained increased numbers of red blood cells (RBCs). Because increased PMNs and RBCs in CSF can also occur in patients with central and peripheral nervous system disease produced by cytomegalovirus (CMV), the differential diagnosis of chronic nervous system infection with increased PMNs and RBCs in CSF should include analyses for both VZV and CMV. (C) 2010 Elsevier B.V. All rights reserved. C1 [Haug, Aaron; Mahalingam, Ravi; Cohrs, Randall J.; Corboy, John R.; Gilden, Don] Univ Colorado Denver, Sch Med, Dept Neurol, Aurora, CO USA. [Schmid, D. Scott] Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. [Gilden, Don] Univ Colorado Denver, Sch Med, Dept Microbiol, Aurora, CO USA. [Corboy, John R.] Denver Vet Affairs Med Ctr, Dept Neurol, Denver, CO USA. RP Gilden, D (reprint author), 12700 E 19th Ave,Mail Stop B182, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU National Institutes of Health [AG006127, NS032623, AG032958] FX This work was supported in part by the Public Health Service grants AG006127, and NS032623 and AG032958 from the National Institutes of Health. The authors thank Marina Hoffman for editorial review and Cathy Allen for manuscript preparation. NR 31 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY 15 PY 2010 VL 292 IS 1-2 BP 85 EP 88 DI 10.1016/j.jns.2010.01.019 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 584WJ UT WOS:000276784100016 PM 20170926 ER PT J AU Herz, HM Madden, LD Chen, ZH Bolduc, C Buff, E Gupta, R Davuluri, R Shilatifard, A Hariharan, IK Bergmann, A AF Herz, Hans-Martin Madden, Laurence D. Chen, Zhihong Bolduc, Clare Buff, Eugene Gupta, Ravi Davuluri, Ramana Shilatifard, Ali Hariharan, Iswar K. Bergmann, Andreas TI The H3K27me3 Demethylase dUTX Is a Suppressor of Notch- and Rb-Dependent Tumors in Drosophila SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID H3 LYSINE-27 METHYLATION; HISTONE METHYLTRANSFERASE ACTIVITY; EMBRYONIC STEM-CELLS; DEVELOPMENTAL REGULATORS; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR; TARGET GENES; CYCLIN-E; POLYCOMB; CANCER AB Trimethylated lysine 27 of histone H3 (H3K27me3) is an epigenetic mark for gene silencing and can be demethylated by the JmjC domain of UTX. Excessive H3K27me3 levels can cause tumorigenesis, but little is known about the mechanisms leading to those cancers. Mutants of the Drosophila H3K27me3 demethylase dUTX display some characteristics of Trithorax group mutants and have increased H3K27me3 levels in vivo. Surprisingly, dUTX mutations also affect H3K4me1 levels in a JmjC-independent manner. We show that a disruption of the JmjC domain of dUTX results in a growth advantage for mutant cells over adjacent wild-type tissue due to increased proliferation. The growth advantage of dUTX mutant tissue is caused, at least in part, by increased Notch activity, demonstrating that dUTX is a Notch antagonist. Furthermore, the inactivation of Retinoblastoma (Rbf in Drosophila) contributes to the growth advantage of dUTX mutant tissue. The excessive activation of Notch in dUTX mutant cells leads to tumor-like growth in an Rbf-dependent manner. In summary, these data suggest that dUTX is a suppressor of Notch- and Rbf-dependent tumors in Drosophila melanogaster and may provide a model for UTX-dependent tumorigenesis in humans. C1 [Herz, Hans-Martin; Chen, Zhihong; Bolduc, Clare; Bergmann, Andreas] Univ Texas Houston, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Grad Program Genes & Dev,Unit 1000, Houston, TX 77030 USA. [Herz, Hans-Martin; Shilatifard, Ali] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Madden, Laurence D.; Hariharan, Iswar K.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Buff, Eugene] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Gupta, Ravi; Davuluri, Ramana] Wistar Inst Anat & Biol, Ctr Syst & Computat Biol, Philadelphia, PA 19104 USA. RP Bergmann, A (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Grad Program Genes & Dev,Unit 1000, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM abergman@mdanderson.org RI Davuluri, Ramana/D-7348-2011 FU Jane Coffins Child Memorial Fund; National Institutes of Health [GM068016, GM081543, GM074977, GM61672, CA089455, GM069905]; Welch Foundation [G-1496] FX H.-M.H. is a recipient of a fellowship by the Jane Coffins Child Memorial Fund. This work was supported by the National Institutes of Health (grants GM068016, GM081543, and GM074977 to A.B.; GM61672 to I.K.H.; and CA089455 and GM069905 to A.S.) and the Welch Foundation (grant G-1496 to A.B.). NR 81 TC 55 Z9 61 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 15 PY 2010 VL 30 IS 10 BP 2485 EP 2497 DI 10.1128/MCB.01633-09 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 588BK UT WOS:000277040900016 PM 20212086 ER PT J AU Meli, VS Osuna, B Ruvkun, G Frand, AR AF Meli, Vijaykumar S. Osuna, Beatriz Ruvkun, Gary Frand, Alison R. TI MLT-10 Defines a Family of DUF644 and Proline-rich Repeat Proteins Involved in the Molting Cycle of Caenorhabditis elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID C-ELEGANS; EXTRACELLULAR-MATRIX; CROSS-LINKING; COLLAGEN STRUCTURE; ESSENTIAL ROLES; DAUER FORMATION; CELL FUSIONS; NEMATODE; CUTICLE; NHR-25 AB The molting cycle of nematodes involves the periodic synthesis and removal of a collagen-rich exoskeleton, but the underlying molecular mechanisms are not well understood. Here, we describe the mlt-10 gene of Caenorhabditis elegans, which emerged from a genetic screen for molting-defective mutants sensitized by low cholesterol. MLT-10 defines a large family of nematode-specific proteins comprised of DUF644 and tandem P-X2-L-(S/T)-P repeats. Conserved nuclear hormone receptors promote expression of the mlt-10 gene in the hypodermis whenever the exoskeleton is remade. Further, a MLT-10::mCherry fusion protein is released from the hypodermis to the surrounding matrices and fluids during molting. The fusion protein is also detected in strands near the surface of animals. Both loss-of-function and gain-of-function mutations of mlt-10 impede the removal of old cuticles. However, the substitution mutation mlt-10(mg364), which disrupts the proline-rich repeats, causes the most severe phenotype. Mutations of mlt-10 are also associated with abnormalities in the exoskeleton and improper development of the epidermis. Thus, mlt-10 encodes a secreted protein involved in three distinct but interconnected aspects of the molting cycle. We propose that the molting cycle of C. elegans involves the dynamic assembly and disassembly of MLT-10 and possibly the paralogs of MLT-10. C1 [Meli, Vijaykumar S.; Osuna, Beatriz; Frand, Alison R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Frand, AR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. EM afrand@mednet.ucla.edu FU David Geffen School of Medicine at UCLA; Jane Coffin Childs Memorial Foundation; MGH Fund for Medical Discovery; National Institutes of Health FX We thank Julie Ahringer and Marc Vidal for providing bacterial clones. We are grateful to Chris Miller, David Eisenberg, Robert Mecham, Fred Keeley, and Creg Darby for helpful discussions. We thank John Kim, Peter Edwards, and Stanford Frand for critical reading of the manuscript. We thank the C. elegans Knockout Consortium, Shohei Mitani of the Tokyo Women's Medical University, and Laurent Segalat for providing additional strains. This work was supported by funds from the David Geffen School of Medicine at UCLA; postdoctoral fellowships from the Jane Coffin Childs Memorial Foundation and the MGH Fund for Medical Discovery to A. F.; and a National Institutes of Health grant to G. R. Some strains used in this study were provided by the Caenorhabditis Genetics Center (CGC). NR 74 TC 15 Z9 31 U1 0 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 15 PY 2010 VL 21 IS 10 BP 1648 EP 1661 DI 10.1091/mbc.E08-07-0708 PG 14 WC Cell Biology SC Cell Biology GA 595PS UT WOS:000277625200002 PM 20335506 ER PT J AU Friedman, JH Alves, G Hagell, P Marinus, J Marsh, L Martinez-Martin, P Goetz, CG Poewe, W Rascol, O Sampaio, C Stebbins, G Schrag, A AF Friedman, Joseph H. Alves, Guido Hagell, Peter Marinus, Johan Marsh, Laura Martinez-Martin, Pablo Goetz, Christopher G. Poewe, Werner Rascol, Olivier Sampaio, Cristina Stebbins, Glenn Schrag, Anette TI Fatigue Rating Scales Critique and Recommendations by the Movement Disorders Society Task Force on Rating Scales for Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Review DE fatigue; Parkinson's disease; rating scales-fatigue rating scales AB Fatigue has been shown to be a consistent and common problem in Parkinson's disease (PD) in multiple countries and cultures. It is one of the most disabling of all symptoms, including motor dysfunction, and appears early, often predating the onset of motor symptoms. Several studies of the epidemiology of fatigue have been published, often using different scales, but few on treatment. The Movement Disorder Society (MDS) commissioned a task force to assess available clinical rating scales, critique their psychometric properties, summarize their clinical properties, and evaluate the evidence in support of their use in clinical studies in PD. Six clinical researchers reviewed all studies published in peer reviewed journals of fatigue in PD, evaluated the scales' previous use, performance parameters, and quality of validation data, if available. Scales were rated according to criteria provided by the MDS. A scale was "recommended" if it has been used in clinical studies beyond the group that developed it, has been used in PD and psychometric studies have established that it is a valid, reliable and sensitive to change in people with PD. Requiring a scale to have demonstrated sensitivity to change in PD specifically rather than in other areas in order to attain a rating of "recommended" differs from the use of this term in previous MDS task force scale reviews. "Suggested" scales failed to meet all the criteria of a "recommended" scale, usually the criterion of sensitivity to change in a study of PD. Scales were "listed" if they had been used in PD studies but had little or no psychometric data to assess. Some scales could be used both to screen for fatigue as well as to assess fatigue severity, but some were only used to assess severity. The Fatigue Severity Scale was "recommended" for both screening and severity rating. The Fatigue Assessment Inventory, an expanded version of the Fatigue severity Scale, is "suggested" for both screening and severity. The Functional Assessment of Chronic Illness Therapy-Fatigue was "recommended" for screening and "suggested" for severity. The Multidimensional Fatigue Inventory was "suggested" for screening and "recommended" for severity. The Parkinson Fatigue Scale was "recommended" for screening and "suggested" for severity rating. The Fatigue Severity Inventory was "listed" for both screening and severity. The Fatigue Impact Scale for Daily Use, an adaptation of the Fatigue Impact Scale was "listed" for screening and "suggested" for severity. Visual Analogue and Global Impression Scales are both "listed" for screening and severity. The committee concluded that current scales are adequate for fatigue studies in PD but that studies on sensitivity and specificity of the scales are still needed. (C) 2010 Movement Disorder Society C1 [Friedman, Joseph H.] Parkinsons Dis & Movement Disorders Ctr, Warwick, RI USA. [Friedman, Joseph H.] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02912 USA. [Alves, Guido] Stavanger Univ Hosp, Norwegian Ctr Movement Disorders, Stavanger, Norway. [Alves, Guido] Stavanger Univ Hosp, Dept Neurol, Stavanger, Norway. [Hagell, Peter] Univ Lund Hosp, Dept Neurol, S-22185 Lund, Sweden. [Marinus, Johan] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [Marsh, Laura] Johns Hopkins Univ Hosp, Dept Psychiat, Baltimore, MD 21287 USA. [Marsh, Laura] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Martinez-Martin, Pablo] Carlos III Inst Hlth, Area Appl Epidemiol, Ctr Epidemiol, Madrid, Spain. [Martinez-Martin, Pablo] Carlos III Inst Hlth, CIBERNED, Madrid, Spain. [Goetz, Christopher G.; Stebbins, Glenn] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Poewe, Werner] Innsbruck Med Univ, Dept Neurol, Innsbruck, Austria. [Rascol, Olivier] CHU, Clin Invest Ctr 9302, INSERM, Toulouse, France. [Rascol, Olivier] CHU, Dept Clin Pharmacol, Toulouse, France. [Rascol, Olivier] CHU, Dept Neurosci, Toulouse, France. [Rascol, Olivier] Univ UPS Toulouse, Toulouse, France. [Sampaio, Cristina] Fac Med Lisbon, Lab Farmacol Clin & Terapeut, Lisbon, Portugal. [Sampaio, Cristina] Fac Med Lisbon, Inst Mol Med, Lisbon, Portugal. [Schrag, Anette] UCL, Inst Neurol, Dept Clin Neurosci, London WC1E 6BT, England. RP Friedman, JH (reprint author), 227 Centerville Rd, Warwick, RI 02886 USA. EM joseph_friedman@brown.edu RI Marinus, Johan/E-4038-2010; Hagell, Peter/F-5915-2010; Hagell, Peter/G-9559-2014; Schrag, Anette/B-4181-2011 OI Hagell, Peter/0000-0003-2174-372X; Hagell, Peter/0000-0003-2174-372X; Alves, Guido/0000-0003-0630-2870; Schrag, Anette/0000-0002-9872-6680 FU Teva; Novartis; Ingelheim-Boehringer; Cephalon; NIH [R01-MH06966]; Valeant; Epivax; Glaxosmithkline; Norwegian Parkinson's disease association; Swedish Research Council; Swedish Parkinson Foundation; Skane County Council Research and Development Foundation; AFA Forsakringar; Faculty of Medicine at Lund University; Eli Lilly; Forest Research Institute; Boehringer-Ingelheim; Michael J. Fox Foundation; Kinetics FoundationParkinson's Disease Foundation; American Cancer Society; Fragile X Foundation; Employment-Rush University Medical Center; Eisai; Solvay; Lundbeck; Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins [P50-NS-58377] FX J.H. Friedman: Consultancies Acadia Pharm, EMD Serono, MJFox Fdn; Advisory Boards: Lewy body dementia association; Honoraria Astra Zeneca, Teva, Novartis, Ingelheim-Boehringer, Glaxosmithkline; Grants Teva, Novartis, Ingelheim-Boehringer, Cephalon, NIH, Valeant, Epivax; Employment-NeuroHeatlh: Royalties Demos. G. Alves: Honoraria H. Lundbeck A/S; Orion Pharma; Grants-Glaxosmithkline; Norwegian Parkinson's disease association; Employment-Stavenger University Hospital. P Hagell: Consultancies-Glaxo SmithKline; Advisory boards H Lundbeck; Partnerships H Lundbeck; Honoraria H Lundbeck, the World Federation of Neuroscience Nurses; Grants-Swedish Research Council, the Swedish Parkinson Foundation, the Skane County Council Research and Development Foundation, AFA Forsakringar, and the Faculty of Medicine at Lund University; Employment-Lund University; J. Marinus: Employment Leiden University. L. Marsh: Consultancies Merck Serono; Grants-NIH, Eli Lilly; Forest Research Institute; Boehringer-Ingelheim; Employment-Johns Hopkins Medical Center; NIH grant R01-MH06966 and the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins (15) provided support for Dr. Marsh to participate in preparation of this manuscript. P. Martinez-Martin: Consultancies Novartis, Solvay, Glaxosmithkline, and UCB; Honoraria Novartis, Solvay, Glaxosmithkline, and UCB; Employment National Center for Epidemiology and CIBERNED, Carlos Ill Institute of Health, Madrid, Spain. W. Poewe: Employment Innsbruck Medical Center; consultancy and lecture fees from Astra-Zeneca, Teva, Novartis, GSK, Boehringer Ingelheim, UCB, Orion Pharma, and ECB Merck Serono in relation to clinical drug development for Parkinson's disease. C.G. Goetz: Disclosures for the past 12 months: Consulting and Advisory Board Membership with honoraria-Allergan, Biogen, Boehringer-Ingelheim, Ceregene, EMD Pharmaceuticals, Embryon, EMD/Merck KGaA, Impax Pharmaceuticals, 13 Research, Juvantia Pharmaceuticals, Kiowa Pharmaceuticals, Merck and Co, Neurim Pharmaceuticals, Novartis Pharmaceuticals, Osmotica Pharmaceuticals, Ovation Pharmaceuticals, Oxford Biomedica, Schering-Plough, Solstice Neurosciences, Solvay Pharmaceuticals, Synergy/Intec, and Teva Pharmaceuticals; Grants/Research-Funding from NIH, Michael J. Fox Foundation, Kinetics Foundation, and directs the Rush Parkinson's Disease Research Center that receives support from the Parkinson's Disease Foundation; Honoraria-Movement Disorder Society, Northwestern University, American Academy of Neurology, Robert Wood Johnson Medical School; Royalties-Oxford University Press, Elsevier Publishers; Salary-Rush University Medical Center. C. Sampaio: Consultancies/Advisory Boards-In all cases the honoraria due are paid to department and not received personally: Lundbeck, Abbott, Bial, Boeringher-LMS GroupSchering-Plough, Solvay. Salary-Instituto de medicina molecular. G. Stebbins: Honoraria-American Academy of Neurology; Movement Disorder Society, Grants-NIH, Michael J. Fox Foundation, American Cancer Society, Fragile X Foundation; Employment-Rush University Medical Center. O. Rascol: Consultancies-Boehringer-Ingelheim, Eisai, Glaxosmithkline, Novartis, Schering, Solvay, Teva, Lundbeck, UCB; Grants-Boehringer-Ingelheim, Eisai, Glaxosmithkline, Novartis, Solvay, Teva, Lundbeck; Employment-Centre d'Investigation Clinique. A. Schrag: Consultancies-Ingelheim-Boehringer, Osmotica Pharm; Employment-University College. NR 141 TC 64 Z9 67 U1 4 U2 18 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY 15 PY 2010 VL 25 IS 7 BP 805 EP 822 DI 10.1002/mds.22989 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA 605IH UT WOS:000278340700001 PM 20461797 ER PT J AU Klein, A Ghosh, SS Avants, B Yeo, BTT Fischl, B Ardekani, B Gee, JC Mann, JJ Parsey, RV AF Klein, Arno Ghosh, Satrajit S. Avants, Brian Yeo, B. T. T. Fischl, Bruce Ardekani, Babak Gee, James C. Mann, J. J. Parsey, Ramin V. TI Evaluation of volume-based and surface-based brain image registration methods SO NEUROIMAGE LA English DT Article ID COORDINATE SYSTEM; ALGORITHMS; CORTEX AB Establishing correspondences across brains for the purposes of comparison and group analysis is almost universally done by registering images to one another either directly or via a template. However, there are many registration algorithms to choose from. A recent evaluation of fully automated nonlinear deformation methods applied to brain image registration was restricted to volume-based methods. The present study is the first that directly compares some of the most accurate of these volume registration methods with surface registration methods, as well as the first study to compare registrations of whole-head and brain-only (de-skulled) images. We used permutation tests to compare the overlap or Hausdorff distance performance for more than 16,000 registrations between 80 manually labeled brain images. We compared every combination of volume-based and surface-based labels, registration, and evaluation. Our primary findings are the following: 1. de-skulling aids volume registration methods; 2. custom-made optimal average templates improve registration over direct pairwise registration; and 3. resampling volume labels on surfaces or converting surface labels to volumes introduces distortions that preclude a fair comparison between the highest ranking volume and surface registration methods using present resampling methods. From the results of this study, we recommend constructing a custom template from a limited sample drawn from the same or a similar representative population, using the same algorithm used for registering brains to the template. (C) 2010 Published by Elsevier Inc. C1 [Klein, Arno; Mann, J. J.; Parsey, Ramin V.] Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. [Ghosh, Satrajit S.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Avants, Brian; Gee, James C.] Univ Penn, Dept Radiol, Penn Image Comp & Sci Lab, Philadelphia, PA 19104 USA. [Yeo, B. T. T.] Harvard Univ, Cognit Neurosci Lab, Cambridge, MA 02138 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. [Ardekani, Babak] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Ardekani, Babak] NYU, Sch Med, New York, NY 10016 USA. RP Klein, A (reprint author), Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. EM arno@binarybottle.com OI Klein, Arno/0000-0002-0707-2889; avants, brian/0000-0002-4212-3362; Ghosh, Satrajit/0000-0002-5312-6729; Yeo, B.T. Thomas/0000-0002-0119-3276 FU National Institutes of Health through NIH [R01 MH084029]; National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R03 EB008673, R03 EB008201]; National Institute of Neurological Disorders and Stroke (NINDS); National Center for Research Resources [P41-RR14075]; CRR BIRN Morphometric [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01 EB006758]; National Institute on Aging [AG02238]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; Mental Illness and Neuroscience Discovery (MIND) Institute; National Alliance for Medical Image Computing (NAMIC); National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149]; Ellison Medical Foundation FX We would like to thank the reviewers for their comments, David Shattuck for making available an early second release of the publicly available LPBA40 whole-head MR and label data, and Douglas Greve for advice on estimating smoothness of the FreeSurfer spherical templates. The first author is grateful to his colleagues in the Division of Molecular Imaging and Neuropathology, and, as always, to his two closest colleagues Deepanjana and Ellora. This work was partially funded by the National Institutes of Health through NIH grant R01 MH084029. Satrajit Ghosh was partially supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant R03 EB008673. The contributions to this paper by Babak A. Ardekani were supported by grant R03 EB008201 from the NIBIB and the National Institute of Neurological Disorders and Stroke (NINDS).; Bruce Fischl would like to acknowledge support provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB006758), the National Institute on Aging (AG02238), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01) as well as the Mental Illness and Neuroscience Discovery (MIND) Institute, and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, grant U54 EB005149. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. NR 25 TC 93 Z9 94 U1 4 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2010 VL 51 IS 1 BP 214 EP 220 DI 10.1016/j.neuroimage.2010.01.091 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 580WC UT WOS:000276480200021 PM 20123029 ER PT J AU Poser, BA Koopmans, PJ Witzel, T Wald, LL Barth, M AF Poser, B. A. Koopmans, P. J. Witzel, T. Wald, L. L. Barth, M. TI Three dimensional echo-planar imaging at 7 Tesla SO NEUROIMAGE LA English DT Article ID FUNCTIONAL MRI; PHYSIOLOGICAL NOISE; FMRI TECHNIQUE; PRESTO-SENSE; BRAIN; SENSITIVITY; EPI; OPTIMIZATION; ACQUISITION; PRINCIPLES AB Functional MRI (fMRI) most commonly employs 2D echo-planar imaging (EPI). The advantages for fMRI brought about by the increasingly popular ultra-high field strengths are best exploited in high-resolution acquisitions, but here 2D EPI becomes unpractical for several reasons, including the very long volume acquisitions times. In this study at 7 T, a 3D EPI sequence with full parallel and partial Fourier imaging capability along both phase encoding axes was implemented and used to evaluate the sensitivity of 3D and corresponding 2D EPI acquisitions at four different spatial resolutions ranging from small to typical voxel sizes (1.5-3.0 mm isotropic). Whole-brain resting state measurements (N = 4) revealed a better, or at least comparable sensitivity of the 3D method for gray and white matter. The larger vulnerability of 3D to physiological effects was outweighed by the much shorter volume TR, which moreover allows whole-brain coverage at high resolution within fully acceptable limits for event-related fMRI: TR was only 3.07 s for 1.5 mm, 1.88 s for 2.0 mm, 1.38 s for 2.5 mm and 1.07 s for 3.0 mm isotropic resolution. In order to investigate the ability to detect and spatially resolve BOLD activation in the visual cortex, functional 3D EPI experiments (N = 8) were performed at 1 mm isotropic resolution with parallel imaging acceleration of 3 x 3, resulting in a TR of only 3.2 s for whole-brain coverage. From our results, and several other practical advantages of 3D over 2D EPI found in the present study, we conclude that 3D EPI provides a useful alternative for whole-brain fMRI at 7 T, not only when high-resolution data are required. (C) 2010 Elsevier Inc. All rights reserved. C1 [Poser, B. A.; Barth, M.] Univ Duisburg Essen, Erwin L Hahn Inst Magnet Resonance Imaging, D-45141 Essen, Germany. [Poser, B. A.; Koopmans, P. J.; Barth, M.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. [Witzel, T.; Wald, L. L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, Charlestown, MA USA. [Witzel, T.; Wald, L. L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Poser, BA (reprint author), Univ Duisburg Essen, Erwin L Hahn Inst Magnet Resonance Imaging, UNESCO World Cultural Heritage Zollverein Arendah, D-45141 Essen, Germany. EM benedikt.poser@donders.ru.nl RI Barth, Markus/B-8446-2008; Poser, Benedikt A/F-4992-2010; Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009 OI Barth, Markus/0000-0002-0520-1843; Poser, Benedikt A/0000-0001-8190-4367; FU National Institutes of Health [NCRR P41RR14075, NIBIB R01EB006847]; Siemens Healthcare FX Two authors (T.W. and L.L.W.) acknowledge support from National Institutes of Health grants: NCRR P41RR14075, NIBIB R01EB006847 and research support from Siemens Healthcare. One of the authors (L.L.W.) has obtained consulting income from Siemens Healthcare. NR 28 TC 80 Z9 80 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2010 VL 51 IS 1 BP 261 EP 266 DI 10.1016/j.neuroimage.2010.01.108 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 580WC UT WOS:000276480200026 PM 20139009 ER PT J AU Karlsson, KAE Windischberger, C Gerstl, F Mayr, W Siegel, JM Moser, E AF Karlsson, K. AE. Windischberger, C. Gerstl, F. Mayr, W. Siegel, J. M. Moser, E. TI Modulation of hypothalamus and amygdalar activation levels with stimulus valence SO NEUROIMAGE LA English DT Article DE fMRI; Hypothalamus; Amygdala; Emotion ID FACIAL EXPRESSIONS; HUMAN NARCOLEPSY; EMOTION; HUMOR; FMRI; NEURONS; HYPOCRETIN/OREXIN; METAANALYSIS; REWARD; EPI AB In spite of long-standing evidence showing that the hypothalamus is instrumental in generating behaviors associated with positive and negative emotions, little is known about the role of the hypothalamus in normal human emotional processing. Recent findings have suggested that the hypothalamus plays a role beyond mere control of HPA-axis function; this is also supported by the existence of rich anatomical connections between the hypothalamus and the amygdala. a region known for its important role in emotional processing. However, evidence of emotion-induced hypothalamic activity from neuroimaging studies has been inconsistent, possibly due to methodological limitations (e.g., low spatial resolution). Taking advantage of recent improvements in fMRI technology we set out to explore a possible valence-dependent modulation of hypothalamic activity. Using second order parametric analysis of high-resolution BOLD fMRI, we assessed hypothalamic activation patterns during passive viewing of visual stimuli of varying valence, and compared the results with the activity pattern in the amygdalae, i.e. nuclei with known valence-dependent activity profiles. We show that both hypothalamic and amygdalar activation is modulated by the second-order stimulus valence term, i.e., there is increased neural activity following the processing of both positive and negative stimuli. Our results suggest that the hypothalamus may serve a role in generating emotions broader than generally assumed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Windischberger, C.; Gerstl, F.; Moser, E.] Med Univ Vienna, MR Ctr Excellence, A-1090 Vienna, Austria. [Karlsson, K. AE.] Reykjavik Univ, Sch Sci & Engn, Dept Biomed Engn, Reykjavik, Iceland. [Windischberger, C.; Mayr, W.; Moser, E.] Med Univ Vienna, Ctr Biomed Engn & Phys, A-1090 Vienna, Austria. [Siegel, J. M.] VA GLAHS Sepulveda, Ctr Sleep Res, Neurobiol Res, Los Angeles, CA USA. [Siegel, J. M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Moser, E.] Univ Penn, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Moser, E (reprint author), Med Univ Vienna, MR Ctr Excellence, Lazarettgasse 14, A-1090 Vienna, Austria. EM ewald.moser@meduniwien.ac.at RI Moser, Ewald/B-3666-2013; OI Moser, Ewald/0000-0001-8278-9583; Windischberger, Christian/0000-0002-9944-0190 FU Icelandic Centre for Research [070431022]; Reykjavik University [14630] FX Financially supported by Icelandic Centre for Research grant no. 070431022 (to KAEK) and Reykjavik University Development fund no. 14630 (to KAEK). We are grateful to M. Fursatz (Vienna) for his support with the initial experiments, as well as H. Arnadottir and I. Johannesdottir (Reykjavik) for collecting and validating the stimulus material. NR 32 TC 8 Z9 9 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2010 VL 51 IS 1 BP 324 EP 328 DI 10.1016/j.neuroimage.2010.02.029 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 580WC UT WOS:000276480200033 PM 20156568 ER PT J AU Maxeiner, A Adkins, CB Zhang, YF Taupitz, M Halpern, EF McDougal, WS Wu, CL Cheng, LL AF Maxeiner, Andreas Adkins, Christen B. Zhang, Yifen Taupitz, Matthias Halpern, Elkan F. McDougal, W. Scott Wu, Chin-Lee Cheng, Leo L. TI Retrospective Analysis of Prostate Cancer Recurrence Potential With Tissue Metabolomic Profiles SO PROSTATE LA English DT Article DE high-resolution magic angle spinning; magnetic resonance spectroscopy; prostatectomy; prostate cancer recurrence ID MORTALITY; NOMOGRAM; ANTIGEN; BIOPSY AB BACKGROUND. In clinical care of prostate cancer patients, an improved method to assess the risk of recurrence after surgical treatment is urgently needed. We aim to retrospectively evaluate the ability of ex vivo tissue magnetic-resonance-spectroscopy-based metabolomic profiles to estimate the risk of recurrence. METHODS. PCa recurrence is defined biochemically as the detection of serum PSA after radical prostatectomy. Sixteen consecutive PCa-recurrent cases, those with an initial PSA increase of 0.69 +/- 0.26 ng/ml monitored 47.7 +/- 2.6 months after prostatectomy were paired by age and Gleason score with cases without recurrence of the same pathological and clinical stages (n = 16/each). We analyzed ex vivo intact-tissue spectroscopy results from these 48 individuals at the time of prostatectomy at 14T. From these spectra, we identified the 27 most common and intense spectral metabolic regions for statistical analyses. RESULTS. Principal component analysis (PCA) on these spectral regions from cases of clinical-stage-matched groups with and without recurrence identified four pathology-related principal components. Canonical analysis of these four and the first nine principal components for cases in the two groups defined metabolomic profiles as the canonical score that can differentiate the two groups with statistical significance. By applying the coefficients from PCA and canonical analysis to the pathological-stage-matched groups, recurrence was predicted with an accuracy of 78%. CONCLUSIONS. Results indicate the potential of tissue metabolomic profiles measured with ex vivo spectroscopy to identify PCa aggressiveness in terms of cancer recurrence. With further study, this may greatly contribute to the future design of clinical strategy for personalized treatment of PCa patients. Prostate 70: 710-717, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Maxeiner, Andreas; Adkins, Christen B.; Zhang, Yifen; Wu, Chin-Lee; Cheng, Leo L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maxeiner, Andreas; Taupitz, Matthias] Charite, Dept Radiol, D-13353 Berlin, Germany. [Halpern, Elkan F.; Cheng, Leo L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [McDougal, W. Scott; Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA USA. RP Cheng, LL (reprint author), Pathol Res CNY 7,149 13th St, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu FU Bertucci Prostate Cancer Fund [CA115746, CA095624]; MGH A. A. Martinos Center for Biomedical Imaging FX This work was supported by CA115746 and CA095624 (to L.L.C.), Bertucci Prostate Cancer Fund (C.-L.W.), and MGH A. A. Martinos Center for Biomedical Imaging. NR 16 TC 18 Z9 18 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2010 VL 70 IS 7 BP 710 EP 717 DI 10.1002/pros.21103 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 591XM UT WOS:000277338800003 PM 20017167 ER PT J AU Wingo, AP Baldessarini, RJ Compton, MT Harvey, PD AF Wingo, Aliza P. Baldessarini, Ross J. Compton, Michael T. Harvey, Philip D. TI Correlates of recovery of social functioning in types I and II bipolar disorder patients SO PSYCHIATRY RESEARCH LA English DT Article DE Bipolar disorder; Depression; Neurocognition; Social functional recovery; Age ID PSYCHOSOCIAL ADJUSTMENT; DEPRESSION; IMPAIRMENT; DISABILITY; MANIA; REMISSION; EDUCATION; SYMPTOMS; INSIGHT; PROGRAM AB Since bipolar disorder (BPD) patients are often functionally impaired, and factors associated with recovery from disability are largely unknown, we investigated demographic, clinical, and neurocognitive correlates of current social functional recovery in 65 stable participants diagnosed with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) type I (n = 42) or II (n = 23) BPD. Regaining highest previous levels of social functioning was rated with the Interpersonal Relationships Questionnaire. We also considered neuropsychological test findings as well as demographic and clinical information including mania and depression symptom-ratings. We examined factors associated with social recovery status using univariate analyses and then multiple logistic regression modeling. Of all subjects, 30 (46%) achieved current social functional recovery and 35 (54%) did not. Younger age (P = 0.005) and lesser current depressive symptoms (P = 0.02) were associated with social functional recovery, even after controlling for time since the last major mood episode, diagnostic type (II vs. I), co-morbid psychiatric illness, and executive functioning status. The findings are consistent with deleterious effects of even residual depressive symptoms in BPD patients. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Wingo, Aliza P.; Compton, Michael T.; Harvey, Philip D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Mailman Res Ctr, Belmont, MA 02478 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Mailman Res Ctr, Belmont, MA 02478 USA. RP Wingo, AP (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 101 Woodruff Circle NE,Suite 4000, Atlanta, GA 30322 USA. EM aliza.wingo@emory.edu FU NIH [UL1 RR-025008]; American Psychiatric Institute for Research Education; Bruce J. Anderson Foundation; McLean Private Donors Research Fund; AstraZeneca FX Supported by NIH grant UL1 RR-025008 and an APIRE research fellowship from the American Psychiatric Institute for Research & Education (to APW), a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund (to RJB).; Disclosures: Dr Wingo has no relevant potential conflicts of interest. Dr. Baldessarini has recently been a consultant or investigator-initiated research collaborator with Auritec, Biotrofix, IFI, Janssen, JDS, Lilly, Luitpold, Merck, NeuroHealing, Novartis, Pfizer, and SK-BioPharmaceuticals Corporations, but is not a member of pharmaceutical speakers' bureaus, nor does he or any family member hold equity positions in biomedical or pharmaceutical corporations. Dr. Compton has no relevant potential conflicts of interest. Dr. Harvey has been a consultant in the past year to Eli Lilly, Johnson & Johnson, Merck, Shire Pharma, Dainippon-Sumitomo/America, and has current research support from AstraZeneca. NR 27 TC 11 Z9 12 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2010 VL 177 IS 1-2 BP 131 EP 134 DI 10.1016/j.psychres.2010.02.020 PG 4 WC Psychiatry SC Psychiatry GA 604KV UT WOS:000278278800023 PM 20334933 ER PT J AU Sirmaci, A Erbek, S Price, J Huang, MQ Duman, D Cengiz, FB Bademci, G Tokgoz-Yilmaz, S Hismi, B Ozdag, H Ozturk, B Kulaksizoglu, S Yildirim, E Kokotas, H Grigoriadou, M Petersen, MB Shahin, H Kanaan, M King, MC Chen, ZY Blanton, SH Liu, XZ Zuchner, S Akar, N Tekin, M AF Sirmaci, Asli Erbek, Seyra Price, Justin Huang, Mingqian Duman, Duygu Cengiz, F. Basak Bademci, Gueney Tokgoez-Yilmaz, Suna Hismi, Burcu Oezdag, Hilal Oeztuerk, Banu Kulaksizoglu, Sevsen Yildirim, Erkan Kokotas, Haris Grigoriadou, Maria Petersen, Michael B. Shahin, Hashem Kanaan, Moien King, Mary-Claire Chen, Zheng-Yi Blanton, Susan H. Liu, Xue Z. Zuchner, Stephan Akar, Nejat Tekin, Mustafa TI A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEINASE-INHIBITOR 6; IDENTIFICATION; EVOLUTION; APOPTOSIS; PROTEASE; DEAFNESS; PATHWAY; TURKEY AB More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DENB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DENB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and sensorineural hearing loss. C1 [Sirmaci, Asli; Price, Justin; Bademci, Gueney; Blanton, Susan H.; Zuchner, Stephan; Tekin, Mustafa] Univ Miami, Miller Sch Med, Dr John T Macdonald Dept Human Genet, Miami, FL 33136 USA. [Sirmaci, Asli; Price, Justin; Bademci, Gueney; Blanton, Susan H.; Liu, Xue Z.; Zuchner, Stephan; Tekin, Mustafa] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Erbek, Seyra] Baskent Univ, Sch Med, Dept Otorhinolaryngol, TR-06490 Ankara, Turkey. [Huang, Mingqian; Chen, Zheng-Yi] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol,Eaton Peabody Lab, Boston, MA 02114 USA. [Duman, Duygu; Cengiz, F. Basak; Tokgoez-Yilmaz, Suna; Hismi, Burcu; Akar, Nejat] Ankara Univ, Sch Med, Dept Pediat, Div Genet, TR-06100 Ankara, Turkey. [Oezdag, Hilal] Ankara Univ, Inst Biotechnol, TR-06100 Ankara, Turkey. [Oeztuerk, Banu] Selcuk Univ, Meram Sch Med, Dept Ophthalmol, TR-42080 Konya, Turkey. [Kulaksizoglu, Sevsen] Baskent Univ, Sch Med, Dept Biochem, TR-42080 Konya, Turkey. [Yildirim, Erkan] Baskent Univ, Sch Med, Dept Radiodiagnost, TR-42080 Konya, Turkey. [Kokotas, Haris; Grigoriadou, Maria; Petersen, Michael B.] Aghia Sophia Childrens Hosp, Inst Child Hlth, Dept Genet, Athens 11527, Greece. [Shahin, Hashem; Kanaan, Moien] Bethlehem Univ, Dept Life Sci, Bethlehem, Israel. [King, Mary-Claire] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Liu, Xue Z.] Univ Miami, Miller Sch Med, Dept Otorhinolaryngol, Miami, FL 33136 USA. RP Tekin, M (reprint author), Univ Miami, Miller Sch Med, Dr John T Macdonald Dept Human Genet, Miami, FL 33136 USA. EM mtekin@med.miami.edu RI Ozdag, Hilal/C-9929-2009; Petersen, Michael Bjorn/D-1483-2017; OI Ozdag, Hilal/0000-0001-7940-2499; Petersen, Michael Bjorn/0000-0003-0316-8207; Bademci, Guney/0000-0002-4052-8833 FU The Scientific & Technological Research Council of Turkey [105S464, 108S045]; University of Miami; NIH [R01 DC006908]; National Natural Science Foundation of China [30728030]; Federick and Ines Yeatts [R01 DC005575]; Oticon Fonden, Denmark FX We are thankful to all participating families. We thank Professor Phillip I. Bird from Monash University, Australia, for helpful suggestions and critical reading of the manuscript. This study was partially supported by The Scientific & Technological Research Council of Turkey Grants (105S464 and 108S045), funds from the University of Miami to M.T., NIH R01 DC006908 to Z.-Y.C., National Natural Science Foundation of China to Z.-Y.C. (30728030), the Federick and Ines Yeatts inner ear hair cell regeneration fellowship to M.H., R01 DC005575 to X.Z.L., and a grant from Oticon Fonden, Denmark, to M.B.P. NR 27 TC 25 Z9 27 U1 3 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY 14 PY 2010 VL 86 IS 5 BP 797 EP 804 DI 10.1016/j.ajhg.2010.04.004 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 601GC UT WOS:000278045300016 PM 20451170 ER PT J AU Greenwood, CMT Sun, SY Veenstra, J Hamel, N Niell, B Gruber, S Foulkes, WD AF Greenwood, Celia M. T. Sun, Shuying Veenstra, Justin Hamel, Nancy Niell, Bethany Gruber, Stephen Foulkes, William D. TI How old is this mutation? - a study of three Ashkenazi Jewish founder mutations SO BMC GENETICS LA English DT Article ID LINKAGE-DISEQUILIBRIUM; HAPLOTYPE RECONSTRUCTION; PHENOTYPE ANALYSIS; COLORECTAL-CANCER; BREAST-CANCER; GENETIC DRIFT; POPULATION; PREVALENCE; FAMILIES; I1307K AB Background: Several founder mutations leading to increased risk of cancer among Ashkenazi Jewish individuals have been identified, and some estimates of the age of the mutations have been published. A variety of different methods have been used previously to estimate the age of the mutations. Here three datasets containing genotype information near known founder mutations are reanalyzed in order to compare three approaches for estimating the age of a mutation. The methods are: (a) the single marker method used by Risch et al., (1995); (b) the intra-allelic coalescent model known as DMLE, and (c) the Goldgar method proposed in Neuhausen et al. (1996), and modified slightly by our group. The three mutations analyzed were MSH2*1906G->C, APC*I1307K, and BRCA2*6174delT. Results: All methods depend on accurate estimates of inter-marker recombination rates. The modified Goldgar method allows for marker mutation as well as recombination, but requires prior estimates of the possible haplotypes carrying the mutation for each individual. It does not incorporate population growth rates. The DMLE method simultaneously estimates the haplotypes with the mutation age, and builds in the population growth rate. The single marker estimates, however, are more sensitive to the recombination rates and are unstable. Mutation age estimates based on DMLE are 16.8 generations for MSH2 (95% credible interval (13, 23)), 106 generations for I1037K (86-129), and 90 generations for 6174delT (71-114). Conclusions: For recent founder mutations where marker mutations are unlikely to have occurred, both DMLE and the Goldgar method can give good results. Caution is necessary for older mutations, especially if the effective population size may have remained small for a long period of time. C1 [Hamel, Nancy; Foulkes, William D.] McGill Univ, Ctr Hlth, Res Inst, Dept Med Genet, Montreal, PQ, Canada. [Niell, Bethany] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gruber, Stephen] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Foulkes, William D.] McGill Univ, Dept Human Genet, Gerald Bronfman Ctr Clin Res Oncol, Montreal, PQ, Canada. [Foulkes, William D.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Foulkes, William D.] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Veenstra, Justin] Univ Western Ontario, Dept Stat & Actuarial Sci, London, ON, Canada. [Sun, Shuying] Case Comprehens Canc Ctr, Cleveland, OH USA. [Greenwood, Celia M. T.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Greenwood, Celia M. T.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. RP Foulkes, WD (reprint author), McGill Univ, Ctr Hlth, Res Inst, Dept Med Genet, Montreal, PQ, Canada. EM william.foulkes@mcgill.ca OI foulkes, william/0000-0001-7427-4651 FU Ontario Genomics Institute and Genome Canada; Mathematics of Information Technology and Complex Systems/Networks of Centres of Excellence Program; Sharon Elghanayan Research Initiative FX David Goldgar provided the original code for estimating mutation age using the likelihood method, and made some helpful suggestions. Thanks to Dr. Nathan Ellis and Dr. Kenneth Offit for providing the data on breast cancer cases carrying the BRCA2*6174delT mutation, and controls. We also acknowledge the assistance of Dr. Vijai Joseph, and give grateful thanks to the authors for DMLE for their assistance. This work was partially funded by the Ontario Genomics Institute and Genome Canada, by the Mathematics of Information Technology and Complex Systems/Networks of Centres of Excellence Program, and was also supported by the Sharon Elghanayan Research Initiative. NR 25 TC 10 Z9 10 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD MAY 14 PY 2010 VL 11 AR 39 DI 10.1186/1471-2156-11-39 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 624YQ UT WOS:000279858600002 PM 20470408 ER PT J AU Tcherkezian, J Brittis, PA Thomas, F Roux, PP Flanagan, JG AF Tcherkezian, Joseph Brittis, Perry A. Thomas, Franziska Roux, Philippe P. Flanagan, John G. TI Transmembrane Receptor DCC Associates with Protein Synthesis Machinery and Regulates Translation SO CELL LA English DT Article ID MESSENGER-RNA LOCALIZATION; PEPTIDYL-TRANSFER-RNA; COLORECTAL-CANCER; GROWTH CONES; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; NETRIN RECEPTOR; GUIDANCE; ACTIN; RIBOSOME AB Extracellular signals regulate protein translation in many cell functions. A key advantage of control at the translational level is the opportunity to regulate protein synthesis within specific cellular subregions. However, little is known about mechanisms that may link extracellular cues to translation with spatial precision. Here, we show that a transmembrane receptor, DCC, forms a binding complex containing multiple translation components, including eukaryotic initiation factors, ribosomal large and small subunits, and monosomes. In neuronal axons and dendrites DCC colocalizes in particles with translation machinery, and newly synthesized protein. The extracellular ligand netrin promoted DCC-mediated translation and disassociation of translation components. The functional and physical association of a cell surface receptor with the translation machinery leads to a generalizable model for localization and extracellular regulation of protein synthesis, based on a transmembrane translation regulation complex. C1 [Tcherkezian, Joseph; Brittis, Perry A.; Flanagan, John G.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Thomas, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roux, Philippe P.] Univ Montreal, Fac Med, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada. [Roux, Philippe P.] Univ Montreal, Fac Med, Dept Pathol & Cell Biol, Montreal, PQ H3T 1J4, Canada. RP Brittis, PA (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM perry_brittis@hms.harvard.edu; flanagan@hms.harvard.edu RI Roux, Philippe/J-3996-2012 OI Roux, Philippe/0000-0002-5962-0250 FU NIH; NCIC; HHMI; CIHR; Canada Research Chair; HFSP FX We thank Marc Kirschner, Dietmar Schmucker, Melissa Hancock, Marc Tessier-Lavigne, Nancy Kadersha, Steven Gygi, Ross Tomaino, Tom Walz, Maria Ericsson, Natalie Farny, Pam Silver, Joachim Hauber, Taka-Aki Sato, Nathalie Lamarche-Vane, John Blenis, Davie Van Vactor, Judy Glaven, Yao Chen, Dan Nowakowski, Miriam Osterfield, and Nicolas Preitner, for help, reagents, advice, and comments on the manuscript. This work was supported by grants from the NIH (J.G.F.) and NCIC (P.P.R.), an HHMI fellowship (P.A.B.), a CIHR fellowship (J.T.), and a Canada Research Chair and HFSP Career Development Award (P.P.R.). NR 51 TC 109 Z9 110 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 14 PY 2010 VL 141 IS 4 BP 632 EP 644 DI 10.1016/j.cell.2010.04.008 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 595PH UT WOS:000277623600016 PM 20434207 ER PT J AU Baron, RM Lopez-Guzman, S Riascos, DF Macias, AA Layne, MD Cheng, GY Harris, C Chung, SW Reeves, R von Andrian, UH Perrella, MA AF Baron, Rebecca M. Lopez-Guzman, Silvia Riascos, Dario F. Macias, Alvaro A. Layne, Matthew D. Cheng, Guiying Harris, Cailin Chung, Su Wol Reeves, Raymond von Andrian, Ulrich H. Perrella, Mark A. TI Distamycin A Inhibits HMGA1-Binding to the P-Selectin Promoter and Attenuates Lung and Liver Inflammation during Murine Endotoxemia SO PLOS ONE LA English DT Article ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; MOBILITY GROUP-I(Y) PROTEIN; NECROSIS-FACTOR-ALPHA; MINOR-GROOVE-BINDING; RESPIRATORY-DISTRESS-SYNDROME; IFN-BETA GENE; ENDOTHELIAL-CELLS; ADHESION MOLECULE; IN-VIVO AB Background: The architectural transcription factor High Mobility Group-A1 (HMGA1) binds to the minor groove of AT-rich DNA and forms transcription factor complexes ("enhanceosomes'') that upregulate expression of select genes within the inflammatory cascade during critical illness syndromes such as acute lung injury (ALI). AT-rich regions of DNA surround transcription factor binding sites in genes critical for the inflammatory response. Minor groove binding drugs (MGBs), such as Distamycin A (Dist A), interfere with AT-rich region DNA binding in a sequence and conformation-specific manner, and HMGA1 is one of the few transcription factors whose binding is inhibited by MGBs. Objectives: To determine whether MGBs exert beneficial effects during endotoxemia through attenuating tissue inflammation via interfering with HMGA1-DNA binding and modulating expression of adhesion molecules. Methodology/Principal Findings: Administration of Dist A significantly decreased lung and liver inflammation during murine endotoxemia. In intravital microscopy studies, Dist A attenuated neutrophil-endothelial interactions in vivo following an inflammatory stimulus. Endotoxin induction of P-selectin expression in lung and liver tissue and promoter activity in endothelial cells was significantly reduced by Dist A, while E-selectin induction was not significantly affected. Moreover, Dist A disrupted formation of an inducible complex containing NF-kappa B that binds an AT-rich region of the P-selectin promoter. Transfection studies demonstrated a critical role for HMGA1 in facilitating cytokine and NF-kappa B induction of P-selectin promoter activity, and Dist A inhibited binding of HMGA1 to this AT-rich region of the P-selectin promoter in vivo. Conclusions/Significance: We describe a novel targeted approach in modulating lung and liver inflammation in vivo during murine endotoxemia through decreasing binding of HMGA1 to a distinct AT-rich region of the P-selectin promoter. These studies highlight the ability of MGBs to function as molecular tools for dissecting transcriptional mechanisms in vivo and suggest alternative treatment approaches for critical illness. C1 [Baron, Rebecca M.; Lopez-Guzman, Silvia; Riascos, Dario F.; Macias, Alvaro A.; Harris, Cailin; Chung, Su Wol; Perrella, Mark A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Baron, Rebecca M.; Perrella, Mark A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Perrella, Mark A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Newborn Med, Boston, MA 02115 USA. [Riascos, Dario F.] Pontificia Univ Javeriana, Dept Physiol Sci, Bogota, Colombia. [Layne, Matthew D.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. [Cheng, Guiying; von Andrian, Ulrich H.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Cheng, Guiying; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chung, Su Wol] Univ Ulsan, Sch Biol Sci, Ulsan 680749, South Korea. [Reeves, Raymond] Washington State Univ, Dept Biochem & Biophys, Pullman, WA 99164 USA. RP Baron, RM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. EM rbaron@partners.org RI Lopez-Guzman, Silvia/G-7595-2012; von Andrian, Ulrich/A-5775-2008; OI Layne, Matthew/0000-0003-0007-4870; Lopez-Guzman, Silvia/0000-0003-0271-3576 FU National Institutes of Health [AI054465, HL091957, AI061246, GM53249, HL60788] FX This work was supported by Grants AI054465 (to R. M. B.), HL091957 (to R. M. B.), AI061246 (to M. A. P.), GM53249 (to M. A. P.), and HL60788 (to M. A. P.), all from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 75 TC 13 Z9 13 U1 0 U2 2 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 MAY 14 PY 2010 VL 5 IS 5 AR e10656 DI 10.1371/journal.pone.0010656 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 597PU UT WOS:000277771600018 PM 20498830 ER PT J AU Ullrich, CK Dussel, V Hilden, JM Sheaffer, JW Lehmann, L Wolfe, J AF Ullrich, Christina K. Dussel, Veronica Hilden, Joanne M. Sheaffer, Jan W. Lehmann, Leslie Wolfe, Joanne TI End-of-life experience of children undergoing stem cell transplantation for malignancy: parent and provider perspectives and patterns of care SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PATIENT-CONTROLLED ANALGESIA; VERSUS-HOST-DISEASE; PALLIATIVE CARE; LUNG TRANSPLANTATION; CYSTIC-FIBROSIS; PEDIATRIC-PATIENTS; TERMINAL CARE; FOLLOW-UP; CANCER AB The end-of-life (EOL) experience of children who undergo stem cell transplantation (SCT) may differ from that of other children with cancer. To evaluate perspectives and patterns of EOL care after SCT, we surveyed 141 parents of children who died of cancer (response rate, 64%) and their physicians. Chart review provided additional information. Children for whom SCT was the last cancer therapy (n = 31) were compared with those for whom it was not (n = 110). SCT parents and physicians recognized no realistic chance for cure later than non-SCT peers (both P < .001) and were more likely to have a primary goal of cure at death (parents, P < .001; physicians, P = .02). SCT children were more likely to suffer highly from their last cancer therapy and die in the intensive care unit (both P < .001), with less opportunity for EOL preparation. SCT parents who recognized no realistic chance for cure more than 7 days before death along with the physician were more likely to prepare for EOL, and if their primary goal was to reduce suffering, to achieve this (P < .001). SCT is associated with significant suffering and less opportunity to prepare for EOL. Children and families undergoing SCT may benefit from ongoing discussions regarding prognosis, goals, and opportunities to maximize quality of life. (Blood. 2010; 115(19): 3879-3885) C1 [Ullrich, Christina K.; Dussel, Veronica; Lehmann, Leslie; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Ullrich, Christina K.; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Ullrich, Christina K.; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Ullrich, Christina K.; Dussel, Veronica; Lehmann, Leslie; Wolfe, Joanne] Childrens Hosp Boston, Dept Med, Boston, MA USA. [Hilden, Joanne M.] Peyton Manning Childrens Hosp St Vincent, Dept Pediat, Indianapolis, IN USA. [Sheaffer, Jan W.] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, St Paul, MN USA. [Sheaffer, Jan W.] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, Minneapolis, MN USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Smith 205,44 Binney St, Boston, MA 02115 USA. EM christina_ullrich@dfci.harvard.edu FU Olive Branch Foundation Scholar of the National Palliative Care Research Center; Gloria Spivak Merit Award; Pine Tree Apple Tennis Classic Oncology Research Fund FX C. K. U. is an Olive Branch Foundation Scholar of the National Palliative Care Research Center. J.W. is the recipient of the Gloria Spivak Merit Award. J.W. S. was supported by the Pine Tree Apple Tennis Classic Oncology Research Fund. NR 50 TC 29 Z9 31 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 13 PY 2010 VL 115 IS 19 BP 3879 EP 3885 PG 7 WC Hematology SC Hematology GA 595NV UT WOS:000277619000008 PM 20228275 ER PT J AU DallaPiazza, M Amorosa, VK Localio, R Kostman, JR Lo Re, V AF DallaPiazza, Michelle Amorosa, Valerianna K. Localio, Russell Kostman, Jay R. Lo Re, Vincent, III TI Prevalence and risk factors for significant liver fibrosis among HIV-monoinfected patients SO BMC INFECTIOUS DISEASES LA English DT Article ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED PATIENTS; ANTIRETROVIRAL DRUGS; INSULIN-RESISTANCE; NONALCOHOLIC STEATOHEPATITIS; COINFECTED PATIENTS; DISEASE; PROGRESSION; STEATOSIS AB Background: HIV-monoinfected patients may be at risk for significant liver fibrosis, but its prevalence and determinants in these patients are unknown. Since HIV-monoinfected patients do not routinely undergo liver biopsy, we evaluated the prevalence and risk factors of significant hepatic fibrosis in this group using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI). Methods: We conducted a cross-sectional study among HIV-infected patients negative for hepatitis B surface antigen and hepatitis C antibody in the Penn Center for AIDS Research Adult/Adolescent Database. Clinical and laboratory data were collected from the database at enrollment. Hypothesized determinants of significant fibrosis were modifiable risk factors associated with liver disease progression, hepatic fibrosis, or hepatotoxicity, including immune dysfunction (i.e., CD4 T lymphocyte count < 200 cells/mm(3), HIV viremia), diseases associated with hepatic steatosis (e. g., obesity, diabetes mellitus), and use of antiretroviral therapy. The primary outcome was an APRI score > 1.5, which suggests significant hepatic fibrosis. Multivariable logistic regression identified independent risk factors for significant fibrosis by APRI. Results: Among 432 HIV-monoinfected patients enrolled in the CFAR Database between November 1999 and May 2008, significant fibrosis by APRI was identified in 36 (8.3%; 95% CI, 5.9-11.4%) patients. After controlling for all other hypothesized risk factors as well as active alcohol use and site, detectable HIV viremia (adjusted OR, 2.56; 95% CI, 1.02-8.87) and diabetes mellitus (adjusted OR, 3.15; 95% CI, 1.12-10.10) remained associated with significant fibrosis by APRI. Conclusions: Significant fibrosis by APRI score was found in 8% of HIV-monoinfected patients. Detectable HIV viremia and diabetes mellitus were associated with significant fibrosis. Future studies should explore mechanisms for fibrosis in HIV-monoinfected patients. C1 [Amorosa, Valerianna K.; Kostman, Jay R.; Lo Re, Vincent, III] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [DallaPiazza, Michelle] NYU, Sch Med, Dept Med, Div Infect Dis, New York, NY USA. [Amorosa, Valerianna K.; Lo Re, Vincent, III] Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA USA. [Localio, Russell; Lo Re, Vincent, III] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Localio, Russell; Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU National Institutes of Health [K01-AI070001] FX This work was supported by National Institutes of Health research grant K01-AI070001 (to V. L. R.). NR 33 TC 42 Z9 43 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD MAY 13 PY 2010 VL 10 AR 116 DI 10.1186/1471-2334-10-116 PG 7 WC Infectious Diseases SC Infectious Diseases GA 603CU UT WOS:000278186900001 PM 20465840 ER PT J AU Singh, JA Lewallen, D AF Singh, Jasvinder A. Lewallen, David TI Predictors of pain and use of pain medications following primary Total Hip Arthroplasty (THA): 5,707 THAs at 2-years and 3,289 THAs at 5-years SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article ID TOTAL KNEE ARTHROPLASTY; QUALITY-OF-LIFE; FUNCTIONAL STATUS; REPLACEMENT; AGE; QUESTIONNAIRE; HEALTH; IMPACT; OSTEOARTHRITIS; SATISFACTION AB Background: Study pain and use of pain medications and their predictors after primary Total Hip Arthroplasty (THA). Methods: We examined whether gender, age (reference, < = 60 yrs), body mass index (BMI; reference, < 25 kg/m(2))), comorbidity measured by Deyo-Charlson index (5-point increase), anxiety and depression predict moderate-severe hip pain and use of pain medications 2- and 5-years after primary THA. Multivariable logistic regression adjusted for these predictors and distance from medical center, operative diagnosis, American Society of Anesthesiologists (ASA) score and implant type. Results: Moderate-severe pain was reported by 8.1% at 2-years and 10.8% at 5-years. Significant predictors of moderate-severe pain at 2-year follow-up were [Odds ratio (95% confidence interval)]: BMI 35-39.9, 1.8 (1.2,2.8); BMI > = 40, 1.7 (1.0,2.9); depression, 2.1 (1.4,3.0). Moderate-severe pain at 5-years was more common in patients with higher BMI: 25-29.9, 1.5 (1.1,2.1); 30-34.9, 1.8 (1.2,2.6); 35-39.9, 1.9 (1.2,3.1); and > = 40, 3.1 (1.7,5.7). Significant predictors of NSAID use were [Odds ratio (95% confidence interval)]: female gender at 2- and 5-years, 1.4 (1.1,1.7) and 1.4 (1.1,1.8); BMI 35-39.9 at 2-years, 1.9 (1.4, 2.6) and 30-34.9 at 2-years, 1.7 (1.2,2.4); and depression at 5-years, 1.8 (1.2,2.8). Significant predictors of opioid medication use were [Odds ratio (95% confidence interval)]: female gender at 2-and 5-years, 2.0 (1.1,3.0) and 2.4 (1.4,4.0); BMI 30-34.9 at 2-years, 2.0 (1.0,3.9); and depression at 2-years, 2.0 (1.1,3.7). Conclusions: Higher BMI and depression impacted moderate-severe pain; and female gender, higher BMI and depression predicted use of pain medications at 2-and 5-years post-primary THA. C1 [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Singh, Jasvinder A.; Lewallen, David] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Singh, JA (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institute of Health (NIH) [1 KL2 RR024151-01] FX This material is the result of work supported with National Institute of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA. NR 38 TC 44 Z9 44 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD MAY 13 PY 2010 VL 11 AR 90 DI 10.1186/1471-2474-11-90 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 606AE UT WOS:000278391600001 PM 20462458 ER PT J AU Dao, TK Youssef, NA Gopaldas, RR Chu, D Bakaeen, F Wear, E Menefee, D AF Dao, Tam K. Youssef, Nagy A. Gopaldas, Raja R. Chu, Danny Bakaeen, Faisal Wear, Emily Menefee, Deleene TI Autonomic cardiovascular dysregulation as a potential mechanism underlying depression and coronary artery bypass grafting surgery outcomes SO JOURNAL OF CARDIOTHORACIC SURGERY LA English DT Article ID HEART-RATE-VARIABILITY; PHYSICAL-ACTIVITY QUESTIONNAIRE; PLASMA NOREPINEPHRINE; MAJOR DEPRESSION; ADMINISTRATIVE DATABASES; COMORBIDITY INDEX; NERVOUS-SYSTEM; RISK-FACTORS; DISEASE; VALIDITY AB Background: Coronary artery bypass grafting (CABG) is often used to treat patients with significant coronary heart disease (CHD). To date, multiple longitudinal and cross-sectional studies have examined the association between depression and CABG outcomes. Although this relationship is well established, the mechanism underlying this relationship remains unclear. The purpose of this study was twofold. First, we compared three markers of autonomic nervous system (ANS) function in four groups of patients: 1) Patients with coronary heart disease and depression (CHD/Dep), 2) Patients without CHD but with depression (NonCHD/Dep), 3) Patients with CHD but without depression (CHD/NonDep), and 4) Patients without CHD and depression (NonCHD/NonDep). Second, we investigated the impact of depression and autonomic nervous system activity on CABG outcomes. Methods: Patients were screened to determine whether they met some of the study's inclusion or exclusion criteria. ANS function (i.e., heart rate, heart rate variability, and plasma norepinephrine levels) were measured. Chi-square and one-way analysis of variance were performed to evaluate group differences across demographic, medical variables, and indicators of ANS function. Logistic regression and multiple regression analyses were used to assess impact of depression and autonomic nervous system activity on CABG outcomes. Results: The results of the study provide some support to suggest that depressed patients with CHD have greater ANS dysregulation compared to those with only CHD or depression. Furthermore, independent predictors of in-hospital length of stay and non-routine discharge included having a diagnosis of depression and CHD, elevated heart rate, and low heart rate variability. Conclusions: The current study presents evidence to support the hypothesis that ANS dysregulation might be one of the underlying mechanisms that links depression to cardiovascular CABG surgery outcomes. Thus, future studies should focus on developing and testing interventions that targets modifying ANS dysregulation, which may lead to improved patient outcomes. C1 [Dao, Tam K.; Wear, Emily] Univ Houston, Houston, TX 77004 USA. [Chu, Danny; Bakaeen, Faisal; Menefee, Deleene] Texas Med Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77021 USA. [Dao, Tam K.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Gopaldas, Raja R.; Chu, Danny; Bakaeen, Faisal; Menefee, Deleene] Baylor Coll Med, Div Cardiothorac Surg, Dept Surg, Houston, TX 77030 USA. [Youssef, Nagy A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Youssef, Nagy A.] VA Med Ctr, Durham, NC 27705 USA. [Dao, Tam K.; Youssef, Nagy A.; Gopaldas, Raja R.; Chu, Danny; Bakaeen, Faisal; Wear, Emily; Menefee, Deleene] Univ S Alabama, Coll Med, Mobile, AL 36617 USA. RP Dao, TK (reprint author), Univ Houston, 4800 Calhoun Rd, Houston, TX 77004 USA. EM tkdao@uh.edu OI Youssef, Nagy/0000-0002-1922-9396 NR 45 TC 13 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8090 J9 J CARDIOTHORAC SURG JI J. Cardiothorac. Surg. PD MAY 13 PY 2010 VL 5 AR 36 DI 10.1186/1749-8090-5-36 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 616WD UT WOS:000279241100001 PM 20465820 ER PT J AU Stadtfeld, M Apostolou, E Akutsu, H Fukuda, A Follett, P Natesan, S Kono, T Shioda, T Hochedlinger, K AF Stadtfeld, Matthias Apostolou, Effie Akutsu, Hidenori Fukuda, Atsushi Follett, Patricia Natesan, Sridaran Kono, Tomohiro Shioda, Toshi Hochedlinger, Konrad TI Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells SO NATURE LA English DT Article ID NUCLEAR TRANSFER; ES CELLS; MICE; EXPRESSION; METHYLATION; FIBROBLASTS; GENERATION; CLUSTER; REGION; DOMAIN AB Induced pluripotent stem cells (iPSCs) have been generated by enforced expression of defined sets of transcription factors in somatic cells. It remains controversial whether iPSCs are molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells. By comparing genetically identical mouse ES cells and iPSCs, we show here that their overall messenger RNA and microRNA expression patterns are indistinguishable with the exception of a few transcripts encoded within the imprinted Dlk1-Dio3 gene cluster on chromosome 12qF1, which were aberrantly silenced in most of the iPSC clones. Consistent with a developmental role of the Dlk1-Dio3 gene cluster, these iPSC clones contributed poorly to chimaeras and failed to support the development of entirely iPSC-derived animals ('all-iPSC mice'). In contrast, iPSC clones with normal expression of the Dlk1-Dio3 cluster contributed to high-grade chimaeras and generated viable all-iPSC mice. Notably, treatment of an iPSC clone that had silenced Dlk1-Dio3 with a histone deacetylase inhibitor reactivated the locus and rescued its ability to support full-term development of all-iPSC mice. Thus, the expression state of a single imprinted gene cluster seems to distinguish most murine iPSCs from ES cells and allows for the prospective identification of iPSC clones that have the full development potential of ES cells. C1 [Stadtfeld, Matthias; Apostolou, Effie; Follett, Patricia; Hochedlinger, Konrad] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Stadtfeld, Matthias; Apostolou, Effie; Shioda, Toshi; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Stadtfeld, Matthias; Apostolou, Effie; Shioda, Toshi; Hochedlinger, Konrad] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Stadtfeld, Matthias; Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Stadtfeld, Matthias; Apostolou, Effie; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Akutsu, Hidenori] Natl Inst Child Hlth & Dev, Dept Reprod Biol, Tokyo 1578535, Japan. [Fukuda, Atsushi; Kono, Tomohiro] Tokyo Univ Agr, Dept Biosci, Tokyo 1568502, Japan. [Natesan, Sridaran] Sanofi Aventis, Cambridge, MA 02139 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Regenerat Med, Harvard Stem Cell Inst, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu OI Stadtfeld, Matthias/0000-0002-5852-9906 FU Schering Foundation; Jane Coffin Childs postdoctoral fellowship; NIH; Harvard Stem Cell Institute; MGH; HHMI FX We are grateful to H. Arnold for assistance with GeneSifter analysis; K. Coser, K. Claycomb and P. August for technical support on Affymetrix expression profiling; S. Sato and M. Machida for technical assistance; V. Greco for advice on keratinocyte isolation; and S. Schubert for advice on miRNA isolation. We thank members of the Hochedlinger laboratory for helpful suggestions and A. Umezawa for discussions and support. M. S. was supported by a postdoctoral fellowship from the Schering Foundation, E. A. was supported by a Jane Coffin Childs postdoctoral fellowship and K. H. was supported by a NIH Director's Innovator Award and by funds provided by the Harvard Stem Cell Institute, MGH and HHMI. NR 50 TC 455 Z9 482 U1 6 U2 63 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 13 PY 2010 VL 465 IS 7295 BP 175 EP U55 DI 10.1038/nature09017 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 594SS UT WOS:000277558500026 PM 20418860 ER PT J AU Lo, AC Guarino, PD Richards, LG Haselkorn, JK Wittenberg, GF Federman, DG Ringer, RJ Wagner, TH Krebs, HI Volpe, BT Bever, CT Bravata, DM Duncan, PW Corn, BH Maffucci, AD Nadeau, SE Conroy, SS Powell, JM Huang, GD Peduzzi, P AF Lo, Albert C. Guarino, Peter D. Richards, Lorie G. Haselkorn, Jodie K. Wittenberg, George F. Federman, Daniel G. Ringer, Robert J. Wagner, Todd H. Krebs, Hermano I. Volpe, Bruce T. Bever, Christopher T., Jr. Bravata, Dawn M. Duncan, Pamela W. Corn, Barbara H. Maffucci, Alysia D. Nadeau, Stephen E. Conroy, Susan S. Powell, Janet M. Huang, Grant D. Peduzzi, Peter TI Robot-Assisted Therapy for Long-Term Upper-Limb Impairment after Stroke SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONSTRAINT-INDUCED MOVEMENT; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; UPPER EXTREMITY; SINGLE-BLIND; FORCED USE; REHABILITATION; INFORMATION; RECOVERY; IMPACT AB BACKGROUND Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.) C1 [Lo, Albert C.] Brown Univ, Providence Vet Affairs Med Ctr, Providence, RI 02909 USA. [Lo, Albert C.] Brown Univ, Ctr Restorat & Regenerat Med, VA Res & Dev Ctr Excellence, Providence, RI 02909 USA. [Guarino, Peter D.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Federman, Daniel G.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Federman, Daniel G.] Yale Univ, New Haven, CT USA. [Richards, Lorie G.; Nadeau, Stephen E.] N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Richards, Lorie G.; Nadeau, Stephen E.] Univ Florida, Gainesville, FL USA. [Haselkorn, Jodie K.; Powell, Janet M.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Haselkorn, Jodie K.; Powell, Janet M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Wittenberg, George F.] VAMC Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Wittenberg, George F.; Bever, Christopher T., Jr.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Bever, Christopher T., Jr.] VA Maryland Healthcare Syst, Res Serv, Baltimore, MD USA. [Conroy, Susan S.] VAMC, Baltimore, MD USA. [Ringer, Robert J.] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA. [Wagner, Todd H.] VA Palo Alto Healthcare Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Krebs, Hermano I.] MIT, Cambridge, MA 02139 USA. [Volpe, Bruce T.] Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY USA. [Bravata, Dawn M.] Richard L Roudebush VAMC, Indianapolis, IN USA. [Duncan, Pamela W.] Duke Univ, Doctor Phys Therapy Program, Duke Div, Durham, NC USA. [Huang, Grant D.] VA Off Res & Dev Serv, Cooperat Studies Program Cent Off, Washington, DC USA. RP Lo, AC (reprint author), Brown Univ, Providence Vet Affairs Med Ctr, 830 Chalkstone Ave,111N, Providence, RI 02909 USA. EM albert.lo@va.gov OI Volpe, Bruce/0000-0002-1098-1848 FU Veterans Affairs Cooperative Studies Program and Rehabilitation Research and Development Service FX Supported by the Veterans Affairs Cooperative Studies Program and Rehabilitation Research and Development Service. NR 32 TC 401 Z9 421 U1 12 U2 73 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 13 PY 2010 VL 362 IS 19 BP 1772 EP 1783 DI 10.1056/NEJMoa0911341 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 594RQ UT WOS:000277555500004 PM 20400552 ER PT J AU Peleg, AY Hooper, DC AF Peleg, Anton Y. Hooper, David C. TI CURRENT CONCEPTS Hospital-Acquired Infections Due to Gram-Negative Bacteria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID VENTILATOR-ASSOCIATED PNEUMONIA; CARE-ASSOCIATED INFECTIONS; BLOOD-STREAM INFECTIONS; URINARY-TRACT-INFECTIONS; RANDOMIZED-TRIAL; ANTIBIOTIC-THERAPY; PSEUDOMONAS-AERUGINOSA; DISEASES-SOCIETY; KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI C1 [Peleg, Anton Y.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Peleg, Anton Y.; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Peleg, Anton Y.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Peleg, Anton Y.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Peleg, Anton Y.] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia. RP Peleg, AY (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St, Boston, MA 02215 USA. EM apeleg@bidmc.harvard.edu OI Peleg, Anton/0000-0002-2296-2126 FU Abbott Molecular; Ortho-McNeil-Janssen; Cubist; Johnson Johnson; Mutabilis; Daiichi-Sankyo FX Dr. Peleg reports receiving consulting fees from Abbott Molecular and Ortho-McNeil-Janssen; and Dr. Hooper, serving on scientific advisory boards for Pfizer and Novexel, receiving consulting fees from Cubist, Johnson & Johnson, and Mutabilis, and receiving lecture fees from Daiichi-Sankyo. No other conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. NR 51 TC 362 Z9 388 U1 5 U2 68 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 13 PY 2010 VL 362 IS 19 BP 1804 EP 1813 DI 10.1056/NEJMra0904124 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 594RQ UT WOS:000277555500007 PM 20463340 ER PT J AU Samuels, MA Pomerantz, BJ Sadow, PM AF Samuels, Martin A. Pomerantz, Benjamin J. Sadow, Peter M. TI A Woman with Dizziness and Falls Pheochromocytoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADRENALINE-SECRETING PHAEOCHROMOCYTOMA; ORTHOSTATIC HYPOTENSION; PARAGANGLIOMAS; TACHYCARDIA; TUMORS C1 [Samuels, Martin A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Pomerantz, Benjamin J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Samuels, Martin A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Pomerantz, Benjamin J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Samuels, MA (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. FU MC Communications FX Dr. Samuels reports receiving consulting fees from MC Communications. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. NR 17 TC 5 Z9 7 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 13 PY 2010 VL 362 IS 19 BP 1815 EP 1823 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 594RQ UT WOS:000277555500010 PM 20463342 ER PT J AU Bishay, P Schmidt, H Marian, C Haussler, A Wijnvoord, N Ziebell, S Metzner, J Koch, M Myrczek, T Bechmann, I Kuner, R Costigan, M Dehghani, F Geisslinger, G Tegeder, I AF Bishay, Philipp Schmidt, Helmut Marian, Claudiu Hauessler, Annett Wijnvoord, Nina Ziebell, Simone Metzner, Julia Koch, Marco Myrczek, Thekla Bechmann, Ingo Kuner, Rohini Costigan, Michael Dehghani, Faramarz Geisslinger, Gerd Tegeder, Irmgard TI R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids SO PLOS ONE LA English DT Article ID PERIPHERAL-NERVE INJURY; ACTIVATED PROTEIN-KINASE; ACID AMIDE HYDROLASE; DORSAL-ROOT GANGLION; SPINAL-CORD; MICROGLIA CONTRIBUTES; INDUCED HYPERALGESIA; MULTIPLE-SCLEROSIS; PROSTAGLANDIN E-2; GAMMA-SECRETASE AB Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPAR gamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain. C1 [Bishay, Philipp; Schmidt, Helmut; Marian, Claudiu; Hauessler, Annett; Wijnvoord, Nina; Ziebell, Simone; Metzner, Julia; Myrczek, Thekla; Geisslinger, Gerd; Tegeder, Irmgard] Goethe Univ Frankfurt, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany. [Bechmann, Ingo] Goethe Univ Frankfurt, Dept Clin Neuroanat, Frankfurt, Germany. [Koch, Marco; Dehghani, Faramarz] Goethe Univ Frankfurt, Dept Expt Neurobiol, Inst Anat, Frankfurt, Germany. [Kuner, Rohini] Univ Heidelberg, Dept Pharmacol, D-6900 Heidelberg, Germany. [Costigan, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Costigan, Michael] Massachusetts Gen Hosp, Neuroplast Res Grp, Dept Anaesthesia, Boston, MA 02114 USA. RP Bishay, P (reprint author), Goethe Univ Frankfurt, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany. EM tegeder@em.uni-frankfurt.de OI Tegeder, Irmgard/0000-0001-7524-8025 FU LOEWE Lipid Signaling Forschungszentrum Frankfurt (LiFF); Else Kroner Fresenius Foundation; PAZ GmbH, Frankfurt; Interdisciplinary Center of Neuroscience Frankfurt, ICNF FX This work was supported by LOEWE Lipid Signaling Forschungszentrum Frankfurt (LiFF, http://www.liff-ffm.de/liff/mission.php; to IT), Else Kroner Fresenius Foundation (http://www.ekfs.de/de/start.html, to IT), PAZ GmbH, Frankfurt (http://www.paz.de/to GG) and the Interdisciplinary Center of Neuroscience Frankfurt, ICNF (http://www.izn-frankfurt.de/web-content_en/index.html, to IT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 39 Z9 39 U1 2 U2 4 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 MAY 13 PY 2010 VL 5 IS 5 AR e10628 DI 10.1371/journal.pone.0010628 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 595SN UT WOS:000277633500016 PM 20498712 ER PT J AU Chafen, JJS Newberry, SJ Riedl, MA Bravata, DM Maglione, M Suttorp, MJ Sundaram, V Paige, NM Towfigh, A Hulley, BJ Shekelle, PG AF Chafen, Jennifer J. Schneider Newberry, Sydne J. Riedl, Marc A. Bravata, Dena M. Maglione, Margaret Suttorp, Marika J. Sundaram, Vandana Paige, Neil M. Towfigh, Ali Hulley, Benjamin J. Shekelle, Paul G. TI Diagnosing and Managing Common Food Allergies A Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID COWS MILK ALLERGY; PLACEBO-CONTROLLED TRIAL; HIGH-RISK INFANTS; ATOPY PATCH TEST; BREAST-FED INFANTS; RANDOMIZED CONTROLLED-TRIAL; BRIEF NEONATAL EXPOSURE; DOUBLE-BLIND TRIAL; SKIN-PRICK TESTS; 1ST 2 YEARS AB Context There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. Objective To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. Data Sources Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. Study Selection Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. Data Extraction Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. Data Synthesis A total of 12 378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. Conclusion The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis. JAMA. 2010; 303(18): 1848-1856 C1 [Chafen, Jennifer J. Schneider; Bravata, Dena M.; Sundaram, Vandana] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Chafen, Jennifer J. Schneider; Sundaram, Vandana] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Newberry, Sydne J.; Maglione, Margaret; Suttorp, Marika J.; Paige, Neil M.; Towfigh, Ali; Hulley, Benjamin J.; Shekelle, Paul G.] Rand Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. [Riedl, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Paige, Neil M.; Towfigh, Ali; Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Chafen, JJS (reprint author), Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, 117 Encina Commons, Stanford, CA 94305 USA. EM jjschnei@stanford.edu RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU National Institutes of Health [HHSN272200800065C]; National Institute of Allergy and Infectious Diseases FX Funding/Support: This work was funded in part by contract HHSN272200800065C from the National Institutes of Health. This work was commissioned by National Institute of Allergy and Infectious Diseases in support of the development of practice guidelines. NR 113 TC 173 Z9 180 U1 11 U2 44 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 2010 VL 303 IS 18 BP 1848 EP 1856 DI 10.1001/jama.2010.582 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 594DK UT WOS:000277513900026 PM 20460624 ER PT J AU Maison, SF Liu, XP Vetter, DE Eatock, RA Nathanson, NM Wess, J Liberman, MC AF Maison, Stephane F. Liu, Xiao-Ping Vetter, Douglas E. Eatock, Ruth Anne Nathanson, Neil M. Wess, Juergen Liberman, M. Charles TI Muscarinic Signaling in the Cochlea: Presynaptic and Postsynaptic Effects on Efferent Feedback and Afferent Excitability SO JOURNAL OF NEUROSCIENCE LA English DT Article ID OUTER HAIR-CELLS; RECEPTOR KNOCKOUT MICE; NICOTINIC CHOLINERGIC-RECEPTOR; GUINEA-PIG COCHLEA; CROSSED-OLIVOCOCHLEAR-BUNDLE; SPIRAL GANGLION NEURONS; ACETYLCHOLINE-RECEPTOR; MAMMALIAN COCHLEA; RAT COCHLEA; ACOUSTIC INJURY AB Acetylcholine is the major neurotransmitter of the olivocochlear efferent system, which provides feedback to cochlear hair cells and sensory neurons. To study the role of cochlear muscarinic receptors, we studied receptor localization with immunohistochemistry and reverse transcription-PCR and measured olivocochlear function, cochlear responses, and histopathology in mice with targeted deletion of each of the five receptor subtypes. M(2), M(4), and M(5) were detected in microdissected immature (postnatal days 10-13) inner hair cells and spiral ganglion cells but not outer hair cells. In the adult (6 weeks), the same transcripts were found in microdissected organ of Corti and spiral ganglion samples. M(2) protein was found, by immunohistochemistry, in olivocochlear fibers in both outer and inner hair cell areas. M(3) mRNA was amplified only from whole cochleas, and M(1) message was never seen in wild-type ears. Auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) were unaffected by loss of G(q)-coupled receptors (M(1), M(3), or M(5)), as were shock-evoked olivocochlear effects and vulnerability to acoustic injury. In contrast, loss of G(i)-coupled receptors (M(2) and/or M(4)) decreased neural responses without affecting DPOAEs (at low frequencies). This phenotype and the expression pattern are consistent with excitatory muscarinic signaling in cochlear sensory neurons. At high frequencies, both ABRs and DPOAEs were attenuated by loss of M(2) and/or M(4), and the vulnerability to acoustic injury was dramatically decreased. This aspect of the phenotype and the expression pattern are consistent with a presynaptic role for muscarinic autoreceptors in decreasing ACh release from olivocochlear terminals during high-level acoustic stimulation and suggest that muscarinic antagonists could enhance the resistance of the inner ear to noise-induced hearing loss. C1 [Maison, Stephane F.; Liu, Xiao-Ping; Eatock, Ruth Anne; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Maison, Stephane F.; Eatock, Ruth Anne; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Maison, Stephane F.; Liu, Xiao-Ping; Eatock, Ruth Anne; Liberman, M. Charles] Harvard Massachusetts Inst Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Vetter, Douglas E.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Nathanson, Neil M.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, US Dept HHS, Bethesda, MD 20892 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU National Institutes of Health [RO1 DC0188, RO1 DC006258, RO1 DC02290, RO1 NS026920, P30 DC5029, P30 NS047243]; National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by National Institutes of Health Grants RO1 DC0188 (M. C. L.), RO1 DC006258 (D. E. V.), RO1 DC02290 (R. A. E.), RO1 NS026920 (N.M.N.), P30 DC5029 (M. C. L.), and P30 NS047243 (D. E. V.). J.W. was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The skillful assistance of Leslie Dodds is gratefully acknowledged, as is the generous gift of the anti-CHT antibody from Dr. Randy Blakely of Vanderbilt University. NR 71 TC 11 Z9 11 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 12 PY 2010 VL 30 IS 19 BP 6751 EP 6762 DI 10.1523/JNEUROSCI.5080-09.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 595ZS UT WOS:000277653600028 PM 20463237 ER PT J AU Boucrot, E Saffarian, S Zhang, RY Kirchhausen, T AF Boucrot, Emmanuel Saffarian, Saveez Zhang, Rongying Kirchhausen, Tomas TI Roles of AP-2 in Clathrin-Mediated Endocytosis SO PLOS ONE LA English DT Article ID GROWTH-FACTOR RECEPTOR; COATED PITS; PLASMA-MEMBRANE; CELLS; TRAFFICKING; INTERNALIZATION; INVAGINATIONS; ENDOSOMES; FM1-43; ARH AB Background: The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway. Methodology/Principal Findings: We report here the use of in vivo imaging data obtained by spinning-disk confocal microscopy to study the formation of clathrin-coated structures at the plasma membranes of BSC1 and HeLa cells depleted by RNAi of the clathrin adaptor, AP-2. Very few clathrin coats continue to assemble after AP-2 knockdown. Moreover, there is a total absence of clathrin-containing structures completely lacking AP-2 while all the remaining coats still contain a small amount of AP-2. These observations suggest that AP-2 is essential for endocytic coated-pit and coated-vesicle formation. We also find that AP-2 knockdown strongly inhibits light-density lipoprotein (LDL) receptor-mediated endocytosis, as long as cells are maintained in complete serum and at 37 degrees C. If cells are first incubated with LDL at 4 degrees C, followed by warming, there is little or no decrease in LDL uptake with respect to control cells. LDL uptake at 37 degrees C is also not affected in AP-2 depleted cells first deprived of LDL by incubation with either serum-starved or LDL-starved cells for 24 hr. The LDL-deprived cells display a significant increase in endocytic structures enriched on deeply invaginated tubes that contain LDL and we suggest that under this condition of stress, LDL might enter through this alternative pathway. Conclusions/Significance: These results suggest that AP-2 is essential for endocytic clathrin coated-pit and coated-vesicle formation. They also indicate that under normal conditions, functional endocytic clathrin coated pits are required for LDL internalization. We also show that under certain conditions of stress, cells can upregulate alternative endocytic structures with the potential to provide compensatory trafficking pathways. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. RP Boucrot, E (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. EM kirchhausen@crystal.harvard.edu FU National Institutes of Health (NIH) [GM 075252]; International Human Frontier Science Program Organization; American Heart Association FX This work was supported by National Institutes of Health (NIH) GM 075252 (T.K.), the International Human Frontier Science Program Organization (E.B.) and the American Heart Association (S.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 64 Z9 64 U1 5 U2 13 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 MAY 12 PY 2010 VL 5 IS 5 AR e10597 DI 10.1371/journal.pone.0010597 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 594UC UT WOS:000277563400009 PM 20485680 ER PT J AU Flores, LM Kindelberger, DW Ligon, AH Capelletti, M Fiorentino, M Loda, M Cibas, ES Janne, PA Krop, IE AF Flores, L. M. Kindelberger, D. W. Ligon, A. H. Capelletti, M. Fiorentino, M. Loda, M. Cibas, E. S. Jaenne, P. A. Krop, I. E. TI Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE circulating tumour cells; breast cancer; lung cancer; HER2; FISH ID PERIPHERAL-BLOOD; SURVIVAL; PROGRESSION; MUTATIONS AB BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n=75) and lung (n=71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (P<0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK: 4 cells (P<0.0001). Recovered CTCs were relatively pure (60-70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour. British Journal of Cancer (2010) 102, 1495-1502. doi:10.1038/sj.bjc.6605676 www.bjcancer.com (C) 2010 Cancer Research UK C1 [Flores, L. M.; Capelletti, M.; Jaenne, P. A.; Krop, I. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Flores, L. M.] Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. [Kindelberger, D. W.; Ligon, A. H.; Loda, M.; Cibas, E. S.; Jaenne, P. A.; Krop, I. E.] Harvard Univ, Sch Med, Boston, MA USA. [Ligon, A. H.; Fiorentino, M.; Loda, M.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Kindelberger, D. W.; Ligon, A. H.; Loda, M.; Cibas, E. S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM pjanne@partners.org; ikrop@partners.org FU National Cancer Institute Lung [SPORE P50CA090578]; Department of Defense [W81XWH06-1-0303]; twoAM fund (IEK); Hazel and Samuel Bellin research fund FX This study is supported by grants from the National Cancer Institute Lung SPORE P50CA090578 (PAJ), the Department of Defense W81XWH06-1-0303 (PAJ), the twoAM fund (IEK) and the Hazel and Samuel Bellin research fund (PAJ). NR 19 TC 69 Z9 74 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 11 PY 2010 VL 102 IS 10 BP 1495 EP 1502 DI 10.1038/sj.bjc.6605676 PG 8 WC Oncology SC Oncology GA 595DK UT WOS:000277590700009 PM 20461092 ER PT J AU Missiou, A Kostlin, N Varo, N Rudolf, P Aichele, P Ernst, S Munkel, C Walter, C Stachon, P Sommer, B Pfeifer, D Zirlik, K MacFarlane, L Wolf, D Tsitsikov, E Bode, C Libby, P Zirlik, A AF Missiou, Anna Koestlin, Natascha Varo, Nerea Rudolf, Philipp Aichele, Peter Ernst, Sandra Muenkel, Christian Walter, Carina Stachon, Peter Sommer, Benjamin Pfeifer, Dietmar Zirlik, Katja MacFarlane, Lindsey Wolf, Dennis Tsitsikov, Erdyni Bode, Christoph Libby, Peter Zirlik, Andreas TI Tumor Necrosis Factor Receptor-Associated Factor 1 (TRAF1) Deficiency Attenuates Atherosclerosis in Mice by Impairing Monocyte Recruitment to the Vessel Wall SO CIRCULATION LA English DT Article DE TNF receptor-associated factor 1; inflammation; atherosclerosis; monocytes ID NF-KAPPA-B; IN-VIVO; GENE-EXPRESSION; CD40 LIGAND; CELLS; ACTIVATION; INFLAMMATION; INHIBITION; INDUCTION; REGULATOR AB Background-Members of the tumor necrosis factor superfamily, such as tumor necrosis factor-alpha, potently promote atherogenesis in mice and humans. Tumor necrosis factor receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins for this group of cytokines. Methods and Results-This study tested the hypothesis that TRAF1 modulates atherogenesis in vivo. TRAF1(-/-)/ LDLR(-/-) mice that consumed a high-cholesterol diet for 18 weeks developed significantly smaller atherosclerotic lesions than LDLR(-/-) (LDL receptor-deficient) control animals. As the most prominent change in histological composition, plaques of TRAF1-deficient animals contained significantly fewer macrophages. Bone marrow transplantations revealed that TRAF1 deficiency in both hematopoietic and vascular resident cells contributed to the reduction in atherogenesis observed. Mechanistic studies showed that deficiency of TRAF1 in endothelial cells and monocytes reduced adhesion of inflammatory cells to the endothelium in static and dynamic assays. Impaired adhesion coincided with reduced cell spreading, actin polymerization, and CD29 expression in macrophages, as well as decreased expression of the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in endothelial cells. Small interfering RNA studies in human cells verified these findings. Furthermore, TRAF1 messenger RNA levels were significantly elevated in the blood of patients with acute coronary syndrome. Conclusions-TRAF1 deficiency attenuates atherogenesis in mice, most likely owing to impaired monocyte recruitment to the vessel wall. These data identify TRAF1 as a potential treatment target for atherosclerosis. (Circulation. 2010;121:2033-2044.) C1 [Missiou, Anna; Koestlin, Natascha; Rudolf, Philipp; Ernst, Sandra; Muenkel, Christian; Walter, Carina; Stachon, Peter; Sommer, Benjamin; Wolf, Dennis; Bode, Christoph; Zirlik, Andreas] Univ Freiburg, Dept Cardiol, D-79106 Freiburg, Germany. [Missiou, Anna; Zirlik, Andreas] Univ Freiburg, Spemann Grad Sch Biol & Med, D-79106 Freiburg, Germany. [Missiou, Anna] Univ Freiburg, Fac Biol, D-79106 Freiburg, Germany. [Aichele, Peter] Univ Freiburg, Inst Med Microbiol & Hyg, Dept Immunol, D-79106 Freiburg, Germany. [Pfeifer, Dietmar; Zirlik, Katja] Univ Freiburg, Dept Hematol & Oncol, D-79106 Freiburg, Germany. [Varo, Nerea] Univ Navarra, Dept Clin Chem, E-31080 Pamplona, Spain. [MacFarlane, Lindsey; Libby, Peter] Brigham & Womens Hosp, Dept Med, Donald W Reynolds Cardiovasc Res Ctr, Boston, MA 02115 USA. [Tsitsikov, Erdyni] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Zirlik, A (reprint author), Univ Freiburg, Dept Cardiol, Breisacherstr 33, D-79106 Freiburg, Germany. EM andreas.zirlik@uniklinik-freiburg.de RI Zirlik, Andreas/A-6400-2011; Wolf, Dennis/G-8299-2012 OI Zirlik, Andreas/0000-0001-6290-3297; FU German Research Foundation (DFG) [ZI743/3-1, 3-2, GSC-4]; US National Heart, Lung, and Blood Institute [HL34636]; Donald W. Reynolds Foundation; Fondation Leducq FX This work was supported by research grants from the German Research Foundation to Dr A. Zirlik (DFG ZI743/3-1 and 3-2) and from the US National Heart, Lung, and Blood Institute to Dr Libby (HL34636). Dr Libby's laboratory also receives research funding from the Donald W. Reynolds Foundation and the Fondation Leducq. Dr Missiou was funded by the Excellence Initiative of the German Research Foundation (DFG GSC-4, Spemann Graduate School). NR 42 TC 32 Z9 34 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 11 PY 2010 VL 121 IS 18 BP 2033 EP 2044 DI 10.1161/CIRCULATIONAHA.109.895037 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593UC UT WOS:000277485500008 PM 20421522 ER PT J AU Agam, Y Liu, HS Papanastassiou, A Buia, C Golby, AJ Madsen, JR Kreiman, G AF Agam, Yigal Liu, Hesheng Papanastassiou, Alexander Buia, Calin Golby, Alexandra J. Madsen, Joseph R. Kreiman, Gabriel TI Robust Selectivity to Two-Object Images in Human Visual Cortex SO CURRENT BIOLOGY LA English DT Article ID INFERIOR TEMPORAL NEURONS; MONKEY INFEROTEMPORAL CORTEX; OBJECT RECOGNITION; ATTENTIONAL MODULATION; RESPONSE PROPERTIES; SINGLE NEURONS; EYE-MOVEMENTS; HUMAN BRAIN; AREA V4; MACAQUE AB We can recognize objects in complex images in a fraction of a second [1-3]. Neuronal responses in macaque areas V4 and inferior temporal cortex [4-15] to preferred stimuli are typically suppressed by the addition of other objects within the receptive field (see, however, [16, 17]). How can this suppression be reconciled with rapid visual recognition in complex scenes? Certain "special categories" could be unaffected by other objects [18], but this leaves the problem unsolved for other categories. Another possibility is that serial attentional shifts help ameliorate the problem of distractor objects [19-21]. Yet, psychophysical studies [1-3], scalp recordings [1], and neurophysiological recordings [14-16, 22-24] suggest that the initial sweep of visual processing contains a significant amount of information. We recorded intracranial field potentials in human visual cortex during presentation of flashes of two-object images. Visual selectivity from temporal cortex during the initial similar to 200 ms was largely robust to the presence of other objects. We could train linear decoders on the responses to isolated objects and decode information in two-object images. These observations are compatible with parallel, hierarchical, and feed-forward theories of rapid visual recognition [25] and may provide a neural substrate to begin to unravel rapid recognition in natural scenes. C1 [Agam, Yigal; Buia, Calin; Kreiman, Gabriel] Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Agam, Yigal; Buia, Calin; Kreiman, Gabriel] Harvard Univ, Childrens Hosp, Sch Med, Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Kreiman, Gabriel] Harvard Univ, Ctr Brain Sci, Boston, MA 02115 USA. [Kreiman, Gabriel] Harvard Univ, Swartz Ctr Theoret Neurosci, Boston, MA 02115 USA. [Liu, Hesheng] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golby, Alexandra J.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Papanastassiou, Alexander; Madsen, Joseph R.] Harvard Univ, Childrens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Kreiman, G (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM gabriel.kreiman@tch.harvard.edu OI Liu, Hesheng/0000-0002-7233-1509 FU Epilepsy Foundation; Klingenstein Fund; Whitehall Foundation; National Institutes of Health (NIH) [1R21EY019710, 1DP2OD006461] FX We would like to thank the patients for their cooperation We also thank Nuo Li, David Cox, Geoffrey Ghose, and Rufin Vogels for comments on the manuscript and Sheryl Manganaro and Paul Dionne for technical assistance We acknowledge financial support from the Epilepsy Foundation, the Klingenstein Fund, the Whitehall Foundation, National Institutes of Health (NIH) grant 1R21EY019710 and an NIH New Innovator Award (1DP2OD006461) NR 40 TC 15 Z9 15 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 11 PY 2010 VL 20 IS 9 BP 872 EP 879 DI 10.1016/j.cub.2010.03.050 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 596KB UT WOS:000277682600032 PM 20417105 ER PT J AU Wang, TJ AF Wang, Thomas J. TI Multiple Biomarkers for Predicting Cardiovascular Events Lessons Learned SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE coronary heart disease; prediction; biomarker ID C-REACTIVE PROTEIN; BRAIN NATRIURETIC PEPTIDE; RISK-FACTORS; MORTALITY; DISEASE; WOMEN; DEATH C1 Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org NR 20 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 11 PY 2010 VL 55 IS 19 BP 2092 EP 2095 DI 10.1016/j.jacc.2010.02.019 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 591LW UT WOS:000277303100009 PM 20447531 ER PT J AU Bonaca, M Scirica, B Sabatine, M Dalby, A Spinar, J Murphy, SA Jarolim, P Braunwald, E Morrow, DA AF Bonaca, Marc Scirica, Benjamin Sabatine, Marc Dalby, Anthony Spinar, Jindrich Murphy, Sabina A. Jarolim, Peter Braunwald, Eugene Morrow, David A. TI Prospective Evaluation of the Prognostic Implications of Improved Assay Performance With a Sensitive Assay for Cardiac Troponin I SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE troponin; prognosis; sensitive; acute coronary syndrome; ACS ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; DECISION-MAKING; EARLY-DIAGNOSIS; ELEVATION; MORTALITY; RECLASSIFICATION; OUTCOMES; EVENTS; RISK AB Objectives The purpose of this study was to investigate the prognostic implications of low-level increases in cardiac troponin I (cTnI) using a current-generation sensitive assay in patients with suspected acute coronary syndrome (ACS). Background Recent enhancements in troponin assays have enabled resolution of the 99th percentile reference limit at progressively lower concentrations. However, the clinical significance of low-level increases with sensitive assays is still debated. Methods We measured cTnI using a sensitive assay (TnI-Ultra, Siemens Healthcare Diagnostics, Deerfield, Illinois) at baseline in 4,513 patients with non-ST-segment elevation ACS randomly assigned to ranolazine or placebo. We applied decision limits at the 99th percentile reference limit (0.04 mu g/l), the cut point of the predecessor assay (0.1 mu g/l), and 1 equivalent to elevation of creatine kinase-myocardial band (1.5 ng/ml). Results Patients with baseline cTnI >= 0.04 mu g/l (n = 2,924) were at higher risk of death/myocardial infarction (MI) at 30 days than were patients with a negative cTnI (6.1% vs. 2.0%, p < 0.001). After adjusting for the TIMI (Thrombolysis In Myocardial Infarction) risk score, cTnI >= 0.04 mu g/l was associated with a 3-fold (95% confidence interval: 2.0 to 4.4, p < 0.001) higher risk of death/MI at 30 days. Moreover, patients with low-level increases (0.04 mu g/l to <0.1 mu g/l), were at significantly higher risk of death/MI at 30 days (5.0% vs. 2.0%, p = 0.001) and death at 12 months (6.4% vs. 2.4%, p = 0.005) than were patients with cTnI <0.04 mu g/l. Conclusions Low-level increases in cTnI using a sensitive assay identify patients at higher risk of death or MI. These findings support current American College of Cardiology/American Heart Association recommendations defining MI, and the incremental value of newer, more sensitive assays in identifying high-risk patients with ACS. (J Am Coll Cardiol 2010;55:2118-24) (C) 2010 by the American College of Cardiology Foundation C1 [Bonaca, Marc] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Jarolim, Peter] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dalby, Anthony] S African Cardiol Clin Trials Grp, Johannesburg, South Africa. [Spinar, Jindrich] Univ Hosp St Ann, Pekarska, Czech Republic. RP Bonaca, M (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Merck; Novartis; AstraZeneca; Daiichi-Sankyo; Bristol-Myers Squibb; Michael Lerner Foundation; BRAHMS; diaDexus; Ortho Clinical Diagnostics; Amgen; Beckman-Coulter; CV Therapeutics; Roche Diagnostics; Accumetrics; Bayer Healthcare; Beckman Coulter; Eli Lilly and Co.; Genentech; Johnson Johnson; Merck and Company; Nanosphere; Novartis Pharmaceuticals; Pfizer; Sanofi-Aventis; Siemens; Singulex; Schering-Plough FX From the *TIMI Study Group and the dagger Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; double dagger South African Cardiology Clinical Trials Group, Johannesburg, South Africa; and the University Hospital St. Ann, Pekarska, Czech Republic. Dr. Scirica has received research support from Merck, Novartis, AstraZeneca, Daiichi-Sankyo, and Bristol-Myers Squibb; honoraria for educational presentations from CV Therapeutics, Novartis, Merck, Schering-Plough, Sanofi-Aventis, Lilly, and Daiichi-Sankyo; has served as a consultant for AstraZeneca, Novartis, Congentus, and Gilead; and is the recipient of an unrestricted grant from the Michael Lerner Foundation. Dr. Sabatine has received research grants from BRAHMS, diaDexus, and Ortho Clinical Diagnostics, and is a consultant for Singulex. Dr. Jarolim has received research support from Amgen, Beckman-Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics, and honoraria for educational presentations from Ortho Clinical Diagnostics. Dr. Braunwald is the chairman of the TIMI Study Group, who receives grant support from Beckman-Coulter, CV Therapeutics (now Gilead Sciences), and Roche Diagnostics. Dr. Morrow has received research/educational grant support through the TIMI Study Group from Accumetrics, AstraZeneca, Bayer Healthcare, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo, Eli Lilly and Co., Genentech, Johnson & Johnson, Merck and Company, Nanosphere, Novartis Pharmaceuticals, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Siemens, Singulex, and Schering-Plough; has received honoraria for educational presentations from CV Therapeutics and Eli Lilly and Co.; and is a consultant/on the advisory board of AstraZeneca, Beckman-Coulter, Cardiokinetix, Gilead, Ikaria, Menarini, Molecular Insight, OrthoClinical Diagnostics, Sanofi-Aventis, Schering-Plough Research Institute, Siemens, and Roche Diagnostics. NR 31 TC 81 Z9 89 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 11 PY 2010 VL 55 IS 19 BP 2118 EP 2124 DI 10.1016/j.jacc.2010.01.044 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 591LW UT WOS:000277303100013 PM 20447535 ER PT J AU Kalogeropoulos, A Georgiopoulou, V Psaty, BM Rodondi, N Smith, AL Harrison, DG Liu, YM Hoffmann, U Bauer, DC Newman, AB Kritchevsky, SB Harris, TB Butler, J AF Kalogeropoulos, Andreas Georgiopoulou, Vasiliki Psaty, Bruce M. Rodondi, Nicolas Smith, Andrew L. Harrison, David G. Liu, Yongmei Hoffmann, Udo Bauer, Douglas C. Newman, Anne B. Kritchevsky, Stephen B. Harris, Tamara B. Butler, Javed CA Hlth ABC Study Investigators TI Inflammatory Markers and Incident Heart Failure Risk in Older Adults The Health ABC (Health, Aging, and Body Composition) Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE elderly; heart failure; inflammation ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; PATHOPHYSIOLOGICALLY RELEVANT CONCENTRATIONS; EXPERIMENTAL DIABETIC CARDIOMYOPATHY; LEFT-VENTRICULAR DYSFUNCTION; FACTOR-ALPHA; TNF-ALPHA; MYOCARDIAL-INFARCTION; MULTIPLE IMPUTATION; EJECTION FRACTION AB Objectives The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. Background Inflammation is associated with HF risk factors and also directly affects myocardial function. Methods The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). Results During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). Conclusions Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification. (J Am Coll Cardiol 2010;55:2129-37) (C) 2010 by the American College of Cardiology Foundation C1 [Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Andrew L.; Harrison, David G.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Liu, Yongmei; Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Butler, J (reprint author), Emory Univ Hosp, Div Cardiol, 1365 Clifton Rd NE,Suite AT 430, Atlanta, GA 30322 USA. EM javed.butler@emory.edu RI Newman, Anne/C-6408-2013; Kalogeropoulos, Andreas/A-9494-2009; OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos, Andreas/0000-0002-1284-429X; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute of Aging, National Institutes of Health, Bethesda, Maryland [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Emory University Heart and Vascular Board FX From the *Emory University, Atlanta, Georgia; dagger University of Washington, Seattle, Washington; double dagger University of Lausanne, Lausanne, Switzerland; Wake Forest University, Winston-Salem, North Carolina; parallel to Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; University of California San Francisco, San Francisco, California; #University of Pittsburgh, Pittsburgh, Pennsylvania; and the **Intramural Research Program, National Institute of Aging, National Institutes of Health, Bethesda, Maryland. This research was supported in part by the Intramural Research Program of the National Institute of Aging, National Institutes of Health, Bethesda, Maryland, and by grants N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. Support for this research was also partially funded through an Emory University Heart and Vascular Board grant titled "Novel Risk Markers and Prognosis Determination in Heart Failure." NR 55 TC 111 Z9 116 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 11 PY 2010 VL 55 IS 19 BP 2129 EP 2137 DI 10.1016/j.jacc.2009.12.045 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 591LW UT WOS:000277303100015 PM 20447537 ER PT J AU Hayden, KM Norton, MC Darcey, D Ostbye, T Zandi, PP Breitner, JCS Welsh-Bohmer, KA AF Hayden, K. M. Norton, M. C. Darcey, D. Ostbye, T. Zandi, P. P. Breitner, J. C. S. Welsh-Bohmer, K. A. CA Cache Cty Study Investigators TI Occupational exposure to pesticides increases the risk of incident AD The Cache County Study SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; HEALTH; RELIABILITY; DEMENTIA; FARMERS; CANADA AB Background: Commonly used organophosphate and organochlorine pesticides inhibit acetylcholinesterase at synapses in the somatic, autonomic, and central nervous systems and may therefore have lasting effects on the nervous system. Few studies have examined the relationship of pesticide exposure and risk of dementia or Alzheimer disease (AD). We sought to examine the association of occupational pesticide exposure and the risk of incident dementia and AD in later life. Methods: Residents of the agricultural community of Cache County, UT, who were aged 65 years and older as of January 1995, were invited to participate in the study. At baseline, participants completed detailed occupational history questionnaires that included information about exposures to various types of pesticides. Cognitive status was assessed at baseline and after 3, 7, and 10 years. Standardized methods were used for detection and diagnosis of dementia and AD. Cox proportional hazards survival analyses were used to evaluate the risk of incident dementia and AD associated with pesticide exposure. Results: Among 3,084 enrollees without dementia, more men than women reported pesticide exposure (p < 0.0001). Exposed individuals (n = 572) had more years of education (p < 0.01) but did not differ from others in age. Some 500 individuals developed incident dementia, 344 with AD. After adjustment for baseline age, sex, education, APOE is an element of 4 status, and baseline Modified Mini-Mental State Examination scores, Cox proportional hazards models showed increased risks among pesticide-exposed individuals for all-cause dementia, with hazard ratio (HR) 1.38 and 95% confidence interval (Cl) 1.09-1.76, and for AD (HR 1.42, 95% Cl 1.06-1.91). The risk of AD associated with organophosphate exposure (HR 1.53,95% Cl 1.05-2.23) was slightly higher than the risk associated with organochlorines (HR 1.49, 95% Cl 0.99-2.24), which was nearly significant. Conclusions: Pesticide exposure may increase the risk of dementia and Alzheimer disease in late life. Neurology (R) 2010;74:1524-1530 C1 [Hayden, K. M.] Duke Univ, Med Ctr, Joseph & Kathleen Bryan ADRC, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Darcey, D.; Ostbye, T.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27705 USA. [Norton, M. C.] Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. [Norton, M. C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Zandi, P. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Breitner, J. C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, J. C. S.] Univ Washington, Seattle, WA 98195 USA. RP Hayden, KM (reprint author), Duke Univ, Med Ctr, Joseph & Kathleen Bryan ADRC, Dept Psychiat & Behav Sci, 2200 W Main St,Suite A-200, Durham, NC 27705 USA. EM khayden@duke.edu RI Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIH/NIA [R01-AG1380, P30-AG 028377] FX Supported by NIH/NIA R01-AG1380 and P30-AG 028377 [APOE genotyping]. NR 32 TC 80 Z9 82 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 11 PY 2010 VL 74 IS 19 BP 1524 EP 1530 DI 10.1212/WNL.0b013e3181dd4423 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 593RE UT WOS:000277477000008 PM 20458069 ER PT J AU Zhong, WM Liu, F Dong, LB Lu, XH Hancock, K Reinherz, EL Katz, JM Sambhara, S AF Zhong, Weimin Liu, Feng Dong, Libo Lu, Xiuhua Hancock, Kathy Reinherz, Ellis L. Katz, Jacqueline M. Sambhara, Suryaprakash TI Significant Impact of Sequence Variations in the Nucleoprotein on CD8 T Cell-Mediated Cross-Protection against Influenza A Virus Infections SO PLOS ONE LA English DT Article ID ORIGINAL ANTIGENIC SIN; HETEROSUBTYPIC IMMUNITY; V-BETA; H5N1; EPITOPE; VACCINE; MICE; RECOGNITION; LYMPHOCYTES; REPERTOIRE AB Background: Memory CD8 T cells to influenza A viruses are widely detectable in healthy human subjects and broadly cross-reactive for serologically distinct influenza A virus subtypes. However, it is not clear to what extent such pre-existing cellular immunity can provide cross-subtype protection against novel emerging influenza A viruses. Methodology/Principal Findings: We show in the mouse model that naturally occurring sequence variations of the conserved nucleoprotein of the virus significantly impact cross-protection against lethal disease in vivo. When priming and challenge viruses shared identical sequences of the immunodominant, protective NP(366)/D(b) epitope, strong cross-subtype protection was observed. However, when they did not share complete sequence identity in this epitope, cross-protection was considerably reduced. Contributions of virus-specific antibodies appeared to be minimal under these circumstances. Detailed analysis revealed that the magnitude of the memory CD8 T cell response triggered by the NP(366)/D(b) variants was significantly lower than those triggered by the homologous NP(366)/D(b) ligand. It appears that strict specificity of a dominant public TCR to the original NP(366)/D(b) ligand may limit the expansion of cross-reactive memory CD8 T cells to the NP(366)/D(b) variants. Conclusions/Significance: Pre-existing CD8 T cell immunity may provide substantial cross-protection against hetero-subtypic influenza A viruses, provided that the priming and the subsequent challenge viruses share the identical sequences of the immunodominant, protective CTL epitopes. C1 [Zhong, Weimin; Liu, Feng; Dong, Libo; Lu, Xiuhua; Hancock, Kathy; Katz, Jacqueline M.; Sambhara, Suryaprakash] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Zhong, WM (reprint author), Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. EM wzhong@cdc.gov FU National Institutes of Health [U19 AI50900] FX This work was supported, in part, by a pilot project grant to WZ from National Institutes of Health (U19 AI50900. Project Director: ELR). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 11 PY 2010 VL 5 IS 5 AR e10583 DI 10.1371/journal.pone.0010583 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 594UB UT WOS:000277563200016 PM 20485501 ER PT J AU Grady, D Redberg, RF AF Grady, Deborah Redberg, Rita F. TI Less Is More How Less Health Care Can Result in Better Health SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID REGIONAL-VARIATIONS; ACQUIRED PNEUMONIA; CONTROLLED TRIAL; RISK; BENEFITS C1 [Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Redberg, Rita F.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, Dept Med, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM Deborah.Grady@ucsf.edu NR 16 TC 67 Z9 67 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 2010 VL 170 IS 9 BP 749 EP 750 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 592EE UT WOS:000277357800002 PM 20458080 ER PT J AU Yeh, RW Go, AS AF Yeh, Robert W. Go, Alan S. TI Rethinking the Epidemiology of Acute Myocardial Infarction Challenges and Opportunities SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CORONARY-HEART-DISEASE; ST-SEGMENT-ELEVATION; CONVERTING-ENZYME-INHIBITOR; UNITED-STATES COMMUNITIES; QUALITY-OF-CARE; TEMPORAL TRENDS; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; REPERFUSION THERAPY; NATIONAL REGISTRY AB Background: During the previous decade, many strategies for preventing acute myocardial infarction found to be efficacious in randomized controlled trials have been adopted by physicians in the community. Although evaluations of quality improvement typically focus on process measures at the hospital, practice, or clinician level, assessment of improvements in health outcomes remains the true test for the successful translation of evidence into practice. Methods: We performed a review of the current literature examining trends in the incidence of myocardial infarction in communities. We focused specifically on the group of population-based studies that have examined trends in myocardial infarction incidence. Results: Few population-based studies have examined recent temporal trends in the incidence of myocardial infarction, overall and by type. Existing studies have been largely limited by modest sample sizes, limited diversity within the study populations, the use of composite endpoints that combine disparate outcomes, and the inability to characterize the effect of long-term outpatient medication use on observed trends in incidence and severity of myocardial infarction. Conclusion: More contemporary assessments of community-wide changes in the epidemiology of myocardial infarction are needed to help assess the effectiveness of primary prevention and to identify areas for potential improvement. Arch Intern Med. 2010;170(9):759-764 C1 [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St, Oakland, CA 94612 USA. EM Alan.S.Go@kp.org FU Schering Plough Corporation; American Heart Association; National Heart, Lung, and Blood Institute FX Financial Disclosure: Dr Yeh was supported by a Future Leaders in CV Medical Research Grant from the Schering Plough Corporation.; Funding/Support: Dr Go has received research funding from the American Heart Association and the National Heart, Lung, and Blood Institute. NR 50 TC 25 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 2010 VL 170 IS 9 BP 759 EP 764 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 592EE UT WOS:000277357800004 PM 20458082 ER PT J AU Yachimski, PS Farrell, EA Hunt, DP Reid, AE AF Yachimski, Patrick S. Farrell, Elizabeth A. Hunt, Daniel P. Reid, Andrea E. TI Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding Effect of Standardized Guidelines on Prescribing Practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID STRESS-ULCER PROPHYLAXIS; ACID-SUPPRESSIVE THERAPY; HOSPITALIZED-PATIENTS; ACQUIRED PNEUMONIA; RISK; INFECTIONS; RANITIDINE AB Background: Proton pump inhibitors (PPIs) are frequently prescribed for prophylaxis of nosocomial upper gastrointestinal tract bleeding. Some inpatients receiving PPIs may have no risk factors for nosocomial upper gastrointestinal tract bleeding, and PPIs may be continued unnecessarily at hospital discharge. We aimed to assess the effect of standardized guidelines on PPI prescribing practices. Methods: Guidelines for PPI use were implemented on the medical service at a tertiary center. We reviewed PPI use among inpatient admissions during the month before implementation of guidelines and then prospectively evaluated PPI use among admissions during the month after implementation of guidelines. Results: Among an overall cohort of 942 patients, 48% were prescribed PPIs while inpatients, and 41% were prescribed PPIs at hospital discharge. Univariate predictors of inpatient PPI use included age, length of hospital stay, history of gastroesophageal reflux disease or upper gastrointestinal tract bleeding, and outpatient PPI, aspirin, or glucocorticoid use. Among patients not on an outpatient regimen of PPIs at admission, implementation of guidelines resulted in lower rates of inpatient PP) use (27% before vs 16% after, P=.001) and PPI prescription at discharge (16% before vs 10% after, P=.03). Conclusion: Introduction of standardized guidelines resulted in lower rates of PPI use among a subset of inpatients and reduced the rate of PPI prescriptions at discharge. Arch Intern Med. 2010;170(9):779-783 C1 [Yachimski, Patrick S.; Reid, Andrea E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Farrell, Elizabeth A.; Hunt, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA USA. RP Yachimski, PS (reprint author), Vanderbilt Univ, Med Ctr, Div Gastroenterol Hepatol & Nutr, 1660 Vanderbilt Clin, Nashville, TN 37232 USA. EM patrick.yachimski@vanderbilt.edu FU National Institutes of Health [T32 DK007191] FX Funding/Support: This research was supported by grant T32 DK007191 from the National Institutes of Health (Dr Yachimski). NR 22 TC 12 Z9 19 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 2010 VL 170 IS 9 BP 779 EP 783 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 592EE UT WOS:000277357800007 PM 20458085 ER PT J AU Arslan, AA Helzlsouer, KJ Kooperberg, C Shu, XO Steplowski, E Bueno-de-Mesquita, HB Fuchs, CS Gross, MD Jacobs, EJ LaCroix, AZ Petersen, GM Stolzenberg-Solomon, RZ Zheng, W Albanes, D Amundadottir, L Bamlet, WR Barricarte, A Bingham, SA Boeing, H Boutron-Ruault, MC Buring, JE Chanock, SJ Clipp, S Gaziano, JM Giovannucci, EL Hankinson, SE Hartge, P Hoover, RN Hunter, DJ Hutchinson, A Jacobs, KB Kraft, P Lynch, SM Manjer, J Manson, JE McTiernan, A McWilliams, RR Mendelsohn, JB Michaud, DS Palli, D Rohan, TE Slimani, N Thomas, G Tjonneland, A Tobias, GS Trichopoulos, D Virtamo, J Wolpin, BM Yu, K Zeleniuch-Jacquotte, A Patel, AV AF Arslan, Alan A. Helzlsouer, Kathy J. Kooperberg, Charles Shu, Xiao-Ou Steplowski, Emily Bueno-de-Mesquita, H. Bas Fuchs, Charles S. Gross, Myron D. Jacobs, Eric J. LaCroix, Andrea Z. Petersen, Gloria M. Stolzenberg-Solomon, Rachael Z. Zheng, Wei Albanes, Demetrius Amundadottir, Laufey Bamlet, William R. Barricarte, Aurelio Bingham, Sheila A. Boeing, Heiner Boutron-Ruault, Marie-Christine Buring, Julie E. Chanock, Stephen J. Clipp, Sandra Gaziano, J. Michael Giovannucci, Edward L. Hankinson, Susan E. Hartge, Patricia Hoover, Robert N. Hunter, David J. Hutchinson, Amy Jacobs, Kevin B. Kraft, Peter Lynch, Shannon M. Manjer, Jonas Manson, JoAnn E. McTiernan, Anne McWilliams, Robert R. Mendelsohn, Julie B. Michaud, Dominique S. Palli, Domenico Rohan, Thomas E. Slimani, Nadia Thomas, Gilles Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Ditnitrios Virtamo, Jarmo Wolpin, Brian M. Yu, Kai Zeleniuch-Jacquotte, Anne Patel, Alpa V. TI Anthropometric Measures, Body Mass Index, and Pancreatic Cancer A Pooled Analysis From the Pancreatic Cancer Cohort Consortium (PanScan) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BASE-LINE CHARACTERISTICS; LIFE-STYLE FACTORS; PHYSICAL-ACTIVITY; NUTRITIONAL FACTORS; WOMENS HEALTH; RISK-FACTORS; OBESITY; INSULIN; MORTALITY; DESIGN AB Background: Obesity has been proposed as a risk factor for pancreatic cancer. Methods: Pooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association, between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, <18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese, 30.0-34.9; and severely obese, >= 35.0). Models were adjusted for potential confounders. Results: In all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI guartile, 1.33; 95% Cl, 1.12-1.58; P-trend<.001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% Cl, 1.04-1.69; P-trend<.03), and in women it was 1.34 (95% Cl, 1.05-1.70; P-trend=.01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% Cl, 1.31-2.69; P-trend=.003) but less so in men. Conclusions: These findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. Arch Intern Med. 2010;170(9):791 -802 C1 [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY 10016 USA. [Helzlsouer, Kathy J.] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Kooperberg, Charles; LaCroix, Andrea Z.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Wolpin, Brian M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiovasc Med, Phys Hlth Study, Boston, MA 02115 USA. [Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Gross, Myron D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Petersen, Gloria M.; Bamlet, William R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Coll Med, Rochester, MN USA. [Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius; Amundadottir, Laufey; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin B.; Mendelsohn, Julie B.; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai] 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. [Barricarte, Aurelio] CIBER Epidemiol & Salud Publ, Barcelona, Spain. [Barricarte, Aurelio] Publ Hlth Inst Navarra, Pamplona, Spain. [Bingham, Sheila A.] Univ Cambridge, MRC Ctr Nutr & Canc, Cambridge, England. [Boeing, Heiner] German Inst Human Nutr, Potsdam, Nuthetal, Germany. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Gaziano, J. Michael] Harvard Univ, Sch Publ Hlth, Massachusetts Vet Epidemiol Res & Informat Ctr, Vet Affairs Boston Healthcare Syst, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Kraft, Peter; Manson, JoAnn E.; Trichopoulos, Ditnitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hutchinson, Amy; Jacobs, Kevin B.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv LLC, Gaithersburg, MD USA. [Manjer, Jonas] Malmo Univ Hosp, Dept Surg, Malmo, Sweden. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Palli, Domenico] Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Slimani, Nadia] Int Agcy Res Canc, F-69372 Lyon, France. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Trichopoulos, Ditnitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Arslan, AA (reprint author), NYU, Dept Obstet & Gynecol, Sch Med, 550 1st Ave,TH 528, New York, NY 10016 USA. EM alan.arslan@nyumc.org RI Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; PALLI, Domenico/0000-0002-5558-2437 FU NCI, National Institutes of Health [HHSN261200800001E]; ATBC [N01-CN-45165, N01-RC-45035]; Intramural Research Program of the NCI [N01-RC37004]; US Public Health Service; National Institute on Aging [5U01AG018033]; NCI [CA105069, CA73790]; Associazione Italiana per la Ricerca sul Cancro FX This project was funded in whole or in part by contract HHSN261200800001E from the NCI, National Institutes of Health. The ATBC was supported by contracts N01-CN-45165, N01-RC-45035, and N01-RC37004 from the Intramural Research Program of the NCI and the US Public Health Service. CLUE II was supported by grant 5U01AG018033 from the National Institute on Aging and by grants CA105069 and CA73790 from the NCI. The EPIC was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005; Ligue contre le Cancer; Societe 3M; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund of the Spanish Ministry of Health, participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (Italy); Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Vasterbotten (Sweden); and World Cancer Research Fund. The New York University Women's Health Study is supported by research grants R01CA034588, R01CA098661, and P3OCA016087 from the NCI and by grant ES000260 from the National Institute of Environmental Health Sciences. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial was supported by contracts from the NCI (University of Colorado: NOICN-25514; Georgetown University: NO I-CN-25522; Pacific Health Research Institute: NOI-CN-25515; Henry Ford Health System: NO1-CN-25512; University of Minnesota: NO I-CN-25513; Washington University: NO1-CN-25516; University of Pittsburgh: NO1-CN25511; University of Utah: NO1-CN-25524; Marshfield Clinic Research Foundation: NO1-CN-25518; University of Alabama at Birmingham: NO1-CN-75022; Westat Inc: NO1-CN-25476; and University of California, Los Angeles: NO1-CN-25404). The SMWHS were supported by extramural research grants RO1 CA82729 and RO1 CA70867 from the NCI and by the Intramural Research Program of the NCI (Division of Cancer Epidemiology and Genetics). The Women's Health Initiative is funded by contracts NO1WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 3211832119, 32122, 42107-26, 42129-32, and 44221 from the National Heart, Lung, and Blood Institute. NR 57 TC 117 Z9 122 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 2010 VL 170 IS 9 BP 791 EP 802 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 592EE UT WOS:000277357800009 PM 20458087 ER PT J AU Washington, BT AF Schwamm, Lee H. TI Measure for Measure New Insights Offered and Challenges Encountered in the Efforts to Improve Acute Stroke Care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID ACUTE-STROKE-REGISTRY C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Washington, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 720,55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 2010 VL 170 IS 9 BP 810 EP 812 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 592EE UT WOS:000277357800011 ER PT J AU Ryu, K Susa, M Choy, E Yang, C Hornicek, FJ Mankin, HJ Duan, ZF AF Ryu, Keinosuke Susa, Michiro Choy, Edwin Yang, Cao Hornicek, Francis J. Mankin, Henry J. Duan, Zhenfeng TI Oleanane triterpenoid CDDO-Me induces apoptosis in multidrug resistant osteosarcoma cells through inhibition of Stat3 pathway SO BMC CANCER LA English DT Article ID BREAST-CANCER CELLS; ACTIVATED SIGNAL TRANSDUCER; MOLECULAR TARGETS; OVARIAN-CANCER; CONSTITUTIVE ACTIVATION; TRANSCRIPTION-3 STAT3; DRUG-RESISTANCE; GROWTH ARREST; HUMAN TUMORS; EXPRESSION AB Background: The activation of signal transducer and activator of transcription 3 (Stat3) pathway correlates with tumor growth, survival, drug resistance and poor prognosis in osteosarcoma. To explore the potential therapeutic values of this pathway, we assessed both the expression and the activation of Stat3 pathway in several pairs of multidrug resistant (MDR) osteosarcoma cell lines, and tissues. To explore the potential therapeutic values of this pathway, we analyzed the ability of the synthetic oleanane triterpenoid, C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me), to inhibit Stat3 expression and activation as well as its effects on doxorubicin sensitivity in osteosarcoma cells. Methods: Expression of Stat3, phosphorylated Stat3 (pStat3) and Stat3 targeted proteins, including Bcl-X(L), Survivin and MCL-1 were determined in drug sensitive and MDR osteosarcoma cell lines and tissues by Western blot analysis. The effect of CDDO-Me on osteosarcoma cell growth was evaluated by MTT and apoptosis by PARP cleavage assay and caspase-3/7 activity. Results: Stat3 pathway was activated in osteosarcoma tissues and in MDR cell lines. CDDO-Me inhibited growth and induced apoptosis in osteosarcoma cell lines. Treatment with CDDO-Me significantly decreased the level of nuclear translocation and phosphorylation of Stat3. The inhibition of Stat3 pathway correlated with the suppression of the antiapoptotic Stat3 targeted genes Bcl-X(L), survivin, and MCL-1. Furthermore, CDDO-Me increased the cytotoxic effects of doxorubicin in the MDR osteosarcoma cell lines. Conclusions: Stat3 pathway is overexpressed in MDR osteosarcoma cells. CDDO-Me significantly inhibited Stat3 phosphorylation, Stat3 nuclear translocation and induced apoptosis in osteosarcoma. This study provides the framework for the clinical evaluation of CDDO-Me, either as monotherapy or perhaps even more effectively in combination with doxorubicin to treat osteosarcoma and overcome drug resistance. C1 [Ryu, Keinosuke; Susa, Michiro; Yang, Cao; Hornicek, Francis J.; Mankin, Henry J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Ryu, Keinosuke; Susa, Michiro; Choy, Edwin; Yang, Cao; Hornicek, Francis J.; Mankin, Henry J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Ryu, Keinosuke] Nihon Univ, Sch Med, Dept Orthopaed Surg, Tokyo 1600015, Japan. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM zduan@partners.org RI Susa, Michiro/L-2291-2013; OI Duan, Zhenfeng/0000-0002-8543-083X; Choy, Edwin/0000-0001-9896-8084 FU Gaetagno and Wechsler funds; Department of Orthopaedic Surgery, Nihon University School of Medicine; Sarcoma Foundation of America; National Cancer Institute, NIH [R01-CA119617]; Jennifer Hunter Yates Foundation FX This project was supported, in part, by a grant from the Gaetagno and Wechsler funds. KR is supported by Department of Orthopaedic Surgery, Nihon University School of Medicine. ZD is supported, in part, by a grant from Sarcoma Foundation of America, and a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617. EC is supported by the Jennifer Hunter Yates Foundation. NR 48 TC 28 Z9 31 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 10 PY 2010 VL 10 AR 187 DI 10.1186/1471-2407-10-187 PG 11 WC Oncology SC Oncology GA 605RW UT WOS:000278365700001 PM 20459702 ER PT J AU Partridge, AH Archer, L Kornblith, AB Gralow, J Grenier, D Perez, E Wolff, AC Wang, XF Kastrissios, H Berry, D Hudis, C Winer, E Muss, H AF Partridge, Ann H. Archer, Laura Kornblith, Alice B. Gralow, Julie Grenier, Debjani Perez, Edith Wolff, Antonio C. Wang, Xiaofei Kastrissios, Helen Berry, Donald Hudis, Clifford Winer, Eric Muss, Hyman TI Adherence and Persistence With Oral Adjuvant Chemotherapy in Older Women With Early-Stage Breast Cancer in CALGB 49907: Adherence Companion Study 60104 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAMOXIFEN; THERAPY; MEDICATION; DISCONTINUATION; PREDICTORS AB Purpose Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial. Patients and Methods Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS. Results Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity. Conclusion Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence. C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp, Stat Ctr B, Durham, NC USA. Univ Washington, Seattle, WA 98195 USA. St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Illinois, Coll Pharm, Chicago, IL USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Vermont, Burlington, VT USA. Vermont Canc Ctr, Burlington, VT USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ahpartridge@partners.org OI Wolff, Antonio/0000-0003-3734-1063 FU National Cancer Institute [CA32291, CA33601, CA32102, CA77202, CA25224, CA21115, CA105409, CA77651, CA77406, CA31946]; Genentech; Novartis; Amgen; Roche; GlaxoSmithKline; Bristol-Meyers Squibb FX Supported in part by Grants. No. CA32291, CA33601, CA32102, CA77202, CA25224, CA21115, CA105409, CA77651, and CA77406 from the National Cancer Institute; Grant No. CA31946 from the National Cancer Institute (to the Cancer and Leukemia Group B [CALGB] and R. L. S.); and Grant No. CA33601 (to the CALGB Statistical Center and S. G.).; Funding: Julie Gralow, Genentech, Novartis, Amgen, Roche, GlaxoSmithKline, Bristol-Meyers Squibb; Antonio C. Wolff, Roche NR 24 TC 52 Z9 53 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 MAY 10 PY 2010 VL 28 IS 14 BP 2418 EP 2422 DI 10.1200/JCO.2009.26.4671 PG 5 WC Oncology SC Oncology GA 592OT UT WOS:000277389600015 PM 20368559 ER PT J AU Zhai, RH Chen, F Liu, G Su, L Kulke, MH Asomaning, K Lin, XH Heist, RS Nishioka, NS Sheu, CC Wain, JC Christiani, DC AF Zhai, Rihong Chen, Feng Liu, Geoffrey Su, Li Kulke, Matthew H. Asomaning, Kofi Lin, Xihong Heist, Rebecca S. Nishioka, Norman S. Sheu, Chau-Chyun Wain, John C. Christiani, David C. TI Interactions Among Genetic Variants in Apoptosis Pathway Genes, Reflux Symptoms, Body Mass Index, and Smoking Indicate Two Distinct Etiologic Patterns of Esophageal Adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTIFACTOR-DIMENSIONALITY REDUCTION; HIGH-ORDER INTERACTIONS; GASTROESOPHAGEAL-REFLUX; LUNG-CANCER; CELL-DEATH; FUNCTIONAL POLYMORPHISMS; PANCREATIC-CANCER; FASL CONTRIBUTE; GASTRIC CARDIA; INCREASED RISK AB Purpose Apoptosis pathway, gastroesophageal reflux symptoms (reflux), higher body mass index (BMI), and tobacco smoking have been individually associated with esophageal adenocarcinoma (EA) development. However, how multiple factors jointly affect EA risk remains unclear. Patients and Methods In total, 305 patients with EA and 339 age- and sex-matched controls were studied. High-order interactions among reflux, BMI, smoking, and functional polymorphisms in five apoptotic genes (FAS, FASL, IL1B, TP53BP, and BAT3) were investigated by entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional logistic regression (LR) models. Results In LR analysis, reflux, BMI, and smoking were significantly associated with EA risk, with reflux as the strongest individual factor. No individual single nucleotide polymorphism was associated with EA susceptibility. However, there was a two-way interaction between IL1B + 3954C>T and reflux (P = .008). In both CART and MDR analyses, reflux was also the strongest individual factor for EA risk. In individuals with reflux symptoms, CART analysis indicated that strongest interaction was among variant genotypes of IL1B + 3954C>T and BAT3S625P, higher BMI, and smoking (odds ratio [OR], 5.76; 95% CI, 2.48 to 13.38), a finding independently found using MDR analysis. In contrast, for participants without reflux symptoms, the strongest interaction was found between higher BMI and smoking (OR, 3.27; 95% CI, 1.88 to 5.68), also echoed by entropy-based MDR analysis. Conclusion Although a history of reflux is an important risk for EA, multifactor interactions also play important roles in EA risk. Gene-environment interaction patterns differ between patients with and without reflux symptoms. C1 [Zhai, Rihong] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Div Hematol Oncol,Dept Med, Canc Ctr,Thorac Surg Div,Pulm & Crit Care Unit, Boston, MA 02114 USA. Univ Toronto, Dept Med, Princess Margaret Hosp, Ontario Canc Inst,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Princess Margaret Hosp, Ontario Canc Inst,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. Univ Toronto, Dept Epidemiol, Princess Margaret Hosp, Ontario Canc Inst,Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. RP Zhai, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM rzhai@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU National Institutes of Health [CA109193, CA110822, CA074386, CA092824]; Flight Attendant Medical Research Institute [062459YCSA] FX Supported by National Institutes of Health Grants No. CA109193, CA110822, CA074386, and CA092824, and by Flight Attendant Medical Research Institute Grant No. 062459YCSA. NR 39 TC 26 Z9 27 U1 0 U2 5 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 MAY 10 PY 2010 VL 28 IS 14 BP 2445 EP 2451 DI 10.1200/JCO.2009.26.2790 PG 7 WC Oncology SC Oncology GA 592OT UT WOS:000277389600019 PM 20385987 ER PT J AU Balch, CM Gershenwald, JE Soong, SJ Thompson, JF Ding, SL Byrd, DR Cascinelli, N Cochran, AJ Coit, DG Eggermont, AM Johnson, T Kirkwood, JM Leong, SP McMasters, KM Mihm, MC Morton, DL Ross, MI Sondak, VK AF Balch, Charles M. Gershenwald, Jeffrey E. Soong, Seng-jaw Thompson, John F. Ding, Shouluan Byrd, David R. Cascinelli, Natale Cochran, Alistair J. Coit, Daniel G. Eggermont, Alexander M. Johnson, Timothy Kirkwood, John M. Leong, Stanley P. McMasters, Kelly M. Mihm, Martin C., Jr. Morton, Donald L. Ross, Merrick I. Sondak, Vernon K. TI Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AMERICAN JOINT COMMITTEE; PRIMARY CUTANEOUS MELANOMA; SENTINEL LYMPH-NODES; LONG-TERM SURVIVAL; TUMOR MITOTIC RATE; MULTICENTER TRIAL; FOLLOW-UP; BIOPSY; VALIDATION; SYSTEM AB Purpose To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and Methods Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. Results Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01). Conclusion In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma. C1 [Balch, Charles M.] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21287 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Univ Sydney, Sydney Melanoma Unit, Sydney, NSW 2006, Australia. Univ Washington, Seattle, WA 98195 USA. Ist Nazl Tumori, I-20133 Milan, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. John Wayne Canc Inst, Santa Monica, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Erasmus Univ, Med Ctr, Daniel Hoed Canc Ctr, Rotterdam, Netherlands. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Louisville, Med Ctr, Louisville, KY 40292 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Balch, CM (reprint author), Johns Hopkins Med Inst, Dept Surg, 600 N Wolfe St,Osler 624, Baltimore, MD 21287 USA. EM balchch@jhmi.edu FU American Joint Committee on Cancer; University of Alabama at Birmingham; SPORE in melanoma at The University of Texas M. D. Anderson Cancer Center in Houston, TX [P50 CA93459]; Schering Plough (Kenilworth, NJ) FX Supported by a grant from the American Joint Committee on Cancer; by research funds from the University of Alabama at Birmingham; by SPORE Grant No. P50 CA93459 in melanoma at The University of Texas M. D. Anderson Cancer Center in Houston, TX; and by an unrestricted educational grant from Schering Plough (Kenilworth, NJ; for AJCC Melanoma Staging Committee meetings). NR 46 TC 174 Z9 175 U1 0 U2 5 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 MAY 10 PY 2010 VL 28 IS 14 BP 2452 EP 2459 DI 10.1200/JCO.2009.27.1627 PG 8 WC Oncology SC Oncology GA 592OT UT WOS:000277389600020 PM 20368546 ER PT J AU Harris, JR Morrow, M AF Harris, Jay R. Morrow, Monica TI Ductal Carcinoma in Situ: Dilemma or Denouement Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID BREAST-CANCER C1 [Harris, Jay R.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10021 USA. RP Harris, JR (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 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 MAY 10 PY 2010 VL 28 IS 14 BP E220 EP E220 DI 10.1200/JCO.2009.27.7111 PG 1 WC Oncology SC Oncology GA 592OT UT WOS:000277389600028 ER PT J AU Yates, JF Ji, LJ Oka, T Lee, JW Shinotsuka, H Sieck, WR AF Yates, J. Frank Ji, Li-Jun Oka, Takashi Lee, Ju-Whei Shinotsuka, Hiromi Sieck, Winston R. TI Indecisiveness and Culture: Incidence, Values, and Thoroughness SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE indecisiveness; indecision; culture; Japanese; Chinese; Americans ID PROBABILITY JUDGMENT ACCURACY; DECISION-MAKING; UNITED-STATES; SELF; EMOTION; JAPAN; CHINA; RISK AB Three studies examined cultural variations in indecisiveness among Chinese, Japanese, and Americans. In Study 1, validated self-report, comprehensive measures of indecisiveness indicated large cultural differences, with Japanese participants exhibiting substantially more indecisiveness than Chinese or Americans. Study 2 provided evidence that such cultural variations correspond to variations in people's positive versus negative values for decisive behaviors, suggesting that such values are plausibly an important means for motivating and sustaining cultural differences in indecisiveness. Study 3 provided direct behavioral instances of the differences in indecisiveness implicated in Studies 1 and 2. It also suggested that thoroughness might be an important cognitive mechanism whereby cultural differences in indecision actually occur, with thoroughness being especially prominent among Japanese decision makers. Suggestions for theory concerning the nature and foundations of indecisiveness and its cultural variations are developed and discussed, along with plausible implications for real-life practical issues, for example, in politics and management. C1 [Yates, J. Frank] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Ji, Li-Jun] Queens Univ, Kingston, ON, Canada. [Oka, Takashi] Nihon Univ, Tokyo, Japan. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shinotsuka, Hiromi] Hokkaido Univ, Dept Behav Sci, Sapporo, Hokkaido 060, Japan. [Sieck, Winston R.] Appl Res Associates, Culture & Cognit Grp, Fairborn, OH USA. RP Yates, JF (reprint author), Univ Michigan, Dept Psychol, 530 Church St, Ann Arbor, MI 48109 USA. EM jfyates@umich.edu NR 30 TC 15 Z9 16 U1 4 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD MAY 10 PY 2010 VL 41 IS 3 BP 428 EP 444 DI 10.1177/0022022109359692 PG 17 WC Psychology, Social SC Psychology GA 583BI UT WOS:000276646200010 ER PT J AU Greenblatt, MB Aliprantis, A Hu, B Glimcher, LH AF Greenblatt, Matthew B. Aliprantis, Antonios Hu, Bella Glimcher, Laurie H. TI Calcineurin regulates innate antifungal immunity in neutrophils SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID C-TYPE LECTIN; CANDIDA-ALBICANS; CYCLOSPORINE-A; HOST-DEFENSE; SIGNALING PATHWAY; FUNGAL-INFECTION; NFAT ACTIVATION; T-CELLS; DECTIN-1; MICE AB Patients taking immunosuppressive drugs, like cyclosporine A (CsA), that inhibit calcineurin are highly susceptible to disseminated fungal infections, although it is unclear how these drugs suppress resistance to these opportunistic pathogens. We show that in a mouse model of disseminated Candida albicans infection, CsA-induced susceptibility to fungal infection maps to the innate immune system. To further define the cell types targeted by CsA, we generated mice with a conditional deletion of calcineurin B (CnB) in neutrophils. These mice displayed markedly decreased resistance to infection with C. albicans, and both CnB-deficient and CsA-treated neutrophils showed a defect in the ex vivo killing of C. albicans. In response to the fungal-derived pathogen-associated molecular pattern zymosan, neutrophils lacking CnB displayed impaired up-regulation of genes (IL-10, Cox2, Egr1, and Egr2) regulated by nuclear factor of activated T cells, the best characterized CnB substrate. This activity was Myd88 independent and was reproduced by stimulation with the beta(1,3) glucan curdlan, indicating that dectin-1, rather than toll-like receptors, is the upstream activator of calcineurin. Our results suggest that disseminated fungal infections seen in CsA-treated patients are not just a general consequence of systemic suppression of adaptive immunity but are, rather, a result of the specific blockade of evolutionarily conserved innate pathways for fungal resistance. C1 [Greenblatt, Matthew B.; Aliprantis, Antonios; Hu, Bella; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Aliprantis, Antonios; Glimcher, Laurie H.] Harvard Univ, Dept Med, Boston, MA 02115 USA. [Aliprantis, Antonios; Glimcher, Laurie H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Glimcher, Laurie H.] Massachusetts Gen Hosp, Ragon Inst, Harvard & MIT, Charlestown, MA 02129 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM lglimche@hsph.harvard.edu FU National Institutes of Health [AI43953, AI31541]; Burroughs Wellcome Fund CAMS award; [K08AR054859] FX This work was supported by National Institutes of Health grants AI43953 and AI31541 (L. H. Glimcher), Burroughs Wellcome Fund CAMS award (A. Aliprantis), and K08AR054859 (A. Aliprantis). NR 48 TC 70 Z9 70 U1 3 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 10 PY 2010 VL 207 IS 5 BP 923 EP 931 DI 10.1084/jem.20092531 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 593KB UT WOS:000277452100005 PM 20421389 ER PT J AU Chen, YB Hochberg, EP Feng, Y Neuberg, D Rawal, B Motyckova, G Fisher, DC Mcafee, SL Spitzer, TR Lacasce, AS AF Chen, Yi-Bin Hochberg, Ephraim P. Feng, Yang Neuberg, Donna Rawal, Bhupendra Motyckova, Gabriela Fisher, David C. Mcafee, Steven L. Spitzer, Thomas R. Lacasce, Ann S. TI Characteristics and outcomes after autologous stem cell transplant for patients with relapsed or refractory diffuse large B-cell lymphoma who failed initial rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone therapy compared to patients who failed cyclophosphamide, adriamycin, vincristine, and prednisone SO LEUKEMIA & LYMPHOMA LA English DT Article ID NON-HODGKINS-LYMPHOMA; HIGH-DOSE CHEMOTHERAPY; PREDICTS AB Autologous stem cell transplant (ASCT) is the standard of care for patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adding rituximab (R) to the initial therapy has improved outcomes; however, the benefit of ASCT for chemosensitive patients who fail R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) is unclear. Patients who underwent ASCT between 1997 and 2006 for DLBCL at two partner institutions were identified. Characteristics and outcomes were compared between patients who received R-CHOP as initial chemotherapy and those who received CHOP. Of the 185 patients evaluated, 137 were initially treated with CHOP and 48 received R-CHOP. Patients who received R-CHOP were older, had shorter remissions, and initially had more advanced stage. With univariate analysis, PFS and OS did not differ; however, multivariable Cox regression analysis suggested a poorer prognosis for patients who underwent ASCT after failing R-CHOP. In conclusion, patients who fail R-CHOP appear to benefit from ASCT, but they may have a worse prognosis compared to patients who fail CHOP alone.-/- mice. NR 40 TC 16 Z9 19 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8090 J9 J CARDIOTHORAC SURG JI J. Cardiothorac. Surg. PD MAY 4 PY 2010 VL 5 AR 32 DI 10.1186/1749-8090-5-32 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604IY UT WOS:000278273900001 PM 20441584 ER PT J AU Herrera, M Roberts, DC Gulbahce, N AF Herrera, Mark Roberts, David C. Gulbahce, Natali TI Mapping the Evolution of Scientific Fields SO PLOS ONE LA English DT Article ID COMPLEX NETWORKS; COMMUNITY STRUCTURE; PREDICTION; SCIENCE; MAPS AB Despite the apparent cross-disciplinary interactions among scientific fields, a formal description of their evolution is lacking. Here we describe a novel approach to study the dynamics and evolution of scientific fields using a network-based analysis. We build an idea network consisting of American Physical Society Physics and Astronomy Classification Scheme (PACS) numbers as nodes representing scientific concepts. Two PACS numbers are linked if there exist publications that reference them simultaneously. We locate scientific fields using a community finding algorithm, and describe the time evolution of these fields over the course of 1985-2006. The communities we identify map to known scientific fields, and their age depends on their size and activity. We expect our approach to quantifying the evolution of ideas to be relevant for making predictions about the future of science and thus help to guide its development. C1 [Herrera, Mark] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Herrera, Mark] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. [Roberts, David C.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. [Roberts, David C.] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. [Gulbahce, Natali] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Gulbahce, Natali] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Gulbahce, Natali] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Herrera, M (reprint author), Univ Maryland, Dept Phys, College Pk, MD 20742 USA. EM dcr@lanl.gov; natali.gulbahce@gmail.com RI Herrera, Mark/I-2446-2012 FU Center for Nonlinear Studies at Los Alamos National Laboratory; Los Alamos Physics Summer School; Feynman Fellowship; National Institutes of Health [P50HG004233] FX All authors were partially funded by the Center for Nonlinear Studies at Los Alamos National Laboratory. MH was also funded by the Los Alamos Physics Summer School, DCR was funded by the Feynman Fellowship, and NG was funded in part by National Institutes of Health grant P50HG004233. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 15 Z9 15 U1 1 U2 14 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 MAY 4 PY 2010 VL 5 IS 5 AR e10355 DI 10.1371/journal.pone.0010355 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591MQ UT WOS:000277305300002 PM 20463949 ER PT J AU Jones, DC Schweitzer, MN Wein, M Sigrist, K Takagi, T Ishii, S Glimcher, LH AF Jones, Dallas C. Schweitzer, Michelle N. Wein, Marc Sigrist, Kirsten Takagi, Tsuyoshi Ishii, Shunsuke Glimcher, Laurie H. TI Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chondrodysplasia; osteoblast; skeletogenesis ID ENDOCHONDRAL OSSIFICATION; SKELETAL DEVELOPMENT; MURINE SCHNURRI-2; CARTILAGE; CELL; EXPRESSION; CHONDRODYSPLASIA; REGULATOR; INTERACTS; MOUSE AB Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mutations in the adapter proteins Schnurri2 (Shn2) and Schnurri3 (Shn3) exhibit defects in patterning of the axial skeleton during embryogenesis. Postnatally, these compound mutant mice develop a unique osteochondrodysplasia. The deletion of Shn2 and Shn3 impairs growth plate maturation during endochondral ossification but simultaneously results in massively elevated trabecular bone formation. Hence, growth plate maturation and bone formation can be uncoupled under certain circumstances. These unexpected findings demonstrate that both unique and redundant functions reside in the Schnurri protein family that are required for proper skeletal patterning and remodeling. C1 [Jones, Dallas C.; Schweitzer, Michelle N.; Wein, Marc; Sigrist, Kirsten; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Jones, Dallas C.; Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Takagi, Tsuyoshi; Ishii, Shunsuke] RIKEN Tsukuba Inst, Mol Genet Lab, Tsukuba, Ibaraki 3050074, Japan. [Glimcher, Laurie H.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. [Glimcher, Laurie H.] Harvard, Boston, MA 02129 USA. RP Jones, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM djones@hsph.harvard.edu; lglimche@hsph.harvard.edu RI Ishii, Shunsuke/A-5271-2016 FU National Institutes of Health [HD055601, K99AR055668]; Merck Pharmaceuticals FX The authors thank Dorothy Zhang for expert histology preparation, Drs. Yukiko Maeda and Despina Sitara for technical assistance with in situ hybridization, and Nicholas Brady for generation of mu CT images and analysis. This work was supported by National Institutes of Health Grants HD055601 (to L. H. G.) and K99AR055668 (to D.C.J.) and by a grant from Merck Pharmaceuticals. NR 28 TC 12 Z9 12 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 4 PY 2010 VL 107 IS 18 BP 8254 EP 8258 DI 10.1073/pnas.1003727107 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591OK UT WOS:000277310400039 PM 20404140 ER PT J AU Vaira, V Fedele, G Pyne, S Fasoli, E Zadra, G Bailey, D Snyder, E Faversani, A Coggi, G Flavin, R Bosari, S Loda, M AF Vaira, Valentina Fedele, Giuseppe Pyne, Saumyadipta Fasoli, Ester Zadra, Giorgia Bailey, Dyane Snyder, Eric Faversani, Alice Coggi, Guido Flavin, Richard Bosari, Silvano Loda, Massimo TI Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug response; ex vivo; human tumor tissue culture; PI3K ID CANCER; SLICES; EFFICACY; SYSTEMS; CELLS; LIVER AB Predicting drug response in cancer patients remains a major challenge in the clinic. We have perfected an ex vivo, reproducible, rapid and personalized culture method to investigate antitumoral pharmacological properties that preserves the original cancer microenvironment. Response to signal transduction inhibitors in cancer is determined not only by properties of the drug target but also by mutations in other signaling molecules and the tumor microenvironment. As a proof of concept, we, therefore, focused on the PI3K/Akt signaling pathway, because it plays a prominent role in cancer and its activity is affected by epithelial-stromal interactions. Our results show that this culture model preserves tissue 3D architecture, cell viability, pathway activity, and global gene-expression profiles up to 5 days ex vivo. In addition, we show pathway modulation in tumor cells resulting from pharmacologic intervention in ex vivo culture. This technology may have a significant impact on patient selection for clinical trials and in predicting response to small-molecule inhibitor therapy. C1 [Vaira, Valentina; Fasoli, Ester; Faversani, Alice; Coggi, Guido; Bosari, Silvano] Univ Milan, Div Pathol, Dept Med Surg & Dent, AO San Paolo, I-20142 Milan, Italy. [Vaira, Valentina; Fasoli, Ester; Faversani, Alice; Coggi, Guido; Bosari, Silvano] Fdn IRCCS Ca Granda Osped Maggiore Policlin, I-20142 Milan, Italy. [Fedele, Giuseppe; Pyne, Saumyadipta; Zadra, Giorgia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bailey, Dyane; Snyder, Eric; Flavin, Richard; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. RP Bosari, S (reprint author), Univ Milan, Div Pathol, Dept Med Surg & Dent, AO San Paolo, I-20142 Milan, Italy. EM silvano.bosari@unimi.it; massimo_loda@dfci.harvard.edu RI Faversani, Alice/K-6509-2016; vaira, valentina/K-6499-2016; Bosari, Silvano/K-7744-2016 OI Faversani, Alice/0000-0002-0970-6208; vaira, valentina/0000-0003-4416-6216; Bosari, Silvano/0000-0002-9744-6951 FU American-Italian Cancer Foundation; Doctorate School of Molecular Medicine at Universita degli Studi di Milano; Prostate Cancer Foundation; National Cancer Institute [R01CA131945, P01CA89021, P50 CA90381]; Linda and Arthur Gelb Center for Translational Research; Nuclea Biomarkers; Loda Laboratory; Dana Farber Cancer Institute-Novartis FX We thank Todd Golub for critical review of the manuscript, Robert Onofrio for technical support with DASL assay, and Yujin Hoshida for valuable suggestions on DASL gene-expression analysis. We are also grateful to Xiaoqiu Wu for automated image analysis and to Lingxian Wu for technical help. G.Z. is supported by a fellowship of the American-Italian Cancer Foundation. A. F. is supported by a fellowship of the Doctorate School of Molecular Medicine at Universita degli Studi di Milano. Support for this work was obtained from the Prostate Cancer Foundation (M. L.), National Cancer Institute Grants R01CA131945, P01CA89021, and P50 CA90381 (to M. L.), the Linda and Arthur Gelb Center for Translational Research (M. L.), a gift from Nuclea Biomarkers to the Jimmy Fund (to M. L.), and the Loda Laboratory (M. L.). M. L. is the recipient of a grant from the Dana Farber Cancer Institute-Novartis Drug Development Program. NR 12 TC 77 Z9 78 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 4 PY 2010 VL 107 IS 18 BP 8352 EP 8356 DI 10.1073/pnas.0907676107 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591OK UT WOS:000277310400056 PM 20404174 ER PT J AU Lin, AL Fox, PT Hardies, J Duong, TQ Gao, JH AF Lin, Ai-Ling Fox, Peter T. Hardies, Jean Duong, Timothy Q. Gao, Jia-Hong TI Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral metabolic rate of oxygen; lactate production ID POSITRON-EMISSION-TOMOGRAPHY; ACTIVATED HUMAN BRAIN; OXIDATIVE-METABOLISM; NEURONAL-ACTIVITY; STIMULATION; VOLUME; TIME; SPECTROSCOPY; DEPENDENCE; DYNAMICS AB The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i. e., ATP production (J(ATP))] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow(CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO(2); i.e., index of aerobic metabolism), and lactate production (J(Lac); i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in JATP were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %Delta J(ATP) being linearly correlated with the percentage change in CMRO(2) (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7-65.1%) and negatively correlated with the percentage change in CMRO(2) (r=-0.64, P=0.024), but positively correlated with %Delta J(Lac) (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand. C1 [Lin, Ai-Ling; Fox, Peter T.; Hardies, Jean; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Lin, Ai-Ling; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Fox, Peter T.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fox, Peter T.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Fox, Peter T.; Duong, Timothy Q.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Gao, Jia-Hong] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Gao, Jia-Hong] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Gao, Jia-Hong] Univ Chicago, Dept Behav Neurosci, Chicago, IL 60637 USA. [Gao, Jia-Hong] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA. RP Lin, AL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. EM lina3@uthscsa.edu; jgao@uchicago.edu RI Hardies, Lou /F-2102-2010; Lin, Ai-Ling/F-3972-2010; Duong, Timothy/B-8525-2008; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU National Institutes of Health; University of Texas Health Science Center at San Antonio General Clinical Research Center [M01 RR01346] FX We express our appreciation to Drs. Silvia Mangia and Xiao-Hong Zhu at the University of Minnesota for fruitful discussions and valuable comments. This work was supported by National Institutes of Health and University of Texas Health Science Center at San Antonio General Clinical Research Center Grant M01 RR01346. NR 47 TC 76 Z9 76 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 4 PY 2010 VL 107 IS 18 BP 8446 EP 8451 DI 10.1073/pnas.0909711107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591OK UT WOS:000277310400072 PM 20404151 ER PT J AU Chastanet, A Vitkup, D Yuan, GC Norman, TM Liu, JS Losick, RM AF Chastanet, Arnaud Vitkup, Dennis Yuan, Guo-Cheng Norman, Thomas M. Liu, Jun S. Losick, Richard M. TI Broadly heterogeneous activation of the master regulator for sporulation in Bacillus subtilis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE noise; Spo0A; bistable switch; cell fate; heterogeneity ID GENE-EXPRESSION; STATIONARY-PHASE; POPULATION HETEROGENEITY; SPO0A; TRANSCRIPTION; INITIATION; PROTEIN; PHOSPHORELAY; BISTABILITY; TRANSITION AB A model system for investigating how developmental regulatory networks determine cell fate is spore formation in Bacillus subtilis. The master regulator for sporulation is Spo0A, which is activated by phosphorylation via a phosphorelay that is subject to three positive feedback loops. The ultimate decision to sporulate is, however, stochastic in that only a portion of the population sporulates even under optimal conditions. It was previously assumed that activation of Spo0A and hence entry into sporulation is subject to a bistable switch mediated by one or more feedback loops. Here we reinvestigate the basis for bimodality in sporulation. We show that none of the feedback loops is rate limiting for the synthesis and phosphorylation of Spo0A. Instead, the loops ensure a just-in-time supply of relay components for rising levels of phosphorylated Spo0A, with phosphate flux through the relay being limiting for Spo0A activation and sporulation. In addition, genes under Spo0A control did not exhibit a bimodal pattern of expression as expected for a bistable switch. In contrast, we observed a highly heterogeneous pattern of Spo0A activation that increased in a nonlinear manner with time. We present a computational model for the nonlinear increase and propose that the phosphorelay is a noise generator and that only cells that attain a threshold level of phosphorylated Spo0A sporulate. C1 [Chastanet, Arnaud; Vitkup, Dennis; Norman, Thomas M.; Losick, Richard M.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Vitkup, Dennis] Columbia Univ, Dept Biomed Informat, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. [Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Vitkup, D (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM dv212@columbia.edu; losick@mcb.harvard.edu FU National Institutes of Health [GM078990]; National Institute of General Medical Sciences [GM079759]; National Centers for Biomedical Computing [U54CA121852]; Agence Nationale de la Recherche [08-JCJC-0024-01] FX This work was supported by National Institutes of Health Grant GM078990 (to J.S.L. and R.M.L.), National Institute of General Medical Sciences Grant GM079759 (to D.V.), and the National Centers for Biomedical Computing Grant U54CA121852 (to D.V. and R.M.L.). A.C. was also supported by Agence Nationale de la Recherche Grant 08-JCJC-0024-01. NR 26 TC 62 Z9 64 U1 3 U2 16 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 MAY 4 PY 2010 VL 107 IS 18 BP 8486 EP 8491 DI 10.1073/pnas.1002499107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 591OK UT WOS:000277310400079 PM 20404177 ER PT J AU Matsuoka, K Kim, HT McDonough, S Bascug, G Warshauer, B Koreth, J Cutler, C Ho, VT Alyea, EP Antin, JH Soiffer, RJ Ritz, J AF Matsuoka, Ken-ichi Kim, Haesook T. McDonough, Sean Bascug, Gregory Warshauer, Ben Koreth, John Cutler, Corey Ho, Vincent T. Alyea, Edwin P. Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome TI Altered regulatory T cell homeostasis in patients with CD4(+) lymphopenia following allogeneic hematopoietic stern cell transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; IN-VIVO; IMMUNE RECONSTITUTION; SUPPRESSIVE FUNCTION; AUTOIMMUNE-DISEASES; PERIPHERAL-BLOOD; SELF-TOLERANCE; TCR REPERTOIRE; CUTTING EDGE AB CD4(+)CD25(+)Foxp3(+) Tregs have an indispensable role in the maintenance of tolerance after allogeneic HSC transplantation (HSCT). Patients with chronic graft-versus-host disease (GVHD) have fewer circulating Tregs, but the mechanisms that lead to this deficiency of Tregs after HSCT are not known. Here, we analyzed reconstitution of Tregs and conventional CD4(+) T cells (Tcons) in patients who underwent allogeneic HSCT after myeloablative conditioning. Following transplant, thymic generation of naive Tregs was markedly impaired, and reconstituting Tregs had a predominantly activated/memory phenotype. In response to CD4(+) lymphopenia after HSCT, Tregs underwent higher levels of proliferation than Tcons, but Tregs undergoing homeostatic proliferation also showed increased susceptibility to Fas-mediated apoptosis. Prospective monitoring of CD4(+) T cell subsets revealed that Tregs rapidly expanded and achieved normal levels by 9 months after HSCT, but Treg levels subsequently declined in patients with prolonged CD4(+) lymphopenia. This resulted in a relative deficiency of Tregs, which was associated with a high incidence of extensive chronic GVHD. These studies indicate that CD4(+) lymphopenia is a critical factor in Treg homeostasis and that prolonged imbalance of Treg homeostasis after HSCT can result in loss of tolerance and significant clinical disease manifestations. C1 [Matsuoka, Ken-ichi; McDonough, Sean; Bascug, Gregory; Warshauer, Ben; Koreth, John; Cutler, Corey; Ho, Vincent T.; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Matsuoka, Ken-ichi; Koreth, John; Cutler, Corey; Ho, Vincent T.; Alyea, Edwin P.; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kim, Haesook T.; Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Kim, Haesook T.; Ritz, Jerome] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ritz, Jerome] Harvard Stem Cell Inst, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM Jerome_Ritz@dfci.harvard.edu FU NIH [AI29530, CA142106]; Ted and Eileen Pasquarello Research Fund FX This work was supported by NIH grants AI29530 and CA142106 and the Ted and Eileen Pasquarello Research Fund. We thank John Daley and Suzan Lazo-Kallanian for excellent assistance with flow cytometric studies; Doreen Hearsey, Gorka Murga, Britt Selland, and Myriam Armant for help obtaining clinical and cord blood samples; Grace Kao for providing composition data of stem cell grafts; and Baldev Vasir for helpful discussions. NR 79 TC 93 Z9 98 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2010 VL 120 IS 5 BP 1479 EP 1493 DI 10.1172/JCI41072 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590SN UT WOS:000277248000016 PM 20389017 ER PT J AU Shimizu, I Minamino, T Toko, H Okada, S Ikeda, H Yasuda, N Tateno, K Moriya, J Yokoyama, M Nojima, A Koh, GY Akazawa, H Shiojima, I Kahn, CR Abel, ED Komuro, I AF Shimizu, Ippei Minamino, Tohru Toko, Haruhiro Okada, Sho Ikeda, Hiroyuki Yasuda, Noritaka Tateno, Kaoru Moriya, Junji Yokoyama, Masataka Nojima, Aika Koh, Gou Young Akazawa, Hiroshi Shiojima, Ichiro Kahn, C. Ronald Abel, E. Dale Komuro, Issei TI Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; MYOCARDIAL FATTY-ACID; HEART-FAILURE; GLUCOSE-METABOLISM; TRANSGENIC MICE; ANGIOTENSIN-II; FAILING HEART; HYPERTROPHY; GROWTH; RESISTANCE AB Although many animal studies indicate insulin has cardioprotective effects, clinical studies suggest a link between insulin resistance (hyperinsulinemia) and heart failure (HF). Here we have demonstrated that excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. Chronic pressure overload induced hepatic insulin resistance and plasma insulin level elevation. In contrast, cardiac insulin signaling was upregulated by chronic pressure overload because of mechanical stretch-induced activation of cardiomyocyte insulin receptors and upregulation of insulin receptor and Irs1 expression. Chronic pressure overload increased the mismatch between cardiomyocyte size and vascularity, thereby inducing myocardial hypoxia and cardiomyocyte death. Inhibition of hyperinsulinemia substantially improved pressure overload-induced cardiac dysfunction, improving myocardial hypoxia and decreasing cardiomyocyte death. Likewise, the cardiomyocyte-specific reduction of insulin receptor expression prevented cardiac ischemia and hypertrophy and attenuated systolic dysfunction due to pressure overload. Conversely, treatment of type 1 diabetic mice with insulin improved hyperglycemia during pressure overload, but increased myocardial ischemia and cardiomyocyte death, thereby inducing HF. Promoting angiogenesis restored the cardiac dysfunction induced by insulin treatment. We therefore suggest that the use of insulin to control hyperglycemia could be harmful in the setting of pressure overload and that modulation of insulin signaling is crucial for the treatment of HF. C1 [Komuro, Issei] Chiba Univ, Dept Cardiovasc Sci & Med, Grad Sch Med, Chuo Ku, Chiba 2608670, Japan. [Minamino, Tohru] Japan Sci & Technol Agcy, PRESTO, Saitama, Japan. [Koh, Gou Young] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Koh, Gou Young] Biomed Res Ctr, Taejon, South Korea. [Shiojima, Ichiro; Komuro, Issei] Osaka Univ, Sch Med, Dept Cardiovasc Med, Osaka, Japan. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Abel, E. Dale] Univ Utah, Sch Med, Program Mol Med, Salt Lake City, UT USA. [Abel, E. Dale] Univ Utah, Sch Med, Div Endocrinol Diabet & Metab, Salt Lake City, UT USA. RP Komuro, I (reprint author), Chiba Univ, Dept Cardiovasc Sci & Med, Grad Sch Med, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM komuro-tky@umin.ac.jp RI Koh, Gou Young /C-1615-2011; OI Minamino, Tohru/0000-0003-1627-6151 FU Ministry of Education, Science, Sports, and Culture and Health and Labor Sciences; Ministry of Education, Culture, Sports, Science and Technology of Japan; Suzuken Memorial Foundation; Japan Diabetes Foundation; Ichiro Kanehara Foundation; Tokyo Biochemical Research Foundation; Takeda Science Foundation; Cell Science Research Foundation; Japan Foundation of Applied Enzymology; Astellas Foundation for Research on Metabolic Disorders FX We thank Morris J. Birnbaum for Aka-deficient mice. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture and Health and Labor Sciences research grants (to I. Komuro); a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and grants from the Suzuken Memorial Foundation; the Japan Diabetes Foundation; the Ichiro Kanehara Foundation; the Tokyo Biochemical Research Foundation; the Takeda Science Foundation; the Cell Science Research Foundation; the Japan Foundation of Applied Enzymology; and the Astellas Foundation for Research on Metabolic Disorders (to T. Minamino). NR 35 TC 64 Z9 65 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2010 VL 120 IS 5 BP 1506 EP 1514 DI 10.1172/JCI40096 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590SN UT WOS:000277248000018 PM 20407209 ER PT J AU Thomason, HA Zhou, HQ Kouwenhoven, EN Dotto, GP Restivo, G Nguyen, BC Little, HL Dixon, MJ van Bokhoven, H Dixon, J AF Thomason, Helen A. Zhou, Huiqing Kouwenhoven, Evelyn N. Dotto, Gian-Paolo Restivo, Gaia Nguyen, Bach-Cuc Little, Hay Ley Dixon, Michael J. van Bokhoven, Hans Dixon, Jill TI Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID POPLITEAL PTERYGIUM SYNDROME; P53-FAMILY MEMBERS P63; P53 HOMOLOG; VARIANTS CONTRIBUTE; THYROID AGENESIS; GENE-EXPRESSION; WOUDE SYNDROME; DIRECT TARGET; CAUSE VAN; IN-VIVO AB Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results in considerable morbidity to affected individuals and their families. The etiology of cleft palate is complex, with both genetic and environmental factors implicated. Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between the key transcription factors p63 and IRF6 has not been determined. Here, we used both mouse models and human primary keratinocytes from patients with cleft palate to demonstrate that IRF6 and p63 interact epistatically during development of the secondary palate. Mice simultaneously carrying a heterozygous deletion of p63 and the Irf6 knockin mutation R84C, which causes cleft palate in humans, displayed ectodermal abnormalities that led to cleft palate. Furthermore, we showed that p63 transactivated IRF6 by binding to an upstream enhancer element; genetic variation within this enhancer element is associated with increased susceptibility to cleft lip. Our findings therefore identify p63 as a key regulatory molecule during palate development and provide a mechanism for the cooperative role of p63 and IRF6 in orofacial development in mice and humans. C1 [Thomason, Helen A.; Dixon, Michael J.; Dixon, Jill] Univ Manchester, Fac Med & Human Sci, Manchester Acad Hlth Sci Ctr, Manchester M13 9PT, Lancs, England. [Zhou, Huiqing; Kouwenhoven, Evelyn N.; van Bokhoven, Hans] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Dotto, Gian-Paolo; Restivo, Gaia] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Nguyen, Bach-Cuc] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Little, Hay Ley; Dixon, Michael J.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. RP Dixon, J (reprint author), Univ Manchester, Fac Med & Human Sci, Manchester Acad Hlth Sci Ctr, Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM H.vanBokhoven@antrg.umcn.nl; jill.dixon@manchester.ac.uk RI van Bokhoven, Hans/D-8764-2012; Zhou, Huiqing/B-1721-2013; Bokhoven, J.H.L.M./H-8015-2014 OI Zhou, Huiqing/0000-0002-2434-3986; FU BBSRC; Wellcome; University of Manchester; Medical Research Council [G0400264, G0400955]; Wellcome Trust [082868]; NIH [P50-DE016215, AR39190]; Healing Foundation; EU [FP6-2004-LIFESCIHEALTH-5, LSH-1.2.1-3, CT-2005-019067]; NIHR Manchester Biomedical Research Centre FX We thank Les Lockey and Samantha Newby (University of Manchester Electron Microscopy Unit) for help and advice, Jane Kott and Robert Fernandez for help with the microscopy, and Marion Lohrum for assistance with Solexa sequencing analysis. The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome, and the University of Manchester Strategic Fund. This research was funded by grants from the Medical Research Council (G0400264 to J. Dixon and G0400955 to M.J. Dixon), Wellcome Trust (082868 to M.J. Dixon), the NIH (P50-DE016215 to M.J.D and AR39190 to G.-P. Dotto), the Healing Foundation (to M.J. Dixon), and EU (EPISTEM FP6-2004-LIFESCIHEALTH-5, Integrated Project LSH-1.2.1-3 to H. von Bokhoven, H. Zhou, and G.-P. Dotto; Sixth Framework Program LSHB-CT-2005-019067 to G.-P. Dotto). M.J. Dixon is supported by the NIHR Manchester Biomedical Research Centre. NR 65 TC 68 Z9 71 U1 0 U2 8 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 MAY PY 2010 VL 120 IS 5 BP 1561 EP 1569 DI 10.1172/JCI40266 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590SN UT WOS:000277248000023 PM 20424327 ER PT J AU Hwang, U Baumlin, K Berman, J Chawla, NK Handel, DA Heard, K Livote, E Pines, JM Valley, M Yadav, K AF Hwang, Ula Baumlin, Kevin Berman, Jeremy Chawla, Neal K. Handel, Daniel A. Heard, Kennon Livote, Elayne Pines, Jesse M. Valley, Morgan Yadav, Kabir TI Emergency Department Patient Volume and Troponin Laboratory Turnaround Time SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Canadian-Association-of-Emergency-Physicians CY JUN 06-10, 2009 CL Calgary, CANADA SP Canadian Assoc Emergency Phys DE emergency department; laboratory turnaround time; emergency department crowding ID LENGTH-OF-STAY; MYOCARDIAL-INFARCTION; CHEST-PAIN; CARE; IMPACT; ASSOCIATION; GUIDELINES; IMPLEMENTATION; MANAGEMENT; SOCIETY AB Objectives: Increases in emergency department (ED) visits may place a substantial burden on both the ED and hospital-based laboratories. Studies have identified laboratory turnaround time (TAT) as a barrier to patient process times and lengths of stay. Prolonged laboratory study results may also result in delayed recognition of critically ill patients and initiation of appropriate therapies. The objective of this study was to determine how ED patient volume itself is associated with laboratory TAT. Methods: This was a retrospective cohort review of patients at five academic, tertiary care EDs in the United States. Data were collected on all adult patients seen in each ED with troponin laboratory testing during the months of January, April, July, and October 2007. Primary predictor variables were two ED patient volume measures at the time the troponin test was ordered: 1) number of all patients in the ED/number of beds (occupancy) and 2) number of admitted patients waiting for beds/beds (boarder occupancy). The outcome variable was troponin turnaround time (TTAT). Adjusted covariates included patient characteristics, triage severity, season (month of the laboratory test), and site. Multivariable adjusted quantile regression was carried out to assess the association of ED volume measures with TTAT. Results: At total of 9,492 troponin tests were reviewed. Median TTAT for this cohort was 107 minutes (interquartile range [IQR] = 73-148 minutes). Median occupancy for this cohort was 1.05 patients (IQR = 0.78-1.38 patients) and median boarder occupancy was 0.21 (IQR = 0.11-0.32). Adjusted quantile regression demonstrated a significant association between increased ED patient volume and longer times to TTAT. For every 100% increase in census, or number of boarders over the number of ED beds, respectively, there was a 12 (95% confidence interval [CI] = 9 to 14) or 33 (95% CI = 24 to 42)-minute increase in TTAT. Conclusions: Increased ED patient volume is associated with longer hospital laboratory processing times. Prolonged laboratory TAT may delay recognition of conditions in the acutely ill, potentially affecting clinician decision-making and the initiation of timely treatment. Use of laboratory TAT as a patient throughput measure and the study of factors associated with its prolonging should be further investigated. ACADEMIC EMERGENCY MEDICINE 2010; 17:501-507 (C) 2010 by the Society for Academic Emergency Medicine C1 [Hwang, Ula; Baumlin, Kevin; Chawla, Neal K.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Hwang, Ula; Livote, Elayne] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Berman, Jeremy; Yadav, Kabir] George Washington Sch Med, Dept Emergency Med, Washington, DC USA. [Chawla, Neal K.] INOVA Fairfax Hosp, Dept Emergency Med, Falls Church, VA USA. [Handel, Daniel A.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. [Heard, Kennon; Valley, Morgan] Univ Colorado, Sch Med, Div Emergency Med, Denver, CO USA. [Pines, Jesse M.] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. EM ula.hwang@mountsinai.org OI Yadav, Kabir/0000-0002-1092-9935 FU NIDA NIH HHS [K08 DA020573, K08 DA020573-03] NR 29 TC 14 Z9 15 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2010 VL 17 IS 5 BP 501 EP 507 DI 10.1111/j.1553-2712.2010.00738.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 587NN UT WOS:000276999500009 PM 20536804 ER PT J AU Landman, AB Bernstein, SL Hsiao, AL Desai, RA AF Landman, Adam B. Bernstein, Steven L. Hsiao, Allen L. Desai, Rani A. TI Emergency Department Information System Adoption in the United States SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Canadian-Association-of-Emergency-Physicians CY JUN 06-10, 2009 CL Calgary, CANADA SP Canadian Assoc Emergency Phys DE Financing; government/legislation and jurisprudence; United States; medical informatics; medical records systems; computerized; emergency service; hospital ID ELECTRONIC HEALTH RECORDS; CARE; TECHNOLOGY; PHYSICIANS; OUTCOMES; QUALITY AB Objectives: The American Recovery and Reinvestment Act of 2009 incentivizes adoption of health care information technology (HIT) based on support for specific standards, policies, and features. Limited data have been published on national emergency department information systems (EDIS) adoption, and to our knowledge, no prior studies have considered functionality measures. This study determined current national estimates of EDIS adoption using both single-response rates of EDIS adoption and a novel feature-based definition and also identified emergency department (ED) characteristics associated with EDIS use. Methods: The 2006 National Hospital Ambulatory Medical Care Survey, a nationally representative sample of ED visits that also surveyed participating EDs on EDIS, was used to estimate EDIS adoption. EDIS adoption rates were calculated using two definitions: 1) single-response-response to a single survey question as to whether the EDIS was complete, partial, or none; and 2) feature-based-based on the reported features supported by the EDIS, systems were categorized as fully functional, basic, other, or none. The relationship of EDIS adoption to specific ED characteristics such as facility type and location was also examined. Results: Using the single-response classification, 16.1% of EDs had a complete EDIS, while 30.4% had a partial EDIS, and 53.5% had none. In contrast, using a feature-based categorization, 1.7% EDs had a fully functional EDIS, 12.3% had basic, 32.1% had other, and 53.9% had none. In multivariable analysis, urban EDs were significantly more likely to have a fully functional or basic EDIS than were rural EDs. Pediatric EDs were significantly more likely than general EDs to have other EDIS. Conclusions: Despite more optimistic single-response estimates, fewer than 2% of our nation's EDs have a fully functional EDIS. EDs in urban areas and those specializing in the care of pediatric patients are more likely to support EDIS. Accurate and consistent EDIS adoption estimates are dependent on whether there are standardized EDIS definitions and classifications of features. To realize the potential value of EDIS for improved emergency care, we need to better understand the extent and correlates of the diffusion of this technology and increase emergency medicine engagement in national HIT policy-making. ACADEMIC EMERGENCY MEDICINE 2010; 17:536-544 (C) 2010 by the Society for Academic Emergency Medicine C1 [Landman, Adam B.; Desai, Rani A.] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. [Landman, Adam B.; Bernstein, Steven L.] Yale Univ, Dept Emergency Med, New Haven, CT USA. [Hsiao, Allen L.] Yale Univ, Dept Pediat Emergency Med, New Haven, CT USA. [Desai, Rani A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Landman, Adam B.; Desai, Rani A.] US Dept Vet Affairs, West Haven, CT USA. RP Landman, AB (reprint author), Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA. EM adam.landman@yale.edu OI Landman, Adam/0000-0002-2166-0521 NR 28 TC 14 Z9 14 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2010 VL 17 IS 5 BP 536 EP 544 DI 10.1111/j.1553-2712.2010.00722.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 587NN UT WOS:000276999500015 PM 20536810 ER PT J AU Oreskovic, NM Kuhlthau, KA Laraque, D Serwint, JR Schuster, MA AF Oreskovic, Nicolas M. Kuhlthau, Karen A. Laraque, Danielle Serwint, Janet R. Schuster, Mark A. TI Health Care Reform for Children: Views From the Academic Pediatric Association SO ACADEMIC PEDIATRICS LA English DT Editorial Material C1 [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Kuhlthau, Karen A.; Schuster, Mark A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Laraque, Danielle] Mt Sinai Sch Med, Div Gen Pediat, Dept Pediat, New York, NY USA. [Serwint, Janet R.] Johns Hopkins Univ, Sch Med, Dept Gen Pediat & Adolescent Med, Baltimore, MD USA. [Schuster, Mark A.] Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA 02115 USA. RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Internal Med, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM noreskovic@partners.org OI Oreskovic, Nicolas/0000-0001-8702-8636 NR 8 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 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2010 VL 10 IS 3 BP 153 EP 154 PG 2 WC Pediatrics SC Pediatrics GA 599XW UT WOS:000277948600001 PM 20452563 ER PT J AU Boudreau, ADA Fluet, CE Reuland, CP Delahaye, J Perrin, JM Kuhlthau, K AF Boudreau, Alexy D. Arauz Fluet, Christina E. Reuland, Colleen Peck Delahaye, Jennifer Perrin, James M. Kuhlthau, Karen TI Associations of Providers' Language and Cultural Skills With Latino Parents' Perceptions of Well-Child Care SO ACADEMIC PEDIATRICS LA English DT Article DE cultural competency; health disparities; language barriers; quality of care; well-child preventive care ID LIMITED ENGLISH PROFICIENCY; PEDIATRIC PREVENTIVE CARE; HEALTH-CARE; PHYSICIAN LANGUAGE; RESEARCH AGENDA; COMPETENCE; QUALITY; DISPARITIES; SERVICES; CONCORDANCE AB Objective.-To assess the associations of parent primary care provider language concordance and providers' self-rated cultural competency items with Latino parent report of well-child care quality. Methods.-A cross-sectional survey of parents with children 10-50 months old and their children's providers in 3 community health centers. We used the mean scores of quality domains of the Promoting Healthy Development Survey to examine associations of parent-provider language concordance and providers' self-rated cultural competency items with the quality of well-child care provided (all scales range 0-100). Results.-Results are based on 462 Latino parent responses and 22 provider responses. Latino parents in language concordant patient-provider relationships did not report higher-quality well-child care. Higher parent-reported quality of care was associated with provider self-reported effectiveness in treating Latino patients in the domains of family-centered care (mean 80.5 vs 70.6; P = .02) and helpfulness of care (mean 84.2 vs 67.9; P = .02). A language cultural competency summary scale was associated with the domain assessing family risk factors (+11.2 points; P = .02) and its subdomain of emotional assessment (+16.1 points; P = .02). Conclusions. Language concordance was not associated with parental reports of quality of well-child care. Provider self-perceived cultural competency was associated with higher scores in domains related to how content is delivered-that is, helpful and family-centered. The language-cultural competency summary score was associated with discussion of sensitive topics. These findings indicate that provider characteristics other than language concordance have greater association with quality of care and may offer opportunities to strengthen cultural competency, even among monolingual providers. C1 [Boudreau, Alexy D. Arauz; Delahaye, Jennifer; Perrin, James M.; Kuhlthau, Karen] Massachusetts Gen Hosp, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Fluet, Christina E.] Massachusetts Dept Mental Hlth, Boston, MA USA. [Reuland, Colleen Peck] Oregon Hlth & Sci Univ, Child & Adolescent Hlth Measurement Initiat, Portland, OR 97201 USA. RP Boudreau, ADA (reprint author), MGH, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM aarauz@partners.org FU Deborah Monroe Noonan Fund; Academic Pediatric Association FX Supported in part by grants to Alexy D. Arauz Boudreau, MD, MPH, from the Deborah Monroe Noonan Fund and the Academic Pediatric Association Young Investigator Award Program. NR 34 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAY-JUN PY 2010 VL 10 IS 3 BP 172 EP 178 PG 7 WC Pediatrics SC Pediatrics GA 599XW UT WOS:000277948600006 ER PT J AU Schlozman, SC Beresin, EV AF Schlozman, Steven C. Beresin, Eugene V. TI Frustration and Opportunity: Teaching Child and Adolescent Psychiatry Throughout Medical Education SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 [Schlozman, Steven C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Yawkey Ctr Outpatient Care,Div Child Psychiat, Boston, MA 02478 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Yawkey Ctr Outpatient Care,Div Child Psychiat, Suite 6900,55 Fruit St, Boston, MA 02478 USA. EM sschlozman@partners.org NR 7 TC 3 Z9 3 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2010 VL 34 IS 3 BP 172 EP 174 PG 3 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 589UP UT WOS:000277180000002 PM 20431092 ER PT J AU Ceranoglu, TA AF Ceranoglu, Tolga Atilla TI Star Wars in Psychotherapy: Video Games in the Office SO ACADEMIC PSYCHIATRY LA English DT Article ID DISTRACTION; CHILDREN; CANCER; MEDIA AB Objective: Video games are used in medical practice during psycho-education in chronic disease management, physical therapy, rehabilitation following traumatic brain injury, and as an adjunct in pain management during medical procedures or cancer chemotherapy. In psychiatric practice, video games aid in social skills training of children with developmental delays and in cognitive behavioral therapy (CBT). This most popular children's toy may prove a useful tool in dynamic psychotherapy of youth. Methods: The author provides a framework for using video games in psychotherapy by considering the characteristics of video games and describes the ways their use has facilitated various stages of therapeutic process. Results: Just as other play techniques build a relationship and encourage sharing of emotional themes, sitting together in front of a console and screen facilitates a relationship and allows a safe path for the patient's conflict to emerge. Conclusion: During video game play, the therapist may observe thought processes, impulsivity, temperament, decision-making, and sharing, among other aspects of a child's clinical presentation. Several features inherent to video games require a thoughtful approach as resistance and transference in therapy may be elaborated differently in comparison to more traditional toys. Familiarity with the video game content and its dynamics benefits child mental health clinicians in their efforts to help children and their families. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Ceranoglu, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM aceranoglu@partners.org NR 20 TC 7 Z9 7 U1 1 U2 18 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2010 VL 34 IS 3 BP 233 EP 236 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 589UP UT WOS:000277180000014 PM 20431107 ER PT J AU Reimer, B Mehler, B D'Ambrosio, LA Fried, R AF Reimer, Bryan Mehler, Bruce D'Ambrosio, Lisa A. Fried, Ronna TI The impact of distractions on young adult drivers with attention deficit hyperactivity disorder (ADHD) SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE Driving simulation; Distracted driving; Attention deficit hyperactivity disorder (ADHD); Driving; Cognitive distraction; Inattention ID DRIVING PERFORMANCE; DEFICIT/HYPERACTIVITY DISORDER; EYE-MOVEMENTS; IMPAIRMENTS; TELEPHONES; SIMULATOR; CHILDREN; BEHAVIOR; DEMANDS AB Young adults with attention deficit hyperactivity disorder (ADHD) are at higher risk for being involved in automobile crashes. Although driving simulators have been used to identify and understand underlying behaviors, prior research has focused largely on single-task, non-distracted driving. However, in-vehicle infotainment and communications systems often vie for a driver's attention, potentially increasing the risk of collision. This paper explores the impact of secondary tasks on individuals with and without ADHD, a medical condition known to affect the regulation of attention. Data are drawn from a validated driving simulation representing periods before, during, and after participation in a secondary cognitive task. A hands-free phone task was employed in a high stimulus, urban setting and a working memory task during low stimulus, highway driving. Drivers with ADHD had more difficulty on the telephone task, yet did not show an increased decrement in driving performance greater than control participants. In contrast, participants with ADHD showed a larger decline in driving performance than controls during a secondary task in a low demand setting. The results suggest that the interaction of the nature of the driving context and the secondary task has a significant influence on how drivers with ADHD allocate attention and, in-turn, on the relative impact on driving performance. Drivers with ADHD appear particularly susceptible to distraction during periods of low stimulus driving. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Reimer, Bryan; Mehler, Bruce; D'Ambrosio, Lisa A.] MIT, AgeLab, Cambridge, MA 02139 USA. [Fried, Ronna] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reimer, B (reprint author), MIT, AgeLab, 77 Massachusetts Ave,Rm E40-291, Cambridge, MA 02139 USA. EM reimer@mit.edu RI Reimer, Bryan/G-6431-2010; Mehler, Bruce/E-4538-2017 OI Reimer, Bryan/0000-0003-4850-8738; Mehler, Bruce/0000-0001-5929-4179 NR 43 TC 32 Z9 32 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD MAY PY 2010 VL 42 IS 3 SI SI BP 842 EP 851 DI 10.1016/j.aap.2009.06.021 PG 10 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 597SP UT WOS:000277781900009 PM 20380911 ER PT J AU Wilbur, DC AF Wilbur, D. C. TI WEB-BASED TELECYTOLOGY: NOVEL APPROACHES USING OLD AND NEW TECHNOLOGY SO ACTA CYTOLOGICA LA English DT Meeting Abstract C1 [Wilbur, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilbur, D. C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAY-JUN PY 2010 VL 54 IS 3 SU S BP 380 EP 380 PG 1 WC Pathology SC Pathology GA 600KZ UT WOS:000277986200054 ER PT J AU Jaafar, HSF Righi, E Van Noorden, S Dina, R Coleman, DV Poznansky, MC AF Jaafar, H. S. F. Righi, E. Van Noorden, S. Dina, R. Coleman, D. V. Poznansky, M. C. TI CORRELATION OF CXCLI2 EXPRESSION AND FOXP3 CELL INFILTRATION WITH HPV INFECTION AND CLINICO-PATHOLOGICAL PROGRESSION IN CERVICAL CANCER SO ACTA CYTOLOGICA LA English DT Meeting Abstract C1 Hammersmith Hosp, Imperial Coll London, Dept Histopathol & Cytopathol, London, England. RIPAS Hosp, Lab Serv, Bandar Seri Begawan, Brunei. Harvard Univ, Sch Med, Dept Infect Dis, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Canc Ctr,DFCI, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAY-JUN PY 2010 VL 54 IS 3 SU S BP 405 EP 406 PG 2 WC Pathology SC Pathology GA 600KZ UT WOS:000277986200130 ER PT J AU Vujanovic, AA Marshall, EC Gibson, LE Zvolensky, MJ AF Vujanovic, Anka A. Marshall, Erin C. Gibson, Laura E. Zvolensky, Michael J. TI Cognitive affective characteristics of smokers with and without posttraumatic stress disorder and panic psychopathology SO ADDICTIVE BEHAVIORS LA English DT Article DE Cognitive-affective; Smoking; PTSD; Panic; Anxiety disorders ID FAGERSTROM TOLERANCE QUESTIONNAIRE; ANXIETY SENSITIVITY INDEX; RECRUITED DAILY SMOKERS; NICOTINE DEPENDENCE; RISK-FACTORS; PSYCHIATRIC-DISORDERS; EMPIRICAL LITERATURE; CAMBODIAN REFUGEES; SMOKING-CESSATION; PERCEIVED CONTROL AB The present study evaluated differences among daily smokers with posttraumatic stress disorder (PTSD). panic disorder (PD), panic attacks (PA), and no axis I psychopathology (past 6 months) in terms of several cognitive-affective variables implicated in both the onset and maintenance of anxiety psychopathology and cigarette smoking. The sample consisted of 123 daily smokers (62% women: M(age) = 29.7, SD = 11.9). Compared to the PA and no psychopathology groups, the PTSD group reported significantly higher levels of anxiety sensitivity, discomfort intolerance, negative affectivity, anxious arousal, and anhedonic depression: and, the PTSD group reported significantly lower levels of perceived control over anxiety-related events than the PA group. The PD group, compared to those in the PA and no psychopathology groups, reported significantly higher levels of anxiety sensitivity, negative affectivity, and anxious arousal: and significantly lower levels of perceived control over anxiety-related events. No significant differences were evident between the PTSD and PD groups. Theoretical and clinical implications of the present findings are discussed in terms of smoking and emotional vulnerability. Published by Elsevier Ltd. C1 [Vujanovic, Anka A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. [Marshall, Erin C.; Gibson, Laura E.; Zvolensky, Michael J.] Univ Vermont, Burlington, VT 05405 USA. RP Vujanovic, AA (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM anka.vujanovic@va.gov FU National Institute on Drug Abuse [1 RO1 MH076629-01, 1 R01 DA018734-01A1, R03 DA16307-01, 1 R03 DA00101-01]; National Research Service Awards [1 F31 DA021006-01, 1 F31 MH080453-01A1] FX This paper was supported by the National Institute on Drug Abuse research grants (1 RO1 MH076629-01, 1 R01 DA018734-01A1, and R03 DA16307-01) awarded to Dr. Michael J. Zvolensky, as well as a National Institute of Drug Abuse research grant (1 R03 DA00101-01) awarded to Dr. Laura E. Gibson. This paper was also supported, in part, by the National Research Service Awards (1 F31 DA021006-01 and 1 F31 MH080453-01A1) granted to Anka A. Vujanovic and Erin C. Marshall, respectively. NR 73 TC 17 Z9 17 U1 5 U2 5 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 MAY PY 2010 VL 35 IS 5 BP 419 EP 425 DI 10.1016/j.addbeh.2009.12.005 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 576BG UT WOS:000276118000007 PM 20060228 ER PT J AU Corliss, HL Rosario, M Wypij, D Wylie, SA Frazier, AL Austin, SB AF Corliss, Heather L. Rosario, Margaret Wypij, David Wylie, Sarah A. Frazier, A. Lindsay Austin, S. Bryn TI Sexual orientation and drug use in a longitudinal cohort study of US adolescents SO ADDICTIVE BEHAVIORS LA English DT Article DE Illicit drug use; Prescription drug misuse; Adolescence; Sexual orientation; Gay, lesbian and bisexual; Longitudinal study ID SUBSTANCE USE; BISEXUAL YOUTH; COLLEGE-STUDENTS; SAME-SEX; SUICIDE ATTEMPTS; CANNABIS USE; GAY; BEHAVIORS; HEALTH; ABUSE AB Adolescents with a minority sexual orientation (e.g., lesbian, gay, and bisexual) are more likely louse substances than their heterosexual peers. This study aimed to increase understanding of the development of drug use in this vulnerable population by: 1) comparing longitudinal patterns of past-year illicit drug use (e.g., marijuana, cocaine, and ecstasy) and misuse of prescription drugs among minority sexual orientation youth relative to heterosexual youth and, 2) examining how sexual orientation sub-group, gender, and age relate to variation in the risk of drug use. Data come from the Growing Up Today Study, a community-based cohort of U.S. adolescents who were assessed three times between 1999 and 2005 with self-administered questionnaires when they ranged in age from 12 to 23 years (N = 12,644: 74.9% of the original cohort). Multivariable repeated measures generalized estimating equations using modified Poisson regression were used to estimate relative risks. Participants indicating their sexual orientation was mostly heterosexual, bisexual, or lesbian/gay were more likely than completely heterosexual youth to report past-year illicit drug use and misuse of prescription drugs. Gender was an important modifier: bisexual females were most likely to report drug use. Age was also an important modifier of risk; differences in drug use between minority sexual orientation and heterosexual youth were larger during adolescence (12-17 years) than during emerging adulthood (18-23 years). Research must focus on identifying reasons why minority sexual orientation youth are at disproportionate risk for drug use. Such information is essential for developing interventions that are critically needed to reduce drug use in this population. Efforts need to begin early because large sexual orientation disparities in drug use are evident by adolescence. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Corliss, Heather L.; Wylie, Sarah A.; Austin, S. Bryn] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Corliss, Heather L.; Wypij, David; Austin, S. Bryn] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Rosario, Margaret] CUNY, City Coll, New York, NY 10021 USA. [Rosario, Margaret] CUNY, Grad Ctr, New York, NY 10021 USA. [Wypij, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wypij, David] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Frazier, A. Lindsay; Austin, S. Bryn] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Corliss, HL (reprint author), Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM heather.corliss@tch.harvard.edu FU National Institutes of Health [DA23610, HD45763, DK46834, HL03533]; American Cancer Society [RSGPB-04-009-01-CPPB]; Robert Wood Johnson Foundation; Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, Health Resources and Services Administration [6T71-MC00009-16] FX This study was funded by grants DA23610, HD45763, DK46834, and HL03533 from the National Institutes of Health, grant RSGPB-04-009-01-CPPB from the American Cancer Society, and the Robert Wood Johnson Foundation. Drs. Corliss and Austin were also supported by the Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, Health Resources and Services Administration grant 6T71-MC00009-16. Funding sources had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 41 TC 70 Z9 72 U1 7 U2 16 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 MAY PY 2010 VL 35 IS 5 BP 517 EP 521 DI 10.1016/j.addbeh.2009.12.019 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 576BG UT WOS:000276118000024 PM 20061091 ER PT J AU Soderland, P Lovekar, S Weiner, DE Brooks, DR Kaufmann, JS AF Soderland, Peter Lovekar, Shachi Weiner, Daniel E. Brooks, Daniel R. Kaufmann, James S. TI Chronic Kidney Disease Associated With Environmental Toxins and Exposures SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Review DE Heavy metals; Aristolochic acid; Environmental exposure; Infectious diseases; Acute kidney injury; Heat ID BLOOD LEAD LEVELS; RENAL TUBULAR DYSFUNCTION; DRINKING-WATER; BALKAN NEPHROPATHY; ARISTOLOCHIC ACID; NATIONAL-HEALTH; UNITED-STATES; CHINESE HERBS; CADMIUM; TOXICITY AB People are exposed to various potentially toxic agents and conditions in their natural and occupational environments. These agents may be physical or chemical, may enter the human body through oral, inhalational, or transdermal routes, and may exert effects on all organ systems. Several well-known as well as lesser known associations exist between chronic kidney disease (CKD) and both environmental agents and conditions, such as heavy metals, industrial chemicals, elevated ambient temperatures, and infections. The effects of these agents may be modulated by genetic susceptibility and other comorbid conditions and may lead to the development of acute and CKD. In this article, we present environmental factors that are associated with CKD. Published by the National Kidney Foundation, Inc. C1 [Soderland, Peter; Lovekar, Shachi; Kaufmann, James S.] Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA. [Weiner, Daniel E.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Brooks, Daniel R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Kaufmann, James S.] VA Boston Healthcare Syst, Renal Sect, Boston, MA 02130 USA. RP Kaufmann, JS (reprint author), VA Boston Healthcare Syst, Renal Sect 111 RE, 150 S Huntington Ave, Boston, MA 02130 USA. EM James.kaufman@va.gov OI Brooks, Daniel/0000-0001-6220-6889 NR 67 TC 55 Z9 58 U1 4 U2 30 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD MAY PY 2010 VL 17 IS 3 BP 254 EP 264 DI 10.1053/j.ackd.2010.03.011 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 599YE UT WOS:000277949400007 PM 20439094 ER PT J AU Giordano, TP Bartsch, G Zhang, YF Tedaldi, E Absalon, J Mannheimer, S Thomas, A MacArthur, RD AF Giordano, Thomas P. Bartsch, Glenn Zhang, Yafeng Tedaldi, Ellen Absalon, Judith Mannheimer, Sharon Thomas, Avis MacArthur, Rodger D. TI Disparities in Outcomes for African American and Latino Subjects in the Flexible Initial Retrovirus Suppressive Therapies (FIRST) Trial SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; UNITED-STATES; VIROLOGICAL FAILURE; RACIAL DISPARITIES; ADHERENCE; CARE; PREVALENCE; PREDICTORS; SURVIVAL AB To benefit maximally from antiretroviral therapy, patients with HIV infection must enter care before their disease is advanced and adhere to care. We sought to determine if and where on this continuum of care racial/ethnic disparities were evident. Data from the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, which evaluated three strategies for initial HIV therapy, were compared for White, African American, and Latino subjects. Outcomes included progression of disease and death, HIV viral suppression, and change in CD4(+) cell count. Multivariate Cox proportional hazard models adjusted for known predictors of survival. There were 1357 subjects, including 368 non-Latino white, 751 non-Latino African American, and 238 Latino subjects. At baseline, the two latter groups were more likely to have had AIDS and had lower CD4(+) cell counts than white subjects. In follow-up, African American subjects had lower self-reported adherence to therapy, lower CD4(+) cell count increases, and lower odds of viral suppression. African American and Latino subjects had unadjusted hazard ratios of progression of disease or death of 1.57 (1.17, 2.10; p - 0.0025) and 1.57 (1.09, 2.26; p - 0.02), respectively. Adjusting for baseline differences and differences in adherence, CD4(+) cell count change, and viral suppression accounted for the disparities in outcomes. Opportunities to reduce disparities in outcomes for African American and Latino patients exist along the continuum of HIV care. Efforts to promote access to HIV testing and care and to improve adherence have the potential to reduce racial/ethnic disparities in outcomes of patients with HIV infection. C1 [Giordano, Thomas P.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Giordano, Thomas P.] Thomas St Hlth Ctr, Houston, TX USA. [Bartsch, Glenn; Zhang, Yafeng; Thomas, Avis] Univ Minnesota, Minneapolis, MN USA. [Tedaldi, Ellen] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Absalon, Judith] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Mannheimer, Sharon] Columbia Univ Coll Phys & Surg, Harlem Hosp, New York, NY 10032 USA. [MacArthur, Rodger D.] Wayne State Univ, Detroit, MI USA. RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [5U01AI042170-10, 5U01 AI046362-03) 058]; National Institute of Mental Health, National Institutes of Health [K23MH067505]; Houston VA HSR&D Center of Excellence [HFP90-020] FX The Flexible Initial Retrovirus Suppressive Therapies (FIRST; CPCRA 058) study was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grants 5U01AI042170-10 and 5U01 AI046362-03) 058). TPG received support from the National Institute of Mental Health, National Institutes of Health, grant K23MH067505 (TPG), and, in part, from the Houston VA HSR&D Center of Excellence (HFP90-020). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 42 TC 24 Z9 24 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAY PY 2010 VL 24 IS 5 BP 287 EP 295 DI 10.1089/apc.2009.0332 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 599LS UT WOS:000277914800003 PM 20438378 ER PT J AU Durazzo, TC Gazdzinski, S Mon, A Meyerhoff, DJ AF Durazzo, Timothy C. Gazdzinski, Stefan Mon, Anderson Meyerhoff, Dieter J. TI Cortical perfusion in alcohol-dependent individuals during short-term abstinence: relationships to resumption of hazardous drinking after treatment SO ALCOHOL LA English DT Article DE Alcohol dependence; Neuroimaging; Brain perfusion; Relapse; Abstinence; Treatment outcome ID DSM-IV ALCOHOL; MAGNETIC-RESONANCE SPECTROSCOPY; CONSUMPTION FOLLOWING TREATMENT; NATIONAL EPIDEMIOLOGIC SURVEY; CHRONIC CIGARETTE-SMOKING; ADDICTED HUMAN BRAIN; UNITED-STATES; USE DISORDERS; PREDICT RELAPSE; DRUG-ADDICTION AB Relapse to hazardous levels of alcohol consumption after treatment for alcohol use disorders is common. Investigation of the neurobiological correlates of resumption of hazardous drinking is necessary to clarify the mechanisms contributing to relapse. Fifty-seven treatment-seeking alcohol-dependent participants (ALC) completed arterial spin labeling perfusion MRI of the frontal and parietal gray matter (GM) at 7 +/- 3 days of abstinence (baseline). ALC participants were restudied after 35 +/- 11 days of abstinence (assessment point 2: AP2). Twenty-eight nonsmoking, light-drinking control participants (nsLD) from the community were studied with perfusion MRI. ALC participants were followed over 12 months after baseline study and were classified as abstainers (no alcohol consumption; n = 19) and resumers (any alcohol consumption; n = 38) at follow-up. Cross-sectional and longitudinal perfusion was compared in abstainers, resumers, and nsLD. At baseline, resumers demonstrated significantly lower frontal and parietal GM perfusion than nsLD and abstainers. Abstainers and nsLD were not different on frontal or parietal GM perfusion. No significant longitudinal perfusion changes were observed in abstainers and resumers. At AP2, resumers showed significantly lower frontal GM perfusion than nsLD and abstainers, whereas no group differences were observed for parietal GM. Abstainers and nsLD were not different on frontal GM perfusion. The significantly decreased frontal GM perfusion in resumers compared with both abstainers and nsLD across the assessment interval suggests premorbid and/or acquired neurobiological abnormalities of the frontal GM in resumers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Durazzo, Timothy C.; Gazdzinski, Stefan; Mon, Anderson; Meyerhoff, Dieter J.] San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mon, Anderson; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIH [AA10788, DA DA24136] FX This material is the result of work supported by NIH AA10788 (DJM) and DA DA24136 (TCD) with resources and the use of facilities at the San Francisco Veterans Administration Medical Center. We thank Mary Rebecca Young, Bill Clift, and Jeanna Eichenbaum of the San Francisco Veterans Administration Substance Abuse Day Hospital and Dr David Pating, Karen Moise and their colleagues at the San Francisco Kaiser Permanente Chemical Dependency Recovery Program for their valuable assistance in recruiting participants. We also wish to extend our gratitude to the study participants, who made this research possible. NR 72 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAY PY 2010 VL 44 IS 3 BP 201 EP 210 DI 10.1016/j.alcohol.2010.03.003 PG 10 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 615AF UT WOS:000279100500001 PM 20682188 ER PT J AU Weiner, MW Aisen, PS Jack, CR Jagust, WJ Trojanowski, JQ Shaw, L Saykin, AJ Morris, JC Cairns, N Beckett, LA Toga, A Green, R Walter, S Soares, H Snyder, P Siemers, E Potter, W Cole, PE Schmidt, M AF Weiner, Michael W. Aisen, Paul S. Jack, Clifford R., Jr. Jagust, William J. Trojanowski, John Q. Shaw, Leslie Saykin, Andrew J. Morris, John C. Cairns, Nigel Beckett, Laurel A. Toga, Arthur Green, Robert Walter, Sarah Soares, Holly Snyder, Peter Siemers, Eric Potter, William Cole, Patricia E. Schmidt, Mark CA Alzheimer's Dis Neuroimaging Initi TI The Alzheimer's Disease Neuroimaging Initiative: Progress report and future plans SO ALZHEIMERS & DEMENTIA LA English DT Review DE ADNI; Alzheimer's disease; MRI; PET; Amyloid; Memory; Tau ID MILD COGNITIVE IMPAIRMENT; BIOMARKERS; DEPOSITION AB The Alzheimer's Disease Neuroimaging, Initiative (ADNI) beg Tilling in October 2004, is a 6-year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls. subjects with mild cognitive impairment. and subjects with Alzheimer's disease (AD) A major goal is to determine and validate MRI. PET images. and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments Structural MRI. FDG PET. C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid beta (A beta) and species of tau. with clinical/cognitive measurements were performed on elderly controls. subjects with mild cognitive impairment. and subjects with AD Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of A beta and tau were significant predictors of cognitive decline and brain atrophy All data are available at UCLA/LONI/ADNI, without embargo ADNI-like projects started in Australia. Europe, Japan. and Korea ADNI provides significant new information concerning the progression of AD (C) 2010 The Alzheimer's Association All rights reserved C1 [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Jagust, William J.] Univ Calif Berkeley, Inst Neurosci, Berkeley, CA 94720 USA. [Trojanowski, John Q.; Shaw, Leslie] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Saykin, Andrew J.] Indiana Univ, Dept Radiol & Imaging Sci, Bloomington, IN USA. [Morris, John C.; Cairns, Nigel] Washington Univ, Dept Neurol, St Louis, MO USA. [Beckett, Laurel A.] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Toga, Arthur] Univ Calif Los Angeles, Dept Neurol LONI, Los Angeles, CA USA. [Green, Robert] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Walter, Sarah] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Soares, Holly] Pfizer Global Res & Dev, Translat Med, Groton, CT USA. [Snyder, Peter] Brown Univ, Dept Bio Med Neurol, Providence, RI 02912 USA. [Siemers, Eric] Eli Lilly & Co, Alzheimers Dis Res, Indianapolis, IN 46285 USA. [Potter, William] Merck Res Labs, Rahway, NJ USA. [Cole, Patricia E.] Imagepace, Cincinnati, OH USA. [Schmidt, Mark] Johnson & Johnson, Pharmaceut Res & Dev, Antwerp Area, Beerse, Belgium. RP Weiner, MW (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RI Jack, Clifford/F-2508-2010; Morris, John/A-1686-2012; Scharre, Douglas/E-4030-2011; Saykin, Andrew/A-1318-2007; Schmidt, Mark/I-5052-2016; OI Jack, Clifford/0000-0001-7916-622X; Saykin, Andrew/0000-0002-1376-8532; Schmidt, Mark/0000-0003-3417-8977; Beckett, Laurel/0000-0002-2418-9843; Snyder, Peter/0000-0003-0555-4654 FU NIA NIH HHS [U01 AG024904, U01 AG024904-05, U19 AG010483] NR 16 TC 170 Z9 173 U1 3 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAY PY 2010 VL 6 IS 3 BP 202 EP 211 DI 10.1016/j.jalz.2010.03.007 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 599RV UT WOS:000277931700002 PM 20451868 ER PT J AU Califf, RM Lokhnygina, Y Cannon, CP Stepanavage, ME McCabe, CH Musliner, TA Pasternak, RC Blazing, MA Giugliano, RP Harrington, RA Braunwald, E AF Califf, Robert M. Lokhnygina, Yuliya Cannon, Christopher P. Stepanavage, Michael E. McCabe, Carolyn H. Musliner, Thomas A. Pasternak, Richard C. Blazing, Michael A. Giugliano, Robert P. Harrington, Robert A. Braunwald, Eugene TI An update on the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; CARDIOVASCULAR OUTCOMES; CLINICAL-TRIALS; STATIN THERAPY; EZETIMIBE; SIMVASTATIN; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; CANCER; NIACIN C1 [Califf, Robert M.] Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA. [Lokhnygina, Yuliya; Blazing, Michael A.; Harrington, Robert A.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Cannon, Christopher P.; McCabe, Carolyn H.; Giugliano, Robert P.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Stepanavage, Michael E.] Merck & Co Inc, Rahway, NJ 07065 USA. [Musliner, Thomas A.; Pasternak, Richard C.] Merck & Co Inc, N Wales, PA USA. RP Califf, RM (reprint author), Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA. NR 24 TC 56 Z9 57 U1 3 U2 9 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 MAY PY 2010 VL 159 IS 5 BP 705 EP 709 DI 10.1016/j.ahj.2010.03.004 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300001 PM 20435175 ER PT J AU Min, SS Turner, JR Nada, A DiMino, TL Hynie, I Kleiman, R Kowey, P Krucoff, MW Mason, JW Phipps, A Newton-Cheh, C Pordy, R Strnadova, C Targum, S Uhl, K Finkle, J AF Min, Sherene S. Turner, J. Rick Nada, Adel DiMino, Tara L. Hynie, Ivo Kleiman, Robert Kowey, Peter Krucoff, Mitchell W. Mason, Jay W. Phipps, Alex Newton-Cheh, Christopher Pordy, Robert Strnadova, Colette Targum, Shari Uhl, Kathleen Finkle, John TI Evaluation of ventricular arrhythmias in early clinical pharmacology trials and potential consequences for later development SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; MITRAL-VALVE-PROLAPSE; QT INTERVAL PROLONGATION; SPONTANEOUS VARIABILITY; AMBULATORY ELECTROCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; PREMATURE COMPLEXES; ELDERLY POPULATION; PSYCHOLOGIC STRESS; HEALTHY-SUBJECTS AB This white paper, prepared by members of the Cardiac Safety Research Consortium, discusses several important issues regarding the evaluation of ventricular arrhythmias in early clinical pharmacology trials and their potential consequences for later clinical drug development. Ventricular arrhythmias are infrequent but potentially important medical events whose occurrence in early clinical pharmacology trials can dramatically increase safety concerns. Given the increasing concern with all potential safety signals and the resultant more extensive electrocardiographic monitoring of subjects participating in early phase trials, an important question must be addressed: Are relatively more frequent observations of ventricular arrhythmias related simply to more extensive monitoring, or are they genuinely related to the drug under development? The discussions in this paper provide current thinking and suggestions for addressing this question. (Am Heart J 2010; 159: 716-29.) C1 [Min, Sherene S.] GlaxoSmithKline, Med Dev Ctr, Res Triangle Pk, NC 27709 USA. [Min, Sherene S.; DiMino, Tara L.; Finkle, John] GlaxoSmithKline, Philadelphia, PA USA. [Turner, J. Rick] Quintiles, Res Triangle Pk, NC USA. [Nada, Adel] Abbott Labs, Waukegan, IL USA. [Hynie, Ivo; Strnadova, Colette] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Kleiman, Robert] ERT, Philadelphia, PA USA. [Kowey, Peter] Lankenau Inst Med Res, Wynnewood, PA USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Mason, Jay W.] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. [Phipps, Alex] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pordy, Robert] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Targum, Shari; Uhl, Kathleen] US FDA, Rockville, MD 20857 USA. RP Min, SS (reprint author), GlaxoSmithKline, Med Dev Ctr, 5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM sherene.s.min@gsk.com NR 70 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAY PY 2010 VL 159 IS 5 BP 716 EP 729 DI 10.1016/j.ahj.2010.02.004 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300004 PM 20435178 ER PT J AU Sowden, G Mastromauro, CA Januzzi, JL Fricchione, GL Huffman, JC AF Sowden, Gillian Mastromauro, Carol A. Januzzi, James L. Fricchione, Gregory L. Huffman, Jeff C. TI Detection of depression in cardiac inpatients: Feasibility and results of systematic screening SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; PATIENT HEALTH QUESTIONNAIRE; MAJOR DEPRESSION; ARTERY-DISEASE; RISK-FACTOR; METAANALYSIS; ASSOCIATION; MORTALITY; VALIDITY AB Background A recent American Heart Association (AHA) Prevention Committee report recommended depression screening of all coronary heart disease patients using 2- and 9-item instruments from the Patient Health Questionnaire (PHQ-2 and PHQ-9) to identify patients who may need further assessment and treatment. Our objective was to assess the feasibility and results of such screening on inpatient cardiac units. Methods In September 2007, the PHQ-2 was added to the nursing interview dataset on 3 cardiac units in a general hospital; this screen was completed as part of routine clinical care. Rates and results of depression screening, reasons for patients not being screened, and results of a nursing satisfaction survey were tabulated, and differences in baseline characteristics between screened and unscreened patients were analyzed via chi(2) and independent-samples t tests. Results For a 12-month period, 4,783 patients were admitted to the cardiac units; 3,504 (73.3%) received PHQ-2 depression screening. Approximately 9% of screened patients had a PHQ-2 score >= 3 and were approached for further depression evaluation (PHQ-9) by a social worker; 74.1% of the positive-screen patients had a PHQ-9 score of >= 10, suggestive of major depression. Nurses (n = 66) reported high satisfaction with the screening process, and mean reported PHQ-2 screening time was 1.4 (+/- 1.1) minutes. Conclusions Systematic depression screening of cardiac patients using methods outlined by the AHA Prevention Committee is feasible, well-accepted, and does not appear markedly resource-intensive. Future studies should link these methods to an efficient and effective program of depression management in this vulnerable population. (Am Heart J 2010; 159: 780-7.) C1 [Sowden, Gillian; Mastromauro, Carol A.; Fricchione, Gregory L.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sowden, Gillian; Januzzi, James L.; Fricchione, Gregory L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit Street Warren 1220C, Boston, MA 02114 USA. EM jhuffman@partners.org NR 31 TC 27 Z9 27 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 MAY PY 2010 VL 159 IS 5 BP 780 EP 787 DI 10.1016/j.ahj.2010.02.029 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300012 PM 20435186 ER PT J AU Buxbaum, J Alexander, A Koziol, J Tagoe, C Fox, E Kitzman, D AF Buxbaum, Joel Alexander, Alice Koziol, James Tagoe, Clement Fox, Ervin Kitzman, Dalane TI Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; LEFT-VENTRICULAR MASS; CARDIAC AMYLOIDOSIS; GREATER-THAN-OR-EQUAL-TO-65 YEARS; ATHEROSCLEROSIS RISK; SYSTOLIC FUNCTION; VARIANT; TISSUE; VELOCITY; V122I AB Background Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the allele frequency and its clinical penetrance in community-dwelling African Americans. Methods Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls. Results One hundred nineteen (3.23%) of 3,712 ARIC and 17 (2.12%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38% vs 15%, relative risk 2.62, P = .04) and mortality (76% vs 53%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender-and ethnically matched controls. In ARIC (all subjects <65 years old), there were no differences between carriers and noncarriers in mortality, frequency of congestive heart failure, or findings consistent with cardiac amyloidosis. Conclusions Heterozygosity for the amyloidogenic TTR V122I mutation is relatively common in community-dwelling African Americans. Before the age of 65 years, the allele has no discernible impact on cardiac function or mortality. After the age of 70 years, carriers show a higher frequency of congestive failure and greater mortality with more echocardiographic evidence suggestive of cardiac amyloidosis, findings consistent with age-dependent clinical penetrance of this autosomal dominant gene. (Am Heart J 2010; 159: 864-70.) C1 [Buxbaum, Joel; Koziol, James] Scripps Res Inst, La Jolla, CA 92037 USA. [Alexander, Alice] VA Boston Healthcare Syst, Boston, MA USA. [Tagoe, Clement] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Fox, Ervin] Univ Mississippi, Sch Med, ARIC, Jackson, MS 39216 USA. [Kitzman, Dalane] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Buxbaum, J (reprint author), Scripps Res Inst, 10550 N Torrey Pines Rd,MEM-230, La Jolla, CA 92037 USA. EM jbux@scripps.edu FU NHLBI NIH HHS [N01 HC075150, N01 HC015103, N01 HC035129, N01 HC045133, N01 HC055015, N01 HC055016, N01 HC055018, N01 HC055019, N01 HC055020, N01 HC055021, N01 HC055022, N01 HC055222, N01 HC085079, N01 HC085086, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC75150, N01HC85079, N01HC85086, U01 HL080295, U01 HL080295-05]; NIA NIH HHS [R01 AG018915, R01 AG019259, R01 AG019259-07, R37 AG018915] NR 38 TC 39 Z9 39 U1 0 U2 2 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 MAY PY 2010 VL 159 IS 5 BP 864 EP 870 DI 10.1016/j.ahj.2010.02.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300023 PM 20435197 ER PT J AU Chirinos, JA Williams, MM Bregman, DB Ashfaq, H Khayyam, U Iqbal, N AF Chirinos, Julio A. Williams, Monica M. Bregman, David B. Ashfaq, Hera Khayyam, Umar Iqbal, Nayyar TI Efficacy of cholesterol uptake inhibition added to statin therapy among subjects following a low-carbohydrate diet: A randomized controlled trial SO AMERICAN HEART JOURNAL LA English DT Article ID LOW-FAT DIET; PRIMARY HYPERCHOLESTEROLEMIA; WEIGHT-LOSS; SEVERE OBESITY; RISK-FACTORS; EZETIMIBE; SIMVASTATIN; ATKINS; ORNISH; WOMEN AB Background Low-carbohydrate diets are frequently used as part of weight-loss programs. These are typically associated with increased fat intake. Therefore, cholesterol absorption inhibition is a logical therapeutic strategy to lower low-density lipoprotein cholesterol (LDL-C) in subjects following a low-carbohydrate diet. However, the efficacy of cholesterol absorption inhibition added to statin therapy has not been studied in this common clinical setting. Methods We performed a randomized controlled trial to compare the effects of ezetimibe on LDL-C when added to simvastatin among subjects following a low-carbohydrate diet. We enrolled 65 subjects who were overweight or obese (body mass index 25-45 kg/m(2)) and had a moderately elevated LDL-C (130-190 mg/dL). During a 4-week diet run-in, subjects were instructed to restrict carbohydrate intake to <30 g/day. Subjects demonstrating adequate adherence to a low-carbohydrate diet (n = 58) were randomized to simvastatin (20 mg) or simvastatin (20 mg) plus ezetimibe (10 mg) for 8 weeks. Results Body weight decreased by 3.1% (95% CI 2.1%-4.0%, P < .0001), but the magnitude of weight change did not differ between the groups (P = .92). The LDL-C decreased by 32 mg/dL (95% CI 21-42 mg/dL) in the simvastatin arm and 60 mg/dL (95% CI 45-75 mg/dL) in the combined simvastatin-ezetimibe arm (P = .002). This corresponded to a 20.9% reduction (95% CI 14.5%-27.4%) in LDL-C on simvastatin alone, compared with a 37.4% reduction (95% CI 29.3%-45.6%) on simvastatin-ezetimibe (P = .002). A significant 15.8% reduction in triglycerides was observed among enrolled subjects, which did not differ between the groups. Conclusions Among subjects following a low-carbohydrate diet, combined statin and cholesterol absorption inhibitor therapy is more effective than statin monotherapy for LDL-C lowering. (Am Heart J 2010; 159: 918.e1-918.e6.) C1 [Chirinos, Julio A.; Williams, Monica M.; Ashfaq, Hera; Khayyam, Umar; Iqbal, Nayyar] Univ Penn, Dept Med, Div Cardiovasc Dis, Philadelphia, PA 19104 USA. [Chirinos, Julio A.; Williams, Monica M.; Ashfaq, Hera; Khayyam, Umar; Iqbal, Nayyar] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bregman, David B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Iqbal, Nayyar] Bristol Myers Squibb Co, New York, NY 10154 USA. RP Chirinos, JA (reprint author), 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu FU Philadelphia VA Medical Center FX This manuscript is dedicated to the memory of Frederick F. Samaha, MD, a friend and mentor. Dr Samaha conceived and led the design of this clinical trial and was the Principal Investigator of this trial until all subjects were closed out from the study.; The authors would like to acknowledge the support of the Philadelphia VA Medical Center and its laboratory staff. NR 15 TC 0 Z9 0 U1 4 U2 5 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 MAY PY 2010 VL 159 IS 5 AR 918.e1 DI 10.1016/j.ahj.2010.02.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 590QY UT WOS:000277243300031 PM 20435205 ER PT J AU Blankstein, R Murphy, MK Nasir, K Gazelle, GS Batlle, JC Al-Mallah, M Shturman, L Hoffmann, U Cury, RC Abbara, S Brady, TJ Lee, TH AF Blankstein, Ron Murphy, Meagan K. Nasir, Khurram Gazelle, G. Scott Batlle, Juan C. Al-Mallah, Mouaz Shturman, Leon Hoffmann, Udo Cury, Ricardo C. Abbara, Suhny Brady, Thomas J. Lee, Thomas H. TI Perceived Usefulness of Cardiac Computed Tomography as Assessed by Referring Physicians and Its Effect on Patient Management SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; ASYMPTOMATIC INDIVIDUALS; RESPONSE RATES; ANGIOGRAPHY; RISK; STRESS AB Despite the growing use of computed tomographic angiography (CTA), the effect on patient management is less clear. We sought to determine the perceived usefulness of the results provided by CTA and to assess whether and how it influences patient management. Comprehensive prospective data were collected from 184 consecutive patients who presented for clinical CTA for the evaluation of coronary artery disease from March to July 2008. In addition, a detailed survey was sent to each referring physician for each patient examined to assess whether they found the results of the CTA useful and whether it had any influence on subsequent patient management. Of 184 CTA examinations, which had been ordered by 82 different providers, 108 surveys (59%) were completed by 53 different physicians. No significant differences were found in either the patient or provider characteristics for the completed versus noncompleted surveys. Of the 184 CTA examinations, the severity of coronary disease detected by CTA was severe for 26%, mild to moderate in 47%, and not present in 27% of the patients. Clinicians considered the test results to be useful in virtually all cases and thought the results led to significant risk reclassification in 58% of the patients. If CTA had not been available, the clinicians indicated that they would have ordered an invasive test for 46% of the patients and noninvasive tests for 32%. After CTA, changes in medical therapies were made for 31%, invasive angiography was planned for 19%, and noninvasive testing was scheduled for 6% of the patients. In conclusion, of 53 different referring clinicians from different medical specialties, CTA was considered to almost always be useful; however, the effect on subsequent medical management was more variable. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1246-1253) C1 [Blankstein, Ron; Shturman, Leon; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. [Blankstein, Ron; Shturman, Leon; Hoffmann, Udo; Cury, Ricardo C.; Abbara, Suhny; Brady, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Murphy, Meagan K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gazelle, G. Scott; Batlle, Juan C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Nasir, Khurram] Johns Hopkins Univ, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Al-Mallah, Mouaz] Henry Ford Hosp, Detroit, MI 48202 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA. [Lee, Thomas H.] Partners HealthCare, Boston, MA USA. RP Blankstein, R (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. EM rblankstein@partners.org OI Al-Mallah, Mouaz/0000-0003-2348-0484 FU National Institutes of Health, Bethesda, Maryland [HL076136-02]; Partners HealthCare, Boston, Massachusetts FX Drs. Blankstein, Nasir, and Shturman received support from grant 1T32 HL076136-02 from the National Institutes of Health, Bethesda, Maryland. This work was partially funded by an internal grant from Partners HealthCare, Boston, Massachusetts. None of the authors have any relation to industry that might pose a conflict of interest. NR 13 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2010 VL 105 IS 9 BP 1246 EP 1253 DI 10.1016/j.amjcard.2009.12.040 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594ZF UT WOS:000277579600008 PM 20403474 ER PT J AU Glauser, J Emerman, CL Bhatt, DL Peacock, WF AF Glauser, Jonathan Emerman, Charles L. Bhatt, Deepak L. Peacock, W. Frank TI Platelet aspirin resistance in ED patients with suspected acute coronary syndrome SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; ARTERY-DISEASE; HIGH-RISK; INTERVENTION; METAANALYSIS; HISTORY; EVENTS; STROKE; DEATH AB Background: Platelet aspirin resistance is reported to be as high as 45%. The prevalence of emergency department (ED) platelet aspirin resistance in suspected acute coronary syndrome (ACS) is not described. Our purpose was to determine the prevalence of platelet aspirin resistance. Methods: We determined platelet aspirin resistance in a convenience sample of ED suspected ACS patients. Eligible patients had longer than 10 minutes of chest pain or an ischemic equivalent. Two hours after receiving 325 mg of aspirin, blood was assessed for platelet function (Accumetrics, San Diego, CA). Definitions are as follows: aspirin resistance, at least 550 aspirin reaction units; positive troponin T, greater than 0.1 ng/mL; significant coronary lesion, at least 70% stenosis. The composite end point was prospectively defined as a 30-day revisit, positive cardiac catheterization, or hospital length of stay (LOS) longer than 3 days. Results: Of 200 patients, 50.5% were male, 50.0% were black, troponin T was positive in 7.5%, cardiac catheterization was done in 10.5%, and 33.3% had a significant stenosis. Final diagnoses were noncardiac in 83.4%, stable angina in 8.0%, and unstable angina in 8.5%. Overall, 6.5% were resistant to aspirin; and high-risk patients trended to more aspirin resistance than non high-risk patients (23.1% [3] vs 9.1% [17]; P value 95% confidence interval [Cl], -0.0929 to 0.373). One-month follow-up found ED revisits in 12.5% of aspirin-resistant vs 4.9% of non aspirin-resistant patients (95% CI, -0.114 to 0.182) and rehospitalization in 12.5% of resistant patients vs 4.3% of nonresistant patients (P value 95% CI, -0.108 to 0.187). Although LOS was similar at index admission, if rehospitalized, LOS was 6.5 for aspirin-resistant patients vs 3.2 days in nonresistant patients (P<.0001). Conclusion: This first report of platelet aspirin resistance in patients presenting to the ED with suggested ACS finds that it is present in 6.5% of patients. (C) 2010 Elsevier Inc. All rights reserved. C1 [Glauser, Jonathan] Case Western Reserve Univ, Cleveland Clin, Inst Emergency Med, Cleveland, OH 44195 USA. [Emerman, Charles L.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44195 USA. [Bhatt, Deepak L.] VA Boston Hlth Care Syst, Boston, MA USA. RP Glauser, J (reprint author), Case Western Reserve Univ, Cleveland Clin, Inst Emergency Med, Cleveland, OH 44195 USA. EM glausej@ccf.org FU Abbott; BAS; Biosite; Brahms; CHF Solutions; Heartscape; Inovise; Inverness; PDL; Medicines Company FX Dr Peacock is on the Scientific Advisory Board of the following companies: Abbott, Beckman-Coulter, Biosite, Inovise, Inverness, Otsuka, Ortho Clinical Diagnostics, and The Medicines Company. He has research grants from the following: Abbott, BAS, Biosite, Brahms, CHF Solutions, Heartscape, Inovise, Inverness, PDL, and The Medicines Company. He has an ownership interest in Vital Sensors. NR 30 TC 4 Z9 4 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2010 VL 28 IS 4 BP 440 EP 444 DI 10.1016/j.ajem.2009.01.004 PG 5 WC Emergency Medicine SC Emergency Medicine GA 600KN UT WOS:000277984800008 PM 20466222 ER PT J AU Tsai, CL Sullivan, AF Ginde, AA Camargo, CA AF Tsai, Chu-Lin Sullivan, Ashley F. Ginde, Adit A. Camargo, Carlos A., Jr. TI Quality of emergency care provided by physician assistants and nurse practitioners in acute asthma SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RANDOMIZED-TRIAL; OUTCOMES; SERVICE; DOCTORS AB Objective: The aim of this study was to evaluate the quality of care provided by physician assistants or nurse practitioners (ie, midlevel providers [MLPs]) in acute asthma, as compared with that provided by physicians. Methods: We performed a secondary analysis of the asthma component of the National Emergency Department Safety Study. We identified emergency department (ED) visits for acute asthma in 63 urban EDs in 23 US states between 2003 and 2006. Quality of care was evaluated based on 12 guideline-recommended process-of-care measures, a composite guideline concordance score, and 2 outcome-of-care measures (admission and ED length of stay). Results: Of the 4029 patients included in this analysis, 3622 (90%) were seen by physicians only, 319 (8%) by MLPs supervised by physicians, and 88(2%) by MLPs not supervised by physicians. After adjustment for patient mix, unsupervised MLPs were less likely to administer inhaled beta-agonists within 15 minutes of ED arrival (odds ratio [On 0.2; 95% confidence interval [CI], 0.1-0.7), less likely to prescribe systemic corticosteroids in the ED (OR, 0.4; 95% Cl. 0.2-0.9), and were more likely to prescribe inappropriate antibiotics at discharge (OR, 2.1; 95% Cl, 1.1-4.1), as compared with physicians. Overall, their composite guideline concordance score was lower than that of physicians (-6 points; 95% Cl, 9 to 3 points). Supervised MLPs provided similar quality of care to that of physicians. Conclusions: The MLPs were involved in 10% of ED patients with acute asthma and provided independent care for 2% of these patients. Compared with care provided by physicians or by supervised MLPs, there are opportunities for improvement in unsupervised M LP care. (C) 2010 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin] Harvard Univ, Sch Med,Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. RP Tsai, CL (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. EM cltsai@post.harvard.edu RI Siry, Bonnie/D-7189-2017; OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, MD) [5 R01 HS013099]; [HL084401] FX Funding: This study was supported by gram 5 R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). Dr Camargo also was funded by grant HL084401 (Bethesda, MD). NR 27 TC 15 Z9 15 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2010 VL 28 IS 4 BP 485 EP 491 DI 10.1016/j.ajem.2009.01.041 PG 7 WC Emergency Medicine SC Emergency Medicine GA 600KN UT WOS:000277984800016 PM 20466230 ER PT J AU Monto, A Schooley, RT Lai, JC Sulkowski, MS Chung, RT Pawlotsky, JM McHutchison, JG Jacobson, IM AF Monto, Alexander Schooley, Robert T. Lai, Jennifer C. Sulkowski, Mark S. Chung, Raymond T. Pawlotsky, Jean-Michel McHutchison, John G. Jacobson, Ira M. TI Lessons From HIV Therapy Applied to Viral Hepatitis Therapy: Summary of a Workshop SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID C VIRUS-REPLICATION; ALPHA-2A PLUS RIBAVIRIN; ANTIRETROVIRAL DRUG-RESISTANCE; CHRONIC HCV INFECTION; SOCIETY-USA PANEL; IN-VITRO; PEGINTERFERON ALPHA-2A; ADEFOVIR DIPIVOXIL; COMBINATION THERAPY; PROTEASE INHIBITORS AB Therapies for hepatitis B virus (HBV) have continued to evolve, and new therapies for hepatitis C virus (HCV) will soon be available in clinical practice. These medications for hepatitis C will mark the first time that direct antivirals that target HCV functions have been used. When such drugs are used as single agents, previously existing mutants with reduced susceptibility to them are rapidly selected. The relationship between these drug-resistant mutants and "wildtype" virus is unclear, but resistant strains likely have the potential to maintain the progression of liver disease despite successful treatment of "wild-type" virus. Resistant HBV and now HCV are already a clinical problem. The same issue was recognized very early in the development of therapy against HIV, with azidothymidine-resistant mutants detected within the first weeks of therapy. Clinical investigation and a progressive understanding of the pathogenesis of the disease overcame this challenge and led to the substantial and durable benefits of antiretroviral therapy that are evident today. To bring experts from the fields of HIV and viral hepatitis virology and therapy together for interactive discussions about how to apply the lessons from HIV to the further development of viral hepatitis therapy, the American Association for the Study of Liver Diseases held a single-topic conference entitled "Viral Hepatitis Therapy: Lessons to be Learned From HIV" on 24-26 July 2008. This article summarizes that conference. C1 [Monto, Alexander] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Monto, Alexander; Lai, Jennifer C.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94121 USA. [Schooley, Robert T.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94121 USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Pawlotsky, Jean-Michel] Univ Paris 12, Hop Henri Mondor, Virol Unit, F-94010 Creteil, France. [Pawlotsky, Jean-Michel] Hop Henri Mondor, INSERM, U841, F-94010 Creteil, France. [McHutchison, John G.] Duke Clin Res Inst, Durham, NC USA. [McHutchison, John G.] Duke Univ, Div Gastroenterol, Durham, NC USA. [Jacobson, Ira M.] New York Hosp, Div Gastroenterol, New York, NY 10021 USA. [Jacobson, Ira M.] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. RP Monto, A (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 4150 Clement St 111, San Francisco, CA 94121 USA. EM alexander.monto@va.gov FU AASLD FX This was one of three annual single-topic conferences sponsored by the AASLD. There was no specific financial support from any organization or company other than AASLD. AASLD receives unrestricted donations from some companies in general support of its educational programs. NR 102 TC 21 Z9 22 U1 0 U2 2 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 MAY PY 2010 VL 105 IS 5 BP 989 EP 1004 DI 10.1038/ajg.2009.726 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 593GE UT WOS:000277440100005 PM 20087331 ER PT J AU Klinger, EV Yeh, YC Churchill, W Clapp, M Reddy, P AF Klinger, Elissa V. Yeh, Yu-Chen Churchill, William Clapp, Margaret Reddy, Prabashni TI Implementation of a center for drug policy across a system of hospitals SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Klinger, Elissa V.; Yeh, Yu-Chen; Reddy, Prabashni] Partners Healthcare Syst, Ctr Drug Policy, Needham, MA USA. [Churchill, William] Brigham & Womens Hosp, Boston, MA 02115 USA. [Clapp, Margaret] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Klinger, EV (reprint author), Partners Healthcare Syst, Ctr Drug Policy, Needham, MA USA. EM prabashni@gmail.com NR 3 TC 1 Z9 1 U1 0 U2 1 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 MAY 1 PY 2010 VL 67 IS 9 BP 702 EP + DI 10.2146/ajhp090319 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 589FA UT WOS:000277130800005 PM 20410543 ER PT J AU Burkitt, KH Sinkowitz-Cochran, RL Obrosky, DS Cuerdon, T Miller, LJ Jain, R Jernigan, JA Fine, MJ AF Burkitt, Kelly H. Sinkowitz-Cochran, Ronda L. Obrosky, D. Scott Cuerdon, Timothy Miller, LaToya J. Jain, Rajiv Jernigan, John A. Fine, Michael J. TI Survey of employee knowledge and attitudes before and after a multicenter Veterans' Administration quality improvement initiative to reduce nosocomial methicillin-resistant Staphylococcus aureus infections SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Methicillin-resistant Staphylococcus aureus; quality improvement; prevention; employee survey; knowledge; attitudes; practices ID BLOOD-STREAM INFECTIONS; ANTIMICROBIAL RESISTANCE; HAND HYGIENE; UNITED-STATES; PERCEPTIONS; HOSPITALS; IMPLEMENTATION; PHYSICIANS; BELIEFS; STAFF AB Background: Although guidelines currently recommend prevention practices to decrease in-hospital transmission of infections, increasing adherence to the practices remains a challenge. This study assessed the effect of a multicenter methicillin-resistant Staphylococcus aureus (MRSA) prevention initiative on changes in employees' knowledge, attitudes, and practices. Methods: Two cross-sectional surveys were distributed at baseline (October 2006) and follow-up (July 2007) at 17 medical centers participating in the Veterans' Administration (VA) MRSA initiative. Results: Surveys were completed by 1362 employees at baseline and 952 employees at follow-up (representing 57% and 56% of eligible respondents, respectively). Respondents included physicians (9%), nurses (38%), allied health professionals (30%), and other support staff (24%). Of the 5 knowledge items, the mean proportion answered correctly increased slightly from baseline to follow-up (from 71% to 73%; P = .07). The percentage of respondents who believed that MRSA was a problem on their unit increased over time (from 56% to 65%; P < .001). Respondents also reported increased comfort with reminding other staff about proper hand hygiene (from 61% to 70%; P < .001) and contact precautions (from 63% to 70%; P < .002). The percentage of respondents reporting at least one barrier to proper hand hygiene decreased over time (from 25% to 20%; P = .003). Conclusions: In this multicenter study of VA employees, implementation of a MRSA quality improvement initiative was associated with temporal improvements in knowledge and perceptions regarding MRSA prevention. C1 [Burkitt, Kelly H.; Obrosky, D. Scott; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Sinkowitz-Cochran, Ronda L.; Jernigan, John A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Cuerdon, Timothy] VA Cent Off, Off Qual & Performance, Washington, DC USA. [Miller, LaToya J.] Atlanta VA Med Ctr, Directors Off, Atlanta, GA USA. [Miller, LaToya J.; Jain, Rajiv] VA Pittsburgh Healthcare Syst, Chief Staffs Off, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Burkitt, KH (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Room A3004N 151C-H, Pittsburgh, PA 15206 USA. EM Kelly.Burkitt@va.gov FU Office of Research and Development, Department of Veterans Affairs; VA Pittsburgh Healthcare System FX This material is based on work supported in part by the Office of Research and Development, Department of Veterans Affairs, and the VA Pittsburgh Healthcare System. None of the authors has any conflict of interest or financial interest associated with this study. The findings and conclusions reported in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention, the Department of Veterans Affairs, or the United States Government. NR 23 TC 5 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2010 VL 38 IS 4 BP 274 EP 282 DI 10.1016/j.ajic.2009.08.019 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 587GZ UT WOS:000276979600004 PM 20137828 ER PT J AU Shurraw, S Majumdar, SR Thadhani, R Wiebe, N Tonelli, M AF Shurraw, Sabin Majumdar, Sumit R. Thadhani, Ravi Wiebe, Natasha Tonelli, Marcello CA Alberta Kidney Dis Network TI Glycemic Control and the Risk of Death in 1,484 Patients Receiving Maintenance Hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Glucose; hemoglobin HbA(1c); mortality; hemodialysis; end-stage renal disease ID CHRONIC-RENAL-FAILURE; BLOOD-GLUCOSE CONTROL; II DIABETIC-PATIENTS; CARDIOVASCULAR-DISEASE; GLYCOSYLATED HEMOGLOBIN; MYOCARDIAL-INFARCTION; FATTY-ACIDS; MELLITUS; SURVIVAL; COMPLICATIONS AB Background: It is controversial whether tighter glycemic control is associated with better clinical outcomes in people with kidney failure. We aim to determine whether worse glycemic control, measured using serum glucose and hemoglobin A(1c) (HbA(1c)) levels, is independently associated with higher mortality in patients undergoing maintenance hemodialysis. Study Design: Retrospective cohort study. Setting & Participants: 1,484 patients starting maintenance hemodialysis therapy in Alberta, Canada, between 2001 and 2007. Predictor: Serum glucose and HbA(1c) levels. Outcome: All-cause mortality. Measurements: Monthly casual glucose levels from specimens drawn immediately before the first dialysis treatment were averaged over 3 months before and after hemodialysis therapy initiation. Similarly, monthly HbA(1c) values in patients with or at risk of diabetes were averaged. Results: Overall, median age was 66 years, 41% were women, 75% were white, and 55% had diabetes. All-cause mortality during 8 years (median, 1.5 years) was 43%; it was 49% in those with diabetes. There was no relation between average glucose level and mortality in unadjusted analysis (HR, 1.00 per 18 mg/dL [1 mmol/L]; P = 0.4) or after adjustment for confounders (HR, 0.98 per 18 mg/dL; 95% CI, 0.96-1.01; P = 0.2). Higher HbA(1c) level was not associated with mortality when analyzed in the unadjusted analysis (HR, 1.01 per 1% HbA(1c); P = 0.9) or after adjustment for confounders (HR, 0.98 per 1% HbA(1c); 95% CI, 0.88-1.08; P = 0.7). Results were similar when HbA(1c) values were divided into prespecified categories (adjusted P > 0.6 for trend). Markers of malnutrition-inflammation (albumin, hemoglobin, and white blood cell values) or the presence of diabetes did not influence the relation between glycemic control and death (all P for interaction > 0.2). Limitations: Registry data; casual serum glucose measurements; HbA(1c) values available for only a subset of participants. Conclusions: Higher casual glucose and HbA(1c) levels were not associated with mortality in maintenance hemodialysis patients with or without diabetes. This may have implications for recommended glycemic targets, quality indicators, and how best to assess glycemic control in this high-risk population. Am J Kidney Dis 55:875-884. (C) 2010 by the National Kidney Foundation, Inc. C1 [Shurraw, Sabin; Wiebe, Natasha; Tonelli, Marcello] Univ Alberta, Div Nephrol, Edmonton, AB T6B 2B7, Canada. [Majumdar, Sumit R.] Univ Alberta, Div Gen Internal Med, Edmonton, AB T6B 2B7, Canada. [Majumdar, Sumit R.; Tonelli, Marcello] Univ Alberta, Dept Publ Hlth, Edmonton, AB T6B 2B7, Canada. [Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Tonelli, Marcello] Univ Alberta, Div Crit Care Med, Edmonton, AB T6B 2B7, Canada. RP Tonelli, M (reprint author), Univ Alberta, Div Nephrol, 7-129 Clin Sci Bldg,8440 112 St, Edmonton, AB T6B 2B7, Canada. EM mtonelli-admin@med.ualberta.ca RI Tonelli, Marcello/B-3028-2009 FU Alberta Heritage Foundation for Medical Research; Alberta Kidney Disease Network FX Support: Drs Tonelli and Majumdar are supported by Health Scholar Awards from Alberta Heritage Foundation for Medical Research. This study was supported by the Alberta Kidney Disease Network. NR 42 TC 39 Z9 43 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2010 VL 55 IS 5 BP 875 EP 884 DI 10.1053/j.ajkd.2009.12.038 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 590QR UT WOS:000277242600011 PM 20346561 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter CA PLoS Med Editors TI Comparative Effectiveness Research: Challenges for Medical Journals SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material C1 [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Sox, Harold C.] Dartmouth Med Sch, Dartmouth Inst, Hanover, NH USA. [Helfand, Mark] Portland VA Med Ctr, Portland, OR USA. [Grimshaw, Jeremy] Ottawa Hosp, Clin Epidemiol Program, Res Inst, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David; PLoS Med Editors] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Helfand, M (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM helfand@ohsu.edu RI Knottnerus, Johannes/A-3829-2009 NR 7 TC 3 Z9 3 U1 0 U2 1 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 MAY PY 2010 VL 16 IS 5 BP E131 EP E133 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 602GF UT WOS:000278125800013 PM 20455639 ER PT J AU Zeliadt, SB Moinpour, CM Blough, DK Penson, DF Hall, IJ Smith, JL Ekwueme, DU Thompson, IM Keane, TE Ramsey, SD AF Zeliadt, Steven B. Moinpour, Carol M. Blough, David K. Penson, David F. Hall, Ingrid J. Smith, Judith Lee Ekwueme, Donatus U. Thompson, Ian M. Keane, Thomas E. Ramsey, Scott D. TI Preliminary Treatment Considerations Among Men With Newly Diagnosed Prostate Cancer SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID QUALITY-OF-LIFE; TREATMENT DECISION-MAKING; OUTCOMES; CARCINOMA; INFORMATION; VALIDATION; CAPSURE; SCALE AB Objective: To assess factors that may influence men's preference for surgery versus nonsurgical options among newly diagnosed patients considering treatments for local-stage prostate cancer. Study Design: Prostate cancer patients were approached at urology clinics after diagnosis but prior to starting treatment in California, South Carolina, and Texas. Using a survey about the treatment decision-making process, patients were asked about their likes and dislikes of 5 common treatment options: surgery (prostatectomy), brachytherapy, external beam radiation therapy, hormone therapy, and watchful waiting. Methods: Logistic regression identified associations between treatment characteristics and choice of prostatectomy compared with nonsurgical options, controlling for demographic, clinical, and psychological covariates. Results: Of the 198 eligible men who returned the baseline survey, 59% indicated they only considered surgery and 41% considered at least 1 nonsurgical option. In multivariate analysis, patients who thought treatment efficacy was a primary concern were significantly more likely to prefer surgery only (odds ratio [OR] = 6.20, 95% confidence interval [95% CI] = 1.74, 22.10); those indicating concern about personal burden were significantly more likely to prefer nonsurgical options (OR = 0.07, 95% CI = 0.02, 0.22). Advice of friends and relatives and concerns over side effects were not significantly associated with preference for surgery versus other treatments. Conclusions: Men's perceptions about treatment efficacy and the personal burden of treatment dominated preferences for surgery versus nonsurgical options. Interventions to aid treatment decision making should account for these elements to minimize the impact of physician biases and patient misperceptions on men's decisions as how best to manage their prostate cancer. (Am J Manag Care. 2010; 16(5): e121-e130) C1 [Zeliadt, Steven B.; Moinpour, Carol M.; Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Blough, David K.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Penson, David F.] Univ So Calif, Dept Urol, Los Angeles, CA USA. [Hall, Ingrid J.; Smith, Judith Lee; Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Keane, Thomas E.] Med Univ S Carolina, Div Urol Serv, Charleston, SC 29425 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU Centers for Disease Control and Prevention [1-U48-DP-000050] FX This publication was supported by Cooperative Agreement 1-U48-DP-000050 from the Centers for Disease Control and Prevention, Prevention Research Centers Program, through the University of Washington Health Promotion Research Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 36 TC 19 Z9 19 U1 2 U2 4 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 MAY PY 2010 VL 16 IS 5 BP E121 EP E130 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 602GF UT WOS:000278125800012 PM 20455638 ER PT J AU Levy, D Splansky, GL Strand, NK Atwood, LD Benjamin, EJ Blease, S Cupples, LA D'Agostino, RB Fox, CS Kelly-Hayes, M Koski, G Larson, MG Mutalik, KM Oberacker, E O'Donnell, CJ Sutherland, P Valentino, M Vasan, RS Wolf, PA Murabito, JM AF Levy, Daniel Splansky, Greta Lee Strand, Nicolle K. Atwood, Larry D. Benjamin, Emelia J. Blease, Susan Cupples, L. Adrienne D'Agostino, Ralph B., Sr. Fox, Caroline S. Kelly-Hayes, Margaret Koski, Greg Larson, Martin G. Mutalik, Karen M. Oberacker, Elizabeth O'Donnell, Christopher J. Sutherland, Patrice Valentino, Maureen Vasan, Ramachandran S. Wolf, Philip A. Murabito, Joanne M. TI Consent for Genetic Research in the Framingham Heart Study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE epidemiology; genetics; genome-wide association; medical ethics; population study ID GENOME-WIDE ASSOCIATION; INFORMED-CONSENT; POPULATION; DISEASE; DESIGN; LOCI AB Extensive efforts have been aimed at understanding the genetic underpinnings of complex diseases that affect humans. Numerous genome-wide association studies have assessed the association of genes with human disease, including the Framingham Heart Study (FHS), which genotyped 550,000 SNPs in 9,000 participants. The success of such efforts requires high rates of consent by participants, which is dependent on ethical oversight, communications, and trust between research participants and investigators. To study this we calculated percentages of participants who consented to collection of DNA and to various uses of their genetic information in two FHS cohorts between 2002 and 2009. The data included rates of consent for providing a DNA sample, creating an immortalized cell line, conducting research on various genetic conditions including those that might be considered sensitive, and for notifying participants of clinically significant genetic findings were above 95%. Only with regard to granting permission to share DNA or genetic findings with for-profit companies was the consent rate below 95%. We concluded that the FHS has maintained high rates of retention and consent for genetic research that has provided the scientific freedom to establish collaborations and address a broad range of research questions. We speculate that our high rates of consent have been achieved by establishing frequent and open communications with participants that highlight extensive oversight procedures. Our approach to maintaining high consent rates via ethical oversight of genetic research and communication with study participants is summarized in this report and should be of help to other studies engaged in similar types of research. Published (C) 2010 Wiley-Liss, Inc. C1 [Levy, Daniel; Splansky, Greta Lee; Strand, Nicolle K.; Atwood, Larry D.; Benjamin, Emelia J.; Blease, Susan; Cupples, L. Adrienne; D'Agostino, Ralph B., Sr.; Fox, Caroline S.; Kelly-Hayes, Margaret; Larson, Martin G.; Mutalik, Karen M.; Oberacker, Elizabeth; O'Donnell, Christopher J.; Sutherland, Patrice; Valentino, Maureen; Vasan, Ramachandran S.; Wolf, Philip A.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Levy, Daniel; Strand, Nicolle K.; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Atwood, Larry D.; Benjamin, Emelia J.; Kelly-Hayes, Margaret; Vasan, Ramachandran S.; Wolf, Philip A.; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Levy, Daniel; Atwood, Larry D.; Benjamin, Emelia J.; Kelly-Hayes, Margaret; Vasan, Ramachandran S.; Wolf, Philip A.; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. [Levy, Daniel; Atwood, Larry D.; Benjamin, Emelia J.; Kelly-Hayes, Margaret; Vasan, Ramachandran S.; Wolf, Philip A.; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Levy, Daniel; Atwood, Larry D.; Benjamin, Emelia J.; Kelly-Hayes, Margaret; Vasan, Ramachandran S.; Wolf, Philip A.; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Levy, Daniel] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [D'Agostino, Ralph B., Sr.; Larson, Martin G.; Vasan, Ramachandran S.] Boston Univ, Dept Math, Boston, MA 02215 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM levyd@nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NIH [N01-HC-25195] FX We would like to acknowledge the members of the Framingham Heart Study Ethics Advisory Board who volunteer their free time to make ours a better and more responsive study; the Framingham Heart Study participants who are the key to our past success and our future aspirations; and the Framingham Heart Study participant coordinators who administer our informed consent process. This study was supported by The Framingham Heart Study is funded by NIH (N01-HC-25195). NR 18 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY PY 2010 VL 152A IS 5 BP 1250 EP 1256 DI 10.1002/ajmg.a.33377 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 597ES UT WOS:000277739800020 PM 20425830 ER PT J AU Grady, D Cauley, JA Stock, JL Cox, DA Mitlak, BH Song, JL Cummings, SR AF Grady, Deborah Cauley, Jane A. Stock, John L. Cox, David A. Mitlak, Bruce H. Song, Jingli Cummings, Steven R. TI Effect of Raloxifene on All-cause Mortality SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 8th International Symposium on Osteoporosis - Translating Research into Clinical Practice CY APR 01-09, 2009 CL Washington, DC DE CORE; MORE; Mortality; Raloxifene, RUTH ID RANDOMIZED CLINICAL-TRIAL; VERTEBRAL FRACTURE RISK; POSTMENOPAUSAL WOMEN; BREAST-CANCER; REDUCTION; OSTEOPOROSIS; OUTCOMES AB OBJECTIVE: Raloxifene, a selective estrogen receptor modulator, reduces osteoporosis and invasive breast cancer risk but increases risk for venous thromboembolism and fatal stroke in women with or at high risk for coronary heart disease. To assess the risk/benefit of raloxifene as a preventative treatment, we analyzed treatment effects on overall and cause-specific mortality. METHODS: A pooled analysis of mortality data was performed from large clinical trials of raloxifene (60 mg/day) versus placebo, including the Multiple Outcomes of Raloxifene Evaluation/Continuing Outcomes Relevant to Evista studies (7705 postmenopausal osteoporotic women followed for 4 years and a subset of 4011 participants followed for an additional 4 years; 110 deaths) and the Raloxifene Use for the Heart trial (10,101 postmenopausal women with coronary disease or multiple risk factors for coronary disease followed for 5.6 years; 1 149 deaths). Cause of death was assessed by blinded adjudicators. Cox proportional hazards regression models compared mortality by treatment assignment in a pooled analysis of trial data from the Multiple Outcomes of Raloxifene Evaluation/Continuing Outcomes Relevant to Evista and Raloxifene Use for the Heart trials. RESULTS: All-cause mortality was 10% lower among women assigned to raloxifene 60 mg/day versus placebo (relative hazard 0.90; 95% confidence interval, 0.80-1.00; P =.05). Lower overall mortality was primarily due to lower rates of noncardiovascular deaths, especially a lower rate of noncardiovascular, noncancer deaths. CONCLUSIONS: All-cause mortality was 10% lower in pooled analyses among older postmenopausal women receiving raloxifene 60 mg/day compared with placebo, due primarily to a reduction in noncardiovascular, noncancer deaths. The mechanism whereby raloxifene might reduce the risk of noncardiovascular death is unclear. (c) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 469.e1-469.e7 C1 [Grady, Deborah; Cummings, Steven R.] Univ Calif San Francisco, San Francisco, CA 94115 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Stock, John L.; Cox, David A.; Mitlak, Bruce H.; Song, Jingli] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. RP Grady, D (reprint author), Univ Calif San Francisco, 1635 Divisadero St, San Francisco, CA 94115 USA. EM deborah.grady@ucsf.edu OI Cauley, Jane A/0000-0003-0752-4408 NR 14 TC 1 Z9 1 U1 1 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 MAY PY 2010 VL 123 IS 5 AR 469.e1 DI 10.1016/j.amjmed.2009.12.018 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 591HD UT WOS:000277289900018 PM 20399327 ER PT J AU Lima, FO Lev, MH Levy, RA Silva, GS Ebril, M de Camargo, EC Pomerantz, S Singhal, AB Greer, DM Ay, H Gonzalez, RG Koroshetz, WJ Smith, WS Furie, KL AF Lima, F. O. Lev, M. H. Levy, R. A. Silva, G. S. Ebril, M. de Camargo, E. C. Pomerantz, S. Singhal, A. B. Greer, D. M. Ay, H. Gonzalez, R. Gilberto Koroshetz, W. J. Smith, W. S. Furie, K. L. TI Functional Contrast-Enhanced CT for Evaluation of Acute Ischemic Stroke Does Not Increase the Risk of Contrast-Induced Nephropathy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID PROGNOSTIC IMPLICATIONS; RENAL-INSUFFICIENCY; COMPUTED-TOMOGRAPHY; SERUM CREATININE; ANGIOGRAPHY; PERFUSION; NEPHROTOXICITY; ACCURACY; FAILURE; SAFETY AB BACKGROUND AND PURPOSE Concerns have recently grown regarding the safety of iodinated contrast agents used for CIA and CTP imaging We tested whether the incidence of AN, defined by a >= 25% increase in the post contrast scan creatinine level, was higher among patients with ischemic stroke who underwent a functional contrast-enhanced CT protocol compared with those who had no iodinated contrast administration MATERIALS AND METHODS The contrast-exposed group consisted of 575 patients with acute ischemic stroke who underwent CIA In = 313), CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography In = 38) within 24 hours of stroke onset and were consecutively enrolled in a prospective cohort study The nonexposed group consisted of 343 patients with ischemic stroke, consecutively admitted to the same institution, who did not receive iodinated contrast material Patients were stratified by baseline eGFR In the primary analysis, the Fisher exact test was used to compare the incidence of AN between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours and on a cumulative basis A secondary analysis compared the incidence of AN in patients who underwent conventional angiography following CTA/CTP versus patients who underwent CTA/CTP only RESULTS: The incidence of AN was 5% in the exposed and 10% in the nonexposed group (P = 0031 Patients who underwent conventional angiography after contrast CT were at no greater risk of AN than patients who underwent CTA/CTP alone (26 patients, 5%, and 2 patients, 5%, respectively, P = 71 CONCLUSIONS Administration of a contrast-enhanced CT protocol involving CTA/CTP and conventional angiography in selected patients does not appear to increase the incidence of CIN C1 [Lima, F. O.] Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. [Lev, M. H.; Pomerantz, S.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Stroke Serv, Boston, MA 02114 USA. [Greer, D. M.] Massachusetts Gen Hosp, Dept Neurol, Neurocrit Care Serv, Boston, MA 02114 USA. [Levy, R. A.] Harvard Univ, Cambridge, MA 02138 USA. [Ebril, M.] Tufts Med Sch, Boston, MA USA. [Ay, H.] Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA USA. [Koroshetz, W. J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Smith, W. S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Lima, FO (reprint author), Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU NIH [1-R01-NS059710-01A2, R01-NS051412, P50 NS051343]; Agency for Healthcare Research and Quality [R01 HS011392]; American Heart Association-Bugher Foundation; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Esther U Sharp Fund; Conway Fellowship Fund; Lakeside Fund; Levitt Fund FX Dr Ay receives grant support from the NIH grant 1-R01-NS059710-01A2 Dr Singhal receives grant support front the NIH giant R01-NS051412 This work was also supported by the Agency for Healthcare Research and Quality R01 HS011392, NIH P50 NS051343, the American Heart Association-Bugher Foundation, and the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke We recognize the generous support of the Esther U Sharp Fund, the Conway Fellowship Fund, the Lakeside Fund, and the Levitt Fund NR 23 TC 32 Z9 32 U1 1 U2 3 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 MAY PY 2010 VL 31 IS 5 BP 817 EP 821 DI 10.3174/ajnr.A1927 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 599MH UT WOS:000277916600006 PM 20044502 ER PT J AU Walhovd, KB Westlye, LT Moe, V Slinning, K Due-Tonnessen, P Bjornerud, A van der Kouwe, A Dale, AM Fjell, AM AF Walhovd, K. B. Westlye, L. T. Moe, V. Slinning, K. Due-Tonnessen, P. Bjornerud, A. van der Kouwe, A. Dale, A. M. Fjell, A. M. TI White Matter Characteristics and Cognition in Prenatally Opiate- and Polysubstance-Exposed Children: A Diffusion Tensor Imaging Study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ALCOHOL SPECTRUM DISORDERS; CENTRAL-NERVOUS-SYSTEM; IN-UTERO; CORPUS-CALLOSUM; OPIOID SYSTEM; BRAIN; MYELINATION; SUBSTANCES; ANISOTROPY; ATTENTION AB BACKGROUND AND PURPOSE. Prenatal drug exposure may influence the developing brain Our aim was to study WM characteristics with DTI in children with prenatal opiate and polysubstance exposure and in controls We assessed whether group differences in FA. DA, and DR could be found and related to cognitive function MATERIALS AND METHODS The study was approved by a committee for medical research ethics Parents signed an Informed consent, children gave spoken consent Our sample included 14 prenatally substance-exposed adopted children (5 girls, age range, 8 6-13 9 years, mean, 11 3 +/- 1 7 years) and 14 control children (7 girls, age range, 9 0-10 2 years, mean, 9 8 +/- 0 3 years) Tract-based spatial statistics were used to define a common WM skeleton for the sample, and FA was compared between groups throughout the skeleton, controlling for age and sex Clusters of significant group differences >= 100 voxels (P < 05) were identified FA, DA, and DR within clusters were correlated with cognitive function RESULTS Ten clusters of FA group differences, mostly in central, posterior, and inferior parts of the brain, were identified (P < 05), showing lower FA in substance-exposed children FA and DA correlated positively and DR, negatively with cognitive function across groups CONCLUSIONS. Prenatally substance-exposed children exhibited lower FA in restricted areas of WM, mostly relatively central, inferior, and posterior, Where myelination occurs early in development Myelin in these areas may be particularly vulnerable to prenatal substance exposure FA and DR related moderately to cognitive function Potential confounding factors existed and were considered C1 [Walhovd, K. B.; Westlye, L. T.; Moe, V.; Fjell, A. M.] Univ Oslo, Dept Psychol, Ctr Study Human Cognit, N-0317 Oslo, Norway. [Moe, V.; Slinning, K.] Adolescent Mental Hlth, Eastern & So Norway, Oslo, Norway. [Slinning, K.] Natl Inst Publ Hlth, Div Mental Hlth, Oslo, Norway. [Due-Tonnessen, P.; Bjornerud, A.] Univ Hosp, Rikshosp, Oslo, Norway. [van der Kouwe, A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Dale, A. M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Dale, A. M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Walhovd, KB (reprint author), Univ Oslo, Dept Psychol, Ctr Study Human Cognit, Forskningsveien 3,PoB 1094 Blindern, N-0317 Oslo, Norway. RI Dale, Anders/A-5180-2010; OI Westlye, Lars T./0000-0001-8644-956X FU Norwegian Research Council; Institute of Psychology at the University of Oslo FX This work was support by the Norwegian Research Council and the Institute of Psychology at the University of Oslo NR 51 TC 22 Z9 22 U1 3 U2 7 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 MAY PY 2010 VL 31 IS 5 BP 894 EP 900 DI 10.3174/ajnr.A1957 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 599MH UT WOS:000277916600022 PM 20203117 ER PT J AU Choi, JH Marshall, RS Neimark, MA Konstas, AA Lin, E Chiang, YT Mast, H Rundek, T Mohr, JP Pile-Spellman, J AF Choi, J. H. Marshall, R. S. Neimark, M. A. Konstas, A. A. Lin, E. Chiang, Y. T. Mast, H. Rundek, T. Mohr, J. P. Pile-Spellman, J. TI Selective Brain Cooling with Endovascular Intracarotid Infusion of Cold Saline: A Pilot Feasibility Study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; CEREBRAL-BLOOD-FLOW; TRANSIENT FOCAL ISCHEMIA; HOSPITAL CARDIAC-ARREST; CENTRAL-NERVOUS-SYSTEM; INDUCED HYPOTHERMIA; ARTERY OCCLUSION; MODERATE HYPOTHERMIA; COMATOSE SURVIVORS; REPERFUSION INJURY AB BACKGROUND AND PURPOSE Endovascular brain cooling as a method for rapid and selective induction of hypothermic neuroprotection has not been systematically studied in humans In this clinical pilot study we investigated the feasibility, safety, and physiologic responses of short-term brain cooling with IC-CSI MATERIALS AND METHODS We studied 18 patients (50 +/- 10 years old, 9 women) undergoing follow-up cerebral angiography after previous treatment of vascular malformations Isotonic saline (4-17 degrees C) was infused into 1 internal carotid artery at 33 mL/min for 10 minutes Brain (JVB) and bladder/esophageal temperature measurements (n = 9) were performed Both MCAs were monitored with transcranial Doppler sonography (n = 13) Arterial and JV blood were sampled to estimate hemodilution and brain oxygen extraction RESULTS JVB temperature dropped similar to 0 84 +/- 013 C and systemic temperature by 0 15 +/- 0 08 degrees C from baseline (JVB versus systemic temperature P = 0006) Systolic MCA-flow velocities decreased from 101 +/- 27 to 73 +/- 18 cm/s on the infused side and from 83 +/- 24 to 78 +/- 21 cm/s on the contralateral side (relative changes, -26 +/- 8% versus -4 +/- 27%, P = 009) Changes in hematocrit (-1 2 +/- 1 1%) and cerebral artenovenous oxygen difference (0 2 +/- 1 0 mL O(2)/100 mL) were not significant Doppler data showed no signs of vascular spasm or microemboli No focal neurologic deficits occurred Pain was not reported CONCLUSIONS The results of this pilot study suggest that brain cooling can be achieved safely, rapidly, and selectively by means of IC-CSI, opening a new potential avenue for acute neuroprotection Clinical investgations with control of infusion parameters and measurements of CBF, oxygen consumption, and brain temperature are warranted C1 [Choi, J. H.] Columbia Univ, New York Presbyterian Hosp, Neurol Inst, Med Ctr,Dept Radiol, New York, NY 10032 USA. [Choi, J. H.; Marshall, R. S.; Mast, H.; Rundek, T.; Mohr, J. P.] Columbia Univ, New York Presbyterian Hosp, Neurol Inst, Med Ctr,Stroke Ctr, New York, NY 10032 USA. [Neimark, M. A.] Columbia Univ, New York Presbyterian Hosp, Dept Biomed Engn, Med Ctr, New York, NY 10032 USA. [Konstas, A. A.; Lin, E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mast, H.] Hirslanden Klin, Dept Neurol, Zurich, Switzerland. RP Choi, JH (reprint author), Columbia Univ, New York Presbyterian Hosp, Neurol Inst, Med Ctr,Dept Radiol, 710 W 168th St,N1-6, New York, NY 10032 USA. FU New York State Office of Science, Technology and Academic Research (NYSTAR); Dana Foundation FX This study was supported by the New York State Office of Science, Technology and Academic Research (NYSTAR) and the Dana Foundation (Clinical Neuroscience Research Grant) NR 52 TC 21 Z9 25 U1 0 U2 3 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 MAY PY 2010 VL 31 IS 5 BP 928 EP 934 DI 10.3174/ajnr.A1961 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 599MH UT WOS:000277916600028 PM 20053807 ER PT J AU Ginde, AA Sullivan, AF Mansbach, JM Camargo, CA AF Ginde, Adit A. Sullivan, Ashley F. Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE epidemiology; nutrition; pregnancy; supplementation; vitamin D ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; D DEFICIENCY; D SUPPLEMENTATION; US POPULATION; 25-HYDROXYVITAMIN-D LEVELS; EARLY-CHILDHOOD; RISK; INFANTS; CHILDREN AB OBJECTIVE: We evaluated vitamin D insufficiency in a nationally representative sample of women and assessed the role of vitamin supplementation. STUDY DESIGN: We conducted secondary analysis of 928 pregnant and 5173 nonpregnant women aged 13-44 years from the National Health and Nutrition Examination Survey 2001-2006. RESULTS: The mean 25-hydroxyvitamin D (25[OH]D) level was 65 nmol/L for pregnant women and 59 nmol/L for nonpregnant women. The prevalence of 25(OH)D <75 nmol/L was 69% and 78%, respectively. Pregnant women in the first trimester had similar 25(OH)D levels as nonpregnant women (55 vs 59 nmol/L), despite a higher proportion taking vitamin D supplementation (61% vs 32%). However, first-trimester women had lower 25(OH)D levels than third-trimester women (80 nmol/L), likely from shorter duration of supplement use. CONCLUSION: Adolescent and adult women of childbearing age have a high prevalence of vitamin D insufficiency. Current prenatal multivitamins (400 IU vitamin D) helped to raise serum 25(OH) D levels, but higher doses and longer duration may be required. C1 [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Sch Med, Aurora, CO 80045 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Mansbach, Jonathan M.] Harvard Univ, Sch Med, Dept Med, Childrens Hosp Boston, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado, Dept Emergency Med, Sch Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu RI Siry, Bonnie/D-7189-2017 FU National Institutes of Health (NIH) [KL2 RR025779, K23 AI077801]; Massachusetts General Hospital Center FX Dr Ginde was supported by National Institutes of Health (NIH) Grant KL2 RR025779; Dr Mansbach, by NIH Grant K23 AI077801; and Dr Camargo, by the Massachusetts General Hospital Center for D-receptor Activation Research. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 49 TC 30 Z9 31 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2010 VL 202 IS 5 AR 436.e1 DI 10.1016/j.ajog.2009.11.036 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 592TM UT WOS:000277403200009 PM 20060512 ER PT J AU Lin, HW Handzel, O Faquin, WC Gopen, Q AF Lin, Harrison W. Handzel, Ophir Faquin, William C. Gopen, Quinton TI Myospherulosis from antibiotic ointment in the postoperative mastoid space SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID SURGERY; DISEASE; EAR C1 [Lin, Harrison W.; Handzel, Ophir] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Gopen, Quinton] Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA. [Lin, Harrison W.; Handzel, Ophir; Gopen, Quinton] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM harrison_lin@mcei.harvard.edu RI Handzel, Ophir/D-8236-2017 OI Handzel, Ophir/0000-0002-6905-3034 NR 9 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 2010 VL 31 IS 3 BP 205 EP 208 DI 10.1016/j.amjoto.2009.01.002 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 595AH UT WOS:000277582600014 PM 20015741 ER PT J AU Badve, S Collins, NR Bhat-Nakshatri, P Turbin, D Leung, S Thorat, M Dunn, SE Geistlinger, TR Carroll, JS Brown, M Bose, S Teitell, MA Nakshatri, H AF Badve, Sunil Collins, Nikail R. Bhat-Nakshatri, Poornima Turbin, Dmitry Leung, Samuel Thorat, Mangesh Dunn, Sandra E. Geistlinger, Tim R. Carroll, Jason S. Brown, Myles Bose, Shikha Teitell, Michael A. Nakshatri, Harikrishna TI Subcellular Localization of Activated AKT in Estrogen Receptor- and Progesterone Receptor-Expressing Breast Cancers Potential Clinical Implications SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID KINASE-ACTIVITY; SURVIVAL; AKT/PKB; PHOSPHORYLATION; PIK3CA; ALPHA; MUTATIONS; APOPTOSIS; BINDING; GROWTH AB Activated v-AKT murine thymoma viral oncogene homolog 1 (AKT)/protein kinase B (PKB) kinase (pAKT) is localized to the plasma membrane, cytoplasm, and/or nucleus in 50% of cancers. The clinical importance of pAKT localization and the mechanism(s) controlling this compartmentalization are unknown. In this study, we examined nuclear and cytoplasmic phospho-AKT (pAKT) expression by immunohistochemistry in a breast cancer tissue microarray (n = 377) with approximate to 15 years follow-up and integrated these data with the expression of estrogen receptor (ER)a, progesterone receptor (PR), and FOXA1. Nuclear localization of pAKT (nuclear-pAKT) was associated with long-term survival (P = 0.004). Within the ER alpha+/PR+ subgroup, patients with nuclear-pAKT positivity had better survival than nuclear-pAKT-negative patients (P <= 0.05). The association of nuclear-pAKT with the ER alpha+/PR+ subgroup was validated in an independent cohort (n = 145). TCL1 family proteins regulate nuclear transport and/or activation of AKT. TCL1B is overexpressed in ER alpha-positive compared with ER alpha-negative breast cancers and in lung metastasis-free breast cancers. Therefore, we examined the possible control of TCL1 family member(s) expression by the estrogen:ER alpha pathway. Estradiol increased TCL1B expression and increased nuclear-pAKT levels in breast cancer cells; short- interfering RNA against TCL1B reduced nuclear-pAKT. Overexpression of nuclear-targeted AKT1 in MCF-7 cells increased cell proliferation without compromising sensitivity to the anti-estrogen, tamoxifen. These results suggest that subcellular localization of activated AKT plays a significant role in determining its function in breast cancer, which in part is dependent on TCL1B expression. (Am J Pathol 2010, 176:2139-2149; DOI: 10.2353/ajpath.2010.090477) C1 [Collins, Nikail R.; Bhat-Nakshatri, Poornima; Nakshatri, Harikrishna] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Badve, Sunil; Thorat, Mangesh] Indiana Univ, Sch Med, Dept Pathol & Internal Med, Indianapolis, IN 46202 USA. [Nakshatri, Harikrishna] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Nakshatri, Harikrishna] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. [Turbin, Dmitry; Leung, Samuel] Vancouver Hosp & Hlth Sci Ctr, Genet Pathol Evaluat Ctr, Vancouver, BC V5Z 1M9, Canada. [Dunn, Sandra E.] Univ British Columbia, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. [Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles] Brigham & Womens Hosp, Div Mol & Cellular Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Geistlinger, Tim R.; Carroll, Jason S.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Bose, Shikha] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA. [Teitell, Michael A.] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. [Teitell, Michael A.] Univ Calif Los Angeles, Sch Med, Broad Stem Cell Res Ctr, Los Angeles, CA 90024 USA. RP Nakshatri, H (reprint author), Indiana Univ, Sch Med, Dept Surg, 1044 W Walnut St,R4-202, Indianapolis, IN 46202 USA. EM sbadve@iupui.edu; hnakshat@iupui.edu RI Thorat, Mangesh/A-9787-2008; OI Thorat, Mangesh/0000-0001-8673-5320; Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [CA90571, CA107300, CA89153]; Leukemia and Lymphoma Society FX Supported by grants from the National Institutes of Health to M.A.T. (CA90571, CA107300) and H.N. (CA89153). M.T. is a Leukemia and Lymphoma Society Scholar. H.N. is Marian J. Morrison Professor of Breast Cancer Research. NR 59 TC 26 Z9 27 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2010 VL 176 IS 5 BP 2139 EP 2149 DI 10.2353/ajpath.2010.090477 PG 11 WC Pathology SC Pathology GA 627XV UT WOS:000280078600010 PM 20228224 ER PT J AU Baba, Y Nosho, K Shima, K Irahara, N Chan, AT Meyerhardt, JA Chung, DC Giovannucci, EL Fuchs, CS Ogino, S AF Baba, Yoshifumi Nosho, Katsuhiko Shima, Kaori Irahara, Natsumi Chan, Andrew T. Meyerhardt, Jeffrey A. Chung, Daniel C. Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji TI HIF1A Overexpression Is Associated with Poor Prognosis in a Cohort of 731 Colorectal Cancers SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL GROWTH-FACTOR; COLON-CANCER; MICROSATELLITE INSTABILITY; FACTOR 1-ALPHA; UP-REGULATION; LINE-1 HYPOMETHYLATION; TUMOR ANGIOGENESIS; BRAF MUTATION AB Tissue hypoxia commonly occurs in tumors. Hypoxia-inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1 alpha) and endothelial PAS domain protein 1 (EPAS1; HIF-2 alpha), are over-expressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3C4, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index >= 30 kg/m(2))(P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications. (Am J Pathol 2010, 176:2292-2301; DOI: 10.2353/ajpath.2010.090972) C1 [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Irahara, Natsumi; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Irahara, Natsumi; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol,Dept P, 44 Binney St,Room JF 215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU U.S. National Institute of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA107412, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation National Colorectal Cancer Research Alliance; Japan Society for Promotion of Science; Damon Runyon Cancer Research Foundation FX Supported by U.S. National Institute of Health grants P01 CA87969 (to S. Hankinson), P01 CA55075 (to W. Willett), P50 CA127003 (to C.S.F.), K07 CA107412 (to A.T.C.), and K07 CA122826 (to S.O.) and in part by grants from the Bennett Family Fund and from the Entertainment Industry Foundation National Colorectal Cancer Research Alliance. K.N. was supported by a fellowship grant from the Japan Society for Promotion of Science. In addition, A.T.C. was supported by a grant from the Damon Runyon Cancer Research Foundation. NR 57 TC 73 Z9 79 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2010 VL 176 IS 5 BP 2292 EP 2301 DI 10.2353/ajpath.2010.090972 PG 10 WC Pathology SC Pathology GA 627XV UT WOS:000280078600024 PM 20363910 ER PT J AU Block, K Gorin, Y New, DD Eid, A Chelmicki, T Reed, A Choudhury, GG Parekh, DJ Abboud, HE AF Block, Karen Gorin, Yves New, David D. Eid, Assaad Chelmicki, Tomasz Reed, Amanda Choudhury, Goutam Ghosh Parekh, Dipen J. Abboud, Hanna E. TI The NADPH Oxidase Subunit p22(phox) Inhibits the Function of the Tumor Suppressor Protein Tuberin SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; HYPOXIA-INDUCIBLE FACTOR-2-ALPHA; MATRIX-METALLOPROTEINASE; AKT ACTIVATION; UP-REGULATION; NOX FAMILY; TARGET; CANCER; IDENTIFICATION AB Mutations in the von Hippel-Lindau (VHL) gene give rise to renal cell carcinoma. Reactive oxygen species, generated by Nox oxidases, are involved in tumorigenesis. We have previously demonstrated that in VHL-deficient cells, p22(phox)-dependent Nox1 and Nox4 oxidases maintain hypoxia inducible factor-2 alpha (HIF-2 alpha) protein expression through an Akt-dependent translational pathway. Phosphorylation of tuberin, by Akt, results in its inactivation. Here we show that diphenyleneiodonium chloride, an inhibitor of Nox oxidases, and small-interfering RNA-mediated down-regulation of p22(phox) inhibit Akt-dependent phosphorylation of tuberin and stabilizes tuberin protein levels in VHL-deficient renal carcinoma cells. p22(phox)-mediated inactivation of tuberin is associated with an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) phosphorylation as well as HIF-2 alpha stabilization. Importantly, we find that marked up-regulation of p22(phox) in human renal cell carcinoma correlates with increased tuberin phosphorylation, decreased tuberin protein levels, and increased phosphorylation of 4E-BP1. Our data provide the first evidence that p22(phox)-based Nox oxidases maintain HIF-2a protein expression through inactivation of tulberin and downstream activation of ribosomal protein S6 kinase 1/4E-BP1 pathway. (Am J Pathol 2010, 176:2447-2455; DOI: 10.2353/ajpath.2010.090606) C1 [Block, Karen; Gorin, Yves; New, David D.; Eid, Assaad; Chelmicki, Tomasz; Choudhury, Goutam Ghosh; Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Reed, Amanda; Parekh, Dipen J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Block, Karen; Choudhury, Goutam Ghosh; Abboud, Hanna E.] S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. RP Block, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu RI Bell, Tiffany/F-4403-2010; OI Gorin, Yves/0000-0003-4048-6925 FU National Institutes of Health [CA131272, DK078971, DK50190]; Veterans Administration Research Service; University of Texas Health Science Center at San Antonio Institute for Integration of Medicine and Science; Veterans Administration FX Supported by the National Institutes of Health (CA131272 to K.B., DK078971 to H.E.A., and DK50190 to G.G.C.), the Veterans Administration Research Service (K.B., G.G.C., and H.E.A.), and the University of Texas Health Science Center at San Antonio Institute for Integration of Medicine and Science mentored career development award (D.J.P. and K.B.). G.G.C. and K.B. are recipients of Veterans Administration Research Career Scientific Awards. NR 38 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 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2010 VL 176 IS 5 BP 2447 EP 2455 DI 10.2353/ajpath.2010.090606 PG 9 WC Pathology SC Pathology GA 627XV UT WOS:000280078600039 PM 20304964 ER PT J AU Xia, XJ Park, E Liu, BG Willette-Brown, J Gong, WH Wang, JM Mitchell, D Fischer, SM Hu, YL AF Xia, Xiaojun Park, Eunmi Liu, Bigang Willette-Brown, Jami Gong, Wanghua Wang, Jiming Mitchell, David Fischer, Susan M. Hu, Yinling TI Reduction of IKK alpha Expression Promotes Chronic Ultraviolet B Exposure-Induced Skin Inflammation and Carcinogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NF-KAPPA-B; SQUAMOUS-CELL CARCINOMAS; INDUCED P53 MUTATIONS; MOUSE SKIN; KINASE-ALPHA; CANCER DEVELOPMENT; UV CARCINOGENESIS; TUMOR PROGRESSION; INDUCED APOPTOSIS; HAIRLESS MICE AB Ultraviolet B light (UVB) is a common cause of human skin cancer. UVB irradiation induces mutations in the tumor suppressor p53 gene as well as chronic inflammation, which are both essential for UVB carcinogenesis. Inhibitor of nuclear factor kappa B kinase-alpha (IKK alpha) plays an important role in maintaining skin homeostasis, and expression of IKK alpha was found to be down-regulated in human and murine skin squamous cell carcinomas. However, the role of IKK alpha in UVB skin carcinogenesis has not been investigated. Thus, here we performed UVB carcinogenesis experiments on Ikk alpha(+/+) and Ikk alpha(+/-) mice. Ikk alpha(+/-) mice were found to develop a twofold greater number of skin tumors than Ikk alpha(+/+) mice after chronic UVB irradiation. In addition, tumor latency was significantly shorter and tumors were bigger in IKK alpha(+/-) than in Ikk alpha(+/+) mice. At an early stage of carcinogenesis, an increase in UVB-induced p53 mutations as well as macrophage recruitment and mitogenic activity, and a decrease in UVB-induced apoptosis, were detected in Ikk alpha(+/-) compared with those in Ikk alpha(+/+) skin. Also, reduction of IKK alpha levels in keratinocytes up-regulated the expression of monocyte chemoattractant protein-1 (MCP-1/CCL2), TNF alpha, IL-1, and IL-6, and elevated macrophage migration, which might promote macrophage recruitment and inflammation. Therefore, these findings suggest that reduction of IKK alpha expression orchestrates UVB carcinogen, accelerating tumorigenesis. (Am J Pathol 2010, 176:2500-2508; DOI: 10.2353/ajpath.2010.091041) C1 [Willette-Brown, Jami; Wang, Jiming; Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Xia, Xiaojun] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Park, Eunmi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Liu, Bigang; Mitchell, David; Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. [Gong, Wanghua] Sci Applicat Int Corp, Basic Res Program, Frederick, MD USA. RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM huy2@mail.nih.gov FU National Cancer Institute [CA102510, CA117314, CA105345] FX Supported by National Cancer Institute grants CA102510, CA117314 (to Y.H.), and CA105345 (to S.M.F.). NR 49 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2010 VL 176 IS 5 BP 2500 EP 2508 DI 10.2353/ajpath.2010.091041 PG 9 WC Pathology SC Pathology GA 627XV UT WOS:000280078600044 PM 20304950 ER PT J AU Rajan, S McNeely, MJ Hammond, M Goldstein, B Weaver, F AF Rajan, Suparna McNeely, Marguerite J. Hammond, Margaret Goldstein, Barry Weaver, Frances TI Association Between Obesity and Diabetes Mellitus in Veterans With Spinal Cord Injuries and Disorders SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Spinal Cord Injury; Body Mass Index; Obesity; Diabetes Mellitus ID BODY-MASS INDEX; DISEASE BURDEN; RISK-FACTORS; HEALTH; OVERWEIGHT; MEN; PARAPLEGIA; MORTALITY; ADULTS; US AB Objectives: To examine the association between body mass index (BMI) and clinically diagnosed diabetes in veterans with spinal cord injuries and disorders. We also sought to determine whether there is evidence to support a 10% reduction in BMI cut points, which would lower the upper limit of normal BMI from 24.99 to 22.49 kg/m(2), for persons with spinal cord injuries and disorders. Design: Cross-sectional analysis using clinical data on 1938 male veterans. Prevalence ratios (95% confidence intervals) were calculated using a generalized linear model and adjusted for age, race, tobacco use, and paraplegia/tetraplegia status. Results: Compared with the National Heart Lung Blood Institute normal BMI category (18.5-24.99 kg/m(2)), the prevalence of diabetes was 50% higher (adjusted prevalence ratio: 1.50, 95% CI: 1.11-2.01) in the overweight category (25-29.99 kg/m(2)) and similar to 3-fold higher (for obese classes 1-3, adjusted prevalence ratio: 2.74-3.03) in the obese category (BMI >= 30 kg/m(2)). Compared with the World Health Organization low-normal category (BMI, 18.5-22.99 kg/m(2)), there was no significant difference in the prevalence of diabetes for those in the high normal weight (BMI, 23-24.99 kg/m(2)) or low overweight (BMI, 25-27.49 kg/m(2)) categories. However, the prevalence of diabetes was 2-fold higher among those in the high overweight category (BMI, 27.5-29.99 kg/m(2); adjusted prevalence ratio: 2.00, 95% CI: 1.33-2.99). Conclusions: BMI >= 25 kg/m(2) was associated with significantly higher diabetes prevalence in male veterans with spinal cord injuries and disorders, and this risk was especially pronounced at BMI >= 27.5 kg/m(2). These findings do not support the need to create spinal cord injuries and disorder-specific BMI definitions of overweight for purposes of determining diabetes risk. C1 [Rajan, Suparna] VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat, Seattle, WA 98108 USA. [McNeely, Marguerite J.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Hammond, Margaret; Goldstein, Barry] Univ Washington, Dept Rehabil Med, Dept Vet Affairs, Spinal Cord Injury Disorders Serv, Seattle, WA 98195 USA. [Weaver, Frances] Northwestern Univ, Dept Vet Affairs, Edward Hines Jr VA Med Ctr, Chicago, IL 60611 USA. RP Rajan, S (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Qual Enhancement Res Initiat, 1660 S Columbian Way,128 NAT, Seattle, WA 98108 USA. FU Department of Veterans Affairs FX This article is based on a work supported by Office of Research and Development, Health Services Research and Development Service, Quality Enhancement Research Initiative of the Department of Veterans Affairs. 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. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 40 TC 7 Z9 8 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2010 VL 89 IS 5 BP 353 EP 361 DI 10.1097/PHM.0b013e3181d896b9 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592OJ UT WOS:000277388600001 PM 20407300 ER PT J AU Collinger, JL Fullerton, B Impink, BG Koontz, AM Boninger, ML AF Collinger, Jennifer L. Fullerton, Bradley Impink, Bradley G. Koontz, Alicia M. Boninger, Michael L. TI Validation of Grayscale-Based Quantitative Ultrasound in Manual Wheelchair Users Relationship to Established Clinical Measures of Shoulder Pathology SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Ultrasound; Grayscale; Tendinopathy; Shoulder ID SPINAL-CORD-INJURY; CHRONIC ACHILLES TENDINOPATHY; MUSCLE ULTRASONOGRAPHY; PAIN; SONOGRAPHY; BIOMECHANICS; DISEASE; IMAGES AB Objective: The primary aim of this study is to establish the validity of grayscale-based quantitative ultrasound (QUS) measures of the biceps and supraspinatus tendons. Design: Nine QUS measures of the biceps and supraspinatus tendons were computed from ultrasound images collected from 67 manual wheelchair users. Shoulder pathology was measured using questionnaires, physical examination maneuvers, and a clinical ultrasound grading scale. Results: Increased age, duration of wheelchair use, and body mass correlated with a darker and more homogenous tendon appearance. Subjects with pain during physical examination tests for biceps tenderness and acromioclavicular joint tenderness exhibited significantly different supraspinatus QUS values. Even when controlling for tendon depth, QUS measures of the biceps tendon differed significantly between subjects with healthy tendons, mild tendinosis, and severe tendinosis. Clinical grading of supraspinatus tendon health was correlated with QUS measures of the supraspinatus tendon. Conclusions: QUS is valid method to quantify tendinopathy and may allow for early detection of tendinosis. Manual wheelchair users are at a high risk for developing shoulder tendon pathology and may benefit from QUS-based research that focuses on identifying interventions designed to reduce this risk. C1 [Collinger, Jennifer L.; Impink, Bradley G.; Koontz, Alicia M.; Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA 15206 USA. [Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Collinger, Jennifer L.; Impink, Bradley G.; Koontz, Alicia M.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Fullerton, Bradley] Patient Phys Partnership & Dell Childrens Med Ctr, Austin, TX USA. [Koontz, Alicia M.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, 7180 Highland Dr,Bldg 4,151R-1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X FU Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs [B3142C]; National Institute of Health [R21HD054529]; National Institute on Disability and Rehabilitation Research (NIDRR) [H133E070024]; NSF FX This article is based on work supported by the Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs, grant B3142C, the National Institute of Health, grant R21HD054529, the National Institute on Disability and Rehabilitation Research (NIDRR) Rehabilitation Engineering Research Center on Spinal Cord Injury, grant H133E070024, and an NSF graduate research fellowship. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 23 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2010 VL 89 IS 5 BP 390 EP 400 DI 10.1097/PHM.0b013e3181d8a238 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 592OJ UT WOS:000277388600006 PM 20407304 ER PT J AU Perlis, RH Smoller, JW Mysore, J Sun, M Gillis, T Purcell, S Rietschel, M Nothen, MM Witt, S Maier, W Iosifescu, DV Sullivan, P Rush, AJ Fava, M Breiter, H Macdonald, M Gusella, J AF Perlis, Roy H. Smoller, Jordan W. Mysore, Jayalakshmi Sun, Mei Gillis, Tammy Purcell, Shaun Rietschel, Marcella Noethen, Markus M. Witt, Stephanie Maier, Wolfgang Iosifescu, Dan V. Sullivan, Patrick Rush, A. John Fava, Maurizio Breiter, Hans Macdonald, Marcy Gusella, James TI Prevalence of Incompletely Penetrant Huntington's Disease Alleles Among Individuals With Major Depressive Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC-SYMPTOMS; TRINUCLEOTIDE REPEAT; MUTATION CARRIERS; QUICK INVENTORY; INCREASED RISK; ASSOCIATION; GENE; SYMPTOMATOLOGY; SCHIZOPHRENIA; CHROMOSOMES AB Objective: Presymptomatic individuals with the Huntingtin (HTT) CAG expansion mutation that causes Huntington's disease may have higher levels of depressive symptoms than healthy comparison populations. However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established. Method: This was a case-control genetic association study of HTT CAG allele size in two discovery cohorts of individuals with major depressive disorder and comparison subjects without major depression as well as a replication cohort of individuals with major depression and comparison subjects without major depression. Results: CAG repeat lengths of 36 or greater were observed in six of 3,054 chromosomes from individuals with major depression, compared with none of 4,155 chromosomes from comparison subjects. In a third cohort, one expanded allele was observed among 1,202 chromosomes in the major depression group, compared with none of 2,678 chromosomes in comparison subjects. No clear pattern of clinical features was shared among individuals with the expanded repeats. Conclusions: In clinical populations of individuals diagnosed with major depression, approximately 3 in 1,000 carried expanded HTT CAG alleles. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Univ Heidelberg, Div Genet Epidemiol Psychiat, Cent Inst Mental Hlth, D-6900 Heidelberg, Germany. Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Carolina Ctr Genome Sci, Chapel Hill, NC USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM rperlis@partners.org OI Rush, Augustus/0000-0003-2004-2382; Nothen, Markus/0000-0002-8770-2464 FU NIMH [R01MH086026, N01 MH-90003]; Bowman Family Foundation; NARSAD; Sidney R. Baer, Jr., Foundation; National Institute on Drug Abuse [14118]; Office of National Drug Control Policy-Counterdrug Technology Assessment Center; Phenotype Genotype Project in Addiction and Depression [DABK39-03-C-0098]; National Institute of Neurological Disorders and Stroke [NS16367] FX Supported by NIMH grant R01MH086026; the Bowman Family Foundation; a Young Investigator Award from NARSAD and the Sidney R. Baer, Jr., Foundation to Dr. Perlis; grant 14118 from the National Institute on Drug Abuse and the Office of National Drug Control Policy-Counterdrug Technology Assessment Center; grant DABK39-03-C-0098 from the Phenotype Genotype Project in Addiction and Depression; and grant NS16367 from the National Institute of Neurological Disorders and Stroke. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was supported by federal funds from NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Dr. Rush, principal investigator). NR 38 TC 23 Z9 23 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2010 VL 167 IS 5 BP 574 EP 579 DI 10.1176/appi.ajp.2009.09070973 PG 6 WC Psychiatry SC Psychiatry GA 590OT UT WOS:000277237100015 PM 20360314 ER PT J AU Lee, EY Kritsaneepaiboon, S Arellano, CMR Grace, RF Zurakowski, D Boiselle, PM AF Lee, Edward Y. Kritsaneepaiboon, Supika Arellano, Claudia Martinez Rios Grace, Rachael F. Zurakowski, David Boiselle, Phillip M. TI Unsuspected Pulmonary Emboli in Pediatric Oncology Patients: Detection With MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE MDCT; neoplasm; pediatric; pulmonary embolism; risk factors; unsuspected findings ID TUMOR EMBOLISM; VENOUS THROMBOEMBOLISM; COMPUTED-TOMOGRAPHY; CT ANGIOGRAPHY; WILMS-TUMOR; CHILDREN; THROMBOSIS; CHILDHOOD; PREVALENCE; REGISTRY AB OBJECTIVE. The purpose of this study was to determine the prevalence, distribution, risk factors, and clinical outcome associated with the detection of unsuspected pulmonary emboli (PE) in routine thoracic MDCT examinations of pediatric oncology patients. MATERIALS AND METHODS. We used our hospital information system to retrospectively identify all consecutively registered pediatric oncology patients 18 years old and younger who underwent contrast-enhanced thoracic MDCT for indications other than PE from July 2004 to May 2008. Two pediatric radiologists in consensus reviewed diagnostic-quality images from consecutive routine thoracic MDCT examinations for the presence and anatomic distribution of PE. The distribution of PE was assessed according to pulmonary arterial level and lobe. Clinical and radiology reports were reviewed for demographic data, type of underlying neoplasm, prospective embolus detection, risk factors, treatment, and outcome. Subgroups of patients with and without PE were compared with respect to type of neoplasm and risk factors. RESULTS. The study sample consisted of 468 children (249 boys, 219 girls; mean age, 9.5 +/- 5.7 years) who underwent a total of 1,002 thoracic MDCT examinations. Nine of the 468 children (1.9%) had PE, including seven with venous thromboembolism and two with tumor emboli. In these nine patients, the pulmonary arterial locations of 17 emboli were nine (53%) segmental, five (29%) lobar, two (12%) central, and one (6%) subsegmental. Classified by lobar location, six of 11 PE (55%) were in the left lower lobe, four (36%) were in the right lower lobe, and one (9%) was in the right upper lobe. PE were not detected prospectively in five of the nine patients (56%). All PE in this subgroup were solitary and located either within the segmental pulmonary arteries (four PE) or a lobar pulmonary artery (one PE). Underlying coagulation disorder (p < 0.001) and history of deep venous thrombosis or PE (p < 0.01) were risk factors for unsuspected PE. Two of nine patients (22%) with unsuspected PE died of causes not directly related to PE. The other seven patients survived, four of whom were not treated for PE. CONCLUSION. PE are unsuspected findings at nearly 2% of routine thoracic MDCT examinations of pediatric oncology patients. More than one half of PE were not detected prospectively at initial CT image interpretation, but lack of diagnosis and treatment did not appear to have a negative influence on patient outcome. Underlying coagulation disorder and a history of deep venous thrombosis or PE were risk factors for unsuspected PE. C1 [Lee, Edward Y.; Kritsaneepaiboon, Supika; Arellano, Claudia Martinez Rios] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Boiselle, Phillip M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Kritsaneepaiboon, Supika] Prince Songkla Univ, Dept Radiol, Hat Yai, Thailand. [Grace, Rachael F.] Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol Oncol, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Lee, EY (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Edward.Lee@childrens.harvard.edu OI Grace, Fergal/0000-0002-3144-5999 NR 37 TC 7 Z9 7 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2010 VL 194 IS 5 BP 1216 EP 1222 DI 10.2214/AJR.09.3463 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586KI UT WOS:000276906400010 PM 20410406 ER PT J AU Sharma, A Digumarthy, SR Kalra, MK Lanuti, M Shepard, JAO AF Sharma, Amita Digumarthy, Subba R. Kalra, Mannudeep K. Lanuti, Michael Shepard, Jo-Anne O. TI Reversible Locoregional Lymph Node Enlargement After Radiofrequency Ablation of Lung Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; lung cancer; lung tumors; lymphadenopathy; radiofrequency ablation; reactive lymph node enlargement ID COMPUTED-TOMOGRAPHY; TISSUE ABLATION; CONTRAST ENHANCEMENT; RABBIT LUNG; THERMAL ABLATION; CT; CANCER; LYMPHADENOPATHY; PREVALENCE; SIZE AB OBJECTIVE. The objective of our study was to assess the characteristics of locoregional lymph node enlargement after successful radiofrequency ablation (RFA) in the treatment of malignant lung tumors. MATERIALS AND METHODS. Follow-up CT examinations of 14 patients (seven men, seven women; age range, 30-90 years) who underwent 16 RFA sessions for the treatment of primary (n = 9) or metastatic (n = 5) lung tumors with a mean follow-up of 35 +/- 15 (SD) months (range, 7-60 months) were retrospectively reviewed by two thoracic radiologists. The site and size of hilar and mediastinal lymph nodes were recorded at baseline and at follow-up 1, 3, and 6 months after RFA sessions. In addition, the size, type, and location of the ablated lesion or lesions were recorded. All complications from RFA were recorded. Data were analyzed using the Fisher's exact test. RESULTS. An increase in lymph node size was detected after 10 of 16 (62.5%) RFA sessions at 1-month follow-up. In four of 10 patients, only one node had enlarged, and in the remaining six patients, more than one nodal region had enlarged. The average increase in nodal size was 3 mm in the short-axis diameter and 4 mm in the long-axis diameter. Twenty-eight percent of RFA sessions were associated with enlargement of at least one lymph node to greater than 10 mm in short-axis diameter at 1-month follow-up. CT showed that nodes had decreased in size at 3-and 6-month follow-ups. Lesion size, location, and complications were not shown to be significantly associated with mediastinal lymph node enlargement (p > 0.05). CONCLUSION. Recognition of reversible locoregional lymph node enlargement after RFA is important to prevent misdiagnosis of nodal metastatic disease. C1 [Sharma, Amita; Digumarthy, Subba R.; Kalra, Mannudeep K.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lanuti, Michael] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM asharma2@partners.org NR 35 TC 9 Z9 9 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 BP 1250 EP 1256 DI 10.2214/AJR.09.3206 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586KI UT WOS:000276906400015 PM 20410411 ER PT J AU Ferreira, RM Lev, MH Goldmakher, GV Kamalian, S Schaefer, PW Furie, KL Gonzalez, RG Sanelli, PC AF Ferreira, Rafael M. Lev, Michael H. Goldmakher, Gregory V. Kamalian, Shahmir Schaefer, Pamela W. Furie, Karen L. Gonzalez, R. Gilberto Sanelli, Pina C. TI Arterial Input Function Placement for Accurate CT Perfusion Map Construction in Acute Stroke SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE acute stroke; arterial input function; CT perfusion; deconvolution method; middle cerebral artery clot; postprocessing perfusion software ID SINGULAR-VALUE DECOMPOSITION; COMPUTED-TOMOGRAPHY; CEREBRAL-ARTERY; MR PERFUSION; VALUES; ISCHEMIA; VOLUME; FLOW AB OBJECTIVE. The objective of our study was to evaluate the effect of varying arterial input function (AIF) placement on the qualitative and quantitative CT perfusion parameters. MATERIALS AND METHODS. Retrospective analysis of CT perfusion data was performed on 14 acute stroke patients with a proximal middle cerebral artery (MCA) clot. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were constructed using a systematic method by varying only the AIF placement in four positions relative to the MCA clot including proximal and distal to the clot in the ipsilateral and contralateral hemispheres. Two postprocessing software programs were used to evaluate the effect of AIF placement on perfusion parameters using a delay-insensitive deconvolution method compared with a standard deconvolution method. RESULTS. One hundred sixty-eight CT perfusion maps were constructed for each software package. Both software programs generated a mean CBF at the infarct core of < 12 mL/100 g/min and a mean CBV of < 2 mL/100 g for AIF placement proximal to the clot in the ipsilateral hemisphere and proximal and distal to the clot in the contralateral hemisphere. For AIF placement distal to the clot in the ipsilateral hemisphere, the mean CBF significantly increased to 17.3 mL/100 g/min with delay-insensitive software and to 19.4 mL/100 g/min with standard software (p < 0.05). The mean MTT was significantly decreased for this AIF position. Furthermore, this AIF position yielded qualitatively different parametric maps, being most pronounced with MTT and CBF. Overall, CBV was least affected by AIF location. CONCLUSION. For postprocessing of accurate quantitative CT perfusion maps, laterality of the AIF location is less important than avoiding AIF placement distal to the clot as detected on CT angiography. This pitfall is less severe with deconvolution-based software programs using a delay-insensitive technique than with those using a standard deconvolution method. C1 [Sanelli, Pina C.] New York Presbyterian Hosp, Dept Radiol, Weill Cornell Med Coll, New York, NY 10065 USA. [Ferreira, Rafael M.; Lev, Michael H.; Goldmakher, Gregory V.; Kamalian, Shahmir; Schaefer, Pamela W.; Furie, Karen L.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sanelli, PC (reprint author), New York Presbyterian Hosp, Dept Radiol, Weill Cornell Med Coll, 525 E 68th St,Starr 630, New York, NY 10065 USA. EM pcs9001@med.cornell.edu OI Kamalian, Shahmir/0000-0002-9640-8144 FU NIH/NINDS [1 P50 NS051343-01A2] FX Supported by NIH/NINDS (grant 1 P50 NS051343-01A2) as part of the Special Program of Translational Research in Acute Stroke (SPOTRIAS). NR 21 TC 16 Z9 18 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 BP 1330 EP 1336 DI 10.2214/AJR.09.2845 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586KI UT WOS:000276906400026 PM 20410422 ER PT J AU Baier, ND Harisinghani, MG Mueller, PR AF Baier, Nina D. Harisinghani, Mukesh G. Mueller, Peter R. TI Biopsy of Thyroid Nodules Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Baier, Nina D.; Harisinghani, Mukesh G.; Mueller, Peter R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Baier, ND (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 BP 1403 EP 1403 DI 10.2214/AJR.09.4107 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586KI UT WOS:000276906400037 ER PT J AU Otonari-Yamamoto, M Nakajima, K Tsuji, Y Otonari, T Curtin, HD Okano, T Sano, T AF Otonari-Yamamoto, Mika Nakajima, Koh Tsuji, Yuriko Otonari, Takamichi Curtin, Hugh D. Okano, Tomohiro Sano, Tsukasa TI Imaging of the Mylohyoid Muscle: Separation of Submandibular and Sublingual Spaces SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; MRI; mylohyoid muscle; sublingual space; submandibular space ID HERNIATION; GLAND; BOUTONNIERE AB OBJECTIVE. This article focuses on the anatomy of the mylohyoid muscle, a crucial landmark in imaging of the oral cavity and upper neck, showing dissected specimens and CT and MR images. CONCLUSION. Identification of the relationship of a lesion in the sublingual space to the mylohyoid muscle using MDCT and high-resolution MRI is a key part of the imaging assessment of the oral cavity and upper neck. C1 [Otonari-Yamamoto, Mika; Otonari, Takamichi; Sano, Tsukasa] Tokyo Dent Coll, Dept Oral & Maxillofacial Radiol, Mihama Ku, Chiba 2618502, Japan. [Nakajima, Koh] Showa Univ, Sch Dent, Dept Oral Anat & Dev Biol, Tokyo 142, Japan. [Tsuji, Yuriko; Okano, Tomohiro] Showa Univ, Sch Dent, Dept Radiol, Tokyo 142, Japan. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Otonari-Yamamoto, M (reprint author), Tokyo Dent Coll, Dept Oral & Maxillofacial Radiol, Mihama Ku, 1-2-2 Masago, Chiba 2618502, Japan. EM myamamoto@tdc.ac.jp NR 10 TC 4 Z9 4 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 MAY PY 2010 VL 194 IS 5 BP W431 EP W438 DI 10.2214/AJR.09.3516 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586KI UT WOS:000276906400053 PM 20410390 ER PT J AU Bhargava, P Oliveira, G Vaidya, S Yeh, M Dighe, M AF Bhargava, P. Oliveira, G. Vaidya, S. Yeh, M. Dighe, M. TI Unusual Presentations of Hepatocellular Carcinoma-A Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Bhargava, P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM bhargp@u.washington.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E275 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000518 ER PT J AU Braschi, M Ramaiya, N Urban, T Kurra, V Harris, G Van den Abbeele, A AF Braschi, M. Ramaiya, N. Urban, T. Kurra, V. Harris, G. Van Den Abbeele, A. TI RECIST 1.1: What is Different From RECIST 1.0? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Braschi, M.; Urban, T.; Kurra, V.; Harris, G.] Massachusetts Gen Hosp, Watertown, MA USA. [Ramaiya, N.; Van Den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM mbraschi@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E180 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000426 ER PT J AU Choi, E Choi, K Masih, S AF Choi, E. Choi, K. Masih, S. TI Handy Imaging Guide to Musculoskeletal Hand Pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Choi, E.; Choi, K.; Masih, S.] Ronald Reagan UCLA Med Ctr, Los Angeles, CA USA. [Choi, K.; Masih, S.] W Los Angeles Vet Adm, Los Angeles, CA USA. EM eugenechoi@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E429 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000671 ER PT J AU Chow, K Lal, M Modarresi, S Masih, S AF Chow, K. Lal, M. Modarresi, S. Masih, S. TI Imaging of Sacroiliac Joint Pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Chow, K.; Lal, M.; Modarresi, S.; Masih, S.] Vet Adm Greater Los Angeles, Los Angeles, CA USA. EM kirachow@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E460 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000702 ER PT J AU Chung, J Lanuti, M El-Sherief, A Rojas, C Abbott, G Shepard, J AF Chung, J. Lanuti, M. El-Sherief, A. Rojas, C. Abbott, G. Shepard, J. TI Staging of Non-small Squamous Cell Lung Cancer: Review of Modalities for Identification and Sampling of Mediastinal Lymph Nodes SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Chung, J.; Lanuti, M.; El-Sherief, A.; Rojas, C.; Abbott, G.; Shepard, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jonherochung@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E106 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000354 ER PT J AU Cronin, C Sharma, A Digumarthy, S Wu, C Gilman, M Shepard, J AF Cronin, C. Sharma, A. Digumarthy, S. Wu, C. Gilman, M. Shepard, J. TI Feasibility of Focal Lung Nodule Biopsy Following Prior Contralateral Pneumonectomy: Our Experience to Date SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Cronin, C.; Sharma, A.; Digumarthy, S.; Wu, C.; Gilman, M.; Shepard, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carmelcronin2000@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 150 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000151 ER PT J AU Cronin, C Prakash, P Daniels, G Kalra, M Palmer, E Blake, M AF Cronin, C. Prakash, P. Daniels, G. Kalra, M. Palmer, E. Blake, M. TI Brown Fat on PET/CT: Correlation with Patient Characteristics SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Cronin, C.; Prakash, P.; Daniels, G.; Kalra, M.; Palmer, E.; Blake, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carmelcronin2000@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 056 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000057 ER PT J AU Dighe, M Bhargava, P Fligner, C Mitsumori, L AF Dighe, M. Bhargava, P. Fligner, C. Mitsumori, L. TI Elevated Alpha Feto Protein Level in Pregnancy-Etiology and Imaging Appearances SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Dighe, M.; Bhargava, P.; Fligner, C.; Mitsumori, L.] Univ Washington, Seattle, WA 98195 USA. [Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM bhargp@u.washington.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E389 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000631 ER PT J AU Dighe, M Bhargava, P Oliveira, G Bush, W Vaidya, S AF Dighe, M. Bhargava, P. Oliveira, G. Bush, W. Vaidya, S. TI Imaging of Adrenal Masses: A pictorial Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Dighe, M.; Bhargava, P.; Oliveira, G.; Bush, W.; Vaidya, S.] Univ Washington, Seattle, WA 98195 USA. [Bhargava, P.; Vaidya, S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM bhargp@u.washington.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E317 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000560 ER PT J AU Duigenan, S Lee, S Oliva, E AF Duigenan, S. Lee, S. Oliva, E. TI Adnexal Torsion: Diagnostic Imaging Features on CT and MRI With Pathologic Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Duigenan, S.; Lee, S.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sduigena@yahoo.ca NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E343 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000585 ER PT J AU Ebuoma, L Lee, S Oliva, E AF Ebuoma, L. Lee, S. Oliva, E. TI Permanent Contraceptive Devices in the Female Pelvis on Multimodality Imaging: Confirming Correct Location and Diagnosing the Complications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Ebuoma, L.; Lee, S.; Oliva, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lebuoma@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E357 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000599 ER PT J AU El-Sherief, A Rojas, C Chung, J Choy, G Medina-Zuluaga, H Abbara, S AF El-Sherief, A. Rojas, C. Chung, J. Choy, G. Medina-Zuluaga, H. Abbara, S. TI Step-by-Step Guide on How to Obtain Standardized Cardiac Imaging Planes and What to Look for Once You Get There SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [El-Sherief, A.; Rojas, C.; Chung, J.; Choy, G.; Medina-Zuluaga, H.; Abbara, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ael-sherief@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E051 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000300 ER PT J AU Franquet, T Abbott, G de Christenson, MR Gimenez, A Hidalgo, A AF Franquet, T. Abbott, G. Rosado de Christenson, M. Gimenez, A. Hidalgo, A. TI Lung Bud Anomalies: Pictorial Essay SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Franquet, T.; Gimenez, A.; Hidalgo, A.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Abbott, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosado de Christenson, M.] St Lukes Hosp, Kansas City, MO USA. EM tfranquet@santpau.cat NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E085 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000334 ER PT J AU Gupta, S Diwan, A Yang, J McLaughlin, V Love, C Vrahas, M AF Gupta, S. Diwan, A. Yang, J. McLaughlin, V. Love, C. Vrahas, M. TI A Multimodality Approach to the Imaging of the Complications of a Hip Arthroplasty With Emphasis on Clinical and Radiologic Aspects SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Gupta, S.; Diwan, A.; Yang, J.; McLaughlin, V.; Love, C.] St Vincents Cathol Med Ctr, New York, NY USA. [Vrahas, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgupta81@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E436 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000678 ER PT J AU Hall, M Jagannathan, J Ramaiya, N Shinagare, A Van den Abbeele, A AF Hall, M. Jagannathan, J. Ramaiya, N. Shinagare, A. Van den Abbeele, A. TI Imaging of Lymphoma Cousins: Likes and Mimics SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Hall, M.; Jagannathan, J.; Ramaiya, N.; Shinagare, A.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM mhall7777@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E174 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000420 ER PT J AU Iqbal, S Donahue, D Mehndiratta, A Torriani, M Gupta, R AF Iqbal, S. Donahue, D. Mehndiratta, A. Torriani, M. Gupta, R. TI Neurogenic Thoracic Outlet Syndrome: A Review of CT and MRI Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Iqbal, S.; Donahue, D.; Mehndiratta, A.; Torriani, M.; Gupta, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM siiqbal@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E535 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000777 ER PT J AU Islam, T Hahn, P Tabatabaei, S Harisinghani, M AF Islam, T. Hahn, P. Tabatabaei, S. Harisinghani, M. TI The Nuts and Bolts of Nodal Staging in Primary Prostate Cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Islam, T.; Harisinghani, M.] Ctr Mol Imaging Res, Boston, MA USA. [Islam, T.; Hahn, P.; Tabatabaei, S.; Harisinghani, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM tinaislam@hotmail.com NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E359 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000601 ER PT J AU Islam, T Hahn, P Lee, S Harisinghani, M AF Islam, T. Hahn, P. Lee, S. Harisinghani, M. TI An Atlas of Nodal Pathways of Metastatic Gynecological Cancers SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Islam, T.; Harisinghani, M.] Ctr Mol Imaging Res, Boston, MA USA. [Islam, T.; Hahn, P.; Lee, S.; Harisinghani, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM tinaislam@hotmail.com NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E336 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000578 ER PT J AU Iyer, V Lubitz, C Stephen, A Hahn, P Harisinghani, M AF Iyer, V. Lubitz, C. Stephen, A. Hahn, P. Harisinghani, M. TI Thyroid Gland Metastases: Overview of Imaging Findings With Pathological Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Iyer, V.; Lubitz, C.; Stephen, A.; Hahn, P.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM viyer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E581 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000822 ER PT J AU Iyer, V Borczuk, D Hahn, P Mueller, P Harisinghani, M AF Iyer, V. Borczuk, D. Hahn, P. Mueller, P. Harisinghani, M. TI Portacaval Lymphadenopathy: Should It be a Cause for Concern in the Absence of Visible Hepatobiliary, Pancreatic and Gastric Pathology? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Iyer, V.; Borczuk, D.; Hahn, P.; Mueller, P.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM viyer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E279 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000522 ER PT J AU Karaosmanoglu, A Arellano, R Mueller, P AF Karaosmanoglu, A. Arellano, R. Mueller, P. TI Common Procedures in Nonvascular Genitourinary Interventional Radiology: How We Do It? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Karaosmanoglu, A.; Arellano, R.; Mueller, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E688 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000929 ER PT J AU Karaosmanoglu, A Arellano, R Mueller, P AF Karaosmanoglu, A. Arellano, R. Mueller, P. TI Imaging Findings of Renal Toxicity in Patients With Chronic Lithium Use SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Karaosmanoglu, A.; Arellano, R.; Mueller, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E333 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000575 ER PT J AU Katkar, A Souza, F Fennessy, F Donald, D AF Katkar, A. Souza, F. Fennessy, F. Donald, D. TI Imaging Features of Pancreatic Neuroendocrine Tumors and Their Metastases on Portal Venous Phase CT-Our Experience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Katkar, A.] UIHC, Iowa City, IA USA. [Souza, F.; Fennessy, F.; Donald, D.] DFCI, Boston, MA USA. EM amolkatkar@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E292 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000535 ER PT J AU Lee, S Hahn, P Scott, J AF Lee, S. Hahn, P. Scott, J. TI A Neural Network to Expedite and Standardize Editorial Review of AJR Manuscripts SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Lee, S.; Hahn, P.; Scott, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM slee0@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 013 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000014 ER PT J AU Ma, X Guo, M Yap, J Jagannathan, J Matulonis, U Harris, G Ramaiya, N AF Ma, X. Guo, M. Yap, J. Jagannathan, J. Matulonis, U. Harris, G. Ramaiya, N. TI The Comparison of Radiological Response Versus Biochemical Response in Ovarian Cancer Patients Receiving Chemotherapy During Phase II Trials SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Ma, X.; Harris, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ma, X.; Guo, M.; Yap, J.; Jagannathan, J.; Matulonis, U.; Ramaiya, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM xma@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 216 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000216 ER PT J AU Munir, R Aslam, R Yeh, B AF Munir, R. Aslam, R. Yeh, B. TI Prevalence and Significance of Periceliac Stranding on Multidetector CT in Asymptomatic Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Munir, R.; Aslam, R.; Yeh, B.] San Francisco VA Med Ctr, San Francisco, CA USA. EM reema.munir@radiology.ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 201 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000201 ER PT J AU O'Regan, K Souza, F Jagannathan, J Ramaiya, N Van den Abbeele, A AF O'Regan, K. Souza, F. Jagannathan, J. Ramaiya, N. Van den Abbeele, A. TI Liposarcoma: Where is the Fat? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [O'Regan, K.; Souza, F.; Jagannathan, J.; Ramaiya, N.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM knoregan@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E457 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000699 ER PT J AU O'Regan, K Souza, F Jagannathan, J Ramaiya, N Van den Abbeele, A AF O'Regan, K. Souza, F. Jagannathan, J. Ramaiya, N. Van den Abbeele, A. TI Malignant Tumors of the Chest Wall: A Pictorial Review of Radiological Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [O'Regan, K.; Souza, F.; Jagannathan, J.; Ramaiya, N.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM knoregan@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E416 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000658 ER PT J AU Oliveira, G Dubinsky, T Dighe, M Warren, W Mitsumori, L Harisinghani, M AF Oliveira, G. Dubinsky, T. Dighe, M. Warren, W. Mitsumori, L. Harisinghani, M. TI Use of Multimodality 3D Imaging to Demonstrate Complex Nodal Drainage Pathways in Common Pelvic Malignancies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Oliveira, G.; Dubinsky, T.; Dighe, M.; Warren, W.; Mitsumori, L.] Univ Washington, Seattle, WA 98195 USA. [Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM grachid@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E335 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000577 ER PT J AU Oliveira, G Bhargava, P Dubinsky, T Harisinghani, M AF Oliveira, G. Bhargava, P. Dubinsky, T. Harisinghani, M. TI What Has Changed Between RECIST and RECIST 1.1? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Oliveira, G.; Bhargava, P.; Dubinsky, T.] Univ Washington, Seattle, WA 98195 USA. [Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM grachid@uw.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E177 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000423 ER PT J AU Oliveira, G Bhargava, P Dubinsky, T Harisinghani, M AF Oliveira, G. Bhargava, P. Dubinsky, T. Harisinghani, M. TI Overview of the Various Existing Radiological Tumor Assessment Criteria for Evaluating Tumor Response SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Oliveira, G.; Bhargava, P.; Dubinsky, T.] Univ Washington, Seattle, WA 98195 USA. [Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM grachid@uw.edu RI Bhargava, Puneet /F-1330-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E175 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000421 ER PT J AU Prabhakar, A Saksena, M Hahn, P Mueller, P Harisinghani, M AF Prabhakar, A. Saksena, M. Hahn, P. Mueller, P. Harisinghani, M. TI Pain in the Neck: Evaluation of Work Habits, Workstation Ergonomics, and Their Influence on Radiologists' Symptoms SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Prabhakar, A.; Saksena, M.; Hahn, P.; Mueller, P.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM amprab@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 012 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000013 ER PT J AU Prakash, P Kalra, M Abujudeh, H Digumarthy, S Gilman, M Shepard, J AF Prakash, P. Kalra, M. Abujudeh, H. Digumarthy, S. Gilman, M. Shepard, J. TI Effect of Age, Indication, and Weight-Based Automatic Exposure Control Technique for Chest CT Scanning SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Prakash, P.; Kalra, M.; Abujudeh, H.; Digumarthy, S.; Gilman, M.; Shepard, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pprakash1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 112 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000114 ER PT J AU Prakash, P Kalra, M Hsieh, J Gilman, M Shepard, J Digumarthy, S AF Prakash, P. Kalra, M. Hsieh, J. Gilman, M. Shepard, J. Digumarthy, S. TI Does ASIR Solve the Issues With Image Quality in Obese Patients? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Prakash, P.; Kalra, M.; Gilman, M.; Shepard, J.; Digumarthy, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pprakash1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 114 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000115 ER PT J AU Ptak, T Milne, L O'Brien, M AF Ptak, T. Milne, L. O'Brien, M. TI Abdominal Plain Film versus MDCT in the Evaluation of Nonspecific Abdominal pain in the Emergency Department: A Model for Evaluating Process, Cost and Effectiveness SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Ptak, T.; Milne, L.; O'Brien, M.] Massachusetts Gen Hosp, Needham, MA USA. EM tptak@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E156 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000403 ER PT J AU Ptak, T O'Brien, M AF Ptak, T. O'Brien, M. TI The Routine Use Of MRI in the Evaluation of Uncomplicated Ligamentous Injury in Conscious Post-Trauma Patients: Literature Review, Meta-Analysis, and Decision Model SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Ptak, T.; O'Brien, M.] Massachusetts Gen Hosp, Needham, MA USA. EM tptak@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E203 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000449 ER PT J AU Rojas, C Medina-Zuluaga, H Chung, J Reingold, J El-Sherief, A Francis, S Abbara, S AF Rojas, C. Medina-Zuluaga, H. Chung, J. Reingold, J. El-Sherief, A. Francis, S. Abbara, S. TI Echocardiography and MDCT, Complimentary Techniques SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Rojas, C.; Medina-Zuluaga, H.; Chung, J.; Reingold, J.; El-Sherief, A.; Francis, S.; Abbara, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carojas@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E052 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000301 ER PT J AU Rojas, C El-Sherief, A Chung, J Choy, G Medina-Zuluaga, H Abbara, S AF Rojas, C. El-Sherief, A. Chung, J. Choy, G. Medina-Zuluaga, H. Abbara, S. TI Embryology, Anatomy, Normal Variants, and Pathology of the Interatrial Septum SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Rojas, C.; El-Sherief, A.; Chung, J.; Choy, G.; Medina-Zuluaga, H.; Abbara, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carojas@partners.org NR 0 TC 0 Z9 0 U1 1 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 MAY PY 2010 VL 194 IS 5 SU S MA E050 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000299 ER PT J AU Sacks, B Sacks, A Pallotta, J Faquin, W AF Sacks, B. Sacks, A. Pallotta, J. Faquin, W. TI Can the Ultrasound Appearance of a Thyroid Nodule Predict Ultimate Cytology Upon Fine-Needle Aspiration? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Sacks, B.] Metrowest Med Ctr, Framingham, MA USA. [Sacks, B.; Pallotta, J.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Sacks, A.] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Faquin, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ari.sacks@bmc.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 178 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000179 ER PT J AU Sainani, N Gervais, D Mueller, P Arellano, R AF Sainani, N. Gervais, D. Mueller, P. Arellano, R. TI CT-Guided Percutaenous Biopsy of Abdominal and Pelvic Lesions - Techniques, Tips and Tricks SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Sainani, N.; Gervais, D.; Mueller, P.; Arellano, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM drnisainani@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E679 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000920 ER PT J AU Shinagare, A Jagannathan, J Ramaiya, N Shore, K Hall, M Van den Abbeele, A AF Shinagare, A. Jagannathan, J. Ramaiya, N. Shore, K. Hall, M. Van den Abbeele, A. TI A to Z of Extragonadal Germ Cell Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Shinagare, A.; Jagannathan, J.; Ramaiya, N.; Shore, K.; Hall, M.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM ashinagare@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E366 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000608 ER PT J AU Shore, K Jagannathan, J Ramaiya, N Shinagare, A Van den Abbeele, A AF Shore, K. Jagannathan, J. Ramaiya, N. Shinagare, A. Van Den Abbeele, A. TI Imaging of Metastatic Neuroendocrine Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Shore, K.; Jagannathan, J.; Ramaiya, N.; Shinagare, A.; Van Den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM kbs2002s@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E249 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000493 ER PT J AU Singh, A Sahani, D Cai, W Harmon, D Yoshida, H Uppot, R McGowan, J Harris, G AF Singh, A. Sahani, D. Cai, W. Harmon, D. Yoshida, H. Uppot, R. McGowan, J. Harris, G. TI The Evolving Face of 3D Imaging as a Biomarker: Clinical Significance and Evidence-based Support SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Singh, A.; Sahani, D.; Cai, W.; Harmon, D.; Yoshida, H.; Uppot, R.; McGowan, J.; Harris, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dranandsingh@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E182 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000428 ER PT J AU Singh, A Harmon, D Rosenthal, D Lawrimore, T Cai, W Yoshida, H Mcgowan, J Harris, G AF Singh, A. Harmon, D. Rosenthal, D. Lawrimore, T. Cai, W. Yoshida, H. Mcgowan, J. Harris, G. TI Tumor Necrosis Quantification on Imaging as a Predictor of Therapy Response for Soft-Tissue Sarcoma-Comparison between Estimates Obtained by MRI Volumetry and Pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Singh, A.; Harmon, D.; Rosenthal, D.; Lawrimore, T.; Cai, W.; Yoshida, H.; Mcgowan, J.; Harris, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dranandsingh@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 164 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000165 ER PT J AU Singh, S Kalra, M Doyle, M Shenoy-Bhangle, A Westra, S AF Singh, S. Kalra, M. Doyle, M. Shenoy-Bhangle, A. Westra, S. TI Comparison of Adaptive Iterative and Filtered Back Projection Reconstruction Techniques for Pediatric CT Acquired at Lower Radiation Dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Singh, S.; Kalra, M.; Doyle, M.; Shenoy-Bhangle, A.; Westra, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ssingh6@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 143 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000144 ER PT J AU Singh, S Kalra, M Sharma, A Forsberg, A Shepard, J Digumarthy, S AF Singh, S. Kalra, M. Sharma, A. Forsberg, A. Shepard, J. Digumarthy, S. TI Prospective Evaluation of Effect of 2D Adaptive Filters on Low Radiation Dose Chest and Abdominal CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Singh, S.; Kalra, M.; Sharma, A.; Shepard, J.; Digumarthy, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forsberg, A.] Sharpview, Linkoping, Sweden. EM ssingh6@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 032 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000033 ER PT J AU Singh, S Kalra, M Hsieh, J Doyle, M Licato, P Blake, M AF Singh, S. Kalra, M. Hsieh, J. Doyle, M. Licato, P. Blake, M. TI Comparison of Iterative and Filtered Nack Projection Techniques for Abdominal CT: A Prospective Double-Blinded Clinical Study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Singh, S.; Kalra, M.; Doyle, M.; Blake, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hsieh, J.; Licato, P.] GE Healthcare, Waukesha, WI USA. EM ssingh6@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 029 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000030 ER PT J AU Souza, F O'regan, K Jagannathan, J Ramaiya, N Van den Abbeele, A AF Souza, F. O'regan, K. Jagannathan, J. Ramaiya, N. Van Den Abbeele, A. TI Imaging of Malignant Pleural Neoplasms SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Souza, F.; O'regan, K.; Jagannathan, J.; Ramaiya, N.; Van Den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM ffsouza@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E082 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000331 ER PT J AU Techasith, T Ghoshhajra, B Drzezga, N Rogers, I Medina-Zuluaga, H Blankstein, R Maurovich-Horvat, P Cury, R AF Techasith, T. Ghoshhajra, B. Drzezga, N. Rogers, I. Medina-Zuluaga, H. Blankstein, R. Maurovich-Horvat, P. Cury, R. TI Optimal Viewing Parameters for Myocardial Stress Perfusion CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Techasith, T.; Ghoshhajra, B.; Drzezga, N.; Medina-Zuluaga, H.; Maurovich-Horvat, P.; Cury, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rogers, I.] Stanford Univ Hosp, Palo Alto, CA USA. [Blankstein, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cury, R.] Baptist Cardiac & Vasc Inst, Miami, FL USA. EM ttechasith@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 194 IS 5 SU S MA E057 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000306 ER PT J AU Tran, D Wang, Z Benedetti, N Prevrhal, S Yeh, B AF Tran, D. Wang, Z. Benedetti, N. Prevrhal, S. Yeh, B. TI Gallstone Detection In Vitro at Dual-Energy Compared With Conventional CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Tran, D.; Wang, Z.; Benedetti, N.; Prevrhal, S.] UCSF, San Francisco, CA USA. [Yeh, B.] San Francisco VA Med Ctr, San Francisco, CA USA. EM ben.yeh@radiology.ucsf.edu NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 198 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000198 ER PT J AU Vinjamoori, A Ramaiya, N Jagannathan, J Van den Abbeele, A AF Vinjamoori, A. Ramaiya, N. Jagannathan, J. Van den Abbeele, A. TI Manifestations of Atypical Metastases of Prostate Cancer: A Ten-Year Retrospective Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2010 CL San Diego, CA SP Amer Roentgen Ray Soc C1 [Vinjamoori, A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ramaiya, N.; Jagannathan, J.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM anant_vinjamoori@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2010 VL 194 IS 5 SU S MA 215 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586RV UT WOS:000276931000215 ER PT J AU Laury, AR Hornick, JL Perets, R Krane, JF Corson, J Drapkin, R Hirsch, MS AF Laury, Anna R. Hornick, Jason L. Perets, Ruth Krane, Jeffrey F. Corson, Joseph Drapkin, Ronny Hirsch, Michelle S. TI PAX8 Reliably Distinguishes Ovarian Serous Tumors From Malignant Mesothelioma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE PAX8; h-caldesmon; serous; borderline; mesothelioma; peritoneal ID HUMAN PROTEIN ATLAS; PAIRED BOX GENE; H-CALDESMON; PERITONEAL MESOTHELIOMA; PLEURAL MESOTHELIOMA; BORDERLINE TUMORS; THYROID-TUMORS; LOW-GRADE; EXPRESSION; CANCER AB Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Mullerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P < 0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker for mesothelioma. C1 [Hirsch, Michelle S.] Brigham & Womens Hosp, Dept Pathol, Womens & Perinatal Pathol Div, Boston, MA 02115 USA. [Perets, Ruth; Drapkin, Ronny] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Hornick, Jason L.; Krane, Jeffrey F.; Corson, Joseph; Drapkin, Ronny; Hirsch, Michelle S.] Harvard Univ, Sch Med, Boston, MA USA. RP Hirsch, MS (reprint author), Brigham & Womens Hosp, Dept Pathol, Womens & Perinatal Pathol Div, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM mhirsch1@partners.org RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU Harvard Medical School Center of Excellence in Women's Health Grant; Dana Farber Cancer Institute Friends Award FX Supported in part by a Harvard Medical School Center of Excellence in Women's Health Grant (MSH) and a Dana Farber Cancer Institute Friends Award (MSH). NR 55 TC 93 Z9 99 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 MAY PY 2010 VL 34 IS 5 BP 627 EP 635 DI 10.1097/PAS.0b013e3181da7687 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 595MN UT WOS:000277614800004 PM 20414098 ER PT J AU Najavits, LM Norman, SB Kivlahan, D Kosten, TR AF Najavits, Lisa M. Norman, Sonya B. Kivlahan, Daniel Kosten, Thomas R. TI Improving PTSD/Substance Abuse Treatment in the VA: A Survey of Providers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE; AFGHANISTAN; VETERANS; IRAQ; DRINKING; PTSD; DUTY; CARE AB We surveyed 205 Veterans Affairs (VA) staff on treatment of posttraumatic stress disorder (PTSD), substance use disorder (SUD), and the combination (PTSD/SUD). The survey was anonymous and VA-wide. PTSD/SUD was perceived as more difficult to treat than either disorder alone; gratification in the work was stronger than difficulty (for PTSD, SUD, and PTSD/SUD); and difficulty and gratification appeared separate constructs. Respondents endorsed views that represent expert treatment for the comorbidity; however, there was also endorsement of "myths." Thus, there is a need for more training, policy clarifications, service integration, and adaptations for veterans returning from Iraq and Afghanistan. Limitations are described. (Am J Addict 2010;19:257-263). C1 [Najavits, Lisa M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Norman, Sonya B.] Univ Calif San Diego, VA San Diego Healthcare Syst, VA Ctr Excellence Stress & Mental Hlth, San Diego, CA 92103 USA. [Kivlahan, Daniel] Univ Washington, VA Puget Sound Healthcare Syst, VA Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98195 USA. [Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Dept Psychiat, Baylor Med Sch, Houston, TX USA. RP Najavits, LM (reprint author), VA Boston Healthcare Syst 116 B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM Lisa.Najavits@va.gov NR 23 TC 10 Z9 10 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2010 VL 19 IS 3 BP 257 EP 263 DI 10.1111/j.1521-0391.2010.00039.x PG 7 WC Substance Abuse SC Substance Abuse GA 584TK UT WOS:000276775800012 PM 20525033 ER PT J AU Cudkowicz, ME Katz, J Moore, DH O'neill, G Glass, JD Mitsumoto, H Appel, S Ravina, B Kieburtz, K Shoulson, I Kaufmann, P Khan, J Simpson, E Shefner, J Levin, B Cwik, V Schoenfeld, D Aggarwal, S McDermott, MP Miller, RG AF Cudkowicz, Merit E. Katz, Jon Moore, Dan H. O'neill, Gilmore Glass, Jonathan D. Mitsumoto, Hiroshi Appel, Stanley Ravina, Bernard Kieburtz, Karl Shoulson, Ira Kaufmann, Petra Khan, Jaffar Simpson, Ericka Shefner, Jeremy Levin, Bruce Cwik, Valerie Schoenfeld, David Aggarwal, Swati McDermott, Michael P. Miller, Robert G. TI Toward more efficient clinical trials for amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Review ID EARLY PARKINSON-DISEASE; RANDOMIZED-TRIAL; ALS; MINOCYCLINE; CREATINE; DESIGN AB More than 30 phase II or III clinical trials have been carried out in amyotrophic lateral sclerosis (ALS). Only riluzole, however, has been shown to extend survival and/or time to tracheostomy. Many early ALS trials lacked solid pharmacodynamic and pharmacokinetic data for the treatment being tested, challenging the interpretation of the efficacy and pathway relevance. Understanding of the genetics and pathophysiology of ALS has improved considerably in the past decade, but biomarkers of disease activity remain lacking. A more efficient approach to early phase clinical trials is needed to accelerate the identification of useful agents for ALS. Here we summarize our current thinking about phase II design options and the potential benefits of a clinical trial network for phase II trials in ALS. C1 [Cudkowicz, Merit E.; Schoenfeld, David; Aggarwal, Swati] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katz, Jon; Moore, Dan H.; Miller, Robert G.] Calif Pacific Med Ctr, San Francisco, CA USA. [O'neill, Gilmore] Biogen Idec Inc, Cambridge, MA USA. [Glass, Jonathan D.; Khan, Jaffar] Emory Univ, Atlanta, GA 30322 USA. [Mitsumoto, Hiroshi; Kaufmann, Petra; Levin, Bruce] Columbia Univ, New York, NY USA. [Appel, Stanley; Simpson, Ericka] Methodist Hosp, Houston, TX 77030 USA. [Ravina, Bernard; Kieburtz, Karl; Shoulson, Ira; McDermott, Michael P.] Univ Rochester, Rochester, NY USA. [Shefner, Jeremy] SUNY Upstate, Syracuse, NY USA. [Cwik, Valerie] Muscular Dystrophy Assoc, Tucson, AZ USA. RP Cudkowicz, ME (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM mcudkowicz@partners.org NR 22 TC 48 Z9 48 U1 0 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD MAY PY 2010 VL 11 IS 3 BP 259 EP 265 DI 10.3109/17482960903358865 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 590KS UT WOS:000277225200001 PM 19961263 ER PT J AU Oakey, J Applegate, RW Arellano, E Di Carlo, D Graves, SW Toner, M AF Oakey, John Applegate, Robert W., Jr. Arellano, Erik Di Carlo, Dino Graves, Steven W. Toner, Mehmet TI Particle Focusing in Staged Inertial Microfluidic Devices for Flow Cytometry SO ANALYTICAL CHEMISTRY LA English DT Article ID SYSTEMS; CELLS; MANIPULATION AB Microfluidic inertial focusing has been demonstrated to be an effective method for passively positioning microparticles and cells without the assistance of sheath fluid. Because inertial focusing produces well-defined lateral equilibrium particle positions in addition to highly regulated interparticle spacing, its value in flow cytometry has been suggested. Particle focusing occurs in straight channels and can be manipulated through cross sectional channel geometry by the introduction of curvature. Here, we present a staged channel design consisting of both curved and straight sections that combine to order particles into a single streamline with longitudinal spacing. We have evaluated the performance of these staged inertial focusing channels using standard flow cytometry methods that make use of calibration microspheres. Our analysis has determined the measurement precision and resolution, as a function of flow velocity and particle concentration that is provided by these channels. These devices were found to operate with increasing effectiveness at higher flow rates and particle concentrations, within the examined ranges, which is ideal for high throughput analysis. Further, the prototype flow cytometer equipped with an inertial focusing microchannel matched the resolution provided by a commercial hydrodynamic focusing flow cytometer. Most notably, our analysis indicates that the inertial focusing channels virtually eliminated particle coincidence at the analysis point. These properties suggest a potentially significant role for inertial focusing in the development of inexpensive flow cytometry-based diagnostics and in applications requiring the analysis of high particle concentrations. C1 [Applegate, Robert W., Jr.; Arellano, Erik; Graves, Steven W.] Univ New Mexico, Dept Chem & Nucl Engn, Ctr Biomed Engn, Albuquerque, NM 87131 USA. [Oakey, John; Toner, Mehmet] Shriners Hosp Children, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Oakey, John; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Applegate, Robert W., Jr.; Graves, Steven W.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Di Carlo, Dino] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. RP Graves, SW (reprint author), Univ New Mexico, Dept Chem & Nucl Engn, Ctr Biomed Engn, Albuquerque, NM 87131 USA. EM graves@unm.edu; mtoner@hms.harvard.edu FU NIH [P41EB002503, RR001315, RR020064, GM-060201] FX J.O. and R.W.A., Jr. contributed equally to this work. This work was supported by NIH-P41EB002503, NIH RR001315, and NIH RR020064. E.A. was supported by NIH GM-060201. The authors wish to thank Octavio Hurtado for microfabrication training and assistance. NR 30 TC 97 Z9 97 U1 2 U2 52 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2010 VL 82 IS 9 BP 3862 EP 3867 DI 10.1021/ac100387b PG 6 WC Chemistry, Analytical SC Chemistry GA 590GO UT WOS:000277213400068 PM 20373755 ER PT J AU Bateman, BT Berman, MF Riley, LE Leffert, LR AF Bateman, Brian T. Berman, Mitchell F. Riley, Laura E. Leffert, Lisa R. TI The Epidemiology of Postpartum Hemorrhage in a Large, Nationwide Sample of Deliveries SO ANESTHESIA AND ANALGESIA LA English DT Article ID RISK-FACTORS; OBSTETRIC HEMORRHAGE; VAGINAL BIRTH; CESAREAN-DELIVERY; UNITED-STATES; OUTCOMES; RATES AB BACKGROUND: In this study, we sought to (1) define trends in the incidence of postpartum hemorrhage (PPH), and (2) elucidate the contemporary epidemiology of PPH focusing on risk factors and maternal outcomes related to this delivery complication. METHODS: Hospital admissions for delivery were extracted from the Nationwide Inpatient Sample, the largest discharge dataset in the United States. Using International Classification of Diseases, Clinical Modification (ninth revision) codes, deliveries complicated by PPH were identified, as were comorbid conditions that may be risk factors for PPH. Temporal trends in the incidence of PPH from 1995 to 2004 were assessed. Logistic regression was used to identify risk factors for the most common etiology of PPH-uterine atony. RESULTS: In 2004, PPH complicated 2.9% of all deliveries; uterine atony accounted for 79% of the cases of PPH. PPH was associated with 19.1% of all in-hospital deaths after delivery. The overall rate of PPH increased 27.5% from 1995 to 2004, primarily because of an increase in the incidence of uterine atony; the rates of PPH from other causes including retained placenta and coagulopathy remained relatively stable during the study period. Logistic regression modeling identified age <20 or >= 40 years, cesarean delivery, hypertensive diseases of pregnancy, polyhydramnios, chorioamnionitis, multiple gestation, retained placenta, and antepartum hemorrhage as independent risk factors for PPH from uterine atony that resulted in transfusion. Excluding maternal age and cesarean delivery, one or more of these risk factors were present in only 38.8% of these patients. CONCLUSION: PPH is a relatively common complication of delivery and is associated with substantial maternal morbidity and mortality. It is increasing in frequency in the United States. PPH caused by uterine atony resulting in transfusion often occurs in the absence of recognized risk factors. (Anesth Analg 2010;110:1368-73) C1 [Bateman, Brian T.; Leffert, Lisa R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Berman, Mitchell F.] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, New York, NY USA. [Riley, Laura E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Med, Boston, MA 02114 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM bbateman@partners.org NR 25 TC 150 Z9 159 U1 2 U2 8 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 MAY PY 2010 VL 110 IS 5 BP 1368 EP 1373 DI 10.1213/ANE.0b013e3181d74898 PG 6 WC Anesthesiology SC Anesthesiology GA 589EZ UT WOS:000277130700021 PM 20237047 ER PT J AU Sulemanji, DS Kacmarek, RM AF Sulemanji, Demet S. Kacmarek, Robert M. TI Adaptive Support Ventilation: An Inappropriate Mechanical Ventilation Strategy for Acute Respiratory Distress Syndrome? Reply SO ANESTHESIOLOGY LA English DT Letter ID ACUTE LUNG INJURY; INFLAMMATORY RESPONSES; PULMONARY-FUNCTION; TIDAL VOLUMES; SURGERY; RELEASE; SAFE C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. EM rkacmarek@partners.org NR 12 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 MAY PY 2010 VL 112 IS 5 BP 1295 EP 1296 DI 10.1097/ALN.0b013e3181d77574 PG 3 WC Anesthesiology SC Anesthesiology GA 591FL UT WOS:000277284800047 ER PT J AU Rudders, SA Espinola, JA Camargo, CA AF Rudders, Susan A. Espinola, Janice A. Camargo, Carlos A., Jr. TI North-south differences in US emergency department visits for acute allergic reactions SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID RESPIRATORY-TRACT INFECTION; VITAMIN-D; ANAPHYLAXIS; HEALTH; PRESCRIPTIONS; EPIDEMIOLOGY; ASSOCIATION; POPULATION; CHILDREN; FOOD AB Background: In a previous study, latitude was positively associated with EpiPen prescription rates. Objective: To determine whether a similar geographic difference exists for emergency department (ED) visits for acute allergic reactions (including anaphylaxis). Methods: We combined National Hospital Ambulatory Medical Care Survey data for ED visits to noninstitutional hospitals from 1993 to 2005. Acute allergic reactions were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 995.0, 995.60-995.69, 995.1, 995.2, 995.3, 989.5, and 693.1, and visit rates were compared across standardized geographic divisions. Results: Between 1993 and 2005, there were 17.3 million ED visits for acute allergic reactions, representing 1.3% (95% confidence interval [CI], 1.2%-1.3%) of all ED visits. Per 1000 population, the Northeast had 5.5 visits (95% CI, 4.7-6.2 visits) and the South had 4.9 visits (95% CI, 4.3-5.6 visits). In a multivariable model, the Northeast had a higher odds ratio (OR) than the South (1.13; 95% CI, 1.01-1.27; P = .04). The association was stronger when restricting the analysis to visits for food-related allergic reactions (OR, 1.33; 95% CI, 1.14-1.56; P < .001). Conclusions: The ED visit rates for acute allergic reactions are higher in northeastern vs southern regions. These observational data are consistent with the hypothesis that vitamin D may play an etiologic role in anaphylaxis, especially food-induced anaphylaxis. Ann Allergy Asthma Immunol. 2010;104:413-416. C1 [Rudders, Susan A.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rudders, Susan A.] Childrens Hosp Boston, Div Allergy & Immunol, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU NIH (Bethesda, USA) [NRSA T32-AI-007512]; Massachusetts General Hospital Center for D-receptor Activation Research (Boston, USA) FX Dr. Rudders is supported by NIH training grant NRSA T32-AI-007512 (Bethesda, USA). Dr Camargo is supported, in part, by the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, USA). NR 22 TC 35 Z9 35 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAY PY 2010 VL 104 IS 5 BP 413 EP 416 DI 10.1016/j.anai.2010.01.022 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 701OO UT WOS:000285830100009 PM 20486331 ER PT J AU Noble, VE Blaivas, M Blankenship, R Chiricolo, G Dean, A Fox, JC Gaspari, R Hoffman, B Jones, R Moore, C Sierzenski, P Tayal, V Tillotson, R AF Noble, Vicki E. Blaivas, Michael Blankenship, Robert Chiricolo, Gerardo Dean, Anthony Fox, J. Christian Gaspari, Romolo Hoffman, Beatrice Jones, Robert Moore, Christopher Sierzenski, Paul Tayal, Vivek Tillotson, Robert TI Decision Rule for Imaging Utilization in Blunt Abdominal Trauma - Where is Ultrasound? SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter ID LAPAROTOMY C1 [Noble, Vicki E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blaivas, Michael] Northside Hosp, Atlanta, GA USA. [Blankenship, Robert] St Vincent Med Ctr NE, Camel, IN USA. [Chiricolo, Gerardo] New York Methodist Hosp, New York, NY USA. [Dean, Anthony] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Fox, J. Christian] Univ Calif Irvine, Med Ctr, Irvine, CA USA. [Gaspari, Romolo] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Hoffman, Beatrice] Johns Hopkins Med Ctr, Baltimore, MD USA. [Jones, Robert] Metro Hlth Med Ctr, Cleveland, OH USA. [Sierzenski, Paul] Christiana Care Hlth Syst, Newark, DE USA. [Tayal, Vivek] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Tillotson, Robert] St Michaels Hosp, Stevens Point, WI USA. [Moore, Christopher] Yale Univ, Med Ctr, New Haven, CT USA. RP Noble, VE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Gaspari, Romolo/I-4649-2014 OI Gaspari, Romolo/0000-0002-8411-0308 NR 7 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2010 VL 55 IS 5 BP 487 EP 489 DI 10.1016/j.annemergmed.2009.11.030 PG 3 WC Emergency Medicine SC Emergency Medicine GA 594YX UT WOS:000277578700024 PM 20417389 ER PT J AU Parker, ED Widome, R Nettleton, JA Pereira, MA AF Parker, Emily D. Widome, Rachel Nettleton, Jennifer A. Pereira, Mark A. TI Food Security and Metabolic Syndrome in US Adults and Adolescents: Findings From the National Health and Nutrition Examination Survey, 1999-2006 SO ANNALS OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 24-27, 2008 CL Chicago, IL SP Soc Epidemiol Res DE Cross-Sectional Studies; Food Security; NHANES; Metabolic Syndrome ID DIETARY ENERGY DENSITY; TREATMENT-PANEL-III; OBESITY PARADOX; INSECURITY; CHILDREN; OVERWEIGHT; DISEASE; WOMEN; RISK; DYSLIPIDEMIA AB PURPOSE: We sought to examine the association of food security and metabolic syndrome in a representative sample of U.S. adults and adolescents We hypothesized that compared with those in food-secure households, adolescents and adults living in food-insecure households would have increased odds of (MetS) METHODS: Data from the National Health and Nutrition Examination Surveys from 1999 to 2006 were combined and analyzed cross-sectionally Logistic regression was used to compute odds ratios and 95% confidence intervals (95% CI) in the association of household food security (fully food secure, marginal, low, and very low food security) and MetS. RESULTS: Compared with those who were food secure, adults in households with marginal food security had 1.80-fold increased odds of MetS (95% CI, 1 30-2.49), and those with very low food security had a 1.65-fold increased odds of MetS (95% CI 1 12-2 42) There was no association with low food security The association of marginal household food security and MetS was not significant: in adolescents In adults and adolescents, very low was food security not associated with increased odds of MetS compared with those who were food secure CONCLUSIONS: Members of households with marginal and very low food security are at increased risk of MetS A mechanism may be that foods that are inexpensive and easily accessible tend to be energy dense and nutrient poor Ann Epidemiol 2010, 20 364-370 (C) 2010 Elsevier Inc All rights reserved C1 [Parker, Emily D.] HealthPartners, HealthPartners Res Fdn, Minneapolis, MN 55440 USA. [Widome, Rachel] US Dept Vet Affairs, CCDOR, Minneapolis, MN USA. [Widome, Rachel] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Nettleton, Jennifer A.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX USA. [Pereira, Mark A.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Parker, ED (reprint author), HealthPartners, HealthPartners Res Fdn, Mail Stop 21111R,8170 33rd Ave S,POB 1524, Minneapolis, MN 55440 USA. FU NCI NIH HHS [U54CA116849] NR 36 TC 28 Z9 30 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2010 VL 20 IS 5 BP 364 EP 370 DI 10.1016/j.annepidem.2010.02.009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 588UX UT WOS:000277101000006 PM 20382337 ER PT J AU Winer, E AF Winer, E. TI WILL NEO-ADJUVANT TRIAL RESULTS IMPACT ON FUTURE TREATMENT PRACTICE? SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2010 CY MAY 06-08, 2010 CL Brussels, BELGIUM SP European Soc Med Oncol C1 [Winer, E.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2010 VL 21 SU 4 MA 13IN BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 597BN UT WOS:000277730800011 ER PT J AU Juul, N Wang, ZC Li, Y Wang, Y Carlton, V Iglehart, JD Garber, JE Silver, DP Szallasi, Z Richardson, AL AF Juul, N. Wang, Z. C. Li, Y. Wang, Y. Carlton, V. Iglehart, J. D. Garber, J. E. Silver, D. P. Szallasi, Z. Richardson, A. L. TI AMOUNT OF ALLELIC IMBALANCE PREDICTS RESPONSE TO CISPLATIN IN BREAST AND OVARIAN CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2010 CY MAY 06-08, 2010 CL Brussels, BELGIUM SP European Soc Med Oncol C1 [Juul, N.] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Wang, Z. C.; Li, Y.; Iglehart, J. D.; Silver, D. P.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Wang, Y.; Carlton, V.] Affymetrix, Santa Clara, CA USA. [Szallasi, Z.] Tech Univ Denmark, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Richardson, A. L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 MAY PY 2010 VL 21 SU 4 MA 33P BP 30 EP 30 PG 1 WC Oncology SC Oncology GA 597BN UT WOS:000277730800027 ER PT J AU Haibe-Kains, B Culhane, A Desmedt, C Bontempi, G Quackenbush, J Sotiriou, C AF Haibe-Kains, B. Culhane, A. Desmedt, C. Bontempi, G. Quackenbush, J. Sotiriou, C. TI ROBUSTNESS OF BREAST CANCER MOLECULAR SUBTYPES IDENTIFICATION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2010 CY MAY 06-08, 2010 CL Brussels, BELGIUM SP European Soc Med Oncol C1 [Haibe-Kains, B.; Culhane, A.; Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Desmedt, C.; Sotiriou, C.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Bontempi, G.] Univ Libre Bruxelles, Brussels, Belgium. RI Haibe-Kains, Benjamin/D-3702-2011 OI Haibe-Kains, Benjamin/0000-0002-7684-0079 NR 0 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2010 VL 21 SU 4 MA 98O BP 49 EP 49 PG 1 WC Oncology SC Oncology GA 597BN UT WOS:000277730800092 ER PT J AU Dirix, LY Badwe, R Sun, Y Paridaens, R Lebrun, F Powell, C Turnbull, K Zacharchuk, C Burstein, HJ AF Dirix, L. Y. Badwe, R. Sun, Y. Paridaens, R. Lebrun, F. Powell, C. Turnbull, K. Zacharchuk, C. Burstein, H. J. TI NERATINIB MONOTHERAPY IN PATIENTS WITH ADVANCED ERBB2-POSITIVE BREAST CANCER: GASTROINTESTINAL AND CARDIOVASCULAR SAFETY PROFILES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT IMPAKT Breast Cancer Conference 2010 CY MAY 06-08, 2010 CL Brussels, BELGIUM SP European Soc Med Oncol C1 [Dirix, L. Y.] AZ St Augustinus, Antwerp, Belgium. [Badwe, R.] Tata Mem Hosp, Dept Surg Oncol, Bombay 400012, Maharashtra, India. [Sun, Y.] Chinese Acad Med Sci, Beijing 100037, Peoples R China. [Paridaens, R.] UZ Leuven, Multidisciplinary Breast Ctr, Leuven, Belgium. [Lebrun, F.] Inst Jules Bordet, B-1000 Brussels, Belgium. [Burstein, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2010 VL 21 SU 4 MA 141P BP 61 EP 62 PG 2 WC Oncology SC Oncology GA 597BN UT WOS:000277730800134 ER PT J AU Sher, DJ Tishler, RB Annino, D Punglia, RS AF Sher, D. J. Tishler, R. B. Annino, D. Punglia, R. S. TI Cost-effectiveness of CT and PET-CT for determining the need for adjuvant neck dissection in locally advanced head and neck cancer SO ANNALS OF ONCOLOGY LA English DT Article DE cost-effectiveness analysis; neck dissection; radiotheraphy; PET-CT ID POSITRON-EMISSION-TOMOGRAPHY; QUALITY-OF-LIFE; PLUS CONCURRENT CISPLATIN; SQUAMOUS-CELL HEAD; PHASE-II TRIAL; ONCOLOGY-GROUP; COLORECTAL-CANCER; RANDOMIZED-TRIAL; LUNG-CANCER; MANAGEMENT AB Background: Patients with node-positive head and neck squamous cell carcinomas (HNC) have a significant risk of residual disease (RD) in the neck after treatment, despite optimal chemoradiotherapy (CRT). Adjuvant neck dissection (ND) after CRT has been considered standard treatment, but its morbidity has led investigators to consider using postCRT imaging to determine the need for surgery. We analyzed the cost-effectiveness of computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) as predictors of the need for ND compared with ND for all patients. Materials and methods: We developed a Markov model to describe health states in the 5 years after CRT for HNC in a 50-year-old man. We compared three strategies: dissect all patients, dissect patients with RD on CT, and dissect patients with RD on PET-CT. Probabilistic sensitivity analyses were carried out to model uncertainty in PET-CT performance, up-front and salvage dissection costs, and patient utilities. Results: ND only for patients with RD on PET-CT was the dominant strategy over a wide range of realistic and exaggerated assumptions. Probabilistic sensitivity analyses confirmed that the PET-CT strategy was almost certainly cost-effective at a societal willingness-to-pay threshold of $ 500 000/ quality-adjusted life year. Conclusion: Adjuvant ND reserved for patients with RD on PET-CT is the dominant and cost-effective strategy. original article C1 [Sher, D. J.; Tishler, R. B.; Punglia, R. S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Annino, D.] Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. [Sher, D. J.; Punglia, R. S.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu FU NCI NIH HHS [K07 CA118269-02, K07 CA118269, K07 CA118269-01, K07 CA118269-03, K07 CA118269-04, K07 CA118269-05] NR 30 TC 23 Z9 23 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2010 VL 21 IS 5 BP 1072 EP 1077 DI 10.1093/annonc/mdp405 PG 6 WC Oncology SC Oncology GA 590KM UT WOS:000277224600027 PM 19833820 ER PT J AU Raza, S Siddiqui, UA Megna, JL Schwartz, TL Batki, SL AF Raza, Shafi Siddiqui, Umar A. Megna, James L. Schwartz, Thomas L. Batki, Steven L. TI Pregabalin Treatment of Anxiety in Patients with Substance Use Disorders SO ANNALS OF PHARMACOTHERAPY LA English DT Letter C1 [Raza, Shafi; Siddiqui, Umar A.; Megna, James L.; Schwartz, Thomas L.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, SUNY Upstate Med Univ, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. RP Raza, S (reprint author), SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. EM schwartt@upstate.edu NR 3 TC 4 Z9 4 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2010 VL 44 IS 5 BP 937 EP 938 DI 10.1345/aph.1M656 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 591JD UT WOS:000277295600022 PM 20388860 ER PT J AU Lee, CN Hultman, CS Sepucha, K AF Lee, Clara N. Hultman, C. Scott Sepucha, Karen TI Do Patients and Providers Agree About the Most Important Facts and Goals for Breast Reconstruction Decisions? SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Southeastern-Society-of-Plastic-and-Reconstructive-Surgeons CY JUN, 2009 CL Rio Mar, PR SP SE Soc Plast & Reconstruct Surg DE breast reconstruction; breast surgery; breast cancer treatment; decision making; preferences; patient provider communication; decision aid; cancer reconstruction AB Decisions about breast reconstruction after mastectomy are some of the most difficult decisions a breast cancer patient makes. To make a good decision, the patient should have adequate knowledge of specific facts related to the decision, and the treatment chosen should be consistent with the patient's personal preferences or goals. We sought to identify the most important facts and goals for decisions about breast reconstruction after mastectomy, and to compare patients' and providers' perspectives. We conducted a cross-sectional survey of breast cancer survivors and providers. Participants rated and ranked the importance of facts and goals/concerns related to breast reconstruction after mastectomy. We compared patients' and providers' rankings using chi(2) tests and compared ratings using t-tests. About 21 patients and 20 providers participated. Facts: Providers were more concerned about the impact of radiation on the success of the reconstruction than patients (60% vs. 24%, 95% CI of the difference: -64, -8). Thirty percent of providers placed the fact that women who do not have reconstruction are equally satisfied as women who have reconstruction in the top 3, whereas almost no patients did (30% vs. 5%, 95% CI: -47, -3). For all 3 of the facts about immediate versus delayed reconstruction, women placed a higher priority on these facts than providers did. Goals: Patients placed greater importance on avoiding use of a prosthesis (33% vs. 0%, 95% CI of the difference: 13, 54). There was a trend toward less patient concern about "looking natural without clothes" compared to providers (24% vs. 40%, 95% CI of the difference: -12, 44). Significant variability exists among patients and between patients and providers, with respect to the most important facts and goals to guide decision making about reconstruction. Providers should ensure that women understand that reconstruction can be performed immediately or delayed, as well as the likelihood and type of complications. Surgeons should ask each woman which goals and concerns are most important to her. Specifically, they should inquire as to how women feel about using a prosthesis, and how they feel about their appearance with and without clothes. C1 [Lee, Clara N.; Hultman, C. Scott] Univ N Carolina, Div Plast & Reconstruct Surg, Chapel Hill, NC USA. [Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, CN (reprint author), UNC Plast Surg, Suite 7041,CB 7195, Chapel Hill, NC 27599 USA. EM cnlee@med.unc.edu FU NCRR NIH HHS [1KL2RR025746-01] NR 8 TC 22 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2010 VL 64 IS 5 BP 563 EP 566 DI 10.1097/SAP.0b013e3181c01279 PG 4 WC Surgery SC Surgery GA 589GO UT WOS:000277135200012 PM 20395809 ER PT J AU Lee, CN Hultman, CS Sepucha, K AF Lee, Clara N. Hultman, Charles Scott Sepucha, Karen TI What Are Patients' Goals and Concerns About Breast Reconstruction After Mastectomy? SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Southeastern-Society-of-Plastic-and-Reconstructive-Surgeons CY JUN, 2009 CL Rio Mar, PR SP SE Soc Plast & Reconstruct Surg DE breast reconstruction; breast surgery; qualitative; information needs; recovery; quality of life; decision making ID WOMEN; SATISFACTION AB Discussions about breast reconstruction should include factual information and consideration of the patient's personal concerns. Providers are familiar with the relevant facts but may not know which personal concerns are important to patients. Experience with breast cancer patients has found that providers frequently do not know their patients' treatment preferences. To help reconstructive surgeons discuss personal preferences with their patients, we sought to identify women's key concerns related to breast reconstruction. We employed a qualitative design and convened a sample of 65 women in 7 focus groups and 15 semi-structured interviews. Women with a recent history of early-stage breast cancer who had a mastectomy with or without reconstruction were included. A variety of backgrounds, including under-served populations, low education levels, and various ages were represented. Qualitative content analysis was performed, and key themes were identified. Five key themes emerged. (1) Magnitude of surgery and recovery. Many women reported that concerns over the number of operations, duration of recovery, and risk of complications strongly affected their decision-making. (2) Using one's own tissue. Several women felt comforted by the notion of using their own tissue for reconstruction. (3) Looking natural in clothing. Many women pointed out the difference between how they look in clothing versus how they look naked. (4) Avoiding an external prosthesis. Several women stressed practical concerns and framed the reconstruction decision in terms of not having to use prosthesis. (5) Considering others' opinions. A few women reported that their partners' opinion strongly influenced their decision. Many women stated that they ultimately followed their doctor's recommendation. Women considering reconstruction have some unmet emotional and physical needs as well as important goals and concerns that can affect their decisions about and experience with reconstruction. In particular, some breast cancer patients are unprepared for the full effect of surgery on their lives and for the recovery process. Discussions about reconstruction would benefit from inclusion of these key concerns. C1 [Lee, Clara N.; Hultman, Charles Scott] Univ N Carolina, Div Plast & Reconstruct Surg, Chapel Hill, NC USA. [Sepucha, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Lee, CN (reprint author), UNC Plast Surg, Suite 7041,CB 7195, Chapel Hill, NC 27599 USA. EM cnlee@med.unc.edu FU NCRR NIH HHS [1KL2RR025746-01, 1KL2RR025746] NR 11 TC 18 Z9 18 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2010 VL 64 IS 5 BP 567 EP 569 DI 10.1097/SAP.0b013e3181bffc9b PG 3 WC Surgery SC Surgery GA 589GO UT WOS:000277135200013 PM 20354433 ER PT J AU Colwell, AS Kpodzo, D Gallico, GG AF Colwell, Amy S. Kpodzo, Dzifa Gallico, G. Gregory, III TI Low Scar Abdominoplasty with Inferior Positioning of the Umbilicus SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Northwestern-Society-of-Plastic-Surgeons CY SEP, 2009 CL Charleston, SC DE abdominoplasty; umbilical float; body contouring ID CLASSIFICATION AB Miniabdominoplasty with umbilical free float has received little attention in the literature in 15 years and has been criticized for an abnormally low umbilicus. We hypothesized the umbilicus in women presenting for abdominal contouring is positioned higher than ideal and thus may benefit from lowering. In addition, we felt modifications of the original umbilical float technique would improve aesthetic results. A retrospective review identified 60 patients aged 34 to 56 who had abdominoplasty with umbilical fascial transection and inferior positioning. Technical modifications included low placement of a full transverse abdominal scar, abdominal flap undermining to the rib cage, more inferior umbilical repositioning, flank liposuction, and plication of diastasis recti from xiphoid to pubis. Patients did not have enough excess skin to allow traditional abdominoplasty without a high-transverse or vertical midline scar. No umbilical or incisional skin necrosis occurred. To assess optimal umbilical position, plastic surgeons were asked to draw the ideal position on pre- and postoperative photographs from 5 patients. The mean ideal umbilical position was 2.2 cm lower than the actual position (P < 0.01) in preoperative photographs and was close to the true position in postoperative photographs. In conclusion, lower abdominoplasty with inferior umbilical positioning is an excellent choice for the middle age, postpartum woman with excess abdominal skin and full length diastasis recti but a normal body mass index. C1 [Colwell, Amy S.; Kpodzo, Dzifa; Gallico, G. Gregory, III] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 8 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2010 VL 64 IS 5 BP 639 EP 644 DI 10.1097/SAP.0b013e3181db759c PG 6 WC Surgery SC Surgery GA 589GO UT WOS:000277135200029 PM 20395799 ER PT J AU Kolker, AR Austen, WG Slavin, SA AF Kolker, Adam R. Austen, William G., Jr. Slavin, Sumner A. TI Endoscopic-Assisted Transaxillary Breast Augmentation Minimizing Complications and Maximizing Results with Improvements in Patient Selection and Technique SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Northwestern-Society-of-Plastic-Surgeons CY SEP, 2009 CL Charleston, SC DE transaxillary endoscopic breast augmentation; breast implants; armpit incision; axillary breast augmentation; endoscopic assisted breast augmentation; breast enlargement with endoscope ID TISSUE EXPANSION; SUBPECTORAL AUGMENTATION; MAMMAPLASTY; RECONSTRUCTION; EXPERIENCE; IMPLANT; SOFT; SATISFACTION AB The use of the transaxillary incision has enabled augmentation mammoplasty with a scarless breast. However, the classic technique has been associated with high rates of asymmetry, malposition, and high riding implants. With the addition of endoscopic assistance, retropectoral pocket visualization and better control of the lower pole has been facilitated. Nevertheless, pitfalls in patient selection and technique abound. In this study, the authors experience with endoscopic transaxillary breast augmentation is reviewed, with particular attention to both the anatomic characteristics associated with favorable and unfavorable outcomes and technical nuances that have improved aesthetic results. One hundred and ninety-seven endoscopic transaxillary breast augmentations were performed during this study. All patients underwent augmentation with saline implants, with a mean volume of 298 mL. Preoperative pseudoptosis or grade I ptosis was present in 14 patients, and 4 patients had mild or moderate tuberous deformity. Thirty-four patients had short lower pole anatomy, with areola-to-inframammary crease length of <= 3.5 cm. There were 19 patients identified with pectoralis major hypertrophy resulting from strength training. One patient (0.5%) required conversion to an open technique for control of bleeding. Three patients (1.5%) required intraoperative conversion to an open technique for inadequate implant position and breast shape (2 with tuberous deformities and 1 with ptosis). Seven patients (3.5%) underwent revision for malposition (5 superior and 2 inferior). There were no infections, seromas, postoperative hematomas, or significant encapsulations. Patient selection is of paramount importance in minimizing complications and optimizing the results of endoscopic-assisted transaxillary breast augmentation. Patients with deficient lower breast poles, sharply defined inframammary creases with short areola-to-fold distances, pectoralis major muscular hypertrophy, ptosis or pseudoptosis, and any form of tuberous breast deformity should be identified carefully and considered judiciously. Technical refinements that maximize safety and improve the aesthetic results with endoscopic-assisted transaxillary breast augmentation are described. C1 [Kolker, Adam R.] Mt Sinai Sch Med, New York, NY 10021 USA. [Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Slavin, Sumner A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Kolker, AR (reprint author), Mt Sinai Sch Med, 710 Pk Ave, New York, NY 10021 USA. EM adam@kolkermd.com NR 37 TC 8 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2010 VL 64 IS 5 BP 667 EP 673 DI 10.1097/SAP.0b013e3181d9aa3d PG 7 WC Surgery SC Surgery GA 589GO UT WOS:000277135200033 PM 20395798 ER PT J AU Weiser, TG Haynes, AB Dziekan, G Berry, WR Lipsitz, SR Gawande, AA AF Weiser, Thomas G. Haynes, Alex B. Dziekan, Gerald Berry, William R. Lipsitz, Stuart R. Gawande, Atul A. CA Safe Surg Saves Lives TI Effect of A 19-Item Surgical Safety Checklist During Urgent Operations in A Global Patient Population SO ANNALS OF SURGERY LA English DT Article ID RISK; INFECTION AB Objective: To assess whether implementation of a 19-item World Health Organization (WHO) Surgical Safety Checklist in urgent surgical cases would improve compliance with basic standards of care and reduce rates of deaths and complications. Background: Use of the WHO Surgical Safety Checklist has been shown to be associated with significant reductions in complications and deaths. Before evaluation of this safety tool, concern was raised about whether its use would be practical or beneficial during urgent surgical procedures. Methods: We prospectively collected clinical process and outcome data for 1750 consecutively enrolled patients 16 years of age or older undergoing urgent noncardiac surgery before and after introduction of the WHO Surgical Safety Checklist in 8 diverse hospitals around the world; 842 underwent urgent surgery-defined as an operation required within 24 hours of assessment to be beneficial-before introduction of the checklist and 908 after introduction of the checklist. The primary end point was the rate of complications, including death, during hospitalization up to 30 days following surgery. Results: The complication rate was 18.4% (n = 151) at baseline and 11.7% (n = 102) after the checklist was introduced (P = 0.0001). Death rates dropped from 3.7% to 1.4% following checklist introduction (P = 0.0067). Adherence to 6 measured safety steps improved from 18.6% to 50.7% (P < 0.0001). Conclusions: Implementation of the checklist was associated with a greater than one-third reduction in complications among adult patients undergoing urgent noncardiac surgery in a diverse group of hospitals. Use of the WHO Surgical Safety Checklist in urgent operations is feasible and should be considered. C1 [Weiser, Thomas G.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Weiser, Thomas G.; Haynes, Alex B.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Dziekan, Gerald] World Hlth Org, Patient Safety Programme, Geneva, Switzerland. [Berry, William R.; Lipsitz, Stuart R.; Gawande, Atul A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Gawande, AA (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM safesurgery@hsph.harvard.edu OI Gawande, Atul/0000-0002-1824-9176 FU World Health Organization; Hopitaux Universitaires de Geneve; Johns Hopkins University School of Medicine; University of the Philippines FX Supported by grants from the World Health Organization.; The authors would like to thank Drs. Didier Pittet (Hopitaux Universitaires de Geneve) and Peter Pronovost (Johns Hopkins University School of Medicine) for early guidance and support, and Dr. Serafin C. Hilvano (University of the Philippines) for his support. NR 14 TC 167 Z9 170 U1 3 U2 20 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 MAY PY 2010 VL 251 IS 5 BP 976 EP 980 DI 10.1097/SLA.0b013e3181d970e3 PG 5 WC Surgery SC Surgery GA 588UZ UT WOS:000277101200028 PM 20395848 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Systemic Treatment of Hepatocellular Carcinoma: Dawn of a New Era? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; FACTOR-RECEPTOR; FACTOR-ALPHA; COMBINATION CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; RAF/MEK/ERK PATHWAY; ANTITUMOR-ACTIVITY AB Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy have failed to demonstrate improved survival in patients with advanced hepatocellular carcinoma (HCC). On the basis of placebo-controlled, randomized phase III trials, sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review. Ongoing studies are evaluating the efficacy and tolerability of combining sorafenib with erlotinib and other targeted agents or chemotherapy. Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Combining targeted agents that inhibit different pathways in hepatocarcinogenesis is an area of active investigation. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers holds promise to individualize patients' treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents. We hope that we will continue to improve the efficacy of systemic therapy in advanced HCC in the coming years. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM azhu@partners.org FU Onyx Pharmaceuticals/Bayer Healthcare Pharmaceuticals FX This educational review is part of a series, "Emerging Therapeutic Approaches to Hepatocellular Carcinoma," which has been supported by an educational grant from Onyx Pharmaceuticals/Bayer Healthcare Pharmaceuticals. NR 73 TC 33 Z9 33 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 2010 VL 17 IS 5 BP 1247 EP 1256 DI 10.1245/s10434-010-0975-6 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 585ZE UT WOS:000276869000005 PM 20405329 ER PT J AU Maduekwe, UN Lauwers, GY Fernandez-del-Castillo, C Berger, DL Ferguson, CM Rattner, DW Yoon, SS AF Maduekwe, Ugwuji N. Lauwers, Gregory Y. Fernandez-del-Castillo, Carlos Berger, David L. Ferguson, Charles M. Rattner, David W. Yoon, Sam S. TI New Metastatic Lymph Node Ratio System Reduces Stage Migration in Patients Undergoing D1 Lymphadenectomy for Gastric Adenocarcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INDEPENDENT PROGNOSTIC-FACTOR; RANDOMIZED CONTROLLED-TRIAL; N-RATIO; TOTAL GASTRECTOMY; COMBINED PANCREATICOSPLENECTOMY; D-2 RESECTIONS; SURGICAL TRIAL; D2 RESECTION; CANCER; CARCINOMA AB The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for gastric cancer incorporates the absolute number of metastatic lymph nodes (N status) and is optimally used when a parts per thousand yen15 nodes are examined. The ratio of metastatic to examined nodes (N ratio) is an effective prognostic tool, but has not been examined in Western patients undergoing primarily D1 lymphadenectomy. Two hundred and fifty seven patients with gastric adenocarcinoma who underwent gastric resection between 1995 and 2005 at our institution were examined. Novel N ratio intervals were determined using the best cutoff approach (Nr0: N ratio = 0 and a parts per thousand yen15 nodes examined; Nr1: 0 a parts per thousand currency sign N ratio a parts per thousand currency sign 0.3; Nr2: 0.3 < N ratio a parts per thousand currency sign 0.7; and Nr3: N ratio > 0.7). Overall survival was examined according to N status and N ratio. 83% of patients underwent D1 lymphadenectomy with a median of 14 lymph nodes examined. Overall survival stratified by N status was significantly different in patients with < 15 nodes examined compared with those with a parts per thousand yen15 nodes examined. When we stratified by N ratio intervals, there was no significant difference in overall survival in patients with < 15 versus a parts per thousand yen 15 nodes examined. On multivariate analysis, N ratio but not N status was retained as an independent prognostic factor. The use of N status for staging patients undergoing primarily D1 lymphadenectomy results in significant stage migration due to varying numbers of nodes examined. Use of N ratio reduces stage migration and may be a more reliable method of staging these patients. C1 [Maduekwe, Ugwuji N.; Fernandez-del-Castillo, Carlos; Berger, David L.; Ferguson, Charles M.; Rattner, David W.; Yoon, Sam S.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Maduekwe, UN (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sam.yoon@uphs.upenn.edu FU Harvard Medical School under National Institutes of Health [1 KL2 RR025757-0 1]; Harvard Clinical and Translational Science Center [KL1] FX The authors would like to thank Carol Venuti of the Massachusetts General Hospital Cancer Data Registry. Dr. Maduekwe was supported by the Scholars in Clinical Science Program at Harvard Medical School under National Institutes of Health grant no. 1 KL2 RR025757-0 1, Harvard Clinical and Translational Science Center (KL1). NR 43 TC 38 Z9 41 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 MAY PY 2010 VL 17 IS 5 BP 1267 EP 1277 DI 10.1245/s10434-010-0914-6 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 585ZE UT WOS:000276869000008 PM 20099040 ER PT J AU Reust, DL Reeves, ST Abernathy, JH Dixon, JA Gaillard, WF Mukherjee, R Koval, CN Stroud, RE Spinale, FG AF Reust, Daryl L. Reeves, Scott T. Abernathy, James H., III Dixon, Jennifer A. Gaillard, William F., Jr. Mukherjee, Rupak Koval, Christine N. Stroud, Robert E. Spinale, Francis G. TI Interstitial Plasmin Activity With Epsilon Aminocaproic Acid: Temporal and Regional Heterogeneity SO ANNALS OF THORACIC SURGERY LA English DT Article ID PERIOPERATIVE BLOOD-TRANSFUSION; CARDIAC-SURGERY; RENAL-FAILURE; FIBRINOLYSIS; APROTININ; INHIBITOR; PHARMACOKINETICS; THROMBOSIS; THERAPY; BYPASS AB Background. Epsilon aminocaproic acid (EACA) is used in cardiac surgery to modulate plasmin activity (PLact). The present study developed a fluorogenic-microdialysis system to measure in vivo region specific temporal changes in PLact after EACA administration. Methods. Pigs (25 to 35 kg) received EACA (75 mg/kg, n = 7) or saline in which microdialysis probes were placed in the liver, myocardium, kidney, and quadricep muscle. The microdialysate contained a plasmin-specific fluorogenic peptide and fluorescence emission, which directly reflected PLact, determined at baseline, 30, 60, 90, and 120 minutes after EACA/vehicle infusion. Results. Epsilon aminocaproic acid caused significant decreases in liver and quadricep PLact at 60, 90, 120 minutes, and at 30, 60, and 120 minutes, respectively (p < 0.05). In contrast, EACA induced significant biphasic changes in heart and kidney PLact profiles with initial increases followed by decreases at 90 and 120 minutes (p < 0.05). The peak EACA interstitial concentrations for all compartments occurred at 30 minutes after infusion, and were fivefold higher in the renal compartment and fourfold higher in the myocardium, when compared with the liver or muscle (p < 0.05). Conclusions. Using a large animal model and in vivo microdialysis measurements of plasmin activity, the unique findings from this study were twofold. First, EACA induced temporally distinct plasmin activity profiles within the plasma and interstitial compartments. Second, EACA caused region-specific changes in plasmin activity profiles. These temporal and regional heterogeneic effects of EACA may have important therapeutic considerations when managing fibrinolysis in the perioperative period. (Ann Thorac Surg 2010; 89: 1538-45) (C) 2010 by The Society of Thoracic Surgeons C1 [Spinale, Francis G.] Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Cardiothorac Surg, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Dept Anesthesiol & Perioperat Med, Strom Thurmond Res Bldg,114 Doughty St,Room 625, Charleston, SC 29403 USA. EM wilburnm@musc.edu FU NIH [HL059165, HL078650]; Veterans Affairs Health Administration FX This study was supported in part by NIH grants HL059165, HL078650 and a Merit Award from the Veterans Affairs Health Administration. The authors gratefully acknowledge the assistance of Danyelle M. Townsend, PhD, and Joachim de Klerk Uys, PhD, of the Medical University of South Carolina Hollings Cancer Center, Drug Metabolism and Clinical Pharmacology Core Facility, in the measurement of plasma and interstitial EACA concentrations. NR 34 TC 2 Z9 2 U1 0 U2 4 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 MAY PY 2010 VL 89 IS 5 BP 1538 EP 1545 DI 10.1016/j.athoracsur.2010.01.051 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 587KO UT WOS:000276991200028 PM 20417774 ER PT J AU Wenk, JF Zhang, ZH Cheng, GM Malhotra, D Acevedo-Bolton, G Burger, M Suzuki, T Saloner, DA Wallace, AW Guccione, JM Ratcliffe, MB AF Wenk, Jonathan F. Zhang, Zhihong Cheng, Guangming Malhotra, Deepak Acevedo-Bolton, Gabriel Burger, Mike Suzuki, Takamaro Saloner, David A. Wallace, Arthur W. Guccione, Julius M. Ratcliffe, Mark B. TI First Finite Element Model of the Left Ventricle With Mitral Valve: Insights Into Ischemic Mitral Regurgitation SO ANNALS OF THORACIC SURGERY LA English DT Article ID 3-DIMENSIONAL STRAIN; CHORDAE TENDINEAE; ANEURYSM; ANNULOPLASTY; PATHOGENESIS; REPLACEMENT; REDUCTION; SURGERY; STRESS; MUSCLE AB Background. Left ventricular remodeling after posterobasal myocardial infarction can lead to ischemic mitral regurgitation. This occurs as a consequence of leaflet tethering due to posterior papillary muscle displacement. Methods. A finite element model of the left ventricle, mitral apparatus, and chordae tendineae was created from magnetic resonance images from a sheep that developed moderate mitral regurgitation after posterobasal myocardial infarction. Each region of the model was characterized by a specific constitutive law that captured the material response when subjected to physiologic pressure loading. Results. The model simulation produced a gap between the posterior and anterior leaflets, just above the infarcted posterior papillary muscle, which is indicative of mitral regurgitation. When the stiffness of the infarct region was reduced, this caused the wall to distend and the gap area between the leaflets to increase by 33%. Additionally, the stress in the leaflets increased around the chordal connection points near the gap. Conclusions. The methodology outlined in this work will allow a finite element model of both the left ventricle and mitral valve to be generated using noninvasive techniques. (Ann Thorac Surg 2010; 89: 1546-54) (C) 2010 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Livermore Software Technol Corp, Livermore, CA USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov FU National Institutes of Health [R01-HL-84431, R01-HL-63348, R01-HL-77921, R01-HL-86400] FX This study was supported by National Institutes of Health grants R01-HL-84431 (Dr Ratcliffe), R01-HL-63348 (Dr Ratcliffe), R01-HL-77921 (Dr Guccione), and R01-HL-86400 (Dr Guccione). This support is gratefully acknowledged. NR 46 TC 54 Z9 54 U1 0 U2 7 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 MAY PY 2010 VL 89 IS 5 BP 1546 EP 1554 DI 10.1016/j.athoracsur.2010.02.036 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 587KO UT WOS:000276991200029 PM 20417775 ER PT J AU Gopaldas, RR Bakaeen, FG Dao, TK Walsh, GL Swisher, SG Chu, D AF Gopaldas, Raja R. Bakaeen, Faisal G. Dao, Tam K. Walsh, Garrett L. Swisher, Stephen G. Chu, Danny TI Video-Assisted Thoracoscopic Versus Open Thoracotomy Lobectomy in a Cohort of 13,619 Patients SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 04-07, 2009 CL Marco Isl, FL SP So Thorac Surg Assoc ID THORACIC-SURGERY LOBECTOMY; LUNG-CANCER; RESECTION; DATABASE AB Background. Video-assisted thoracoscopic surgery (VATS) is becoming increasingly popular for lung resection in some centers. However, the issue of whether VATS or open thoracotomy is better remains controversial. We compared outcomes of open and VATS lobectomy in a national database. Methods. Using the 2004 and 2006 Nationwide Inpatient Sample database, we identified 13,619 discharge records of patients who underwent pulmonary lobectomy by means of thoracotomy (n = 12,860) or VATS (n = 759). Student's t and chi(2) tests were used to compare the two groups. Multivariable analysis was used to identify independent predictors of outcome measures. Results. The two groups of patients had similar demo-graphics and preoperative comorbidities. They also had similar in-hospital mortality rates (3.1% versus 3.4%; p = 0.67); lengths of stay (9.3 +/- 0.1 versus 9.2 +/- 0.4 days; p = 0.84); hospitalization costs ($23,862 +/- $206 versus $25,125 +/- $ 1,093; p = 0.16); and rates of wound infection (0.8% versus 1.3%; p = 0.15), pulmonary complications (32.2% versus 31.2%; p = 0.55), and cardiovascular complications (3.4% versus 3.9%; p = 0.43). However, multivariable analysis showed that the VATS group had a significantly higher incidence of intraoperative complications than the thoracotomy group (odds ratio, 1.6; 95% confidence interval, 1.0 to 2.4; p = 0.04). A higher percentage of patients with annual income greater than $59,000 underwent VATS lobectomy than patients with income less than $59,000 (35.7% versus 25.4%; p < 0.0001). Conclusions. Patients who underwent VATS lobectomy were 1.6 times more likely to have intraoperative complications than patients who underwent open lobectomy. However, short-term mortality, lengths of stay, and hospitalization costs were similar between the two groups of patients. There seems to be a socioeconomic disparity between VATS and open thoracotomy patients. (Ann Thorac Surg 2010; 89: 1563-70) (C) 2010 by The Society of Thoracic Surgeons C1 [Chu, Danny] Univ Houston, Texas Heart Inst,St Lukes Episcopal Hosp, Div Cardiothorac Surg,Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr,Dept Surg, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Chu, D (reprint author), Univ Houston, Texas Heart Inst,St Lukes Episcopal Hosp, Div Cardiothorac Surg,Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr,Dept Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchumd@gmail.com NR 23 TC 68 Z9 74 U1 0 U2 5 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 MAY PY 2010 VL 89 IS 5 BP 1563 EP 1570 DI 10.1016/j.athoracsur.2010.02.026 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 587KO UT WOS:000276991200031 PM 20417778 ER PT J AU Nachiappan, AC Sharma, A Shepard, JAO Lanuti, M AF Nachiappan, Arun C. Sharma, Amita Shepard, Jo-Anne O. Lanuti, Michael TI Radiofrequency Ablation in the Lung Complicated by Positive Airway Pressure Ventilation SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID BRONCHOPLEURAL FISTULA; TUMORS; PNEUMOTHORAX; CANCER AB A patient receiving bilevel positive airway pressure therapy underwent radiofrequency ablation of a pulmonary metastasis from a primary malignant fibrous histiocytoma of the scapula. The patient's postablation course was complicated by a bronchopleural fistula, which was exacerbated by the detrimental effects of positive airway pressure on necrotic lung tissue after the ablation. The use of positive airway pressure devices, including bilevel positive airway pressure and continuous positive airway pressure, in patients undergoing radiofrequency ablation of the lung should be considered as an added risk for developing bronchopleural fistula. (Ann Thorac Surg 2010;89:1665-7) (C) 2010 by The Society of Thoracic Surgeons C1 [Sharma, Amita] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM asharma2@partners.org NR 7 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2010 VL 89 IS 5 BP 1665 EP 1667 DI 10.1016/j.athoracsur.2009.09.086 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 587KO UT WOS:000276991200060 PM 20417811 ER PT J AU Peck, MA Crawford, RS Abularrage, CJ Patel, VI Conrad, MF Yoo, JH Watkins, MT Albadawi, H AF Peck, Michael A. Crawford, Robert S. Abularrage, Christopher J. Patel, Virendra I. Conrad, Mark F. Yoo, Jin Hyung Watkins, Michael T. Albadawi, Hassan TI A Functional Murine Model of Hindlimb Demand Ischemia SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 4th Annual-Academic-Surgical-Congress CY FEB 03-06, 2009 CL Ft Myers, FL SP Assoc Acad Surg, Soc Univ Surg ID PERIPHERAL ARTERIAL-DISEASE; SKELETAL-MUSCLE; LIMB ISCHEMIA; LASER-DOPPLER; INTERMITTENT CLAUDICATION; REACTIVE HYPEREMIA; MORTALITY; MOUSE; REVASCULARIZATION; ANGIOGENESIS AB Background: To date, murine models of treadmill exercise have been used to study general exercise physiology and angiogenesis in ischemic hindlimbs. The purpose of these experiments was to develop a murine model of demand ischemia in an ischemic limb to mimic claudication in humans. The primary goal was to determine whether treadmill exercise reflected a hemodynamic picture which might be consistent with the hyperemic response observed in humans. Methods: Aged hypercholesterolemic ApoE null mice (ApoE(-/-), n = 13) were subjected to femoral artery ligation (FAL) and allowed to recover from the acute ischemic response. Peripheral perfusion of the hindlimbs at rest was determined by serial evaluation using laser Doppler imaging (LDI) on days 0, 7, and 14 following FAL. During the experiments, mice were also assessed on an established five-point clinical ischemic score, which assessed the degree of digital amputation, necrosis, and cyanosis compared to the nonischemic contralateral limb. After stabilization of the LDI ratio (ischemic limb flux/contralateral nonischemic limb flux) and clinical ischemic score, mice underwent 2 days of treadmill training (10 min at 10 m/min, incline of 10 degrees) followed by 60 min of daily treadmill exercise (13 m/min, incline of 10 degrees) through day 25. An evaluation of preexercise and postexercise perfusion using LDI was performed on two separate occasions following the onset of daily exercise. During the immediate 15 min postexercise evaluation, LDI scanning was obtained in quadruplicate, to allow identification of peak flux ratios. Statistical analysis included unpaired t-tests and analysis of variance. Results: After FAL, the LDI flux ratio reached a nadir between days 1 and 2, then stabilized by day 14 and remained stable through day 25. The clinical ischemic score stabilized at day 7 and remained stable throughout the rest of the experiment. Based on stabilization of both the clinical ischemic score and LDI ratio, exercise training began on day 15. The peak 15 min postexercise LDI ratio increased significantly compared to the preexercise ratio on day 17 (0.48 +/- 0.04 vs. 0.34 +/- 0.04, p < 0.05) and day 25 (0.37 +/- 0.03 vs. 0.27 +/- 0.03, p < 0.01). Within 2 hr of exercise, the LDI ratio returned to preexercise levels on both days 17 and 25. Conclusion: Clinical and hemodynamic stabilization of limb perfusion is evident by 14 days after FAL. FAL followed by demand ischemia results in a reversible relative hyperemic response similar to that observed in exercising human claudicants. A murine model of FAL associated with demand ischemia may be useful to evaluate the metabolic, inflammatory, and flow-related changes associated with claudication in humans. C1 [Peck, Michael A.; Crawford, Robert S.; Abularrage, Christopher J.; Patel, Virendra I.; Conrad, Mark F.; Yoo, Jin Hyung; Watkins, Michael T.; Albadawi, Hassan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02114 USA. RP Albadawi, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg,Dept Surg, 80 Blossom St,Edwards 301, Boston, MA 02114 USA. EM halbadawi@partners.org FU NIAMS NIH HHS [1R01AR055843, R01 AR055843-01A1, R01 AR055843] NR 38 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY PY 2010 VL 24 IS 4 BP 532 EP 537 DI 10.1016/j.avsg.2009.12.003 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 592SQ UT WOS:000277400700016 PM 20363101 ER PT J AU Ishaque, BM Ge, PS Rigberg, D de Virgilio, C AF Ishaque, Brandon M. Ge, Phillip S. Rigberg, David de Virgilio, Christian TI Acute Thrombosis of an Abdominal Aortic Aneurysm followed by Delayed Rupture Associated with Bacterial Infection SO ANNALS OF VASCULAR SURGERY LA English DT Article ID ACUTE OCCLUSION; LIGATION AB Sudden thrombosis of an abdominal aortic aneurysm (AAA) is distinctly rare and is associated with up to 50% mortality. Almost equally rare is infection of a preexisting AAA. We report an extremely unusual case of an AAA that thrombosed leading to acute limb ischemia. This was followed several months later by a delayed rupture of the thrombosed AAA associated with an Escherichia coli infection. We suspect the aortic thrombus was hematogenously seeded by a urinary tract infection. A review of the literature revealed that bacterial infection of a previously thrombosed AAA, leading to a delayed rupture, has not been previously reported. C1 [Ishaque, Brandon M.; Ge, Phillip S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rigberg, David; de Virgilio, Christian] W Los Angeles VA Med Ctr, Div Vasc Surg, Los Angeles, CA USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Dept Surg, 1000 W Carson St Torrance, Torrance, CA 90309 USA. EM cdevirgilio@labiomed.org NR 29 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 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY PY 2010 VL 24 IS 4 AR 524.e1 DI 10.1016/j.avsg.2009.07.029 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 592SQ UT WOS:000277400700014 PM 20036505 ER PT J AU Nurmemmedov, E Yengo, RK Ladomery, MR Thunnissen, MMGM AF Nurmemmedov, Elmar Yengo, Raymond K. Ladomery, Michael R. Thunnissen, Marjolein M. G. M. TI Kinetic behaviour of WT 1's zinc finger domain in binding to the alpha-actinin-1 mRNA SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE WT 1; Transcription factor; Zinc finger; Surface plasmon resonance; RNA binding; ACT 34; Alpha-actinin 1 ID WILMS-TUMOR SUPPRESSOR; TRANSCRIPTION FACTOR-IIIA; INDIVIDUAL AMINO-ACIDS; DOUBLE-STRANDED-RNA; PROTEIN WT1; COMPLEX REVEALS; GENE-PRODUCT; XENOPUS; RECOGNITION; EXPRESSION AB The zinc finger transcription factor Wilms tumour protein (WF 1) is known for its essential involvement in the development of the genitourinary system as well as of other organs and tissues. WT 1 is capable of selectively binding either DNA or mRNA targets. A KTS insertion due to alternative splicing between the zinc fingers 3 and 4 and an unconventional zinc finger 1 are the unique features that distinguish WT 1 from classical DNA-binding C2H2-type zinc finger proteins. The DNA binding characteristics of WT 1 are well studied. Due to lack of information about its native RNA targets, no extensive research has been directed at how WT 1 binds RNA. Using surface plasmon resonance, this study attempts to understand the binding behaviour of WT 1 zinc fingers with its recently reported and first putative mRNA target. ACT 34, whose stem-loop structure is believed to be critical for the interactions with WT 1. We have analysed the interactions of five WT 1 zinc finger truncations with wild-type ACT 34 and four variants. Our results indicate that WT 1 zinc fingers bind ACT 34 in a specific manner, and that this occurs as interplay of all four zinc fingers. We also report that a sensitive kinetic balance, which is equilibrated by both zinc finger 1 and KTS, regulates the interaction with ACT 34. The stem-loop and the flanking nucleotides are important elements for specific recognition by WT 1 zinc fingers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Nurmemmedov, Elmar; Yengo, Raymond K.; Thunnissen, Marjolein M. G. M.] Lund Univ, Ctr Chem, S-22100 Lund, Sweden. [Nurmemmedov, Elmar] Harvard Univ, Div Hematol Oncol, Harvard Stem Cell Inst, Sch Med,Childrens Hosp Boston, Boston, MA 02115 USA. [Nurmemmedov, Elmar] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Ladomery, Michael R.] Univ W England, Fac Hlth & Life Sci, Biomed Res Ctr, Bristol BS16 1QY, Avon, England. RP Nurmemmedov, E (reprint author), Lund Univ, Ctr Chem, Getingevagen 60, S-22100 Lund, Sweden. EM nurmemmedov@mbfys.lu.se; Raymond.Yengo@mbfys.lu.se; Michael.Ladomery@uwe.ac.uk; Marjolein.Thunnissen@mblys.lu.se RI Thunnissen, Marjolein/B-9366-2011 NR 55 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY PY 2010 VL 497 IS 1-2 BP 21 EP 27 DI 10.1016/j.abb.2010.02.013 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 594KY UT WOS:000277537800003 PM 20193655 ER PT J AU Lindsay, RW Heaton, JT Edwards, C Smitson, C Vakharia, K Hadlock, TA AF Lindsay, Robin W. Heaton, James T. Edwards, Colin Smitson, Christopher Vakharia, Kalpesh Hadlock, Tessa A. TI Daily Facial Stimulation to Improve Recovery After Facial Nerve Repair in Rats SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID FUNCTIONAL RECOVERY; MANUAL STIMULATION; WHISKER MOVEMENTS; RHYTHMIC WHISKING; PERIPHERAL-NERVE; ADULT RATS; INJURY; MUSCLE; TRANSECTION; MOTONEURONS AB Objective: To establish whether daily mechanical stimulation improves functional recovery of whisking after facial nerve transection injury and repair in rats. Methods: Forty rats underwent facial nerve transection injury and repair and subsequent quantitative facial movement testing. Animals were randomized into 2 experimental groups (n = 20 each). Both groups received daily 5-minute manual stimulation of their whiskers, with one group undergoing whisker protraction and the other, whisker retraction. Rats were tested on postoperative weeks 1, 4 through 8, and 15 via a validated, quantitative whisking kinematics apparatus. Whisks were counted and analyzed for whisking amplitude, velocity, and acceleration. Results: Animals receiving manual stimulation by passive protraction of their whiskers demonstrated significantly improved functional recovery at multiple time points during the 15 weeks compared with historical controls (P<.005; 1-tailed t test). Recovery was similar in the protraction and retraction groups, trending toward better whisking recovery in the protraction group. Conclusions: Daily mechanical whisker stimulation via either protraction or retraction significantly improves recovery of whisking after facial nerve transection and repair. This finding supports the role of early soft-tissue manipulation after facial nerve repair and may have clinical implications for the postoperative management of patients after facial nerve manipulations. C1 [Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lindsay, Robin W.; Edwards, Colin; Smitson, Christopher; Vakharia, Kalpesh; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu FU National Institutes of Health [K-08 DEO15665-01 A2] FX This work was supported by National Institutes of Health grant K-08 DEO15665-01 A2. NR 33 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAY-JUN PY 2010 VL 12 IS 3 BP 180 EP 185 PG 6 WC Surgery SC Surgery GA 597QE UT WOS:000277772900007 PM 20479434 ER PT J AU DeRosa, J Hamilton, MM AF DeRosa, Jaimie Hamilton, Mark M. TI Young Physician Survey: What Are the New Facial Plastic Surgeons Up To? SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Letter ID TRENDS C1 [DeRosa, Jaimie] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. [Hamilton, Mark M.] St Francis Hosp, Dept Otolaryngol Head & Neck Surg, Indianapolis, IN USA. RP DeRosa, J (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM jaimie_derosa@meei.harvard.edu NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAY-JUN PY 2010 VL 12 IS 3 BP 202 EP 204 PG 3 WC Surgery SC Surgery GA 597QE UT WOS:000277772900011 PM 20479438 ER PT J AU Goldstein, JM Buka, SL Seidman, LJ Tsuang, MT AF Goldstein, Jill M. Buka, Stephen L. Seidman, Larry J. Tsuang, Ming T. TI Specificity of Familial Transmission of Schizophrenia Psychosis Spectrum and Affective Psychoses in the New England Family Study's High-Risk Design SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID EDINBURGH HIGH-RISK; JERUSALEM INFANT-DEVELOPMENT; FINNISH ADOPTIVE FAMILY; COPENHAGEN-HIGH-RISK; NUT ARECA-CATECHU; FOLLOW-UP; BIPOLAR DISORDER; UNAFFECTED RELATIVES; SAMPLE CHARACTERISTICS; CHILDREN AB Context: There is a long history of research on the familial transmission of schizophrenia and other psychoses. However, few studies have investigated the specificity of the transmission of schizophrenia-psychosis spectrum (SPS) disorders and affective psychoses (APs) or observed high-risk offspring into mid-adulthood. Objectives: To investigate the transmission of psychoses from parents to their offspring and the specificity of transmission across psychosis subtypes. Design: High-risk follow-up study. Setting: New England Family Study's High-Risk Study, with population-based community sampling from Boston, Massachusetts, and Providence, Rhode Island. Participants: A total of 203 high-risk offspring of 159 parents with diagnoses of psychoses (SPS and AP) and 147 control offspring of 114 control parents. Main Outcome Measures: Systematically assessed research DSM-IV psychiatric diagnoses for adult offspring. Results: Compared with those of control parents, offspring of parentswith SPS had a significant, almost 6-fold elevated risk of SPS disorders and a nonsignificant doubling of risk for AP. Offspring of parents with AP had a significant 14-fold elevated risk for AP compared with offspring of controls; for SPS disorders, the risk doubled but was not significant. Conclusion: Having a parent with psychosis significantly increased the risk for psychosis among offspring and demonstrated specificity for the transmission of SPS disorders and APs within families. C1 [Goldstein, Jill M.] Brigham & Womens Hosp, Div Womens Hlth, Mary Horrigan Connors Ctr Womens Hlth & Gender Bi, Boston, MA 02120 USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA. [Goldstein, Jill M.; Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Boston, MA 02114 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Goldstein, Jill M.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Div Publ Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA USA. [Goldstein, Jill M.; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, Mary Horrigan Connors Ctr Womens Hlth & Gender Bi, 1 Brigham Cir,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU National Institute of Mental Health [RO1 MH50647, RO1 MH63951]; Stanley Medical Research Institute; NARSAD FX This work was funded primarily by grant RO1 MH50647 from the National Institute of Mental Health (1999-2003, principal investigator Dr Tsuang; 2003-2006, principal investigator Dr Goldstein). Additional funding included National Institute of Mental Health grant RO1 MH63951 (Dr Seidman), Stanley Medical Research Institute (Drs Buka and Seidman), and NARSAD (Dr Seidman). NR 86 TC 27 Z9 28 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2010 VL 67 IS 5 BP 458 EP 467 PG 10 WC Psychiatry SC Psychiatry GA 590XH UT WOS:000277261200004 PM 20439827 ER PT J AU Byers, AL Yaffe, K Covinsky, KE Friedman, MB Bruce, ML AF Byers, Amy L. Yaffe, Kristine Covinsky, Kenneth E. Friedman, Michael B. Bruce, Martha L. TI High Occurrence of Mood and Anxiety Disorders Among Older Adults The National Comorbidity Survey Replication SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WORLD-HEALTH-ORGANIZATION; DSM-IV DISORDERS; LATE-LIFE; MENTAL-DISORDERS; NCS-R; 12-MONTH PREVALENCE; DEPRESSION SCALE; FUTURE-RESEARCH; EPIDEMIOLOGY; SYMPTOMS AB Context: Little is known about prevalence rates of DSM-IV disorders across age strata of older adults, including common conditions such as individual and coexisting mood and anxiety disorders. Objective: To determine nationally representative estimates of 12-month prevalence rates of mood, anxiety, and comorbid mood-anxiety disorders across young-old, mid-old, old-old, and oldest-old community-dwelling adults. Design: The National Comorbidity Survey Replication (NCS-R) is a population-based probability sample of 9282 participants 18 years and older, conducted between February 2001 and April 2003. The NCS-R survey used the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Setting: Continental United States. Participants: We studied the 2575 participants 55 years and older who were part of NCS-R (43%, 55-64 years; 32%, 65-74 years; 20%, 75-84 years; 5%, >= 85 years). This included only noninstitutionalized adults, as all NCS-R participants resided in households within the community. Main Outcome Measures: Twelve-month prevalence of mood disorders (major depressive disorder, dysthymia, bipolar disorder), anxiety disorders (panic disorder, agoraphobia, specific phobia, social phobia, generalized anxiety disorder, posttraumatic stress disorder), and coexisting mood-anxiety disorder were assessed using DSM-IV criteria. Prevalence rates were weighted to adjust for the complex design to infer generalizability to the US population. Results: The likelihood of having a mood, anxiety, or combined mood-anxiety disorder generally showed a pattern of decline with age (P<.05). Twelve-month disorders showed higher rates in women compared with men, a statistically significant trend with age. In addition, anxiety disorders were as high if not higher than mood disorders across age groups (overall 12-month rates: mood, 5% and anxiety, 12%). No differences were found between race/ethnicity groups. Conclusion: Prevalence rates of DSM-IV mood and anxiety disorders in late life tend to decline with age, but remain very common, especially in women. These results highlight the need for intervention and prevention strategies. C1 [Byers, Amy L.] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. [Friedman, Michael B.] Geriatr Mental Hlth Alliance, New York, NY USA. [Bruce, Martha L.] Weill Cornell Med Coll, Weill Cornell Inst Geriatr Psychiat, Dept Psychiat, White Plains, NY USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM amy.byers@ucsf.edu FU National Institute of Mental Health [MH079093, U01-MH60220]; National Institute on Aging [AG031155]; National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044708]; John W. Alden Trust FX Dr Byers is supported by K01 Career Development Award MH079093 from the National Institute of Mental Health. Dr Yaffe is supported, in part, by K24 Midcareer Investigator Award AG031155 from the National Institute on Aging. The NCS-R was supported by National Institute of Mental Health grant U01-MH60220, with supplemental support from the National Institute of Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation grant 044708, and the John W. Alden Trust. NR 45 TC 177 Z9 181 U1 2 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2010 VL 67 IS 5 BP 489 EP 496 PG 8 WC Psychiatry SC Psychiatry GA 590XH UT WOS:000277261200007 PM 20439830 ER PT J AU Skelton, F Kunik, ME Regev, T Naik, AD AF Skelton, Felicia Kunik, Mark E. Regev, Tziona Naik, Aanand D. TI Determining if an older adult can make and execute decisions to live safely at home: A capacity assessment and intervention model SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE Older adults; Capacity; Decision making; Independent Living; Assessment ID GUARDIANSHIP; CLINICIAN; COMMUNITY AB Determining an older adult's capacity to live safely and independently in the community presents a serious and complicated challenge to the health care system. Evaluating one's ability to make and execute decisions regarding safe and independent living incorporates clinical assessments, bioethical considerations, and often legal declarations of capacity. Capacity assessments usually result in life changes for patients and their families, including a caregiver managing some everyday tasks, placement outside of the home, and even legal guardianship. The process of determining capacity and recommending intervention is often inefficient and highly variable in most cases. Physicians are rarely trained to conduct capacity assessments and assessment methods are heterogeneous. An interdisciplinary team (IDT) of clinicians developed the capacity assessment and intervention (CAI) model at a community outpatient geriatrics clinic to address these critical gaps. This report follows one patient through the entire CAI model, describing processes for a typical case. It then examines two additional case reports that highlight common challenges in capacity assessment. The CAI model uses assessment methods common to geriatrics clinical practice and conducts assessments and interventions in a standardized fashion. Reliance on common, validated measures increases generalizability of the model across geriatrics practice settings and patient populations. Published by Elsevier Ireland Ltd. C1 [Kunik, Mark E.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77021 USA. [Skelton, Felicia; Kunik, Mark E.; Naik, Aanand D.] Baylor Coll Med, Alkek Dept Internal Med, Houston, TX 77030 USA. [Kunik, Mark E.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX 77030 USA. [Kunik, Mark E.] Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. [Regev, Tziona; Naik, Aanand D.] Harris Cty Hosp Dist, Geriatr Program, Quentin Mease Community Hosp, Houston, TX 77004 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2450 Holcombe Blvd, Houston, TX 77021 USA. EM anaik@bcm.tmc.edu FU Greenwall Foundation (Naik, PI); Hartford Foundation; Atlantic Philanthropies; Harris County Hospital District; Houston VA HSR&D Center of Excellence [HFP90-020]; NIA K23 [5K23AG027144]; American Foundation on Aging Research FX This study was supported by a bioethics project grant from the Greenwall Foundation (Naik, PI), the Practice Change Fellows Program (Regev) supported by the Hartford Foundation and Atlantic Philanthropies. The capacity assessment and intervention model receives ongoing support from the Harris County Hospital District and the Houston VA HSR&D Center of Excellence (HFP90-020). Dr. Naik is also supported by an NIA K23 grant (5K23AG027144). Felicia Skelton was supported by a medical student training in aging research (MSTAR) grant from the American Foundation on Aging Research. None of the funding agencies played a role in the design and conduct of the study, analysis and interpretation of the data, or the preparation and approval of the manuscript. NR 16 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD MAY-JUN PY 2010 VL 50 IS 3 BP 300 EP 305 DI 10.1016/j.archger.2009.04.016 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 580NB UT WOS:000276454900011 PM 19481271 ER PT J AU Weintraub, D Koester, J Potenza, MN Siderowf, AD Stacy, M Voon, V Whetteckey, J Wunderlich, GR Lang, AE AF Weintraub, Daniel Koester, Juergen Potenza, Marc N. Siderowf, Andrew D. Stacy, Mark Voon, Valerie Whetteckey, Jacqueline Wunderlich, Glen R. Lang, Anthony E. TI Impulse Control Disorders in Parkinson Disease A Cross-Sectional Study of 3090 Patients SO ARCHIVES OF NEUROLOGY LA English DT Article ID BINGE-EATING DISORDER; DOPAMINE AGONISTS; UNITED-STATES; PREVALENCE; BEHAVIORS; DYSREGULATION; EPIDEMIOLOGY; ASSOCIATION; COMORBIDITY; ADDICTIONS AB Context: Anassociation between dopamine-replacement therapies and impulse control disorders (ICDs) in Parkinson disease(PD) has been suggested in preliminary studies. Objectives: To ascertain point prevalence estimates of 4 ICDs in PD and examine their associations with dopamine-replacement therapies and other clinical characteristics. Design: Cross-sectional study using an a priori established sampling procedure for subject recruitment and raters blinded to PD medication status. Patients: Three thousand ninety patients with treated idiopathic PD receiving routine clinical care at 46 movement disorder centers in the United States and Canada. Main Outcome Measures: The Massachusetts Gambling Screen score for current problem/pathological gambling, the Minnesota Impulsive Disorders Interview score for compulsive sexual behavior and buying, and Diagnostic and Statistical Manual of Mental Disorders research criteria for binge-eating disorder. Results: An ICD was identified in 13.6% of patients (gambling in 5.0%, compulsive sexual behavior in 3.5%, compulsive buying in 5.7%, and binge-eating disorder in 4.3%), and 3.9% had 2 or more ICDs. Impulse control disorders were more common in patients treated with a dopamine agonist than in patients not taking a dopamine agonist (17.1% vs 6.9%; odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.54; P<.001). Impulse control disorder frequency was similar for pramipexole and ropinirole (17.7% vs 15.5%; OR, 1.22; 95% CI, 0.94-1.57; P=.14). Additional variables independently associated with ICDs were levodopa use, living in the United States, younger age, being unmarried, current cigarette smoking, and a family history of gambling problems. Conclusions: Dopamine agonist treatment in PD is associated with 2-to 3.5-fold increased odds of having an ICD. This association represents a drug class relationship across ICDs. The association of other demographic and clinical variables with ICDs suggests a complex relationship that requires additional investigation to optimize prevention and treatment strategies. C1 [Weintraub, Daniel; Siderowf, Andrew D.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Potenza, Marc N.] Yale Univ, Sch Med, New Haven, CT USA. [Stacy, Mark] Duke Univ, Med Ctr, Durham, NC USA. [Voon, Valerie; Lang, Anthony E.] Univ Toronto, Toronto, ON, Canada. [Whetteckey, Jacqueline] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Wunderlich, Glen R.] Boehringer Ingelheim Canada Ltd, Burlington, ON, Canada. [Koester, Juergen] Boehringer Ingelheim pharm GmbH & Co KG, Ingelheim, Germany. RP Weintraub, D (reprint author), Univ Penn, Sch Med, 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Boehringer Ingelheim; BrainCells; Merck Serono; Novartis; Ovation; Wyeth; Somaxon; Mohegan Sun Casino; Forest Laboratories pharmaceuticals; National Center for Responsible Gaming and its affiliate; Institute for Research on Gambling Disorders; Teva; Allergan; Osmotica; Biogen; General Electric; Kyowa; Neurologix; Synosia; Ceregene; Eisai; Medtronic; Prestwick; Solvay; Taro FX Dr Weintraub has received consulting fees, honoraria, or grant support from Boehringer Ingelheim, BrainCells, Merck Serono, Novartis, Ovation, and Wyeth. Dr Potenza has received consulting fees or honoraria from Boehringer Ingelheim, has consulted for and has financial interests in Somaxon, has received research support from Mohegan Sun Casino and Forest Laboratories pharmaceuticals, and has consulted for law offices and the federal public defender's office on issues related to ICDs. He has also received support from the National Center for Responsible Gaming and its affiliate, the Institute for Research on Gambling Disorders. Dr Siderowf has received consulting fees or honoraria from Boehringer Ingelheim, Merck Serono, and Teva. Dr Stacy has received consulting fees or honoraria from Allergan, Boehringer Ingelheim, Osmotica, Biogen, General Electric, Kyowa, Neurologix, Novartis, Synosia, and Teva. Dr Lang has received consulting fees or honoraria from Boehringer Ingelheim, Ceregene, Eisai, Medtronic, Novartis, Prestwick, Merck Serono, Solvay, Taro, and Teva. NR 35 TC 487 Z9 495 U1 7 U2 41 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 MAY PY 2010 VL 67 IS 5 BP 589 EP 595 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 593OF UT WOS:000277467000011 PM 20457959 ER PT J AU Yu, CE Marchani, E Nikisch, G Muller, U Nolte, D Hertel, A Wijsman, EM Bird, TD AF Yu, Chang-En Marchani, Elizabeth Nikisch, Georg Mueller, Ulrich Nolte, Dagmar Hertel, Andreas Wijsman, Ellen M. Bird, Thomas D. TI The N141I Mutation in PSEN2 Implications for the Quintessential Case of Alzheimer Disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID AUGUSTE D; CHROMOSOME-1; PATIENT; LOCUS AB Objective: To connect a new family with early-onset Alzheimer disease (EOAD) in Germany to the American Volga German pedigrees. Design: Pedigree molecular genetic analysis. Setting: University Medical Centers in Fulda and Giessen, Germany, and in Seattle, Washington. Results: The families from Fulda, Germany, and the American Volga German families with EOAD share the same N141I PSEN2 mutation on an identical haplotypic background. This establishes that the N141I mutation occurred prior to emigration of the families from the Hesse region to Russia in the 1760s, and documents that relatives of the original immigrant families are presently living in Germany with the mutation and the disease. Conclusion: A family with the N141I mutation in PSEN2 that presently lives in Germany has been connected to the haplotype that carries the same mutation in pedigrees descended from the Volga Germans. This raises the possibility that the original patient with Alzheimer disease (Auguste D.), who had EOAD and lived in this same region of Germany, may also have had the PSEN2 N141I mutation. C1 [Yu, Chang-En; Bird, Thomas D.] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Marchani, Elizabeth; Wijsman, Ellen M.; Bird, Thomas D.] Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Nikisch, Georg] Klinikum Fulda GAG, Dept Psychiat & Psychotherapy, Fulda, Germany. [Hertel, Andreas] Klinikum Fulda GAG, Dept Nucl Med, Fulda, Germany. [Mueller, Ulrich; Nolte, Dagmar] Univ Giessen, Inst Humangenet, Giessen, Germany. RP Bird, TD (reprint author), Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-182 GRECC, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu FU Veterans Affairs Research funds; National Institutes of Health/National Institute on Aging [AG005136-24] FX This study was supported by Veterans Affairs Research funds and National Institutes of Health/National Institute on Aging grant AG005136-24. NR 9 TC 9 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2010 VL 67 IS 5 BP 631 EP 633 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 593OF UT WOS:000277467000017 PM 20457965 ER PT J AU Fang, TJ Li, HY Gliklich, RE Chen, YH Wang, PC Chuang, HF AF Fang, Tuan-Jen Li, Hsueh-Yu Gliklich, Richard E. Chen, Ya-Hui Wang, Pa-Chun Chuang, Hsiu-Feng TI Outcomes of Fat Injection Laryngoplasty in Unilateral Vocal Cord Paralysis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID LARYNGEAL NERVE PARALYSIS; TERM-FOLLOW-UP; AUTOLOGOUS FAT; FOLD PARALYSIS; MEDIALIZATION; VALIDATION AB Objective: To analyze outcomes following fat injection laryngoplasty in patients with unilateral vocal cord paralysis. Design: Longitudinal outcomes evaluation study. Setting: Tertiary referral voice center. Patients: Thirty-three consecutive patients with unilateral vocal cord paralysis undergoing autologous fat injection laryngoplasty with preoperative and serial postoperative follow-up at Chang Gung Memorial Hospital, Taipei, Taiwan. Intervention: Autologous fat injection laryngoplasty. Main Outcome Measures: Voice laboratory measurements, Voice Outcome Survey, and 36-item Short Form Health Survey. Results: Except for the physical functioning dimension of global health, voice-related subjective outcomes and acoustic variables of the patients significantly improved after surgery (P < .05). Compared with population norms, the mean (SD) scores of patients were inferior on the 36-item Short Form Health Survey dimensions of physical functioning (80.7 [22.3] vs 90.2 [17.4]) and role functioning physical problems (65.0 [36.2] vs 80.2 [36.2]). Overall, 88.9% (24 of 27) of the patients were satisfied with their surgery. Conclusions: Fat injection laryngoplasty seems to be effective in enhancing acoustic and quality of life outcomes in patients with unilateral vocal cord paralysis. The effect is sustainable over 12 months. C1 [Wang, Pa-Chun] Cathay Gen Hosp, Dept Otolaryngol, Taipei 106, Taiwan. [Fang, Tuan-Jen; Chuang, Hsiu-Feng] Chang Gung Mem Hosp, Dept Otolaryngol, Chilung, Taiwan. [Fang, Tuan-Jen; Li, Hsueh-Yu] Chang Gung Univ, Sch Med, Tao Yuan, Taiwan. [Wang, Pa-Chun] Fu Jen Catholic Univ, Sch Med, Taipei, Taiwan. [Li, Hsueh-Yu] Chang Gung Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. [Chen, Ya-Hui] Cathay Med Res Inst, Taipei, Taiwan. [Wang, Pa-Chun] China Med Univ, Sch Publ Hlth, Taichung, Taiwan. [Gliklich, Richard E.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Gliklich, Richard E.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Wang, PC (reprint author), Cathay Gen Hosp, Dept Otolaryngol, 280 Jen Ai Rd,Sect 4, Taipei 106, Taiwan. EM drtony@tpts4.seed.net.tw NR 25 TC 9 Z9 9 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2010 VL 136 IS 5 BP 457 EP 462 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 594CH UT WOS:000277510300008 PM 20479375 ER PT J AU Koontz, AM Brindle, ED Kankipati, P Feathers, D Cooper, RA AF Koontz, Alicia M. Brindle, Eric D. Kankipati, Padmaja Feathers, David Cooper, Rory A. TI Design Features That Affect the Maneuverability of Wheelchairs and Scooters SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Architectural accessibility; Rehabilitation; Wheelchairs ID USERS; PARTICIPATION; PROPULSION; POSITION; RECLINE; TILT AB Objective: To determine the minimum space required for wheeled mobility device users to perform 4 maneuverability tasks and to investigate the impact of selected design attributes on space. Design: Case series. Setting: University laboratory, Veterans Affairs research facility, vocational training center, and a national wheelchair sport event. Participants: The sample of convenience included manual wheelchair (MWC; n=109), power wheelchair (PWC; n=100), and scooter users (n=14). Intervention: A mock environment was constructed to create passageways to form an L-turn, 360 degrees-turn in place, and a U-turn with and without a barrier. Passageway openings were increased in 5-cm increments until the user could successfully perform each task without hitting the walls. Structural dimensions of the device and user were collected using an electromechanical probe. Mobility devices were grouped into categories based on design features and compared using I-way analysis of variance and post hoc pairwise Bonferroni-corrected tests. Main Outcome Measure: Minimum passageway widths for the 4 maneuverability tasks. Results: Ultra light MWCs with rear axles posterior to the shoulder had the shortest lengths and required the least amount of space compared with all other types of MWCs (P<.05). Mid-wheel-drive PWCs required the least space for the 360 degrees-turn in place compared with front-wheel-drive and rear-wheel-drive PWCs (P<.01) but performed equally as well as front-wheel-drive models on all other turning tasks. PWCs with seat functions required more space to perform the tasks. Conclusions: Between 10% and 100% of users would not be able to maneuver in spaces that meet current Accessibility Guidelines for Buildings and Facilities specifications. This study provides data that can be used to support wheelchair prescription and home modifications and to update standards to improve the accessibility of public areas. C1 [Koontz, Alicia M.; Brindle, Eric D.; Kankipati, Padmaja; Cooper, Rory A.] Vet Affairs Pittsburgh HealthCare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Koontz, Alicia M.; Brindle, Eric D.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Koontz, Alicia M.; Kankipati, Padmaja; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Feathers, David] Cornell Univ, Dept Design & Environm Analy, Ithaca, NY USA. RP Koontz, AM (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1H, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu FU United States Access Board [070213]; Department of Veterans Affairs Rehabilitation Research & Development Service [B3142C]; National Science Foundation [EEC 0552351] FX Supported by the United States Access Board (project no. 070213). Department of Veterans Affairs Rehabilitation Research & Development Service (project no. B3142C), and the National Science Foundation (grant no. EEC 0552351). NR 14 TC 10 Z9 10 U1 3 U2 14 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 MAY PY 2010 VL 91 IS 5 BP 759 EP 764 DI 10.1016/j.apmr.2010.01.009 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 594LK UT WOS:000277539000013 PM 20434614 ER PT J AU Harrington, DT Phillips, B Machan, J Zacharias, N Velmahos, GC Rosenblatt, MS Winston, E Patterson, L Desjardins, S Winchell, R Brotman, S Churyla, A Schulz, JT Maung, AA Davis, KA AF Harrington, David T. Phillips, Benjamin Machan, Jason Zacharias, Nikos Velmahos, George C. Rosenblatt, Michael S. Winston, Eleanor Patterson, Lisa Desjardins, Steven Winchell, Robert Brotman, Sheldon Churyla, Andrei Schulz, John T. Maung, Adrian A. Davis, Kimberly A. CA ReCONECT TI Factors Associated With Survival Following Blunt Chest Trauma in Older Patients Results From a Large Regional Trauma Cooperative SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the New-England-Surgical-Society CY SEP 11, 2009 CL Newport, RI SP New England Surg Soc ID MULTIPLE RIB FRACTURES; EPIDURAL ANALGESIA; GERIATRIC-PATIENTS; EARLY TRACHEOSTOMY; MANAGEMENT; INJURY; MORTALITY; MORBIDITY; OUTCOMES AB Hypothesis: We hypothesized that patient factors, injury patterns, and therapeutic interventions influence outcomes among older patients incurring traumatic chest injuries. Design: Patients older than 50 years with at least 1 rib fracture (RF) were retrospectively studied, including institutional data, patient data, clinical interventions, and complications. Univariable and multivariable analyses were performed. Setting: Eight trauma centers. Patients: A total of 1621 patients. Main Outcome Measure: Survival. Results: Patient data collected include the following: age (mean, 70.1 years), number of RFs (mean, 3.7), Abbreviated Injury Scale chest score (mean, 2.7), Injury Severity Score (mean, 11.7), and mortality (overall, 4.6%). On univariable analysis, increased mortality was associated with admission to high-volume trauma centers and level I centers, preexisting coronary artery disease or congestive heart failure, intubation or development of pneumonia, and increasing age, Injury Severity Score, and number of RFs. On multivariable analysis, strongest predictors of mortality were admission to high-volume trauma centers, preexisting congestive heart failure, intubation, and increasing age and Injury Severity Score. Using this predictive model, tracheostomy and patient-controlled analgesia had protective effects on survival. Conclusions: In a large regional trauma cooperative, increasing age and Injury Severity Score were independent predictors of survival among older patients incurring traumatic RFs. Admission to high-volume trauma centers, preexisting congestive heart failure, and intubation added to mortality. Therapies associated with improved survival were patient-controlled analgesia and tracheostomy. Further regional cooperation should allow development of standard care practices for these challenging patients. C1 [Harrington, David T.; Phillips, Benjamin; Machan, Jason] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Surg, Providence, RI 02903 USA. [Zacharias, Nikos; Velmahos, George C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenblatt, Michael S.] Lahey Clin Fdn, Burlington, MA USA. [Winston, Eleanor; Patterson, Lisa] Baystate Med Ctr, Springfield, MA 01199 USA. [Brotman, Sheldon; Churyla, Andrei] Berkshire Med Ctr, Pittsfield, MA USA. [Desjardins, Steven; Winchell, Robert] Maine Med Ctr, Portland, ME USA. [Schulz, John T.] Bridgeport Hosp, Bridgeport, CT USA. [Maung, Adrian A.; Davis, Kimberly A.] Yale Univ, Sch Med, New Haven, CT USA. [Maung, Adrian A.; Davis, Kimberly A.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. RP Harrington, DT (reprint author), Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Surg, 593 Eddy St,Ambulatory Patient Care Bldg,Room 443, Providence, RI 02903 USA. EM dharrington@usasurg.org RI Machan, Jason/D-3897-2013 OI Machan, Jason/0000-0003-2048-4914 NR 31 TC 21 Z9 22 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2010 VL 145 IS 5 BP 432 EP 437 PG 6 WC Surgery SC Surgery GA 597SV UT WOS:000277782800004 PM 20479340 ER PT J AU Ferguson, CM AF Ferguson, Charles M. TI A Rose by Another Name INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. RP Ferguson, CM (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, 5 Parkman St,WACC 465, Boston, MA 02114 USA. EM cferguson@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2010 VL 145 IS 5 BP 451 EP 451 PG 1 WC Surgery SC Surgery GA 597SV UT WOS:000277782800009 PM 20491162 ER PT J AU Zacharias, N Velmahos, GC Salama, A Alam, HB de Moya, M King, DR Novelline, RA AF Zacharias, Nikos Velmahos, George C. Salama, Ahmed Alam, Hasan B. de Moya, Marc King, David R. Novelline, Robert A. TI Diagnosis of Necrotizing Soft Tissue Infections by Computed Tomography SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the New-England-Surgical-Society CY SEP 11, 2009 CL Newport, RI SP New England Surg Soc ID FASCIITIS; NECK; CT AB Hypothesis: In contrast to previous beliefs, we hypothesize that computed tomography (CT) scanning is sensitive and specific for the diagnosis of necrotizing soft tissue infections (NSTIs). Design: Retrospective and prospective case series. Setting: Academic medical center. Patients: Patients who were clinically suspected of having NSTIs from January 1, 2003, through April 30, 2009, and who underwent imaging with a 16- or 64-section helical CT scanner were studied. The CT result was considered positive if inflamed and necrotic tissue with or without gas or fluid collections across tissue planes was found. The disease (NSTI) was considered present if surgical exploration revealed elements of infection and necrosis of the soft tissues and pathological analysis confirmed the findings. The disease was considered absent if surgical exploration and pathological analysis failed to identify any of these findings or the patient was successfully treated without surgical exploration. Main Outcome Measures: Sensitivity and specificity of CT for diagnosing NSTI. Results: Of 67 patients with study inclusion criteria, 58 underwent surgical exploration, and NSTI was confirmed in 25 (43%). The remaining 42 patients had either nonnecrotizing infections during surgical exploration (n=33) or were treated nonoperatively with successful resolution of the symptoms (n=9). The sensitivity of CT to identify NSTI was 100%, specificity was 81%, positive predictive value was 76%, and negative predictive value was 100%. No differences were found in demographics, white blood cell count on admission, symptoms, or site of infection between those with a false-or true-positive CT result. Conclusions: A negative CT result reliably excludes the diagnosis of NSTI. A positive CT result correctly identifies the disease with a high likelihood. C1 [Zacharias, Nikos; Velmahos, George C.; Salama, Ahmed; Alam, Hasan B.; de Moya, Marc; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Novelline, Robert A.] Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. NR 15 TC 28 Z9 29 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2010 VL 145 IS 5 BP 452 EP 455 PG 4 WC Surgery SC Surgery GA 597SV UT WOS:000277782800010 PM 20479343 ER PT J AU Velmahos, GC Zacharias, N Emhoff, TA Feeney, JM Hurst, JM Crookes, BA Harrington, DT Gregg, SC Brotman, S Burke, PA Davis, KA Gupta, R Winchell, RJ Desjardins, S Alouidor, R Gross, RI Rosenblatt, MS Schulz, JT Chang, YC AF Velmahos, George C. Zacharias, Nikos Emhoff, Timothy A. Feeney, James M. Hurst, James M. Crookes, Bruce A. Harrington, David T. Gregg, Shea C. Brotman, Sheldon Burke, Peter A. Davis, Kimberly A. Gupta, Rajan Winchell, Robert J. Desjardins, Steven Alouidor, Reginald Gross, Ronald I. Rosenblatt, Michael S. Schulz, John T. Chang, Yuchiao TI Management of the Most Severely Injured Spleen A Multicenter Study of the Research Consortium of New England Centers for Trauma (ReCONECT) SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the New-England-Surgical-Society CY SEP 11, 2009 CL Newport, RI SP New England Surg Soc ID BLUNT SPLENIC INJURIES; NONOPERATIVE MANAGEMENT; ORGAN INJURY; FAILURE; ADULTS; LIVER; EMBOLIZATION; ANGIOGRAPHY; ASSOCIATION; SUCCESS AB Objective: To determine the rate and predictors of failure of nonoperative management (NOM) in grade IV and V blunt splenic injuries (BSI). Design: Retrospective case series. Setting: Fourteen trauma centers in New England. Patients: A total of 388 adult patients with a grade IV or V BSI who were admitted between January 1, 2001, and August 31, 2008. Main Outcome Measures: Failure of NOM (f-NOM). Results: A total of 164 patients (42%) were operated on immediately. Of the remaining 224 who were offered a trial of NOM, the treatment failed in 85 patients (38%). At the end, 64% of patients required surgery. Multivariate analysis identified 2 independent predictors of f-NOM: grade V BSI and the presence of a brain injury. The likelihood of f-NOM was 32% if no predictor was present, 56% if 1 was present, and 100% if both were present. The mortality of patients for whom NOM failed was almost 7-fold higher than those with successful NOM (4.7% vs 0.7%; P=.07). Conclusions: Nearly two-thirds of patients with grade IV or V BSI require surgery. A grade V BSI and brain injury predict failure of NOM. This data must be taken into account when generalizations are made about the overall high success rates of NOM, which do not represent severe BSI. C1 [Velmahos, George C.; Zacharias, Nikos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02030 USA. [Velmahos, George C.; Zacharias, Nikos] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Emhoff, Timothy A.] Univ Massachusetts, Mem Hosp, Worcester, MA USA. [Feeney, James M.] Hartford Hosp, Hartford, CT 06115 USA. [Feeney, James M.] Univ Connecticut, Hartford, CT 06112 USA. [Hurst, James M.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Crookes, Bruce A.] Fletcher Allen Healthcare, Burlington, MA USA. [Crookes, Bruce A.] Univ Vermont, Burlington, VT 05405 USA. [Harrington, David T.; Gregg, Shea C.] Rhode Isl Hosp, Providence, RI USA. [Harrington, David T.; Gregg, Shea C.] Brown Univ, Providence, RI 02912 USA. [Brotman, Sheldon] Berkshire Med Ctr, Pittsfield, MA USA. [Burke, Peter A.] Boston Med Ctr, Boston, MA USA. [Burke, Peter A.] Boston Univ, Boston, MA 02215 USA. [Davis, Kimberly A.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Davis, Kimberly A.] Yale Univ, New Haven, CT USA. [Gupta, Rajan; Winchell, Robert J.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Winchell, Robert J.; Desjardins, Steven] Maine Med Ctr, Portland, ME USA. [Alouidor, Reginald; Gross, Ronald I.] Baystate Med Ctr, Springfield, MA USA. [Rosenblatt, Michael S.] Lahey Clin Fdn, Burlington, MA USA. [Schulz, John T.] Bridgeport Hosp, Bridgeport, CT USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Clin Epidemiol, Boston, MA 02030 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02030 USA. EM gvelmahos@partners.org NR 20 TC 32 Z9 36 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2010 VL 145 IS 5 BP 456 EP 460 PG 5 WC Surgery SC Surgery GA 597SV UT WOS:000277782800012 PM 20479344 ER PT J AU LaFemina, J Vagefi, PA Warshaw, AL Fernandez-del Castillo, C AF LaFemina, Jennifer Vagefi, Parsia A. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Transgastric Pancreaticogastric Anastomosis An Alternative Operative Approach for Middle Pancreatectomy SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the New-England-Surgical-Society CY SEP 11, 2009 CL Newport, RI SP New England Surg Soc ID CHRONIC-PANCREATITIS; DISTAL PANCREATECTOMY; MEDIAL PANCREATECTOMY; RESECTION; PANCREATICODUODENECTOMY; NECK; PANCREATODUODENECTOMY; EXPERIENCE; MANAGEMENT; MORBIDITY AB Objective: To determine short-term outcomes following middle pancreatectomy with transgastric pancreati-cogastric anastomosis. Design, Setting, and Patients: A retrospective analysis of 23 patients who underwent middle pancreatectomy with transgastric pancreaticogastric anastomosis at the Massachusetts General Hospital, Boston, from June 22, 2005, through April 29, 2009. Main Outcome Measures: Indications for procedure, operative time, length of stay, morbidity, mortality, and need for readmission, antibiotics, reoperation, additional procedures, or transfusion. Results: The mean age of 15 women and 8 men who underwent middle pancreatectomy with transgastric pancreaticogastric anastomosis was 55.0 years. The median follow-up time was 12.9 months. The most commonly resected tumors were intraductal papillary mucinous neoplasms (n=9), serous cystadenomas (n=5), and neuroendocrine tumors (n=4). The mean (SD) operative time was 191 (39) minutes. No patients required intraoperative transfusion. The median hospital stay was 5 days. The most common complications were pancreatic fistula (n=6), intra-abdominal abscess (n=4), and superficial skin infection (n=4). Three patients had splenic artery pseudoaneurysms. Seven patients required readmission; 2 required reoperation. No patients developed postoperative new or worsening endocrine or exocrine insufficiency. There were no deaths. Conclusions: Middle pancreatectomy with transgastric pancreaticogastric anastomosis offers a safe alternative to the traditional Roux-en-y pancreaticojejunostomy and may be technically simpler. C1 [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WAC 4-460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 37 TC 7 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2010 VL 145 IS 5 BP 476 EP 481 PG 6 WC Surgery SC Surgery GA 597SV UT WOS:000277782800016 PM 20479347 ER PT J AU Chang, A Hochberg, M Song, J Dunlop, D Chmiel, JS Nevitt, M Hayes, K Eaton, C Bathon, J Jackson, R Kwoh, CK Sharma, L AF Chang, Alison Hochberg, Marc Song, Jing Dunlop, Dorothy Chmiel, Joan S. Nevitt, Michael Hayes, Karen Eaton, Charles Bathon, Joan Jackson, Rebecca Kwoh, C. Kent Sharma, Leena TI Frequency of Varus and Valgus Thrust and Factors Associated With Thrust Presence in Persons With or at Higher Risk of Developing Knee Osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MAXIMAL ISOMETRIC STRENGTH; AFRICAN-AMERICANS; MUSCLE STRENGTH; WEDGED INSOLES; WOMEN; MEN; CAUCASIANS; ALIGNMENT; HEALTHY; PROJECT AB Objective. Varus thrust observed during gait has been shown to be associated with a 4-fold increase in the risk of medial knee osteoarthritis (OA) progression. Valgus thrust is believed to be less common than varus thrust; the prevalence of each is uncertain. Racial differences in risk factors may help explain variations in the natural history of knee OA. We undertook this study to determine the frequency of varus and valgus thrust in African Americans and Caucasians and to identify factors associated with thrust presence. Methods. The Osteoarthritis Initiative cohort includes men and women who have knee OA or are at increased risk of developing it. Trained examiners assessed thrust presence by gait observation. Logistic regression with generalized estimating equations was used to identify factors associated with thrust presence, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results. Compared with Caucasians, African Americans had lower odds of varus thrust, controlling for age, sex, body mass index (BMI), injury, surgery, disease severity, strength, pain, and alignment in persons without knee OA (adjusted OR 0.50 [95% CI 0.36, 0.72]) and in those with knee OA (adjusted OR 0.46 [95% CI 0.34, 0.61]). Also independently associated with varus thrust were age, sex, BMI, disease severity, strength, and alignment. The odds of valgus thrust were greater for African Americans than for Caucasians in persons without knee OA (adjusted OR 1.69 [95% CI 1.02, 2.80]) and in those with knee OA (adjusted OR 1.98 [95% CI 1.35, 2.91]). Also independently associated with valgus thrust were disease severity and malalignment. Conclusion. Compared with Caucasians, African Americans had lower odds of varus thrust and greater odds of valgus thrust. These findings may help explain the difference between these groups in the pattern of OA involvement at the knee. C1 [Sharma, Leena] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Hochberg, Marc] Univ Maryland, Baltimore, MD 21201 USA. [Nevitt, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eaton, Charles] Brown Univ, Pawtucket, RI USA. [Bathon, Joan] Johns Hopkins Univ, Baltimore, MD USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Sharma, L (reprint author), Northwestern Univ, Feinberg Sch Med, Div Rheumatol, 240 E Huron St,Suite M300, Chicago, IL 60611 USA. EM L-Sharma@northwestern.edu RI Chang, Alison/D-8203-2011; OI Chang, Alison/0000-0001-7309-9687 FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS]) [R01-AR-52918]; OAI; NIH [N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, N01-AR-2-2262]; Merck Research Laboratories; Novartis Pharmaceuticals Corporation; GlaxoSmithKline; Pfizer, Inc.; Roche; Crescendo Biosciences FX Supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] grant R01-AR-52918) and the OAI. The OAI is a public-private partnership comprising five contracts (N01-AR-2-2258, N01-AR-2-2259, N01-AR-2-2260, N01-AR-2-2261, and N01-AR-2-2262) funded by the NIH and conducted by the OAI Study Investigators. Private funding partners include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer, Inc. Private sector funding for the OAI is managed by the Foundation for the NIH. This article was prepared using an OAI public use data set in addition to data obtained within an NIH/NIAMS-funded ancillary grant.; Dr. Hayes receives royalties for the Manual for Physical Agents, 5th edition, Prentice Hall, 2000. Dr. Bathon has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000) and Crescendo Biosciences (more than $10,000). NR 23 TC 22 Z9 22 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2010 VL 62 IS 5 BP 1403 EP 1411 DI 10.1002/art.27377 PG 9 WC Rheumatology SC Rheumatology GA 619LT UT WOS:000279432400023 PM 20213800 ER PT J AU Chu, CR Williams, A Tolliver, D Kwoh, CK Bruno, S Irrgang, JJ AF Chu, Constance R. Williams, Ashley Tolliver, David Kwoh, C. Kent Bruno, Stephen, III Irrgang, James J. TI Clinical Optical Coherence Tomography of Early Articular Cartilage Degeneration in Patients With Degenerative Meniscal Tears SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; KNEE OSTEOARTHRITIS; MRI; T2; DEGRADATION; RUPTURE; DISEASE; IMPACT; REPAIR; T-2 AB Objective. Quantitative and nondestructive methods for clinical diagnosis and staging of articular cartilage degeneration are important to the evaluation of potential disease-modifying treatments in osteoarthritis (OA). Optical coherence tomography (OCT) is a novel imaging technology that can generate microscopic-resolution cross-sectional images of articular cartilage in near real-time. This study tested the hypotheses that OCT can be used clinically to identify early cartilage degeneration and that OCT findings correlate with magnetic resonance imaging (MRI) T2 values and arthroscopy results. Methods. Patients undergoing arthroscopy for degenerative meniscal tears were recruited under Institutional Review Board-approved protocols. Thirty consecutive subjects completing preoperative 3.0T MRI, arthroscopy, and intraoperative OCT comprised the study group. Qualitative and quantitative OCT results and MRI T2 values were compared with modified Outerbridge cartilage degeneration scores (0-4 scale) assigned at arthroscopy. Results. Arthroscopic grades showed cartilage abnormality in 23 of the 30 patients. OCT grades were abnormal in 28 of the 30 patients. Both qualitative and quantitative OCT strongly correlated with the arthroscopy results (P = 0.004 and P = 0.0002, respectively, by Kruskal-Wallis test). Neither the superficial nor the deep cartilage T2 values correlated with the arthroscopy results. The quantitative OCT results correlated with the T2 values in the superficial cartilage (Pearson's r = 0.39, P = 0.03). Conclusion. These data show that OCT can be used clinically to provide qualitative and quantitative assessments of early articular cartilage degeneration that strongly correlate with arthroscopy results. The correlation between the quantitative OCT values and T2 values for the superficial cartilage further supports the utility of OCT as a clinical research tool, providing quantifiable microscopic resolution data on the articular cartilage structure. New technologies for nondestructive quantitative assessment of human articular cartilage degeneration may facilitate the development of strategies to delay or prevent the onset of OA. C1 [Chu, Constance R.] Univ Pittsburgh, Cartilage Restorat Ctr, Pittsburgh, PA 15213 USA. [Tolliver, David] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Chu, CR (reprint author), Univ Pittsburgh, Cartilage Restorat Ctr, 3471 5th Ave,Suite 911, Pittsburgh, PA 15213 USA. EM chucr@upmc.edu FU NIH [1-R01-AR-052784-CRC] FX Supported by the NIH (grant 1-R01-AR-052784-CRC). NR 35 TC 37 Z9 39 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2010 VL 62 IS 5 BP 1412 EP 1420 DI 10.1002/art.27378 PG 9 WC Rheumatology SC Rheumatology GA 619LT UT WOS:000279432400024 PM 20213801 ER PT J AU Kristo, F Hardy, GJ Anderson, TJT Sinha, S Ahluwalia, N Lin, AY Passeri, J Scherrer-Crosbie, M Gerszten, RE AF Kristo, Fjoralba Hardy, Gregory J. Anderson, Thomas J. T. Sinha, Sumita Ahluwalia, Neil Lin, Alexander Y. Passeri, Jonathan Scherrer-Crosbie, Marielle Gerszten, Robert E. TI Pharmacological inhibition of BLT1 diminishes early abdominal aneurysm formation SO ATHEROSCLEROSIS LA English DT Article DE Abdominal aortic aneurysm; BLT1; Angiotensin II ID LEUKOTRIENE B-4 RECEPTORS; E-DEFICIENT MICE; SMOOTH-MUSCLE-CELLS; N-TERMINAL KINASE; AORTIC-ANEURYSM; 5-LIPOXYGENASE PATHWAY; ATHEROSCLEROTIC LESIONS; ANTAGONIST CP-105,696; MYOCARDIAL-INFARCTION; BLT1-DEFICIENT MICE AB Leukotriene B4 (LTB4) is a pro-inflammatory lipid mediator generated by the enzymes 5-lipoxygenase (5-LO) and LTA4-hydrolase. LTB4 signals primarily through its G protein-coupled receptor BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. Here we tested the hypothesis that pharmacological inhibition of BLT1 diminishes abdominal aortic aneurysm (AAA) formation, a major complication associated with atherosclerotic vascular disease. Chow-fed Apoe(-/-) mice were treated with a 4-week infusion of Angiotensin II (AngII, 1000 ng/(kg min)) beginning at 10 weeks of age, in a well-established murine AAA model. Administration of the selective BLT1 antagonist CP-105,696 beginning simultaneously with AngII infusion reduced the incidence of AAA formation from 82% to 40% (p < 0.05). There was a concordant reduction in maximal aortic diameter from 2.35 mm to 1.56 mm (p < 0.05). While administration of the antagonist on day 14 after the onset of AngII infusion diminished lesional macrophage accumulation, it did not significantly alter the size of AAA by day 42. Thus, pharmacological inhibition of BLT1 may ultimately hold clinical promise, but early intervention may be critical. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Ahluwalia, Neil; Lin, Alexander Y.; Passeri, Jonathan; Scherrer-Crosbie, Marielle; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. [Kristo, Fjoralba; Hardy, Gregory J.; Anderson, Thomas J. T.; Sinha, Sumita; Ahluwalia, Neil; Lin, Alexander Y.; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Gerszten, Robert E.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, 149,13th St,Room 8307, Charlestown, MA 02129 USA. EM rgerszten@partners.org OI Hardy, Gregory/0000-0002-6191-4530; Kristo, Fjoralba/0000-0002-8045-9756; Anderson, Thomas/0000-0002-2762-6703 FU NIH [S10RR022586] FX This work was funded in part by NIH grant S10RR022586. NR 29 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2010 VL 210 IS 1 BP 107 EP 113 DI 10.1016/j.atherosclerosis.2009.11.031 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 588PR UT WOS:000277085300017 PM 20035940 ER PT J AU Cavusoglu, E Ruwende, C Chopra, V Poludasu, S Yanamadala, S Frishman, WH Eng, C Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Ruwende, Cyril Chopra, Vineet Poludasu, Shyam Yanamadala, Sunitha Frishman, William H. Eng, Calvin Pinsky, David J. Marmur, Jonathan D. TI Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography SO ATHEROSCLEROSIS LA English DT Article DE Biomarker; Nitric oxide; ADMA; Diabetes mellitus; Myocardial infarction; Prognosis ID ASYMMETRIC DIMETHYLARGININE ADMA; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL DYSFUNCTION; ENDOGENOUS INHIBITOR; OXIDATIVE STRESS; ARTERY-DISEASE; EVENTS; RISK; NEPHROPATHY; DEATH AB Background: Patients with diabetes mellitus (DM) have been shown to have higher levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Higher plasma levels of ADMA have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis by lowering NO levels. High baseline plasma levels of ADMA in patients with DM have been shown to predict diabetes related complications. However, there are limited data on the prognostic significance of baseline ADMA levels in patients with established DM. Methods: The present study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 170 high-risk diabetic men with known or suspected coronary artery disease who were referred for coronary angiography. All patients were followed prospectively for the development of vascular outcomes, including all-cause mortality. Results: After controlling for a variety of baseline variables (including established biomarkers such as hs-CRP and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of all-cause mortality (HR 2.63, 95% CI 1.13-6.11, p = 0.0247) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality or MI (fatal or non-fatal) (HR 2.44, 95% CI 1.26-4.72, p = 0.0079), as well as the composite outcome of all-cause mortality, MI (fatal or nonfatal), or stroke (HR 2.00, 95% CI 1.10-3.62, p = 0.0232). Conclusion: These data demonstrate that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including all-cause mortality) in patients with DM. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Cavusoglu, Erdal; Poludasu, Shyam; Marmur, Jonathan D.] Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Ruwende, Cyril; Yanamadala, Sunitha; Pinsky, David J.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Frishman, William H.] New York Med Coll, Dept Med, Westchester Med Ctr, Valhalla, NY 10595 USA. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, Dept Med, Div Cardiol, 450 Clarkson Ave,Box 1199, Brooklyn, NY 11203 USA. EM ECavusoglu@aol.com NR 31 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2010 VL 210 IS 1 BP 226 EP 231 DI 10.1016/j.atherosclerosis.2009.10.034 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 588PR UT WOS:000277085300037 PM 19944421 ER PT J AU Turner, AP Jakupcak, M AF Turner, Aaron P. Jakupcak, Matthew TI Behavioral Activation for Treatment of PTSD and Depression in an Iraqi Combat Veteran with Multiple Physical Injuries SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY LA English DT Article DE Behavioral activation; PTSD; depression; rehabilitation; veteran ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN; THERAPY; WAR AB Background: Physical injury and psychological trauma associated with combat in the wars in Iraq and Afghanistan frequently lead to a constellation of symptoms including pain, post traumatic stress disorder (PTSD), and depression. Method: This single case study describes the application of a behaviorally-based psychotherapy known as behavioral activation for the treatment of post traumatic stress disorder (PTSD) and depressive symptoms in a recent combat veteran with multiple physical injuries sustained from a blast injury. Treatment was provided concurrently with other rehabilitation services and consisted of weekly individual sessions for 4 months, followed by monthly sessions for 4 months. Results: Clinically significant reductions in PTSD and depressive symptoms were noted between baseline and 1 year follow-up. Conclusion: Preliminary evidence from this case suggests that behavioral activation may be a promising treatment for PTSD and depression, and can be readily tailored to individuals with physical limitations such as pain and mobility restriction. Treatment can be provided in the context of concurrent interdisciplinary medical and rehabilitation care. C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM aaron.turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 17 TC 8 Z9 9 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1352-4658 J9 BEHAV COGN PSYCHOTH JI Behav. Cognit. Psychther. PD MAY PY 2010 VL 38 IS 3 BP 355 EP 361 DI 10.1017/S1352465810000081 PG 7 WC Psychology, Clinical SC Psychology GA 603LC UT WOS:000278209100007 PM 20374670 ER PT J AU Head, D Isom, M AF Head, Denise Isom, Marlisa TI Age effects on wayfinding and route learning skills SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Response learning; Place learning; Cognitive map; Virtual reality ID MEDIAL PREFRONTAL CORTEX; HUMAN SPATIAL NAVIGATION; FORNIX AND/OR ABLATION; MORRIS WATER MAZE; ALZHEIMERS-DISEASE; TEMPORAL-ORDER; ELDERLY ADULTS; COGNITIVE MAPS; FIMBRIA-FORNIX; HUMAN BRAIN AB While existing evidence suggests that older adults have compromised spatial navigation abilities, the effects of age on specific aspects of navigational skill are less well specified. The current study examined age effects on spatial navigation abilities considering the multiple cognitive and neural factors that contribute to successful navigation. Young and older adults completed wayfinding and route learning tasks in a virtual environment and aspects of environmental knowledge were assessed. Prefrontal, caudate and hippocampal volumes were obtained in a subset of older adults. Age differences were observed in both wayfinding and route learning. For wayfinding, there were age effects in recalling landmarks, and recognizing environmental scenes. In the route learning condition, older adults evidenced difficulty with the location, temporal order and directional information of landmarks. In both conditions, there was evidence of age-related differences in the acquisition of configural knowledge. Wayfinding was associated with the hippocampus whereas route learning was associated with the caudate nucleus. These results provide indications of specific aspects of navigational learning that may contribute to age-related declines and potential neural substrates. (C) 2010 Elsevier B.V. All rights reserved. C1 [Head, Denise] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Head, Denise] Washington Univ, Dept Radiol, St Louis, MO 63130 USA. [Isom, Marlisa] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Head, D (reprint author), Washington Univ, Dept Psychol, Campus Box 1125,1 Brookings Dr, St Louis, MO 63130 USA. EM dhead@wustl.edu FU McDonnell Center for Higher Brain FX This work was supported in part by the McDonnell Center for Higher Brain functions. We thank Paul Speigel and Rachel Bock for virtual reality programming, and Dana Cooper, Jennifer Travis and Tanya Antonini for assistance with data collection. NR 71 TC 66 Z9 66 U1 5 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAY 1 PY 2010 VL 209 IS 1 BP 49 EP 58 DI 10.1016/j.bbr.2010.01.012 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 582FW UT WOS:000276582900007 PM 20085784 ER PT J AU Ifediba, MA Medarova, Z Ng, SW Yang, JZ Moore, A AF Ifediba, Marytheresa A. Medarova, Zdravka Ng, Shu-wing Yang, Junzheng Moore, Anna TI siRNA Delivery to CNS Cells using a Membrane Translocation Peptide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IN-VIVO; PENETRATING PEPTIDES; MAMMALIAN-CELLS; INTERFERING RNA; PROTEIN; SYSTEM; GENE AB RNA interference (RNAi) is a sequence-specific gene silencing technique that has been applied to multiple pathological conditions. In this report, we describe the generation and in vitro characterization of an RNAi-based fluorescent probe for use as a therapeutic in the setting of ischemic stroke. Probe delivery to bEnd.3 brain endothelial cells and primary cortical neurons and astrocytes was promoted by incorporating small interfering RNA (siRNA) into complexes with fluorescently labeled myristoylated polyarginine peptides. The resulting probe was partially protected form serum nuclease degradation and was efficiently internalized by cells as confirmed by flow cytometry and confocal microscopy. In addition, application of the siRNA probe directed against c-Src, a protein implicated in stroke pathology, led to statistically significant reduction of endogenous c-src mRNA levels in all cell types tested. Results demonstrate the proof-of-principle that functionalized peptide siRNA probes can be used as potential tools for dual imaging and therapeutic applications. C1 [Moore, Anna] Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp,Mol Imaging Lab, Charlestown, MA 02129 USA. [Ng, Shu-wing; Yang, Junzheng] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Ifediba, Marytheresa A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Ifediba, Marytheresa A.] MIT, Harvard MIT Div Hlth Sci & Technol HST, Cambridge, MA 02139 USA. RP Ifediba, MA (reprint author), Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp,Mol Imaging Lab, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering (NIBIB) [T32 EB001680] FX This publication was made possible through partial grant support by grant T32 EB001680 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB). NR 20 TC 21 Z9 22 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY PY 2010 VL 21 IS 5 BP 803 EP 806 DI 10.1021/bc900488e PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 596KI UT WOS:000277683300002 PM 20420373 ER PT J AU Koenigsberg, HW Fan, J Liu, X Guise, K Ochsner, KN Guerreri, S New, AS Goodman, M Siever, LJ AF Koenigsberg, Harold W. Fan, Jin Liu, Xun Guise, Kevin Ochsner, Kevin N. Guerreri, Stephanie New, Antonia S. Goodman, Marianne Siever, Larry J. TI Sensitization and Habituation of Neural Networks in Response to Aversive Social Cues in Borderline and Avoidant Personality Disorder Patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Koenigsberg, Harold W.; Fan, Jin; Liu, Xun; Guise, Kevin; Guerreri, Stephanie; New, Antonia S.; Goodman, Marianne; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA. [Koenigsberg, Harold W.; New, Antonia S.; Goodman, Marianne; Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. [Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. RI Liu, Xun/C-2400-2009 OI Liu, Xun/0000-0003-1366-8926 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 59 BP 19S EP 19S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200059 ER PT J AU Petryshen, T Lewis, M Pan, J Clore, E Berry-Scott, E Riley, M Holson, E Haggarty, S AF Petryshen, Tracey Lewis, Michael Pan, Jennifer Clore, Elizabeth Berry-Scott, Erin Riley, Misha Holson, Ed Haggarty, Stephen TI Highly Selective GSK3 Inhibition Modulates Affective Behaviors in Mouse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Petryshen, Tracey; Lewis, Michael; Clore, Elizabeth; Berry-Scott, Erin; Riley, Misha] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Petryshen, Tracey; Lewis, Michael; Pan, Jennifer; Clore, Elizabeth; Berry-Scott, Erin; Riley, Misha; Holson, Ed; Haggarty, Stephen] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Petryshen, Tracey; Haggarty, Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Petryshen, Tracey] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Haggarty, Stephen] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen] Massachusetts Gen Hosp, Dept Neurol, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 83 BP 26S EP 26S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200083 ER PT J AU Milad, M Igoe, SA AF Milad, Mohammed Igoe, Sarah A. TI Estrogen and Progesterone Facilitate Recall of Fear Extinction in Rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Milad, Mohammed; Igoe, Sarah A.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 98 BP 31S EP 31S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200098 ER PT J AU Shiovitz, RN Mitsis, EM Weiner, DM Bang, C Elder, GA Tang, CY Hazlett, EA AF Shiovitz, Rachel N. Mitsis, Effie M. Weiner, Daniel M. Bang, Charlene Elder, Gregory A. Tang, Cheuk Y. Hazlett, Erin A. TI Relationship between DTI White Matter Abnormalities and Impulsivity in OIF/OEF Combat Veterans with Blast-Related Mild TBI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Shiovitz, Rachel N.; Mitsis, Effie M.; Bang, Charlene; Tang, Cheuk Y.; Hazlett, Erin A.] Mt Sinai Sch Med, New York, NY USA. [Hazlett, Erin A.] James J Peters VAMC, MIRECC, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 154 BP 48S EP 48S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200154 ER PT J AU Leussis, MP Berry-Scott, E de Haan, G Riley, MM Richards, K Petryshen, TL AF Leussis, Melanie P. Berry-Scott, Erin de Haan, Georgius Riley, Misha M. Richards, Keenan Petryshen, Tracey L. TI Characterization of the Ankyrin 3 Bipolar Disorder Risk Gene in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Leussis, Melanie P.; de Haan, Georgius; Richards, Keenan; Petryshen, Tracey L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Leussis, Melanie P.; Berry-Scott, Erin; de Haan, Georgius; Riley, Misha M.; Petryshen, Tracey L.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Leussis, Melanie P.; Petryshen, Tracey L.] Harvard Univ, Sch Med, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 162 BP 50S EP 50S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200162 ER PT J AU Maussion, G Ernst, C Yerko, V Yang, J Turecki, G AF Maussion, Gilles Ernst, Carl Yerko, Volodymyr Yang, Jennie Turecki, Gustavo TI Functional Analysis of microRNA Expression Profiles in Brain Tissue from Suicide Completers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Maussion, Gilles; Ernst, Carl; Yerko, Volodymyr; Yang, Jennie; Turecki, Gustavo] Douglas Hosp, Dept Psychiat, Mental Hlth Univ Inst, Montreal, PQ, Canada. [Ernst, Carl] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Ctr Human Genet Res, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 178 BP 55S EP 55S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200178 ER PT J AU Kocsis, B Lanre-Amos, T AF Kocsis, Bernat Lanre-Amos, Tope TI Hippocampal Oscillations in the Rodent Model of Schizophrenia Induced by Amygdale Gaba Receptor Blockade SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Kocsis, Bernat; Lanre-Amos, Tope] Harvard Univ, Sch Med, BIDMC, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 228 BP 71S EP 71S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200228 ER PT J AU Ghorashi, S McCarley, RW Spencert, KM AF Ghorashi, Shahab McCarley, Robert W. Spencert, Kevin M. TI Attentional Load and Visual Gamma Oscillations in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Ghorashi, Shahab; Spencert, Kevin M.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Ghorashi, Shahab; McCarley, Robert W.; Spencert, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [McCarley, Robert W.] VA Boston Healthcare Syst, Mental Hlth Serv, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 266 BP 83S EP 83S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200265 ER PT J AU Pizzagalli, DA Holmes, AJ Dillon, DG Bogdan, R Dutra, SJ Perlis, RH Fava, M AF Pizzagalli, Diego A. Holmes, Avram J. Dillon, Daniel G. Bogdan, Ryan Dutra, Sunny J. Perlis, Roy H. Fava, Maurizio TI Major Depression and Variation in TREK1 Gene are Associated with Blunted Striatal Responses to Rewards SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Pizzagalli, Diego A.; Holmes, Avram J.; Dillon, Daniel G.; Bogdan, Ryan; Dutra, Sunny J.] Harvard Univ, Cambridge, MA 02138 USA. [Perlis, Roy H.; Fava, Maurizio] 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 352 BP 101S EP 101S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200324 ER PT J AU Houston, JP Perlis, R Dharia, S Jacobson, J Fijal, B AF Houston, John P. Perlis, Roy Dharia, Sweta Jacobson, Jennie Fijal, Bonnie TI Comparison of Pharmacogenomic Associations with Clinical Change in Olanzapine Fluoxetine Combination Treatment of Patients with Treatment Resistant Depression vs. Bipolar I Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Houston, John P.] Eli Lilly & Co, Indianapolis, IN USA. [Perlis, Roy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dharia, Sweta] i3 Statprobe, United Hlth Grp, Ann Arbor, MI USA. [Jacobson, Jennie; Fijal, Bonnie] Lilly USA LLC, Indianapolis, IN 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 452 BP 128S EP 128S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200408 ER PT J AU Hoogenboom, WS Perlis, RH Smoller, JW Zeng-Treitler, Q Gainer, VS Murphy, SN Churchill, SE Kohane, I Shenton, ME Iosifescu, DV AF Hoogenboom, Wouter S. Perlis, Roy H. Smoller, Jordan W. Zeng-Treitler, Qing Gainer, Vivian S. Murphy, Shawn N. Churchill, Susanne E. Kohane, Isaac Shenton, Martha E. Iosifescu, Dan V. TI Atlas-Based Segmentation of White Matter in Major Depressive Disorder Using DTI Collected as Part of Routine Clinical Treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Hoogenboom, Wouter S.; Perlis, Roy H.; Smoller, Jordan W.; Iosifescu, Dan V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02115 USA. [Hoogenboom, Wouter S.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Zeng-Treitler, Qing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Boston, MA 02115 USA. [Gainer, Vivian S.; Murphy, Shawn N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. [Churchill, Susanne E.; Kohane, Isaac] Harvard Univ, Brigham & Womens Hosp, Sch Med, i2b2 Natl Ctr Biomed Comp, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 487 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200443 ER PT J AU Makris, N Seidman, LJ Valera, EM Monuteaux, MC Kaiser, JR Liang, L Hodge, SM Brown, AB Aleardi, M Boriel, DL Henderson, CS Giddens, M Papadimitriou, G Albaugh, MD Tulloch, S Howard, J Faraone, SV Biederman, J AF Makris, Nikos Seidman, Larry J. Valera, Eve M. Monuteaux, Michael C. Kaiser, Jonathan R. Liang, Lichen Hodge, Steven M. Brown, Ariel B. Aleardi, Megan Boriel, Denise L. Henderson, Carly S. Giddens, Michelle Papadimitriou, George Albaugh, Matthew D. Tulloch, Seann Howard, James Faraone, Stephen V. Biederman, Joseph TI Fronto-Limbic Abnormalities in Adults with Attention-Deficit/Hyperactivity Disorder Comorbid with Bipolar Disorder using a Cortical Thickness MRI Analysis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Makris, Nikos; Kaiser, Jonathan R.; Liang, Lichen; Hodge, Steven M.; Brown, Ariel B.; Boriel, Denise L.; Giddens, Michelle; Papadimitriou, George; Albaugh, Matthew D.; Tulloch, Seann; Howard, James] Massachusetts Gen Hosp, Charlestown, MA USA. [Seidman, Larry J.; Valera, Eve M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Monuteaux, Michael C.; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 514 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200470 ER PT J AU Gurrera, RJ Caroff, SN Cohen, A AF Gurrera, Ronald J. Caroff, Stanley N. Cohen, Abigail TI International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome Using the Delphi Technique SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Gurrera, Ronald J.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Gurrera, Ronald J.] VA Boston Healthcare Syst, Brockton, MA USA. [Caroff, Stanley N.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Caroff, Stanley N.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Cohen, Abigail] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RI Cohen, Abigail/K-9180-2013 OI Cohen, Abigail/0000-0002-7425-7218 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 520 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200476 ER PT J AU Mitsis, EM Shiovitz, R Nikolskaya, G Elder, G Bang, C Cristian, A Hazlett, E Buchsbaum, MS AF Mitsis, Effie M. Shiovitz, Rachel Nikolskaya, Galina Elder, Gregory Bang, Charlene Cristian, Adrian Hazlett, Erin Buchsbaum, Monte S. TI FDG-PET Regional Glucose Abnormalities in White Matter in Civilian Impact and Military Blast-Related Mild Traumatic Brain Injury SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Mitsis, Effie M.; Shiovitz, Rachel; Elder, Gregory; Bang, Charlene; Cristian, Adrian; Hazlett, Erin] Mt Sinai Sch Med, New York, NY USA. [Mitsis, Effie M.; Elder, Gregory; Bang, Charlene; Cristian, Adrian] James J Peters VAMC, Bronx, NY USA. [Nikolskaya, Galina; Buchsbaum, Monte S.] Univ Calif San Diego, San Diego, CA 92103 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 521 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200477 ER PT J AU Terry, DP Rausch, AC Whitford, TJ Nestor, PG O'Donnell, L Bobrow, LH Westin, CF Kikinis, R Shenton, ME Kubicki, M AF Terry, Douglas P. Rausch, Andrew C. Whitford, Thomas J. Nestor, Paul G. O'Donnell, Lauren Bobrow, Laurel H. Westin, Carl-Fredrik Kikinis, Ron Shenton, Martha E. Kubicki, Marek TI Factor Analysis of Automatic White Matter Clustering and Neuropsychology Measures in Patients with Schizophrenia. SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Westin, Carl-Fredrik; Kikinis, Ron; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,MRI Div,Surg Planning Lab, Boston, MA USA. [Whitford, Thomas J.] Univ Melbourne & Melbourne Heath, Melbourne Neuropsychiat Ctr, Dept Psychiat, Melbourne, Vic, Australia. [Nestor, Paul G.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Clin Neurosci Div, Lab Neurosci,VA Boston Healthcare Syst, Brockton, MA 02401 USA. [O'Donnell, Lauren; Westin, Carl-Fredrik] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Math Imaging, Boston, MA USA. [O'Donnell, Lauren] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Golby Lab, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 543 BP 157S EP 158S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200499 ER PT J AU Gurrera, RJ Mahowald, T Salisbury, D AF Gurrera, Ronald J. Mahowald, Toni Salisbury, Dean TI First Episode Schizophrenia and Bipolar Disorder Associated with Distinct Personality Trait Profiles SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Gurrera, Ronald J.; Salisbury, Dean] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Gurrera, Ronald J.] VA Boston Healthcare Syst, Brockton, MA USA. [Mahowald, Toni; Salisbury, Dean] McLean Hosp, Belmont, MA 02178 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 553 BP 160S EP 160S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200508 ER PT J AU Stewart, SE AF Stewart, S. Evelyn TI Glutamate Modulating Agents in Treatment-Refractory Obsessive-Compulsive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Stewart, S. Evelyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stewart, S. Evelyn] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. RI Stewart, Evelyn/K-6961-2014 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 651 BP 183S EP 183S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200581 ER PT J AU Ostacher, MJ AF Ostacher, Michael J. TI STEP-BD: Lessons Learned, Outcomes and Directions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Ostacher, Michael J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Ostacher, Michael J.] 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 659 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200589 ER PT J AU Iosifescu, DV Renshaw, PF AF Iosifescu, Dan V. Renshaw, Perry F. TI Magnesium and Abnormal Brain Bioenergetics in Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Iosifescu, Dan V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Renshaw, Perry F.] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA. [Renshaw, Perry F.] Univ Utah, Sch Med, Inst Brain, Salt Lake City, UT 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 691 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200621 ER PT J AU Killgore, WDS Price, LM Britton, JC Simon, NM Pollack, MH Schwab, ZJ Weiner, MR Rosso, IM Rauch, SL AF Killgore, William D. S. Price, Lauren M. Britton, Jennifer C. Simon, Naomi M. Pollack, Mark H. Schwab, Zachary J. Weiner, Melissa R. Rosso, Isabelle M. Rauch, Scott L. TI Paralimbic Responses to Masked Emotional Faces in PTSD: Disorder and Valence Specificity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Killgore, William D. S.; Price, Lauren M.; Schwab, Zachary J.; Weiner, Melissa R.; Rosso, Isabelle M.; Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Killgore, William D. S.; Simon, Naomi M.; Pollack, Mark H.; Rosso, Isabelle M.; Rauch, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Britton, Jennifer C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Simon, Naomi M.; Pollack, Mark H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Britton, Jennifer/J-4501-2013 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 732 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200662 ER PT J AU Zeidan, MA Pitman, RK Klibanski, A Rauch, SL Goldstein, JM Milad, MR AF Zeidan, Mohamed A. Pitman, Roger K. Klibanski, Anne Rauch, Scott L. Goldstein, Jill M. Milad, Mohammed R. TI The Influence of Gonadal Hormones on Conditioned Fear Extinction in Healthy Humans, an fMRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Zeidan, Mohamed A.; Pitman, Roger K.; Rauch, Scott L.; Goldstein, Jill M.; Milad, Mohammed R.] Massachusetts Gen Hosp, Charlestown, MA USA. [Zeidan, Mohamed A.; Pitman, Roger K.; Rauch, Scott L.; Goldstein, Jill M.; Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Goldstein, Jill M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 736 BP 210S EP 210S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200666 ER PT J AU Rosso, IM Makris, N Britton, JC Price, LM Gold, AL Deckersbach, T Killgore, WDS Rauch, SL AF Rosso, Isabelle M. Makris, Nikos Britton, Jennifer C. Price, Lauren M. Gold, Andrea L. Deckersbach, Thilo Killgore, William D. S. Rauch, Scott L. TI Anxiety Sensitivity Correlates with Insular Cortex Volume and Thickness in Specific Animal Phobia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Rosso, Isabelle M.; Price, Lauren M.; Killgore, William D. S.; Rauch, Scott L.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. [Britton, Jennifer C.; Gold, Andrea L.; Deckersbach, Thilo] Massachusetts Gen Hosp, Martinos Biomed Imaging Ctr, Charlestown, MA USA. RI Britton, Jennifer/J-4501-2013 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 739 BP 211S EP 211S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200669 ER PT J AU Perlis, RH Fijal, B Dharia, S Heinloth, AN Houston, JP AF Perlis, Roy H. Fijal, Bonnie Dharia, Sweta Heinloth, Alexandra N. Houston, John P. TI Potential Differences in Pharmacogenomic Associations with Improvement in Anxiety During Duloxetine Treatment of Generalized Anxiety Disorder and Major Depressive Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fijal, Bonnie] Lilly USA LLC, US Stat, Indianapolis, IN USA. [Dharia, Sweta; Heinloth, Alexandra N.] i3Stratprobe, United Hlth Grp, Ann Arbor, MI USA. [Houston, John P.] Lilly USA LLC, MD Zyrexa Symbyax, Indianapolis, IN USA. [Houston, John P.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 748 BP 214S EP 214S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200678 ER PT J AU Gale, JT Baker, KB Cash, SS Machado, AG Dougherty, DD Stypulkowski, P Rezai, A Eskandar, EN Malone, D AF Gale, John T. Baker, Kenneth B. Cash, Sydney S. Machado, Andre G. Dougherty, Darin D. Stypulkowski, Paul Rezai, Ali Eskandar, Emad N. Malone, Donald TI Cortical Evoked Potentials in Response to Deep Brain Stimulation for Depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Gale, John T.; Cash, Sydney S.; Dougherty, Darin D.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Baker, Kenneth B.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. [Stypulkowski, Paul] Medtronic, Neuromodulat, Fridley, MN USA. [Machado, Andre G.; Malone, Donald] Cleveland Clin Fdn, Neurol Inst, Cleveland, OH 44195 USA. RI Machado, Andre/B-7572-2014 OI Machado, Andre/0000-0002-8132-5610 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 802 BP 231S EP 231S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200732 ER PT J AU Rosell, DR Thompson, JL Slifstein, M Xu, XY Frankle, WG New, AS Goodman, M Weinstein, SC Laruelle, M Abi-Dargham, A Siever, LJ AF Rosell, Daniel R. Thompson, Judy L. Slifstein, Mark Xu, Xiaoyan Frankle, W. Gordon New, Antonia S. Goodman, Marianne Weinstein, Shauna C. Laruelle, Marc Abi-Dargham, Anissa Siever, Larry J. TI Evidence Increased 5-HT2A Receptor Availability in the Orbitofrontal Cortex is Associated with Impulsive Physical Aggression in a State Dependent Manner SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Rosell, Daniel R.; New, Antonia S.; Goodman, Marianne; Weinstein, Shauna C.; Siever, Larry J.] James J Peters VA Med Ctr, Bronx, NY USA. [Thompson, Judy L.; Slifstein, Mark; Xu, Xiaoyan; Abi-Dargham, Anissa] Columbia Univ, Med Ctr, New York, NY USA. [Thompson, Judy L.; Slifstein, Mark; Xu, Xiaoyan; Abi-Dargham, Anissa] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Frankle, W. Gordon] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Laruelle, Marc] Imperial Coll London, London, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 848 BP 246S EP 246S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200778 ER PT J AU Mathalon, DH Jorgensen, KW Roach, BJ Calhoun, VD Diaz, MT Brown, GG Notestine, R Bischoff-Grethe, A Greve, D McCarthy, G Belger, A Turner, JA Potkin, SG Wible, CG Mueller, BA Lauriello, J Glover, GH Lim, KO O'Leary, DS Preda, A Keator, D Van Erp, T Ford, JM AF Mathalon, Daniel H. Jorgensen, Kasper W. Roach, Brian J. Calhoun, Vince D. Diaz, Michele T. Brown, Gregory G. Notestine, Randy Bischoff-Grethe, Amanda Greve, Doug McCarthy, Gregory Belger, Aysenil Turner, Jessica A. Potkin, Steven G. Wible, Cindy G. Mueller, Bryon A. Lauriello, John Glover, Gary H. Lim, Kelvin O. O'Leary, Daniel S. Preda, Adian Keator, David Van Erp, Theo Ford, Judith M. CA FBIRN TI Failure of Normal Aging-Related Hemispheric Asymmetry Reduction in Brain Activity During Target Detection in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Mathalon, Daniel H.; Jorgensen, Kasper W.; Roach, Brian J.; Ford, Judith M.] UCSF, San Francisco, CA USA. [Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Calhoun, Vince D.; Lauriello, John] Univ New Mexico, Albuquerque, NM 87131 USA. [Diaz, Michele T.] Duke Univ, Brain Imaging & Anal Ctr, Durham, NC USA. [Brown, Gregory G.; Notestine, Randy; Bischoff-Grethe, Amanda] UCSD, San Diego, CA USA. [Greve, Doug; Wible, Cindy G.] Harvard Univ, Cambridge, MA 02138 USA. [Greve, Doug] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Belger, Aysenil] Univ N Carolina, Durham, NC USA. [Turner, Jessica A.; Potkin, Steven G.; Preda, Adian; Keator, David] UCI, Irvine, CA USA. [Wible, Cindy G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mueller, Bryon A.; Lim, Kelvin O.] Univ Minnesota, Minneapolis, MN USA. [Glover, Gary H.] Stanford Univ, Stanford, CA 94305 USA. [O'Leary, Daniel S.] Univ Iowa, Iowa City, IA USA. [Van Erp, Theo] Univ Calif Los Angeles, Los Angeles, CA USA. [FBIRN] Funct Biomed Informat Res Network, San Francisco, CA USA. RI Potkin, Steven/A-2021-2013 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 865 BP 252S EP 252S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200795 ER PT J AU Levitt, JJ Lucia, DM Bobrow, LH McCarley, RW Shenton, ME AF Levitt, James J. Lucia, Diandra M. Bobrow, Laurel H. McCarley, Robert W. Shenton, Martha E. TI Anterior Cingulate Gyrus and Paracingulate Sulcal Patterns in Schizophrenia: An MRI Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Levitt, James J.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Levitt, James J.; Lucia, Diandra M.; Bobrow, Laurel H.; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 871 BP 254S EP 254S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200801 ER PT J AU Rosso, IM Makris, N Thermenos, HW Hodge, SM Brown, A Kennedy, D Caviness, VS Faraone, SV Tsuang, MT Seidman, LJ AF Rosso, Isabelle M. Makris, Nikos Thermenos, Heidi W. Hodge, Steven M. Brown, Ariel Kennedy, David Caviness, Verne S. Faraone, Stephen V. Tsuang, Ming T. Seidman, Larry J. TI Regional Temporal Lobe Gray Matter Volumes and Memory Functioning in Youth at Familial Risk for Schizophrenia from the Harvard Adolescent High Risk Study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Rosso, Isabelle M.; Thermenos, Heidi W.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Makris, Nikos; Hodge, Steven M.; Brown, Ariel; Kennedy, David; Caviness, Verne S.] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 878 BP 256S EP 256S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200808 ER PT J AU Schneiderman, JS Whitford, TJ Pelavin, PE Lucia, DM Atwood, SB Mesholam-Gately, RI Seidman, LJ Goldstein, JM McCarley, RW Kubicki, M Shenton, ME AF Schneiderman, Jason S. Whitford, Thomas J. Pelavin, Paula E. Lucia, Diandra M. Atwood, Samuel B. Mesholam-Gately, Raquelle I. Seidman, Larry J. Goldstein, Jill M. McCarley, Robert W. Kubicki, Marek Shenton, Martha E. TI Diffusion Tensor Imaging of the Uncinate Fasciculus in First Episode Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Schneiderman, Jason S.; Whitford, Thomas J.; Pelavin, Paula E.; Lucia, Diandra M.; Atwood, Samuel B.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Mesholam-Gately, Raquelle I.; Seidman, Larry J.; Goldstein, Jill M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02115 USA. [McCarley, Robert W.] VA Boston Healthcare Syst, Dept Psychiat, Div Neurosci, Brockton, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 880 BP 257S EP 257S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200810 ER PT J AU Pence, SG Gard, DE Cooper, S Grotewold, S Mahayni, A Woo, J Fisher, M Vinogradov, S AF Pence, Sunny G. Gard, David E. Cooper, Shanna Grotewold, Susan Mahayni, Ali Woo, Jessica Fisher, Melissa Vinogradov, Sophia TI Reducing Cognitive Demand in Ecological Momentary Assessment in Schizophrenia: A Feasibility Study Using Cellular Telephones SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Pence, Sunny G.; Gard, David E.; Cooper, Shanna; Grotewold, Susan; Mahayni, Ali; Woo, Jessica; Fisher, Melissa] San Francisco State Univ, San Francisco, CA 94132 USA. [Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 896 BP 262S EP 262S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200826 ER PT J AU Mears, RP McCarley, RW Spencer, KM AF Mears, Ryan P. McCarley, Robert W. Spencer, Kevin M. TI NMDA Receptor Hypofunction in the Auditory Cortex in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Mears, Ryan P.; Spencer, Kevin M.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Mears, Ryan P.; McCarley, Robert W.; Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. [McCarley, Robert W.] VA Boston Healthcare Syst, Mental Hlth Serv, Brockton, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 913 BP 267S EP 267S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200843 ER PT J AU Kaplan, GB Heinrichs, SC Kantak, KM Leite-Morris, KA AF Kaplan, Gary B. Heinrichs, Stephen C. Kantak, Kathleen M. Leite-Morris, Kimberly A. TI Rapid Extinction of Morphine Conditioned Place Preference in C57BL/6 Mice: Effects of D-Cycloserine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 65th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 20-22, 2010 CL New Orleans, LA SP Soc Biol Psychiat C1 [Kaplan, Gary B.; Heinrichs, Stephen C.; Leite-Morris, Kimberly A.] VA Boston Healthcare Syst, Boston, MA USA. [Kaplan, Gary B.; Leite-Morris, Kimberly A.] Boston Univ, Sch Med, Boston, MA 02215 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 SU S MA 919 BP 269S EP 269S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IX UT WOS:000277064200849 ER PT J AU Sakurai, T Ramoz, N Barreto, M Gazdoiu, M Takahashi, N Gertner, M Dorr, N Sosa, MAG De Gasperi, R Perez, G Schmeidler, J Mitropoulou, V Le, HC Lupu, M Hof, PR Elder, GA Buxbaum, JD AF Sakurai, Takeshi Ramoz, Nicolas Barreto, Marta Gazdoiu, Mihaela Takahashi, Nagahide Gertner, Michael Dorr, Nathan Sosa, Miguel A. Gama De Gasperi, Rita Perez, Gissel Schmeidler, James Mitropoulou, Vivian Le, H. Carl Lupu, Mihaela Hof, Patrick R. Elder, Gregory A. Buxbaum, Joseph D. TI Slc25a12 Disruption Alters Myelination and Neurofilaments: A Model for a Hypomyelination Syndrome and Childhood Neurodevelopmental Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Malate/aspartate shuttle; mitochondria; N-acetylaspartate (NAA); neuron-oligodendrocyte interactions; pyruvate ID MAGNETIC-RESONANCE-SPECTROSCOPY; AUTISM SPECTRUM DISORDERS; ASPARTATE-GLUTAMATE; BRAIN-METABOLITES; WHITE-MATTER; CARRIER; GENE; ASSOCIATION; CHILDREN; MITOCHONDRIA AB Background: SLC25A12, a susceptibility gene for autism spectrum disorders that is mutated in a neurodevelopmental syndrome, encodes a mitochondrial aspartate-glutamate carrier (aspartate-glutamate carrier isoform 1 [AGC1]). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidative phosphorylation and adenosine triphosphate production. Methods: We characterized mice with a disruption of the Slc25a12 gene, followed by confirmatory in vitro studies. Results: Slc25a12-knockout mice, which showed no AGC1 by immunoblotting, were born normally but displayed delayed development and died around 3 weeks after birth. In postnatal day 13 to 14 knockout brains, the brains were smaller with no obvious alteration in gross structure. However, we found a reduction in myelin basic protein (MBP)-positive fibers, consistent with a previous report. Furthermore, the neocortex of knockout mice contained abnormal neurofilamentous accumulations in neurons, suggesting defective axonal transport and/or neurodegeneration. Slice cultures prepared from knockout mice also showed a myelination defect, and reduction of Slc25a12 in rat primary oligodendrocytes led to a cell-autonomous reduction in MBP expression. Myelin deficits in slice cultures from knockout mice could be reversed by administration of pyruvate, indicating that reduction in AGC1 activity leads to reduced production of aspartate/N-acetylaspartate and/or alterations in the dihydronicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide(+) ratio, resulting in myelin defects. Conclusions: Our data implicate AGC1 activity in myelination and in neuronal structure and indicate that while loss of AGC1 leads to hypomyelination and neuronal changes, subtle alterations in AGC1 expression could affect brain development, contributing to increased autism susceptibility. C1 [Sakurai, Takeshi; Ramoz, Nicolas; Barreto, Marta; Gazdoiu, Mihaela; Takahashi, Nagahide; Gertner, Michael; Dorr, Nathan; Sosa, Miguel A. Gama; De Gasperi, Rita; Perez, Gissel; Schmeidler, James; Mitropoulou, Vivian; Elder, Gregory A.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Sakurai, Takeshi; Ramoz, Nicolas; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Sakurai, Takeshi] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY 10029 USA. [Hof, Patrick R.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Le, H. Carl; Lupu, Mihaela] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY USA. RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu RI Le, Hongbiao /H-4735-2011; Barreto, Marta/F-5591-2012; ramoz, nicolas/K-3316-2015 OI Barreto, Marta/0000-0001-6464-548X; Buxbaum, Joseph/0000-0001-8898-8313; FU New York State Spinal Cord Injury [C020935]; Stanley Medical Research Institute [06R-1427]; Seaver Foundation; National Institute of Mental Health [MH066673]; National Institutes of Health (NIH) [R24CA83084, P30CA08748] FX TS is a Seaver Fellow and supported in part by New York State Spinal Cord Injury contract (C020935) and Stanley Medical Research Institute research grant (06R-1427). This research was supported by the Seaver Foundation (TS and JDB) and the National Institute of Mental Health (MH066673, JDB). Technical services at the Memorial Sloan-Kettering Cancer Center Small-Animal Imaging Core Facility were supported in part by National Institutes of Health (NIH) Small-Animal Imaging Research Program Grant R24CA83084 and NIH Center Grant P30CA08748. NR 31 TC 23 Z9 25 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2010 VL 67 IS 9 BP 887 EP 894 DI 10.1016/j.biopsych.2009.08.042 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 588IW UT WOS:000277064100013 PM 20015484 ER PT J AU Kilpatrick, LA Ornitz, E Ibrahimovic, H Treanor, M Craske, M Nazarian, M Labus, JS Mayer, EA Naliboff, BD AF Kilpatrick, L. A. Ornitz, E. Ibrahimovic, H. Treanor, M. Craske, M. Nazarian, M. Labus, J. S. Mayer, E. A. Naliboff, B. D. TI Sex-related differences in prepulse inhibition of startle in irritable bowel syndrome (IBS) SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Irritable bowel syndrome; Functional bowel disorders; Acoustic startle response; Prepulse inhibition of startle; Sex differences; Hypervigilence ID REGIONAL BRAIN RESPONSE; ACOUSTIC STARTLE; MENSTRUAL-CYCLE; GASTROINTESTINAL-DISEASE; SCHIZOPHRENIA-PATIENTS; VISCERAL STIMULI; SENSORIMOTOR; DISORDER; DEFICITS; MODULATION AB Alterations in central networks involved in the regulation of arousal, attention, and cognition may be critical for irritable bowel syndrome (IBS) symptom maintenance and exacerbation. Differential sensitivities in these networks may underlie sex differences noted in IBS. The current study examined prepulse inhibition (PPI), a measure of sensorimotor gating, in male and female IBS patients. Relationships between PPI and symptom severity were examined, as well as potential menstrual status effects. Compared to healthy controls, male IBS patients had significantly reduced PPI; whereas female IBS patients (particularly naturally cycling women) had significantly enhanced PPI suggesting hypervigilance. Considering previously demonstrated sex-related differences in perceptual and brain imaging findings in IBS patients, the current findings suggest that different neurobiological mechanisms underlie symptom presentation in male and female IBS patients. Compromised filtering of information in male IBS patients may be due to compromised top down (prefrontal, midcingulate) control mechanisms while increased attention to threat due to increased limbic and paralimbic circuits may be characteristic of female IBS patients. Published by Elsevier B.V. C1 [Kilpatrick, L. A.; Ornitz, E.; Ibrahimovic, H.; Labus, J. S.; Mayer, E. A.; Naliboff, B. D.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90073 USA. [Ornitz, E.; Mayer, E. A.; Naliboff, B. D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Kilpatrick, L. A.; Mayer, E. A.] Univ Calif Los Angeles, Dept Physiol & Med, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. [Ornitz, E.; Labus, J. S.; Mayer, E. A.] Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Treanor, M.; Craske, M.; Nazarian, M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90073 USA. [Naliboff, B. D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, CURE Bld 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu RI Kilpatrick, Lisa/E-6995-2015 FU NIH [NR007768, P50 DK64539, R24 AT002681]; VA Medical Research FX Supported in part by NIH grants NR007768 (BN), P50 DK64539 (EM), R24 AT002681 (EM), VA Medical Research (BN), and a gift from the Virginia Friedhofer Charitable Trust (EO). NR 59 TC 16 Z9 16 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAY PY 2010 VL 84 IS 2 BP 272 EP 278 DI 10.1016/j.biopsycho.2010.02.012 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 616GQ UT WOS:000279197500013 PM 20193731 ER PT J AU Sloan, DM Sandt, AR AF Sloan, Denise M. Sandt, Arthur R. TI Depressed mood and emotional responding SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Emotion; Motivation; Eyeblink startle; Postauricular reflex; Depression ID ANXIETY STRESS SCALES; POSTAURICULAR REFLEX; STARTLE MODULATION; PSYCHOMETRIC PROPERTIES; RESPONSES; PICTURES; STIMULI; SENSITIVITY; MOTIVATION; DISORDERS AB The current study examined emotional responding in a sample of 57 college students who varied in depression symptom scores. Participants viewed pleasant, unpleasant and neutral emotional-eliciting pictures. Response measures included autonomic activity, subjective report of emotion, eyeblink startle reflex, and postauricular reflex. Findings indicated that greater depression symptoms predicted blunted responding with the postauricular reflex and eyeblink startle reflex measures. However, greater depression symptoms were not associated with blunted or heightened responding as indexed by the autonomic reactivity and self-report measures. Taken together, these results suggest that depression may be associated with both appetitive and defensive responding deficits, which has important implications for emotional responding. The findings underscore the importance of using multiple measures when investigating emotional responding associated with depression. Published by Elsevier B.V. C1 [Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Sandt, Arthur R.] Temple Univ, Philadelphia, PA 19122 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM Denise.Sloan@va.gov OI Sloan, Denise/0000-0002-0962-478X NR 52 TC 13 Z9 13 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAY PY 2010 VL 84 IS 2 BP 368 EP 374 DI 10.1016/j.biopsycho.2010.04.004 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 616GQ UT WOS:000279197500025 PM 20416354 ER PT J AU Bishop, MR Alyea, EP Cairo, MS Falkenburg, JHF June, CH Kroger, N Little, RF Miller, JS Pavletic, SZ Porter, D Riddell, SR van Besien, K Wayne, AS Weisdorf, DJ Wu, R Giralt, S AF Bishop, Michael R. Alyea, Edwin P., III Cairo, Mitchell S. Falkenburg, J. H. Frederik June, Carl H. Kroeger, Nicolaus Little, Richard F. Miller, Jeffrey S. Pavletic, Steven Z. Porter, David Riddell, Stanley R. van Besien, Koen Wayne, Alan S. Weisdorf, Daniel J. Wu, Roy Giralt, Sergio TI Introduction to the Reports from the National Cancer Institute First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSIONS; LEUKEMIA; LONG; EBMT C1 [Bishop, Michael R.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Cairo, Mitchell S.] Columbia Univ, Dept Pediat, Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY 10027 USA. [Falkenburg, J. H. Frederik] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands. [June, Carl H.; Porter, David] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Kroeger, Nicolaus] Univ Hosp Hamburg Eppendorf, Ctr Stem Cell Transplantat, Hamburg, Germany. [Little, Richard F.; Wu, Roy] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Miller, Jeffrey S.; Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Riddell, Stanley R.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [van Besien, Koen] Univ Chicago, Sch Med, Dept Med, Chicago, IL 60637 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. [Bishop, Michael R.; Alyea, Edwin P., III; Cairo, Mitchell S.; Falkenburg, J. H. Frederik; June, Carl H.; Kroeger, Nicolaus; Little, Richard F.; Miller, Jeffrey S.; Pavletic, Steven Z.; Porter, David; Riddell, Stanley R.; van Besien, Koen; Wayne, Alan S.; Weisdorf, Daniel J.; Wu, Roy; Giralt, Sergio] Natl Canc Inst First Int Workshop Biol Prevent &, Organizing Comm, Bethesda, MD USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,CRC Room 4-3152, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov RI van Besien, Koen/G-4221-2012; OI van Besien, Koen/0000-0002-8164-6211; Miller, Jeffrey S/0000-0002-0339-4944 FU Intramural NIH HHS [ZIA BC011239-01]; NCI NIH HHS [R01 CA136551] NR 16 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2010 VL 16 IS 5 BP 563 EP 564 DI 10.1016/j.bbmt.2010.02.025 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 589QR UT WOS:000277168200001 PM 20202482 ER PT J AU Miller, JS Warren, EH van den Brink, MRM Ritz, J Shlomchik, WD Murphy, WJ Barrett, AJ Kolb, HJ Giralt, S Bishop, MR Blazar, BR Falkenburg, JHF AF Miller, Jeffrey S. Warren, Edus H. van den Brink, Marcel R. M. Ritz, Jerome Shlomchik, Warren D. Murphy, William J. Barrett, A. John Kolb, Hans Jochem Giralt, Sergio Bishop, Michael R. Blazar, Bruce R. Falkenburg, J. H. Frederik TI NCI First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biology Underlying Recurrence of Malignant Disease following Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE HCT; relapse; Graft-versus-host disease; Immune modulation; Graft-versus-leukemia reaction ID MINOR HISTOCOMPATIBILITY ANTIGEN; CD8(+) T-CELLS; NATURAL-KILLER-CELLS; DONOR LYMPHOCYTE INFUSION; CHRONIC MYELOGENOUS LEUKEMIA; KIR LIGAND INCOMPATIBILITY; ACUTE MYELOID-LEUKEMIA; MHC CLASS-I; ACUTE LYMPHOBLASTIC-LEUKEMIA; SUPERIOR ANTITUMOR IMMUNITY AB The success of allogeneic hematopoietic stem cell transplantation (HSCT) depends on the infusion of benign stem cells as well as lymphocytes capable of participating in a graft-versus-tumor/leukemia (GVL) reaction. Clinical proof of concept is derived from studies showing increased relapse after the infusion of lymphocyte depleted hematopoietic grafts as well as the therapeutic efficacy of donor lymphocyte infusions without chemotherapy to treat relapse in some diseases. Despite this knowledge, relapse after allogeneic HSCT is common with rates approaching 40% in those with high-risk disease. In this review, we cover the basic biology and potential application to exploit adaptive T cell responses, minor histocompatibility antigens, contraction and suppression mechanisms that hinder immune responses, adaptive B cell responses and innate NK cell responses, all orchestrated in a GVL reaction. Optimal strategies to precisely balance immune responses to favor GVL without harmful graft-versus-host disease (GVHD) are needed to protect against relapse, treat persistent disease and improve disease-free survival after HSCT. C1 [Miller, Jeffrey S.; Blazar, Bruce R.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Warren, Edus H.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA. [Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Shlomchik, Warren D.] Yale Univ, Sch Med, Ctr Canc, Sect Med Oncol, New Haven, CT USA. [Murphy, William J.] Univ Calif, Davis Med Ctr, Sacramento, CA USA. [Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kolb, Hans Jochem] Univ Munich, Dept Med 3, Munich, Germany. [Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Falkenburg, J. H. Frederik] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands. RP Miller, JS (reprint author), Univ Minnesota, Blood & Marrow Transplant Program, 420 Delaware St,SE,MMC 806, Minneapolis, MN 55455 USA. EM mille011@umn.edu OI Miller, Jeffrey S/0000-0002-0339-4944 FU NCI NIH HHS [P01 CA065493, P01 CA142106, P01 CA111412-05, P01 CA111412] NR 183 TC 61 Z9 61 U1 0 U2 7 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 MAY PY 2010 VL 16 IS 5 BP 565 EP 586 DI 10.1016/j.bbmt.2010.02.005 PG 22 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 589QR UT WOS:000277168200002 PM 20152921 ER PT J AU Powers, DE Millman, JR Bonner-Weir, S Rappel, MJ Colton, CK AF Powers, Daryl E. Millman, Jeffrey R. Bonner-Weir, Susan Rappel, Michael J. Colton, Clark K. TI Accurate Control of Oxygen Level in Cells During Culture on Silicone Rubber Membranes with Application to Stem Cell Differentiation SO BIOTECHNOLOGY PROGRESS LA English DT Article DE embryonic stem cells; oxygen; hypoxia; differentiation; silicone rubber ID PLASMA; SURFACES; GROWTH; VITRO; ADSORPTION; STABILITY; PHENOTYPE; DIFFUSION; KINETICS; ADHESION AB Oxygen level in mammalian cell culture is often controlled by placing culture vessels in humidified incubators with a defined gas phase partial pressure of oxygen (pO(2gas)). Because the cells are consuming oxygen supplied by diffusion, a difference between pO(2gas) and that experienced by the cells (pO(2cell)) arises, which is maximal when cells are cultured in vessels with little or no oxygen permeability. Here, we demonstrate theoretically that highly oxygen-permeable silicone rubber membranes can be used to control pO(2cell) during culture of cells in monolayers and aggregates much more accurately and can achieve more rapid transient response following a disturbance than on polystyrene and fluorinated ethylene-propylene copolymer membranes. Cell attachment on silicone rubber was achieved by physical adsorption of fibronectin or Matrigel. We use these membranes for the differentiation of mouse embryonic stem cells to cardiomyocytes and compare the results with culture on polystyrene or on silicone rubber on top of polystyrene. The fraction of cells that are cardioniyoute-like increases with decreasing pO(2) only when using oxygen-permeable silicone membrane-based dishs, which contract on silicone rubber but not polystyrene. The high permeability of silicone rubber results in pO(2cell) being equal to pO(2gas) at the tissue-membrane inteiface. This, together with geometric information from histological sections, facilitates development of a model from which the pO(2) distribution within the resulting aggregates is computed. Silicone rubber membranes have significant advantages over polystyrene in controlling pO(2cell), and these results suggest they are a valuable tool for investigating pO(2) effects in many applications such as stem cell differentiation. (C) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 26: 805-818, 2010 C1 [Powers, Daryl E.; Millman, Jeffrey R.; Rappel, Michael J.; Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Bonner-Weir, Susan] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Bonner-Weir, Susan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM ckcolton@msit.edu FU NIH (NCRR ICR) [U4ZPR 16606, ROI-KD063108 OIA]; JDRF center for Islet Transplantation at Harvard Medical School FX This study was supported in part by grants from the NIH (NCRR ICR U4ZPR 16606 and ROI-KD063108 OIA) and the JDRF center for Islet Transplantation at Harvard Medical School. Helpful discussions and technical assistance with aspects of the work were provided by Anna Pisania, and Jit Hin Tan (Chemical Engineering, MIT). NR 44 TC 9 Z9 9 U1 1 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 2010 VL 26 IS 3 BP 805 EP 818 DI 10.1002/btpr.359 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 615HG UT WOS:000279124800025 PM 20039374 ER PT J AU Wingo, AP Baldessarini, RJ Holtzheimer, PE Harvey, PD AF Wingo, Aliza P. Baldessarini, Ross J. Holtzheimer, Paul E. Harvey, Philip D. TI Factors associated with functional recovery in bipolar disorder patients SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; education; functional recovery; illness duration; marital status; neurocognition ID MONTGOMERY-ASBERG DEPRESSION; COGNITIVE IMPAIRMENT; MARITAL-STATUS; II DISORDERS; HOSPITALIZATION; RECURRENCE; REMISSION; EDUCATION; SYMPTOMS; HAMILTON AB Objectives: Among bipolar disorder (BPD) patients, functional recovery, defined as regaining individual premorbid residential and vocational status, is far less common than symptomatic recovery. As several factors have tentatively been implicated in outcomes in BPD, we investigated predictors of functional recovery among BPD patients, including demographic, clinical, and neurocognitive factors. Methods: We assessed functional recovery status with standardized residential and occupational indices, assessed neurocognitive functioning with performance-based neuropsychological tests, and collected demographic and clinical information for 65 euthymic or residually depressed Structured Clinical Interview for DSM-IV-defined type I or II BPD patients. We examined predictors of functional recovery with multiple logistic regression modeling. Results: More education (p = 0.006), fewer years of illness (p = 0.037), and being married (p = 0.045) were associated independently with functional recovery, even after controlling for residual depressive symptoms, diagnostic type (I versus II), and psychiatric comorbidity. Functionally unrecovered BPD patients performed less well than recovered patients on verbal fluency (effect size = 0.54, p = 0.03), a measure of executive functioning, but this difference was not significant when adjusted for residual mood symptoms and education. Conclusions: Among euthymic or mildly depressed BPD patients, functional recovery was associated with more education, being married, and fewer years of illness. C1 [Wingo, Aliza P.; Holtzheimer, Paul E.; Harvey, Philip D.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Baldessarini, Ross J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Psychopharmacol Program, Belmont, MA USA. [Baldessarini, Ross J.] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Wingo, AP (reprint author), Emory Univ, Dept Psychiat & Behav Sci, 101 Woodruff Circle NE,Suite 4000, Atlanta, GA 30322 USA. EM aliza.wingo@emory.edu RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 FU American Psychiatric Institute of Research & Education (APIRE) (APW); Bruce J. Anderson Foundation; McLean Private Donors Research Fund; NIH [UL1 RR025008] FX This project was supported by a research fellowship from the American Psychiatric Institute of Research & Education (APIRE) (APW), a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Research Fund (RJB), and NIH grant UL1 RR025008 (APW). We thank Mitchel Klein and Azhar Nizam for valuable statistical advice, and Chloe Ekelem, Carla Heyler, and Summer Niazi for excellent assistance with data collection. NR 40 TC 24 Z9 24 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAY PY 2010 VL 12 IS 3 BP 319 EP 326 DI 10.1111/j.1399-5618.2010.00808.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 594FU UT WOS:000277522200011 PM 20565439 ER PT J AU Hernandez-Diaz, S Mittendorf, R Holmes, LB AF Hernandez-Diaz, S. Mittendorf, R. Holmes, L. B. TI Comparative Safety of Topiramate during Pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Hernandez-Diaz, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mittendorf, R.] Loyola Univ, Chicago, IL 60611 USA. [Holmes, L. B.] MassGen Hosp Children, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2010 VL 88 IS 5 BP 408 EP 408 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 605AV UT WOS:000278320600153 ER PT J AU Deshmukh, US Adams, J Dhillon, R McCarthy, KD Macklin, E Holmes, LB AF Deshmukh, U. S. Adams, J. Dhillon, R. McCarthy, K. D. Macklin, E. Holmes, L. B. TI Developmental Delay in Children Exposed to Valproate: A Follow-Up Study for the North American Antiepileptic Drug (AED) Pregnancy Registry SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Deshmukh, U. S.; McCarthy, K. D.; Macklin, E.; Holmes, L. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adams, J.] Univ Massachusetts, Boston, MA 02125 USA. [Holmes, L. B.] Harvard Univ, Sch Med, Boston, MA USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2010 VL 88 IS 5 BP 411 EP 411 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 605AV UT WOS:000278320600158 ER PT J AU Choueiri, TK Duh, MS Clement, J Brick, AJ Rogers, MJ Kwabi, C Shah, K Percy, AG Antras, L Jayawant, SS Chen, K Wang, ST Luka, A Neary, MP McDermott, D Oh, WK AF Choueiri, Toni K. Duh, Mei Sheng Clement, Jessica Brick, Ashley J. Rogers, Miranda J. Kwabi, Christabel Shah, Karishma Percy, Andrew G. Antras, Lucia Jayawant, Sujata S. Chen, Kristina Wang, Si-Tien Luka, Andi Neary, Maureen P. McDermott, David Oh, William K. TI Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review SO BJU INTERNATIONAL LA English DT Review DE renal cell carcinoma; angiogenesis inhibitor; effectiveness; safety ID INTERFERON-ALPHA; RANDOMIZED-TRIAL; SUNITINIB; CANCER; BEVACIZUMAB; SORAFENIB AB OBJECTIVE To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Lank Ctr Genitournary Oncol, Boston, MA 02115 USA. [Duh, Mei Sheng; Antras, Lucia; Jayawant, Sujata S.; Chen, Kristina; Wang, Si-Tien; Luka, Andi] Anal Grp Inc, Boston, MA USA. [Clement, Jessica; Kwabi, Christabel; Shah, Karishma; Percy, Andrew G.; McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Neary, Maureen P.] GlaxoSmithKline Inc, Collegeville, PA USA. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Lank Ctr Genitournary Oncol, 44 Binney St, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 20 TC 38 Z9 40 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2010 VL 105 IS 9 BP 1247 EP 1254 DI 10.1111/j.1464-410X.2009.08972.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 580YL UT WOS:000276486900011 PM 19863525 ER PT J AU Nakabayashi, M Oh, WK Jacobus, S Regan, MM Taplin, ME Kantoff, PW Rosenberg, JE AF Nakabayashi, Mari Oh, William K. Jacobus, Susanna Regan, Meredith M. Taplin, Mary-Ellen Kantoff, Philip W. Rosenberg, Jonathan E. TI Activity of ketoconazole after taxane-based chemotherapy in castration-resistant prostate cancer SO BJU INTERNATIONAL LA English DT Article DE ketoconazole; castration-resistant prostate cancer; taxane chemotherapy; secondary hormonal therapy; PSA response ID LOW-DOSE KETOCONAZOLE; PHASE-II; DIETHYLSTILBESTROL DIPHOSPHATE; BILATERAL ADRENALECTOMY; TRIAL; CARCINOMA; INHIBITOR; ANDROGENS; THERAPY AB OBJECTIVE To assess the efficacy of the androgen-synthesis inhibitor ketoconazole as a secondary hormonal therapy in patients with castration-resistant prostate cancer (CRPC) previously treated with chemotherapy, as persistent androgens appear to play a role in the development and maintenance of CRPC. PATIENTS AND METHODS We retrospectively identified 34 patients with CRPC who were treated with ketoconazole as a secondary hormonal therapy after paclitaxel- or docetaxel-based chemotherapy for CRPC. They were treated with ketoconazole 200-400 mg three times daily with or without hydrocortisone. Patients with previous use of ketoconazole were excluded. Half the patients had received estramustine as part of their chemotherapy regimen. The primary endpoint was the proportion of patients with a decline of >= 50% in their prostate-specific antigen (PSA) level. PSA progression was defined by the PSA Working Group 1 Criteria. RESULTS Eight of the 32 evaluable patients (25%) had a PSA decline of >= 50%. The median time to progression (TTP) was 3 months (95% confidence interval, 1.2-5.4). A history of previous response to taxane-based chemotherapy was not associated with the response to ketoconazole. However, previous use of oestrogens for CRPC was significantly associated with a shorter TTP on ketoconazole (1.5 vs 10.2 months; P = 0.03). CONCLUSIONS Ketoconazole has moderate activity as secondary hormonal therapy in patients with CRPC previously treated with taxane-based chemotherapy, although the TTP was short. Previous treatment with oestrogenic therapy is associated with a shorter TTP. C1 [Nakabayashi, Mari; Oh, William K.; Taplin, Mary-Ellen; Kantoff, Philip W.; Rosenberg, Jonathan E.] Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Jacobus, Susanna; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenberg, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM jonathan_rosenberg@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Bing-Sound Wong Fund for Prostate Cancer Research; Charles Laverty Fund FX We thank Helen Gee, Brian Schurko and Michelle Dyke for their excellent administrative support. Supported by the Bing-Sound Wong Fund for Prostate Cancer Research and the Charles Laverty Fund (to W. K. O.). NR 24 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD MAY PY 2010 VL 105 IS 10 BP 1392 EP 1396 DI 10.1111/j.1464-410X.2009.08971.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 589CQ UT WOS:000277122900011 PM 19863532 ER PT J AU Katz, MS Efstathiou, JA D'Amico, AV Kattan, MW Sanda, MG Nguyen, PL Smith, MR Carroll, PR Zietman, AL AF Katz, Matthew S. Efstathiou, Jason A. D'Amico, Anthony V. Kattan, Michael W. Sanda, Martin G. Nguyen, Paul L. Smith, Matthew R. Carroll, Peter R. Zietman, Anthony L. TI The 'CaP Calculator': an online decision support tool for clinically localized prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; decision support; surgery; radiotherapy; shared decision-making ID PREDICT PATHOLOGICAL STAGE; RADICAL PROSTATECTOMY; PRETREATMENT NOMOGRAM; PREOPERATIVE NOMOGRAM; GLEASON SCORE; DISEASE RECURRENCE; RADIATION-THERAPY; RADIOTHERAPY; ANTIGEN; RISK AB OBJECTIVE To design a decision-support tool to facilitate evidence-based treatment decisions in clinically localized prostate cancer, as individualized risk assessment and shared decision-making can decrease distress and decisional regret in patients with prostate cancer, but current individual models vary or only predict one outcome of interest. METHODS We searched Medline for previous reports and identified peer-reviewed articles providing pretreatment predictive models that estimated pathological stage and treatment outcomes in men with biopsy-confirmed, clinical T1-3 prostate cancer. Each model was entered into a spreadsheet to provide calculated estimates of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node involvement (LNI). Estimates of the prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) or radiotherapy (RT), and clinical outcomes after RT, were also entered. The data are available at http://www.capcalculator.org. RESULTS Entering a patient's 2002 clinical T stage, Gleason score and pretreatment PSA level, and details from core biopsy findings, into the CaP Calculator provides estimates from predictive models of pathological extent of disease, four models for ECE, four for SVI and eight for LNI. The 5-year estimates of PSA relapse-free survival after RT and 10-year estimates after RP were available. A printout can be generated with individualized results for clinicians to review with each patient. CONCLUSIONS The CaP Calculator is a free, online 'clearing house' of several predictive models for prostate cancer, available in an accessible, user-friendly format. With further development and testing with patients, the CaP Calculator might be a useful decision-support tool to help doctors promote evidence-based shared decision-making in prostate cancer. C1 [Katz, Matthew S.] St Med Ctr, Dept Radiat Oncol, Radiat Oncol Associates, Lowell, MA 01852 USA. [Katz, Matthew S.; Efstathiou, Jason A.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [D'Amico, Anthony V.; Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.; Nguyen, Paul L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kattan, Michael W.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Sanda, Martin G.] Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02114 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Carroll, Peter R.] Univ Calif San Francisco, Med Ctr, Dept Urol, San Francisco, CA 94143 USA. RP Katz, MS (reprint author), St Med Ctr, Dept Radiat Oncol, Radiat Oncol Associates, Lowell, MA 01852 USA. EM matt@roa-ne.com RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 FU NCI NIH HHS [K24 CA121990, K24 CA121990-05] NR 30 TC 14 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 MAY PY 2010 VL 105 IS 10 BP 1417 EP 1422 DI 10.1111/j.1464-410X.2010.09290.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 589CQ UT WOS:000277122900015 PM 20346051 ER PT J AU Saless, N Franco, GEL Litscher, S Kattappuram, RS Houlihan, MJ Vanderby, R Demant, P Blank, RD AF Saless, Neema Franco, Gloria E. Lopez Litscher, Suzanne Kattappuram, Robbie S. Houlihan, Meghan J. Vanderby, Ray Demant, Peter Blank, Robert D. TI Linkage mapping of femoral material properties in a reciprocal intercross of HcB-8 and HcB-23 recombinant mouse strains SO BONE LA English DT Article DE Recombinant congenic mice; Biomechanics; Linkage mapping; Systems biology; Bone quality ID QUANTITATIVE TRAIT LOCI; CONGENIC MICE; MECHANICAL-PROPERTIES; GENETIC DISSECTION; SKELETAL TRAITS; UTAH PARADIGM; BONE STRENGTH; RISK-FACTORS; POPULATION; GEOMETRY AB Skeletal fragility is an important health problem with a large genetic component. We performed a 603 animal F2 reciprocal intercross of the recombinant congenic strains HcB-8 and HcB-23 to genetically map quantitative trait loci (QTLs) for tissue-level femoral biomechanical performance. These included elastic and post-yield strain, Young's modulus, elastic and maximum stress, and toughness and were calculated from 3-point bend testing of femora by the application of standard beam equations. We mapped these with R/qtl and QTL Cartographer and established significance levels empirically by permutation testing. Significant QTLs for at least one trait are present on chromosomes 1, 6, and 10 in the full F2 population, with additional QTLs evident in subpopulations defined by sex and cross direction. On chromosome 10, we find a QTL for post-yield strain and toughness, phenotypes that have not been mapped previously. Notably, the HcB-8 allele at this QTL increases post-yield strain and toughness, but decreases bone mineral density (BMD), while the material property QTLs on chromosomes 1, 6, and at a second chromosome 10 QTL are independent of BMD. We find significant sex x QTL and cross direction x QTL interactions. A robust, pleiotropic chromosome 4 QTL that we previously reported at the whole-bone level showed no evidence of linkage at the tissue-level, supporting our interpretation that modeling capacity is its primary phenotype. Our data demonstrate an inverse relationship between femoral perimeter and Young's modulus, with R(2) = 0.27, supporting the view that geometric and material bone properties are subject to an integrated set of regulatory mechanisms. Mapping QTLs for tissue-level biomechanical performance advances understanding of the genetic basis of bone quality. Published by Elsevier Inc. C1 [Saless, Neema; Franco, Gloria E. Lopez; Litscher, Suzanne; Kattappuram, Robbie S.; Houlihan, Meghan J.; Vanderby, Ray; Blank, Robert D.] Univ Wisconsin, Madison, WI USA. [Saless, Neema; Franco, Gloria E. Lopez; Litscher, Suzanne; Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Demant, Peter] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Blank, RD (reprint author), H4-556 CSC 5148,600 Highland Ave, Madison, WI 53792 USA. EM rdb@medicine.wisc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU Office of Research and Development; Biomedical Laboratory RD Service; Department of Veterans Affairs; NIH [AR54753] FX This material is based upon work supported by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs (RDB) and performed in the Geriatrics Research, Education, and Clinical Center at the William S. Middleton Memorial Veterans Hospital. This report is Madison GRECC manuscript 2009-11. This work is also supported in part by NIH grant AR54753 (RDB). NR 45 TC 12 Z9 12 U1 0 U2 1 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 MAY PY 2010 VL 46 IS 5 BP 1251 EP 1259 DI 10.1016/j.bone.2010.01.375 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586VC UT WOS:000276941000005 PM 20102754 ER PT J AU Armand, P Deeg, HJ Kim, HT Lee, H Armistead, P de Lima, M Gupta, V Soiffer, RJ AF Armand, P. Deeg, H. J. Kim, H. T. Lee, H. Armistead, P. de Lima, M. Gupta, V. Soiffer, R. J. TI Multicenter validation study of a transplantation-specific cytogenetics grouping scheme for patients with myelodysplastic syndromes SO BONE MARROW TRANSPLANTATION LA English DT Article DE myelodysplastic syndromes; Allo-SCT; cytogenetics; therapy-related disease ID ACUTE MYELOID-LEUKEMIA; WORLD-HEALTH-ORGANIZATION; DE-NOVO; SCORING SYSTEM; PROGNOSTIC-SIGNIFICANCE; POOR-PROGNOSIS; THERAPY; ABNORMALITIES; CLASSIFICATION; DISEASE AB Cytogenetics is an important prognostic factor for patients with myelodysplastic syndromes (MDS). However, existing cytogenetics grouping schemes are based on patients treated with supportive care, and may not be optimal for patients undergoing allo-SCT. We proposed earlier an SCT-specific cytogenetics grouping scheme for patients with MDS and AML arising from MDS, based on an analysis of patients transplanted at the Dana-Farber Cancer Institute/Brigham and Women's Hospital. Under this scheme, abnormalities of chromosome 7 and complex karyotype are considered adverse risk, whereas all others are considered standard risk. In this retrospective study, we validated this scheme on an independent multicenter cohort of 546 patients. Adverse cytogenetics was the strongest prognostic factor for outcome in this cohort. The 4-year relapse-free survival and OS were 42 and 46%, respectively, in the standard-risk group, vs 21 and 23% in the adverse group (P<0.0001 for both comparisons). This grouping scheme retained its prognostic significance irrespective of patient age, disease type, earlier leukemogenic therapy and conditioning intensity. Therapy-related disease was not associated with increased mortality in this cohort, after taking cytogenetics into account. We propose that this SCT-specific cytogenetics grouping scheme be used for patients with MDS or AML arising from MDS who are considering or undergoing SCT. Bone Marrow Transplantation (2010) 45, 877-885; doi: 10.1038/bmt.2009.253; published online 28 September 2009 C1 [Armand, P.; Soiffer, R. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Deeg, H. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kim, H. T.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Lee, H.] Long Isl Jewish Med Ctr, Dept Med, New Hyde Pk, NY 11042 USA. [de Lima, M.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cell Therapy, Houston, TX 77030 USA. [Gupta, V.] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org FU National Heart, Lung and Blood Institute [NIAID U19 AI 29530, PO1 HL070149]; Ted and Eileen Pasquarello Research Fund; Leukemia and Lymphoma Society; NIH [HL036444, HL082941, CA018029] FX This work was funded in part by NIAID U19 AI 29530, PO1 HL070149 from the National Heart, Lung and Blood Institute, and the Ted and Eileen Pasquarello Research Fund. PA is also supported by a fellowship from the Leukemia and Lymphoma Society. HJD is supported by NIH grants HL036444, HL082941 and CA018029. NR 29 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2010 VL 45 IS 5 BP 877 EP 885 DI 10.1038/bmt.2009.253 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 595FS UT WOS:000277596700013 PM 19784076 ER PT J AU Serrano-Pozo, A William, CM Ferrer, I Uro-Coste, E Delisle, MB Maurage, CA Hock, C Nitsch, RM Masliah, E Growdon, JH Frosch, MP Hyman, BT AF Serrano-Pozo, Alberto William, Christopher M. Ferrer, Isidro Uro-Coste, Emmanuelle Delisle, Marie-Bernadette Maurage, Claude-Alain Hock, Christoph Nitsch, Roger M. Masliah, Eliezer Growdon, John H. Frosch, Matthew P. Hyman, Bradley T. TI Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology SO BRAIN LA English DT Article DE Alzheimer's disease; amyloid; immunization; AN1792 ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; A-BETA; IN-VIVO; A-BETA-42 IMMUNIZATION; PARVOPYRAMIDAL LAYER; SENILE PLAQUES; SYNAPSE LOSS; MEMORY LOSS; FOLLOW-UP AB Anti-amyloid-b immunization leads to amyloid clearance in patients with Alzheimer's disease, but the effect of vaccination on amyloid-b-induced neuronal pathology has not been quantitatively examined. The objectives of this study were to address the effects of anti-amyloid-b active immunization on neurite trajectories and the pathological hallmarks of Alzheimer's disease in the human hippocampus. Hippocampal sections from five patients with Alzheimer's disease enrolled in the AN1792 Phase 2a trial were compared with those from 13 non-immunized Braak-stage and age-matched patients with Alzheimer's disease, and eight age-matched non-demented controls. Analyses included neurite curvature ratio as a quantitative measure of neuritic abnormalities, amyloid and tau loads, and a quantitative characterization of plaque-associated neuritic dystrophy and astrocytosis. Amyloid load and density of dense-core plaques were decreased in the immunized group compared to non-immunized patients (P < 0.01 and P < 0.001, respectively). The curvature ratio in non-immunized patients with Alzheimer's disease was elevated compared to non-demented controls (P < 0.0001). In immunized patients, however, the curvature ratio was normalized when compared to non-immunized patients (P < 0.0001), and not different from non-demented controls. In the non-immunized patients, neurites close to dense-core plaques (within 50 mu m) were more abnormal than those far from plaques (i. e. beyond < 0 mm) (P < 0.0001). By contrast, in the immunized group neurites close to and far from the remaining dense-core plaques did not differ, and both were straighter compared to the non-immunized patients (P < 0.0001). Compared to non-immunized patients, dense-core plaques remaining after immunization had similar degree of astrocytosis (P= 0.6060), more embedded dystrophic neurites (P < 0.0001) and were more likely to have mitochondrial accumulation (P < 0.001). In addition, there was a significant decrease in the density of paired helical filament-1-positive neurons in the immunized group as compared to the non-immunized (P < 0.05 ), but not in the density of Alz50 or thioflavin-S positive tangles, suggesting a modest effect of anti-amyloid-b immunization on tangle pathology. Clearance of amyloid plaques upon immunization with AN1792 effectively improves a morphological measure of neurite abnormality in the hippocampus. This improvement is not just attributable to the decrease in plaque load, but also occurs within the halo of the remaining dense-core plaques. However, these remaining plaques still retain some of their toxic potential. Anti-amyloid-b immunization might also ameliorate the hippocampal tau pathology through a decrease in tau phosphorylation. These data agree with preclinical animal studies and further demonstrate that human anti-amyloid-b immunization does not merely clear amyloid from the Alzheimer's disease brain, but reduces some of the neuronal alterations that characterize Alzheimer's disease. C1 [Serrano-Pozo, Alberto; William, Christopher M.; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Sch Med,Massachusetts Alzheimer Dis Res Ctr, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Serrano-Pozo, Alberto] Hosp Univ Virgen del Rocio, Inst Biomed Sevilla, Serv Neurol, Seville 41013, Spain. [Ferrer, Isidro] Hosp Univ Bellvitge, IDIBELL, Inst Neuropatol, Serv Anat Patol, Barcelona 08907, Spain. [Uro-Coste, Emmanuelle; Delisle, Marie-Bernadette] CHU Toulouse, Fac Med Rangueil, INSERM,U858, Serv Anat Pathol & Histol Cytol, F-31432 Toulouse, France. [Maurage, Claude-Alain] Univ Lille Nord France, INSERM, U837, F-59000 Lille, France. [Hock, Christoph; Nitsch, Roger M.] Univ Zurich, Div Psychiat Res, CH-8008 Zurich, Switzerland. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Bldg 114,16th St 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org RI SERRANO-POZO, ALBERTO/F-5119-2013; LICEND, CEMND/F-1296-2015; OI William, Christopher/0000-0001-8933-1639; SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU NIA NIH HHS [AG08487, P50AG05134] NR 53 TC 81 Z9 82 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2010 VL 133 BP 1312 EP 1327 DI 10.1093/brain/awq056 PN 5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590KV UT WOS:000277225700012 PM 20360050 ER PT J AU Voineskos, AN Lobaugh, NJ Bouix, S Rajji, TK Miranda, D Kennedy, JL Mulsant, BH Pollock, BG Shenton, ME AF Voineskos, Aristotle N. Lobaugh, Nancy J. Bouix, Sylvain Rajji, Tarek K. Miranda, Dielle Kennedy, James L. Mulsant, Benoit H. Pollock, Bruce G. Shenton, Martha E. TI Diffusion tensor tractography findings in schizophrenia across the adult lifespan SO BRAIN LA English DT Article DE schizophrenia; diffusion tensor; ageing; white matter fibre pathways ID FRONTAL-CORTEX CONNECTIONS; MYELINATION-RELATED GENES; LATE-ONSET SCHIZOPHRENIA; WHITE-MATTER CHANGES; HUMAN BRAIN; UNCINATE FASCICULUS; COGNITIVE FUNCTION; BIPOLAR DISORDER; NOGO-66 RECEPTOR; EXPRESSION AB In healthy adult individuals, late life is a dynamic time of change with respect to the microstructural integrity of white matter tracts. Yet, elderly individuals are generally excluded from diffusion tensor imaging studies in schizophrenia. Therefore, we examined microstructural integrity of frontotemporal and interhemispheric white matter tracts in schizophrenia across the adult lifespan. Diffusion tensor imaging data from 25 younger schizophrenic patients (< 55 years), 25 younger controls, 25 older schizophrenic patients (>= 56 years) and 25 older controls were analysed. Patients with schizophrenia in each group were individually matched to controls. Whole-brain tractography and clustering segmentation were employed to isolate white matter tracts. Groups were compared using repeated measures analysis of variance with 12 within-group measures of fractional anisotropy: (left and right) uncinate fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, inferior occipito-frontal fasciculus, cingulum bundle, and genu and splenium of the corpus callosum. For each white matter tract, fractional anisotropy was then regressed against age in patients and controls, and correlation coefficients compared. The main effect of group (F(3,92) = 12.2, P < 0.001), and group by tract interactions (F(26,832) = 1.68, P = 0.018) were evident for fractional anisotropy values. Younger patients had significantly lower fractional anisotropy than younger controls (Bonferonni-corrected alpha = 0.0042) in the left uncinate fasciculus (t(48) = 3.7, P = 0.001) and right cingulum bundle (t(48) = 3.6, P = 0.001), with considerable effect size, but the older groups did not differ. Schizophrenic patients did not demonstrate accelerated age-related decline compared with healthy controls in any white matter tract. To our knowledge, this is the first study to examine the microstructural integrity of frontotemporal white matter tracts across the adult lifespan in schizophrenia. The left uncinate fasciculus and right cingulum bundle are disrupted in younger chronic patients with schizophrenia compared with matched controls, suggesting that these white matter tracts are related to frontotemporal disconnectivity. The absence of accelerated age-related decline, or differences between older community-dwelling patients and controls, suggests that these patients may possess resilience to white matter disruption. C1 [Voineskos, Aristotle N.; Rajji, Tarek K.; Miranda, Dielle; Mulsant, Benoit H.; Pollock, Bruce G.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Geriatr Mental Hlth Program, Toronto, ON M5T 1R8, Canada. [Voineskos, Aristotle N.; Kennedy, James L.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Dept Neurosci, Toronto, ON M5T 1R8, Canada. [Voineskos, Aristotle N.; Kennedy, James L.] Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Schizophrenia Program, Toronto, ON M5T 1R8, Canada. [Lobaugh, Nancy J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med, Toronto, ON M4N 3M5, Canada. [Bouix, Sylvain; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Brockton, MA 02301 USA. RP Voineskos, AN (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Geriatr Mental Hlth Program, 7th Floor,250 Coll St, Toronto, ON M5T 1R8, Canada. EM aristotle_voineskos@camh.net RI Voineskos, Aristotle/J-5014-2013; OI Bouix, Sylvain/0000-0003-1326-6054 FU Canadian Institutes of Health Research Clinician Scientist Award; APA/APIRE Astra-Zeneca Young Minds in Psychiatry Award; Canadian Institutes of Health Research Fellowship; National Institutes of Health (NIH) [R01, MH074794, MH 50740]; NIH [1P50, MH08272]; NIG/HS NIH [U54, GM072977-01]; VA MERIT; VA Schizophrenia Center; Sandra A. Rotman Research Institute; Centre for Addiction and Mental Health FX Canadian Institutes of Health Research Clinician Scientist Award (to A. N. V.); APA/APIRE Astra-Zeneca Young Minds in Psychiatry Award (to A. N. V.); Canadian Institutes of Health Research Fellowship (to T. K. R.); National Institutes of Health (NIH) (R01, grant number MH074794) (to M. E. S.), (R01, grant number MH 50740) (to M. E. S.), NIH (1P50, grant number MH08272) (to M. E. S.), NIG/HS NIH (U54 grant number GM072977-01) (to M. E. S.), VA MERIT (to M. E. S.), VA Schizophrenia Center Grant (to M. E. S.), NIH (R01, grant number MH082918) (to S. B.), the Sandra A. Rotman Research Institute (to B. G. P.) and the Centre for Addiction and Mental Health. NR 64 TC 77 Z9 77 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2010 VL 133 BP 1494 EP 1504 DI 10.1093/brain/awq040 PN 5 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590KV UT WOS:000277225700027 PM 20237131 ER PT J AU Watson, GS Leverenz, JB AF Watson, G. Stennis Leverenz, James B. TI Profile of Cognitive Impairment in Parkinson's Disease SO BRAIN PATHOLOGY LA English DT Article DE Parkinson's disease; dementia; cognitive impairment; neuropsychology ID LEWY BODIES; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; WORKING-MEMORY; DEMENTIA; INCIDENT; DEFICITS; NEUROPATHOLOGY; METAANALYSIS; PERFORMANCE AB Cognitive impairment (CI) is a common nonmotor complication of Parkinson's disease (PD), and is associated with significant disability for patients and burden for caregivers. Similar to motor symptoms, the characteristics of CI in PD can be quite variable, both in terms of what cognitive domains are impaired, and the timing of onset and rate of progression. This review will examine the profile of cognitive domain impairments observed in PD, with a focus on early CI (without dementia). We will also discuss possible relationships between specific cognitive domain impairments in PD and pathological processes such as Lewy-related pathology and Alzheimer's disease. It is our hypothesis that the specific characteristics of CI observed in individual PD patients provide clues to the underlying pathological processes, and that understanding the biological basis of this clinical phenomenon will assist in directing disease-specific treatments. Given the high lifetime risk for CI in PD, it is imperative that we improve our understanding and treatments for this common and disabling problem in PD. C1 [Leverenz, James B.] VA Puget Sound Hlth Care Syst, MIRECC 116MIRECC, Seattle Div, Mental Illness Ctr, Seattle, WA 98108 USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, MIRECC 116MIRECC, Seattle Div, Parkinsons Dis Ctr, Seattle, WA 98108 USA. [Watson, G. Stennis] VA Puget Sound Hlth Care Syst, MIRECC 116MIRECC, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Leverenz, James B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Watson, G. Stennis; Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Leverenz, JB (reprint author), VA Puget Sound Hlth Care Syst, MIRECC 116MIRECC, Seattle Div, Mental Illness Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM leverenz@u.washington.edu FU NIA NIH HHS [K01 AG023640, K01 AG023640-05]; NINDS NIH HHS [P50 NS062684-01A16220, P50 NS062684-01A1, P50 NS062684]; PHS HHS [P50MS062684-01A1] NR 58 TC 24 Z9 26 U1 3 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD MAY PY 2010 VL 20 IS 3 BP 640 EP 645 DI 10.1111/j.1750-3639.2010.00373.x PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 582MQ UT WOS:000276602100013 PM 20522089 ER PT J AU Silva, MD Bastos, M Netto, EM Gouvea, NAD Torres, AJL Kallas, E Watkins, DI Altfeld, M Brites, C AF Silva, Marcio de Oliveira Bastos, Milena Netto, Eduardo Martins de Lima Gouvea, Nancy Alves Leite Torres, Alex Jose Kallas, Esper Watkins, David I. Altfeld, Marcus Brites, Carlos TI Acute HIV infection with rapid progression to AIDS SO BRAZILIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; acute infection; progression; AIDS ID IMMUNODEFICIENCY-VIRUS TYPE-1; HLA-B35; PLASMA; COHORT; MEN; HLA AB Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm(3) within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r) was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm(3) and 10 months to HIV-RNA to become undetectable. C1 [Silva, Marcio de Oliveira; Bastos, Milena; Netto, Eduardo Martins; Leite Torres, Alex Jose; Brites, Carlos] Univ Fed Bahia, BR-41170290 Salvador, BA, Brazil. [de Lima Gouvea, Nancy Alves; Kallas, Esper] Fac Med, Sao Paulo, Brazil. [Altfeld, Marcus] Massachusetts Gen Hosp, Infect Dis Unit, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Silva, MD (reprint author), Rua Jorge Simoes 156 Ed San Juan,Apt 302, BR-40415720 Salvador, BA, Brazil. EM oliveiras_m@yahoo.com.br RI Kallas, Esper/C-9539-2012; Netto, Eduardo/D-1432-2013 OI Netto, Eduardo/0000-0003-1691-6761 NR 20 TC 1 Z9 1 U1 0 U2 1 PU CONTEXTO PI SALVADOR PA RUA ALFREDO MAGALHAES, 04-BARRA, SALVADOR, BAHIA 40140-140, BRAZIL SN 1413-8670 J9 BRAZ J INFECT DIS JI Braz. J. Infect. Dis. PD MAY-JUN PY 2010 VL 14 IS 3 BP 291 EP 293 DI 10.1590/S1413-86702010000300016 PG 3 WC Infectious Diseases SC Infectious Diseases GA 648KU UT WOS:000281693400016 ER PT J AU Wolff, AC Wang, ML Li, HL Pins, MR Pretorius, FJ Rowland, KM Sparano, JA Davidson, NE AF Wolff, Antonio C. Wang, Molin Li, Hailun Pins, Michael R. Pretorius, Florence J. Rowland, Kendrith M. Sparano, Joseph A. Davidson, Nancy E. TI Phase II trial of pegylated liposomal doxorubicin plus docetaxel with and without trastuzumab in metastatic breast cancer: Eastern Cooperative Oncology Group Trial E3198 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Pegylated liposomal doxorubicin; Trastuzumab; Docetaxel; Metastatic breast cancer; Cardiotoxicity ID COLONY-STIMULATING FACTOR; REDUCED CARDIOTOXICITY; STEALTH LIPOSOMES; KAPOSIS-SARCOMA; CHEMOTHERAPY; PACLITAXEL; MULTICENTER; PHARMACOKINETICS; TOXICITY; EFFICACY AB The purpose of this trial was to determine cardiac toxicity and overall efficacy of the pegylated liposome doxorubicin (PLD)-docetaxel couplet alone if HER2-negative metastatic breast cancer (internal control) or with trastuzumab if HER2-positive disease. Upon central HER2 confirmation, 84 eligible patients received induction with PLD (30 mg/m(2)) and docetaxel (60 mg/m(2)) every 3 weeks (maximum eight cycles), alone if HER2-negative (arm A; N = 38) or plus trastuzumab (4 mg/kg once, then 2 mg/kg weekly) if HER2-positive disease (arm B; N = 46) as first-line therapy. Maintenance therapy (without PLD) allowed. Primary objectives were to determine whether congestive heart failure (CHF) rate > 3% and the efficacy/toxicity of each arm. CHF rate was < 3% in each arm. Response rate, median progression-free-, and overall survival in arms A and B were 47.4 and 45.7%, 11 and 10.6 months, and 24.6 and 31.8 months, respectively. Trastuzumab arm was associated with higher rates of hand foot syndrome (grade 3: 22 vs. 38%; P = 0.16; overall 51 vs. 75%, P = 0.03) and treatment discontinuation due to toxicity/patient withdrawal (13 vs. 28%; P = 0.11). Febrile neutropenia occurred in similar to 10% of patients. In conclusion, concurrent administration of trastuzumab with PLD-docetaxel was not associated with higher risk of cardiac toxicity compared with PLD-docetaxel alone, but led to excessive hand-foot syndrome. C1 [Wolff, Antonio C.; Davidson, Nancy E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Wang, Molin; Li, Hailun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pins, Michael R.] Northwestern Univ, Chicago, IL 60611 USA. [Pretorius, Florence J.] Univ Pretoria, ZA-0002 Pretoria, South Africa. [Rowland, Kendrith M.] Carle Clin Assoc, Urbana, IL USA. [Sparano, Joseph A.] Albert Einstein Coll Med, Montefiore Einstein Canc Ctr, Bronx, NY 10467 USA. RP Wolff, AC (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1650 Orleans St,CRB1-189, Baltimore, MD 21231 USA. EM awolff@jhmi.edu OI Wolff, Antonio/0000-0003-3734-1063 FU Ortho Biotech Products, L.P.; Department of Health and Human Services; National Institutes of Health [CA23318, CA66636, CA21115, CA16116, CA59307, CA13650, CA14958] FX We acknowledge the support from Ortho Biotech Products, L.P., for the provision of investigational drug and financial support for central HER2 testing and from Genentech, Inc., for the provision of investigational drugs. We are also grateful to Dako A/S and Abbott Molecular for their support with free assay kits for central HER2 testing, and to Adekunle Raji, Susan Edgerton, and other members of the ECOG Pathology Coordinating Office. This work 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 and chairman's office, CA16116 to The Johns Hopkins Kimmel Cancer Center, CA59307 to the University of Pretoria, CA13650 to the Mayo Clinic (Carle Clinic), and CA14958 to the Albert Einstein College of Medicine. NR 34 TC 16 Z9 17 U1 2 U2 5 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 MAY PY 2010 VL 121 IS 1 BP 111 EP 120 DI 10.1007/s10549-010-0838-7 PG 10 WC Oncology SC Oncology GA 584NC UT WOS:000276758200011 PM 20333545 ER PT J AU Maiorano, E Regan, MM Viale, G Mastropasqua, MG Colleoni, M Castiglione-Gertsch, M Price, KN Gelber, RD Goldhirsch, A Coates, AS AF Maiorano, Eugenio Regan, Meredith M. Viale, Giuseppe Mastropasqua, Mauro G. Colleoni, Marco Castiglione-Gertsch, Monica Price, Karen N. Gelber, Richard D. Goldhirsch, Aron Coates, Alan S. TI Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer: Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Central necrosis; Fibrosis; Chemotherapy; Endocrine therapy; Breast cancer ID INVASIVE DUCTAL CARCINOMA; EARLY DISTANT RELAPSE; FIBROTIC FOCUS; TUMOR HYPOXIA; EXPRESSION; RESISTANCE; PARAMETER; RESPONSIVENESS; CHEMOTHERAPY; METASTASES AB A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1,850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. CNF was present in 84 of 1,850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine) = 0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR = 0.34 CNF-present, 0.96 CNF-absent]. The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported. C1 [Regan, Meredith M.; Price, Karen N.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr,Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA. [Maiorano, Eugenio] Univ Bari, Dept Pathol Anat, Bari, Italy. [Viale, Giuseppe; Mastropasqua, Mauro G.] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, I-20141 Milan, Italy. [Colleoni, Marco] European Inst Oncol, Res Unit Med Senol, Milan, Italy. [Castiglione-Gertsch, Monica] IBCSG Coordinating Ctr, Bern, Switzerland. [Goldhirsch, Aron] European Inst Oncol, Dept Med, I-20141 Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. RP Price, KN (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr,Frontier Sci & Technol Res Fdn, 44 Binney St,Mailstop CLSB 11007, Boston, MA 02115 USA. EM emaiorano@anatopat.uniba.it; mregan@jimmy.harvard.edu; giuseppe.viale@ieo.it; Mauro.Mastropasqua@ieo.it; marco.colleoni@ieo.it; monica.castiglione@bluewin.ch; price@jimmy.harvard.edu; gelber@jimmy.harvard.edu; aron.goldhirsch@ibcsg.org; alan.coates@ibcsg.org RI Maiorano, Eugenio/F-1382-2015; OI Maiorano, Eugenio/0000-0002-0472-5338 FU Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; The Cancer Council Australia; National Health Medical Research Council [920876, 950328, 980379, 100925]; National Cancer Institute [CA-75362]; Swedish Cancer Society; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); Cancer Association of South Africa; Oncosuisse/Cancer Research Switzerland FX We thank the local pathologists who submitted tumor blocks and slides, Rosita Kammler and the pathology team in Bern, Stefania Andrighetto at the pathology office in Milan, and Barry Gusterson and Elizabeth Mallon for central pathology review. We thank the patients, physicians, nurses and data managers who participate in the International Breast Cancer Study Group trials. The International Breast Cancer Study Group is supported by Swiss Group for Clinical Cancer Research, Frontier Science and Technology Research Foundation, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council Grants No. 920876, 950328, 980379, and 100925), National Cancer Institute (Grant No. CA-75362), Swedish Cancer Society, Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK), Cancer Association of South Africa (for South African participation), and Oncosuisse/Cancer Research Switzerland (for collection of tumor blocks within Switzerland). NR 24 TC 13 Z9 13 U1 1 U2 4 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 MAY PY 2010 VL 121 IS 1 BP 211 EP 218 DI 10.1007/s10549-009-0360-y PG 8 WC Oncology SC Oncology GA 584NC UT WOS:000276758200022 PM 19280340 ER PT J AU Kim, K Kong, SY Fulciniti, M Li, XF Song, WH Nahar, S Burger, P Rumizen, MJ Podar, K Chauhan, D Hideshima, T Munshi, NC Richardson, P Clark, A Ogden, J Goutopoulos, A Rastelli, L Anderson, KC Tai, YT AF Kim, Kihyun Kong, Sun-Young Fulciniti, Mariateresa Li, Xianfeng Song, Weihua Nahar, Sabikun Burger, Peter Rumizen, Mathew J. Podar, Klaus Chauhan, Dharminder Hideshima, Teru Munshi, Nikhil C. Richardson, Paul Clark, Ann Ogden, Janet Goutopoulos, Andreas Rastelli, Luca Anderson, Kenneth C. Tai, Yu-Tzu TI Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma (MM); MEK1; 2 inhibitor; bone marrow stromal cells (BMSCs); novel kinase inhibitor therapy ID HUMAN MULTIPLE-MYELOMA; ACTIVATING RAS MUTATIONS; PROTEIN-KINASE CASCADE; PLASMA-CELL LEUKEMIA; BONE-MARROW; N-RAS; VEGF SECRETION; GENE-MUTATIONS; ONCOGENIC RAS; BRAF GENE AB P>This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine-induced osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G(0)-G(1) cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib, rapamycin) anti-MM therapies. Significant tumour growth reduction in AS703026- vs. vehicle-treated mice bearing H929 MM xenograft tumours correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels in vivo. Moreover, AS703026 (< 200 nmol/l) was cytotoxic against the majority of tumour cells tested from patients with relapsed and refractory MM (84%), regardless of mutational status of RAS and BRAF genes. Importantly, BMSC-induced viability of MM patient cells was similarly blocked within the same dose range. Our results therefore support clinical evaluation of AS703026, alone or in combination with other anti-MM agents, to improve patient outcome. C1 [Kim, Kihyun; Kong, Sun-Young; Fulciniti, Mariateresa; Li, Xianfeng; Song, Weihua; Nahar, Sabikun; Burger, Peter; Rumizen, Mathew J.; Podar, Klaus; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil C.; Richardson, Paul; Anderson, Kenneth C.; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Kim, Kihyun; Kong, Sun-Young; Fulciniti, Mariateresa; Li, Xianfeng; Song, Weihua; Nahar, Sabikun; Burger, Peter; Rumizen, Mathew J.; Podar, Klaus; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil C.; Richardson, Paul; Anderson, Kenneth C.; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kim, Kihyun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Haematol Oncol, Seoul, South Korea. [Clark, Ann; Ogden, Janet; Goutopoulos, Andreas; Rastelli, Luca] EMD Serono Res Inst, Rockland, MA USA. RP Tai, YT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, M551,44 Binney St, Boston, MA 02115 USA. EM yu-tzu_tai@dfci.harvard.edu RI Kim, Kihyun/D-5175-2013 OI Kim, Kihyun/0000-0002-5878-8895 FU Multiple Myeloma Research Consortium; National Institutes of Health [RO-1 50947, PO1-78378]; SPORE [P50CA100707]; Lebow Fund FX We thank Dr. William Dalton at Lee Moffitt Cancer Center, Tampa, FL; Dr. Steven Rosen at Northwestern University, Chicago, IL; Dr. Takemi Otsuki at Kawasaki Medical School, Okayama, Japan; Dr. Steven Rosen at Northwestern University, Chicago, IL; Dr. Renate Burger at University of Erlangen-Nuernberg, Erlangen, Germany; Dr. Megumu Ogawa at Osaka University, Osaka, Japan for MM lines used in the study. The authors thank Dr Ender Soydan, Giovanni Tonon, and Sophia Adamia for help and suggestions on animal work, RAS gene mutation, and microphotography. We thank the nursing staff and clinical research coordinators of the LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center of Dana-Farber Cancer Institute for their constant help in providing primary tumour specimens for this study. Multiple Myeloma Research Consortium (Y.-T.Tai); National Institutes of Health Grants RO-1 50947, PO1-78378 and SPORE P50CA100707; and the Lebow Fund to Cure Myeloma (K.C.A.). NR 42 TC 40 Z9 42 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2010 VL 149 IS 4 BP 537 EP 549 DI 10.1111/j.1365-2141.2010.08127.x PG 13 WC Hematology SC Hematology GA 588BI UT WOS:000277040700008 PM 20331454 ER PT J AU Singh, AV Palladino, MA Lloyd, GK Potts, BC Chauhan, D Anderson, KC AF Singh, Ajita V. Palladino, Michael A. Lloyd, George Kenneth Potts, Barbara C. Chauhan, Dharminder Anderson, Kenneth C. TI Pharmacodynamic and efficacy studies of the novel proteasome inhibitor NPI-0052 (marizomib) in a human plasmacytoma xenograft murine model SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; pharmacology; apoptosis ID MULTIPLE-MYELOMA CELLS; MOLECULAR-WEIGHT PROTEASES; PROTEIN-DEGRADATION; BORTEZOMIB; ATP; POLYPEPTIDE; UBIQUITIN; DISTINCT; COMPLEX; SALINOSPORAMIDE AB P>Our previous study showed that the novel proteasome inhibitor NPI-0052 induces apoptosis in multiple myeloma (MM) cells resistant to conventional and bortezomib (Velcade (TM), Takeda, Boston, MA, USA) therapies. In vivo studies using human MM-xenografts demonstrated that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for an ongoing phase-1 clinical trial of NPI-0052 in relapsed/refractory MM patients. Here we performed pharmacodynamic (PD) studies of NPI-0052 using human MM xenograft murine model. Our results showed that NPI-0052: (i) rapidly left the vascular compartment in an active form after intravenous (i.v.) administration, (ii) inhibited 20S proteasome chymotrypsin-like (CT-L, beta 5), trypsin-like (T-L, beta 2), and caspase-like (C-L, beta 1) activities in extra-vascular tumours, packed whole blood (PWB), lung, liver, spleen, and kidney, but not brain and (iii) triggered a more sustained (> 24 h) proteasome inhibition in tumours and PWB than in other organs (< 24 h). Tissue distribution analysis of radiolabeled compound (3H-NPI-0052) in mice demonstrated that NPI-0052 left the vascular space and entered organs as the parent compound. Importantly, treatment of MM.1S-bearing mice with NPI-0052 showed reduced tumour growth without significant toxicity, which was associated with prolonged inhibition of proteasome activity in tumours and PWB but not normal tissues. C1 [Singh, Ajita V.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Singh, Ajita V.; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Palladino, Michael A.; Lloyd, George Kenneth; Potts, Barbara C.] Nereus Pharmaceut, San Diego, CA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Mayer Bldg Room 561,44 Binney St, Boston, MA 02115 USA. EM Dharminder_Chauhan@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu FU NIH [SPORE-P50100707, PO1-CA078378, RO1CA050947]; The LeBow Family Fund FX This investigation was supported by NIH grants SPORE-P50100707, PO1-CA078378, and RO1CA050947; and The LeBow Family Fund to Cure Myeloma. NR 33 TC 34 Z9 35 U1 3 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2010 VL 149 IS 4 BP 550 EP 559 DI 10.1111/j.1365-2141.2010.08144.x PG 10 WC Hematology SC Hematology GA 588BI UT WOS:000277040700009 PM 20331453 ER PT J AU Stewart, AJ Khan, AJ Devlin, PM AF Stewart, A. J. Khan, A. J. Devlin, P. M. TI Partial breast irradiation: a review of techniques and indications SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID DOSE-RATE BRACHYTHERAPY; INTRAOPERATIVE RADIOTHERAPY IORT; CONFORMAL RADIATION-THERAPY; 20-YEAR FOLLOW-UP; ENERGY X-RAYS; CONSERVING SURGERY; RANDOMIZED-TRIAL; CANCER PATIENTS; TUMOR BED; ELECTRONIC BRACHYTHERAPY AB The addition of whole-breast external beam radiotherapy (EBRT) to breast-conserving surgery results in a significant reduction in the risk of death due to breast cancer, but this may be offset by an increase in deaths from other causes and toxicity to surrounding organs. Because of this, and with a view to patterns of local recurrence, irradiation of the tumour bed has been explored in selected patients with early breast cancer using a variety of radiotherapeutic modalities. This review article explores the treatment options for partial breast irradiation and examines their role within the field of breast cancer treatment. C1 [Stewart, A. J.] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Guildford GU2 7XX, Surrey, England. [Khan, A. J.] Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ USA. [Devlin, P. M.] Harvard Univ, Sch Med, Dana Faber Brigham & Womens Canc Ctr, Div Brachytherapy,Dept Radiat Oncol, Boston, MA USA. RP Stewart, AJ (reprint author), Royal Surrey Cty Hosp, St Lukes Canc Ctr, Egerton Rd, Guildford GU2 7XX, Surrey, England. EM alexandra.stewart@royalsurrey.nhs.uk OI Khan, Atif/0000-0001-8640-8530 NR 56 TC 9 Z9 10 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 MAY PY 2010 VL 83 IS 989 BP 369 EP 378 DI 10.1259/bjr/11505970 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 592CO UT WOS:000277352900008 PM 20223911 ER PT J AU Van Meir, EG Hadjipanayis, CG Norden, AD Shu, HK Wen, PY Olson, JJ AF Van Meir, Erwin G. Hadjipanayis, Costas G. Norden, Andrew D. Shu, Hui-Kuo Wen, Patrick Y. Olson, Jeffrey J. TI Exciting New Advances in Neuro-Oncology The Avenue to a Cure for Malignant Glioma SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMAS; ENDOTHELIAL GROWTH-FACTOR; BRAIN-TUMOR CONSORTIUM; CHEMOATTRACTANT PROTEIN-1 MCP-1; INTEGRATED GENOMIC ANALYSIS; CEREBROSPINAL-FLUID; FACTOR RECEPTOR AB Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development for patients, their families, and medical professionals alike. CA Cancer J Clin 2010;60:166-193. (c) 2010 American Cancer Society, Inc. C1 [Van Meir, Erwin G.] Emory Univ, Sch Med, Dept Neurosurg, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Van Meir, Erwin G.; Hadjipanayis, Costas G.; Shu, Hui-Kuo; Olson, Jeffrey J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Dept Neurol, Boston, MA 02115 USA. [Shu, Hui-Kuo] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. RP Van Meir, EG (reprint author), Emory Univ, Sch Med, Dept Neurosurg, Dept Hematol & Med Oncol, 1365C Clifton Rd NE, Atlanta, GA 30322 USA. EM evanmei@emory.edu; jolson@emory.edu RI Waha, Andreas/J-2950-2014; OI Van Meir, Erwin G./0000-0003-2444-7707 FU National Institutes of Health (NIH) [CA86335, CA116804, NS053454]; Goldhirsh Foundation; Brain Tumor Funders Collaborative; Southeastern Brain Tumor Foundation; American Brain Tumor Association; Georgia Cancer Coalition Distinguished Cancer Clinicians and Scientists Program; Dana Foundation; Genentech; Amgen; Exelixis; Schering; Novartis; AstraZeneca; Boehringer; Merck; Schering-Plough FX Supported by National Institutes of Health (NIH) grants CA86335 and CA116804, the Goldhirsh Foundation, the Brain Tumor Funders Collaborative, the Southeastern Brain Tumor Foundation (to E.G.V.M.), NIH NS053454, the American Brain Tumor Association, the Southeastern Brain Tumor Foundation, the Georgia Cancer Coalition Distinguished Cancer Clinicians and Scientists Program, and the Dana Foundation (to C.G.H.). Dr. Norden has received honoraria from Genentech for serving on the advisory board and from Schering-Plough for serving on the speaker's bureau. Dr. Wen has received research support from Amgen, Genentech, Exelixis, Schering, Novartis, AstraZeneca, Boehringer, and Merck. The authors report no other conflicts of interest. NR 132 TC 524 Z9 533 U1 18 U2 119 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2010 VL 60 IS 3 BP 166 EP 193 DI 10.3322/caac.20069 PG 28 WC Oncology SC Oncology GA 595LS UT WOS:000277612600004 PM 20445000 ER PT J AU Levine, GN D'Amico, AV Berger, P Clark, PE Eckel, RH Keating, NL Milani, RV Sagalowsky, AI Smith, MR Zakai, N AF Levine, Glenn N. D'Amico, Anthony V. Berger, Peter Clark, Peter E. Eckel, Robert H. Keating, Nancy L. Milani, Richard V. Sagalowsky, Arthur I. Smith, Matthew R. Zakai, Neil CA Amer Heart Assoc Amer Canc Soc Amer Urological Assoc TI Androgen-Deprivation Therapy in Prostate Cancer and Cardiovascular Risk A Science Advisory From the American Heart Association, American Cancer Society, and American Urological Association Endorsed by the American Society for Radiation Oncology SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID HORMONE AGONIST TREATMENT; BONE-MINERAL DENSITY; LEAN BODY-MASS; METABOLIC SYNDROME; SUPPRESSION THERAPY; ARTERIAL STIFFNESS; RANDOMIZED-TRIAL; RTOG 85-31; FOLLOW-UP; DISEASE C1 [Levine, Glenn N.] Baylor Coll Med, Cardiol Sect, Houston, TX 77030 USA. [Levine, Glenn N.] Michael E DeBakey VA Med Ctr, Cardiac Care Unit, Houston, TX USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Med, Dept Hlth Care Policy, Boston, MA USA. [Berger, Peter] Geisinger Hlth Syst, Danville, PA USA. [Clark, Peter E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Eckel, Robert H.] Univ Colorado, Div Endocrinol Metab & Diabet & Cardiol, Denver, CO 80202 USA. [Milani, Richard V.] Ochsner Hlth Syst, Dept Cardiovasc Dis, New Orleans, LA USA. [Sagalowsky, Arthur I.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Genitourinary Unit Oncol, Boston, MA 02114 USA. [Zakai, Neil] Univ Vermont, Burlington, VT USA. RP Levine, GN (reprint author), Michael E DeBakey Med Ctr, Sect Cardiol 111B, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM glenn.levine@bcm.tmc.edu RI Clark, Peter/E-1423-2011; Milani, Richard/A-6045-2011 OI Clark, Peter/0000-0002-8006-7015; FU Sanofi-Aventis; Lance Armstrong Foundation; Prostate Cancer Foundation FX Robert H. Eckel is on the speakers' bureau of Innovia (Sanofi-Aventis-sponsored event), and has a research grant dagger and is a consultant to Sanofi-Aventis.; Arthur I. Sagalowsky is a consultant to Bioniche/Parexel,* and is on the data monitoring committee for the Bioniche* bladder cancer trial.; Matthew R. Smith receives research support from the Lance Armstrong Foundation and the Prostate Cancer Foundation and is a consultant to GTXt. NR 45 TC 82 Z9 82 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2010 VL 60 IS 3 BP 194 EP 201 DI 10.3322/caac.20061 PG 8 WC Oncology SC Oncology GA 595LS UT WOS:000277612600005 PM 20124400 ER PT J AU Kaul, D Wu, CL Adkins, CB Jordan, KW Defeo, EM Habbel, P Peterson, RT McDougal, WS Pohl, U Cheng, LL AF Kaul, David Wu, Chin-Lee Adkins, Christen B. Jordan, Kate W. Defeo, Elita M. Habbel, Piet Peterson, Randall T. McDougal, W. Scott Pohl, Ute Cheng, Leo L. TI Assessing prostate cancer growth with mRNA of spermine metabolic enzymes SO CANCER BIOLOGY & THERAPY LA English DT Article DE prostate cancer; PSA velocity; spermine; laser capture microdissection; real-time quantitative PCR; ornithine decarboxylase ID MAGNETIC-RESONANCE-SPECTROSCOPY; PREOPERATIVE PSA VELOCITY; TUMOR-SUPPRESSOR GENE; ORNITHINE-DECARBOXYLASE; RADICAL PROSTATECTOMY; PROTON NMR; C-MYC; POLYAMINES; RESOLUTION; TISSUE AB Statistical data from prostate cancer (PCa) clinics indicates that a large patient population discovered by annual prostate specific antigen (PSA) screening may have a latent form of the disease. However, current medical tests cannot differentiate slow from fast growing PCa, resulting in many unnecessary radical treatments and morbidities. It is thus necessary to find new screening tests that enable us to differentiate between fast- and slow-growing tumors. Inspired by the reported functions of spermine in carcinogenesis, we analyzed spermine and mRNA expression levels of rate-limiting enzymes in the spermine metabolic pathway for nine cases of PCa with accurately defined PSA velocity (Vpsa). Using MR spectroscopy, histopathology, laser-capture microdissection and real-time PCR techniques, we analyzed relationships between changes in spermine levels, mRNA expression levels of spermine anabolic and catabolic enzymes and human prostate cancer growth rates represented by serum Vpsa. The expression levels of spermine anabolic enzymes: ornithine decarboxylase (ODC1) and S-adenosylmethionine decarboxylase (AMD1) in benign epithelia surrounding cancer glands was logarithmically reduced with the increase of Vpsa (ODC1, p < 0.016; AMD1, p < 0.048), and antizyme (OAZ1) expression in cancer cells was increased with the increase of Vpsa (p < 0.001). Finally, we observed an inverse correlation between ODC1 and OAZ1 (p < 0.019) measured in cancer cells. These correlations may function to evaluate the aggressiveness of human prostate cancer, and assist patients and clinicians to select appropriate treatment strategies based on biological activities of individual tumors. C1 [Kaul, David; Wu, Chin-Lee; Adkins, Christen B.; Jordan, Kate W.; Defeo, Elita M.; Pohl, Ute; Cheng, Leo L.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Wu, Chin-Lee; McDougal, W. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Cheng, Leo L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kaul, David; Habbel, Piet] Charite, Inst Cell Biol & Neurobiol, Ctr Anat, D-13353 Berlin, Germany. RP Cheng, LL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM cheng@nmr.mgh.harvard.edu FU NCI NIH HHS [CA095624, CA115746] NR 27 TC 6 Z9 6 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY 1 PY 2010 VL 9 IS 9 BP 736 EP 742 DI 10.4161/cbt.9.9.11549 PG 7 WC Oncology SC Oncology GA 662TR UT WOS:000282836300011 PM 20215859 ER PT J AU Bajaj, A Driver, JA Schernhammer, ES AF Bajaj, Archna Driver, Jane A. Schernhammer, Eva S. TI Parkinson's disease and cancer risk: a systematic review and meta-analysis SO CANCER CAUSES & CONTROL LA English DT Article DE Neurodegenerative diseases; Neoplasm; Meta-analysis ID MALIGNANT-MELANOMA; MORTALITY; COHORT; DEATH; DIAGNOSIS; SURVIVAL; PROGRESSION; LEVODOPA; SMOKING; EPIDEMIOLOGY AB To appraise the existing literature on cancer risk among patients with Parkinson's disease (PD), determine the overall cancer risk ratio among patients with PD, explore reasons for variations in study results, and assess the potential for publication bias. Studies reporting cancer risk in patients with PD were identified by searching electronic databases through 18 November 2009 using the terms PARKINSON DISEASE, NEOPLASM, and CANCER. Reviewers individually performed data extraction and scored each study using a quality assessment instrument. Cancer risk in all patients with PD was calculated overall, and after excluding melanoma and other skin cancers. We tested for heterogeneity and publication bias, and stratified for gender, smoking-related versus non-smoking-related cancers, and study quality. We pooled effect sizes using fixed-effects and random-effects models. We included 29 studies in the overall analysis for a total of 107,598 patients with PD. Compared to controls, the aggregate risk for cancer in patients with PD was 0.73 (95% confidence interval [CI], 0.63-0.83), and after excluding skin tumors, 0.69 (95% CI, 0.62-0.78). These risks varied by gender (males, RR = 0.71, 95% CI, 0.57-0.88; females, RR = 0.82; 95% CI, 0.68-0.98). After strictly excluding skin tumors, both smoking-related (RR = 0.61; 95% CI, 0.58-0.65) and non-smoking-related cancer rates (RR = 0.76; 95% CI, 0.65-0.89) were significantly lower among patients with PD . Studies on cancer risk among patients with PD collectively show significantly reduced cancer risk ratios. Further research to explain the biological mechanisms, particularly for the association with non-smoking-related cancers, appears warranted. C1 [Bajaj, Archna; Schernhammer, Eva S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Bajaj, Archna; Schernhammer, Eva S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bajaj, Archna] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Driver, Jane A.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Driver, Jane A.] Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Schernhammer, Eva S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schernhammer, Eva S.] LBI ACR CTO, Vienna, Austria. [Schernhammer, Eva S.] CEADDP, ACR ITR VIEnna, Vienna, Austria. RP Bajaj, A (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM n2baj@channing.harvard.edu NR 61 TC 95 Z9 98 U1 0 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2010 VL 21 IS 5 BP 697 EP 707 DI 10.1007/s10552-009-9497-6 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 584QX UT WOS:000276768500006 PM 20054708 ER PT J AU Rathkopf, D Wong, BY Ross, RW Anand, A Tanaka, E Woo, MM Hu, J Dzik-Jurasz, A Yang, W Scher, HI AF Rathkopf, Dana Wong, Bryan Y. Ross, Robert W. Anand, Aseem Tanaka, Erika Woo, Margaret M. Hu, Jing Dzik-Jurasz, Andy Yang, Wei Scher, Howard I. TI A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Genitourinary Cancer Symposium of the American-Society-of-Clinical-Oncology CY FEB 14-16, 2008 CL San Francisco, CA SP Amer Soc Clin Oncol DE Prostate cancer; Castration-resistant; Histone deacetylase inhibitor; Panobinostat; Docetaxel ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; CIRCULATING TUMOR-CELLS; ANDROGEN RECEPTOR; CLINICAL-TRIALS; END-POINTS; PET; REPRODUCIBILITY; RECOMMENDATIONS; MALIGNANCIES AB Purpose Histone deacetylase inhibitors have demonstrated anticancer activity against a range of tumors. We aimed to define the maximum tolerated dose, toxicity, activity, and pharmacokinetics of oral panobinostat, a pan-deacetylase inhibitor, alone and in combination with docetaxel for the treatment of castration-resistant prostate cancer (CRPC). Methods Sixteen patients were enrolled, eight in each arm. Eligible patients had CRPC and adequate organ function. In arm I, oral panobinostat (20 mg) was administered on days 1, 3, and 5 for 2 consecutive weeks followed by a 1-week break. In arm II, oral panobinostat (15 mg) was administered on the same schedule in combination with docetaxel 75 mg/m(2) every 21 days. Results Dose-limiting toxicities were grade 3 dyspnea (arm I) and grade 3 neutropenia > 7 days (arm II). In arm I, all patients developed progressive disease despite accumulation of acetylated histones in peripheral blood mononuclear cells. In arm II, five of eight patients (63%) had a, >= 50% decline in prostate-specific antigen (PSA), including one patient whose disease had previously progressed on docetaxel. Conclusions Oral panobinostat with and without docetaxel is feasible, and docetaxel had no apparent effect on the pharmacokinetics of panobinostat. Since preclinical studies suggest a dose-dependent effect of panobinostat on PSA expression, and other phase I data demonstrate that intravenous panobinostat produces higher peak concentrations (>20- to 30-fold) and area under the curve (3.5x-5x), a decision was made to focus the development of panobinostat on the intravenous formulation to treat CRPC. C1 [Rathkopf, Dana; Anand, Aseem; Tanaka, Erika; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA. [Rathkopf, Dana; Anand, Aseem; Tanaka, Erika; Scher, Howard I.] Cornell Univ, Dept Med, Joan & Sanford I Weill Med Coll, New York, NY 10021 USA. [Wong, Bryan Y.] Mayo Clin, Scottsdale, AZ USA. [Ross, Robert W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Woo, Margaret M.; Hu, Jing; Dzik-Jurasz, Andy; Yang, Wei] Novartis Oncol, Florham Pk, NJ USA. RP Rathkopf, D (reprint author), Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, 1275 York Ave, New York, NY 10065 USA. EM rathkopd@mskcc.org RI Anand, Aseem/P-1214-2014; OI Anand, Aseem/0000-0002-3606-540X; Rathkopf, Dana/0000-0002-4503-7582 FU NCI NIH HHS [PC051382] NR 28 TC 65 Z9 70 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2010 VL 66 IS 1 BP 181 EP 189 DI 10.1007/s00280-010-1289-x PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 591US UT WOS:000277331100021 PM 20217089 ER PT J AU Spivey, KA Banyard, J Solis, LM Wistuba, II Barletta, JA Gandhi, L Feldman, HA Rodig, SJ Chirieac, LR Zetter, BR AF Spivey, Kristin A. Banyard, Jacqueline Solis, Luisa M. Wistuba, Ignacio I. Barletta, Justine A. Gandhi, Leena Feldman, Henry A. Rodig, Scott J. Chirieac, Lucian R. Zetter, Bruce R. TI Collagen XXIII: A Potential Biomarker for the Detection of Primary and Recurrent Non-Small Cell Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EXPRESSION; DIAGNOSIS; MUTATIONS; MARKERS; CARCINOMA; SMOKERS; PROTEIN; BREATH; FURIN; PANEL AB Background: Collagen XXIII is a transmembrane collagen previously shown to be upregulated in metastatic prostate cancer. The purpose of this study was to determine the protein expression of collagen XXIII in tumor tissues from a variety of cancers and to assess the utility of collagen XXIII as a biomarker for non-small cell lung cancer (NSCLC). Methods: A multicancer tissue microarray was used for the immunohistochemical examination of collagen XXIII protein expression in a variety of cancers. Subsequently, collagen XXIII expression was analyzed in three separate cohorts using tissue microarrays with representative tumor and control lung tissues from NSCLC patients. In addition, NSCLC patient urine samples were analyzed for the presence of collagen XXIII through Western blot. Results: Collagen XXIII was present in tissue samples from a variety of cancers. Within lung cancer tissues, collagen XXIII staining was enriched in NSCLC subtypes. Collagen XXIII was present in 294 of 333 (88%) lung adenocarcinomas and 97 of 133 (73%) squamous cell carcinomas. In urine, collagen XXIII was present in 23 of 29 (79%) NSCLC patient samples but only in 15 of 54 (28%) control samples. High collagen XXIII staining intensity correlated with shorter recurrence-free survival in NSCLC patients. Conclusions: We show the capability of collagen XXIII as a tissue and urinary biomarker for NSCLC, in which positivity in tissue or urine significantly correlates with the presence of NSCLC and high staining intensity is a significant recurrence predictor. Impact: Inclusion of collagen XXIII in a tissue-or urine-based cancer biomarker panel could inform NSCLC patient treatment decisions. Cancer Epidemiol Biomarkers Prev; 19(5); 1362-72.(C)2010 AACR. C1 [Spivey, Kristin A.; Banyard, Jacqueline; Zetter, Bruce R.] Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. [Feldman, Henry A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Gandhi, Leena] Dana Farber Canc Inst, Thorac Oncol Program, Boston, MA 02115 USA. [Barletta, Justine A.; Rodig, Scott J.; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Solis, Luisa M.; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. RP Zetter, BR (reprint author), Karp Family Res Labs, Dept Surg, Room 11-125,1 Blackfan Circle, Boston, MA 02115 USA. EM Bruce.Zetter@childrens.harvard.edu OI Gandhi, Leena/0000-0002-2398-9179 FU Department of Defense [W81XWH-05-2-0027]; Specialized Program of Research Excellence in Lung Cancer [P50CA70907]; NIH [CA90578, CA074386, CA092824] FX Grant Support; Grants from the Department of Defense grant W81XWH-05-2-0027 (I. I. Wistuba); the Specialized Program of Research Excellence in Lung Cancer Grant P50CA70907 (I. I. Wistuba); and NIH grant no. CA90578, CA074386, and CA092824 (L. R. Chirieac). NR 38 TC 10 Z9 11 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2010 VL 19 IS 5 BP 1362 EP 1372 DI 10.1158/1055-9965.EPI-09-1095 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607HI UT WOS:000278489800025 PM 20447926 ER PT J AU Penney, KL Schumacher, FR Li, HJ Kraft, P Morris, JS Kurth, T Mucci, LA Hunter, DJ Kantoff, PW Stampfer, MJ Ma, J AF Penney, Kathryn L. Schumacher, Fredrick R. Li, Haojie Kraft, Peter Morris, J. Steven Kurth, Tobias Mucci, Lorelei A. Hunter, David J. Kantoff, Philip W. Stampfer, Meir J. Ma, Jing TI A Large Prospective Study of SEP15 Genetic Variation, Interaction with Plasma Selenium Levels, and Prostate Cancer Risk and Survival SO CANCER PREVENTION RESEARCH LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; GLYCOPROTEIN GLUCOSYLTRANSFERASE; ENDOPLASMIC-RETICULUM; 15-KDA SELENOPROTEIN; UDP-GLUCOSE; PREVENTION; PROTEIN; TRIAL; SUPPLEMENTATION; POLYMORPHISM AB The role of selenium in prostate cancer (PCa) risk remains controversial, but many epidemiologic studies suggest an inverse association with more aggressive disease. A recently discovered selenoprotein, SEP15, which is highly expressed in the prostate, may play a role either independently or by modifying the effects of selenium. We genotyped four common single-nucleotide polymorphisms capturing common variation (frequency >5%; R(2) > 0.8) within SEP15, as well as rs5859 in the 3' untranslated region, previously reported to reduce the efficiency of selenium incorporation into SEP15. We examined the association of these single-nucleotide polymorphisms with PCa risk and PCa-specific mortality, as well as their interactions with plasma selenium levels, in the Physicians' Health Study. In this nested case-control study (1,286 cases and 1,267 controls), SEP15 polymorphisms were not significantly associated with PCa risk. However, among the cases, three variants were significantly associated with PCa-specific mortality [rs479341 hazard ratio (HR), 1.94; 95% confidence interval (95% CI), 1.15-3.25; rs1407131 HR, 2.85; 95% CI, 1.45-5.59; rs561104 HR, 1.54; 95% CI, 1.12-2.11] with a recessive model. Additionally, rs561104 significantly modified the association of plasma selenium with PCa survival (P(interaction) = 0.02); an inverse relationship of high levels of selenium with PCa mortality was apparent only among those without the increased risk genotype. This study provides evidence that SEP15 genetic variation may influence PCa mortality. Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype. Cancer Prev Res; 3(5); 604-10. (C) 2010 AACR. C1 [Penney, Kathryn L.; Kraft, Peter; Kurth, Tobias; Mucci, Lorelei A.; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Penney, Kathryn L.; Mucci, Lorelei A.; Hunter, David J.; Stampfer, Meir J.; Ma, Jing] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Li, Haojie] GlaxoSmithKline R&D, Worldwide Epidemiol Oncol, Collegeville, PA USA. [Morris, J. Steven] Univ Missouri, Res Reactor Ctr, Columbia, MO USA. RP Penney, KL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM kpenney@hsph.harvard.edu; jing.ma@channing.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU Department of Defense [PC050569, PC073618]; National Cancer Institute [CA-42182, CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute, Bethesda, Maryland [HL-26490, HL-34595]; National Research Service [T32 CA009001-32, R25 CA098566] FX Department of Defense grants PC050569 and PC073618. The PHS was supported by grants CA-42182, CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. K. L. Penney was supported by National Research Service Awards T32 CA009001-32 and R25 CA098566. NR 22 TC 41 Z9 45 U1 0 U2 6 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 MAY PY 2010 VL 3 IS 5 BP 604 EP 610 DI 10.1158/1940-6207.CAPR-09-0216 PG 7 WC Oncology SC Oncology GA 591IP UT WOS:000277294000006 PM 20424130 ER PT J AU Giampieri, S Pinner, S Sahai, E AF Giampieri, Silvia Pinner, Sophie Sahai, Erik TI Intravital Imaging Illuminates Transforming Growth Factor beta Signaling Switches during Metastasis SO CANCER RESEARCH LA English DT Review ID BREAST-CANCER CELLS; MOTILITY IN-VIVO; TGF-BETA; MESENCHYMAL TRANSITIONS; GENE-EXPRESSION; RHO-GTPASES; INVASION; TUMOR; MELANOMA; INTRAVASATION AB Transforming growth factor beta (TGF beta) has seemingly contradictory roles in tumor progression: it can promote metastatic invasion but also act as a tumor suppressor. Recently, two studies have used intravital imaging to unravel the role of TGF beta at different stages of the metastatic process. TGF beta promotes single cell motility, which enables invasion into blood vessels. However the activation of TGF beta signaling is a transient event and is not maintained at distant sites. The downregulation of TGF beta signaling at secondary sites then permits growth of secondary tumors. In the absence of TGF beta, cells are restricted to collective movement and lymphatic spread. Here, we discuss these findings and their potential implications. Cancer Res; 70(9); 3435-9. (C) 2010 AACR. C1 [Sahai, Erik] Canc Res UK, Tumor Cell Biol Lab, London WC2A 3PX, England. [Giampieri, Silvia] UCL Canc Inst, Radiat Biol Lab, London, England. [Pinner, Sophie] Dana Farber Canc Inst, Canc Immunol & AIDS Dept, Boston, MA 02115 USA. RP Sahai, E (reprint author), Canc Res UK, Tumor Cell Biol Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM erik.sahai@cancer.org.uk RI Acton, Sophie/G-9784-2012; OI Acton, Sophie/0000-0003-2704-716X; Giampieri, Silvia/0000-0001-5484-3140; Sahai, Erik/0000-0002-3932-5086 FU Breast Cancer Campaign; Cancer Research UK FX S. Giampieri was funded by the Breast Cancer Campaign (May 12, 2005), E. Sahai and S. Pinner were funded by Cancer Research UK. NR 27 TC 34 Z9 36 U1 1 U2 8 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 MAY 1 PY 2010 VL 70 IS 9 BP 3435 EP 3439 DI 10.1158/0008-5472.CAN-10-0466 PG 5 WC Oncology SC Oncology GA 607GD UT WOS:000278486200003 PM 20424121 ER PT J AU Wong, HK Lahdenranta, J Kamoun, WS Chan, AW McClatchey, AI Plotkin, SR Jain, RK di Tomaso, E AF Wong, Hon Kit Lahdenranta, Johanna Kamoun, Walid S. Chan, Annie W. McClatchey, Andrea I. Plotkin, Scott R. Jain, Rakesh K. di Tomaso, Emmanuelle TI Anti-Vascular Endothelial Growth Factor Therapies as a Novel Therapeutic Approach to Treating Neurofibromatosis-Related Tumors SO CANCER RESEARCH LA English DT Article ID BLOOD-NERVE BARRIER; TYROSINE KINASE INHIBITOR; SCHWANNOMA CELL-LINE; ANTIANGIOGENIC THERAPY; FACTOR RECEPTOR; VASCULAR NORMALIZATION; VESTIBULAR SCHWANNOMA; RECTAL-CANCER; ANTI-VEGF; VESSELS AB Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti-vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2(-/-) cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2(-/-) tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling. Cancer Res; 70(9); 3483-93. (C) 2010 AACR. C1 [Wong, Hon Kit; Lahdenranta, Johanna; Kamoun, Walid S.; Jain, Rakesh K.; di Tomaso, Emmanuelle] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. [Chan, Annie W.; McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Plotkin, Scott R.] Harvard Univ, Sch Med, Boston, MA USA. RP di Tomaso, E (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM Emmanuelle.di_tomaso@novartis.com RI Wong, Hon-Kit/G-3944-2014 OI Wong, Hon-Kit/0000-0003-0049-8454 FU Claflin Award; Children's Tumor Foundation; Damon Runyon Cancer Research Foundation; Flight Attendant Medical Research Institute; Federal Share/NCI Proton Beam Program; [PO1CA80124] FX Grant Support; Claflin Award (E. di Tomaso), Drug Discovery Initiative Award from Children's Tumor Foundation (E. di Tomaso), Damon Runyon Cancer Research Foundation (J. Lahdenranta), The Flight Attendant Medical Research Institute (A. W. Chan), The Federal Share/NCI Proton Beam Program income grants (E. di Tomaso and R. K. Jain), and PO1CA80124 (R. K. Jain). NR 41 TC 45 Z9 48 U1 3 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2010 VL 70 IS 9 BP 3483 EP 3493 DI 10.1158/0008-5472.CAN-09-3107 PG 11 WC Oncology SC Oncology GA 607GD UT WOS:000278486200008 PM 20406973 ER PT J AU Liao, SL Elmariah, S van der Zee, S Sealove, BA Fuster, V AF Liao, Steve L. Elmariah, Sammy van der Zee, Sarina Sealove, Brett A. Fuster, Valentin TI Does Medical Therapy for Thoracic Aortic Aneurysms Really Work? Are beta-Blockers Truly Indicated? CON SO CARDIOLOGY CLINICS LA English DT Article DE Aortic aneurysm; Medical therapy; beta-Dockers ID ANGIOTENSIN-II BLOCKADE; SMOOTH-MUSCLE-CELLS; MARFAN-SYNDROME; MATRIX METALLOPROTEINASES; ADRENERGIC-BLOCKADE; EXPANSION RATE; SIMVASTATIN SUPPRESSES; EXTRACELLULAR-MATRIX; ROOT DILATION; DOUBLE-BLIND AB Thoracic aortic aneurysms (TAA) often represent the final manifestation of hereditary or degenerative disease processes. TAA are primarily caused by age-related degenerative changes. In this article, the authors highlight the most common pathophysiologic mechanisms responsible for TAA formation and review the paucity of evidence supporting the spectrum of medical therapies for TAA other than renin-angiotensin inhibition. More clinical trials on TAA are required before medical therapies such as beta-blockers, statins, and macrolide antibiotics can be recommended. C1 [Liao, Steve L.; Elmariah, Sammy; van der Zee, Sarina; Sealove, Brett A.; Fuster, Valentin] Mt Sinai Sch Med, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Liao, Steve L.] James J Peters Vet Affairs Med Ctr, Dept Med, Div Cardiovasc, Bronx, NY USA. [Fuster, Valentin] Ctr Nacl Invest Cardiovasc, Madrid, Spain. RP Fuster, V (reprint author), Mt Sinai Sch Med, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM valentin.fuster@mssm.edu RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 75 TC 3 Z9 3 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 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD MAY PY 2010 VL 28 IS 2 BP 261 EP + DI 10.1016/j.cc1.2010.01.002 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604UT UT WOS:000278304700016 PM 20452539 ER PT J AU Ide, T Chu, K Aaronson, SA Lee, SW AF Ide, Takao Chu, Kiki Aaronson, Stuart A. Lee, Sam W. TI GAMT joins the p53 network Branching into metabolism SO CELL CYCLE LA English DT Article DE p53; cancer cell metabolism; GAMT; creatine metabolism; fatty acid oxidation ID CREATINE-KINASE ACTIVITY; ACTIVATED PROTEIN-KINASE; NORMAL-TISSUES; BREAST-CANCER; INBORN ERROR; BB-ISOENZYME; FATTY-ACID; DEFICIENCY; APOPTOSIS; TRANSFORMATION AB The p53 protein functions to prevent tumor development by restricting proliferation, motility and survival of abnormal or stressed cells. In addition to well-established roles, recent discoveries indicate a role for p53 in the regulation of pathways involved in energy metabolism. The metabolic functions of p53 can inhibit the shift to glycolysis that is characteristically seen in cancer cells, while favoring the energy production by mitochondrial oxidative phosphorylation. Identification of guanidinoacetate methyltransferase (GAMT) as a new p53 target connects p53 to creatine metabolism critical in the regulation of ATP homeostasis. The involvement of GAMT in both genotoxic and metabolic stress-induced apoptosis, as well as the requirement of p53-dependent upregulation of GAMT in glucose starvation-mediated fatty acid oxidation (FAO), demonstrate a further role of p53 in coordinating stress response with changes in cellular metabolism. Such activities of p53 would help to bring a better understanding of how cancer cells acquire unique metabolic features to maintain their own survival and proliferation, and might provide interesting clues toward the development of novel therapies. C1 [Ide, Takao; Chu, Kiki; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Ide, Takao; Chu, Kiki; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [Ide, Takao] Saga Univ, Dept Surg, Fac Med, Saga 840, Japan. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM swlee@partners.org FU National Institutes of Health [CA149477, CA142805, CA085681, CA80058] FX We would like to thank the other members of the Lee laboratory for helpful discussion. This work was supported by National Institutes of Health grants (CA149477, CA142805, CA085681 and CA80058). NR 58 TC 12 Z9 12 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2010 VL 9 IS 9 BP 1706 EP 1710 PG 5 WC Cell Biology SC Cell Biology GA 592TC UT WOS:000277402200017 PM 20404548 ER PT J AU Podar, K Anderson, KC AF Podar, Klaus Anderson, Kenneth C. TI A therapeutic role for targeting c-Myc/Hif-1-dependent signaling pathways SO CELL CYCLE LA English DT Article DE HIF; c-Myc; targeted therapy; tumor microenvironment ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL-GROWTH-FACTOR; HISTONE DEACETYLASE INHIBITORS; MYC TRANSCRIPTIONAL ACTIVITY; SMALL-MOLECULE INHIBITORS; C-MYC/MAX DIMERIZATION; FACTOR-I-ALPHA; CANCER CELLS; TUMOR PROGRESSION; MULTIPLE-MYELOMA AB Deregulated c-Myc occurs in similar to 30% of human cancers. Similarly, hypoxiainducible factor (HIF) is commonly overexpressed in a variety of human malignancies. Under physiologic conditions, HIF inhibits c-Myc activity; however, when deregulated oncogenic c-Myc collaborates with HIF in inducing the expression of VEGF, PDK1 and hexokinase 2. Most of the knowledge of HIF derives from studies investigating a role of HIF under hypoxic conditions, however, HIF-1 alpha stabilization is also found in normoxic conditions. Specifically, under hypoxic conditions HIF-1-mediated regulation of oncogenic c-Myc plays a pivotal role in conferring metabolic advantages to tumor cells as well as adaptation to the tumorigenic micromilieu. In addition, our own results show that under normoxic conditions oncogenic c-Myc is required for constitutive high HIF-1 protein levels and activity in Multiple Myeloma (MM) cells, thereby influencing VEGF secretion and angiogenic activity within the bone marrow microenvironment. Further studies are needed to delineate the functional relevance of HIF, MYC, and the HIF-MYC collaboration in MM and other malignancies, also integrating the tumor microenvironment and the cellular context. Importantly, early studies already demonstrate promising preclinical of novel agents, predominantly small molecules, which target c-Myc, HIF or both. C1 [Podar, Klaus; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Podar, Klaus] Univ Heidelberg, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU National Institutes of Health [RO CA50947, PO-1 CA78378, P50 CA100707]; Doris Duke Distinguished Clinical Research Scientist Award FX This work was supported by a National Institutes of Health Grants RO CA50947, PO-1 CA78378, and P50 CA100707; and the Doris Duke Distinguished Clinical Research Scientist Award (to K.C.A.). NR 136 TC 40 Z9 43 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2010 VL 9 IS 9 BP 1722 EP 1728 PG 7 WC Cell Biology SC Cell Biology GA 592TC UT WOS:000277402200020 PM 20404562 ER PT J AU Scheiman, J Jamieson, KV Ziello, J Tseng, JC Meruelo, D AF Scheiman, J. Jamieson, K. V. Ziello, J. Tseng, J-C Meruelo, D. TI Extraribosomal functions associated with the C terminus of the 37/67 kDa laminin receptor are required for maintaining cell viability SO CELL DEATH & DISEASE LA English DT Article DE laminin receptor; extraribosomal; viability; translation; silent mutant ID BINDING-PROTEIN; MAMMALIAN-CELLS; GREEN TEA; PRECURSOR; VIRUS; APOPTOSIS; HOMOLOGY; CANCER; IDENTIFICATION; POLYPEPTIDE AB The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly. LAMR is important for cell viability; however, it is unclear which of its functions are essential. We developed a silent mutant LAMR construct, resistant to siRNA, to rescue the phenotypic effects of knocking down endogenous LAMR, which include inhibition of protein synthesis, cell cycle arrest, and apoptosis. In addition, we generated a C-terminal-truncated silent mutant LAMR construct structurally homologous to the Archaeoglobus fulgidus S2 ribosomal protein and missing the C-terminal 75 residues of LAMR, which displays more sequence divergence. We found that HT1080 cells stably expressing either silent mutant LAMR construct still undergo arrest in the G(1) phase of the cell cycle when treated with siRNA. However, the expression of full-length silent mutant LAMR rescues cell viability, whereas the expression of the C-terminal-truncated LAMR does not. Interestingly, we also found that both silent mutant constructs restore protein translation and localize to the nucleus. Our findings indicate that the ability of LAMR to regulate viability is associated with its C-terminal 75 residues. Furthermore, this function is distinct from its role in cell proliferation, independent of its ribosomal functions, and may be regulated by a nonnuclear localization. Cell Death and Disease (2010) 1, e42; doi:10.1038/cddis.2010.19; published online 13 May 2010 Subject Category: Cancer C1 [Scheiman, J.; Jamieson, K. V.; Ziello, J.; Meruelo, D.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Scheiman, J.; Jamieson, K. V.; Ziello, J.; Meruelo, D.] NYU, Sch Med, NYU Canc Inst, NYU Gene Therapy Ctr, New York, NY 10016 USA. [Tseng, J-C] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meruelo, D (reprint author), NYU, Sch Med, Dept Pathol, 550 1st Ave, New York, NY 10016 USA. EM DM01@mac.com FU National Cancer Institutes [CA100687]; National Institutes of Health; Department of Health and Human Services; Litwin Foundation FX We thank Dr. Christine Pampeno for the critical reading of this paper. US Public Health grants CA100687 from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services supported this study. Funding was also provided by a gift from the Litwin Foundation. NR 40 TC 24 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD MAY PY 2010 VL 1 AR e42 DI 10.1038/cddis.2010.19 PG 9 WC Cell Biology SC Cell Biology GA 624KW UT WOS:000279818500003 PM 21243100 ER PT J AU Ghosh-Choudhury, N Mandal, CC Ghosh-Choudhury, N Choudhury, GG AF Ghosh-Choudhury, Nayana Mandal, Chandi Charan Ghosh-Choudhury, Nandini Choudhury, Goutam Ghosh TI Simvastatin induces derepression of PTEN expression via NF kappa B to inhibit breast cancer cell growth SO CELLULAR SIGNALLING LA English DT Article DE Statin; Breast tumor; Bcl(XL); Akt kinase ID HMG-COA REDUCTASE; TUMOR-SUPPRESSOR PTEN; PROTEIN-KINASE; IN-VITRO; COLORECTAL-CANCER; SIGNALING PATHWAY; INDUCED APOPTOSIS; PI3K PATHWAY; COLON CARCINOGENESIS; AKT/MAMMALIAN TARGET AB Sustained activation of Akt kinase acts as a focal regulator to increase cell growth and survival, which causes tumorigenesis including breast cancer. Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, display anticancer activity. The molecular mechanisms by which statins block cancer cell growth are poorly understood. We demonstrate that in the tumors derived from MDA-MB-231 human breast cancer cell xenografts, simvastatin significantly inhibited phosphorylation of Akt with concomitant attenuation of the expression of the anti-apoptotic protein Bcl(XL). In many cancer cells, Bcl(XL) is a target of NF kappa B. Simvastatin inhibited the DNA binding and transcriptional activities of NF kappa B resulting in marked reduction in transcription of Bcl(XL). Signals transmitted by anti-neoplastic mechanism implanted in the cancer cells serve to obstruct the initial outgrowth of tumors. One such mechanism represents the action of the tumor suppressor protein PTEN, which negatively regulates Akt kinase activity. We provide the first evidence for significantly increased levels of PTEN in the tumors of simvastatin-administered mice. Importantly, simvastatin markedly prevented binding of NF kappa B to the two canonical recognition elements, NFRE-1 and NFRE-2 present in the PTEN promoter. Contrary to the transcriptional suppression of Bcl(XL), simmastatin significantly increased the transcription of PTEN. Furthermore, expression of NF kappa B p65 subunit inhibited transcription of PTEN, resulting in reduced protein expression, which leads to enhanced phosphorylation of Akt. Taken together, our data present a novel bifaceted mechanism where simmastatin acts on a nodal transcription factor NF kappa B, which attenuates the expression of anti-apoptotic Bcl(XL) and simultaneously derepresses the expression of anti-proliferative/proapoptotic tumor suppressor PTEN to prevent breast cancer cell growth. Published by Elsevier Inc. C1 [Ghosh-Choudhury, Nayana; Mandal, Chandi Charan; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res, Educ & Clin Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU NIH [RO1 AR52425, RO1 DK50190]; VA Research Service Merit Review; Department of Veterans Affairs; Juvenile Diabetes Research Foundation [1-2008-185] FX The authors thank Patricia St Clair for excellent technical assistance. We thank Brent Wagner, M.D., for critically reading the manuscript. This work was supported by NIH RO1 AR52425 and VA Research Service Merit Review grants (NGC). GGC is a recipient of a Senior Research Career Scientist Award from the Department of Veterans Affairs. GGC is supported by NIH RO1 DK50190, VA Research Service Merit Review and Juvenile Diabetes Research Foundation 1-2008-185 grants. NR 116 TC 71 Z9 71 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAY PY 2010 VL 22 IS 5 BP 749 EP 758 DI 10.1016/j.cellsig.2009.12.010 PG 10 WC Cell Biology SC Cell Biology GA 574JG UT WOS:000275984600005 PM 20060890 ER PT J AU Nahas, SJ Young, WB Terry, R Kim, A Van Dell, T Guarino, AJ Silberstein, SD AF Nahas, S. J. Young, W. B. Terry, R. Kim, A. Van Dell, T. Guarino, A. J. Silberstein, S. D. TI Right-to-left shunt is common in chronic migraine SO CEPHALALGIA LA English DT Article DE Right-to-left shunt; chronic migraine; transcranial Doppler; patent foramen ovale; headache symptoms; aura; migraine ID PATENT FORAMEN OVALE; CONTRAST TRANSCRANIAL DOPPLER; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANSCATHETER CLOSURE; PERCUTANEOUS CLOSURE; STROKE PATIENTS; SEPTAL REPAIR; PREVALENCE; HEADACHE; AURA AB Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura (P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined. C1 [Nahas, S. J.; Young, W. B.; Silberstein, S. D.] Thomas Jefferson Univ Hosp, Dept Neurol, Philadelphia, PA 19107 USA. [Terry, R.; Kim, A.; Van Dell, T.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Guarino, A. J.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Nahas, SJ (reprint author), 111 S 11th St,Suite 8130, Philadelphia, PA 19107 USA. EM stephanie.nahas@jefferson.edu NR 35 TC 7 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 2010 VL 30 IS 5 BP 535 EP 542 DI 10.1111/j.1468-2982.2009.02002.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 605SK UT WOS:000278367100005 PM 19732069 ER PT J AU Celli, JP Spring, BQ Rizvi, I Evans, CL Samkoe, KS Verma, S Pogue, BW Hasan, T AF Celli, Jonathan P. Spring, Bryan Q. Rizvi, Imran Evans, Conor L. Samkoe, Kimberley S. Verma, Sarika Pogue, Brian W. Hasan, Tayyaba TI Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization SO CHEMICAL REVIEWS LA English DT Review ID OPTICAL COHERENCE TOMOGRAPHY; INDUCED PROTOPORPHYRIN-IX; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; ACID-INDUCED PROTOPORPHYRIN; ENDOTHELIAL GROWTH-FACTOR; HEXAMINOLEVULINATE FLUORESCENCE CYSTOSCOPY; SINGLET OXYGEN LUMINESCENCE; SQUAMOUS-CELL CARCINOMA; INDUCED PORPHYRIN FLUORESCENCE; DELTA-AMINOLEVULINIC-ACID C1 [Celli, Jonathan P.; Spring, Bryan Q.; Rizvi, Imran; Evans, Conor L.; Verma, Sarika; Pogue, Brian W.; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Celli, Jonathan P.; Spring, Bryan Q.; Rizvi, Imran; Evans, Conor L.; Verma, Sarika; Pogue, Brian W.; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rizvi, Imran; Samkoe, Kimberley S.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU National Institutes of Health [P01 CA084203-06]; National Cancer Institute/National Institutes of Health [R01 CA119388]; Department of Defense; Wellman Center for Photomedicine FX We are grateful to the late Dr. Thomas F. Deutsch for first introducing T.H. to the tremendous potential of imaging in PDT, almost 2 decades ago. This work was supported by National Institutes of Health Grant Number P01 CA084203-06, National Cancer Institute/National Institutes of Health Grant Number R01 CA119388, the Department of Defense Medical Free Electron Laser Program, and Wellman Center for Photomedicine core funds. NR 403 TC 634 Z9 644 U1 63 U2 423 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 EI 1520-6890 J9 CHEM REV JI Chem. Rev. PD MAY PY 2010 VL 110 IS 5 BP 2795 EP 2838 DI 10.1021/cr900300p PG 44 WC Chemistry, Multidisciplinary SC Chemistry GA 598CW UT WOS:000277811600010 PM 20353192 ER PT J AU Rotili, D Tarantino, D Carafa, V Lara, E Meade, S Botta, G Nebbioso, A Schemies, J Jung, M Kazantsev, AG Esteller, M Fraga, MF Altucci, L Mai, A AF Rotili, Dante Tarantino, Domenico Carafa, Vincenzo Lara, Ester Meade, Sarah Botta, Giorgia Nebbioso, Angela Schemies, Joerg Jung, Manfred Kazantsev, Aleksey G. Esteller, Manel Fraga, Mario F. Altucci, Lucia Mai, Antonello TI Identification of Tri- and Tetracyclic Pyrimidinediones as Sirtuin Inhibitors SO CHEMMEDCHEM LA English DT Article DE antiproliferation; apoptosis; diazabenzoanthracene; inhibitors; sirtuins ID HISTONE DEACETYLASE INHIBITORS; SMALL-MOLECULE INHIBITORS; BIOLOGICAL EVALUATION; THERAPEUTIC TARGETS; CANCER; DISCOVERY; DISEASES; FAMILY; ACETYLTRANSFERASE; ANALOGS C1 [Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Mai, Antonello] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Chim & Tecnol Farmaco, I-00185 Rome, Italy. [Carafa, Vincenzo; Nebbioso, Angela; Altucci, Lucia] Univ Naples 2, Dipartimento Patol Gen, I-80138 Naples, Italy. [Lara, Ester; Fraga, Mario F.] Natl Ctr Biotechnol CNB CSIC, Dept Immunol & Oncol, Madrid, Spain. [Meade, Sarah; Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Schemies, Joerg; Jung, Manfred] Univ Freiburg, Inst Pharmaceut Sci, D-79104 Freiburg, Germany. [Esteller, Manel] Catalan Inst Oncol ICO, Canc Epigenet & Biol Program PEBC, Barcelona, Spain. RP Mai, A (reprint author), Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Chim & Tecnol Farmaco, Ple A Moro 5, I-00185 Rome, Italy. EM antonello.mai@uniroma1.it RI Esteller, Manel/L-5956-2014; Rotili, Dante/J-9157-2016; Jung, Manfred/Q-8029-2016; NEBBIOSO, Angela/C-3566-2016; OI Esteller, Manel/0000-0003-4490-6093; Jung, Manfred/0000-0002-6361-7716; NEBBIOSO, Angela/0000-0001-5374-3527; altucci, lucia/0000-0002-7312-5387; Rotili, Dante/0000-0002-8428-8763; Mai, Antonello/0000-0001-9176-2382 FU AIRC; FIRB; RETI FIRB; European Union (Cancerdip; ATLAS); Fondazione Roma; R.J.G. and Carmen's Foundations FX This work was supported by grants from AIRC, FIRB, RETI FIRB, European Union (Cancerdip; ATLAS), Fondazione Roma, and R.J.G. and Carmen's Foundations. NR 35 TC 26 Z9 26 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD MAY PY 2010 VL 5 IS 5 BP 674 EP 677 DI 10.1002/cmdc.201000030 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 596ZP UT WOS:000277725100005 PM 20391556 ER PT J AU Afessa, B Shorr, A Anzueto, AR Craven, DE Schinner, R Kollef, MH AF Afessa, Bakele Shorr, Andrew Anzueto, Antonio R. Craven, Donald E. Schinner, Regina Kollef, Marin H. TI Association Between a Silver-Coated Endotracheal Tube and Reduced Mortality in Patients With Ventilator-Associated Pneumonia SO CHEST LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; MECHANICAL VENTILATION; STAPHYLOCOCCUS-AUREUS; SUBGLOTTIC SECRETIONS; CONTINUOUS ASPIRATION; NOSOCOMIAL PNEUMONIA; DOUBLE-BLIND; DECONTAMINATION; COLONIZATION; INFECTION AB Background: A silver-coated endotracheal tube (ETT) reduced the incidence of ventilator-associated pneumonia (VAP) compared with an uncoated ETT in the North American Silver-Coated Endotracheal Tube (NASCENT) study. Methods: To evaluate the effect of an ETT and risk factors on mortality, we performed a retrospective cohort analysis in patients who developed VAP in the NASCENT study. We determined causes of death and VAP due to potentially multidrug-resistant bacteria (eg, Pseudomonas, Acinetobacter) and performed stepwise multivariate logistic regression with the following predefined variables: treatment group, Acute Physiology and Chronic Health Evaluation (APACHE) 11 score, continuous sedation, coma, COPD, emergency surgery/trauma, immunodeficiency, potentially multidrug-resistant bacteria, and inappropriate initial antibiotics. Results: The silver-coated ETT was associated with reduced mortality in patients with VAP (silver vs control, 5/37 [14%] vs 20/56 [36%], P = .03), but not in those without VAP (228/729 [31%] vs 178/687 [26%], P = .03). The only between-group difference in leading causes of death was respiratory failure (silver vs control, 45/233 [19%] vs 22/198 [11%], P = .02). Of the VAP-related deaths, one in the silver group was caused by Acinetobacter sepsis. In the control group, six deaths were caused by sepsis and three by pneumonia; six of nine pathogens were potentially multidrug resistant. In multivariate analysis, the treatment group was a predictor of mortality (odds ratio, silver vs control, 0.28; 95% CI, 0.09-0.89; P = .03). APACHE II >= 20 and inappropriate antibiotics also remained in the model (P < .1). Conclusions: These findings suggest that a silver-coated ETT was associated with reduced mortality in patients who developed VAP in the NASCENT study. Studies are needed to confirm these exploratory findings. CHEST 2010; 137(5):1015-1021 C1 [Afessa, Bakele] Mayo Clin, Div Pulm & Crit Care Med, Coll Med, Rochester, MN 55905 USA. [Shorr, Andrew] Washington Hosp Ctr, Washington, DC 20010 USA. [Anzueto, Antonio R.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Anzueto, Antonio R.] Univ Hosp, San Antonio, TX USA. [Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Craven, Donald E.] Lahey Clin Med Ctr, Burlington, MA 01803 USA. [Craven, Donald E.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Schinner, Regina] FGK Clin Res GmbH, Munich, Germany. [Kollef, Marin H.] Washington Univ, Sch Med, St Louis, MO USA. RP Afessa, B (reprint author), Mayo Clin, Div Pulm & Crit Care Med, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM Afessa.bekele@mayo.edu FU C. R. Bard, Inc.; Johnson Johnson; Astellas; Pfizer; Bayer-Schering Pharma; GlaxoSmithKline; Boehringer Ingelheim; Schering-Plough; KCI; sanofi-aventis; Bard; Covidien; Merck; Ortho-McNeil; Wyeth; Arpida; Bayer-Nektar; Cubist; Elan FX Funding/Support: This study, including statistical analysis and manuscript preparation, was supported by a pint from C. R. Bard, Inc.; Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Shorr reported receiving grant support from Johnson & Johnson and Pfizer; consulting fees from Astellas, Johnson & Johnson, and Pfizer; and lecture fees from Johnson & Johnson, Merck, and Pfizer Dr Anzueto reported receiving grant support from Bayer-Schering Pharma and GlaxoSmithKline and consulting and lecture fees from Bayer-Schering Pharma, Boehringer Ingelheim, GlaxoSmithKline, Schering-Plough, Pfizer, KCI (lecturing only), and sanofi-aventis (consulting only). Dr Craven reported receiving grant support from Bard; lecture fees from Covidien, Merck, Ortho-McNeil, Pfizer, and Wyeth; and consulting fees from Arpida, Bayer-Nektar, Cubist, Johnson & Johnson, and Wyeth. Dr Kollef reported receiving consulting fee from Kimberly Clark and lecture fees and grant support from Bard, Elan, Merck, Ortho-McNeil (lecture fees only), and Pfizer. Dr Afessa and Ms Schirmer have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 22 TC 22 Z9 24 U1 1 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2010 VL 137 IS 5 BP 1015 EP 1021 DI 10.1378/chest.09-0391 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 594MR UT WOS:000277542300004 PM 20038737 ER PT J AU O'Donnell, CR Bankier, AA Stiebellehner, L Reilly, JJ Brown, R Loring, SH AF O'Donnell, Carl R. Bankier, Alexander A. Stiebellehner, Leopold Reilly, John J. Brown, Robert Loring, Stephen. H. TI Comparison of Plethysmographic and Helium Dilution Lung Volumes Which Is Best for COPD? SO CHEST LA English DT Article ID THORACIC GAS VOLUME; OBSTRUCTIVE PULMONARY-DISEASE; FUNCTIONAL RESIDUAL CAPACITY; AIR-FLOW OBSTRUCTION; BODY PLETHYSMOGRAPHY; REDUCTION SURGERY; FREQUENCY-DEPENDENCE; COMPUTED-TOMOGRAPHY; EMPHYSEMA; MORTALITY AB Background: Theoretical considerations and limited scientific evidence suggest that whole-body plethysmography overestimates lung volume in patients with severe airflow obstruction. We sought to compare plethysmography (Pleth)-, helium dilution (He)- and CT scan-derived lung volume measurements in a sample containing many patients with severe airflow obstruction. Methods: We measured total lung capacity (TLC) in 132 patients at three hospitals, with monitored application of recommended techniques for Pleth and He measurements of lung volume and by thoracic CT scans obtained during breath hold at full inspiration. Results: Average TLC among 132 subjects was 6.18 L (+/- 1.69 L) by Pleth-derived TLC, 5.55 L (+/- 1.39 L) by He-derived TLC, and 5.31 L (+/- 1.47) by CT scan-derived TLC. Pleth-derived TLC was significantly greater than either He-derived TLC or CT scan-derived TLC (P <= .001), whereas there was no significant difference between He-derived and CT scan-derived values. When examined separately, there were significant within-subject differences in TLC by measurement technique among subjects with airflow obstruction, but not among those without airflow obstruction. Plethysmographic overestimation of TLC was greatest among subjects with FEV(1) <30% of predicted. Conclusions: In the setting of airflow obstruction, Pleth systematically overestimates lung volume relative to He or thoracic imaging despite adherence to current recommendations for proper measurement technique. CHEST 2010; 137(5):1108-1115 C1 [O'Donnell, Carl R.; Loring, Stephen. H.] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Bankier, Alexander A.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Reilly, John J.] Brigham & Womens Hosp, Dept Pulm & Crit Care Med, Boston, MA 02115 USA. [Brown, Robert] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Brown, Robert] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [O'Donnell, Carl R.; Bankier, Alexander A.; Reilly, John J.; Brown, Robert; Loring, Stephen. H.] Harvard Univ, Sch Med, Boston, MA USA. [Stiebellehner, Leopold] Med Univ Vienna, Dept Pulmonol, Vienna, Austria. RP O'Donnell, CR (reprint author), Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Dana 717,330 Brookline Ave, Boston, MA 02215 USA. EM codonne1@bidmc.harvard.edu RI Reilly, John/H-8755-2012 FU National Heart, Lung, and Blood Institute [HL-52586] FX Funding/Support: This work was supported in part by the National Heart, Lung, and Blood Institute [Grant HL-52586]. NR 33 TC 37 Z9 37 U1 2 U2 12 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2010 VL 137 IS 5 BP 1108 EP 1115 DI 10.1378/chest.09-1504 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 594MR UT WOS:000277542300017 PM 20022972 ER PT J AU Esan, A Hess, DR Raoof, S George, L Sessler, CN AF Esan, Adebayo Hess, Dean R. Raoof, Suhail George, Liziamma Sessler, Curtis N. TI Severe Hypoxemic Respiratory Failure Part 1-Ventilatory Strategies SO CHEST LA English DT Article ID ACUTE LUNG INJURY; FREQUENCY OSCILLATORY VENTILATION; INVERSE RATIO VENTILATION; END-EXPIRATORY PRESSURE; CONVENTIONAL MECHANICAL VENTILATION; EXTRACORPOREAL MEMBRANE-OXYGENATION; RANDOMIZED CONTROLLED-TRIAL; DISTRESS-SYNDROME; AIRWAY PRESSURE; PERCUSSIVE VENTILATION AB Approximately 16% of deaths in patients with ARDS results from refractory hypoxemia, which is the inability to achieve adequate arterial oxygenation despite high levels of inspired oxygen or the development of barotrauma. A number of ventilator-focused rescue therapies that can be used when conventional mechanical ventilation does not achieve a specific target level of oxygenation are discussed. A literature search was conducted and narrative review written to summarize the use of high levels of positive end-expiratory pressure, recruitment maneuvers, airway pressure-release ventilation, and high-frequency ventilation. Each therapy reviewed has been reported to improve oxygenation in patients with ARDS. However, none of them have been shown to improve survival when studied in heterogeneous populations of patients with ARDS. Moreover, none of the therapies has been reported to be superior to another for the goal of improving oxygenation. The goal of improving oxygenation must always be balanced against the risk of further lung injury. The optimal time to initiate rescue therapies, if needed, is within 96 h of the onset of ARDS, a time when alveolar recruitment potential is the greatest. A variety of ventilatory approaches are available to improve oxygenation in the setting of refractory hypoxemia and ARDS. Which, if any, of these approaches should be used is often determined by the availability of equipment and clinician bias. CHEST 2010; 137(5):1203-1216 C1 [Esan, Adebayo; Raoof, Suhail; George, Liziamma] New York Methodist Hosp, Div Pulm & Crit Care Med, Brooklyn, NY 11215 USA. [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Sessler, Curtis N.] Virginia Commonwealth Univ, Richmond, VA USA. RP Raoof, S (reprint author), New York Methodist Hosp, Div Pulm & Crit Care Med, 506 6th St, Brooklyn, NY 11215 USA. EM sur9016@nyp.org FU AstraZeneca; Pfizer; Penexel; Talceda FX Financial/nonfinancial disclosures: The authors have reported to the CHEST the following conflicts of interest: Dr Hess has received royalties from Impact. He was a consultant for Respironics and Pari. He also discloses relationships with Cardinal (CaseFusion) and Ikaria. Dr George was a consultant to Eubien, Boehringer Ingelheim, from 2006 to 2007. She has received money from AstraZeneca, Pfizer, Penexel, and Talceda. Drs Esan, Raoof, and Sessler report that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 115 TC 61 Z9 65 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2010 VL 137 IS 5 BP 1203 EP 1216 DI 10.1378/chest.09-2415 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 594MR UT WOS:000277542300032 PM 20442122 ER PT J AU Robinson, KS Morin, PC Shupe, JAC Izquierdo, R Ploutz-Snyder, R Meyer, S Teresi, JA Starren, J Shea, S Weinstock, RS AF Robinson, Kate S. Morin, Philip C. Shupe, Jo Ann C. Izquierdo, Roberto Ploutz-Snyder, Robert Meyer, Suzanne Teresi, Jeanne A. Starren, Justin Shea, Steven Weinstock, Ruth S. TI Use of Three Computer Training Methods in Elderly Underserved Rural Patients Enrolled in a Diabetes Telemedicine Program SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article DE Diabetes telemedicine program; Elderly; Home telemedicine unit; Medically underserved; Regional nurse installer; Rural ID COLUMBIA-UNIVERSITY INFORMATICS; OLDER-ADULTS; IDEATEL PROJECT; EDUCATION; TECHNOLOGY; DESIGN; HOMES AB A telephone survey of Medicare beneficiaries with diabetes living in rural underserved areas and enrolled in the Informatics for Diabetes Education and Telemedicine project identified 109 subjects who requested further training in functions of the home telemedicine unit after initial in-home training by regional nurse installers. The initial training provided the skills needed to videoconferences with nurse case managers and to transmit blood glucose and blood pressure readings, but further instruction was needed for access to Web-based education features and messaging. This study evaluated these elderly patients' perceptions of the helpfulness of three additional telemedicine training methods: in-home visit with an regional nurse installer referencing a user's manual, unassisted patient use of the user's manual, and telephone-based training not using regional nurse installers reinforcing the user's manual. Eligible subjects rated the helpfulness of the three computer training methods on a five-point Likert scale (1 = "not helpful at all," 5 = "very helpful"). Participants rated "in-home" training with an regional nurse installer significantly higher than they did for the user's manual alone (P < .01). In response to this finding and other companion usability studies, Informatics for Diabetes Education and Telemedicine deployed home telemedicine units with enhanced remote training capabilities to better emulate characteristics of in-person training. C1 [Weinstock, Ruth S.] SUNY Upstate Med Univ, Dept Med, Div Endocrinol Diabet & Metab, Syracuse, NY 13210 USA. [Meyer, Suzanne] Joslin Diabet Ctr, Syracuse, NY USA. [Teresi, Jeanne A.] Hebrew Home Riverdale, Bronx, NY USA. [Teresi, Jeanne A.] NY Psychiat Inst, New York, NY USA. [Teresi, Jeanne A.] Columbia Univ, Stroud Ctr, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Starren, Justin] Marshfield Clin Fdn Med Res & Educ, Marshfield, MN USA. [Weinstock, Ruth S.] VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. RP Weinstock, RS (reprint author), SUNY Upstate Med Univ, Dept Med, Div Endocrinol Diabet & Metab, Room 353 CWB,750 E Adams St, Syracuse, NY 13210 USA. EM weinstor@upstate.edu NR 14 TC 1 Z9 1 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD MAY-JUN PY 2010 VL 28 IS 3 BP 172 EP 177 DI 10.1097/NCN.0b013e3181d785d5 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 592OK UT WOS:000277388700006 PM 20431360 ER PT J AU Hoffmann, U Truong, QA AF Hoffmann, Udo Truong, Quynh A. TI Computed Tomography Coronary Plaque Imaging as a Secondary End Point for Randomized Pharmaceutical Trials More Bang for the Buck? SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE Editorials; coronary artery disease; coronary CT angiography; inflammation; plaque progression; vulnerable plaque ID C-REACTIVE PROTEIN; LIPID-LOWERING THERAPY; CARDIOVASCULAR-DISEASE; STATIN THERAPY; EVENTS; ATHEROSCLEROSIS; CALCIUM; RISK; PROGRESSION C1 [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 25 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2010 VL 3 IS 3 BP 225 EP 227 DI 10.1161/CIRCIMAGING.110.957316 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 597RU UT WOS:000277779300001 PM 20484111 ER PT J AU Velagaleti, RS Gona, P Chuang, ML Salton, CJ Fox, CS Blease, SJ Yeon, SB Manning, WJ O'Donnell, CJ AF Velagaleti, Raghava S. Gona, Philimon Chuang, Michael L. Salton, Carol J. Fox, Caroline S. Blease, Susan J. Yeon, Susan B. Manning, Warren J. O'Donnell, Christopher J. TI Relations of Insulin Resistance and Glycemic Abnormalities to Cardiovascular Magnetic Resonance Measures of Cardiac Structure and Function The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE insulin resistance; diabetes; left ventricular mass; left ventricular remodeling; cardiovascular MRI; glycemia ID LEFT-VENTRICULAR MASS; TYPE-2 DIABETES-MELLITUS; SEX-RELATED DIFFERENCES; ESSENTIAL-HYPERTENSION; GLUCOSE-METABOLISM; SYSTOLIC FUNCTION; RISK-FACTORS; DB/DB MOUSE; ELDERLY-MEN; HYPERTROPHY AB Background-Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. Methods and Results-A total of 1603 Framingham Heart Study Offspring participants (age, 64 +/- 9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht(2.7) and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Conclusions-Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling. (Circ Cardiovasc Imaging. 2010; 3: 257-263.) C1 [Velagaleti, Raghava S.; Gona, Philimon; Fox, Caroline S.; Blease, Susan J.; O'Donnell, Christopher J.] NHLBI Framingham Heart Study, Framingham, MA 01702 USA. [Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA USA. [Manning, Warren J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP O'Donnell, CJ (reprint author), NHLBI Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov FU National Heart, Lung, and Blood Institute [NO1-HC-25193, RO1-HL70279] FX This study was supported by National Heart, Lung, and Blood Institute contract No. NO1-HC-25193 and grant RO1-HL70279. NR 38 TC 41 Z9 43 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2010 VL 3 IS 3 BP 257 EP U60 DI 10.1161/CIRCIMAGING.109.911438 PG 16 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 597RU UT WOS:000277779300006 PM 20208015 ER PT J AU Hou, JB Qi, H Zhang, MM Meng, LB Han, ZG Yu, B Jang, IK AF Hou, Jingbo Qi, Hai Zhang, Maomao Meng, Lingbo Han, Zhigang Yu, Bo Jang, Ik-Kyung TI Pulmonary Vascular Changes in Pulmonary Hypertension Optical Coherence Tomography Findings SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 [Hou, Jingbo; Qi, Hai; Zhang, Maomao; Meng, Lingbo; Han, Zhigang; Yu, Bo] Harbin Med Coll, Dept Cardiol, Affiliated Hosp 2, Harbin 150086, Peoples R China. [Hou, Jingbo; Qi, Hai; Zhang, Maomao; Meng, Lingbo; Han, Zhigang; Yu, Bo] Harbin Med Coll, Key Lab Educ Minist Myocardial Ischemia Mech & Tr, Harbin 150086, Peoples R China. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Coll, Dept Cardiol, Affiliated Hosp 2, Harbin 150086, Peoples R China. EM yubodr@163.com NR 0 TC 11 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAY PY 2010 VL 3 IS 3 BP 344 EP 345 DI 10.1161/CIRCIMAGING.109.882498 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 597RU UT WOS:000277779300016 PM 20484114 ER PT J AU Nasir, K McClelland, RL Blumenthal, RS Goff, DC Hoffmann, U Psaty, BM Greenland, P Kronmal, RA Budoff, MJ AF Nasir, Khurram McClelland, Robyn L. Blumenthal, Roger S. Goff, David C., Jr. Hoffmann, Udo Psaty, Bruce M. Greenland, Philip Kronmal, Richard A. Budoff, Matthew J. TI Coronary Artery Calcium in Relation to Initiation and Continuation of Cardiovascular Preventive Medications The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE coronary artery calcification; computed tomography; medications; adherence; prevention ID BEAM COMPUTED-TOMOGRAPHY; LIFE-STYLE BEHAVIORS; BLOOD-PRESSURE; STATIN THERAPY; UNITED-STATES; ASPIRIN; HYPERTENSION; DISEASE; CHOLESTEROL; ADHERENCE AB Background-Whether measuring and reporting of coronary artery calcium scores (CACS) might lead to changes in cardiovascular risk management is not established. In this observational study, we examined whether high baseline CACS were associated with the initiation as well continuation of new lipid-lowering medication (LLM), blood pressure-lowering medication (BPLM), and regular aspirin (ASA) use in a multi-ethnic population-based cohort. Methods and Results-The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6814 participants free of clinical cardiovascular disease at entry who underwent CAC testing at baseline examination (examination 1). Information on LLM, BPLM, and regular ASA usage was also obtained at baseline and at exams 2 and 3 (average of 1.6 and 3.2 years after baseline, respectively). In this study, we examined (1) initiation of these medications at examination 2 among participants not taking these medications at baseline; and (2) continuation of medication use to examination 3 among participants already on medication at baseline. Among MESA participants, initiation of LLM, BPLM, and ASA was greater in those with higher CACS. After taking into account age, sex, race, MESA site, LDL cholesterol, diabetes mellitus, body mass index, smoking status, hypertension, systolic blood pressure, and socioeconomic status (income, education, and health insurance), the risk ratios for medication initiation comparing those with CACS >400 versus CACS = 0 were 1.53 (95% confidence interval [CI], 1.08, 2.15) for LLM, 1.55 (95% CI, 1.10 to 2.17) for BPLM, and 1.32 (95% CI, 1.03 to 1.69) for ASA initiation, respectively. The risk ratios for medication continuation among those with CAC >400 versus CACS = 0 were 1.10 (95% CI, 1.01 to 1.20) for LLM, 1.05 (95% CI, 1.02 to 1.08) for BPLM, and 1.14 (95% CI, 1.04 to 1.25) for ASA initiation, respectively. Conclusions-CACS >400 was associated with a higher likelihood of initiation and continuation of LLM, BPLM, and ASA. The association was weaker for continuation than for initiation of these preventive therapies. (Circ Cardiovasc Qual Outcomes. 2010; 3: 228-235.) C1 [Nasir, Khurram; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Nasir, Khurram] Boston Med Ctr, Dept Internal Med, Boston, MA USA. [McClelland, Robyn L.; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Goff, David C., Jr.] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI PET CT Program, Boston, MA USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Clin & Translat Sci Inst, Chicago, IL 60611 USA. [Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA 90509 USA. RP Nasir, K (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Blalock 524 C,600 N Wolfe St, Baltimore, MD 21287 USA. EM knasir1@jhmi.edu FU National Heart, Lung, and Blood Institute [R01-HL-63963-01A1, N01-HC-95159, N01-HC-95165, N01 HC 95169] FX This research was supported by R01-HL-63963-01A1 and contracts N01-HC-95159 through N01-HC-95165 and N01 HC 95169 from the National Heart, Lung, and Blood Institute. NR 24 TC 34 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2010 VL 3 IS 3 BP 228 EP 235 DI 10.1161/CIRCOUTCOMES.109.893396 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597RN UT WOS:000277778400004 PM 20371760 ER PT J AU Ho, PM Tsai, TT Maddox, TM Powers, JD Carroll, NM Jackevicius, C Go, AS Margolis, KL DeFor, TA Rumsfeld, JS Magid, DJ AF Ho, P. Michael Tsai, Thomas T. Maddox, Thomas M. Powers, J. David Carroll, Nikki M. Jackevicius, Cynthia Go, Alan S. Margolis, Karen L. DeFor, Terese A. Rumsfeld, John S. Magid, David J. TI Delays in Filling Clopidogrel Prescription After Hospital Discharge and Adverse Outcomes After Drug-Eluting Stent Implantation Implications for Transitions of Care SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE stents; drugs; epidemiology ID MYOCARDIAL-INFARCTION; THROMBOSIS; PREVALENCE; PREDICTORS; DISCONTINUATION; INTERVENTION; MORTALITY; REGISTRY; THERAPY; EVENTS AB Background-Adjuvant clopidogrel therapy is essential after drug-eluting stent (DES) implantation. The frequency with which patients delay filling a clopidogrel prescription after DES implantation and the association of this delay with adverse outcomes is unknown. Methods and Results-This was a retrospective cohort study of patients discharged after DES implantation from 3 large integrated health care systems. Filling a clopidogrel prescription was based on pharmacy dispensing data. The primary end point was all-cause mortality or myocardial infarction (MI). Of 7402 patients discharged after DES implantation, 16% (n = 1210) did not fill a clopidogrel prescription on day of discharge and the median time delay was 3 days (interquartile range, 1 to 23 days). Compared with patients filling clopidogrel on day of discharge, patients with any delay in filling clopidogrel had higher death/MI rates during follow-up (14.2% versus 7.9%; P<0.001). In multivariable analysis, patients with any delay had increased risk of death/MI (hazard ratio, 1.53; 95% confidence interval, 1.25 to 1.87). Patients with any delay remained at increased risk of adverse outcomes when the delay cutoff was changed to >1, >3, or >5 days after discharge. Factors associated with delay included older age, prior MI, diabetes, renal failure, prior revascularization, cardiogenic shock, in-hospital bleeding, and clopidogrel use within 24 hours of admission. Conclusions-One in 6 patients delay filling their index clopidogrel prescription after hospital discharge after DES implantation. This delay was associated with increased risk of adverse outcomes and highlights the importance of the transition period from hospital discharge to outpatient setting as a potential opportunity to improve care delivery and patient outcomes. (Circ Cardiovasc Qual Outcomes. 2010; 3: 261-266.) C1 [Ho, P. Michael; Tsai, Thomas T.; Maddox, Thomas M.; Powers, J. David; Carroll, Nikki M.; Rumsfeld, John S.; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Ho, P. Michael; Tsai, Thomas T.; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Ho, P. Michael; Tsai, Thomas T.; Maddox, Thomas M.; Rumsfeld, John S.; Magid, David J.] Univ Colorado Denver, Denver, CO USA. [Jackevicius, Cynthia] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Jackevicius, Cynthia] Univ Toronto, Toronto, ON, Canada. [Jackevicius, Cynthia] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia] Western Univ, Pomona, CA 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. [Margolis, Karen L.; DeFor, Terese A.] HealthPartners Res Fdn, Minneapolis, MN USA. RP Ho, PM (reprint author), 1055 Clermont St 111B, Denver, CO 80220 USA. EM Michael.ho@coloradooutcomes.org FU Agency for Healthcare Research and Quality (AHRQ) [1U18HS016955]; NHLBI [U19HL091179]; AHA Pharmaceutical Roundtable Outcomes Research Center [AHA 0875162N]; VA Research and Development Career Development Award [05-026-2] FX This study was supported by a grant to The HMO Research Network Center for Education and Research on Therapeutics (CERTs) (1U18HS016955) from the Agency for Healthcare Research and Quality (AHRQ). The Effective Health Care Cardiovascular Consortium by DEcIDE contributed to the development of the stent database used in the study. Drs Magid and Go are supported by the Cardiovascular Research Network (CVRN), which is funded by NHLBI (U19HL091179). Dr Go is also supported by an AHA Pharmaceutical Roundtable Outcomes Research Center (AHA No. 0875162N). Dr Ho is supported by a VA Research and Development Career Development Award (05-026-2) and serves as a consultant for Wellpoint, Inc. NR 16 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2010 VL 3 IS 3 BP 261 EP 266 DI 10.1161/CIRCOUTCOMES.109.902031 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597RN UT WOS:000277778400008 PM 20407117 ER PT J AU Fonarow, GC Reeves, MJ Smith, EE Saver, JL Zhao, X Olson, DW Hernandez, AF Peterson, ED Schwamm, LH AF Fonarow, Gregg C. Reeves, Mathew J. Smith, Eric E. Saver, Jeffrey L. Zhao, Xin Olson, Dai Wai Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. CA GWTG-Stroke Steering Comm Investig TI Characteristics, Performance Measures, and In-Hospital Outcomes of the First One Million Stroke and Transient Ischemic Attack Admissions in Get With The Guidelines-Stroke SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute stroke; transient ischemic attack; quality of care; registry ID QUALITY-OF-CARE; INTRACEREBRAL HEMORRHAGE; NEUROLOGY AFFIRMS; SEX-DIFFERENCES; REGISTRY; IMPROVEMENT; MORTALITY; COUNCIL; PROGRAM AB Background-Stroke results in substantial death and disability. To address this burden, Get With The Guideline (GWTG)-Stroke was developed to facilitate the measurement, tracking, and improvement in quality of care and outcomes for acute stroke and transient ischemic attack (TIA) patients in the United States. Methods and Results-We analyzed the characteristics, performance measures, and in-hospital outcomes in the first 1 000 000 acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and TIA admissions from 1392 hospitals that participated in the GWTG-Stroke Program 2003 to 2009. Patients were 53.5% women, 73.3% white, and with mean age of 70.1 +/- 14.9 years. There were 601 599 (60.2%) ischemic strokes, 108 671 (10.9%) intracerebral hemorrhages, 34 945 (3.5%) subarachnoid hemorrhages, 26 977 (2.7%) strokes not classified, and 227 788 (22.8%) TIAs. Performance measures showed small to moderate differences by cerebrovascular event type. In-hospital mortality rate was highest among intracerebral hemorrhage (25.0%) and subarachnoid hemorrhage (20.4%), and intermediate in ischemic stroke (5.5%) patients and lowest among TIA patients (0.3%). Significant improvements over time from 2003 to 2009 in quality of care were observed: all-or-none measure, 44.0% versus 84.3% (+40.3%, P < 0.0001). After adjustment for patient and hospital variables, the cumulative adjusted odds ratio for the all-or-none measure over the 6 years was 9.4 (95% confidence interval, 8.3 to 10.6, P<0.0001). Temporal improvements in length of stay and risk-adjusted in-hospital mortality rate (for ischemic stroke and TIA) were also observed. Conclusions-With more than 1 million patients enrolled, GWTG-Stroke represents an integrated stroke and TIA registry that supports national surveillance, innovative research, and sustained quality improvement efforts facilitating evidence-based stroke/TIA care. (Circ Cardiovasc Qual Outcomes. 2010; 3:291-302.) C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, Los Angeles, CA 90095 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Div Neurol, Los Angeles, CA 90095 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Zhao, Xin; Olson, Dai Wai; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Fonarow, GC (reprint author), Univ Calif Los Angeles, Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Saver, Jeffrey/0000-0001-9141-2251 FU program of the American Heart Association/American Stroke Association; Merck/Schering-Plough Pharmaceutical FX GWTG-Stroke is a program of the American Heart Association/American Stroke Association and is supported in part by an unrestricted educational grant from Merck/Schering-Plough Pharmaceutical, which did not participate in the design, analysis, manuscript preparation, review, or approval of this manuscript. NR 21 TC 153 Z9 159 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2010 VL 3 IS 3 BP 291 EP U122 DI 10.1161/CIRCOUTCOMES.109.921858 PG 25 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597RN UT WOS:000277778400012 PM 20177051 ER PT J AU Ho, PM Tsai, TT Wang, TY Shetterly, SM Clarke, CL Go, AS Sedrakyan, A Rumsfeld, JS Peterson, ED Magid, DJ AF Ho, P. Michael Tsai, Thomas T. Wang, Tracy Y. Shetterly, Susan M. Clarke, Christina L. Go, Alan S. Sedrakyan, Art Rumsfeld, John S. Peterson, Eric D. Magid, David J. TI Adverse Events After Stopping Clopidogrel in Post-Acute Coronary Syndrome Patients Insights From a Large Integrated Healthcare Delivery System SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE drugs; epidemiology; myocardial infarction ID POSTTREATMENT PLATELET REACTIVITY; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; ARTERY-DISEASE; INCREASED RISK; MEDICATION; OUTCOMES; DEATH AB Background-A prior study from the Veterans Health Administration found a clustering of cardiovascular events after clopidogrel cessation. We sought to confirm and expand these findings. Methods and Results-This was a retrospective cohort study of 2017 patients with acute coronary syndrome discharged on clopidogrel from an integrated health care delivery system. Rates of all-cause mortality or acute myocardial infarction (MI) within 1 year after stopping clopidogrel were assessed among patients who did not have an event before stopping clopidogrel. Death/MI occurred in 4.3% (n = 71) of patients. The rates of death/MI were 3.07, 1.62, 0.70, and 0.95 per 10 000 patient-days for the time intervals of 0 to 90, 91 to 180, 181 to 270, and 271 to 360 days after stopping clopidogrel. In multivariable analysis, the 0- to 90-day interval after stopping clopidogrel was associated with higher risk of death/MI (incidence rate ratio, 2.74; 95% confidence interval, 1.69 to 4.44) compared with 91- to 360-day interval. There was a similar trend of increased events after stopping clopidogrel for various subgroups (women versus men, medical therapy versus percutaneous coronary intervention, stent type, and >= 6 months or <6 months of clopidogrel treatment). Among patients taking clopidogrel but stopping ACE inhibitor medications, the event rates were similar in the 0- to 90-day versus the 91- to 360-day interval (2.67 versus 2.91 per 10 000 patient-days; P=0.91). Conclusions-We observed a clustering of adverse events in the 0 to 90 days after stopping clopidogrel. This clustering of events was not present among patients stopping ACE inhibitors. These findings are consistent with a possible rebound platelet hyper-reactivity after stopping clopidogrel and additional platelet studies are needed to confirm this effect. (Circ Cardiovasc Qual Outcomes. 2010; 3:303-308.) C1 [Ho, P. Michael; Tsai, Thomas T.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Ho, P. Michael; Tsai, Thomas T.; Shetterly, Susan M.; Clarke, Christina L.; Rumsfeld, John S.; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Ho, P. Michael; Tsai, Thomas T.; Rumsfeld, John S.; Magid, David J.] Univ Colorado Denver, Denver, CO USA. [Wang, Tracy Y.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 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 Ho, PM (reprint author), 1055 Clermont St 111B, Denver, CO 80220 USA. EM michael.ho@coloradooutcomes.org FU Agency for Healthcare Research and Quality; US Department of Health and Human Services; Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) FX This project was funded under Contract No. 290-05-0033 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 18 TC 27 Z9 31 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2010 VL 3 IS 3 BP 303 EP 308 DI 10.1161/CIRCOUTCOMES.109.890707 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597RN UT WOS:000277778400013 PM 20354221 ER PT J AU Peterson, PN Rumsfeld, JS Liang, L Hernandez, AF Peterson, ED Fonarow, GC Masoudi, FA AF Peterson, Pamela N. Rumsfeld, John S. Liang, Li Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. Masoudi, Frederick A. CA Amer Heart Assoc TI Treatment and Risk in Heart Failure Gaps in Evidence or Quality? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; pharmacotherapy; health policy and outcomes research ID CONVERTING ENZYME-INHIBITORS; VENTRICULAR EJECTION FRACTIONS; ACUTE CORONARY SYNDROMES; MORBIDITY PROGRAM; MORTALITY; SURVIVAL; ENALAPRIL; STRATIFICATION; ASSOCIATION; CANDESARTAN AB Background-Although the absolute benefits of an intervention are proportional to patients' underlying risk, studies in heart failure have noted a paradoxical inverse relationship between treatment and risk. The extent to which this reflects higher rates of contraindications in patients with higher risk or larger gaps in care quality has not been explored. Methods and Results-We studied 18 307 patients with left ventricular systolic dysfunction surviving hospitalization between January 2005 and June 2007 from 194 hospitals participating in Get With The Guidelines (GWTG)-Heart Failure. Patients were categorized according to their estimated risk for in-hospital mortality using a validated risk score. The proportions of patients with documented contraindications to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers as well as the use of these medications among patients without contraindications at hospital discharge was determined across levels of risk. For each therapy, the proportion of patients with contraindications was significantly higher with increasing patient risk (P<0.001 for each). Even after excluding those with contraindications, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers was significantly lower with increasing risk (P<0.001 for each). Conclusions-The use of evidence-based therapies is lower in patients with heart failure at higher risk of mortality both because of higher rates of contraindications to therapy and lower rates of use among eligible patients. Optimizing heart failure outcomes will require both the expansion of the evidence base for treating the highest-risk patients as well as the development of effective strategies to assure that eligible high-risk patients receive all appropriate therapies. (Circ Cardiovasc Qual Outcomes. 2010; 3:309-315.) C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Peterson, Pamela N.; Rumsfeld, John S.; Masoudi, Frederick A.] Univ Colorado Denver, Denver, CO USA. [Peterson, Pamela N.; Rumsfeld, John S.; Masoudi, Frederick A.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Liang, Li; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. RP Peterson, PN (reprint author), Div Cardiol, Mail Code 0960,777 Bannock St, Denver, CO 80204 USA. EM Pamela.Peterson@ucdenver.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association; GlaxoSmithKline; Medtronic; American Heart Association Pharmaceutical Roundtable [067001N, 0675060N]; American Heart Association Young Investigator Database Research Seed FX Get With The Guidelines Heart Failure is a program of the American Heart Association and was supported in part by unrestricted educational grants from GlaxoSmithKline and Medtronic. Dr P. N. Peterson is supported by an American Heart Association Pharmaceutical Roundtable grant 067001N and an American Heart Association Young Investigator Database Research Seed grant. Dr Hernandez is supported by an American Heart Association Pharmaceutical Roundtable grant 0675060N. None of the funders had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 28 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2010 VL 3 IS 3 BP 309 EP 315 DI 10.1161/CIRCOUTCOMES.109.879478 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597RN UT WOS:000277778400014 PM 20388872 ER PT J AU Mohammed, AA van Kimmenade, RRJ Richards, M Bayes-Genis, A Pinto, Y Moore, SA Januzzi, JL AF Mohammed, Asim A. van Kimmenade, Roland R. J. Richards, Mark Bayes-Genis, Antoni Pinto, Yigal Moore, Stephanie A. Januzzi, James L., Jr. TI Hyponatremia, Natriuretic Peptides, and Outcomes in Acutely Decompensated Heart Failure Results From the International Collaborative of NT-proBNP Study SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; hyponatremia; natriuretic peptides ID CONVERTING-ENZYME-INHIBITION; SERUM SODIUM CONCENTRATION; WORSENING RENAL-FUNCTION; EMERGENCY-DEPARTMENT; PROGNOSTIC IMPORTANCE; SYSTOLIC FUNCTION; TOLVAPTAN; DYSPNEA; TRIAL; PREDICTION AB Background-Hyponatremia is a well-known predictor of mortality in patients with acutely decompensated heart failure. Associations between hyponatremia and other prognostic variables in acutely decompensated heart failure, such as amino-terminal pro-B type natriuretic peptide remain unclear. Methods and Results-Six hundred twenty-eight patients presenting to the emergency department with acutely decompensated heart failure were studied. All were hospitalized. Serum sodium (Na) concentration at presentation was examined as a function of mortality at 1 year, alone and relative to other predictors of death. Hyponatremia (Na <= 135 mmol/L) was diagnosed in 24% (n=149) patients. Compared with those without hyponatremia, those affected were less likely to be male or to have hypertension or coronary artery disease but were more likely to have severe symptoms, to be anemic, and to have higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations (all P <= 0.05). When examined as a function of Na deciles (ranging from Na <132 mmol/L to Na <= 142 mmol/L), a U-shaped association was found between Na level and 1-year mortality. In multivariate Cox proportional hazards analysis, hyponatremia was an independent predictor of 1-year mortality (hazards ratio=1.72; 95% CI=1.22 to 2.37; P=0.001) as was an NT-proBNP concentration above the median value of 4690 pg/mL (hazards ratio=1.49; 95% CI=1.10 to 2.00; P=0.009). Those with hyponatremia and more elevated NT-proBNP were more likely to develop worsening renal function during their hospitalization and had highest rates of 1-year death. Notably, however, hyponatremia predicted only 1-year mortality in those with an elevated NT-proBNP. Conclusion-Hyponatremia is associated with adverse outcome in patients with acutely decompensated heart failure; however, the prognostic value of low Na is mainly evident in those with more pronounced elevation of NT-proBNP concentrations. (Circ Heart Fail. 2010;3:354-361.) C1 [Mohammed, Asim A.; Moore, Stephanie A.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mohammed, Asim A.; Moore, Stephanie A.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands. [Richards, Mark] Christchurch Sch Med & Hlth Sci, Dept Med, Christchurch, New Zealand. [Bayes-Genis, Antoni] Hosp Badalona Germans Trias & Pujol, Dept Cardiol, Badalona, Spain. [Pinto, Yigal] Univ Amsterdam, Dept Cardiol, NL-1012 WX Amsterdam, Netherlands. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org RI Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Bayes-Genis, Antoni/0000-0002-3044-197X; FU Balson Scholar Fund; Roche Diagnostics; Siemens; Critical Diagnostics FX Dr Januzzi was supported in part by the Balson Scholar Fund. Dr Januzzi reports research grant support from Roche Diagnostics, Siemens, and Critical Diagnostics. NR 34 TC 33 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2010 VL 3 IS 3 BP 354 EP U42 DI 10.1161/CIRCHEARTFAILURE.109.915280 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 598HK UT WOS:000277825800004 PM 20332419 ER PT J AU Arena, R Myers, J Abella, J Pinkstaff, S Brubaker, P Kitzman, D Peberdy, MA Bensimhon, D Chase, P Forman, DE Guazzi, M AF Arena, Ross Myers, Jonathan Abella, Joshua Pinkstaff, Sherry Brubaker, Peter Kitzman, Dalane Peberdy, Mary Ann Bensimhon, Daniel Chase, Paul Forman, Daniel E. Guazzi, Marco TI Defining the Optimal Prognostic Window for Cardiopulmonary Exercise Testing in Patients With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE exercise; heart failure; oxygen; prognosis; ventilation ID LEFT-VENTRICULAR DYSFUNCTION; AEROBIC CAPACITY; RECOMMENDATIONS; PERFORMANCE; STATEMENT; TIME AB Background-Ventilatory efficiency (VE/Vco(2) slope) and peak oxygen consumption (Vo) provide robust prognostic information in patients with heart failure undergoing cardiopulmonary exercise testing (CPX). The purpose of this study is to assess the change in prognostic characteristics of CPX at different time intervals. Methods and Results-Seven hundred ninety-one subjects (74% male, mean age: 60.7 +/- 12.9 years, ejection fraction: 34.6 +/- 15.0%, ischemic etiology: 51%) underwent CPX and were tracked for major cardiac events over a 4-year period. All event-free subjects were tracked for at least 3 years. Mean VE/Vco(2) slope and peak Vo(2) were 35.0 +/- 10.0 and 16.0 +/- 6.4 mL O-2 . kg(-1) . min(-1), respectively. There were a total of 263 major cardiac events (199 deaths, 45 transplants, and 19 left ventricular assist device implantations). Both continuous and dichotomous expressions of the VE/Vco(2) slope and peak Vo(2) were prognostically significant up to 18 months post-CPX. Continuous and dichotomous expressions of the VE/Vco(2) slope remained prognostically significant up to 36 months post-CPX, whereas peak Vo(2) was not predictive during the third and fourth year of follow-up. In a multivariate analysis, the VE/Vco(2) slope was consistently the superior prognostic marker, whereas peak Vo(2) added predictive value and was retained in the regression up to 18 months post-CPX. Conclusions-These results indicate that commonly assessed CPX variables retain prognostic value for at least 2 years. The VE/Vco(2) slope is the superior predictor of adverse events throughout follow-up, although peak Vo(2) provides additive prognostic information during the first 2 years of follow-up. (Circ Heart Fail. 2010;3:405-411.) C1 [Arena, Ross; Pinkstaff, Sherry] Virginia Commonwealth Univ, Dept PT, Richmond, VA 23298 USA. [Myers, Jonathan; Abella, Joshua] VA Palo Alto Hlth Care Syst, Div Cardiol, Palo Alto, CA USA. [Brubaker, Peter; Kitzman, Dalane] Wake Forest Univ, Bowman Gray Sch Med, Cardiol Sect, Winston Salem, NC USA. [Arena, Ross; Peberdy, Mary Ann] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. [Bensimhon, Daniel; Chase, Paul] LeBauer Cardiovasc Res Fdn, Greensboro, NC USA. [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Forman, Daniel E.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Guazzi, Marco] Univ Milan, Div Cardiol, San Paolo Hosp, Milan, Italy. RP Arena, R (reprint author), Virginia Commonwealth Univ, Dept PT, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM raarena@vcu.edu RI Arena, Ross/A-3141-2008; Guazzi, Marco/J-3165-2016 OI Arena, Ross/0000-0002-6675-1996; Chase, Paul/0000-0003-2127-0889; Guazzi, Marco/0000-0002-8456-609X FU NIH [R37AG18915, P60AG10484] FX Supported in part by NIH grants R37AG18915 and P60AG10484. NR 18 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2010 VL 3 IS 3 BP 405 EP 411 DI 10.1161/CIRCHEARTFAILURE.109.906446 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 598HK UT WOS:000277825800010 PM 20200329 ER PT J AU Ross, JS Krumholz, HM AF Ross, Joseph S. Krumholz, Harlan M. TI Response to Letter Regarding Article, "Recent National Trends in Readmission Rates After Heart Failure Hospitalization" SO CIRCULATION-HEART FAILURE LA English DT Letter ID CLINICAL-OUTCOMES C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Med,Dept Epidemiol & Publ Hlth, Dept Med,Sect Hlth Policy & Adm, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAY PY 2010 VL 3 IS 3 BP E17 EP E17 DI 10.1161/CIRCHEARTFAILURE.110.952895 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 598HK UT WOS:000277825800026 ER PT J AU Molano, I Mathenia, J Ruiz, P Gilkeson, GS Zhang, XK AF Molano, I. Mathenia, J. Ruiz, P. Gilkeson, G. S. Zhang, X. K. TI Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE bone marrow transplantation; Fli-1 transcription factor; hematopoietic cells; lupus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR; MARGINAL ZONE; RENAL-DISEASE; ETS FAMILY; B-CELLS; PATHOGENESIS; MEMBER; GENE; GLOMERULONEPHRITIS AB P>The transcription factor Fli-1 is implicated in the pathogenesis of both murine and human lupus. Decreased expression of Fli-1 in heterozygous (Fli-1+/-) Murphy Roths Large (MRL)/lpr mice resulted in significantly lower kidney pathological scores and markedly increased survival. In this study, bone marrow (BM) transplantation was used to investigate the role of decreased expression of Fli-1 in haematopoietic versus non-haematopoietic cell lineages in autoimmune disease development. Wild-type (WT) MRL/lpr that received BM from Fli-1+/- MRL/lpr mice had statistically significantly lower autoantibodies, less proteinuria, reduced renal disease and prolonged survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Although not statistically significant, Fli-1+/- MRL/lpr mice that received BM from WT MRL/lpr mice also had lower autoantibodies and improved survival compared to WT MRL/lpr mice that received BM from WT MRL/lpr mice. Our data indicate that expression of Fli-1 in haematopoietic cell lineages has a significant effect on disease development in MRL/lpr mice. C1 [Molano, I.; Gilkeson, G. S.; Zhang, X. K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Mathenia, J.; Gilkeson, G. S.; Zhang, X. K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. [Ruiz, P.] Univ Miami, Sch Med, Miami, FL USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Suite 912,96 Jonathan Lucas St MSC637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU National Institutes of Health [AR054546]; Medical Research Service, Department of Veterans Affairs FX This study was supported by National Institutes of Health grants (AR054546 to X. K. Z.) and the Medical Research Service, Department of Veterans Affairs (to X. Z. and G. G.). NR 25 TC 9 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2010 VL 160 IS 2 BP 275 EP 282 DI 10.1111/j.1365-2249.2009.04080.x PG 8 WC Immunology SC Immunology GA 581CT UT WOS:000276499400016 PM 20015093 ER PT J AU Jones-Jordan, LA Chitkara, M Coffey, B Jackson, JM Manny, RE Rah, MJ Walline, JJ AF Jones-Jordan, Lisa A. Chitkara, Monica Coffey, Bradley Jackson, John Mark Manny, Ruth E. Rah, Marjorie J. Walline, Jeffrey J. TI A comparison of spectacle and contact lens wearing times in the ACHIEVE study SO CLINICAL AND EXPERIMENTAL OPTOMETRY LA English DT Article DE clinical trial; contact lenses; glasses; paediatrics; spectacles; wearing time ID RANDOMIZED-TRIAL; MYOPIA PROGRESSION; CHILDREN; ADOLESCENT AB Purpose: The aim was to compare vision correction wearing time between myopic children and teenagers in a clinical trial of contact lenses and spectacles. Methods: Parents of subjects in the Adolescent and Child Health Initiative for Vision Empowerment (ACHIEVE) study provided wearing times for spectacle and contact lens wear. Hours wearing primary correction and total correction were compared between the two treatment groups. Other factors hypothesised to be associated with wearing time were analysed. Results: The average wearing time of the primary correction differed significantly with the wearing time for the spectacles group being 91.5 hours per week compared to 80.3 hours per week for the contact lens wearers (p < 0.0001). Total correction time was slightly higher for the contact lens wearers, 97.5 hours per week, after accounting for time wearing spectacles. Higher refractive error was strongly related to longer wearing times (p < 0.0002). Age and treatment group were associated with wearing time (p = 0.005). Young contact lens wearers wore their lenses less than young spectacle wearers and older contact lens wearers. Low scores on an appearance quality-of-life scale were associated with longer wearing time in spectacle wearers compared to the low-and high-scoring contact lens wearers. Gender, spectacle satisfaction and activities were not related to wearing time. Conclusions: While contact lens wearers, on average, wear their contact lenses less than spectacle wearers, they spend roughly the same amount of time wearing a refractive correction. Higher refractive error resulted in longer wearing times for both spectacle and contact lens wearers. Younger contact lens wearers wore their contact lenses for shorter periods than the spectacle wearers, but still wore them, on average, 74.4 hours per week (about 10 hours per day), suggesting that contact lenses are a viable alternative mode of correction for children. C1 [Jones-Jordan, Lisa A.; Walline, Jeffrey J.] Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA. [Coffey, Bradley] Pacific Univ, Coll Optometry, Forest Grove, OR USA. [Jackson, John Mark] So Coll Optometry, Memphis, TN USA. [Manny, Ruth E.] Univ Houston, Coll Optometry, Houston, TX USA. [Rah, Marjorie J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jones-Jordan, LA (reprint author), 338 W 10th Ave 649 Fry Hall, Columbus, OH 43210 USA. EM ljordan@optometry.osu.edu FU Johnson & Johnson Vision Care; Vision Care Institute, LLC FX This study received financial support from Johnson & Johnson Vision Care and the Vision Care Institute, LLC, which reviewed and approved the manuscript. NR 14 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0816-4622 J9 CLIN EXP OPTOM JI Clin. Exp. Optom. PD MAY PY 2010 VL 93 IS 3 BP 157 EP 163 DI 10.1111/j.1444-0938.2010.00480.x PG 7 WC Ophthalmology SC Ophthalmology GA 592TU UT WOS:000277404100005 PM 20557557 ER PT J AU Potash, J Anderson, KC AF Potash, Jesse Anderson, Kenneth C. TI Fighting Cancer Gets Personal SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Potash, Jesse; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2010 VL 16 IS 9 BP 2485 EP 2485 DI 10.1158/1078-0432.CCR-10-0611 PG 1 WC Oncology SC Oncology GA 608OX UT WOS:000278596100001 ER PT J AU Lovely, RS Kazmierczak, SC Massaro, JM D'Agostino, RB O'Donnell, CJ Farrell, DH AF Lovely, Rehana S. Kazmierczak, Steven C. Massaro, Joseph M. D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. Farrell, David H. TI gamma ' Fibrinogen: Evaluation of a New Assay for Study of Associations with Cardiovascular Disease SO CLINICAL CHEMISTRY LA English DT Article ID INDIVIDUAL PARTICIPANT METAANALYSIS; SPLICE VARIANT; EXOSITE-II; CHAIN; THROMBIN; IDENTIFICATION; FIBRINOLYSIS; HEMOSTASIS; PEPTIDE; RISK AB BACKGROUND: Studies of disease associations with gamma' fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay. METHODS: We developed an immunometric technique to measure gamma' fibrinogen concentrations in plasma and studied the clinical utility of this test in samples from healthy individuals enrolled in the Framingham Off-spring Study and in a separate case/control study of coronary artery disease (CAD). Monoclonal antibody 2.G2.H9, specific for the unique carboxyl terminal peptide of the fibrinogen gamma' chain, was used as capture antibody. Sheep antihuman fibrinogen/horseradish peroxidase conjugate was used for detection, with 3,3',5,5'-tetramethylbenzidine as substrate. We evaluated the linearity, imprecision, analytical specificity, and lower limit of quantification of the assay. We determined the reference interval for gamma' fibrinogen in healthy individuals from the Framingham Offspring Study (n = 2879) and quantified associations between gamma' fibrinogen and cardiovascular disease risk factors. The sensitivity and specificity of gamma' fibrinogen in evaluating CAD patients (n = 133) was determined with ROC curve analysis. RESULTS: The gamma' fibrinogen ELISA had within-run CVs of 13.4% at 0.127 g/L and 4.8% at 0.416 g/L. The limit of quantification at an imprecision of 20% was 0.10 g/L. The reference interval for healthy individuals was 0.088-0.551 g/L. ROC curve analysis of results from patients with CAD yielded an area under the curve of 0.76, with a diagnostic accuracy of 0.78 at a decision threshold of 0.30 g/L. CONCLUSIONS: gamma' Fibrinogen shows excellent utility for cardiovascular risk analysis. (C) 2010 American Association for Clinical Chemistry C1 [Kazmierczak, Steven C.; Farrell, David H.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Lovely, Rehana S.] SW Missouri State Univ, Dept Biomed Sci, Springfield, MO 65802 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Farrell, DH (reprint author), Oregon Hlth & Sci Univ, Dept Pathol, L113,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM farrelld@ohsu.edu OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Heart Association [0865486G]; National Heart, Lung, and Blood Institute of the NIH [R21-HL-75006, R21-HL-97298]; Office of Naval Research [N000140610411] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195), by grant 0865486G from the American Heart Association (to R. S. Lovely), and by grants R21-HL-75006 and R21-HL-97298 from the National Heart, Lung, and Blood Institute of the NIH and N000140610411 from the Office of Naval Research (to D. H. Farrell). NR 28 TC 25 Z9 25 U1 0 U2 1 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 MAY PY 2010 VL 56 IS 5 BP 781 EP 788 DI 10.1373/clinchem.2009.138347 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 589OM UT WOS:000277160800020 PM 20348406 ER PT J AU Delgado-Borrego, A Jordan, SH Negre, B Healey, D Lin, WY Kamegaya, Y Christofi, M Ludwig, DA Lok, ASF Chung, RT AF Delgado-Borrego, Aymin Jordan, Sergio H. Negre, Betania Healey, David Lin, Wenyu Kamegaya, Yoshitaka Christofi, Marielle Ludwig, David A. Lok, Anna S. F. Chung, Raymond T. CA HALT C Trial Grp TI Reduction of Insulin Resistance With Effective Clearance of Hepatitis C Infection: Results From the HALT-C Trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE HALT-C; Cirrhosis; HOMA; Interferon; Adiponectin ID LONG-TERM TREATMENT; VIRUS-INFECTION; LIVER-CIRRHOSIS; HCV; RNA AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is associated with an increased prevalence of diabetes and insulin resistance (IR); whether this is a causal relationship has not been established. METHODS: We performed a longitudinal study within the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial to evaluate whether suppression of hepatitis C is associated with improvement in IR. Participants had advanced hepatic fibrosis and carried non-3 HCV genotypes (n = 96). Patients underwent 24 weeks of pegylated interferon and ribavirin therapy and were categorized into HCV clearance groups at week 20 on the basis of HCV RNA levels; null responders had <1 log(10) decline (n = 38), partial responders had >= 1 log(10) decline (n = 37) but detectable HCV RNA, and complete responders had no detectable HCV RNA (n = 21). The primary outcome was change (week 20 minus week 0) in IR by using the homeostasis model assessment (HOMA2-IR). RESULTS: Adjusting only for baseline HOMA2-IR, mean HOMA2-IR differences were -2.23 (complete responders), 0.90 (partial responders), and +0.18 (null responders) (P = .036). The observed differences in mean HOMA2-IR scores were ordered in a linear fashion across response groups (P = .01). The association between HCV clearance and improvement in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis factor-alpha and was independent of potential confounders including age, gender, ethnicity, body mass index, duration of infection, medications used, and fibrosis. CONCLUSIONS: HCV suppression correlates with improvement in IR. These data provide further support for a role of HCV in the development of insulin resistance. C1 [Healey, David; Lin, Wenyu; Kamegaya, Yoshitaka; Christofi, Marielle; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Delgado-Borrego, Aymin; Jordan, Sergio H.; Negre, Betania; Ludwig, David A.] Univ Miami, Dept Pediat, Batchelor Childrens Res Inst, Miami, FL 33152 USA. [Lok, Anna S. F.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM rtchung@partners.org OI Yang, Shuman/0000-0002-9638-0890 FU NIH [K08 DK070022, DK078772, P60 DK020572, N01-DK-9-2323]; Robert Wood Johnson Foundation FX This work was supported by NIH K08 DK070022 (A.D.B.), NIH DK078772 (R.T.C.), the Robert Wood Johnson Foundation (A.D.B.), NIH P60 DK020572 (Michigan Diabetes Research and Training Center), and NIH Contract N01-DK-9-2323 (A.S.L.). NR 20 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2010 VL 8 IS 5 BP 458 EP 462 DI 10.1016/j.cgh.2010.01.022 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 593XQ UT WOS:000277496900016 PM 20156586 ER PT J AU Lewis-Ximenez, LL Lauer, GM zur Wiesch, JS de Sousa, PSF Ginuino, CF Paranhos-Baccala, G Ulmer, H Pfeiffer, KP Goebel, G Pereira, JL de Oliveira, JM Yoshida, CFT Lampe, E Velloso, CE Pinto, MA Coelho, HS Almeida, AJ Fernandes, CA Kim, AY Strasak, AM AF Lewis-Ximenez, Lia L. Lauer, Georg M. zur Wiesch, Julian Schulze Fonseca de Sousa, Paulo Sergio Ginuino, Cleber F. Paranhos-Baccala, Glaucia Ulmer, Hanno Pfeiffer, Karl P. Goebel, Georg Pereira, Joao Luiz de Oliveira, Jaqueline Mendes Tachibana Yoshida, Clara Fumiko Lampe, Elisabeth Velloso, Carlos Eduardo Pinto, Marcelo Alves Coelho, Henrique Sergio Almeida, Adilson Jose Fernandes, Carlos Augusto Kim, Arthur Y. Strasak, Alexander M. TI Prospective Follow-Up of Patients with Acute Hepatitis C Virus Infection in Brazil SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SPONTANEOUS VIRAL CLEARANCE; CELLULAR IMMUNE-RESPONSES; HCV INFECTION; UNITED-STATES; DRUG-USERS; DIAGNOSIS; COHORT; SEROCONVERSION; DISEASE; VIREMIA AB Background. The natural outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. However, little is known about host and viral factors associated with a self-limiting or chronic evolution of HCV infection. Methods. From 1 January 2001 through 31 December 2008, a consecutive series of 65 patients from Rio de Janeiro, Brazil, with a well-documented diagnosis of acute HCV infection, acquired via various routes, were enrolled in this study. Patients were prospectively followed up for a median of 40 months after the estimated date of HCV infection with serial measurements of serum alanine aminotransferase, HCV RNA, and anti-HCV antibodies. Spontaneous viral clearance (SVC) was defined as undetectable levels of HCV RNA in serum, in the absence of treatment, for 3 consecutive HCV polymerase chain reaction tests within the first 6 months of follow-up. Cox proportional hazards regression was used to identify host and viral predictors of SVC. Results. The cumulative rate of SVC was 44.6% (95% confidence interval, 32.3%-57.5%). Compared with chronic HCV evolution, patients with self-limiting disease had significantly lower peak levels of anti-HCV antibodies (median, 109.0 vs 86.7 optical density-to-cutoff ratio [od/co]; P < .02), experienced disease symptoms more frequently (69.4% vs 100%; P < .001), and had lower viral load at first clinical presentation (median, 4.3 vs 0.0 log copies; P = .01). In multivariate analyses, low peak anti-HCV level (<93.5 od/co) was the only independent predictor for SVC; the hazard ratio compared with high anti-HCV levels (>= 93.5 od/co) was 2.62 (95% confidence interval, 1.11-6.19; P = .03). Conclusion. Our data suggest that low levels of anti-HCV antibodies during the acute phase of HCV infection are independently related to spontaneous viral clearance. C1 [Lewis-Ximenez, Lia L.; Fonseca de Sousa, Paulo Sergio; Ginuino, Cleber F.; Tachibana Yoshida, Clara Fumiko; Lampe, Elisabeth; Velloso, Carlos Eduardo; Almeida, Adilson Jose] Fiocruz MS, Inst Oswaldo Cruz, Viral Hepatitis Lab, BR-21045900 Rio De Janeiro, Brazil. [de Oliveira, Jaqueline Mendes; Pinto, Marcelo Alves] Fiocruz MS, Inst Oswaldo Cruz, Viral Technol Lab, BR-21045900 Rio De Janeiro, Brazil. [Pereira, Joao Luiz] Fed Univ State Rio Janeiro, Bonsucesso Gen Hosp, Hepatol Clin, Rio De Janeiro, Brazil. [Coelho, Henrique Sergio] Fed Univ State Rio Janeiro, Liver Dis Clin, Clementino Fraga Filho Univ Hosp, Rio De Janeiro, Brazil. [Almeida, Adilson Jose] Fed Univ State Rio Janeiro, Gaffree & Guinle Univ Hosp, Hematol Unit, Rio De Janeiro, Brazil. [Fernandes, Carlos Augusto] Cent Publ Hlth Lab, Hepatitis Div, Rio De Janeiro, Brazil. [Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [zur Wiesch, Julian Schulze] Univ Klinikum Eppendorf, Med Klin 1, Hamburg, Germany. [Paranhos-Baccala, Glaucia] Merieux Fdn, Lab Emerging Pathogens, Lyon, France. [Paranhos-Baccala, Glaucia] Merieux Fdn, Christoph Merieux Lab, Lyon, France. [Ulmer, Hanno; Pfeiffer, Karl P.; Goebel, Georg; Strasak, Alexander M.] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria. RP Lewis-Ximenez, LL (reprint author), Fiocruz MS, Inst Oswaldo Cruz, Viral Hepatitis Lab, Sala B09,Av Brasil 4365, BR-21045900 Rio De Janeiro, Brazil. EM lialewis.fiocruz@gmail.com RI Goebel, Georg/P-6909-2015; Ulmer, Hanno/C-3488-2011; Fernandes, Carlos/F-9968-2012 OI Ulmer, Hanno/0000-0001-5911-1002; Fernandes, Carlos/0000-0003-2941-4744 FU National Institute of Health [AI066345-05]; Coordenacao Geral de Laboratorios de Saude Publica/Ministry of Health in Brasilia, Brazil FX Our research was supported by National Institute of Health grant AI066345-05 and Coordenacao Geral de Laboratorios de Saude Publica/Ministry of Health in Brasilia, Brazil. NR 38 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2010 VL 50 IS 9 BP 1222 EP 1230 DI 10.1086/651599 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UA UT WOS:000276248300003 PM 20235831 ER PT J AU Chan, KE Thadhani, R Lazarus, JM Hakim, RM AF Chan, Kevin E. Thadhani, Ravi Lazarus, J. Michael Hakim, Raymond M. TI Modeling the 4D Study: Statins and Cardiovascular Outcomes in Long-Term Hemodialysis Patients with Diabetes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; RANDOMIZED CLINICAL-TRIALS; TREATMENT PANEL-III; C-REACTIVE PROTEIN; DIALYSIS PATIENTS; CHOLESTEROL LEVELS; MORTALITY; ATORVASTATIN; SIMVASTATIN; EVENTS AB Background and objectives: Randomized, controlled trials (RCTs) are the gold standard for defining causal inferences but are sometimes not feasible because of cost, ethical, or time considerations. We explored the accuracy and potential use of a "simulated trial" through the modeling of a previously published RCT, Die Deutsche Diabetes Dialyse Studie (4D Study), a landmark study that investigated the cardiovascular benefit of atorvastatin use in 1255 patients with ESRD. Design, setting, participants, & measurements: Using a large historical database of interventions and outcomes in dialysis patients, we conducted an observational model of the 4D Study in dialysis patients who had type 2 diabetes and were prescribed a statin (5144 patients) and matched to a non-statin user (5144 control subjects) before multivariate modeling. Inclusion, exclusion, and outcome parameters of the study, as prespecified by the 4D Study, were strictly modeled in this analysis. Results: In covariate- and propensity-adjusted Cox regression, statin use (versus nonuse) was associated with a decrease in the composite primary outcome of cardiac death, nonfatal myocardial infarction, and stroke. Statin use was also associated with a decrease in cardiovascular mortality and all cardiac events combined. The hazard ratios in this observational model were numerically comparable to the hazard ratios reported in the 4D Study; however, because of the larger number of patients "enrolled," results in this simulated study achieved statistical significance. Conclusions: Statin use was associated with some cardiovascular benefit in a simulated trial of patients with ESRD; however, the size of benefit was considerably smaller than that seen in the general population. Such simulated trials may represent an exploratory, cost-effective option when RCTs are not immediately feasible. Clin J Am Sac Nephrol 5: 856-866, 2010. doi: 10.2215/CJN.07161009 C1 [Chan, Kevin E.; Lazarus, J. Michael; Hakim, Raymond M.] Fresenius Med Care N Amer, Waltham, MA USA. [Chan, Kevin E.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. RP Chan, KE (reprint author), 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com NR 49 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2010 VL 5 IS 5 BP 856 EP 866 DI 10.2215/CJN.07161009 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 593TJ UT WOS:000277483300019 PM 20338963 ER PT J AU Reese, PP Tehrani, T Lim, MA Asch, DA Blumberg, EA Simon, MK Bloom, RD Halpern, SD AF Reese, Peter P. Tehrani, Tara Lim, Mary Ann Asch, David A. Blumberg, Emily A. Simon, Maureen K. Bloom, Roy D. Halpern, Scott D. TI Determinants of the Decision to Accept a Kidney from a Donor at Increased Risk for Blood-Borne Viral Infection SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID INFORMING CANDIDATES; CONJOINT-ANALYSIS; TRANSPLANTATION; RECIPIENT; DISEASE AB Background and objectives: The use of kidneys from donors at increased risk for viral infections (DIRVI) such as HIV could increase the number of transplants and decrease waiting times. This study aimed to identify the proportion of kidney transplant candidates that would accept a kidney from a DIRVI and the factors that influenced this decision. Design, setting, participants, & measurements: Conjoint analysis was used to assess the conditions in which renal transplant candidates would accept a DIRVI kidney. Candidates completed 12 scenarios in which the waiting time for a kidney, the donor age as a surrogate for kidney quality, and the risk of contracting HIV were systematically varied. Results: Among 175 respondents, 42 (24.0%) rejected DIRVI kidneys under all conditions, 103 (58.9%) accepted DIRVI kidneys under some conditions, and 31 (17.7%) always accepted DIRVI kidneys. In multivariable logistic regression, patients were more likely to accept a DIRVI kidney when waiting time was longer, the donor was younger, and HIV risk was lower (P < 0.01 for each variable). Patients on dialysis (P < 0.01) and older patients (P = 0.04) more commonly accepted DIRVI kidneys, but self-rated sense of health was not associated with DIRVI kidney acceptance. Conclusions: Most renal transplant candidates would accept a DIRVI kidney under some circumstances. These findings suggest that recipients can be allowed to make prospective choices regarding DIRVI kidney acceptance without hindering placement of these organs. Clin J Am Soc Nephrol 5: 917-923, 2010. doi: 10.2215/CJN.08251109 C1 [Reese, Peter P.] Univ Penn, Dept Med, Div Renal, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Reese, Peter P.; Asch, David A.; Halpern, Scott D.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Reese, Peter P.; Simon, Maureen K.; Bloom, Roy D.] Univ Penn, Penn Transplant Inst, Philadelphia, PA 19104 USA. [Blumberg, Emily A.] Univ Penn, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Div Pulm, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Reese, PP (reprint author), Univ Penn, Dept Med, Div Renal, Ctr Clin Epidemiol & Biostat, 908 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.reese@uphs.upenn.edu OI Asch, David/0000-0002-7970-286X FU National Institutes of Health Career Development [K23-DK078688-01]; Greenwall Foundation FX Dr. Reese is supported by a National Institutes of Health Career Development Award, K23-DK078688-01. Dr. Halpern is supported by a Greenwall Foundation Faculty Scholar Award in Bioethics. Preliminary 10. data from this study were presented at the May 30 through June 3, 2009 American Transplant Congress in Boston, Massachusetts. NR 21 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2010 VL 5 IS 5 BP 917 EP 923 DI 10.2215/CJN.08251109 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 593TJ UT WOS:000277483300027 PM 20338966 ER PT J AU Rosner, M Abdel-Rahman, E Williams, ME AF Rosner, Mitchell Abdel-Rahman, Emaad Williams, Mark E. CA ASN Advisory Grp Geriatric Nephrol TI Geriatric Nephrology: Responding to a Growing Challenge SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; BLOOD-PRESSURE; UNITED-STATES; MYOCARDIAL-INFARCTION; ELDERLY-PEOPLE; PREVALENCE; OLDER; COMMUNITY; OUTCOMES AB Changing demographics of the global population predict that the number of people age 65 years or greater will triple over the coming decades. Because the incidence and prevalence of kidney disease increase with advancing age, nephrologists will be increasingly confronted with a population of patients who are elderly and have a large number of comorbid conditions requiring ongoing care. Furthermore, it is increasingly understood that aging leads to its own unique aspects of nephrologic diagnosis and treatment. Although it is known that elderly patients constitute a group with special needs and present unique challenges to the nephrologist, traditional nephrology fellowship training has not included a focus on the geriatric population. In response to this need for greater education and awareness, the American Society of Nephrology has initiated a program of educational activities in geriatric nephrology and has chartered a specific advisory council. The priority being given to geriatric nephrology is a hopeful sign that issues such as treatment options, the efficacy of treatments, and their effect on quality of life for the elderly patient with kidney disease will be improved in the coming years. Clin J Am Soc Nephrol 5: 936-942, 2010. doi: 10.2215/CJN.08731209 C1 [Rosner, Mitchell; Abdel-Rahman, Emaad] Univ Virginia, Div Nephrol, Charlottesville, VA USA. [Williams, Mark E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Rosner, M (reprint author), Univ Virginia Hlth Syst, Div Nephrol, Charlottesville, VA 22908 USA. EM mhr9r@virginia.edu NR 52 TC 23 Z9 25 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2010 VL 5 IS 5 BP 936 EP 942 DI 10.2215/CJN.08731209 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 593TJ UT WOS:000277483300030 PM 20185600 ER PT J AU Simon, MV Michaelides, C Wang, S Chiappa, KH Eskandar, EN AF Simon, Mirela V. Michaelides, Costas Wang, Sonya Chiappa, Keith H. Eskandar, Emad N. TI The effects of EEG suppression and anesthetics on stimulus thresholds in functional cortical motor mapping SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Cortical mapping; Cortical excitability; EEG burst suppression; Anesthetics; Stimulus thresholds; Age ID BURST-SUPPRESSION; EVOKED-POTENTIALS; BRAIN-TUMORS; ELECTRICAL-STIMULATION; ISOFLURANE ANESTHESIA; VOLATILE ANESTHETICS; SURGICAL-MANAGEMENT; CORTEX; PROPOFOL; GLIOMAS AB Objective: To investigate the effects of EEG suppression and anesthetics on variability of electrical stimulus thresholds during functional cortical motor mapping, and the possible influences of age, lesion location and pathology. Methods: Multivariate regression analysis was performed to study these relationships in 60 cases of successful mapping using the monopolar multipulse train technique. Results: An increase in the length of EEG "flats" by 1 s produced an increase in stimulus threshold by 1.08 mA (p = 0.0004). Administration of TIVA (total intravenous anesthesia) or inhalational agents produced an additional increase in threshold by 1.27 mA (p = 0.38) or 4.84 mA (p = 0.04) respectively, when compared to awake patients. Conclusions: Depth of cortical suppression impacts the stimulus thresholds. The effect of TIVA on thresholds is mediated by its effect on cortical excitability. The effects of inhalational agents on thresholds involve their influence on excitability at other levels of the neuraxis. Significance: The study represents an important step towards building a predictive model for stimulus thresholds. It also improves our understanding of the relationships of anesthetics, EEG burst suppression pattern and age with cortical excitability. (C) 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Simon, Mirela V.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Simon, Mirela V.; Michaelides, Costas; Wang, Sonya; Chiappa, Keith H.] Dept Neurol, Clin Neurophysiol Div, Boston, MA USA. RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org NR 52 TC 9 Z9 12 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2010 VL 121 IS 5 BP 784 EP 792 DI 10.1016/j.clinph.2010.01.002 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 575TM UT WOS:000276091300020 PM 20117047 ER PT J AU Howlett, MSL Alexander, GA Tsuchiya, B AF Howlett, Mary Susan L. Alexander, Gail A. Tsuchiya, Brenda TI Health Care Providers' Attitudes Regarding Family Presence During Resuscitation of Adults An Integrated Review of the Literature SO CLINICAL NURSE SPECIALIST LA English DT Article DE attitude of health personnel; cardiopulmonary resuscitation; professional-family relations ID NURSES; PHYSICIANS; BELIEFS; MEMBERS AB Purpose: Family presence (FP) during resuscitation is a controversial practice that leads to disagreement among health care professionals. A systematic review of the literature was performed to answer the question: What are the attitudes of health care providers regarding family presence during resuscitation of adults? Methods: MEDLINE, PubMed, and CINAHL databases were searched using the following terms: family, family presence, family witnessed, cardiopulmonary resuscitation, nurses, personnel, patient, attitudes, attitude of health personnel, and ethics. Criteria for inclusion consisted of research studies addressing health care providers' attitudes toward family presence during adult resuscitation conducted in the United States that were published between 1998 and 2008. Results: The literature search produced 480 titles. Thirteen full-text articles met criteria for inclusion in the evidence tables. Findings of this integrated literature indicate that: between and within discipline differences in attitudes, perceived burden on staff, perceived effects on family, lack of medical knowledge of family, and existence of a hospital policy influence provider attitudes toward FP. Conclusions and Implications: More research is needed to determine if FP is evidence based; however, there is sufficient evidence to consider implementing FP. There is wide variation in support for FP among health care professionals, although nurses generally are more favorable. If an institution elects to implement an FP policy or evidence-based practice guideline, it must carefully consider the many provider, patient, family, and system-level factors that can hinder or promote the success of this initiative. C1 [Howlett, Mary Susan L.] Univ Massachusetts, Family Nurse Practitioner Program, Boston, MA 02125 USA. [Howlett, Mary Susan L.] Massachusetts Nurses Assoc, Div Nursing, Canton, MA USA. [Alexander, Gail A.] Univ Massachusetts, Crit Care Clin Nurse Specialist Program, Boston, MA 02125 USA. [Alexander, Gail A.] Massachusetts Gen Hosp, Norman Knight Nursing Ctr Clin & Profess Dev, Boston, MA 02114 USA. [Tsuchiya, Brenda] Bellingham Med Ctr, Bellingham, MA USA. RP Howlett, MSL (reprint author), 340 Turnpike St, Canton, MA 02021 USA. EM mhowlett@mnarn.org NR 19 TC 17 Z9 18 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAY-JUN PY 2010 VL 24 IS 3 BP 161 EP 174 DI 10.1097/NUR.0b013e3181dc548a PG 14 WC Nursing SC Nursing GA 592LH UT WOS:000277379900009 PM 20404625 ER PT J AU Shargorodsky, J Lin, HW Gopen, Q AF Shargorodsky, Josef Lin, Harrison W. Gopen, Quinton TI Facial Nerve Palsy in the Pediatric Population SO CLINICAL PEDIATRICS LA English DT Editorial Material ID RAMSAY-HUNT-SYNDROME; BELLS-PALSY; LYME-DISEASE; EARLY-DIAGNOSIS; GRADING SYSTEM; PARALYSIS; CHILDREN; MANAGEMENT; PREDNISONE; ACYCLOVIR C1 [Shargorodsky, Josef; Lin, Harrison W.; Gopen, Quinton] Harvard Univ, Sch Med, Boston, MA USA. [Gopen, Quinton] Childrens Hosp, Boston, MA 02115 USA. RP Shargorodsky, J (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM josef_shargorodsky@meei.harvard.edu NR 53 TC 16 Z9 16 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAY PY 2010 VL 49 IS 5 BP 411 EP 417 DI 10.1177/0009922809347798 PG 7 WC Pediatrics SC Pediatrics GA 588RK UT WOS:000277091000001 PM 20139107 ER PT J AU Eisner, L Deckersbach, T AF Eisner, Lori Deckersbach, Thilo TI When Someone You Love Is Bipolar: Help and Support for You and Your Partner SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Book Review ID DISORDER; BURDEN C1 [Eisner, Lori] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Eisner, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM leisner@partners.org NR 4 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 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2010 VL 17 IS 2 BP 233 EP 234 PG 2 WC Psychology, Clinical SC Psychology GA 587JI UT WOS:000276987000013 ER PT J AU Chasson, GS AF Chasson, Gregory S. TI Overcoming Obsessive Compulsive Disorder: A Self-Help Guide Using Cognitive Behavioral Techniques SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Book Review C1 [Chasson, Gregory S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Chasson, Gregory S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chasson, GS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Floor 2, Boston, MA 02114 USA. EM gchasson@gmail.com NR 1 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 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD MAY PY 2010 VL 17 IS 2 BP 235 EP 235 PG 1 WC Psychology, Clinical SC Psychology GA 587JI UT WOS:000276987000014 ER PT J AU Petersen, OW Polyak, K AF Petersen, Ole William Polyak, Kornelia TI Stem Cells in the Human Breast SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; ADULT HUMAN BREAST; MONOCLONAL-ANTIBODIES; MYOEPITHELIAL CELLS; DEFINED MEDIUM; IN-VITRO; GROWTH; CANCER; DIFFERENTIATION; IMMORTALIZATION AB The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main mammary cell lineages, producing an increasing number of cells with distinct properties. Understanding the biological characteristics of human breast stem cells and their progeny is crucial in attempts to compare the features of normal stem cells and cancer precursor cells and distinguish these from nonprecursor cells and cells from the bulk of a tumor. A historical overview of research on human breast stem cells in primary tissue and in culture reveals the progress that has been made in this area, whereas a focus on the cell-of-origin and reprogramming that occurs during neoplastic conversion provides insight into the enigmatic way in which human breast cancers are skewed toward the luminal epithelial lineage. C1 [Petersen, Ole William] Univ Copenhagen, Dept Cellular & Mol Med, Fac Hlth Sci, DK-2200 Copenhagen N, Denmark. [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Petersen, OW (reprint author), Univ Copenhagen, Dept Cellular & Mol Med, Fac Hlth Sci, Panum Bldg, DK-2200 Copenhagen N, Denmark. EM o.w.petersen@sund.ku.dk FU National Cancer Institute [CA89393, CA116235, CA143233, CA080111]; Department of Defense [W81XWH-07-1-0294, W81XWH-09-1-0131]; Avon Foundation; Susan G. Komen Breast Cancer Research Foundation; Breast Cancer Research Foundation; Novartis Oncology; Danish Cancer Society; Dansk Kraeftforskningsfond; EuroCSC [037632]; Lundbeck Foundation; Novo Nordic Foundation; Danish Research Agency [2107-05-0006]; DAN-ED; NIH [R01CA064786]; Friis Foundation; Simon Spies Foundation FX The authors thank members of their laboratories for their critical reading of the manuscript and constructive discussions. Work in the authors' laboratories is supported by the National Cancer Institute (CA89393, CA116235, CA143233, and CA080111), Department of Defense (W81XWH-07-1-0294 and W81XWH-09-1-0131), Avon Foundation, Susan G. Komen Breast Cancer Research Foundation, Breast Cancer Research Foundation, and Novartis Oncology grants awarded to KP, and The Danish Cancer Society; Dansk Kraeftforskningsfond; The EuroCSC contract no: 037632; The Lundbeck Foundation; The Novo Nordic Foundation; The Danish Research Agency, contract no. 2107-05-0006; DAN-ED; NIH, contract no. R01CA064786; The Friis Foundation and The Simon Spies Foundation awarded to OWP. The use of human material has been reviewed by the Regional Scientific Ethical Committees for Copenhagen and Frederiksberg and approved with reference to (KF) (11) 263995. Marianne T. Lund is acknowledged for expert technical assistance. NR 60 TC 45 Z9 45 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD MAY PY 2010 VL 2 IS 5 AR a003160 DI 10.1101/cshperspect.a003160 PG 15 WC Cell Biology SC Cell Biology GA 625GI UT WOS:000279882700014 PM 20452965 ER PT J AU Zou, L Feng, Y Chen, YJ Si, R Shen, SQ Zhou, QC Ichinose, F Scherrer-Crosbie, M Chao, W AF Zou, Lin Feng, Yan Chen, Yu-Jung Si, Rui Shen, Shiqian Zhou, Qichang Ichinose, Fumito Scherrer-Crosbie, Marielle Chao, Wei TI Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE Toll-like receptor 2; sepsis; cardiac dysfunction; inflammation; neutrophils ID PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; LEFT-VENTRICULAR CONTRACTILITY; REGIONAL MYOCARDIAL-FUNCTION; SEPTIC SHOCK; CHEMOKINE RECEPTOR; DOPPLER-ECHOCARDIOGRAPHY; QUANTITATIVE ASSESSMENT; ISCHEMIA-REPERFUSION; CECAL LIGATION; UNITED-STATES AB Objective: To determine the role of toll-like receptor 2 in cardiac dysfunction during polymicrobial sepsis. Design: Controlled animal study. Setting: University hospital research laboratory. Subjects: Male C57BL/6, wild-type, toll-like receptor 2(- /-). Intervention: Polymicrobial peritonitis, a clinically relevant model of sepsis, was generated by cecum ligation and puncture. Wild-type and toll-like receptor 2(-/-) mice were divided into sham and cecum ligation and puncture groups. The sham animals underwent laparotomy but without cecum ligation and puncture. Twenty-four hours after surgeries, the cardiac function was assessed by serial echo-cardiography in vivo, a pressure transducer catheter was inserted into the left ventricles of isolated hearts (Langendorff model), and in vitro measurement of Ca(2+) transients and sarcomere shortening in adult cardiomyocytes were isolated from the sham and septic animals. In addition, myocardial and serum cytokines, blood white blood cell counts, peritoneal neutrophil recruitment, chemokine receptor expression, and survival rates were examined. Measurements and Results: Compared to septic wild-type mice, toll-like receptor 2(-/-) mice had markedly improved cardiacfunction during sepsis, as demonstrated by in vivo tissue Doppler imaging, better-preserved left ventricle function in isolated heart, and improved sarcomere shortening measured in single cardiomyocytes. There was also a significant survival benefit in toll-like receptor 2(-/-) mice compared to wild-type mice. These favorable outcomes in toll-like receptor 2(-/-) mice were associated with attenuated cardiodepressant cytokine levels in the myocardium and serum and enhanced neutrophil migratory function. Conclusions: These studies suggest that toll-like receptor 2 signaling plays a critical role in mediating cardiomyopathy, deleterious myocardial and systemic inflammation, and high mortality during polymicrobial sepsis. (Crit Care Med 2010; 38:1335-1342) C1 [Zou, Lin; Feng, Yan; Chen, Yu-Jung; Si, Rui; Shen, Shiqian; Ichinose, Fumito; Chao, Wei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02163 USA. [Scherrer-Crosbie, Marielle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. [Zou, Lin; Zhou, Qichang] Cent S Univ, Dept Ultrasound Med, Changsha, Hunan, Peoples R China. RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02163 USA. EM wchao@partners.org RI Feng, Yan/H-5808-2012 FU National Institutes of Health [GM-080906]; American Heart Association [0755890T] FX This work was supported by National Institutes of Health grant GM-080906 and American Heart Association grant 0755890T. NR 42 TC 36 Z9 39 U1 0 U2 8 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 MAY PY 2010 VL 38 IS 5 BP 1335 EP 1342 DI 10.1097/CCM.0b013e3181d99e67 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 593JD UT WOS:000277449100014 PM 20228680 ER PT J AU Swinburn, P Lloyd, A Nathan, P Choueiri, TK Cella, D Neary, MP AF Swinburn, Paul Lloyd, Andrew Nathan, Paul Choueiri, Toni K. Cella, David Neary, Maureen P. TI Elicitation of health state utilities in metastatic renal cell carcinoma SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Adverse effects; Economic evaluation; Health-related quality of life; Renal cancer; Utility ID QUALITY-OF-LIFE; INTERFERON-ALPHA; KIDNEY CANCER; LUNG-CANCER; SUNITINIB; SURVIVAL AB Objective: The aim of the study was to obtain United Kingdom societal preferences for receiving newly developed treatments for metastatic renal cell carcinoma. Methods: Health states were developed based on a literature review and in-depth interviews with clinical experts. These states described the burden of both stable and progressive disease, and a variety of commonly encountered toxicities associated with first-line therapies (fatigue, diarrhoea, nausea/vomiting, mucositis, hand/foot syndrome, hypertension and anaemia). These states were further reviewed by additional clinicians and patients to ensure their validity. One hundred members of the general public rated the states using the time trade-off (TTO) methodology to determine health state utility. Results: Stable disease had a utility value of 0.795 whilst progressive disease demonstrated a significant decline with a value of 0.355. The range of toxicities showed a variable impact in line with their toxicity grading from fatigue grade I/II (0.751) to hand/foot syndrome grade III (0.469). Conclusions: This study highlights the burden associated with a number of common toxicities encountered with current first-line mRCC treatments. Practical constraints coupled with the societal nature of the valuation exercise limited the amount of direct involvement by patients. However, these utility values should better permit the consideration of toxicity profiles in establishing the cost-effectiveness of future treatments. C1 [Nathan, Paul] Mt Vernon Canc Ctr, Northwood, Middx, England. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Neary, Maureen P.] GlaxoSmithKline Inc, Collegeville, PA USA. [Cella, David] Northwestern Univ, Lurie Canc Ctr, Chicago, IL 60611 USA. EM Paul.Swinburn@oxfordoutcomes.com FU GlaxoSmithKline FX This study was funded by GlaxoSmithKline. NR 30 TC 15 Z9 16 U1 1 U2 4 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 MAY PY 2010 VL 26 IS 5 BP 1091 EP 1096 DI 10.1185/03007991003712258 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 583MO UT WOS:000276680900011 PM 20225993 ER PT J AU Eikermann-Haerter, K Ayata, C AF Eikermann-Haerter, Katharina Ayata, Cenk TI Cortical Spreading Depression and Migraine SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Cortical spreading depression (CSD); Migraine; Familial hemiplegic migraine (FHM); Hormones; Aura; Trigger ID FAMILIAL HEMIPLEGIC MIGRAINE; TRIGEMINAL NUCLEUS; NEOCORTICAL SLICES; CALCIUM-CHANNELS; CLASSIC MIGRAINE; CEREBRAL-CORTEX; MOUSE MODELS; MUTANT MICE; CA2+ INFLUX; HUMAN BRAIN AB Cortical spreading depression, a slowly propagating wave of transient neuronal and glial depolarization, is widely accepted as the electrophysiologic substrate of migraine aura and a trigger for headache. Recent clinical and experimental evidence reinforces the putative role of cortical spreading depression in migraine pathophysiology. Imaging studies in migraineurs demonstrated hemodynamic changes consistent with cortical spreading depression during aura, whereas recent animal studies helped unravel pathophysiologic aspects such as the triggering mechanisms, genetic and hormonal modulation, and potential therapeutic targets. Here, we provide an overview of recent advances in our understanding of migraine pathophysiology and treatment. C1 [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Neurosci Intens Care Unit, Boston, MA 02114 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Eikermann-Haerter, Katharina; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, 55 Fruit St, Boston, MA 02114 USA. EM khaerter@partners.org; cayata@partners.org NR 76 TC 46 Z9 48 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD MAY PY 2010 VL 10 IS 3 BP 167 EP 173 DI 10.1007/s11910-010-0099-1 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 602AY UT WOS:000278111700002 PM 20425031 ER PT J AU Arora, P Newton-Cheh, C AF Arora, Pankaj Newton-Cheh, Christopher TI Blood pressure and human genetic variation in the general population SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE association; blood pressure; genetics ID GENOME-WIDE ASSOCIATION; ATRIAL-NATRIURETIC-PEPTIDE; EPITHELIAL SODIUM-CHANNEL; NA-CL COTRANSPORTER; CALCIUM-SENSING RECEPTOR; COMPLEX HUMAN-DISEASES; HUMAN HYPERTENSION; BARTTERS-SYNDROME; COMMON VARIANTS; ADRENOGENITAL SYNDROME AB Purpose of review Hypertension is a complex trait with multiple environmental and genetic contributors. Until recently, linkage studies of rare Mendelian disorders of hypertension and hypotension have produced the most notable progress toward understanding the heritable basis of blood pressure (BP). Association studies to identify common variants have been limited in the past by small sample sizes and most findings have lacked replication. Recent findings Recently, well powered, targeted candidate gene and genome-wide association studies have reported reproducible associations between rare and common genetic variants and BP and hypertension at the population level. Summary Identification of novel genes will lead to an improved understanding of BP regulation and the potential for novel therapies. C1 [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Arora, Pankaj; Newton-Cheh, Christopher] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM cnewtoncheh@chgr.mgh.harvard.edu RI Arora, Pankaj/F-3437-2011 OI Arora, Pankaj/0000-0003-2420-3550 FU NIH [K23-HL080025, R01-HL098283]; Doris Duke Charitable Foundation; Burroughs Wellcome Fund Career Award for Medical Scientists FX Dr Newton-Cheh is supported by NIH (K23-HL080025 and R01-HL098283), a Doris Duke Charitable Foundation Clinical Scientist Development Award and a Burroughs Wellcome Fund Career Award for Medical Scientists. NR 89 TC 12 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2010 VL 25 IS 3 BP 229 EP 237 DI 10.1097/HCO.0b013e3283383e2c PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586CQ UT WOS:000276879500010 PM 20224392 ER PT J AU Pirruccello, J Kathiresan, S AF Pirruccello, James Kathiresan, Sekar TI Genetics of lipid disorders SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE cholesterol; genetics; genome-wide association; lipids; triglycerides ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; STATIN THERAPY; PCSK9; VARIANTS; RISK; LOCI; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; TORCETRAPIB AB Purpose of review In this review, we will highlight recent advances in identifying genes and gene regions responsible for the variation in serum lipid levels. We will also consider the next directions for research based on these advances. Recent findings Large-scale genome-wide association studies have successfully screened common variants across the genome for association with serum lipids and have generated novel hypotheses about the causes of serum lipid variation. Summary Deep sequencing of genome-wide association signals promises to expand the catalogue of variants responsible for serum lipid variation and, with a full catalogue of variants, we may develop a panel of polymorphisms with clinical utility. In parallel, functional exploration of the genome-wide association signals should expand our knowledge of lipoprotein metabolism and generate targets for pharmacologic intervention. C1 [Pirruccello, James; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Pirruccello, James; Kathiresan, Sekar] Broad Inst, Cambridge, MA USA. [Pirruccello, James] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org FU Sarnoff Cardiovascular Research Foundation; NIH [RC2 HL101864, RC1 HL099793, RC1 HL099634] FX J.P. is a research fellow supported by Sarnoff Cardiovascular Research Foundation; S. K. is supported by NIH RC2 HL101864, NIH RC1 HL099793, and NIH RC1 HL099634. NR 20 TC 15 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2010 VL 25 IS 3 BP 238 EP 242 DI 10.1097/HCO.0b013e328338574d PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586CQ UT WOS:000276879500011 PM 20224388 ER PT J AU Loubiere, S Meiners, C Sloan, C Freedberg, KA Yazdanpanah, Y AF Loubiere, Sandrine Meiners, Constance Sloan, Caroline Freedberg, Kenneth A. Yazdanpanah, Yazdan TI Economic evaluation of ART in resource-limited countries SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE antiretroviral therapy; cost; cost-effectiveness; HIV/AIDS; resource-limited countries ID ACTIVE ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS ANALYSIS; HIV-1-INFECTED PATIENTS; DRUG-RESISTANCE; NAIVE PATIENTS; INCOME COUNTRIES; SETTINGS; TENOFOVIR; COMBINATION; STRATEGIES AB Purpose of review In the face of increasing economic constraints, it is critically important to evaluate how best to utilize available resources. In this article, we review the growing number of cost-effectiveness analyses of HIV treatment with antiretroviral therapy (ART) in resource-limited settings. We focus on studies that evaluate when to start therapy, what therapy to start with and what to switch to based on what criteria. Recent findings Recent findings show that earlier ART initiation based on CD4 cell count criteria (CD4 cell counts <350 cells/mu l) can be cost effective in most resource-limited settings. They also suggest that initiating ART with tenofovir as a component of the first-line regimen is an efficient use of resources compared with initiating ART with stavudine. Finally, they show that HIV RNA monitoring combined with CD4 monitoring is more effective than CD4 monitoring alone, although this strategy was not yet found to be cost effective in all studies. Nearly all studies demonstrate, however, that the cost-effectiveness ratio of HIV RNA monitoring will become more attractive as the cost of HIV RNA tests and second-line ART regimens decrease. Summary Substantial research shows that ART for HIV disease in resource-limited settings is cost effective. Improved initial regimens and increased laboratory monitoring may provide both clinical benefit and good value for money. Further price reductions of laboratory tests and recent antiretroviral drugs are needed to guarantee the cost-effectiveness of these required improvements. C1 [Loubiere, Sandrine; Meiners, Constance] Univ Mediterranean, INSERM, IRD, UMR Econ & Social Sci Hlth Syst & Soc 912, Marseille, France. [Loubiere, Sandrine; Meiners, Constance] Univ Mediterranean, INSERM, IRD, SE Hlth Reg Observ ORS PACA, Marseille, France. [Meiners, Constance] Univ Fed Rio de Janeiro, Inst Econ, BR-21941 Rio De Janeiro, Brazil. [Meiners, Constance] Minist Planning Budget & Adm, Brasilia, DF, Brazil. [Sloan, Caroline; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Sloan, Caroline; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Sloan, Caroline; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Harvard Ctr AIDS Res, Dept Med,Med Sch, Boston, MA USA. [Yazdanpanah, Yazdan] Serv Univ Malad Infect & Voyageur, Ctr Hosp Tourcoing, Fac Med Lille, Lille, France. [Yazdanpanah, Yazdan] Fac Med Lille, EA2694, F-59045 Lille, France. RP Loubiere, S (reprint author), INSERM, ORS PACA U912, 23 Rue Stanislas Torrents, F-13006 Marseille, France. EM sandrine.loubiere@inserm.fr FU National Institute of Allergy and Infectious Diseases [R01 AI058736]; French National Agency for Research on AIDS and Viral Hepatitis FX Funding source: The work was supported by grants from the National Institute of Allergy and Infectious Diseases (R01 AI058736) and the French National Agency for Research on AIDS and Viral Hepatitis. NR 48 TC 13 Z9 14 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2010 VL 5 IS 3 BP 225 EP 231 DI 10.1097/COH.0b013e3283384a9d PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828NF UT WOS:000295507600005 PM 20539078 ER PT J AU Flaherty, KT Hodi, FS Bastian, BC AF Flaherty, Keith T. Hodi, F. Stephen Bastian, Boris C. TI Mutation-driven drug development in melanoma SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE BRAF; CKIT; melanoma; oncogene ID METASTATIC MELANOMA; MALIGNANT-MELANOMA; UVEAL MELANOMA; SOMATIC MUTATIONS; IMATINIB MESYLATE; CLINICAL-EFFICACY; BRAF MUTATIONS; RAS MUTATIONS; KINASE DOMAIN; COPY NUMBER AB Purpose of review The identification of mutations in signal transduction pathways that are central in melanoma pathophysiology has provided new therapeutic targets for drug development. The purpose of this review is to define those oncogenes for which there are preclinical data supporting clinical trials and to summarize results from clinical investigations. Recent findings CKIT mutations were first reported in 2005 but are present in only a small subpopulation of melanoma patients. The validation of inhibitors developed in gastrointestinal stromal tumors has taken several years, but recent evidence suggests that responses can be seen in CKIT mutant melanoma. First reported in 2002, BRAF is mutated in 50% of all melanomas and subsets of other cancers. The melanoma field is leading the clinical trials evaluating the value of targeting BRAF and MEK in BRAF mutant tumors. Results from the first clinical trial with a potent and selective BRAF inhibitor clearly show the therapeutic promise of this approach. Summary Larger clinical trials are needed to fully define the efficacy of BRAF and CKIT-directed therapy in melanoma, but early results suggest that this strategy will transform treatment options. Additional potential targets have been identified, and clinical trials evaluating novel drugs against them are underway. C1 [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM ktflaherty@partners.org FU NCI NIH HHS [R01 CA142873, R01 CA131524, R01 CA131524-02, R01 CA131524-03, R01 CA142873-02] NR 46 TC 63 Z9 66 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2010 VL 22 IS 3 BP 178 EP 183 DI 10.1097/CCO.0b013e32833888ee PG 6 WC Oncology SC Oncology GA 592LL UT WOS:000277380300003 PM 20401974 ER PT J AU Marques, L LeBlanc, NJ Weingarden, HM Timpano, KR Jenike, M Wilhelm, S AF Marques, Luana LeBlanc, Nicole J. Weingarden, Hilary M. Timpano, Kiara R. Jenike, Michael Wilhelm, Sabine TI BARRIERS TO TREATMENT AND SERVICE UTILIZATION IN AN INTERNET SAMPLE OF INDIVIDUALS WITH OBSESSIVE-COMPULSIVE SYMPTOMS SO DEPRESSION AND ANXIETY LA English DT Article DE OCD; treatment utilization; barriers to treatment; internet study ID QUALITY-OF-LIFE; COGNITIVE-BEHAVIOR THERAPY; FUNCTIONAL IMPAIRMENT; FAMILY BURDEN; HEALTH-CARE; DISORDER; COMORBIDITY; IMPACT; SCALE; PREVALENCE AB Background: Despite the increasing dissemination of treatment for Obsessive Compulsive Disorder (OCD) in the past decade, the majority of individuals with OCD are not receiving appropriate treatment. This study examined rates of treatment utilization and barriers to treatment in an internet sample of individuals with self-reported OCD. Methods: One hundred and seventy-five participants completed an online survey examining OCD symptoms, psychosocial measures, barriers to treatment, and treatment utilization. Results: Sixty percent of the sample reported receiving treatment for their OCD symptoms. The majority of participants who sought pharmacotherapy received SSRIs, whereas the majority who sought psychotherapeutic treatment received "talk therapy." The cost of treatment, lack of insurance coverage, shame, and doubt that treatment would be effective were the most commonly endorsed barriers to treatment among the sample. Conclusions: Findings demonstrated relatively low treatment utilization rates among the sample, with many participants receiving treatments other than the gold-standard medication and psychotherapy treatments (i.e. SSRIs and cognitive behavioral therapy, respectively). Furthermore, a large portion of the sample endorsed many barriers to treatment seeking, such as logistic and financial barriers; stigma, shame, and discrimination barriers; and treatment perception and satisfaction barriers. This study highlights the need for more effective treatment dissemination in OCD. Depression and Anxiety 27:470-475, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Obsess Compuls & Related Disorders Program, Boston, MA 02114 USA. [LeBlanc, Nicole J.; Weingarden, Hilary M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Jenike, Michael] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Obsess Compuls & Related Disorders Program, 185 Cambridge St, Boston, MA 02114 USA. EM lmarques@partners.org RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722 NR 43 TC 60 Z9 62 U1 0 U2 12 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 MAY PY 2010 VL 27 IS 5 BP 470 EP 475 DI 10.1002/da.20694 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 593PS UT WOS:000277472200009 PM 20455248 ER PT J AU Ingelsson, E Langenberg, C Hivert, MF Prokopenko, I Lyssenko, V Dupuis, J Magi, R Sharp, S Jackson, AU Assimes, TL Shrader, P Knowles, JW Zethelius, B Abbasi, FA Bergman, RN Bergmann, A Berne, C Boehnke, M Bonnycastle, LL Bornstein, SR Buchanan, TA Bumpstead, SJ Bottcher, Y Chines, P Collins, FS Cooper, CC Dennison, EM Erdos, MR Ferrannini, E Fox, CS Graessler, J Hao, K Isomaa, B Jameson, KA Kovacs, P Kuusisto, J Laakso, M Ladenval, C Mohlke, KL Morken, MA Narisu, N Nathan, DM Pascoe, L Payne, F Petrie, JR Sayer, AA Schwarz, PEH Scott, LJ Stringham, HM Stumvoll, M Swift, AJ Syvanen, AC Tuomi, T Tuomilehto, J Tonjes, A Valle, TT Williams, GH Lind, L Barroso, I Quertermous, T Walker, M Wareham, NJ Meigs, JB McCarthy, MI Groop, L Watanabe, RM Florez, JC AF Ingelsson, Erik Langenberg, Claudia Hivert, Marie-France Prokopenko, Inga Lyssenko, Valeriya Dupuis, Josee Maegi, Reedik Sharp, Stephen Jackson, Anne U. Assimes, Themistocles L. Shrader, Peter Knowles, Joshua W. Zethelius, Bjorn Abbasi, Fahim A. Bergman, Richard N. Bergmann, Antje Berne, Christian Boehnke, Michael Bonnycastle, Lori L. Bornstein, Stefan R. Buchanan, Thomas A. Bumpstead, Suzannah J. Boettcher, Yvonne Chines, Peter Collins, Francis S. Cooper, Cyrus C. Dennison, Elaine M. Erdos, Michael R. Ferrannini, Ele Fox, Caroline S. Graessler, Juergen Hao, Ke Isomaa, Bo Jameson, Karen A. Kovacs, Peter Kuusisto, Johanna Laakso, Markku Ladenval, Claes Mohlke, Karen L. Morken, Mario A. Narisu, Narisu Nathan, David M. Pascoe, Laura Payne, Felicity Petrie, John R. Sayer, Avan A. Schwarz, Peter E. H. Scott, Laura J. Stringham, Heather M. Stumvoll, Michael Swift, Amy J. Syvanen, Ann-Christine Tuomi, Tiinamaija Tuomilehto, Jaakko Tonjes, Anke Valle, Timo T. Williams, Gordon H. Lind, Lars Barroso, Ines Quertermous, Thomas Walker, Mark Wareham, Nicholas J. Meigs, James B. McCarthy, Mark I. Groop, Leif Watanabe, Richard M. Florez, Jose C. CA MAGIC Investigators TI Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans SO DIABETES LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the American-Society-of-Human-Genetics CY OCT 20-24, 2009 CL Honolulu, HI SP Amer Soc Human Genet ID BETA-CELL FUNCTION; FASTING PLASMA-GLUCOSE; ZINC TRANSPORTER ZNT8; TYPE-2 DIABETES RISK; FATTY-ACIDS; RELATIVE CONTRIBUTIONS; 1ST-DEGREE RELATIVES; NONDIABETIC HUMANS; SENSITIVITY INDEX; GLUCOKINASE GENE AB OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010 C1 [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ingelsson, Erik; Zethelius, Bjorn] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Langenberg, Claudia; Sharp, Stephen; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England. [Hivert, Marie-France] Univ Sherbrooke, Ctr Rech Med, Sherbrooke, PQ J1K 2R1, Canada. [Prokopenko, Inga; Maegi, Reedik; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Prokopenko, Inga; Maegi, Reedik; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Lyssenko, Valeriya; Ladenval, Claes; Groop, Leif] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Jackson, Anne U.; Boehnke, Michael; Scott, Laura J.; Stringham, Heather M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Abbasi, Fahim A.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Bergman, Richard N.; Buchanan, Thomas A.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Bergmann, Antje] Tech Univ Dresden, Med Fac Carl Gustav Carus, Hlth Care Ctr, Dresden, Germany. [Berne, Christian; Syvanen, Ann-Christine; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Bonnycastle, Lori L.; Chines, Peter; Collins, Francis S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Bornstein, Stefan R.; Graessler, Juergen; Schwarz, Peter E. H.] Univ Dresden, Dept Med 3, Prevent & Care Diabet Div, Dresden, Germany. [Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Med, Div Endocrinol & Diabet, Los Angeles, CA 90033 USA. [Bumpstead, Suzannah J.] Wellcome Trust Sanger Inst, Cambridge, England. [Boettcher, Yvonne; Stumvoll, Michael; Tonjes, Anke] Univ Leipzig, Dept Med, Leipzig, Germany. [Cooper, Cyrus C.; Dennison, Elaine M.; Jameson, Karen A.; Sayer, Avan A.] Univ Southampton, Southampton Gen Hosp, MRC, Epidemiol Resource Ctr, Southampton, Hants, England. [Ferrannini, Ele] Univ Pisa, Dept Internal Med, Pisa, Italy. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.; Williams, Gordon H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Hao, Ke] Rosetta Inpharmat LLC, Seattle, WA USA. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Isomaa, Bo] Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland. [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Nathan, David M.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Nathan, David M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Pascoe, Laura; Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England. [Petrie, John R.] Univ Glasgow, British Heart Fdn Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland. [Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Tuomilehto, Jaakko; Valle, Timo T.] Univ Helsinki, Hjelt Inst, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf Helsinki, Unit Diabet Prevent, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Tonjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Ingelsson, E (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. EM erik.ingelsson@ki.se; Leif.Groop@med.lu.se; rwatanab@usc.edu; jcflorez@partners.org RI Aihie Sayer, Avan/A-4359-2012; Prokopenko, Inga/H-3241-2014; Schwarz, Peter/B-5127-2013; OI Prokopenko, Inga/0000-0003-1624-7457; Schwarz, Peter/0000-0001-6317-7880; Magi, Reedik/0000-0002-2964-6011; Aihie Sayer, Avan/0000-0003-1283-6457; Tuomi, Tiinamaija/0000-0002-8306-6202; Payne, Felicity/0000-0003-4228-581X; Dupuis, Josee/0000-0003-2871-3603 FU Medical Research Council [G0701863, MC_U106179471, MC_U147574213, MC_U147574239, MC_UP_A620_1014, MC_UP_A620_1015]; NHLBI NIH HHS [R01 HL087647]; NIDDK NIH HHS [R01 DK029867, R01 DK072193] NR 55 TC 134 Z9 139 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2010 VL 59 IS 5 BP 1266 EP 1275 DI 10.2337/DB09-1568 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 594RI UT WOS:000277554700019 PM 20185807 ER PT J AU Lipsky, BA Berendt, AR AF Lipsky, Benjamin A. Berendt, Anthony R. TI Hyperbaric Oxygen Therapy for Diabetic Foot Wounds Has hope hurdled hype? SO DIABETES CARE LA English DT Editorial Material ID ULCERS C1 [Lipsky, Benjamin A.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Berendt, Anthony R.] Nuffield Orthopaed Ctr NHS Trust, Bone Infect Unit, Oxford, England. RP Lipsky, BA (reprint author), Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. EM dblipsky@hotmail.com OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 18 TC 16 Z9 18 U1 0 U2 2 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 MAY PY 2010 VL 33 IS 5 BP 1143 EP 1145 DI 10.2337/dc10-0393 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 595RV UT WOS:000277631200039 PM 20427686 ER PT J AU Boyko, EJ AF Boyko, Edward J. TI ACCORD Glycemia Results Continue to Puzzle SO DIABETES CARE LA English DT Editorial Material ID EPIDEMIOLOGIC ANALYSIS; SEVERE HYPOGLYCEMIA C1 [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM eboyko@uw.edu FU NIDDK NIH HHS [P30 DK017047] NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2010 VL 33 IS 5 BP 1149 EP 1150 DI 10.2337/dc10-0432 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 595RV UT WOS:000277631200041 PM 20427688 ER PT J AU Boyko, EJ AF Boyko, Edward J. TI Utility of Homeostasis Model Assessment of beta-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans Response SO DIABETES CARE LA English DT Letter C1 [Boyko, Edward J.] Seattle Epidemiol Res & Informat Ctr ERIC, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. RP Boyko, EJ (reprint author), Seattle Epidemiol Res & Informat Ctr ERIC, VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM eboyko@u.washington.edu NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2010 VL 33 IS 5 BP E71 EP E71 DI 10.2337/dc10-0196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V26BN UT WOS:000208521200007 PM 20427680 ER PT J AU Alleyn, CR Volkening, LK Wolfson, J Rodriguez-Ventura, A Wood, JR Laffel, LMB AF Alleyn, C. R. Volkening, L. K. Wolfson, J. Rodriguez-Ventura, A. Wood, J. R. Laffel, L. M. B. TI Occurrence of microalbuminuria in young people with Type 1 diabetes: importance of age and diabetes duration SO DIABETIC MEDICINE LA English DT Article DE children; glycated haemoglobin; microalbuminuria; puberty; Type 1 diabetes mellitus ID URINARY ALBUMIN EXCRETION; GLOMERULAR-FILTRATION-RATE; INCREASED KIDNEY SIZE; NATURAL-HISTORY; NEPHROPATHY; INSULIN; COMPLICATIONS; ADOLESCENTS; PREVALENCE; RISK AB P>Aims To determine the occurrence of microalbuminuria in young people with Type 1 diabetes mellitus followed prospectively for 2 years and to relate the presence of persistent elevations in urinary albumin excretion (UAE) to age, diabetes duration, puberty and other factors. Methods During a 2 year period, random urine samples were obtained from 471 patients, aged 8-18 years (mean +/- sd 12.9 +/- 2.3 years) with Type 1 diabetes duration 5.6 +/- 3.0 years, as part of routine clinical care. Urine albumin and creatinine concentrations were measured in 1310 samples (median, 3 samples per patient) and the albumin:creatinine ratio was calculated (in micrograms albumin per milligram creatinine). Height, weight, blood pressure (BP), glycated haemoglobin (HbA(1c)), blood glucose monitoring frequency and Tanner staging were collected from patients' medical records. Results Twenty-three per cent of patients had one or more sample with elevated UAE (>= 20 mu g/mg) and 9.3% had persistent elevations (>= 2 samples >= 20 mu g/mg). Those with and without persistent microalbuminuria did not differ significantly in age, diabetes duration, z-score for body mass index, pubertal status or BP percentile. Ten per cent of children < 13 years old and 9% of children >= 13 years old had persistent microalbuminuria. Persistent microalbuminuria was significantly associated with diabetes duration only in older children (duration 0.5-3 years, 4%; 4-6 years, 8%; >= 7 years, 14%; P = 0.02, trend test). Mean HbA(1c) over the 2 years was 8.7 +/- 1.2%. In a logistic regression model, mean HbA(1c) was the only significant predictor of persistent microalbuminuria (odds ratio 1.3, 95% confidence interval 1.0-1.6, P = 0.05). Conclusions Microalbuminuria in older children with Type 1 diabetes is likely to be clinically significant. In younger children, it may reflect functional, reversible renal changes. Longitudinal analysis is needed to confirm the probable transient nature of microalbuminuria in young patients with Type 1 diabetes. C1 [Alleyn, C. R.; Volkening, L. K.; Wolfson, J.; Rodriguez-Ventura, A.; Wood, J. R.; Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Wood, J. R.] Childrens Hosp Los Angeles, Div Endocrinol & Metab, Los Angeles, CA 90027 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIH [R01DK046887, P30DK036836, T32DK007260]; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund FX This study was supported by NIH grants R01DK046887, P30DK036836, and T32DK007260 and the Charles H. Hood Foundation, the Maria Griffin Drury Pediatric Fund, and the Katherine Adler Astrove Youth Education Fund. NR 29 TC 17 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 2010 VL 27 IS 5 BP 532 EP 537 DI 10.1111/j.1464-5491.2010.02983.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586XM UT WOS:000276948600005 PM 20536948 ER PT J AU Lipsky, BA Tabak, YP Johannes, RS Vo, L Hyde, L Weigelt, JA AF Lipsky, B. A. Tabak, Y. P. Johannes, R. S. Vo, L. Hyde, L. Weigelt, J. A. TI Skin and soft tissue infections in hospitalised patients with diabetes: culture isolates and risk factors associated with mortality, length of stay and cost SO DIABETOLOGIA LA English DT Article DE Diabetes; Foot infections; Hospitalised patients; Length of stay; Mortality; MRSA; Skin and soft tissue infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; LARGE US DATABASE; COMPLICATED SKIN; FOOT INFECTIONS; SURGICAL SITE; DOUBLE-BLIND; ECONOMIC OUTCOMES; UNITED-STATES; EPIDEMIOLOGY; PATHOGENS AB Skin and soft tissue infections (SSTIs) cause substantial morbidity in persons with diabetes. There are few data on pathogens or risk factors associated with important outcomes in diabetic patients hospitalised with SSTIs. Using a clinical research database from CareFusion, we identified 3,030 hospitalised diabetic patients with positive culture isolates and a diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the culture isolates and analysed their association with the anatomic location of infection, mortality, length of stay and hospital costs. The only culture isolate with a significantly increased prevalence was methicillin-resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was increased from 11.6 to 21.9% (p < 0.0001) and for non-foot locations from 14.0% to 24.6% (p = 0.006). Patients with non-foot (vs foot) infections were more severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p < 0.05). Significant independent risk factors associated with higher mortality rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR 3.1), a monomicrobial culture with other gram-negatives (OR 8.9), greater illness severity (OR 1.9) and being transferred from another hospital (OR 5.1). These factors and need for major surgery were also independently associated with longer length of stay and higher costs. Among diabetic patients hospitalised with SSTI from 2003 to 2007, only MRSA increased in prevalence. Patients with non-foot (vs foot) infections were more severely ill. Independent risk factors for increased mortality rates, length of stay and costs included more severe illness, transfer from another hospital and wound cultures with Pseudomonas or other gram-negatives. C1 [Lipsky, B. A.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Tabak, Y. P.; Johannes, R. S.; Hyde, L.] CareFusion, Clin Res, Marlborough, MA USA. [Johannes, R. S.] Harvard Univ, Sch Med, Div Gastroenterol, Boston, MA USA. [Vo, L.] Ortho McNeil Janssen Sci Affairs LLC, Raritan, NJ USA. [Weigelt, J. A.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. RP Lipsky, BA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98195 USA. EM balipsky@uw.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Ortho-McNeil Janssen Scientific Affairs, LLC FX B. A. Lipsky and J. A. Weigelt served as consultants for Ortho-McNeil Janssen Scientific Affairs, LLC, Raritan, NJ, USA. Y. P. Tabak, R. S. Johannes and L. Hyde are employees of CareFusion, Marlborough, MA, USA. L. Vo is an employee of Ortho-McNeil Janssen Scientific Affairs. This study was supported by Ortho-McNeil Janssen Scientific Affairs, LLC. NR 44 TC 47 Z9 51 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2010 VL 53 IS 5 BP 914 EP 923 DI 10.1007/s00125-010-1672-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 580CK UT WOS:000276424300015 PM 20146051 ER PT J AU O'Sullivan, ES Johnson, AS Omer, A Hollister-Lock, J Bonner-Weir, S Colton, CK Weir, GC AF O'Sullivan, E. S. Johnson, A. S. Omer, A. Hollister-Lock, J. Bonner-Weir, S. Colton, C. K. Weir, G. C. TI Rat islet cell aggregates are superior to islets for transplantation in microcapsules SO DIABETOLOGIA LA English DT Article DE Alginate; Aggregates; Beta cell; Bioengineering capsules; Diabetes; Hypoxia; Islet cell; Oxygen; Transplantation ID PANCREATIC-ISLETS; OXYGEN-CONSUMPTION; BETA-CELLS; HYPOXIA; ALGINATE AB Islet transplantation is a promising treatment for type 1 diabetes but is hampered by a shortage of donor human tissue and early failure. Research on islet cell transplantation includes finding new sources of cells and immunoisolation to protect from immune assault and tumourigenic potential. Small islet cell aggregates were studied to determine if their survival and function were superior to intact islets within microcapsules because of reduced oxygen transport limitation and inflammatory mediators. Islet cell aggregates were generated by dispersing rat islets into single cells and allowing them to re-aggregate in culture. Rat islets and islet cell aggregates were encapsulated in barium alginate capsules and studied when cultured in low (0.5% or 2%) or normal (20%) oxygen, or transplanted into mice. Encapsulated islet cell aggregates were able to survive and function better than intact islets in terms of oxygen-consumption rate, nuclei counts, insulin-to-DNA ratio and glucose-stimulated insulin secretion. They also had reduced expression of pro-inflammatory genes. Islet cell aggregates showed reduced tissue necrosis in an immunodeficient transplant model and a much greater proportion of diabetic xenogeneic transplant recipients receiving islet cell aggregates (tissue volume of only 85 islet equivalents) had reversal of hyperglycaemia than recipients receiving intact islets. These aggregates were superior to intact islets in terms of survival and function in low-oxygen culture and during transplantation and are likely to provide more efficient utilisation of islet tissue, a finding of importance for the future of cell therapy for diabetes. C1 [O'Sullivan, E. S.; Omer, A.; Hollister-Lock, J.; Bonner-Weir, S.; Weir, G. C.] Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [O'Sullivan, E. S.; Omer, A.; Bonner-Weir, S.; Weir, G. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Johnson, A. S.; Colton, C. K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU NIH [RO1 DK 50657]; Juvenile Diabetes Research Foundation; Diabetes Research and Wellness Foundation; Joslin Diabetes and Endocrinology Research Center [36836]; National University of Ireland FX This research was supported by RO1 DK 50657 from the NIH, the Juvenile Diabetes Research Foundation, the Diabetes Research and Wellness Foundation and the AdvancedMicroscopy Cores of the Joslin Diabetes and Endocrinology Research Center (DERC grant, DK 36836). E. S. O'Sullivan was the recipient of a travelling studentship from the National University of Ireland. Advice on real-time RT-PCR was received from A. Vetere, W-C. Li and J. Thorne. Biospherix provided the Xvivo for use in these experiments. NR 29 TC 53 Z9 54 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2010 VL 53 IS 5 BP 937 EP 945 DI 10.1007/s00125-009-1653-8 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 580CK UT WOS:000276424300017 PM 20101386 ER PT J AU Farkash, EA Yaeger, KA Pitman, MB AF Farkash, Evan A. Yaeger, Kurt A. Pitman, Martha Bishop TI Emperipolesis in Rosai-Dorfman Disease Presenting as a Peritonsillar Mass SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material C1 [Farkash, Evan A.; Yaeger, Kurt A.; Pitman, Martha Bishop] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Farkash, EA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM efarkash@partners.org NR 3 TC 0 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2010 VL 38 IS 5 BP 349 EP 350 DI 10.1002/dc.21175 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 591TM UT WOS:000277327400008 PM 19795487 ER PT J AU Brau, N AF Brau, Norbert TI In Memoriam: Edmund J. Bini, MD, MPH (1967-2010) SO DIGESTIVE DISEASES AND SCIENCES LA English DT Biographical-Item C1 [Brau, Norbert] Bronx Vet Affairs Med Ctr, New York, NY USA. [Brau, Norbert] Mt Sinai Sch Med, New York, NY USA. RP Brau, N (reprint author), Bronx Vet Affairs Med Ctr, New York, NY USA. EM Norbert.Brau@va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2010 VL 55 IS 5 BP 1193 EP 1193 DI 10.1007/s10620-010-1224-3 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 591EZ UT WOS:000277283500001 PM 20383583 ER PT J AU Kovacs, TO Freston, JW Haber, MM Atkinson, S Hunt, B Peura, DA AF Kovacs, Thomas O. Freston, James W. Haber, Marian M. Atkinson, Stuart Hunt, Barbara Peura, David A. TI Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Quality of life; Lansoprazole; Erosive esophagitis; Gastroesophageal reflux disease; Long-term maintenance therapy ID GASTROESOPHAGEAL-REFLUX DISEASE; GERD PATIENTS; PRIMARY-CARE; SURVEY SF-36; RANITIDINE; OMEPRAZOLE; QUESTIONNAIRE; SYMPTOMS; RELIEF AB Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P a parts per thousand currency sign 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and 'bothersomeness' of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P < 0.001) from open-label baseline at each time-point. Maintenance treatment with lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment. C1 [Kovacs, Thomas O.] VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Freston, James W.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Haber, Marian M.] Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19104 USA. [Atkinson, Stuart] Takeda Global Res & Dev Ctr Inc, Dept Clin Sci, Deerfield, IL USA. [Hunt, Barbara] Takeda Global Res & Dev Ctr Inc, Dept Stat, Deerfield, IL USA. [Peura, David A.] Univ Virginia Hlth Syst, Div Gastroenterol & Hepatol, Charlottesville, VA USA. RP Kovacs, TO (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM TKovacs@mednet.ucla.edu NR 27 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2010 VL 55 IS 5 BP 1325 EP 1336 DI 10.1007/s10620-009-0871-8 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 591EZ UT WOS:000277283500019 PM 19582579 ER PT J AU Sounni, NE Dehne, K van Kempen, L Egeblad, M Affara, NI Cuevas, I Wiesen, J Junankar, S Korets, L Lee, J Shen, J Morrison, CJ Overall, CM Krane, SM Werb, Z Boudreau, N Coussens, LM AF Sounni, Nor E. Dehne, Kerstin van Kempen, Leon Egeblad, Mikala Affara, Nesrine I. Cuevas, Ileana Wiesen, Jane Junankar, Simon Korets, Lidiya Lee, Jake Shen, Jennifer Morrison, Charlotte J. Overall, Christopher M. Krane, Stephen M. Werb, Zena Boudreau, Nancy Coussens, Lisa M. TI Stromal regulation of vessel stability by MMP14 and TGF beta SO DISEASE MODELS & MECHANISMS LA English DT Article ID GROWTH-FACTOR-BETA; TYPE-1 MATRIX-METALLOPROTEINASE; CAPILLARY ENDOTHELIAL-CELLS; INTERSTITIAL FLUID PRESSURE; TRANSFORMING GROWTH-FACTOR-BETA-1; SOLID TUMORS; I COLLAGEN; MOUSE MODEL; ANGIOGENESIS; ACTIVATION AB Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) and transforming growth factor beta 1 (TGF beta(1)). Whereas plasma proteins rapidly extravasate out of vasculature in wild-type mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGF beta(1), or an activin-like kinase 5 (ALK5) inhibitor significantly enhanced vessel leakage. By contrast, in a mouse model of age-related dermal fibrosis, where MMP14 activity and TGF beta bioavailability are chronically elevated, or in mice that ectopically express TGF beta in the epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if the fibrotic mice are pretreated with metalloproteinase inhibitors or TGF beta signaling antagonists. Neoplastic tissues, however, are in a constant state of tissue damage and exhibit altered hemodynamics owing to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into the interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGF beta that mediates vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. C1 [Sounni, Nor E.; Dehne, Kerstin; van Kempen, Leon; Junankar, Simon; Lee, Jake; Shen, Jennifer; Coussens, Lisa M.] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. [Affara, Nesrine I.; Wiesen, Jane; Korets, Lidiya; Coussens, Lisa M.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Egeblad, Mikala; Werb, Zena] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Cuevas, Ileana; Boudreau, Nancy] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Werb, Zena; Boudreau, Nancy; Coussens, Lisa M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Morrison, Charlotte J.; Overall, Christopher M.; Krane, Stephen M.] Univ British Columbia, Ctr Blood Res, Inst Life Sci, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada. [Morrison, Charlotte J.; Overall, Christopher M.] Univ British Columbia, Ctr Blood Res, Inst Life Sci, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Coussens, LM (reprint author), Univ Calif San Francisco, Canc Res Inst, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM Lisa.Coussens@ucsf.edu RI van kempen, leon/A-8598-2012; OI Egeblad, Mikala/0000-0002-3371-1445 FU NCI NIH HHS [P01 CA072006, R01 CA140943, R01 CA057621, U54 CA126552, R01 CA140943-01, R01 CA094168, R01 CA098075, U01 CA105379, R01 CA130980]; NCRR NIH HHS [U54 RR020843]; NIAID NIH HHS [P01 AI053194]; NIAMS NIH HHS [R01 AR044815]; NINDS NIH HHS [P01 NS044155] NR 89 TC 40 Z9 42 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY-JUN PY 2010 VL 3 IS 5-6 BP 317 EP 332 DI 10.1242/dmm.003863 PG 16 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 622YA UT WOS:000279701700016 PM 20223936 ER PT J AU Mangos, S Lam, PY Zhao, A Liu, Y Mudumana, S Vasilyev, A Liu, AP Drummond, IA AF Mangos, Steve Lam, Pui-ying Zhao, Angela Liu, Yan Mudumana, Sudha Vasilyev, Aleksandr Liu, Aiping Drummond, Iain A. TI The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation SO DISEASE MODELS & MECHANISMS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; CYST FORMATION; MDCK CELLS; INTRACRANIAL ANEURYSMS; BONE-DEVELOPMENT; EXPRESSION; ZEBRAFISH AB Mutations in polycystin1 (PKD1) account for the majority of autosomal dominant polycystic kidney disease (ADPKD). PKD1 mutations are also associated with vascular aneurysm and abdominal wall hernia, suggesting a role for polycystin1 in extracellular matrix (ECM) integrity. In zebrafish, combined knockdown of the PKD1 paralogs pkd1a and pkd1b resulted in dorsal axis curvature, hydrocephalus, cartilage and craniofacial defects, and pronephric cyst formation at low frequency (10-15%). Dorsal axis curvature was identical to the axis defects observed in pkd2 knockdown embryos. Combined pkd1a/b, pkd2 knockdown demonstrated that these genes interact in axial morphogenesis. Dorsal axis curvature was linked to notochord collagen overexpression and could be reversed by knockdown of col2a1 mRNA or chemical inhibition of collagen crosslinking. pkd1a/b- and pkd2-deficient embryos exhibited ectopic, persistent expression of multiple collagen mRNAs, suggesting a loss of negative feedback signaling that normally limits collagen gene expression. Knockdown of pkd1a/b also dramatically sensitized embryos to low doses of collagen-crosslinking inhibitors, implicating polycystins directly in the modulation of collagen expression or assembly. Embryos treated with wortmannin or LY-29400 also exhibited dysregulation of col2a1 expression, implicating phosphoinositide 3-kinase (PI3K) in the negative feedback signaling pathway controlling matrix gene expression. Our results suggest that pkd1a/b and pkd2 interact to regulate ECM secretion or assembly, and that altered matrix integrity may be a primary defect underlying ADPKD tissue pathologies. C1 [Mangos, Steve; Lam, Pui-ying; Zhao, Angela; Liu, Yan; Mudumana, Sudha; Vasilyev, Aleksandr; Liu, Aiping; Drummond, Iain A.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA. [Mangos, Steve; Lam, Pui-ying; Zhao, Angela; Liu, Yan; Mudumana, Sudha; Vasilyev, Aleksandr; Liu, Aiping; Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIH [DK53093, DK54711]; PKD Foundation FX This work was supported by NIH grants DK53093 and DK54711 to I. A. D.; PKD Foundation fellowship grants to S. Mangos and A.Z.; and a PKD Foundation Grant in aid to I. A. D. We also acknowledge the assistance of our colleagues David Beier for sequencing a pkd1b bac, Richard Sandford for help in cloning pkd1b, Shannon Fisher for sharing her col1a1:GFP transgenic, Nathan Hellman and Alexandra Petrova for editing the manuscript, and Amin Arnaout for helpful suggestions. Deposited in PMC for release after 12 months. NR 75 TC 47 Z9 49 U1 4 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY-JUN PY 2010 VL 3 IS 5-6 BP 354 EP 365 DI 10.1242/dmm.003194 PG 12 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 622YA UT WOS:000279701700019 PM 20335443 ER PT J AU Cao, SS Hewett, JW Yokoi, F Lu, J Buckley, AC Burdette, AJ Chen, P Nery, FC Li, YQ Breakefield, XO Caldwell, GA Caldwell, KA AF Cao, Songsong Hewett, Jeffrey W. Yokoi, Fumiaki Lu, Jun Buckley, Amber Clark Burdette, Alexander J. Chen, Pan Nery, Flavia C. Li, Yuqing Breakefield, Xandra O. Caldwell, Guy A. Caldwell, Kim A. TI Chemical enhancement of torsinA function in cell and animal models of torsion dystonia SO DISEASE MODELS & MECHANISMS LA English DT Article ID CAENORHABDITIS-ELEGANS; NUCLEAR-ENVELOPE; ENDOPLASMIC-RETICULUM; MUTANT TORSINA; DYT1 DYSTONIA; PARKINSONS-DISEASE; SECRETORY PATHWAY; ALPHA-SYNUCLEIN; IDIOPATHIC DYSTONIA; PROTEIN TORSINA AB Movement disorders represent a significant societal burden for which therapeutic options are limited and focused on treating disease symptomality. Early-onset torsion dystonia (EOTD) is one such disorder characterized by sustained and involuntary muscle contractions that frequently cause repetitive movements or abnormal postures. Transmitted in an autosomal dominant manner with reduced penetrance, EOTD is caused in most cases by the deletion of a glutamic acid (DE) in the DYT1 (also known as TOR1A) gene product, torsinA. Although some patients respond well to anticholingerics, therapy is primarily limited to either neurosurgery or chemodenervation. As mutant torsinA (DE) expression results in decreased torsinA function, therapeutic strategies directed toward enhancement of wild-type (WT) torsinA activity in patients who are heterozygous for mutant DYT1 may restore normal cellular functionality. Here, we report results from the first-ever screen for candidate small molecule therapeutics for EOTD, using multiple activity-based readouts for torsinA function in Caenorhabditis elegans, subsequent validation in human DYT1 patient fibroblasts, and behavioral rescue in a mouse model of DYT1 dystonia. We exploited the nematode to rapidly discern chemical effectors of torsinA and identified two classes of antibiotics, quinolones and aminopenicillins, which enhance WT torsinA activity in two separate in vivo assays. Representative molecules were assayed in EOTD patient fibroblasts for improvements in torsinA-dependent secretory function, which was improved significantly by ampicillin. Furthermore, a behavioral defect associated with an EOTD mouse knock-in model was also rescued following administration of ampicillin. These combined data indicate that specific small molecules that enhance torsinA activity represent a promising new approach toward therapeutic development for EOTD, and potentially for other diseases involving the processing of mutant proteins. C1 [Cao, Songsong; Buckley, Amber Clark; Burdette, Alexander J.; Chen, Pan; Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. [Hewett, Jeffrey W.; Nery, Flavia C.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hewett, Jeffrey W.; Nery, Flavia C.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hewett, Jeffrey W.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Yokoi, Fumiaki; Lu, Jun; Li, Yuqing; Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Yokoi, Fumiaki; Lu, Jun; Li, Yuqing; Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. RP Caldwell, KA (reprint author), Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA. EM kcaldwel@bama.ua.edu RI Li, Yuqing/G-1596-2011 OI Li, Yuqing/0000-0003-1211-5529 FU Bachmann-Strauss Dystonia and Parkinson Foundation; Dystonia Medical Research Foundation; Jack Fasciana Fund for Dystonia Research; NIH [NS037409, NS043176, NS047692, NS54246, NS57098, NS47466] FX This work was supported by the Bachmann-Strauss Dystonia and Parkinson Foundation (K. A. C., G. A. C. and X.O.B.), Dystonia Medical Research Foundation (K. A. C., G. A. C. and Y.L.), Jack Fasciana Fund for Dystonia Research (X.O.B.) and the NIH (NS037409 to X. O. B.; NS043176 to G. A. C.; NS047692, NS54246, NS57098 and NS47466 to Y. L.). Deposited in PMC for release after 12 months. NR 61 TC 37 Z9 37 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY-JUN PY 2010 VL 3 IS 5-6 BP 386 EP 396 DI 10.1242/dmm.003715 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 622YA UT WOS:000279701700022 PM 20223934 ER PT J AU Kunitake, H Zingmond, DS Ryoo, J Ko, CY AF Kunitake, Hiroko Zingmond, David S. Ryoo, Joan Ko, Clifford Y. TI Caring for Octogenarian and Nonagenarian Patients with Colorectal Cancer: What Should Our Standards and Expectations Be? SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY MAY 02-06, 2009 CL Hollywood, FL SP Amer Soc Colon & Rectal Surg DE Outcomes research; Colon and rectal surgery ID ELDERLY-PATIENTS; RECTAL-CANCER; POSTOPERATIVE MORTALITY; SURGERY; OLDER; AGE; OUTCOMES; COMPLICATIONS; CARE AB PURPOSE: Octogenarians and nonagenarians constitute a rapidly growing segment of patients undergoing colorectal cancer resection. We describe their outcomes in a large population cohort and aim to establish expectations and improvements for their care. METHODS: All patients undergoing surgical resection for colorectal cancer in California (1994-2005) were identified in the California Cancer Registry, which was linked with the California Office of Statewide Health Planning and Development Patient Discharge Database and the 2000 United States Census. Multivariate logistic regression was used to determine significant outcome predictors. RESULTS: Octogenarians and nonagenarians comprised 26% of all patients undergoing colon cancer resection and 16% of all patients undergoing rectal cancer resection from 1994 to 2005. This cohort had more comorbidities but less distant disease than patients <65 years old (P < .001). Twelve percent of patients with rectal cancer and 17% of patients with colon cancer who were 80 years or older had emergent surgery vs 5% and 12%, respectively, for patients <65 years old (P < .001). Patients 80 years or older had nearly twice the readmission incidence rate (417 readmissions per thousand patient-years) of patients <65 years old. Twenty-seven percent of 90-day readmissions were for surgical complications, 52% of which required a subsequent procedure. Patients 80 years or older had high in-hospital mortality (6%) and one-year mortality (29%). Medical complications, increasing comorbidities, and cancer stage were predictive of in-hospital and 1-year mortality. CONCLUSIONS: Octogenarians and nonagenarians represent a large segment of patients with colorectal cancer undergoing surgical resection with high rates of morbidity, mortality, and readmission. Medical optimization and excellent continuity of care may contribute to improved outcomes following surgery for these complex patients. C1 [Kunitake, Hiroko; Ryoo, Joan; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RP Kunitake, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM hkunitake@hotmail.com NR 17 TC 26 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD MAY PY 2010 VL 53 IS 5 BP 735 EP 743 DI 10.1007/DCR.0b013e3181cdd658 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 589PG UT WOS:000277163700007 PM 20389207 ER PT J AU Bridges, TM LeBois, EP Hopkins, CR Wood, MR Jones, CK Conn, PJ Lindsley, CW AF Bridges, Thomas M. LeBois, Evan P. Hopkins, Corey R. Wood, Michael R. Jones, Carrie K. Conn, P. Jeffrey Lindsley, Craig W. TI THE ANTIPSYCHOTIC POTENTIAL OF MUSCARINIC ALLOSTERIC MODULATION SO DRUG NEWS & PERSPECTIVES LA English DT Article ID RECEPTOR AGONIST XANOMELINE; PROTEIN-COUPLED RECEPTORS; CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTOR; IN-VIVO; N-DESMETHYLCLOZAPINE; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; RAT-BRAIN; DOPAMINERGIC TRANSMISSION AB The cholinergic hypothesis of schizophrenia emerged over 50 years ago based on clinical observations with both anticholinergics and pan-muscarinic agonists. Not until the 1990s did the cholinergic hypothesis of schizophrenia receive renewed enthusiasm based on clinical data with xanometine, a muscarinic acetylcholine receptor M(1)/M(4)-preferring orthosteric agonist. In a clinical trial with Alzheimer's patients, xanometine not only improved cognitive performance, but also reduced psychotic behaviors. This encouraging data spurred a second clinical trial in schizophrenic patients, wherein xanomeline significantly improved the positive, negative and cognitive symptom clusters. However, the question remained: Was the antipsychotic efficacy due to activation of M(1), M(4) or both M(1)/M(4)? Classical orthosteric ligands lacked the muscarinic receptor subtype selectivity required to address this key question. More recently, functional assays have allowed for the discovery of ligands that bind at allosteric sites, binding sites distinct from the orthosteric (acetylcholine) site, which are structurally less conserved and thereby afford high levels of receptor subtype selectivity. Recently, allosteric ligands, with unprecedented selectivity for either M(1) or M(4), have been discovered and have demonstrated comparable efficacy to xanometine in preclinical antipsychotic and cognition models. These data suggest that selective allosteric activation of either M(1) or M(4) has antipsychotic potential through distinct, yet complimentary mechanisms. C1 [Hopkins, Corey R.; Wood, Michael R.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Hopkins, Corey R.; Wood, Michael R.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Vanderbilt Specialized Chem Ctr MLPCN, Nashville, TN 37232 USA. [Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, TVHS, Nashville, TN USA. RP Lindsley, CW (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, 12415-D MRBIV Langford, Nashville, TN 37232 USA. EM craig.lindsley@vanderbilt.edu RI Conn, Peter/D-7848-2012 FU Merck Co.; Johnson Johnson; Hoffman-La Roche; GlaxoSmithKline; Lundbeck Research USA; Epix Pharmaceuticals; Invitrogen Life Technologies; Evotec Inc.; Addex Pharmaceuticals; Michael J. Fox Foundation; Seaside Therapeutics; Cephalon Inc.; AstraZeneca USA; NeurOp Inc.; Forest Research Institute; LEK Consulting; The Frankel Group; Prestwick Chemical Co.; Millipore Corp.; Genentech; IMS Health; Primary Insight; Otsuka; University of Toronto; American Society for Bone and Mineral Research; University of Alabama Birmingham; University of Michigan; Southern Research Inst.; Harvard Medical School; University of North Carolina; NIH; Vanderbilt University; NIH/NIMH [R01 MH086601-01] FX T.M. Bridges, E.P. LeBois, C.R. Hopkins, M.R. Wood and C.W. Lindsley state that they have no potential conflicts of interest to disclose. P.J. Conn has received compensation over the past 2 years as a consultant from Merck & Co., Johnson & Johnson, Hoffman-La Roche, GlaxoSmithKline, Lundbeck Research USA, Epix Pharmaceuticals, Invitrogen Life Technologies, Evotec Inc., Addex Pharmaceuticals, Michael J. Fox Foundation, Seaside Therapeutics, Cephalon Inc., AstraZeneca USA, NeurOp Inc., Forest Research Institute, LEK Consulting, The Frankel Group, Prestwick Chemical Co., Millipore Corp., Genentech, IMS Health, Primary Insight and Otsuka. Dr. Conn has also received honoraria as a speaker from University of Toronto, American Society for Bone and Mineral Research, University of Alabama Birmingham, University of Michigan, Southern Research Inst., Harvard Medical School and the University of North Carolina. Dr. Conn receives research support that includes salary support from NIH, Michael J. Fox Foundation, Seaside Therapeutics, and Vanderbilt University. C.K. Jones is the recipient of Research Grant R01 MH086601-01 (PI, Jones) NIH/NIMH, M, positive allosteric modulators for the treatment of schizophrenia. NR 106 TC 28 Z9 28 U1 1 U2 4 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD MAY PY 2010 VL 23 IS 4 BP 229 EP 240 DI 10.1358/dnp.2010.23.4.1416977 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 620SL UT WOS:000279519900002 PM 20520852 ER PT J AU Dias-Santagata, D Akhavanfard, S David, SS Vernovsky, K Kuhlmann, G Boisvert, SL Stubbs, H McDermott, U Settleman, J Kwak, EL Clark, JW Isakoff, SJ Sequist, LV Engelman, JA Lynch, TJ Haber, DA Louis, DN Ellisen, LW Borger, DR Lafrate, AJ AF Dias-Santagata, Dora Akhavanfard, Sara David, Serena S. Vernovsky, Kathy Kuhlmann, Georgiana Boisvert, Susan L. Stubbs, Hannah McDermott, Ultan Settleman, Jeffrey Kwak, Eunice L. Clark, Jeffrey W. Isakoff, Steven J. Sequist, Lecia V. Engelman, Jeffrey A. Lynch, Thomas J. Haber, Daniel A. Louis, David N. Ellisen, Leif W. Borger, Darrell R. Lafrate, A. John TI Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine SO EMBO MOLECULAR MEDICINE LA English DT Article DE cancer; genotyping; profiling; targeted therapies ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; FACTOR RECEPTOR MUTATIONS; HUMAN BREAST-CANCER; SOMATIC MUTATIONS; COLORECTAL CANCERS; EGFR MUTATIONS; GENE FAMILY; GEFITINIB; ADENOCARCINOMA AB Targeted cancer therapy requires the rapid and accurate identification of genetic abnormalities predictive of therapeutic response. We sought to develop a high-throughput genotyping platform that would allow prospective patient selection to the best available therapies, and that could readily and inexpensively be adopted by most clinical laboratories. we developed a highly sensitive multiplexed clinical assay that performs very well with nucleic acid derived from formalin fixation and paraffin embedding (FFPE) tissue, and tests for 120 previously described mutations in 13 cancer genes. Genetic profiling of 250 primary tumours was consistent with the documented oncogene mutational spectrum and identified rare events in some cancer types. The assay is currently being used for clinical testing of tumour samples and contributing to cancer patient management. This work therefore establishes a platform for real-time targeted genotyping that can be widely adopted. We expect that efforts like this one will play an increasingly important role in cancer management. C1 [Dias-Santagata, Dora; Kuhlmann, Georgiana; Stubbs, Hannah; Louis, David N.; Lafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dias-Santagata, Dora; Akhavanfard, Sara; David, Serena S.; Vernovsky, Kathy; Kuhlmann, Georgiana; Boisvert, Susan L.; Stubbs, Hannah; Kwak, Eunice L.; Clark, Jeffrey W.; Isakoff, Steven J.; Sequist, Lecia V.; Engelman, Jeffrey A.; Lynch, Thomas J.; Haber, Daniel A.; Louis, David N.; Ellisen, Leif W.; Borger, Darrell R.; Lafrate, A. John] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Akhavanfard, Sara; David, Serena S.; Vernovsky, Kathy; Boisvert, Susan L.; Kwak, Eunice L.; Clark, Jeffrey W.; Isakoff, Steven J.; Sequist, Lecia V.; Engelman, Jeffrey A.; Lynch, Thomas J.; Haber, Daniel A.; Ellisen, Leif W.; Borger, Darrell R.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. [McDermott, Ultan; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, Charlestown, MA USA. [McDermott, Ultan; Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA USA. RP Dias-Santagata, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM ddiassantagata@partners.org OI McDermott, Ultan/0000-0001-9032-4700 NR 44 TC 234 Z9 234 U1 3 U2 28 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD MAY PY 2010 VL 2 IS 5 BP 146 EP 158 DI 10.1002/emmm.201000070 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 607OL UT WOS:000278513700002 PM 20432502 ER PT J AU Rabiee, A Dwyer, AA Caronia, LM Hayes, FJ Yialamas, MA Andersen, DK Thomas, B Torriani, M Elahi, D AF Rabiee, Atoosa Dwyer, Andrew A. Caronia, Lisa M. Hayes, Frances J. Yialamas, Maria A. Andersen, Dana K. Thomas, Bijoy Torriani, Martin Elahi, Dariush TI Impact of Acute Biochemical Castration on Insulin Sensitivity in Healthy Adult Men SO ENDOCRINE RESEARCH LA English DT Article DE Testosterone; Insulin Sensitivity; Body Composition ID HORMONE-BINDING GLOBULIN; MIDDLE-AGED MEN; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; NUTRITION EXAMINATION SURVEY; DEPENDENT DIABETES-MELLITUS; 3RD NATIONAL-HEALTH; LEAN BODY-MASS; OLDER MEN; PROSTATE-CANCER; YOUNG MEN AB Introduction. Evidence supports an inverse relationship between serum testosterone (T) and insulin resistance in men. However, data with respect to causality are limited. The aim of this study was to explore the impact of acute biochemical castration on insulin sensitivity in healthy adult men. Methods. Ten healthy, adult males (mean age 41.0 +/- 3.9 yr) were studied. Subjects were studied at baseline and after 2 and 4 weeks of biochemical castration. Outpatient hospital research setting. Body composition (dual-energy x-ray absorptiometry), energy expenditure (indirect calorimetry), abdominal and visceral adiposity (MRI), skeletal muscle intramyocellular lipid content ([IMCL] Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures. C1 [Fisher, Robert] Stanford Univ, Dept Neurol, Sch Med, Stanford, CA 94305 USA. [Salanova, Vicenta; Witt, Thomas; Worth, Robert] Indiana Univ, Indianapolis, IN 46204 USA. [Henry, Thomas; Gross, Robert; Epstein, Charles] Emory Univ, Atlanta, GA 30322 USA. [Oommen, Kalarickal] Univ Oklahoma, Oklahoma City, OK USA. [Osorio, Ivan; Nazzaro, Jules] Univ Kansas, Kansas City, KS USA. [Labar, Douglas; Kaplitt, Michael] Weill Cornell, New York, NY USA. [Sperling, Michael] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sandok, Evan; Neal, John] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Handforth, Adrian; DeSalles, Antonio] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Stern, John] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Chung, Steve; Shetter, Andrew] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Bergen, Donna; Bakay, Roy] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [French, Jacqueline; Baltuch, Gordon; Pollard, John] Univ Penn, Philadelphia, PA 19104 USA. [Marks, William; Garcia, Paul; Barbaro, Nicolas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fountain, Nathan] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Bazil, Carl; Goodman, Robert; McKhann, Guy] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Krishnamurthy, K. Babu; Papavassiliou, Steven] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Tonder, Lisa; Grebin, Joan; Coffey, Robert; Graves, Nina] Medtronic, Minneapolis, MN USA. RP Fisher, R (reprint author), Stanford Univ, Dept Neurol, Sch Med, Room A343,300 Pasteur Dr, Stanford, CA 94305 USA. EM robert.fisher@stanford.edu RI Graves, Nicholas/A-3052-2011; French, Jacqueline/G-6795-2013; OI Henderson, Jaimie/0000-0002-3276-2267; French, Jacqueline/0000-0003-2242-8027; Henry, Thomas/0000-0002-5708-903X; Herman, Susan/0000-0002-6556-083X FU Medtronic, Inc. (Minneapolis, MN); NIH [R01 NS39344-01] FX The study was supported by Medtronic, Inc. (Minneapolis, MN) and an NIH grant R01 NS39344-01 to RSF to assist with planning of the study. Dr. Fisher, who primarily wrote the article, receives no personal financial support from Medtronic and does not own Medtronic equities. Dr. Fisher is supported by the Maslah Saul MD Chair, James and Carrie Anderson Epilepsy Research Laboratory, and the Susan Horngren Fund. NR 27 TC 462 Z9 482 U1 12 U2 68 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 MAY PY 2010 VL 51 IS 5 BP 899 EP 908 DI 10.1111/j.1528-1167.2010.02536.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 587OA UT WOS:000277000900024 PM 20331461 ER PT J AU Tomson, T Battino, D Craig, J Hernandez-Diaz, S Holmes, LB Lindhout, D Morrow, J French, J AF Tomson, Torbjorn Battino, Dina Craig, John Hernandez-Diaz, Sonia Holmes, Lewis B. Lindhout, Dick Morrow, Jim French, Jacqueline CA ILAE Commission Therapeutic Strate TI Pregnancy registries: Differences, similarities, and possible harmonization SO EPILEPSIA LA English DT Article DE Epilepsy; Pregnancy; Malformations ID ANTIEPILEPTIC DRUGS; UK-EPILEPSY; CONGENITAL-MALFORMATIONS; PRELIMINARY EXPERIENCE; INFANTS; VALPROATE AB P>Epilepsy and pregnancy registries have been operational for more than 10 years, have accrued considerable experience, and collected an impressive amount of data. As findings have been published, it has become important to understand how observations from the different registries are comparable, especially since their methodologies differ somewhat. In September 2008, representatives of the UK Epilepsy and Pregnancy Register, the North American AED Pregnancy Registry (NAAPR), and the European and International Registry of Antiepileptic Drugs in Pregnancy (EURAP) met for a workshop. Their objectives were to exchange information on their methodologies and to discuss areas where harmonization might be possible. This report summarizes these discussions. C1 [Tomson, Torbjorn] Karolinska Univ Hosp, Dept Neurol, Karolinska Inst, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. [Battino, Dina] Ist Neurol Carlo Besta, Fdn IRCCS, Milan, Italy. [Craig, John; Morrow, Jim] Royal Victoria Hosp, Dept Neurol, UK Epilepsy & Pregnancy Register, Belfast BT12 6BA, Antrim, North Ireland. [Hernandez-Diaz, Sonia; Holmes, Lewis B.] MassGen Hosp Children, N Amer AED Pregnancy Registry, Boston, MA USA. [Lindhout, Dick] Univ Med Ctr Utrecht, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands. [French, Jacqueline] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. RP Tomson, T (reprint author), Karolinska Univ Hosp, Dept Neurol, Karolinska Inst, Dept Clin Neurosci, SE-17176 Stockholm, Sweden. EM torbjorn.tomson@karolinska.se RI French, Jacqueline/G-6795-2013; OI French, Jacqueline/0000-0003-2242-8027; Lindhout, Dick/0000-0001-9580-624X FU Milken Family Foundation FX The financial support for the workshop provided by the Milken Family Foundation is gratefully acknowledged. We thank Dr. Frank Vajda for contributing information from the Australian register and Sanjeev Thomas for information on the Kerala registry as summarized in Table 1.We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 17 TC 36 Z9 38 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2010 VL 51 IS 5 BP 909 EP 915 DI 10.1111/j.1528-1167.2010.02525.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 587OA UT WOS:000277000900025 PM 20196792 ER PT J AU Sakurai, K Takeda, Y Tanaka, N Kurita, T Shiraishi, H Takeuchi, F Nakane, S Sueda, K Koyama, T AF Sakurai, Kotaro Takeda, Youji Tanaka, Naoaki Kurita, Tsugiko Shiraishi, Hideaki Takeuchi, Fumiya Nakane, Shingo Sueda, Keitaro Koyama, Tsukasa TI Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: A MEG study SO EPILEPSY RESEARCH LA English DT Article DE Generalized spike-wave discharges; Absence epilepsy; Magnetoencephalo-graphy; Default mode network; Dynamic statistical parametric mapping ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; EEG-FMRI; COORDINATE SYSTEM; BRAIN ACTIVITY; SEIZURES; MAGNETOENCEPHALOGRAPHY; RECONSTRUCTION; ACTIVATION; CORTEX AB This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW. (C) 2009 Elsevier B.V. All rights reserved. C1 [Sakurai, Kotaro; Takeda, Youji; Kurita, Tsugiko; Koyama, Tsukasa] Hokkaido Univ, Sch Med, Dept Psychiat & Neurol, Sapporo, Hokkaido 0608638, Japan. [Tanaka, Naoaki] Massachusetts Gen Hosp, Martinous Ctr Biomed Imaging, Charlestown, MA USA. [Shiraishi, Hideaki; Sueda, Keitaro] Hokkaido Univ, Sch Med, Dept Pediat, Sapporo, Hokkaido 0608638, Japan. [Takeuchi, Fumiya] Hokkaido Univ, Sch Med, Dept Hlth Sci, Sapporo, Hokkaido 0608638, Japan. [Nakane, Shingo] Hokkaido Univ Hosp, Div Magnetoencephalog, Sapporo, Hokkaido 060, Japan. RP Sakurai, K (reprint author), Hokkaido Univ, Sch Med, Dept Psychiat & Neurol, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM kootaroo@ab.auone-net.jp RI Shiraishi, Hideaki/A-8427-2012 NR 30 TC 16 Z9 16 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2010 VL 89 IS 2-3 BP 176 EP 184 DI 10.1016/j.eplepsyres.2009.12.004 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 598XJ UT WOS:000277872900002 PM 20061122 ER PT J AU Wu, JC Ho, CY Skali, H Abichandani, R Wilcox, WR Banikazemi, M Packman, S Sims, K Solomon, SD AF Wu, Justina C. Ho, Carolyn Y. Skali, Hicham Abichandani, Rekha Wilcox, William R. Banikazemi, Maryam Packman, Seymour Sims, Katherine Solomon, Scott D. TI Cardiovascular manifestations of Fabry disease: relationships between left ventricular hypertrophy, disease severity, and alpha-galactosidase A activity SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiomyopathy; Echocardiography; Genetics; Hypertrophy; Fabry; alpha-Galactosidase ID ENZYME REPLACEMENT THERAPY; CLINICAL-MANIFESTATIONS; CARDIAC MANIFESTATIONS; OUTCOME SURVEY; CARDIOMYOPATHY; FEMALES; COHORT; ECHOCARDIOGRAPHY; RECOMMENDATIONS; REGISTRY AB Fabry disease is a rare X-linked deficiency of alpha-galactosidase A (alpha gal), which causes glycosphingolipid accumulation. This study analysed the cardiovascular manifestations of a cohort of Fabry patients, and sought to define relationships between disease severity, alpha gal activity, and cardiac abnormalities. We prospectively analysed Fabry patients (139 subjects: 92 males and 47 females) undergoing screening for potential enzyme replacement therapy. Baseline echocardiograms, electrocardiograms, and exams were obtained as part of two multinational clinical trials. Cardiovascular symptoms were present in 60.4%. By echocardiography, the mean left ventricular mass index (LVMI) was increased at 165.5 +/- 66.9 g/m(2), and 84.8% of patients displayed concentric left ventricular hypertrophy (LVH). Electrocardiographic LVH was present in > 50% of adult subjects. In females, log-corrected plasma alpha gal activity was inversely associated with LVMI (r = -0.45, P < 0.040). Males with extremely low alpha gal activity and renal disease displayed the most LVH and cardiac symptoms, but LVH was prevalent even in females < 20 years old. Concentric LVH was the predominant cardiac pathology seen in patients with Fabry disease, and was prevalent in both genders by the third decade of life. Left ventricular mass index was inversely correlated with alpha gal activity, but was prevalent even in younger females. C1 [Wu, Justina C.; Ho, Carolyn Y.; Skali, Hicham; Solomon, Scott D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Abichandani, Rekha] Genzyme Corp, Cambridge, MA USA. [Wilcox, William R.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Banikazemi, Maryam] Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. [Packman, Seymour] Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA 94143 USA. [Sims, Katherine] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Wu, JC (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM jcwu@partners.org RI Solomon, Scott/I-5789-2013; OI Ho, Carolyn/0000-0002-7334-7924 FU Genzyme Corporation; GCRC [M01-RR00425] FX This work was supported by a research grant from Genzyme Corporation to J.C.W., C.Y.H., H.S., M.B., K.S., S.D.S.; and a GCRC Grant M01-RR00425 to W. R. W. NR 22 TC 15 Z9 15 U1 1 U2 1 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 MAY PY 2010 VL 31 IS 9 BP 1088 EP 1097 DI 10.1093/eurheartj/ehp588 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 593IU UT WOS:000277448100017 PM 20061327 ER PT J AU Ducrocq, G Wallace, JS Baron, G Ravaud, P Alberts, MJ Wilson, PWF Ohman, EM Brennan, DM D'Agostino, RB Bhatt, DL Steg, PG AF Ducrocq, Gregory Wallace, Joshua S. Baron, Gabriel Ravaud, Philippe Alberts, Mark J. Wilson, Peter W. F. Ohman, Erik Magnus Brennan, Danielle M. D'Agostino, Ralph B. Bhatt, Deepak L. Steg, Philippe Gabriel CA REACH Investigators TI Risk score to predict serious bleeding in stable outpatients with or at risk of atherothrombosis SO EUROPEAN HEART JOURNAL LA English DT Article DE Bleeding risk; Atherothrombosis; Antithrombotic therapy ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; CARDIOVASCULAR-DISEASE; EXTERNAL VALIDITY; ADVERSE OUTCOMES; CLOPIDOGREL; ASPIRIN; MODELS; VALIDATION; PREVENTION AB To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis. We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32-1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0-23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score < 6); 0.95% (7-8); 1.25% (9-10); 2.76% (>= 11). The score's discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c(2) = 4.74; P = 0.69). Bleeding risk increased substantially with a score > 10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients. C1 [Ducrocq, Gregory; Steg, Philippe Gabriel] Ctr Hosp Univ Bichat Claude Bernard, Dept Cardiol, INSERM, Rech Clin Atherothrombose U698, F-75877 Paris 18, France. [Wallace, Joshua S.; Baron, Gabriel; Ravaud, Philippe] Hop Bichat Claude Bernard, AP HP, Dept Epidemiol Biostat & Rech Clin, F-75877 Paris, France. [Wallace, Joshua S.; Baron, Gabriel; Ravaud, Philippe] INSERM, U738, Paris, France. [Wallace, Joshua S.; Baron, Gabriel; Ravaud, Philippe] Univ Paris 07, UFR Med, Paris, France. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Wilson, Peter W. F.] Emory Sch Med, Atlanta, GA USA. [Ohman, Erik Magnus] Duke Univ, Durham, NC USA. [Brennan, Danielle M.] Cleveland Clin, Cleveland, OH 44106 USA. [D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ducrocq, G (reprint author), Ctr Hosp Univ Bichat Claude Bernard, Dept Cardiol, INSERM, Rech Clin Atherothrombose U698, 46 Rue Henri Huchard, F-75877 Paris 18, France. EM gregory.ducrocq@bch.aphp.fr OI Ravaud, Philippe/0000-0001-8264-9206 FU sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX This work was supported by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). Funding to pay the Open Access publication charges for this article was provided by sanofiaventis and Bristol Myers Squibb. NR 25 TC 32 Z9 32 U1 0 U2 1 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 MAY PY 2010 VL 31 IS 10 BP 1257 EP 1265 DI 10.1093/eurheartj/ehq021 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 597CE UT WOS:000277732600019 PM 20181681 ER PT J AU Zipser, MC Mangana, J Oberholzer, PA French, LE Dummer, R AF Zipser, Marie C. Mangana, Joanna Oberholzer, Patrick A. French, Lars E. Dummer, Reinhard TI Melanoma after laser therapy of pigmented lesions - circumstances and outcome SO EUROPEAN JOURNAL OF DERMATOLOGY LA English DT Article DE laser; lentigo maligna; melanoma; naevus; pigmented naevus ID SWITCHED RUBY-LASER; CARBON-DIOXIDE LASER; LENTIGO MALIGNA; AESTHETIC MEDICINE; CUTANEOUS MELANOMA; MELANOCYTIC NEVUS; DERMATOLOGY; IRRADIATION; EXPRESSION; PROGRESS AB The use of laser therapy in the treatment of pigmented lesions is a controversial issue as it can delay melanoma diagnosis and may negatively impact mortality. Few cases of melanoma after laser therapy have been reported. It is still unknown whether melanoma can be induced by lasers. We discuss the outcomes of twelve patients presenting with melanoma subsequent to previous treatment with laser. In four patients, a skin biopsy was performed before laser treatment. Histology was re-evaluated by a panel of experienced dermatopathologists and analyzed in the context of clinical and photo-optical data. There was evidence for pathological misdiagnosis in two cases. The other two cases initially presented with non-suspicious features before laser treatment and were clearly diagnosed as melanoma thereafter, opening the possibility of melanoma induction by laser treatment. Most patients were female and presented with facial lesions. Three patients have already died of melanoma and two are in stage IV, showing progressive disease with distant metastases. Laser therapy is a common treatment for pigmented lesions, increasing the risk of delayed melanoma diagnosis. This prevents appropriate and timely therapy, and may therefore lead to a fatal outcome. A careful examination of all pigmented lesions using surface microscopy and representative biopsies in combination with a close follow-up is recommended. C1 [Zipser, Marie C.; Mangana, Joanna; Oberholzer, Patrick A.; French, Lars E.; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Oberholzer, Patrick A.] MIT & Harvard, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Oberholzer, Patrick A.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dummer, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM reinhard.dummer@usz.ch NR 28 TC 12 Z9 12 U1 0 U2 3 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1167-1122 EI 1952-4013 J9 EUR J DERMATOL JI Eur. J. Dermatol. PD MAY-JUN PY 2010 VL 20 IS 3 BP 334 EP 338 DI 10.1684/ejd.2010.0933 PG 5 WC Dermatology SC Dermatology GA 607IW UT WOS:000278496500015 PM 20423817 ER PT J AU Metra, M Cleland, JG Weatherley, BD Dittrich, HC Givertz, MM Massie, BM O'Connor, CM Ponikowski, P Teerlink, JR Voors, AA Cotter, G AF Metra, Marco Cleland, John G. Weatherley, Beth Davison Dittrich, Howard C. Givertz, Michael M. Massie, Barry M. O'Connor, Christopher M. Ponikowski, Piotr Teerlink, John R. Voors, Adriaan A. Cotter, Gad TI Dyspnoea in patients with acute heart failure: an analysis of its clinical course, determinants, and relationship to 60-day outcomes in the PROTECT pilot study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Dyspnoea; Prognosis; Rolofylline; Adenosine antagonists ID WORSENING RENAL-FUNCTION; IN-HOSPITAL MORTALITY; RANDOMIZED CONTROLLED TRIAL; A(1) RECEPTOR ANTAGONIST; EUROPEAN-SOCIETY; OF-CARDIOLOGY; TASK-FORCE; ASSOCIATION; IMPAIRMENT; ADMISSION AB Dyspnoea is the most common symptom leading to hospitalization for acute heart failure (AHF). Its early and persistent relief is an important goal of therapy, but little is known about its course, determinants, and prognostic significance. In a post hoc analysis, we studied changes in dyspnoea and in-hospital course in 303 subjects with AHF enrolled in the PROTECT pilot trial. Changes in dyspnoea were assessed by patient self-report using a seven-point Likert scale daily to discharge and at Days 7 and 14. We defined dyspnoea relief as a moderate to marked improvement of dyspnoea at both 24 and 48 h, and treatment success as dyspnoea relief without worsening HF or renal function or death during the first 7 days. Dyspnoea relief occurred in 54% of the patients, while treatment success was achieved in 44% of the patients. By Day 14, only 75% of patients reported a moderate or marked improvement in dyspnoea. Both dyspnoea relief and treatment success were associated with greater improvement in signs of congestion, shorter hospitalization duration, and a lower 60-day mortality rate. Treatment success, but not dyspnoea relief, was also associated with a lower incidence of 60-day death or re-hospitalization for HF or renal failure. Half of patients admitted for AHF do not have substantial improvement in dyspnoea at 24 h and 25% do not have substantial improvement at 7 and 14 days from admission. Dyspnoea relief and treatment success are associated with shorter length of stay and lower 60-day mortality. These analyses should be confirmed in larger studies. C1 [Metra, Marco] Univ Brescia, I-25100 Brescia, Italy. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Weatherley, Beth Davison; Cotter, Gad] Momentum Res Inc, Durham, NC USA. [Dittrich, Howard C.] NovaCardia Inc, San Diego, CA USA. [Givertz, Michael M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Ponikowski, Piotr] Kardiol Klin, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. RP Metra, M (reprint author), Univ Brescia, I-25100 Brescia, Italy. EM metramarco@libero.it RI Teerlink, John/D-2986-2012; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU NovaCardia, Inc FX This study was funded by NovaCardia, Inc. As of September 2007, NovaCardia is a wholly owned subsidiary of Merck & Co, Inc. NR 35 TC 26 Z9 27 U1 1 U2 3 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 MAY PY 2010 VL 12 IS 5 BP 499 EP 507 DI 10.1093/eurjhf/hfq021 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 587MW UT WOS:000276997600012 PM 20228387 ER PT J AU Kim, JI Sonawane, SB Lee, MK Lee, SH Duff, PE Moore, DJ O'Connor, MR Lian, MM Deng, SP Choi, Y Yeh, H Caton, AJ Markmann, JF AF Kim, James I. Sonawane, Samsher B. Lee, Major K. Lee, Seoung-Hoon Duff, Patrick E. Moore, Daniel J. O'Connor, Matthew R. Lian, Moh-Moh Deng, Shaoping Choi, Yongwon Yeh, Heidi Caton, Andrew J. Markmann, James F. TI Blockade of GITR-GITRL interaction maintains Treg function to prolong allograft survival SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE GITR; Inflammation; Treg; Tolerance; Transplant ID IMMUNOLOGICAL SELF-TOLERANCE; REGULATORY T-CELLS; TRANSGENIC MICE; RECEPTOR; TRANSPLANTATION; INFLAMMATION; PEPTIDE; LIGAND; LUNG AB Involvement of Treg in transplant tolerance has been demonstrated in multiple models. During the active process of graft rejection, these regulatory cells are themselves regulated and inactivated, a process termed counter-regulation. We hypothesize that ligation of the costimulatory molecule glucocorticoid-induced TNF receptor-related protein (GITR) on Treg inhibits their ability to promote graft survival, and by blocking GITR ligation graft survival can be prolonged. To this aim, we have designed a soluble GITR fusion protein (GITR-Fc), which binds GITR ligand and inhibits activation of GITR. Here, we show that GITR-Fc prolonged mouse skin graft survival, and this prolongation is dependent on Treg. In a full MHC-mismatched skin graft setting, GITR-Fc significantly improved graft survival when used in combination with MR1, anti-CD40L, while GITR-Fc alone did not demonstrate graft prolongation. These results demonstrate that disruption of binding of GITR with GITR ligand may be an important strategy in prolonging allograft survival. C1 [Kim, James I.; Duff, Patrick E.; O'Connor, Matthew R.; Lian, Moh-Moh; Deng, Shaoping; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sonawane, Samsher B.; Lee, Major K.] Hosp Univ Penn, Harrison Dept Surg Res, Philadelphia, PA 19104 USA. [Lee, Seoung-Hoon; Choi, Yongwon] Univ Penn, Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. [Moore, Daniel J.] Vanderbilt Childrens Hosp, Dept Pediat, Nashville, TN USA. [Caton, Andrew J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jmarkmann@partners.org RI Moore, Daniel/A-4924-2008 OI Moore, Daniel/0000-0002-6889-9345 FU NIH [R01 AI-048820, K01 DK079207-02, T32DK007006-33] FX This research was made possible by NIH grants: R01 AI-048820 (J. F. M.), K01 DK079207-02 (J. I. K.), and T32DK007006-33 (S. B. S.). NR 23 TC 12 Z9 13 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2010 VL 40 IS 5 BP 1369 EP 1374 DI 10.1002/eji.200940046 PG 6 WC Immunology SC Immunology GA 605JJ UT WOS:000278343500014 PM 20148423 ER PT J AU Fahey, FH Abramson, ZR Padwa, BL Zimmerman, RE Zurakowski, D Nissenbaum, M Kaban, LB Treves, ST AF Fahey, Frederic H. Abramson, Zachary R. Padwa, Bonnie L. Zimmerman, Robert E. Zurakowski, David Nissenbaum, Mark Kaban, Leonard B. Treves, S. Ted TI Use of Tc-99m-MDP SPECT for assessment of mandibular growth: development of normal values SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Tc-99m-MDP SPECT; Mandibular asymmetry; Standardized imaging approach ID UNILATERAL CONDYLAR HYPERPLASIA; EMISSION COMPUTED-TOMOGRAPHY; BONE-SCINTIGRAPHY; SKELETAL SCINTIGRAPHY; HEMIMANDIBULAR HYPERPLASIA; PLANAR; ASYMMETRY; CONDYLECTOMY; MANAGEMENT; DIAGNOSIS AB Planar scintigraphy using Tc-99m-labeled methylene diphosphonate (Tc-99m-MDP) has been established as a method for evaluating mandibular growth and asymmetry. However, Tc-99m-MDP single photon emission computed tomography (SPECT) provides improved image contrast and quantitative capability potentially allowing the clinician to make a more accurate assessment of the stage of activity of normal and asymmetric mandibular growth. The purpose of this study was to utilize Tc-99m-MDP SPECT in normal subjects to develop a standardized approach to imaging the mandible that could subsequently be used to evaluate patients with potential for mandibular growth abnormalities. Thirty-two patients (22 females, 10 males, 8-25 years of age, mean of 14 years) having Tc-99m-MDP bone scans (7.4 MBq/kg, maximum of 518 MBq) for indications not involving the head were asked to have an additional SPECT that included the mandibular condyles. Internal (clivus) and external (source of known activity included within the field of view) standards were both investigated. Two- and three-dimensional (2-D and 3-D) regions of interest (ROI) were drawn over each condyle and the clivus in a single slice containing the maximum pixel value within the structure. A 3-D ROI was also drawn about the external standard. Maximum and average pixel values within the 2-D and 3-D ROIs were recorded. Correlation analysis indicated that essentially the same information was obtained whether the maximum or average pixel value within a 2-D or 3-D ROI was used. The right to left ratio provided a parameter that can be used to assess the magnitude of mandibular metabolic asymmetry. Use of an external standard provides the potential for quantifying condylar uptake for assessment of the activity of mandibular growth. Normal ranges for different age groups were determined for condylar uptake using both internal and external standards. Tc-99m-MDP SPECT provides a quantitative method for assessing mandibular condylar uptake as a reflection of the activity of mandibular growth. The maximum pixel value of a 2-D ROI using external standardization and the right to left ratio of the condylar uptake provide the potential for quantitative evaluation of patients with mandibular asymmetry. These parameters will be further evaluated in an upcoming clinical investigation. C1 [Fahey, Frederic H.; Treves, S. Ted] Childrens Hosp, Div Nucl Med, Boston, MA 02115 USA. [Fahey, Frederic H.; Padwa, Bonnie L.; Zimmerman, Robert E.; Zurakowski, David; Kaban, Leonard B.; Treves, S. Ted] Harvard Univ, Sch Med, Boston, MA USA. [Abramson, Zachary R.; Padwa, Bonnie L.; Nissenbaum, Mark; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Padwa, Bonnie L.] Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Zimmerman, Robert E.] Brigham & Womens Hosp, Div Nucl Med, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Orthopaed, Boston, MA 02115 USA. [Abramson, Zachary R.; Nissenbaum, Mark; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Fahey, FH (reprint author), Childrens Hosp, Div Nucl Med, 300 Longwood Ave, Boston, MA 02115 USA. EM frederic.fahey@childrens.harvard.edu NR 29 TC 15 Z9 18 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD MAY PY 2010 VL 37 IS 5 BP 1002 EP 1010 DI 10.1007/s00259-009-1337-0 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583HN UT WOS:000276664600018 PM 20033153 ER PT J AU Simms, LJ Zelazny, K Yam, WH Gros, DF AF Simms, Leonard J. Zelazny, Kerry Yam, Wern How Gros, Daniel F. TI Self-informant Agreement for Personality and Evaluative Person Descriptors: Comparing Methods for Creating Informant Measures SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article DE self-informant agreement, Big Five; Big Seven; evaluative traits, informant measures ID CROSS-CULTURAL GENERALITY; BIG-7 FACTOR MODEL; 5-FACTOR MODEL; REPORTED PERSONALITY; PSYCHIATRIC-PATIENT; MENTAL-HEALTH; TRAITS; BEHAVIOR; ACQUAINTANCESHIP; PERSPECTIVE AB Little attention typically is paid to the way self-report measures are translated for use in self-informant agreement studies. We studied two possible methods for creating informant measures (a) the traditional method in which self-report items were translated from the first- to the third-person and (14 an alternative meta-perceptual method in which informants were directed to rate their perception of the targets' self perception. We hypothesized that the latter method would yield stronger self-informant agreement for evaluative personality dimensions measured by indirect item markers We studied these methods in a sample of 303 undergraduate friendship dyads. Results revealed mean-level differences between methods, similar self-informant agreement across methods. stronger agreement for Big Five dimensions than for evaluative dimensions, and incremental validity for meta-perceptual informant rating methods Limited power reduced the interpretability of several sparse acquaintanceship effects. We conclude that traditional informant methods are appropriate for most personality traits. but meta-perceptual methods may be more appropriate when personality questionnaire items reflect indirect indicators of the trait being measured, which is particularly likely for evaluative traits Copyright (C) 2010 John Wiley & Sons, Ltd C1 [Simms, Leonard J.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. [Gros, Daniel F.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC USA. RP Simms, LJ (reprint author), SUNY Buffalo, Dept Psychol, Pk Hall 218, Buffalo, NY 14260 USA. FU NIMH NIH HHS [R01 MH080086, R01 MH080086-03] NR 49 TC 10 Z9 10 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAY PY 2010 VL 24 IS 3 SI SI BP 207 EP 221 DI 10.1002/per.763 PG 15 WC Psychology, Social SC Psychology GA 599IW UT WOS:000277905900004 PM 21541262 ER PT J AU Stolzmann, P Alkadhi, H Scheffel, H Hennemuth, A Kuehnel, C Baumueller, S Kozerke, S Falk, V Marincek, B Donati, OF AF Stolzmann, Paul Alkadhi, Hatem Scheffel, Hans Hennemuth, Anja Kuehnel, Caroline Baumueller, Stephan Kozerke, Sebastian Falk, Volkmar Marincek, Borut Donati, Olivio F. TI Image fusion of coronary CT angiography and cardiac perfusion MRI: a pilot study SO EUROPEAN RADIOLOGY LA English DT Article DE Computed tomography; Integrative imaging; Myocardial perfusion; Magnetic resonance imaging; Image fusion; Image registration ID ARTERY-DISEASE; SHOOT MODE AB To develop a tool for the image fusion of computed tomography coronary angiography (CTCA) and cardiac magnetic resonance imaging (CMR). Surface representations and volume-rendered images from fused CTCA/CMR data of five patients with significant coronary artery disease (CAD) on CTCA and perfusion deficits on CMR were generated using a newly developed software prototype. The spatial relationship of significant coronary artery stenosis at CTCA and myocardial defects at CMR was evaluated. Registration of CTCA and CMR images was possible in all patients. The comprehensive three-dimensional visualisation of fused CTCA and CMR data accurately demonstrated the relationship between coronary artery stenoses and myocardial defects in all patients. The introduced tool enables image fusion of CTCA and CMR data sets and allows for correct superposition of the coronary arteries derived from CTCA onto the corresponding myocardial segments derived from CMR. The method facilitates the comprehensive assessment of the functionally relevant CAD by the exact allocation of culprit coronary stenoses to corresponding myocardial defects at a low radiation dose. C1 [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, Paul; Alkadhi, Hatem; Scheffel, Hans; Baumueller, Stephan; Marincek, Borut; Donati, Olivio F.] Univ Zurich Hosp, Inst Diagnost Radiol, Zurich, Switzerland. [Hennemuth, Anja; Kuehnel, Caroline] Fraunhofer MEVIS, Bremen, Germany. [Kozerke, Sebastian] Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. [Kozerke, Sebastian] ETH, Zurich, Switzerland. [Falk, Volkmar] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland. RP Alkadhi, H (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM halkadhi@partners.org RI Kozerke, Sebastian/J-3209-2015 OI Kozerke, Sebastian/0000-0003-3725-8884 FU National Center of Competence in Research; Swiss National Science Foundation FX This study was supported by the National Center of Competence in Research, Computer Aided and Image Guided Medical Interventions of the Swiss National Science Foundation. NR 13 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAY PY 2010 VL 20 IS 5 BP 1174 EP 1179 DI 10.1007/s00330-010-1746-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 580CY UT WOS:000276425700019 PM 20204639 ER PT J AU Putrino, D Mastaglia, FL Ghosh, S AF Putrino, David Mastaglia, Frank L. Ghosh, Soumya TI Neural integration of reaching and posture: interhemispheric spike correlations in cat motor cortex SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Movement control; Callosal connections; Postural control; Spike synchrony ID CORPUS-CALLOSUM; SUPPLEMENTARY MOTOR; SENSORIMOTOR CORTEX; CROSS-CORRELATION; MOVEMENT REPRESENTATIONS; CORTICAL SYNCHRONIZATION; INTRINSIC CONNECTIONS; NEURONAL-ACTIVITY; STRUCTURAL BASIS; AWAKE MONKEYS AB To study the interlimb coordination of reaching and postural movements, chronically implanted microelectrodes were used to record single unit activity from the primary motor cortex (MI) of cats during performance of a trained reaching task. Recordings were made from both cerebral hemispheres to record neurons that modulated their activity during reaching (reach-related neurons) and supportive (posture-related neurons) movements of either forelimb. Evidence of temporal associations in the activities of simultaneously recorded reach- and posture-related neurons was evaluated using shuffle-corrected cross correlograms. The spike activity of approximately 34% of reach-related neurons was temporally correlated with the spike activity of simultaneously recorded posture-related neurons in the opposite motor cortex. Significant associations in the spike activity of neurons recorded from homotopic representational areas of the motor cortex in opposite hemispheres have not previously been reported. These interactions may have an important role in the coordination of opposite forelimbs during reaching movements and postural actions. C1 [Mastaglia, Frank L.; Ghosh, Soumya] Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, QEII Med Ctr, Nedlands, WA 6009, Australia. [Putrino, David] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Putrino, David] Harvard MIT, Dept Brain & Cognit Sci, Div Hlth Sci & Technol, Cambridge, MA USA. RP Ghosh, S (reprint author), Univ Western Australia, Ctr Neuromuscular & Neurol Disorders, QEII Med Ctr, A Block 4th Floor, Nedlands, WA 6009, Australia. EM sghosh@cyllene.uwa.edu.au OI Putrino, David/0000-0002-2232-3324 FU Australian Neuromuscular Research Institute; Curtin University of Technology FX We thank the Australian Neuromuscular Research Institute and Curtin University of Technology for support, and the staff of Animal House in A Block, QEII Medical Centre for help with animals. NR 67 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2010 VL 202 IS 4 BP 765 EP 777 DI 10.1007/s00221-010-2180-z PG 13 WC Neurosciences SC Neurosciences & Neurology GA 587VZ UT WOS:000277024400004 PM 20165839 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Beyond sorafenib: novel targeted therapies for advanced hepatocellular carcinoma SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; FACTOR-RECEPTOR; ANTITUMOR-ACTIVITY; FACTOR-ALPHA; PROGNOSTIC-SIGNIFICANCE; RAF/MEK/ERK PATHWAY; TUMOR PROGRESSION; CANCER-THERAPY AB Areas covered in this review: The aim of this review was to summarize the key data of sorafenib Phase III studies and the lessons and unanswered questions with sorafenib in HCC. It extensively updated the current ongoing studies combining sorafenib with erlotinib and other targeted agents or chemotherapy, and many molecularly targeted agents under development that inhibit angiogenesis, EGFR, and mammalian target of rapamycin (mTOR). What the reader will gain: A comprehensive understanding of the current status of drug development of targeted agents in advanced HCC and insights into the challenges of developing these agents in HCC. Take home message: Sorafenib is the first and only approved agent in advanced HCC. Several Phase III studies are ongoing with other drugs in advanced HCC. Many early clinical trials are conducted to assess other molecularly targeted agents that inhibit different pathways of hepatocarcinogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 55 Fruit St,LH POB 232, Boston, MA 02114 USA. EM azhu@partners.org NR 66 TC 14 Z9 15 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAY PY 2010 VL 19 IS 5 BP 663 EP 672 DI 10.1517/13543781003767426 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 585HM UT WOS:000276815800007 PM 20367287 ER PT J AU Dietrich, J Diamond, EL Kesari, S AF Dietrich, Joerg Diamond, Eli L. Kesari, Santosh TI Glioma stem cell signaling: therapeutic opportunities and challenges SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE angiogenesis; beta-catenin; Bmi1; brain tumors; cancer stem cells; EGF; glioblastoma; miRNA; neural stem cells; notch; PDGF; receptor tyrosine kinases; signaling; Sonic hedgehog; VEGF; Wnt ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CENTRAL-NERVOUS-SYSTEM; PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; ADULT HIPPOCAMPAL NEUROGENESIS; NEURAL PROGENITOR CELLS; BRAIN-TUMOR CONSORTIUM; FACTOR ALPHA-RECEPTOR; IN-VIVO AB The field of cancer research has experienced significant momentum from the discovery that most malignant tumors harbor subpopulations of cancer cells with stem cell features. Consequently, identification and characterization of so-called 'cancer-initiating cells' or 'cancer stem cells' has also provided novel insights into the biology of malignant brain tumors. Despite an ongoing debate regarding the exact role and identity of cancer stem cells, several studies have suggested that this subpopulation is critical for tumor initiation, tumor progression, angiogenesis and resistance to available therapies. The study of signaling pathways critical to normal neural stem and progenitor cells has also increased our understanding of the mechanisms that drive cancer stem cell-associated tumorigenesis and tumor progression. Novel treatment strategies are being developed to selectively target the molecular pathways relevant to cancer stem cells. This review summarizes important signaling pathways employed by both normal and cancer stem cells and highlights promising molecular-targeted therapies interfering with those signaling pathways in malignant gliomas. C1 [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores Canc Ctr, La Jolla, CA 92093 USA. [Dietrich, Joerg; Diamond, Eli L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dietrich, Joerg] Harvard Univ, Sch Med, MGH Canc Ctr, Boston, MA USA. [Dietrich, Joerg] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Kesari, Santosh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kesari, S (reprint author), Univ Calif San Diego, Dept Neurosci, Moores Canc Ctr, 3855 Hlth Sci Dr 0819,Room 3336, La Jolla, CA 92093 USA. EM skesari@ucsd.edu RI Kesari, Santosh/E-8461-2013 FU Joanna Bruner Brain Tumor Research Foundation; Stephen E and Catherine Pappas Foundation; NIH [K-12, K-08, CA 124804]; Sontag Foundation; James S McDonnell Foundation; Adnexus; Bristol-Myers Squibb; Novartis FX The authors gratefully acknowledge the support of the Joanna Bruner Brain Tumor Research Foundation.; Jorg Dietrich is a recipient of the Paul Calabresi Career Development Award for Clinical Oncology (NIH K-12). This work has been supported by the Stephen E and Catherine Pappas Foundation Award for Brain Tumor Research (to Jorg Dietrich), by an NIH K-08 award (CA 124804, to Santosh Kesari), a Sontag Foundation Distinguished Scientist Grant (to Santosh Kesari), and the James S McDonnell Foundation (to Santosh Kesari). Santosh Kesari has been a member of the speaker's bureau for Enzon and has received research funding from Adnexus, Bristol-Myers Squibb and Novartis. 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 205 TC 25 Z9 30 U1 0 U2 14 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 MAY PY 2010 VL 10 IS 5 BP 709 EP 722 DI 10.1586/ERA.09.190 PG 14 WC Oncology SC Oncology GA 609EH UT WOS:000278637500018 PM 20470003 ER PT J AU Yadav, V Shinto, L Bourdette, D AF Yadav, Vijayshree Shinto, Lynne Bourdette, Dennis TI Complementary and alternative medicine for the treatment of multiple sclerosis SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Article DE antioxidants; complementary and alternative medicine; dietary supplements; essential fatty acids; lipoic acid; low-fat diet; multiple sclerosis ID ALPHA-LIPOIC ACID; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; TUMOR-NECROSIS-FACTOR; SYMPTOMATIC DIABETIC POLYNEUROPATHY; POLYUNSATURATED FATTY-ACIDS; STIMULATES CAMP PRODUCTION; PLANT CANNABIS EXTRACTS; CENTRAL-NERVOUS-SYSTEM AB Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area. C1 [Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol L226, Portland, OR 97239 USA. [Bourdette, Dennis] Portland VA Med Ctr, Portland, OR USA. RP Yadav, V (reprint author), Oregon Hlth & Sci Univ, Dept Neurol L226, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM yadavv@ohsu.edu FU National MS Society [PP0921, CA 1055-A-3]; NIH [P50AT00066-01]; Department of Veterans Affairs; Nancy Davis Center Without Walls FX Vijayshree Yadav has received personal compensation for activities with Biogen Idec as a speaker. Dennis Bourdette has received personal compensation for activities with Biogen Idec, EMD Serono, Pfizer Inc. and Teva Neurosciences as a speaker or faculty member. This study was supported by the National MS Society (PP0921 and CA 1055-A-3), the NIH (P50AT00066-01), the Department of Veterans Affairs and the Nancy Davis Center Without Walls. 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 168 TC 23 Z9 24 U1 1 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD MAY PY 2010 VL 6 IS 3 BP 381 EP 395 DI 10.1586/ECI.10.12 PG 15 WC Immunology SC Immunology GA 602VI UT WOS:000278166600014 PM 20441425 ER PT J AU Bhardwaj, A Januzzi, JL AF Bhardwaj, Anju Januzzi, James L., Jr. TI ST2: a novel biomarker for heart failure SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE B-type natriuretic peptide; biomarker; dyspnea; heart failure; myocardial infarction; pro-B-type natriuretic peptide; prognosis; ST2 ID RECEPTOR FAMILY-MEMBER; SOLUBLE ST2; MYOCARDIAL-INFARCTION; PLASMA-CONCENTRATIONS; 1-YEAR MORTALITY; GENE-EXPRESSION; ACUTE DYSPNEA; SERUM-LEVELS; HYPERTROPHY; CYTOKINES AB ST2, an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms, was originally described in the context of inflammatory and autoimmune diseases. However, after the identification of IL-33 as the functional ligand for ST2, and conceptualization of the role of ST2/IL-33 signaling in cardiac remodeling, sST2 has emerged as a novel cardiovascular biomarker for the presence of ventricular biomechanical overload. Concentrations of sST2 have been implicated in the presence and severity of heart failure with particular value for prognostication. We will review the use of sST2 as a prognostic marker in heart failure, including present and future directions in this exciting area. C1 [Bhardwaj, Anju; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 28 TC 28 Z9 31 U1 1 U2 9 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2010 VL 10 IS 4 BP 459 EP 464 DI 10.1586/ERM.10.25 PG 6 WC Pathology SC Pathology GA 601FB UT WOS:000278042600009 PM 20465500 ER PT J AU Giani, A Sabella, P Eandi, CM Staurenghi, G AF Giani, A. Sabella, P. Eandi, C. M. Staurenghi, G. TI Spectral-domain optical coherence tomography findings in a case of frosted retinal branch angiitis SO EYE LA English DT Letter C1 [Giani, A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Giani, A.; Sabella, P.; Staurenghi, G.] Univ Milan, Dept Clin Sci Luigi Sacco, Eye Clin, Sacco Hosp, Milan, Italy. [Eandi, C. M.] Univ Turin, Dept Clin Physiopathol, Eye Clin, Turin, Italy. RP Giani, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM andrea_giani@meei.harvard.edu OI Eandi, Chiara Maria/0000-0003-3656-1689 NR 5 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD MAY PY 2010 VL 24 IS 5 BP 943 EP 944 DI 10.1038/eye.2009.228 PG 3 WC Ophthalmology SC Ophthalmology GA 595EG UT WOS:000277592900039 PM 19730449 ER PT J AU Jang, YC Lustgarten, MS Liu, YH Muller, FL Bhattacharya, A Liang, HY Salmon, AB Brooks, SV Larkin, L Hayworth, CR Richardson, A Van Remmen, H AF Jang, Youngmok C. Lustgarten, Michael S. Liu, Yuhong Muller, Florian L. Bhattacharya, Arunabh Liang, Hanyu Salmon, Adam B. Brooks, Susan V. Larkin, Lisa Hayworth, Christopher R. Richardson, Arlan Van Remmen, Holly TI Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration SO FASEB JOURNAL LA English DT Article DE apoptosis; oxidative stress; sarcopenia ID SKELETAL-MUSCLE; OXIDATIVE STRESS; MOTOR-NEURONS; MYONUCLEAR NUMBER; MOUSE HINDLIMB; FIBER TYPES; CELL-DEATH; DENERVATION; APOPTOSIS; MICE AB Oxidative stress has been implicated in the etiology of age-related muscle loss (sarcopenia). However, the underlying mechanisms by which oxidative stress contributes to sarcopenia have not been thoroughly investigated. To directly examine the role of chronic oxidative stress in vivo, we used a mouse model that lacks the antioxidant enzyme CuZnSOD (Sod1). Sod1(-/-) mice are characterized by high levels of oxidative damage and an acceleration of sarcopenia. In the present study, we demonstrate that muscle atrophy in Sod1(-/-) mice is accompanied by a progressive decline in mitochondrial bioenergetic function and an elevation of mitochondrial generation of reactive oxygen species. In addition, Sod1(-/-) muscle exhibits a more rapid induction of mitochondrial-mediated apoptosis and loss of myonuclei. Furthermore, aged Sod1(-/-) mice show a striking increase in muscle mitochondrial content near the neuromuscular junctions (NMJs). Despite the increase in content, the function of mitochondria is significantly impaired, with increased denervated NMJs and fragmentation of acetylcholine receptors. As a consequence, contractile force in aged Sod1(-/-) muscles is greatly diminished. Collectively, we show that Sod1(-/-) mice display characteristics of normal aging muscle in an accelerated manner and propose that the superoxide-induced NMJ degeneration and mitochondrial dysfunction are potential mechanisms of sarcopenia.-Jang, Y. C., Lustgarten, M. S., Liu, Y., Muller, F. L., Bhattacharya, A., Liang, H., Salmon, A. B., Brooks, S. V., Larkin, L., Hayworth, C. R., Richardson, A., and Van Remmen, H. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB J. 24, 1376-1390 (2010). www.fasebj.org C1 [Jang, Youngmok C.; Liu, Yuhong; Muller, Florian L.; Bhattacharya, Arunabh; Liang, Hanyu; Salmon, Adam B.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. [Lustgarten, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Jang, Youngmok C.; Lustgarten, Michael S.; Liu, Yuhong; Muller, Florian L.; Bhattacharya, Arunabh; Liang, Hanyu; Salmon, Adam B.; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Brooks, Susan V.; Larkin, Lisa] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Hayworth, Christopher R.] Univ Texas Austin, Neurobiol Sect, Austin, TX 78712 USA. [Hayworth, Christopher R.] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA. [Richardson, Arlan; Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu FU American Federation for Aging Research [P01AG020591] FX The authors thank Drs. Charles Epstein (University of California, San Francisco, CA, USA) and Ting Ting Huang (Stanford University, Palo Alto, CA, USA) for providing Sod1-null breeders, Corinne Price for proofreading our manuscript, and Drs. Asish Chaudhuri, Anson Pierce, James Lechleiter, Walter Ward, and Victoria Frohlich for their input and technical assistance. This work was supported by P01AG020591 (to H. V. R., A. R., S. V. B., L. L.), and a Julie Martin Mid-Career grant from the American Federation for Aging Research (to H. V. R.). NR 58 TC 96 Z9 98 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2010 VL 24 IS 5 BP 1376 EP 1390 DI 10.1096/fj.09-146308 PG 15 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 589OD UT WOS:000277158900011 PM 20040516 ER PT J AU Zhang, ZY Liew, CW Handy, DE Zhang, YY Leopold, JA Hu, J Guo, LL Kulkarni, RN Loscalzo, J Stanton, RC AF Zhang, Zhaoyun Liew, Chong Wee Handy, Diane E. Zhang, Yingyi Leopold, Jane A. Hu, Ji Guo, Lili Kulkarni, Rohit N. Loscalzo, Joseph Stanton, Robert C. TI High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis SO FASEB JOURNAL LA English DT Article DE diabetes mellitus; islets; antioxidants; pentose phosphate pathway ID ENZYME GENE-EXPRESSION; PANCREATIC RAT ISLETS; GLUTATHIONE-PEROXIDASE; DIABETIC-PATIENTS; INSULIN RELEASE; OXIDANT STRESS; IN-VITRO; TOXICITY; 6-AMINONICOTINAMIDE; OVEREXPRESSION AB Patients with type 2 diabetes lose beta cells, but the underlying mechanisms are incompletely understood. Glucose-6-phosphate dehydrogenase (G6PD) is the principal source of the major intracellular reductant, NADPH, which is required by many enzymes, including enzymes of the antioxidant pathway. Previous work from our laboratory has shown that high glucose impairs G6PD activity in endothelial and kidney cells, which leads to decreased cell survival. Pancreatic beta cells are highly sensitive to increased ROS. This study aimed to determine whether G6PD and NADPH play central roles in beta-cell survival. Human and mouse islets, MIN6 cell line, and G6PD deficient mice were studied. High glucose inhibited G6PD expression and activity. Inhibition of G6PD with siRNA led to increased ROS and apoptosis, decreased proliferation, and impaired insulin secretion. High glucose decreased insulin secretion, which was improved by overexpressing G6PD. G6PD-deficient mice had smaller islets and impaired glucose tolerance compared with control mice, which suggests that G6PD deficiency per se leads to beta-cell dysfunction and death. G6PD plays an important role in beta-cell function and survival. High-glucose-mediated decrease in G6PD activity may provide a mechanistic explanation for the gradual loss of beta cells in patients with diabetes.-Zhang, Z., Liew, C. W., Handy, D. E., Zhang, Y., Leopold, J. A., Hu, J., Guo, L., Kulkarni, R. N., Loscalzo, J., Stanton, R. C. High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis. FASEB J. 24, 1497-1505 (2010). www.fasebj.org C1 [Zhang, Zhaoyun; Liew, Chong Wee; Hu, Ji; Guo, Lili; Kulkarni, Rohit N.; Stanton, Robert C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. [Handy, Diane E.; Zhang, Yingyi; Leopold, Jane A.; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. [Zhang, Zhaoyun] Huashan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Div Renal, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu FU U.S. National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK54380]; NIH/National Heart, Lung, and Blood Institute (NHLBI) [HL 61795, N01 HV 28178, P01 HL 81857, U54 HL 070819, HL 089734]; NIH [RO1 DK 68721, RO1 DK 67536, T32DK007260]; Diabetes Endocrinology Research Center (DERC) [P30DK036836] FX The authors thank Dan Kawamori, Xiaodan Wang, Wan-Chun Li, Jiang Hu, and Hui Li for technical assistance. This work was supported by U.S. 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 (NHLBI) grants HL 61795, N01 HV 28178, P01 HL 81857, and U54 HL 070819 to J.A.L.; and NIH/NHLBI grant HL 089734 to D.E.H. with Jacob Joseph (Brigham and Women's Hospital, Boston, MA, USA). R.N.K. was supported by NIH grants RO1 DK 68721 and RO1 DK 67536; and C.L.W. is supported by NIH training grant T32DK007260. The Joslin Core Facilities were used for islet isolation and other measurements, which are funded by Diabetes Endocrinology Research Center (DERC) grant P30DK036836. The authors declare no conflicts of interests. NR 50 TC 71 Z9 81 U1 1 U2 16 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 MAY PY 2010 VL 24 IS 5 BP 1497 EP 1505 DI 10.1096/fj.09-136572 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 589OD UT WOS:000277158900022 PM 20032314 ER PT J AU Sun, DW Nakao, S Xie, F Zandi, S Schering, A Hafezi-Moghadam, A AF Sun, Dawei Nakao, Shintaro Xie, Fang Zandi, Souska Schering, Alexander Hafezi-Moghadam, Ali TI Superior sensitivity of novel molecular imaging probe: simultaneously targeting two types of endothelial injury markers SO FASEB JOURNAL LA English DT Article DE early diagnosis; ocular inflammation; leukocyte-endothelial interaction; adhesion molecules ID ENDOTOXIN-INDUCED UVEITIS; SELECTIN GLYCOPROTEIN LIGAND-1; ROLLING IN-VIVO; P-SELECTIN; UP-REGULATION; CELLS; ADHESION; ICAM-1; LFA-1; DISEASE AB The need remains great for early diagnosis of diseases. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule up-regulation, we generated novel imaging agents that target two distinct types of endothelial molecules, a mediator of rolling, P-selectin, and one that mediates firm adhesion, ICAM-1. Interactions of these double-conjugated fluorescent microspheres (MSs) in retinal or choroidal microvasculature were visualized in live animals by scanning laser ophthalmoscopy. The new imaging agents showed significantly higher sensitivity for detection of endothelial injury than singly conjugated MSs (rPSGL-1- or alpha-ICAM-1-conjugated), both in terms of rolling (P<0.01) and firm adhesion (P<0.01). The rolling flux of alpha-ICAM-1-conjugated MSs did not differ in EIU animals, whereas double-conjugated MSs showed significantly higher rolling flux (P<0.01), revealing that ICAM-1 in vivo supports rolling, once MS interaction with the endothelium is initiated. Double-conjugated MSs specifically detected firmly adhering leukocytes (P<0.01), allowing in vivo quantification of immune response. Antiinflammatory treatment with dexamethasone led to reduced leukocyte accumulation (P<0.01) as well as MS interaction (P<0.01), which suggests that treatment success and resolution of inflammation is quantitatively reflected with this molecular imaging approach. This work introduces novel imaging agents for noninvasive detection of endothelial injury in vivo. Our approach may be developed further to diagnose human disease at a much earlier stage than currently possible.-Sun, D., Nakao, S., Xie, F., Zandi, S., Schering, A., Hafezi-Moghadam, A. Superior sensitivity of novel molecular imaging probe: simultaneously targeting two types of endothelial injury markers. FASEB J. 24, 1532-1540 (2010). www.fasebj.org C1 [Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Schering, Alexander; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med,Angiogenesis Lab, Boston, MA 02114 USA. [Sun, Dawei] Harbin Med Coll, Dept Ophthalmol, Affiliated Hosp 2, Harbin, Peoples R China. RP Hafezi-Moghadam, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med,Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM ali_hafezi-moghadam@hms.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU U.S. National Institute of Health (NIH) [AI050775, HL086933]; Science and Technology project of Heilongjiang Province, China [GB06C40104] FX Recombinant PSGL-1 (Y's PSGL) was a generous gift of Y's Therapeutics, Inc. (San Bruno, CA, USA). The authors thank Mark I. Melhorn and Rebecca C. Garland for their help in the preparation of this manuscript. This work was supported by U.S. National Institute of Health (NIH) grants AI050775 (A.H.-M.) and HL086933 (Alan Cross, University of Maryland, College Park, MD, USA), the American Health Assistance Foundation (A.H.-M.), and a Science and Technology project of Heilongjiang Province, China (GB06C40104 to D. S.). The authors thank the Massachusetts Lions Eye Research Fund Inc., Research to Prevent Blindness, and the Marion W. and Edward F. Knight AMD Fund. Author contributions: A.H.-M. designed research; D.S., S.N., F.X., and S.Z. performed research; D.S., A.S., and A.H.-M. analyzed data; D. S. and A.H.-M. wrote the paper. NR 23 TC 18 Z9 18 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2010 VL 24 IS 5 BP 1532 EP 1540 DI 10.1096/fj.09-148981 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 589OD UT WOS:000277158900026 PM 20103715 ER PT J AU Kojic, N Chung, E Kho, AT Park, JA Huang, A So, PTC Tschumperlin, DJ AF Kojic, Nikola Chung, Euiheon Kho, Alvin T. Park, Jin-Ah Huang, Austin So, Peter T. C. Tschumperlin, Daniel J. TI An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium SO FASEB JOURNAL LA English DT Article DE airway epithelium; mechanical stress; lateral intercellular space ID EPIDERMAL-GROWTH-FACTOR; LATERAL INTERCELLULAR SPACES; PHASIC SHEAR-STRESS; C-ERBB RECEPTORS; SIGNAL-TRANSDUCTION; ARTICULAR-CARTILAGE; DIFFERENTIAL REGULATION; TYROSINE PHOSPHATASES; BRONCHIAL EPITHELIUM; MECHANICAL-STRESS AB The mechanical landscape in biological systems can be complex and dynamic, with contrasting sustained and fluctuating loads regularly superposed within the same tissue. How resident cells discriminate between these scenarios to respond accordingly remains largely unknown. Here, we show that a step increase in compressive stress of physiological magnitude shrinks the lateral intercellular space between bronchial epithelial cells, but does so with strikingly slow exponential kinetics (time constant similar to 110 s). We confirm that epidermal growth factor (EGF)-family ligands are constitutively shed into the intercellular space and demonstrate that a step increase in compressive stress enhances EGF receptor (EGFR) phosphorylation with magnitude and onset kinetics closely matching those predicted by constant-rate ligand shedding in a slowly shrinking intercellular geometry. Despite the modest degree and slow nature of EGFR activation evoked by compressive stress, we find that the majority of transcriptomic responses to sustained mechanical loading require ongoing activity of this autocrine loop, indicating a dominant role for mechanotransduction through autocrine EGFR signaling in this context. A slow deformation response to a step increase in loading, accompanied by synchronous increases in ligand concentration and EGFR activation, provides one means for cells to mount a selective and context-appropriate response to a sustained change in mechanical environment.-Kojic, N., Chung, E., Kho, A. T., Park, J.-A., Huang, A., So, P. T. C., Tschumperlin, D. J. An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium. FASEB J. 24, 1604-1615 (2010). www.fasebj.org C1 [Park, Jin-Ah; Tschumperlin, Daniel J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kojic, Nikola; Chung, Euiheon; Kho, Alvin T.; Huang, Austin] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA. [Chung, Euiheon] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kho, Alvin T.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. [So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Tschumperlin, DJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dtschump@hsph.harvard.edu FU National Institutes of Health (NIH) [HL082856, HL88028, NS040828] FX The authors thank J. Drazen, J. Fredberg, and D. Lauffen-burger for helpful discussions. This work was funded by National Institutes of Health (NIH) grants HL082856 and HL88028, and A.T.K. is funded by NIH NS040828. NR 83 TC 14 Z9 16 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2010 VL 24 IS 5 BP 1604 EP 1615 DI 10.1096/fj.09-145367 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 589OD UT WOS:000277158900032 PM 20056713 ER PT J AU Chavarro, JE Toth, TL Wright, DL Meeker, JD Hauser, R AF Chavarro, Jorge E. Toth, Thomas L. Wright, Diane L. Meeker, John D. Hauser, Russ TI Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic SO FERTILITY AND STERILITY LA English DT Article DE BMI; obesity; semen analysis; sperm DNA; hormones; infertility ID DECREASED ANDROGEN LEVELS; NEUTRAL COMET ASSAY; OBESE MEN; BINDING GLOBULIN; INHIBIN-B; ERECTILE DYSFUNCTION; LUTEINIZING-HORMONE; GONADAL-FUNCTION; RISK-FACTORS; WEIGHT-LOSS AB Objective: To examine the association between body weight and measures of male reproductive potential. Design: Cross-sectional study. Setting: Fertility clinic in an academic medical center. Patient(s): Four hundred eighty-three male partners of subfertile couples. Intervention(s): None. Main Outcome Measure(s): Standard semen analysis, sperm DNA fragmentation, and serum levels of reproductive hormones. Result(s): As expected, body mass index (BMI) was positively related to estradiol levels and inversely related to total testosterone and sex hormone-binding glogulin (SHBG) levels. There was also a strong inverse relation between BMI and inhibin B levels and a lower testosterone: LH ratio among men with a BMIR >= 35 kg/m(2). Body mass index was unrelated to sperm concentration, motility, or morphology. Ejaculate volume decreased steadily with increasing BMI levels. Further, men with BMI >= 35 kg/m(2) had a lower total sperm count (concentration x volume) than normal weight men (adjusted difference in the median [95% confidence interval] = -86 x 10(6) sperm [-134, -37]). Sperm with high DNA damage were significantly more numerous in obese men than in normal-weight men. Conclusion(s): These data suggest that despite major differences in reproductive hormone levels with increasing body weight, only extreme levels of obesity may negatively influence male reproductive potential. (Fertil Steril (R) 2010;93:2222-31. (C)2010 by American Society for Reproductive Medicine.) C1 [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Chavarro, Jorge E.; Toth, Thomas L.; Wright, Diane L.; Hauser, Russ] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Toth, Thomas L.; Wright, Diane L.; Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM jchavarr@hsph.harvard.edu RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences (NIEHS) [ES009718, ES00002]; Yerby Postdoctoral Fellowship Program FX Supported by National Institute of Environmental Health Sciences (NIEHS) Grants ES009718 and ES00002, and the Yerby Postdoctoral Fellowship Program. NR 72 TC 119 Z9 134 U1 3 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY 1 PY 2010 VL 93 IS 7 BP 2222 EP 2231 DI 10.1016/j.fertnstert.2009.01.100 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 595KD UT WOS:000277608200019 PM 19261274 ER PT J AU Augustinack, JC Helmer, K Huber, KE Kakunoori, S Zollei, L Fischl, B AF Augustinack, Jean C. Helmer, Karl Huber, Kristen E. Kakunoori, Sita Zollei, Lilla Fischl, Bruce TI Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE entorhinal cortex; dentate gyrus; hippocampus; subiculum; presubiculum; resolution ID SUSTAINED ELECTRICAL-STIMULATION; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; RHESUS-MONKEY; CORTICAL AFFERENTS; EFFERENT CONNECTIONS; ENTORHINAL CORTEX; CINGULATE CORTEX; MACAQUE MONKEYS; DENTATE GYRUS AB Ex vivo magnetic resonance imaging yields high resolution images that reveal detailed cerebral anatomy and explicit cytoarchitecture in the cerebral cortex, subcortical structures, and white matter in the human brain. Our data illustrate neuroanatomical correlates of limbic circuitry with high resolution images at high field. In this report, we have studied ex vivo medial temporal lobe samples in high resolution structural MRI and high resolution diffusion MRI. Structural and diffusion MRIs were registered to each other and to histological sections stained for myelin for validation of the perforant pathway. We demonstrate probability maps and fiber tracking from diffusion tensor data that allows the direct visualization of the perforant pathway. Although it is not possible to validate the DTI data with invasive measures, results described here provide an additional line of evidence of the perforant pathway trajectory in the human brain and that the perforant pathway may cross the hippocampal sulcus. C1 [Augustinack, Jean C.; Helmer, Karl; Huber, Kristen E.; Kakunoori, Sita; Zollei, Lilla; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Zollei, Lilla; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Augustinack, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jean@nmr.mgh.harvard.edu FU NIH [AG028521] FX The authors would like to thank Alex de Crespigny and George Dai for excellent technical assistance and advice with DTI. This research was supported by NIH AG028521. NR 70 TC 28 Z9 28 U1 0 U2 1 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY PY 2010 VL 4 AR 42 DI 10.3389/fnhum.2010.000421985 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 605MQ UT WOS:000278352100003 PM 20577631 ER PT J AU Goel, A Xicola, RM Nguyen, TP Doyle, BJ Sohn, VR Bandipalliam, P Rozek, LS Reyes, J Cordero, C Balaguer, F Castells, A Jover, R Andreu, M Syngal, S Boland, CR Llor, X AF Goel, Ajay Xicola, Rosa M. Nguyen, Thuy Phuong Doyle, Brian J. Sohn, Vanessa R. Bandipalliam, Prathap Rozek, Laura S. Reyes, Josep Cordero, Carmen Balaguer, Francesc Castells, Antoni Jover, Rodrigo Andreu, Montserrat Syngal, Sapna Boland, C. Richard Llor, Xavier TI Aberrant DNA Methylation in Hereditary Nonpolyposis Colorectal Cancer Without Mismatch Repair Deficiency SO GASTROENTEROLOGY LA English DT Article DE Colorectal Cancer; Microsatellite Stable, Hereditary Nonpolyposis Colorectal Cancer; Non-Lynch HNPCC ID MICROSATELLITE INSTABILITY; CHROMOSOMAL INSTABILITY; LINE-1 HYPOMETHYLATION; AMSTERDAM CRITERIA; PHENOTYPE CIMP; LYNCH SYNDROME; COLON-CANCER; MUTATIONS; TUMORS; FAMILIES AB BACKGROUND & AIMS: Approximately half of the families that fulfill Amsterdam criteria for Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) do not have evidence of the germline mismatch repair gene mutations that define this syndrome and result in microsatellite instability (MSI). The carcinogenic pathways and the best diagnostic approaches to detect microsatellite stable (MSS) HNPCC tumors are unclear. We investigated the contribution of epigenetic alterations to the development of MSS HNPCC tumors. METHODS: Colorectal cancers were divided into 4 groups: (1) microsatellite stable, Amsterdam-positive (MSS HNPCC) (N = 22); (2) Lynch syndrome cancers (identified mismatch repair mutations) (N = 21); (3) sporadic MSS (N = 92); and (4) sporadic MSI (N = 46). Methylation status was evaluated for CACNAG1, SOCS1, RUIVX3, IVEUROG1, MLH1, and long interspersed nucleotide element-1 (LINE-1). KRAS and BRAF mutation status was analyzed. RESULTS: MSS HNPCC tumors displayed a significantly lower degree of LINE-1 methylation, a marker for global methylation, than any other group. Although most MSS HNPCC tumors had some degree of CpG island methylation, none presented a high index of methylation. MSS HNPCC tumors had KRAS mutations exclusively in codon 12, but none harbored V600E BRAF mutations. CONCLUSIONS: Tumors from Amsterdam-positive patients without mismatch repair deficiency (MSS HNPCC) have certain molecular features, including global hypomethylation, that distinguish them from all other colorectal cancers. These characteristics could have an important impact on tumor behavior or treatment response. Studies are underway to further assess the cause and effects of these features. C1 [Xicola, Rosa M.; Doyle, Brian J.; Sohn, Vanessa R.; Llor, Xavier] Univ Illinois, Dept Med, Chicago, IL 60612 USA. [Xicola, Rosa M.; Doyle, Brian J.; Sohn, Vanessa R.; Llor, Xavier] Univ Illinois, Ctr Canc, Chicago, IL 60612 USA. [Goel, Ajay; Nguyen, Thuy Phuong; Balaguer, Francesc; Boland, C. Richard] Baylor Univ, Med Ctr, Dept Med, Div Gastroenterol, Dallas, TX USA. [Bandipalliam, Prathap; Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Bandipalliam, Prathap; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Rozek, Laura S.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Reyes, Josep] Hosp Comarcal Inca, Dept Gastroenterol, Mallorca, Spain. [Cordero, Carmen] Hosp Virgen Rocio, Dept Gastroenterol, Seville, Spain. [Castells, Antoni] Univ Barcelona, Dept Gastroenterol, Hosp Clin, IDIBAPS,CIBERehd, Barcelona, Spain. [Jover, Rodrigo] Hosp Gen Univ, Gastroenterol Unit, Alicante, Spain. [Andreu, Montserrat] Hosp Mar, Dept Gastroenterol, Barcelona, Catalonia, Spain. RP Llor, X (reprint author), Univ Illinois, Dept Med, 840 S Wood St,M-C 716, Chicago, IL 60612 USA. EM ajay.goel@baylorhealth.edu; xllor@uic.edu RI Andreu, Montserrat/D-9911-2015; BALAGUER, FRANCESC/G-2389-2016; OI Andreu, Montserrat/0000-0003-4286-1098; Castells, Antoni/0000-0001-8431-2033 FU Sirazi Foundation; Raymond Cole Memorial Foundation; Department of Medicine and the Cancer Center of the University of Illinois at Chicago; National Institutes of Health [CA72851]; Baylor Research Institute; Spanish Ministerio de Ciencia e Innovacion [SAF 07-64873] FX Supported by the Sirazi Foundation, Raymond Cole Memorial Foundation, and an internal grant from the Department of Medicine and the Cancer Center of the University of Illinois at Chicago (X.L.); National Institutes of Health grants CA72851 and funds from the Baylor Research Institute (C.R.B. and A.G.); and a grant from the Spanish Ministerio de Ciencia e Innovacion (SAF 07-64873 to A.C.). NR 42 TC 58 Z9 59 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2010 VL 138 IS 5 BP 1854 EP U57 DI 10.1053/j.gastro.2010.01.035 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587LA UT WOS:000276992600032 PM 20102720 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI How many polyps are there? SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLONOSCOPY AB Background: Frequently, there is disagreement between consecutive endoscopies about the true number of mucosal lesions. Objective: To develop a simple means to estimate the total number of mucosal lesions and the number of lesions missed during consecutive endoscopies. Design: Probability modeling of endoscopic outcomes. Patients: Subjects undergoing 2 consecutive endoscopies. Main Outcome Measurements: Total number of mucosal lesions and number of missed lesions. Results: If a represents the number of lesions seen by the first endoscopist, b the number of lesions seen by the second endoscopist, and c the number of identical lesions seen by both, then the total number of lesions is given by T = ab/c, and the number of lesions missed by both is given by M = (a - c)(b - c)/c. The estimated numbers for all lesions and for missed lesions increase as the number of identical lesions seen by both endoscopists decreases. If the number of identical lesions seen by both endoscopists matches the number of lesions found by any one endoscopist, the numbers of estimated and found polyps are identical and the number of missed polyps equals zero. Limitations: The analysis assumes that both endoscopists work independently of each other and are equally qualified. The formulas also fail to account for varying characteristics of similar lesions. Conclusion: The analysis presents a simple, unbiased means to estimate the total number of mucosal lesions if 2 consecutive endoscopies yield slightly conflicting results. (Gastrointest Endosc 2010;71:1009-12.) C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 5 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2010 VL 71 IS 6 BP 1009 EP 1012 DI 10.1016/j.gie.2009.11.050 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 596QQ UT WOS:000277700500019 PM 20231022 ER PT J AU Willingham, FF Turner, BG Gee, DW Cizginer, S Sohn, DK Sylla, P Kambadakone, A Sahani, D Mino-Kenudson, M Rattner, DW Brugge, WR AF Willingham, Field F. Turner, Brian G. Gee, Denise W. Cizginer, Sevdenur Sohn, Dae K. Sylla, Patricia Kambadakone, Avinash Sahani, Dushyant Mino-Kenudson, Mari Rattner, David W. Brugge, William R. TI Leaks and endoscopic assessment of break of integrity after NOTES gastrotomy: the LEAKING study, a prospective, randomized, controlled trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LAPAROSCOPIC GASTRIC BYPASS; INTRAABDOMINAL PRESSURE; GASTROINTESTINAL LEAKS; INTRAGASTRIC PRESSURE; DISTAL PANCREATECTOMY; MORBID-OBESITY; RESECTION; SURGERY; FEASIBILITY; MANAGEMENT AB Background: Gastric leak testing after natural orifice transluminal endoscopic surgery (NOTES) gastrotomy closure may help reduce the risk of leaks after transgastric procedures. Objective: To develop a novel endoscopy-based system to determine the presence of a leak after NOTES gastrotomy and to compare this system prospectively with radiographic leak testing. Design: Prospective, randomized, controlled trial. Setting: Academic Medical Center laboratory. Subjects: Fifty swine. Intervention: During the pretrial phase, an endoscopic system for the measurement of intragastric pressure was developed. In the trial phase, swine with a NOTES gastrotomy were randomized to endoscopic versus radiographic leak testing. If a leak was demonstrated, the gastrotomy was reclosed by using a second-generation prototype T-anchor system. The primary outcome was leak detection after gastrotomy closure. The secondary outcome variables included necropsy findings, peritoneal fluid analysis, histologic examination, and clinical outcome. Results: Fourteen swine were included in the pretrial phase and 36 in the randomized trial. Swine were survived for a mean of 9 days postoperatively. Endoscopic pressure monitoring demonstrated a reproducible change in intragastric pressure with insufflation; r = 0.735, P = .001 and r = 0.769, P <= .000 for the total and maximum pressures, respectively. Post-peritoneoscopy, there was a detectable and significant decrease in the mean total and mean maximum pressures versus baseline (P = .006 and P = .009). There was no significant difference between the radiologic and endoscopic arms in leak detection rate (4/18 vs 3/18, respectively, P = .500). Clinical outcomes and mean weight gain were equivalent. There was 1 operative abdominal wall injury and no deaths. Limitations: Animal study. Conclusion: Endoscopic pressure monitoring was reproducible, demonstrated the presence of gastric leak, and was as reliable as contrast-based radiographic leak testing. (Gastrointest Endosc 2010;71:1018-24.) C1 [Willingham, Field F.; Turner, Brian G.; Cizginer, Sevdenur; Brugge, William R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Gee, Denise W.; Sohn, Dae K.; Sylla, Patricia; Rattner, David W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kambadakone, Avinash; Sahani, Dushyant] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. OI Willingham, Field/0000-0002-7071-3001 FU Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) FX This study was supported by a research grant from the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) awarded to F. F. Willingham, D. W. Gee. D. W Rattner; and W. R. Brugge. All authors disclosed no financial relationships relevant to this publication. NR 21 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2010 VL 71 IS 6 BP 1018 EP 1024 DI 10.1016/j.gie.2009.10.053 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 596QQ UT WOS:000277700500021 PM 20185125 ER PT J AU Okada, T Suehiro, Y Ueno, K Mitomori, S Kaneko, S Nishioka, M Okayama, N Sakai, K Higaki, S Hazama, S Hirata, H Sakaida, I Oka, M Hinoda, Y AF Okada, Toshiyuki Suehiro, Yutaka Ueno, Koji Mitomori, Shoko Kaneko, Sayaka Nishioka, Mitsuaki Okayama, Naoko Sakai, Kouhei Higaki, Shingo Hazama, Shoichi Hirata, Hiroshi Sakaida, Isao Oka, Masaaki Hinoda, Yuji TI TWIST1 Hypermethylation Is Observed Frequently in Colorectal Tumors and its Overexpression Is Associated with Unfavorable Outcomes in Patients with Colorectal Cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID METHYLATION-SPECIFIC PCR; BREAST-CANCER; MESENCHYMAL TRANSITION; PANCREATIC-CANCER; REGULATORS SNAIL; DNA METHYLATION; MULTIPLE GENES; UP-REGULATION; METASTASIS; EXPRESSION AB Although growing evidence demonstrates that TWIST1 is an interesting tumor biomarker, little is known about the clinical significance of TWIST1 expression and TWIST1 methylation in human primary colorectal cancer. In this study, we examined the association of TWIST1 expression and TWIST1 methylation with clinicopathologic features in human primary colorectal tumors. Primary colorectal cancer (CRC) specimens from 319 patients, corresponding normal colorectal nontumorous mucosa from 251 patients with cancer, and colorectal adenomas from 189 patients were used. Methylation and expression levels of TWIST1 were compared with clinicopathologic features. The TWIST1 methylation level was higher in colorectal adenoma and cancer than in normal colorectal mucosa. Elevated TWIST1 mRNA expression in normal colorectal mucosa in patients with CRC as well as in primary CRC specimens was associated with unfavorable outcomes. There was no correlation between TWIST1 methylation and TWIST1 expression. Our results suggest that TWIST1 methylation may be a useful biomarker for screening colorectal tumors. In addition, TWIST1 mRNA expression is a possible molecular marker for predicting the outcome in patients with CRC. Confirmatory studies using independent data sets are needed to confirm our findings. (C) 2010 Wiley-Liss, Inc. C1 [Okada, Toshiyuki; Suehiro, Yutaka; Ueno, Koji; Mitomori, Shoko; Kaneko, Sayaka; Nishioka, Mitsuaki; Okayama, Naoko; Sakai, Kouhei; Hinoda, Yuji] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Yamaguchi 7558505, Japan. [Higaki, Shingo; Sakaida, Isao] Yamaguchi Univ, Grad Sch Med, Dept Mol Sci & Appl Med Gastroenterol & Hepatol, Yamaguchi 7558505, Japan. [Hazama, Shoichi; Oka, Masaaki] Yamaguchi Univ, Grad Sch Med, Dept Digest Surg & Surg Oncol Surg 2, Yamaguchi 7558505, Japan. [Hirata, Hiroshi] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hirata, Hiroshi] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. RP Suehiro, Y (reprint author), Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, 1-1-1 Minami Kogushi, Yamaguchi 7558505, Japan. EM ysuehiro@yamaguchi-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology, Japan [21590626] FX Ministry of Education, Culture, Sports, Science and Technology, Japan, Grant number: 21590626. NR 45 TC 29 Z9 32 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2010 VL 49 IS 5 BP 452 EP 462 DI 10.1002/gcc.20755 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 575BH UT WOS:000276037900005 PM 20140954 ER PT J AU Zimmerman, RS Cox, S Lakdawala, NK Cirino, A Mancini-DiNardo, D Clark, E Leon, A Duffy, E White, E Baxter, S Alaamery, M Farwell, L Weiss, S Seidman, CE Seidman, JG Ho, CY Rehm, HL Funke, BH AF Zimmerman, Rebekah S. Cox, Stephanie Lakdawala, Neal K. Cirino, Allison Mancini-DiNardo, Debora Clark, Eugene Leon, Annette Duffy, Elizabeth White, Emily Baxter, Samantha Alaamery, Manal Farwell, Lisa Weiss, Scott Seidman, Christine E. Seidman, Jonathan G. Ho, Carolyn Y. Rehm, Heidi L. Funke, Birgit H. TI A novel custom resequencing array for dilated cardiomyopathy SO GENETICS IN MEDICINE LA English DT Article DE dilated cardiomyopathy; resequencing array; genetic test; locus heterogeneity ID DREIFUSS MUSCULAR-DYSTROPHY; MUSCLE LIM PROTEIN; DELTA-SARCOGLYCAN GENE; HYPERTROPHIC CARDIOMYOPATHY; LAMIN-A/C; HEART-FAILURE; LMNA MUTATIONS; EARLY-ONSET; DESMIN; PHOSPHOLAMBAN AB Purpose: Genetic tests for the most commonly mutated genes in dilated cardiomyopathy (DCM) can confirm a clinical diagnosis in the proband and inform family management. Presymptomatic family members can be identified, allowing for targeted clinical monitoring to minimize adverse outcomes. However, the marked locus and allelic heterogeneity associated with DCM have made clinical genetic testing challenging. Novel sequencing platforms have now opened up avenues for more comprehensive diagnostic testing while simultaneously decreasing test cost and turn around time. Methods: By using a custom design based on triplicate resequencing and separate genotyping of known disease-causing variants, we developed the DCM CardioChip for efficient analysis of 19 genes previously implicated in causing DCM. Results: The chip's analytical sensitivity for known and novel substitution variants is 100% and 98%, respectively. In screening 73 previously tested DCM patients who did not carry clinically significant variants in 10 genes, 7 variants of likely clinical significance were identified in the remaining 9 genes included on the chip. Compared with traditional Sanger-based sequencing, test cost and turn around time were reduced by similar to 50%. Conclusions: The DCM CardioChip is a highly efficient screening test with a projected clinical sensitivity of 26-29%. Genet Med 2010:12(5):268-278. C1 [Zimmerman, Rebekah S.; Cox, Stephanie; Mancini-DiNardo, Debora; Clark, Eugene; Leon, Annette; Duffy, Elizabeth; White, Emily; Baxter, Samantha; Alaamery, Manal; Farwell, Lisa; Weiss, Scott; Rehm, Heidi L.; Funke, Birgit H.] Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA 02139 USA. [Lakdawala, Neal K.; Cirino, Allison; Ho, Carolyn Y.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Seidman, Christine E.; Seidman, Jonathan G.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Rehm, Heidi L.; Funke, Birgit H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Funke, Birgit H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Funke, BH (reprint author), Partners HealthCare Ctr Personalized Genet Med, Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bfunke@partners.org OI Ho, Carolyn/0000-0002-7334-7924 FU Brigham and Women's Hospital; NIH [5R01HL080494, 1R01HL084553] FX C.Y.H. was supported in part by the J. Ira and Nicki Harris Family Research Award in the Division of Cardiovascular Medicine, Brigham and Women's Hospital, and J.G.S. was supported by NIH Grants 5R01HL080494 and 1R01HL084553. The authors thank Raju Kucherlapati for his continued support in developing clinical array based sequencing tests and Alison Brown at the Partners HealthCare Center for Personalized Genetic Medicine for performing the healthy control studies. NR 72 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY PY 2010 VL 12 IS 5 BP 268 EP 278 DI 10.1097/GIM.0b013e3181d6f7c0 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 595GJ UT WOS:000277598400004 PM 20474083 ER PT J AU Chan, AT AF Chan, Andrew T. TI COX-2 expression in adenoma: an imperfect marker for chemoprevention SO GUT LA English DT Editorial Material ID PREVENT COLORECTAL ADENOMAS; RANDOMIZED-TRIAL; ASPIRIN; CANCER C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU NCI NIH HHS [R01 CA137178, R01 CA137178-03, K07 CA107412, K07 CA107412-05] NR 13 TC 4 Z9 5 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAY PY 2010 VL 59 IS 5 BP 568 EP 569 DI 10.1136/gut.2009.200014 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 588RO UT WOS:000277091500004 PM 20427388 ER PT J AU Lesnock, J Darcy, K Tian, C DeLoia, J Armstrong, D Birrer, M Gallion, H Krivak, T AF Lesnock, J. Darcy, K. Tian, C. DeLoia, J. Armstrong, D. Birrer, M. Gallion, H. Krivak, T. TI Association of Single Nucleotide Polymorphisms in 5 Loci of BRCA1 with Clinical Outcome in Epithelial Ovarian Cancer Patients Treated with Cisplatin and Paclitaxel: A Gynecologic Oncology Group Study SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Lesnock, J.] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Darcy, K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Tian, C.] New York State Dept Hlth, Roswell Pk Mem Inst, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [DeLoia, J.] Georgetown Univ, Washington, DC USA. [Armstrong, D.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Birrer, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallion, H.] Precis Therapeut Inc, Pittsburgh, PA USA. [Krivak, T.] Univ Pittsburgh, Magee Womens Hosp, Sewickley, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2010 VL 117 IS 2 BP 394 EP 395 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 594LG UT WOS:000277538600051 ER PT J AU Hussein, M Berenson, JR Niesvizky, R Munshi, N Matous, J Sobecks, R Harrop, K Drachman, JG Whiting, N AF Hussein, Mohamad Berenson, James R. Niesvizky, Ruben Munshi, Nikhil Matous, Jeffrey Sobecks, Ronald Harrop, Kate Drachman, Jonathan G. Whiting, Nancy TI A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE multiple myeloma; dacetuzumab; SGN-40; CD40; immunotherapy ID CLINICAL-IMPLICATIONS; CANCER STATISTICS; CYTOTOXICITY; SURVIVAL; THERAPY AB This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid premedication). An initial dose of 4 mg/kg dacetuzumab exceeded the maximum-tolerated dose for uniform weekly dosing. Intrapatient dose escalation with steroid premedication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. Adverse events potentially related to dacetuzumab included cytokine release syndrome symptoms, non-infectious ocular inflammation, and elevated hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing. Clinical trials.gov identifier: NCT00079716 C1 [Hussein, Mohamad; Sobecks, Ronald] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Berenson, James R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. [Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA. [Munshi, Nikhil] Boston VA Healthcare Syst, Dana Farber Canc Inst, Boston, MA USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Harrop, Kate; Drachman, Jonathan G.; Whiting, Nancy] Seattle Genet Inc, Bothell, WA USA. RP Hussein, M (reprint author), Celgene, 86 Morris Ave, Summit, NJ 07901 USA. EM mhussein@celgene.com FU Seattle Genetics, Inc. (Bothell, WA, USA); Seattle Genetics FX Funding: this work was supported by Seattle Genetics, Inc. (Bothell, WA, USA). KH, JGD, and NW are employees and stockholders of Seattle Genetics and JGD is named on one or more patent applications concerning dacetuzumab. NM reported receipt of a consultancy fee (less than $10,000 USD) from Seattle Genetics. MH, JRB, RN, NM, JM, and RS received research funding from Seattle Genetics to conduct this study. NR 12 TC 70 Z9 74 U1 1 U2 5 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 EI 1592-8721 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAY PY 2010 VL 95 IS 5 BP 845 EP 848 DI 10.3324/haematol.2009.008003 PG 4 WC Hematology SC Hematology GA 600GR UT WOS:000277974000025 PM 20133895 ER PT J AU Billings, JA Churchill, LR Payne, R AF Billings, J. Andrew Churchill, Larry R. Payne, Richard TI Severe Brain Injury and the Subjective Life SO HASTINGS CENTER REPORT LA English DT Article ID MINIMALLY CONSCIOUS STATE; PERSISTENT VEGETATIVE STATE; MEDICAL ASPECTS; PAIN; DISORDERS; STIMULATION; MODULATION; AWARENESS C1 [Billings, J. Andrew] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Cambridge, MA 02138 USA. [Churchill, Larry R.] Vanderbilt Univ, Nashville, TN 37235 USA. [Payne, Richard] Duke Univ, Durham, NC 27706 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 1 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAY-JUN PY 2010 VL 40 IS 3 BP 17 EP 21 PG 5 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 604UN UT WOS:000278304100017 PM 20545105 ER PT J AU Scott, AR Faquin, WC Deschler, DG AF Scott, Andrew R. Faquin, William C. Deschler, Daniel G. TI PAROTID MASS IN A WOMAN WITH MULTIPLE CUTANEOUS CYLINDROMAS SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE parotid gland; basal cell adenoma; cylindroma ID TUMOR-SUPPRESSOR GENE; FAMILIAL CYLINDROMATOSIS; TURBAN TUMOR; GLAND; INVOLVEMENT; CYLD AB Background. Familial autosomal dominant cylindromatosis (FADC) is a rare disease characterized by multiple cutaneous cylindromas, trichoepitheliomas, and spiradenomas. We present a case of a woman with scalp lesions and a parotid mass. Methods. Biopsy of a skin nodule demonstrated cylindroma, and fine-needle aspiration of the parotid mass suggested membranous basal cell adenoma, which was confirmed following superficial parotidectomy. The study includes case report and review of the literature. Results. Eighteen cases of cylindromatosis with coexistent salivary gland membranous basal cell adenoma were reported. Seventeen cases involved the parotid gland; there are 2 reports of malignant transformation. Conclusion. FADC should be considered in anyone with coexistent dermal and salivary gland neoplasms. Membranous basal cell adenoma may be mistaken for adenoid cystic carcinoma on cytologic or histologic examination. Total parotidectomy with facial nerve preservation or superficial parotidectomy with close follow-up is recommended, as multi-focality and malignant transformation exist. (C) 2009 Wiley Periodicals, Inc. Head Neck 32: 684-687, 2010 C1 [Scott, Andrew R.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Head & Neck Surg,Massachusetts Eye & Ear Infi, Boston, MA 02115 USA. [Faquin, William C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Scott, AR (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Head & Neck Surg,Massachusetts Eye & Ear Infi, Boston, MA 02115 USA. EM andrew_scott@meei.harvard.edu NR 9 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAY PY 2010 VL 32 IS 5 BP 684 EP 687 DI 10.1002/hed.21133 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 592AO UT WOS:000277347100018 PM 19455704 ER PT J AU Browne, K Roseman, D Shaller, D Edgman-Levitan, S AF Browne, Katherine Roseman, Deborah Shaller, Dale Edgman-Levitan, Susan TI Measuring Patient Experience As A Strategy For Improving Primary Care SO HEALTH AFFAIRS LA English DT Editorial Material ID MEDICAID MANAGED CARE; PSYCHOMETRIC PROPERTIES; HEALTH PLANS; VOLUNTARY DISENROLLMENT; CONSUMER ASSESSMENT; PHYSICIANS; OUTCOMES; QUALITY; CAHPS(R); ASSESSMENTS AB Patients value the interpersonal aspects of their health care experiences. However, faced with multiple resource demands, primary care practices may question the value of collecting and acting upon survey data that measure patients' experiences of care. The Consumer Assessment of Healthcare Providers and Systems (CAHPS) suite of surveys and quality improvement tools supports the systematic collection of data on patient experience. Collecting and reporting CAHPS data can improve patients' experiences, along with producing tangible benefits to primary care practices and the health care system. We also argue that the use of patient experience information can be an important strategy for transforming practices as well as to drive overall system transformation. C1 [Browne, Katherine] George Washington Univ, Dept Hlth Policy, Ctr Hlth Care Qual, Washington, DC 20052 USA. [Shaller, Dale] Shaller Consulting, Stillwater, MN USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. RP Browne, K (reprint author), George Washington Univ, Dept Hlth Policy, Ctr Hlth Care Qual, Washington, DC 20052 USA. EM katherine.browne@gwumc.edu NR 41 TC 69 Z9 69 U1 2 U2 20 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 MAY-JUN PY 2010 VL 29 IS 5 BP 921 EP 925 DI 10.1377/hlthaff.2010.0238 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 590VL UT WOS:000277256300025 PM 20439881 ER PT J AU Ravicz, ME Slama, MCC Rosowski, JJ AF Ravicz, Michael E. Slama, Michael C. C. Rosowski, John J. TI Middle-ear pressure gain and cochlear partition differential pressure in chinchilla SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Middle-ear sound transmission; Intracochlear sound pressure; Middle-ear gain; Cochlear impedance; Chinchilla ID STAPES VELOCITY; SOUND; TRANSMISSION; GERBIL; CAT; ADMITTANCE; MECHANICS; MEMBRANE; HEARING; BASE AB An important step to describe the effects of inner-ear impedance and pathologies on middle- and inner-ear mechanics is to quantify middle- and inner-ear function in the normal ear. We present middle-ear pressure gain G(MEP) and trans-cochlear-partition differential sound pressure Delta P(CP) in chinchilla from 100 Hz to 30 kHz derived from measurements of intracochlear sound pressures in scala vestibuli P(SV) and scala tympani P(ST) and ear-canal sound pressure near the tympanic membrane P(TM). These measurements span the chinchilla's auditory range. G(MEP) had constant magnitude of about 20 dB between 300 Hz and 20 kHz and phase that implies a 40-mu s delay, values with some similarities to previous measurements in chinchilla and other species. Delta P(CP) was similar to G(MEP) below about 10 kHz and lower in magnitude at higher frequencies, decreasing to 0 dB at 20 kHz. The high-frequency rolloff correlates with the audiogram and supports the idea that middle-ear transmission limits high-frequency hearing, providing a stronger link between inner-ear macromechanics and hearing. We estimate the cochlear partition impedance Z(CP). from these and previous data. The chinchilla may be a useful animal model for exploring the effects of non-acoustic inner-ear stimulation such as "bone conduction" on cochlear mechanics. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ravicz, Michael E.; Slama, Michael C. C.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. [Ravicz, Michael E.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Slama, Michael C. C.; Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Mike_Ravicz@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-26] NR 37 TC 15 Z9 15 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 MAY PY 2010 VL 263 IS 1-2 SI SI BP 16 EP 25 DI 10.1016/j.heares.2009.11.014 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700004 PM 19945521 ER PT J AU Voss, SE Adegoke, MF Horton, NJ Sheth, KN Rosand, J Shera, CA AF Voss, Susan E. Adegoke, Modupe F. Horton, Nicholas J. Sheth, Kevin N. Rosand, Jonathan Shera, Christopher A. TI Posture systematically alters ear-canal reflectance and DPOAE properties SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ ID PRODUCT OTOACOUSTIC EMISSIONS; INTRACRANIAL-PRESSURE CHANGES; TYMPANIC MEMBRANE DISPLACEMENT; DISTORTION-PRODUCT; MIDDLE-EAR; IMPEDANCE; BEHAVIOR; ADULTS; REPEATABILITY; TRANSMISSION AB Several studies have demonstrated that the auditory system is sensitive to changes in posture, presumably through changes in intracranial pressure (ICP) that in turn alter the intracochlear pressure, which affects the stiffness of the middle-ear system. This observation has led to efforts to develop an ear-canal based noninvasive diagnostic measure for monitoring ICP, which is currently monitored invasively via access through the skull or spine. Here, we demonstrate the effects of postural changes, and presumably ICP changes, on distortion product otoacoustic emissions (DPOAE) magnitude, DPOAE angle, and power reflectance. Measurements were made on 12 normal-hearing subjects in two postural positions: upright at 90 degrees and tilted at -45 degrees to the horizontal. Measurements on each subject were repeated five times across five separate measurement sessions. All three measures showed significant changes (p < 0.001) between upright and tilted for frequencies between 500 and 2000 Hz, and DPOAE angle changes were significant at all measured frequencies (500-4000 Hz). Intra-subject variability, assessed via standard deviations for each subject's multiple measurements, were generally smaller in the upright position relative to the tilted position. (C) 2010 Elsevier B.V. All rights reserved. C1 [Voss, Susan E.; Adegoke, Modupe F.] Smith Coll, Picker Engn Program, Northampton, MA 01063 USA. [Horton, Nicholas J.] Smith Coll, Dept Math & Stat, Northampton, MA 01063 USA. [Sheth, Kevin N.] Univ Maryland, Sch Med, Dept Neurol, Div Stroke & Neurocrit Care, Baltimore, MD 21201 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA USA. RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA. EM svoss@smith.edu; madegoke@smith.edu; nhorton@smith.edu; kshethmd@gmail.com; rosand@chgr.mgh.harvard.edu; shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC003687, R01 DC003687-12] NR 43 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2010 VL 263 IS 1-2 SI SI BP 43 EP 51 DI 10.1016/j.heares.2010.03.003 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700008 PM 20227475 ER PT J AU Cheng, JT Aarnisalo, AA Harrington, E Hernandez-Montes, MD Furlong, C Merchant, SN Rosowski, JJ AF Cheng, Jeffrey Tao Aarnisalo, Antti A. Harrington, Ellery Hernandez-Montes, Maria del Socorro Furlong, Cosme Merchant, Saumil N. Rosowski, John J. TI Motion of the surface of the human tympanic membrane measured with stroboscopic holography SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Tympanic membrane; Wave motion; Stroboscopic holography; Middle ear mechanics ID TIME-AVERAGED HOLOGRAPHY; MIDDLE-EAR TRANSMISSION; FINITE-ELEMENT METHOD; VIBRATION MEASUREMENT; SOUND-TRANSMISSION; CAT EARDRUM; MODEL; GERBIL; KHZ AB Sound-induced motion of the surface of the human tympanic membrane (TM) was studied by stroboscopic holographic interferometery, which measures the amplitude and phase of the displacement at each of about 40,000 points on the surface of the TM. Measurements were made with tonal stimuli of 0.5, 1, 4 and 8 kHz. The magnitude and phase of the sinusoidal displacement of the TM at each driven frequency were derived from the fundamental Fourier component of the raw displacement data computed from stroboscopic holograms of the TM recorded at eight stimulus phases. The correlation between the Fourier estimates and measured motion data was generally above 0.9 over the entire TM surface. We used three data presentations: (i) plots of the phasic displacements along a single chord across the surface of the TM, (ii) phasic surface maps of the displacement of the entire TM surface, and (iii) plots of the Fourier derived amplitude and phase-angle of the surface displacement along four diameter lines that define and bisect each of the four quadrants of the TM. These displays led to some common conclusions: at 0.5 and 1 kHz, the entire TM moved roughly in-phase with some small phase delay apparent between local areas of maximal displacement in the posterior half of the TM. At 4 and 8 kHz, the motion of the TM became more complicated with multiple local displacement maxima arranged in rings around the manubrium. The displacements at most of these maxima were roughly in-phase, while some moved out-of-phase. Superposed on this in- and out-of-phase behavior were significant cyclic variations in-phase with location of less than 0.2 cycles or occasionally rapid half-cycle step-like changes in-phase. The high frequency displacement amplitude and phase maps discovered in this study can not be explained by any single wave motion, but are consistent with a combination of low and higher order modal motions plus some small traveling-wave-like components. The observations of the dynamics of TM surface motion from this study will help us better understand the sound-receiving function of the TM and how it couples sound to the ossicular chain and inner ear. (C) 2009 Elsevier B.V. All rights reserved. C1 [Cheng, Jeffrey Tao; Aarnisalo, Antti A.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Cheng, Jeffrey Tao; Aarnisalo, Antti A.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Bioscience & Technol Program, Cambridge, MA 02139 USA. [Harrington, Ellery; Hernandez-Montes, Maria del Socorro; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. [Hernandez-Montes, Maria del Socorro; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. RP Cheng, JT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Tao_Cheng@meei.harvard.edu FU NIDCD NIH HHS [F32 DC009949-01, 1F32DC009949-01, F32 DC009949, F32 DC009949-02, R01 DC004798, R01 DC004798-08, R01 DC008642, R01 DC008642-03, R01 DC008642-05, R01-DC008642, R03 DC011617-01, R03 DC011617-02] NR 31 TC 64 Z9 65 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2010 VL 263 IS 1-2 SI SI BP 66 EP 77 DI 10.1016/j.heares.2009.12.024 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700010 PM 20034549 ER PT J AU Aarnisalo, AA Cheng, JT Ravicz, ME Furlong, C Merchant, SN Rosowski, JJ AF Aarnisalo, Antti A. Cheng, Jeffrey T. Ravicz, Michael E. Furlong, Cosme Merchant, Saumil N. Rosowski, John J. TI Motion of the tympanic membrane after cartilage tympanoplasty determined by stroboscopic holography SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Tympanic membrane; Tympanoplasty; Stroboscopic holography ID FINITE-ELEMENT-ANALYSIS; HUMAN EAR; IMPEDANCE; RECONSTRUCTION; MYRINGOPLASTY; TRANSMISSION; OPTIMIZATION; REFLECTANCE; VIBRATION; EARDRUM AB Stroboscopic holography was used to quantify dynamic deformations of the tympanic membrane (TM) of the entire surface of the TM before and after cartilage tympanoplasty of the posterior or posterior-superior part of the TM. Cartilage is widely used in tympanoplasties to provide mechanical stability for the TM. Three human cadaveric temporal bones were used. A 6 mm x 3 mm oval cartilage graft was placed through the widely opened facial recess onto the medial surface of the posterior or posterior-superior part of the TM. The graft was either in contact with the bony tympanic rim and manubrium or not. Graft thickness was either 0.5 or 1.0 mm. Stroboscopic holography produced displacement amplitude and phase maps of the TM surface in response to stimulus sound. Sound stimuli were 0.5, 1, 4 and 7 (or 8) kHz tones. Middle-ear impedance was measured from the motion of the entire TM. Cartilage placement generally produced reductions in the motion of the TM apposed to the cartilage, especially at 4 kHz and 7 or 8 kHz. Some parts of the TM showed altered motion compared to the control in all three cases. In general, middle-ear impedance was either unchanged or increased somewhat after cartilage reconstruction both at low (0.5 and 1 kHz) and high (4 and 7 kHz) frequencies. At 4 kHz, with the 1.0 mm thick graft that was in contact with the bony tympanic rim, the impedance slightly decreased. While our earlier work with time-averaged holography allowed us to observe differences in the pattern of TM motion caused by application of cartilage to the TM, stroboscopic holography is more sensitive to TM motions and allowed us to quantify the magnitude and phase of motion of each point on the TM surface. Nonetheless, our results are similar to those of our earlier work: The placement of cartilage on the medial surface of TM reduces the motion of the TM that apposes the cartilage. These obvious local changes occur even though the cartilage had little effect on the sound-induced motion of the stapes. (C) 2009 Elsevier B.V. All rights reserved. C1 [Aarnisalo, Antti A.; Cheng, Jeffrey T.; Ravicz, Michael E.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Aarnisalo, Antti A.; Cheng, Jeffrey T.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. [Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Aarnisalo, AA (reprint author), Univ Helsinki, Cent Hosp, Dept Otorhinolaryngol, POB 220, Hus Helsinki 00029, Finland. EM antti.aarnisalo@helsinki.fi FU NIDCD NIH HHS [R01 DC004798, R01 DC004798-08, R01 DC008642, R01 DC008642-03, R01 DC008642-05] NR 28 TC 16 Z9 16 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2010 VL 263 IS 1-2 SI SI BP 78 EP 84 DI 10.1016/j.heares.2009.11.005 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700011 PM 19909803 ER PT J AU Qin, ZB Wood, M Rosowski, JJ AF Qin, Zhaobing Wood, Melissa Rosowski, John J. TI Measurement of conductive hearing loss in mice SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Middle-ear pathology; Distortion-product otoacoustic emissions; Auditory brainstem responses; Umbo velocity; Mouse ID PRODUCT OTOACOUSTIC EMISSIONS; MIDDLE-EAR FUNCTION; TYMPANIC-MEMBRANE; THRESHOLD ESTIMATION; COCHLEAR DISORDERS; UMBO VELOCITY; GUINEA-PIGS; TRANSMISSION; DIFFERENTIATION; PERFORATION AB In order to discriminate conductive hearing loss from sensorineural impairment, quantitative measurements were used to evaluate the effect of artificial conductive pathology on distortion-product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs) and laser-Doppler vibrometry (LDV) in mice. The conductive manipulations were created by perforating the pars flaccida of the tympanic membrane, filling or partially filling the middle-ear cavity with saline, fixing the ossicular chain, and interrupting the incudo-stapedial joint. In the saline-filled and ossicular-fixation groups, averaged DPOAE thresholds increased relative to the control state by 20-36 and 25-39 dB, respectively with the largest threshold shifts occurring at frequencies less than 20 kHz, while averaged ABR thresholds increased 12-19 and 12-25 dB, respectively without the predominant low-frequency effect. Both DPOAE and ABR thresholds were elevated by less than 10 dB in the half-filled saline condition; no significant change was observed after pars flaccida perforation. Conductive pathology generally produced a change in DPOAE threshold in dB that was 1.5-2.5 times larger than the ABR threshold change at frequencies less than 30 kHz; the changes in the two thresholds were nearly equal at the highest frequencies. While mild conductive pathology (ABR threshold shifts of <10 dB) produced parallel shifts in DPOAE growth with level functions, manipulations that produced larger conductive hearing losses (ABR threshold shifts >10 dB) were associated with significant deceases in DPOAE growth rate. Our LDV measurements are consistent with others and suggest that measurements of umbo velocity are not an accurate indicator of conductive hearing loss produced by ossicular lesions in mice. (C) 2009 Elsevier B.V. All rights reserved. C1 [Qin, Zhaobing; Wood, Melissa; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Qin, Zhaobing] Zhengzhou Univ, Teaching Hosp 1, Zhengzhou 450052, Henan, Peoples R China. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM john_Rosowski@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000194-20A1, R01 DC000194] NR 46 TC 28 Z9 29 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 MAY PY 2010 VL 263 IS 1-2 SI SI BP 93 EP 103 DI 10.1016/j.heares.2009.10.002 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700013 PM 19835942 ER PT J AU Nakajima, HH Merchant, SN Rosowski, JJ AF Nakajima, Hideko Heidi Merchant, Saumil N. Rosowski, John J. TI Performance considerations of prosthetic actuators for round-window stimulation SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ DE Round window; Middle ear; Cochlea; Scala vestibuli; Scala tympani; Prosthesis ID SOUND PRESSURE MEASUREMENTS; MIDDLE-EAR IMPLANT; VIBRANT SOUNDBRIDGE; COCHLEA; RECONSTRUCTION; OVAL AB Round-window (RW) stimulation has improved speech perception in patients with mixed hearing loss. In cadaveric temporal bones, we recently showed that RW stimulation with an active prosthesis produced differential pressure across the cochlear partition (a measure related to cochlear transduction) similar to normal forward sound stimulation above 1 kHz, when contact area between the prosthesis and RW is secured. However, there is large variability in the hearing improvement in patients implanted with existing modified prosthesis. This is likely because the middle-ear prosthesis used for RW stimulation was designed for a very different application. In this paper, we utilize recently developed experimental techniques that allow for the calculation of performance specifications for a RW actuator. In cadaveric human temporal bones (N = 3), we simultaneously measure scala vestibuli and scala tympani intracochlear pressures, as well as stapes velocity and ear-canal pressure, during normal forward sound stimulation as well as reverse RW stimulation. We then calculate specifications such as the impedance the actuator will need to oppose at the RW, the force with which it must push against the RW, and the velocity and distance by which it must move the RW to obtain cochlear stimulation equivalent to that of specific levels of ear-canal pressure under normal sound stimulation. This information is essential for adapting existing prostheses and for designing new actuators specifically for RW stimulation. (C) 2009 Elsevier B.V. All rights reserved. C1 [Nakajima, Hideko Heidi; Merchant, Saumil N.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Nakajima, Hideko Heidi; Merchant, Saumil N.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Merchant, Saumil N.; Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Bioscience & Technol Program, Cambridge, MA 02139 USA. RP Nakajima, HH (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM heidi_nakajima@meei.harvard.edu; saumil_-merchant@meei.harvard.edu; john_rosowski@meei.harvard.edu FU NIDCD NIH HHS [T32 DC00020, R01 DC004798, T32 DC000020, R01 DC04798, R01 DC004798-09] NR 19 TC 15 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2010 VL 263 IS 1-2 SI SI BP 114 EP 119 DI 10.1016/j.heares.2009.11.009 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700015 PM 19941946 ER PT J AU Merchant, SN Ravicz, ME Chien, W Montgomery, S Warren, M Nadol, JB Rosowski, JJ AF Merchant, Saumil N. Ravicz, Michael E. Chien, Wade Montgomery, Stuart Warren, Michael Nadol, Joseph B., Jr. Rosowski, John J. TI A novel implant for therapy of non-aerated middle ears SO HEARING RESEARCH LA English DT Meeting Abstract CT 5th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO 2009) CY JUN 24-28, 2009 CL Stanford Univ, Stanford, CA HO Stanford Univ C1 [Merchant, Saumil N.; Ravicz, Michael E.; Chien, Wade; Nadol, Joseph B., Jr.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, Boston, MA 02115 USA. [Merchant, Saumil N.; Ravicz, Michael E.; Chien, Wade; Nadol, Joseph B., Jr.; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02139 USA. [Merchant, Saumil N.; Nadol, Joseph B., Jr.; Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. [Montgomery, Stuart; Warren, Michael] Boston Med Prod Inc, Westborough, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2010 VL 263 IS 1-2 SI SI BP 235 EP 236 DI 10.1016/j.heares.2010.03.018 PG 2 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 608KU UT WOS:000278583700039 ER PT J AU Merchant, FM Heist, EK McCarty, D Kumar, P Das, S Blendea, D Ellinor, PT Mela, T Picard, MH Ruskin, JN Singh, JP AF Merchant, Faisal M. Heist, E. Kevin McCarty, David Kumar, Prabhat Das, Saumya Blendea, Dan Ellinor, Patrick T. Mela, Theofanie Picard, Michael H. Ruskin, Jeremy N. Singh, Jagmeet P. TI Impact of segmental left ventricle lead position on cardiac resynchronization therapy outcomes SO HEART RHYTHM LA English DT Article DE Heart failure; Pacemakers; Cardiac resynchronization therapy; Myocardial contraction; Remodeling ID CORONARY VENOUS ANATOMY; CHRONIC HEART-FAILURE; PLACEMENT; PREDICTS; MORTALITY; DISTANCE; DELAY; SITE AB BACKGROUND The optimal pacing site for cardiac resynchronization therapy (CRT) is along the left ventricle (LV) lateral or posterolateral wall. However, little is known about the impact of segmental pacing site on outcomes. OBJECTIVE We assessed the impact of segmental LV lead position on CRT outcomes. METHODS Patients (n = 115) undergoing CRT were followed prospectively. Segmental LV lead position along the longitudinal axis (apical, midventricle, or basal) was determined retrospectively by examining coronary sinus (CS) venograms and chest X-rays. The primary outcome was a combined endpoint of heart failure hospitalization, cardiac transplantation, or all-cause mortality. Secondary outcomes included change in New York Heart Association (NYHA) functional class and degree of LV reverse remodeling. RESULTS Patients were divided into two groups based on LV lead position: apical (n = 25) and basal/midventricle (n = 90). The apical group was older (72.9 +/- 8.9 vs. 66.5 +/- 13.3 years; P = .010) and more likely to have ischemic cardiomyopathy (77% vs. 52%, P < .001). During a mean follow-up of 15.1 +/- 9.0 months, event-free survival was significantly lower in the apical group: 52% vs. 79%, hazard ratio [HR] 2.7 (95% confidence interval [CI] 1.5-5.5, P = .006). The adverse impact of apical lead placement remained significant after adjusting for clinical covariates: HR 2.3 (95% CI 1.1-4.8, P = .03). The apical group also experienced less improvement in NYHA functional class and less LV reverse remodeling. CONCLUSIONS Apical LV lead placement is associated with worse CRT outcomes. Preferential positioning of LV leads in the basal/midventricle segments may improve outcomes. C1 [Singh, Jagmeet P.] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Merchant, Faisal M.; Heist, E. Kevin; McCarty, David; Das, Saumya; Blendea, Dan; Ellinor, Patrick T.; Mela, Theofanie; Picard, Michael H.; Ruskin, Jeremy N.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 FU St. Jude Medical Corp.; Medtronic Inc.; Sorin/ELA; Biotronik; Boston Scientific Corp.; Sorin; Sanofi Aventis FX E. Kevin Heist has received a lecture honorarium, consulting, and research grants from St. Jude Medical Corp., Medtronic Inc., Sorin/ELA, Biotronik, and Boston Scientific Corp., all modest; M. H. Picard has received research support from St. Jude Medical Corp., modest; J.N. Ruskin is a consultant for Medtronic Inc., has received honoraria from St. Jude Medical Corp. and fellowship grant support from Medtronic Inc., St. Jude Medical Corp., and Boston Scientific Corp.; J.P. Singh has received research support from St. Jude Medical Corp., Medtronic Inc., Boston Scientific Corp., and Biotronik, all significant; he is on the advisory board of, has received lecture honoraria from, and is a consultant for Boston Scientific Corp., Biotronik, St. Jude Medical Corp., Medtronic Inc., Sorin, and Sanofi Aventis, all modest. NR 26 TC 53 Z9 55 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2010 VL 7 IS 5 BP 639 EP 644 DI 10.1016/j.hrthm.2010.01.035 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 592DA UT WOS:000277354400013 PM 20298819 ER PT J AU Kuniholm, MH Kovacs, A Gao, XJ Xue, XN Marti, D Thio, CL Peters, MG Terrault, NA Greenblatt, RM Goedert, JJ Cohen, MH Minkoff, H Gange, SJ Anastos, K Fazzari, M Harris, TG Young, MA Strickler, HD Carrington, M AF Kuniholm, Mark H. Kovacs, Andrea Gao, Xiaojiang Xue, Xiaonan Marti, Darlene Thio, Chloe L. Peters, Marion G. Terrault, Norah A. Greenblatt, Ruth M. Goedert, James J. Cohen, Mardge H. Minkoff, Howard Gange, Stephen J. Anastos, Kathryn Fazzari, Melissa Harris, Tiffany G. Young, Mary A. Strickler, Howard D. Carrington, Mary TI Specific Human Leukocyte Antigen Class I and II Alleles Associated with Hepatitis C Virus Viremia SO HEPATOLOGY LA English DT Article ID SPONTANEOUS VIRAL CLEARANCE; INHIBITORY RECEPTOR GENES; INJECTION-DRUG USERS; T-CELL RESPONSES; MHC CLASS-I; RHEUMATOID-ARTHRITIS; HUMAN IMMUNODEFICIENCY; AUTOIMMUNE HEPATITIS; INFECTED PATIENTS; IMMUNE-RESPONSES AB Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed. Conclusion: HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized. (HEPATOLOGY 2010;51: 1514-1522.) C1 [Kuniholm, Mark H.; Xue, Xiaonan; Anastos, Kathryn; Fazzari, Melissa; Harris, Tiffany G.; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Kovacs, Andrea] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Thio, Chloe L.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Peters, Marion G.; Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Cohen, Mardge H.] Cook Cty Bur Hlth Serv, CORE Ctr, Chicago, IL USA. [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. [Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Carrington, Mary] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer Bldg 1308, Bronx, NY 10461 USA. EM mark.kuniholm@einstein.yu.edu OI Gange, Stephen/0000-0001-7842-512X 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, 5R01A1057006-04]; 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 (UCSF-CTSI) [UL1 RR024131]; NCI, NIH [HHSN261200800001E]; NIH, NCI, Center for Cancer Research FX Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); the Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gang). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-A1-35004, 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 also provided by the National Center for Research Resources (UCSF-CTSI Grant number UL1 RR024131). Additional funding for this project was provided by a grant from the National Institute of Allergy and Infectious Diseases (5R01A1057006-04 to H.D.S.). This project was funded in part with federal funds from the NCI, NIH, under Contract No, HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 60 TC 53 Z9 55 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2010 VL 51 IS 5 BP 1514 EP 1522 DI 10.1002/hep.23515 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 590XJ UT WOS:000277261400008 PM 20169624 ER PT J AU Schertler, T Trindade, PT Leschka, S Stolzmann, P Scheffel, H Alkadhi, H AF Schertler, Thomas Trindade, Pedro Trigo Leschka, Sebastian Stolzmann, Paul Scheffel, Hans Alkadhi, Hatem TI Biventricular Noncompaction and Bilateral Outflow Obstruction SO HERZ LA English DT Editorial Material ID MYOCARDIUM C1 [Alkadhi, Hatem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Schertler, Thomas; Leschka, Sebastian; Stolzmann, Paul; Scheffel, Hans; Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost Radiol, Zurich, Switzerland. [Trindade, Pedro Trigo] Univ Zurich Hosp, Ctr Cardiovasc, Zurich, Switzerland. RP Alkadhi, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM halkadhi@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 J9 HERZ JI Herz PD MAY PY 2010 VL 35 IS 3 BP 211 EP 212 DI 10.1007/s00059-010-3303-9 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 596UN UT WOS:000277711100011 PM 20467934 ER PT J AU Langers, DRM AF Langers, Dave R. M. TI Unbiased Group-Level Statistical Assessment of Independent Component Maps by Means of Automated Retrospective Matching SO HUMAN BRAIN MAPPING LA English DT Article DE functional magnetic resonance imaging (fMRI); independent component analysis (ICA); group-level statistics; bias ID FUNCTIONAL MRI DATA; TIME-SERIES; FMRI DATA; BLIND SEPARATION; IMAGING DATA; HUMAN-BRAIN; GROUP ICA; CONNECTIVITY; ALGORITHMS; ACTIVATION AB This report presents and validates a method for the group-level statistical assessment of independent component analysis (ICA) outcomes. The method is based on a matching of individual component maps to corresponding aggregate maps that are obtained from concatenated data. Group-level statistics are derived that include an explicit correction for selection bias. Outcomes were validated by means of calculations with artificial null data. Although statistical inferences were found to be incorrect if bias was neglected, the use of the proposed bias correction sufficed to obtain valid results. This was further confirmed by extensive calculations with artificial data that contained known effects of interest. While uncorrected statistical assessments systematically violated the imposed confidence level thresholds, the corrected method was never observed to exceed the allowed false positive rate. Yet, bias correction was found to result in a reduced sensitivity and a moderate decrease in discriminatory power. The method was also applied to analyze actual fMRI data. Various effects of interest that were detectable in the aggregate data were similarly revealed by the retrospective matching method. In particular, stimulus-related responses were extensive. Nevertheless, differences were observed regarding their spatial distribution. The presented findings indicate that the proposed method is suitable for neuroimaging analyses. Finally, a number of generalizations are discussed. It is concluded that the proposed method provides a framework that may supplement many of the currently available group ICA methods with validated unbiased group inferences. Hunt Brain Mapp 31:727-742, 2010. (C) 2009 Wiley-Liss. Inc. C1 [Langers, Dave R. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol Head & Neck Surg, NL-9713 AV Groningen, Netherlands. [Langers, Dave R. M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Langers, DRM (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Otorhinolaryngol Head & Neck Surg, NL-9713 AV Groningen, Netherlands. EM d.r.m.langers@med.umcg.nl RI Langers, Dave/F-6249-2011 OI Langers, Dave/0000-0002-1053-5645 FU Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw) [016.096.011] FX Contract grant sponsor: Netherlands Organization for Scientific Research (NWO) and Netherlands Organization for Health Research and Development (ZonMw); Contract grant number: 016.096.011 (VENI grant). NR 46 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2010 VL 31 IS 5 BP 727 EP 742 DI 10.1002/hbm.20901 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 593YI UT WOS:000277498800006 PM 19823986 ER PT J AU Taube, R Braun, SE Zhu, Q Wong, FE Murakami, A Kamau, E Dwyer, M Carville, A Johnson, RP Marasco, WA AF Taube, R. Braun, S. E. Zhu, Q. Wong, F. Eng Murakami, A. Kamau, E. Dwyer, M. Carville, A. Johnson, R. P. Marasco, W. A. TI In Vivo Selection of CD4(+) T Cells Transduced with a Gamma-Retroviral Vector Expressing a Single-Chain Intrabody Directed Against HIV-1 Tat SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 7th Annual Conference of the Israeli-Society-of-Gene-and-Cell-Therapy CY MAY 05, 2010 CL Tel Hashomer, ISRAEL SP Israeli Assoc Study Diabetes, Sheba Med Ctr, Israeli Soc Gene & Cell Therapy C1 [Taube, R.] Ben Gurion Univ Negev, Dept Virol & Dev Genet, Beer Sheva, Israel. [Taube, R.] Ben Gurion Univ Negev, NIBN, Beer Sheva, Israel. [Taube, R.; Zhu, Q.; Murakami, A.; Kamau, E.; Dwyer, M.; Marasco, W. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Braun, S. E.; Wong, F. Eng; Carville, A.; Johnson, R. P.] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Johnson, R. P.] Massachusetts Gen Hosp, Partners AIDS Res Unit, Charlestown, MA 02129 USA. [Johnson, R. P.] Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. EM rantaube@bgu.ac.il NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2010 VL 21 IS 5 BP 655 EP 655 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 591EL UT WOS:000277282000049 ER PT J AU Crittenden, JR Dunn, DE Merali, FI Woodman, B Yim, M Borkowska, AE Frosch, MP Bates, GP Housman, DE Lo, DC Graybiel, AM AF Crittenden, Jill R. Dunn, Denise E. Merali, Farhan I. Woodman, Ben Yim, Michael Borkowska, Anna E. Frosch, Matthew P. Bates, Gillian P. Housman, David E. Lo, Donald C. Graybiel, Ann M. TI CalDAG-GEFI down-regulation in the striatum as a neuroprotective change in Huntington's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; GENE-EXPRESSION; TRANSGENIC MICE; MOUSE MODEL; TRANSCRIPTIONAL DYSREGULATION; PROJECTION NEURONS; BASAL GANGLIA; CAIDAG-GEFI; REPEAT; POLYGLUTAMINE AB Huntingtin protein (Htt) is ubiquitously expressed, yet Huntington's disease (HD), a fatal neurologic disorder produced by expansion of an Htt polyglutamine tract, is characterized by neurodegeneration that occurs primarily in the striatum and cerebral cortex. Such discrepancies between sites of expression and pathology occur in multiple neurodegenerative disorders associated with expanded polyglutamine tracts. One possible reason is that disease-modifying factors are tissue-specific. Here, we show that the striatum-enriched protein, CalDAG-GEFI, is severely down-regulated in the striatum of mouse HD models and is down-regulated in HD individuals. In the R6/2 transgenic mouse model of HD, striatal neurons with the largest aggregates of mutant Htt have the lowest levels of CalDAG-GEFI. In a brain-slice explant model of HD, knock-down of CalDAG-GEFI expression rescues striatal neurons from pathology induced by transfection of polyglutamine-expanded Htt exon 1. These findings suggest that the striking down-regulation of CalDAG-GEFI in HD could be a protective mechanism that mitigates Htt-induced degeneration. C1 [Crittenden, Jill R.; Merali, Farhan I.; Yim, Michael; Borkowska, Anna E.; Graybiel, Ann M.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Crittenden, Jill R.; Merali, Farhan I.; Yim, Michael; Borkowska, Anna E.; Graybiel, Ann M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Crittenden, Jill R.; Borkowska, Anna E.; Housman, David E.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Dunn, Denise E.; Lo, Donald C.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. [Dunn, Denise E.; Lo, Donald C.] Duke Univ, Med Ctr, Ctr Drug Discovery, Durham, NC 27710 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Woodman, Ben; Bates, Gillian P.] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. RP Graybiel, AM (reprint author), MIT, McGovern Inst Brain Res, 43 Vassar St,Bldg 46-6133, Cambridge, MA 02139 USA. EM graybiel@mit.edu RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU National Institute of Child Health and Development [R01-HD28341]; James and Pat Poitras Research Fund; National Institutes of Mental Health [F32-MH065815]; Wellcome Trust; Cure Huntington's Disease Initiative, Inc.; Hereditary Disease Foundation; Neuropathology Cores of the Massachusetts Alzheimer Disease Research Center [P50-AG005134]; MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research [P50-NS038372] FX This work was supported by the National Institute of Child Health and Development (R01-HD28341 to A. M. G.); the James and Pat Poitras Research Fund to A. M. G.; the National Institutes of Mental Health (F32-MH065815 to J. R. C.); the Wellcome Trust to G. P. B.; the Cure Huntington's Disease Initiative, Inc. to D. C. L.; the Hereditary Disease Foundation to D. C. L. and D. E. H.; Neuropathology Cores of the Massachusetts Alzheimer Disease Research Center (P50-AG005134 to M. P. F.) and the MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research (P50-NS038372 to M. P. F.). NR 55 TC 13 Z9 13 U1 0 U2 1 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 MAY 1 PY 2010 VL 19 IS 9 BP 1756 EP 1765 DI 10.1093/hmg/ddq055 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 581MF UT WOS:000276526700010 PM 20147317 ER PT J AU Sun, Q Cornelis, MC Kraft, P Qi, L van Dam, RM Girman, CJ Laurie, CC Mirel, DB Gong, HZ Sheu, CC Christiani, DC Hunter, DJ Mantzoros, CS Hu, FB AF Sun, Qi Cornelis, Marilyn C. Kraft, Peter Qi, Lu van Dam, Rob M. Girman, Cynthia J. Laurie, Cathy C. Mirel, Daniel B. Gong, Huizi Sheu, Chau-Chyun Christiani, David C. Hunter, David J. Mantzoros, Christos S. Hu, Frank B. TI Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID INSULIN-RESISTANCE; GENE POLYMORPHISMS; BOUND FRACTION; BODY-WEIGHT; ADIPONECTIN; OBESITY; WOMEN; ADIPOSITY; RISK; HOMEOSTASIS AB Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 x 10(-8)); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 x 10(-9), 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 x 10(-4)). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits. C1 [Sun, Qi; Cornelis, Marilyn C.; Kraft, Peter; Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [van Dam, Rob M.; Christiani, David C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Sheu, Chau-Chyun; Christiani, David C.; Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Qi, Lu; van Dam, Rob M.; Hunter, David J.; Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Mirel, Daniel B.] Harvard Univ, Cambridge, MA 02142 USA. [Girman, Cynthia J.] Merck Res Labs, Dept Epidemiol, N Wales, PA 19454 USA. [Laurie, Cathy C.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Mirel, Daniel B.] MIT, Broad Inst, Ctr Genotyping & Anal, Cambridge, MA 02142 USA. [Gong, Huizi; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Kaohsiung 807, Taiwan. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM fhu@hsph.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU National Human Genome Research Institute [U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG 004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033]; National Institute of Dental & Craniofacial Research) [U01D E018993, U01DE018903]; National Institutes of Health GEI [U01HG04424, U01HG004438]; National Institutes of Health [HHSN268200782096C, RO1 HL71981, DK58785, DK79929, DK81913]; National Cancer Institute [P01CA087969, P01CA055075]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK058845]; Merck Co., Inc.; Cyprus Research Promotion Foundation [EPYE/0205/10]; Boston Obesity Nutrition Research Center [DK46200]; Canadian Institutes of Health; American Heart Association; Beth Israel Deaconess Medical Center FX The NHS type 2 diabetes GWA study (U01HG004399) is a component of a collaborative project that includes 13 other GWA studies (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG 004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728 and RFAHG006033 funded by the National Human Genome Research Institute, as well as U01D E018993 and U01DE018903 funded by the National Institute of Dental & Craniofacial Research) as part of the Gene Environment-Association Studies (GENEVA) under the National Institutes of Health Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of Massachusetts Institute of Technology and Harvard University, with funding support from the National Institutes of Health GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the National Institutes of Health GEI (U01HG004438) and the National Institutes of Health contract 'High throughput genotyping for studying the genetic contributions to human disease' (HHSN268200782096C). Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845), the Merck & Co., Inc. and the Cyprus Research Promotion Foundation (EPYE/0205/10). Q. S. is supported by the Pilot and Feasibility program sponsored by the Boston Obesity Nutrition Research Center (DK46200). M. C. C. is a recipient of a Canadian Institutes of Health Research Fellowship. L. Q. is supported by National Institutes of Health grants RO1 HL71981, American Heart Association Scientist Development Award and the Boston Obesity Nutrition Research Center (DK46200). C. S. M. and the performance of sOB-R assays were supported by National Institutes of Health grants DK58785, DK79929, DK81913, and a discretionary grant from the Beth Israel Deaconess Medical Center. NR 43 TC 25 Z9 27 U1 0 U2 3 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 MAY 1 PY 2010 VL 19 IS 9 BP 1846 EP 1855 DI 10.1093/hmg/ddq056 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 581MF UT WOS:000276526700018 PM 20167575 ER PT J AU Li, CQ Pitsillides, C Runnels, JM Cote, D Lin, CP AF Li, Chunqiang Pitsillides, Costas Runnels, Judith M. Cote, Daniel Lin, Charles P. TI Multiphoton Microscopy of Live Tissues With Ultraviolet Autofluorescence SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE In vivo imaging; multiphoton-excited fluorescence microscopy (MPM); tryptophan autofluorescence; video-rate imaging ID EXCITATION FLUORESCENCE MICROSCOPY; LASER-SCANNING MICROSCOPY; AROMATIC-AMINO-ACIDS; MOUSE SKIN TISSUES; IN-VIVO; 2-PHOTON EXCITATION; 2ND-HARMONIC GENERATION; 3-PHOTON EXCITATION; IMAGING MICROSCOPY; IMMUNE-SYSTEM AB Current research on multiphoton autofluorescence microscopy is primarily focused on imaging the signal from reduced nicotinamide adenine dinucleatide (NADH) in tissue. NADH levels in cells are useful reporters of metabolic information, as well as early indicators in precancer and cancer diagnosis. While NADH is typically imaged in the 400-500 nm spectral window, the amino acid tryptophan is the major source of tissue fluorescence in the Ultraviolet range. Here, we briefly review current progress in multiphoton autofluorescence imaging of live tissues and cells, and report our recent findings of in vivo mouse skin imaging based on multiphoton excited tryptophan autofluorescence. This new method enables noninvasive imaging of skin tissue at video-rate and allows for the visualization and identification of cellular components in the epidermis, dermis, and muscle layers. It is also possible to image through small blood vessels in the mouse skin and observe circulating leukocytes in situ. C1 [Li, Chunqiang; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Adv Microscopy Program, Boston, MA 02114 USA. [Li, Chunqiang; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pitsillides, Costas; Runnels, Judith M.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA. [Pitsillides, Costas] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Runnels, Judith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cote, Daniel] Univ Laval, Ctr Rech Univ Laval Robert Giffard, Dept Phys, Quebec City, PQ G1J 2G3, Canada. RP Li, CQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Adv Microscopy Program, Boston, MA 02114 USA. EM li.chunqiang@mgh.harvard.edu; pitsillides@helix.mgh.harvard.edu; runnels.judith@mgh.harvard.edu; daniel.cote@crulrg.ulaval.ca; lin@helix.mgh.harvard.edu RI Cote, Daniel/D-5185-2011 FU National Institutes of Health [CA111519-01]; Johnson and Johnson, Inc. FX This work was supported in part by the National Institutes of Health under Grant CA111519-01, and in part by Johnson and Johnson, Inc. NR 63 TC 13 Z9 13 U1 2 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAY-JUN PY 2010 VL 16 IS 3 BP 516 EP 523 DI 10.1109/JSTQE.2009.2031619 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 607WN UT WOS:000278538100005 ER PT J AU He, LL Orten, B Do, S Karl, WC Kambadakone, A Sahani, DV Pien, H AF He, Lili Orten, Burkay Do, Synho Karl, W. Clem Kambadakone, Avinish Sahani, Dushyant V. Pien, Homer TI A Spatio-Temporal Deconvolution Method to Improve Perfusion CT Quantification SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Deconvolution; perfusion computed tomography (CT); singular value decomposition; spatial and temporal correlations ID CEREBRAL-BLOOD-FLOW; SINGULAR-VALUE DECOMPOSITION; RESIDUE FUNCTION; CONTRAST MRI; VALIDATION; BRAIN; MODEL; REGULARIZATION; STROKE AB Perfusion imaging is a useful adjunct to anatomic imaging in numerous diagnostic and therapy-monitoring settings. One approach to perfusion imaging is to assume a convolution relationship between a local arterial input function and the tissue enhancement profile of the region of interest via a "residue function" and subsequently solve for this residue function. This ill-posed problem is generally solved using singular-value decomposition based approaches, and the hemodynamic parameters are solved for each voxel independently. In this paper, we present a formulation which incorporates both spatial and temporal correlations, and show through simulations that this new formulation yields higher accuracy and greater robustness with respect to image noise. We also show using rectal cancer tumor images that this new formulation results in better segregation of normal and cancerous voxels. C1 [He, Lili; Do, Synho; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Lab Med Imaging & Computat, Boston, MA 02114 USA. [He, Lili; Do, Synho; Kambadakone, Avinish; Sahani, Dushyant V.; Pien, Homer] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Orten, Burkay] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Karl, W. Clem] Boston Univ, Dept Elect & Comp Engn & Biomed Engn, Boston, MA 02215 USA. RP He, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Lab Med Imaging & Computat, Boston, MA 02114 USA. EM lhe2@partners.org; borten@bu.edu; sdo@partners.org; wckarl@bu.edu; akambadakone@partners.org; dsahani@partners.org; hpien@partners.org FU Center for Integration of Medicine and Innovative Technology (CIMIT); U.S. Army Medical Research; National Science Foundation (NSF) Engineering Research Centers (ERC) FX Manuscript received January 11, 2010; revised February 09, 2010; accepted February 10, 2010. First published April 08, 2010; current version published April 30, 2010. This work was supported in part by grants from the Center for Integration of Medicine and Innovative Technology (CIMIT), U.S. Army Medical Research, and also in part by the National Science Foundation (NSF) Engineering Research Centers (ERC) grant to the Center for Subsurface Sensing and Imaging Systems (CenSSIS). Asterisk indicates corresponding author. NR 35 TC 12 Z9 14 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAY PY 2010 VL 29 IS 5 BP 1182 EP 1191 DI 10.1109/TMI.2010.2043536 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 591WU UT WOS:000277336700007 PM 20378468 ER PT J AU Lieberman, J AF Lieberman, Judy TI Anatomy of a murder: how cytotoxic T cells and NK cells are activated, develop, and eliminate their targets SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material ID GRANZYME-B; APOPTOSIS; DELIVERY C1 [Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave,WAB 255, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 NR 25 TC 18 Z9 19 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2010 VL 235 BP 5 EP 9 PG 5 WC Immunology SC Immunology GA 591FO UT WOS:000277285400001 PM 20536551 ER PT J AU Pipkin, ME Rao, A Lichtenheld, MG AF Pipkin, Matthew E. Rao, Anjana Lichtenheld, Mathias G. TI The transcriptional control of the perforin locus SO IMMUNOLOGICAL REVIEWS LA English DT Review DE natural killer cells; cytotoxic T cells; transcription factors; cell differentiation; perforin; gene regulation ID CD8(+) T-CELLS; PROTEIN GENE-EXPRESSION; NATURAL-KILLER-CELLS; VIRUS-INFECTED MICE; TH2 CYTOKINE LOCUS; IN-VIVO; CYTOLYTIC ACTIVITY; CONTROL REGION; NK CELLS; FUNCTIONAL MATURATION AB Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) use cytotoxic granules containing perforin and granzymes to lyse infected or malignant host cells, thereby providing immunity to intracellular microbes and tumors. Perforin is essential for cytotoxic granule-mediated killing. Perforin expression is regulated transcriptionally and correlates tightly with the development of cells that can exhibit cytotoxic activity. Although a number of genes transcribed by T cells and NK cells have been studied, the cell-specificity of perforin gene expression makes it an ideal model system in which to clarify the transcriptional mechanisms that guide the development and activation of cytotoxic lymphocytes. In this review, we discuss what is known about perforin expression and its regulation, then elaborate on recent studies that utilized chromosome transfer and bacterial artificial chromosome transgenics to define a comprehensive set of cis-regulatory regions that control transcription of the human PRF1 gene in a near-physiologic context. In addition, we compare the human and murine Prf1 loci and discuss how transcription factors known to be important for driving CTL differentiation might also directly regulate the cis-acting domains that control Prf1. Our review emphasizes how studies of PRF1/Prf1 gene transcription can illuminate not only the mechanisms of cytotoxic lymphocyte differentiation but also some basic principles of transcriptional regulation. C1 [Pipkin, Matthew E.] La Jolla Inst Allergy & Immunol, Dept Signaling & Gene Express, La Jolla, CA 92037 USA. [Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rao, Anjana] Immune Dis Inst, Boston, MA USA. [Lichtenheld, Mathias G.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Microbiol & Immunol, Miami, FL 33136 USA. RP Pipkin, ME (reprint author), La Jolla Inst Allergy & Immunol, Dept Signaling & Gene Express, 9420 Athena Circle,Room 2300, La Jolla, CA 92037 USA. EM mpipkin@liai.org FU NIH [AI44432, AI707088]; University of Miami Developmental Center for AIDS Research (D-CFAR) [5P30AI073961-02]; National Cancer Institute [F32CA126247] FX The authors thank Dr Fernando Cruz-Guilloty and members of both the Rao and Lichtenheld laboratories for helpful discussions. This work was funded by NIH grants AI44432 and AI707088 (to A.R.), the University of Miami Developmental Center for AIDS Research (D-CFAR): 5P30AI073961-02 (to M.G.L.), and the National Cancer Institute F32CA126247 (to M.E.P). NR 85 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2010 VL 235 BP 55 EP 72 PG 18 WC Immunology SC Immunology GA 591FO UT WOS:000277285400005 PM 20536555 ER PT J AU Lieberman, J AF Lieberman, Judy TI Granzyme A activates another way to die SO IMMUNOLOGICAL REVIEWS LA English DT Review DE granzyme A; cytotoxic T cell; SET complex; NDUFS3; NM23-H1; TREX1 ID CYTOTOXIC T-LYMPHOCYTES; SECRETORY TRYPSIN-INHIBITOR; SERINE-PROTEASE GRANZYME; CYTOCHROME-C RELEASE; PERFORIN-MEDIATED APOPTOSIS; PAPILLON-LEFEVRE-SYNDROME; PLASMA-MEMBRANE-REPAIR; DNA-BINDING ACTIVITY; B-INDUCED APOPTOSIS; INDUCED CELL-DEATH AB Granzyme A (GzmA) is the most abundant serine protease in killer cell cytotoxic granules. GzmA activates a novel programed cell death pathway that begins in the mitochondrion, where cleavage of NDUFS3 in electron transport complex I disrupts mitochondrial metabolism and generates reactive oxygen species (ROS). ROS drives the endoplasmic reticulum-associated SET complex into the nucleus, where it activates single-stranded DNA damage. GzmA also targets other important nuclear proteins for degradation, including histones, the lamins that maintain the nuclear envelope, and several key DNA damage repair proteins (Ku70, PARP-1). Cells that are resistant to the caspases or GzmB by overexpressing bcl-2 family anti-apoptotic proteins or caspase or GzmB protease inhibitors are sensitive to GzmA. By activating multiple cell death pathways, killer cells provide better protection against a variety of intracellular pathogens and tumors. GzmA also has proinflammatory activity; it activates pro-interleukin-1 beta and may also have other proinflammatory effects that remain to be elucidated. C1 [Lieberman, Judy] Harvard Univ, Childrens Hosp, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Lieberman, J (reprint author), 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIH [AI045587, AI063430] FX I am indebted to the members of my laboratory, past and present, who have worked to unravel the cell death pathway activated by GzmA. This work was supported by NIH grants AI045587 and AI063430. NR 145 TC 51 Z9 51 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2010 VL 235 BP 93 EP 104 PG 12 WC Immunology SC Immunology GA 591FO UT WOS:000277285400007 PM 20536557 ER PT J AU Freeman, GJ Casasnovas, JM Umetsu, DT DeKruyff, RH AF Freeman, Gordon J. Casasnovas, Jose M. Umetsu, Dale T. DeKruyff, Rosemarie H. TI TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity SO IMMUNOLOGICAL REVIEWS LA English DT Review DE TIM; phosphatidylserine; asthma; galectin-9; phagocytosis; costimulation; tolerance ID HEPATITIS-A-VIRUS; KIDNEY INJURY MOLECULE-1; CHINESE HAN POPULATION; T-CELL; APOPTOTIC CELLS; AIRWAY INFLAMMATION; MULTIPLE-SCLEROSIS; ADHESION MOLECULE; MUCIN-DOMAIN; IN-VIVO AB The TIM (T cell/transmembrane, immunoglobulin, and mucin) gene family plays a critical role in regulating immune responses, including allergy, asthma, transplant tolerance, autoimmunity, and the response to viral infections. The unique structure of TIM immunoglobulin variable region domains allows highly specific recognition of phosphatidylserine (PtdSer), exposed on the surface of apoptotic cells. TIM-1, TIM-3, and TIM-4 all recognize PtdSer but differ in expression, suggesting that they have distinct functions in regulating immune responses. TIM-1, an important susceptibility gene for asthma and allergy, is preferentially expressed on T-helper 2 (Th2) cells and functions as a potent costimulatory molecule for T-cell activation. TIM-3 is preferentially expressed on Th1 and Tc1 cells, and generates an inhibitory signal resulting in apoptosis of Th1 and Tc1 cells. TIM-3 is also expressed on some dendritic cells and can mediate phagocytosis of apoptotic cells and cross-presentation of antigen. In contrast, TIM-4 is exclusively expressed on antigen-presenting cells, where it mediates phagocytosis of apoptotic cells and plays an important role in maintaining tolerance. TIM molecules thus provide a functional repertoire for recognition of apoptotic cells, which determines whether apoptotic cell recognition leads to immune activation or tolerance, depending on the TIM molecule engaged and the cell type on which it is expressed. C1 [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Casasnovas, Jose M.] CSIC, Ctr Nacl Biotecnol, Madrid, Spain. [Umetsu, Dale T.; DeKruyff, Rosemarie H.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Umetsu, Dale T.; DeKruyff, Rosemarie H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Immunol, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NIH [P01 AI054456, HL069507]; MICINN [BFU2008-00971] FX This work was supported by NIH P01 AI054456 (to GJF, DTU, RDK), NIH HL069507 (RDK) and MICINN grant BFU2008-00971 (JMC). NR 113 TC 183 Z9 208 U1 5 U2 26 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2010 VL 235 BP 172 EP 189 PG 18 WC Immunology SC Immunology GA 591FO UT WOS:000277285400013 PM 20536563 ER PT J AU Paust, S Senman, B von Andrian, UH AF Paust, Silke Senman, Balimkiz von Andrian, Ulrich H. TI Adaptive immune responses mediated by natural killer cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE natural killer cells; memory; liver ID MURINE CYTOMEGALOVIRUS-INFECTION; IMMUNOGLOBULIN-LIKE RECEPTORS; RESPIRATORY SYNCYTIAL VIRUS; COMPLEX CLASS-I; HUMAN NK CELLS; DENDRITIC CELLS; INFLUENZA INFECTION; T-CELLS; L-SELECTIN; HYPERSENSITIVITY REACTIONS AB Adaptive immunity has traditionally been considered a unique feature of vertebrate physiology. Unlike innate immune responses, which remain essentially unchanged upon exposure to a recurrent challenge with the same stimulus, adaptive immune cells possess the ability to learn and remember. Thus, secondary adaptive responses to a previously encountered challenge are qualitatively and/or quantitatively distinct from those elicited by a primary encounter. Besides this capacity to acquire long-lived memory, the second cardinal feature of adaptive immunity is antigen specificity. It has been generally believed that only T and B cells can develop antigen-specific immunologic memory, because these lymphocytes uniquely express recombination-activating gene (RAG) proteins, which are necessary for somatic rearrangement of V(D)J gene segments to assemble diverse antigen-specific receptors. However, recent work has uncovered discrete subsets of murine natural killer (NK) cells capable of mediating long-lived, antigen-specific recall responses to a variety of hapten-based contact sensitizers. These NK cells appear to use distinct, RAG-independent mechanisms to generate antigen specificity. Murine NK cells have also recently been shown to develop memory upon viral infection. Here, we review recent evidence indicating that at least some NK cells are capable of mediating what appears to be adaptive immunity and discuss potential mechanisms that may contribute to RAG-independent generation of antigenic diversity and longevity. C1 [Paust, Silke; Senman, Balimkiz; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Paust, Silke; Senman, Balimkiz; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU Cancer Research Institute; Ragon Institute; NIH [AI069259, AI072252, AI078897] FX This work was supported, in part, by fellowships from the Cancer Research Institute and the Ragon Institute to S.P. and by NIH grants AI069259, AI072252 and AI078897 to U.H.v.A. NR 86 TC 62 Z9 67 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2010 VL 235 BP 286 EP 296 PG 11 WC Immunology SC Immunology GA 591FO UT WOS:000277285400020 PM 20536570 ER PT J AU Pai, SY Notarangelo, LD AF Pai, Sung-Yun Notarangelo, Luigi D. TI Hematopoietic Cell Transplantation for Wiskott-Aldrich Syndrome: Advances in Biology and Future Directions for Treatment SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article DE Wiskott-Aldrich syndrome; Chimerism; X-linked thrombocytopenia; Hematopoietic cell transplantation; Immunodeficiency ID BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; X-LINKED THROMBOCYTOPENIA; FLOW-CYTOMETRIC ANALYSIS; SINGLE-CENTER EXPERIENCE; SYNDROME PROTEIN WASP; REGULATORY T-CELLS; DENDRITIC CELLS; CONGENITAL NEUTROPENIA AB The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by a triad of diagnostic clinical elements: immunodeficiency, eczema, and hemorrhage caused by thrombocytopenia with small-sized platelets. Hematopoietic cell transplantation (HOT) can cure WAS, and is most often performed using myeloablative conditioning regimens. Our growing understanding of the biology of WASp has revealed cell-type specific functions that impact immune and hematopoietic outcome after HCT. Shortand long-term toxicities associated with HCT remain the main obstacle to safe and effective cure for every patient with WAS. Optimal management strategies for patients with milder forms of the disease (including X-linked thrombocytopenia) remain to be defined. C1 [Notarangelo, Luigi D.] Childrens Hosp, Karp Family Res Labs, Div Immunol, Boston, MA 02115 USA. [Notarangelo, Luigi D.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Pai, Sung-Yun] Childrens Hosp, Karp Family Res Labs, Div Hematol Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Notarangelo, LD (reprint author), Childrens Hosp, Karp Family Res Labs, Div Immunol, 9th Floor,Room 9210,1 Blackfan Circle, Boston, MA 02115 USA. EM Luigi.Notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU Children's Hospital Boston; Manton Foundation; NIHP01-HL-059561-11A1 [P01-HL-059561-11A1] FX Dr Pal receives support from the Translational Investigator Service Award from Children's Hospital Boston. Dr Notarangelo receives support from The Manton Foundation. This work was also supported by NIH grant P01-HL-059561-11A1 (to LDN). NR 85 TC 16 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2010 VL 30 IS 2 BP 179 EP + DI 10.1016/j.iac.2010.02.001 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 615EC UT WOS:000279115200005 PM 20493395 ER PT J AU Chowdhury, F Begum, YA Alam, MM Khan, AI Ahmed, T Bhuiyan, MS Harris, JB LaRocque, RC Faruque, ASG Endtz, H Ryan, ET Cravioto, A Svennerholm, AM Calderwood, SB Qadri, F AF Chowdhury, Fahima Begum, Yasmin A. Alam, Mohammad Murshid Khan, Ashraful I. Ahmed, Tanvir Bhuiyan, M. Saruar Harris, Jason B. LaRocque, Regina C. Faruque, Abu S. G. Endtz, Hubert Ryan, Edward T. Cravioto, Alejandro Svennerholm, Ann-Mari Calderwood, Stephen B. Qadri, Firdausi TI Concomitant Enterotoxigenic Escherichia coli Infection Induces Increased Immune Responses to Vibrio cholerae O1 Antigens in Patients with Cholera in Bangladesh SO INFECTION AND IMMUNITY LA English DT Article ID HEAT-LABILE ENTEROTOXIN; MONOCLONAL-ANTIBODIES; COLONIZATION FACTORS; TRAVELERS DIARRHEA; ENTERIC PATHOGENS; ADJUVANT ACTIVITY; VACCINE STRAIN; BLOOD-GROUP; TOXIN; PREVALENCE AB Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens that cause dehydrating disease requiring hospitalization of children and adults. The cholera toxin (CT) produced by V. cholerae O1 and the heat-labile toxin (LT) and/or heat-stable toxin (ST) of ETEC are responsible for secretory diarrhea. We have observed that about 13% of hospitalized diarrheal patients are concomitantly infected with V. cholerae O1 and ETEC. In order to understand the outcome of such dual infections on the clinical and immunological responses in cholera patients, we studied patients infected with V. cholerae O1 (group VC; n = 25), those infected with both V. cholerae O1 and ETEC (group VCET; n = 25), and those infected with ETEC only (group ET; n = 25). The VCET group showed more severe dehydration and had a higher intake of intravenous fluid and more vomiting than the ETEC group (P = 0.01 to 0.003). The VCET patients showed higher vibriocidal responses and increased antibody titers to cholera toxin and lipopolysaccharide (LPS) in plasma than did the V. cholerae O1 patients (P = 0.02 to < 0.001). All responses in the V. cholerae O1 and in the VCET groups were more robust than those seen in the group infected with ETEC only (P = 0.01 to < 0.001). We thus show that concomitant colonization with ETEC induces immune responses to V. cholerae antigens that are more robust than those seen with V. cholerae O1 infection alone. It is possible that LT or other factors expressed by ETEC may play a role as a mucosal adjuvant in enhancing the immune responses to V. cholerae O1. C1 [Chowdhury, Fahima; Begum, Yasmin A.; Alam, Mohammad Murshid; Khan, Ashraful I.; Ahmed, Tanvir; Bhuiyan, M. Saruar; Faruque, Abu S. G.; Endtz, Hubert; Cravioto, Alejandro; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Jason B.; LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Svennerholm, Ann-Mari] Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Gothenburg, Sweden. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU ICDDR,B [U01 AI058935, RO3 AI063079, U01 AI077883]; Swedish Agency for Research and Economic Cooperation (Sida-SAREC) [B-HN-01-AV]; Fogarty International Center at the National Institutes of Health [D43 TW005572] FX This research was supported by the ICDDR,B; by grants U01 AI058935 (S. B. C.), RO3 AI063079 (F. Q.), and U01 AI077883 (E. T. R.); and by the Swedish Agency for Research and Economic Cooperation (F. Q. and A.-M. S.) (Sida-SAREC; grant INT-ICDDR, B-HN-01-AV). F. C. is a recipient of the Fogarty/Ellison Fellowship in Global Health awarded by the Fogarty International Center at the National Institutes of Health (grant D43 TW005572). NR 51 TC 7 Z9 7 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2010 VL 78 IS 5 BP 2117 EP 2124 DI 10.1128/IAI.01426-09 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 584UL UT WOS:000276778700032 PM 20176796 ER PT J AU Restrepo, MI Anzueto, A Arroliga, AC Afessa, B Atkinson, MJ Ho, NJ Schinner, R Bracken, RL Kollef, MH AF Restrepo, Marcos I. Anzueto, Antonio Arroliga, Alejandro C. Afessa, Bekele Atkinson, Mark J. Ho, Ngoc J. Schinner, Regina Bracken, Ronald L. Kollef, Marin H. TI Economic Burden of Ventilator-Associated Pneumonia Based on Total Resource Utilization SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID EVIDENCE-BASED GUIDELINES; COST; PREVENTION; PROGRAM; PAYMENT; SYSTEM; IMPACT AB OBJECTIVES. To characterize the current economic burden of ventilator-associated pneumonia (VAP) and to determine which services increase the cost of VAP in North American hospitals. DESIGN AND SETTING. We performed a retrospective, matched cohort analysis of mechanically ventilated patients enrolled in the North American Silver-Coated Endotracheal Tube ( NASCENT) study, a prospective, randomized study conducted from 2002 to 2006 in 54 medical centers, including 45 teaching institutions (83.3%). METHODS. Case patients with microbiologically confirmed VAP (n = 30) were identified from 542 study participants with claims data and were matched by use of a primary diagnostic code, and subsequently by the Acute Physiology and Chronic Health Evaluation II score, to control patients without VAP (n = 90). Costs were estimated by applying hospital-specific cost-to-charge ratios based on all-payer inpatient costs associated with VAP diagnosis-related groups. RESULTS. Median total charges per patient were $ 198,200 for case patients and $ 96,540 for matched control patients (P < .001); corresponding median hospital costs were $ 76,730 for case patients and $ 41,250 for control patients (P = .001). After adjusting for diagnosis-related group payments, median losses to hospitals were $ 32,140 for case patients and $ 19,360 for control patients (P = .151). The median duration of intubation was longer for case patients than for control patients (10.1 days vs 4.7 days; P < .001), as were the median duration of intensive care unit stay (18.5 days vs 8.0 days; P < .001) and the median duration of hospitalization (26.5 days vs 14.0 days; P < .001). Examples of services likely to be directly related to VAP and having higher median costs for case patients were hospital care (P < .05) and respiratory therapy (P < .05). CONCLUSIONS. VAP was associated with increased hospital costs, longer duration of hospital stay, and a higher number of hospital services being affected, which underscores the need for bundled measures to prevent VAP. trial registration. NASCENT study ClinicalTrials. gov Identifier: NCT00148642. Infect Control Hosp Epidemiol 2010; 31(5):509-515 C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX USA. [Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Anzueto, Antonio] Univ Hosp, San Antonio, TX USA. [Arroliga, Alejandro C.] Scott & White & Texas A&M Hlth Sci Ctr Coll Med, Temple, TX USA. [Afessa, Bekele] Mayo Clin, Coll Med, Rochester, MN USA. [Atkinson, Mark J.] Univ Calif San Diego, Hlth Serv Res Ctr, San Diego, CA USA. [Ho, Ngoc J.] Kaiser Permanente, Dept Res & Evaluat, Pasadena, CA USA. [Bracken, Ronald L.] CR Bard, Covington, GA USA. [Kollef, Marin H.] Washington Univ, Sch Med, St Louis, MO USA. [Schinner, Regina] FGK Clin Res GmbH, Munich, Germany. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, Dept Med, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 FU Bard FX This study, including the statistical analysis and manuscript preparation, was supported by a research grant from Bard. The Aequitas Group and Hamilton House received compensation from Bard for their contributions. NR 25 TC 40 Z9 44 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 2010 VL 31 IS 5 BP 509 EP 515 DI 10.1086/651669 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 577WR UT WOS:000276255200010 PM 20302428 ER PT J AU Yamamoto-Furusho, JK Barnich, N Hisamatsu, T Podolsky, DK AF Yamamoto-Furusho, Jesus K. Barnich, Nicolas Hisamatsu, Tadakazu Podolsky, Daniel K. TI MDP-NOD2 Stimulation Induces HNP-1 Secretion, Which Contributes to NOD2 Antibacterial Function SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; NOD2; HNP-1; invasive bacteria ID INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; ALPHA-DEFENSIN EXPRESSION; ILEAL CROHNS-DISEASE; ANTIMICROBIAL PEPTIDES; INNATE IMMUNITY; HOST-DEFENSE; LRR PROTEINS; SUSCEPTIBILITY; BOWEL AB Background: Human neutrophil peptide 1 (HNP-1) is a defensin with antibacterial activity secreted by various cells as a component of the innate immune host defense. NOD2 is a cytoplasmic protein that recognizes bacterial derived muramyl dipeptide, and is involved in bacterial clearance. The aim of the present study was to investigate the relationship between antibacterial activity of NOD2 and HNP-1 expression in epithelial cell lines. Methods: Gentamicin protection assay using Salmonella typhimurium was performed in Caco-2 cells. The mRNA level was determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and defensin expression was assessed by Western blot and enzyme-linked immunosorbent assay (ELISA). Nuclear factor-kappa B activation was assessed using pIV luciferase and Renilla plasmids. A NOD2 mutant was generated by site-directed mutagenesis. Results: Among the defensins tested, only HNP-1 expression is induced in colonic epithelial model HCT116 cells after MDP-LD stimulation. HNP-1 secretion is significantly increased after MDP-LD stimulation in the cell supernatant of intestinal epithelial cells expressing endogenous NOD2, but not in cells that lack endogenous NOD2 expression. HNP-1 is required for NOD2-dependent NF-kappa B activation after MDP-LD stimulation since hnp-1 siRNA transfection abrogated the response to MDP-LD stimulation. The antibacterial function of NOD2 against S. typhimurium was impaired when expression of HNP-1 was blocked by siRNA. Conclusions: HNP-1 secretion depends on NOD2 stimulation by MDP-LD and contributes to antibacterial activity in intestinal epithelial cells expressing endogenous NOD2, but not NOD2 3020insC mutant associated with increased susceptibility to Crohn's disease. C1 [Podolsky, Daniel K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Yamamoto-Furusho, Jesus K.; Barnich, Nicolas; Hisamatsu, Tadakazu; Podolsky, Daniel K.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Yamamoto-Furusho, Jesus K.; Barnich, Nicolas; Hisamatsu, Tadakazu; Podolsky, Daniel K.] Harvard Univ, Sch Med, Boston, MA USA. [Yamamoto-Furusho, Jesus K.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Gastroenterol, Inflammatory Bowel Dis Clin, Mexico City, DF, Mexico. [Barnich, Nicolas] Univ Clermont 1, USC INRA 2018, Clermont Ferrand, France. RP Podolsky, DK (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM daniel.podolsky@utsouthwestern.edu FU National Institutes of Health [DK069344, DK43351]; Mexican and American Gastroenterological Associations; Harvard Foundation in Mexico; National Research System, CONACYT; FUNSALUD, Mexico FX Supported by grants from the National Institutes of Health (DK069344 and DK43351). J.K.Y.F. was supported by postdoctoral fellowships from the Mexican and American Gastroenterological Associations (Jon Isenberg International Scholar Award); Harvard Foundation in Mexico (Harvard University Award); National Research System, CONACYT; and the program "Incubacion de talentos" FUNSALUD, Mexico. NR 41 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2010 VL 16 IS 5 BP 736 EP 742 DI 10.1002/ibd.21144 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 592ND UT WOS:000277385200009 PM 19856414 ER PT J AU Gonzalez, M Arroliga, AC Frutos-Vivar, F Raymondos, K Esteban, A Putensen, C Apezteguia, C Hurtado, J Desmery, P Tomicic, V Elizalde, J Abroug, F Arabi, Y Moreno, R Anzueto, A Ferguson, ND AF Gonzalez, Marco Arroliga, Alejandro C. Frutos-Vivar, Fernando Raymondos, Konstantinos Esteban, Andres Putensen, Christian Apezteguia, Carlos Hurtado, Javier Desmery, Pablo Tomicic, Vinko Elizalde, Jose Abroug, Fekri Arabi, Yaseen Moreno, Rui Anzueto, Antonio Ferguson, Niall D. TI Airway pressure release ventilation versus assist-control ventilation: a comparative propensity score and international cohort study SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Airway pressure release ventilation; Assist-control ventilation; Mortality; Epidemiology; Propensity score ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; SUPPORT AB To compare characteristics and clinical outcomes of patients receiving airway pressure release ventilation (APRV) or biphasic positive airway pressure (BIPAP) to assist-control ventilation (A/C) as their primary mode of ventilatory support. The objective was to estimate if patients ventilated with APRV/BIPAP have a lower mortality. Secondary analysis of an observational study in 349 intensive care units from 23 countries. A total of 234 patients were included who were ventilated only with APRV/BIPAP and 1,228 patients who were ventilated only with A/C. A case-matched analysis according to a propensity score was used to make comparisons between groups. In logistic regression analysis, the most important factor associated with the use of APRV/BIPAP was the country (196 of 234 patients were from German units). Patients with coma or congestive heart failure as the reason to start mechanical ventilation, pH < 7.15 prior to mechanical ventilation, and patients who developed respiratory failure (SOFA score > 2) after intubation with or without criteria of acute respiratory distress syndrome were less likely to be ventilated with APRV/BIPAP. In the case-matched analysis there were no differences in outcomes, including mortality in the intensive care unit, days of mechanical ventilation or weaning, rate of reintubation, length of stay in the intensive care unit or hospital, and mortality in the hospital. In this study, the APRV/BIPAP ventilation mode is being used widely across many causes of respiratory failure, but only in selected geographic areas. In our patient population we could not demonstrate any improvement in outcomes with APRV/BIPAP compared with assist-control ventilation. C1 [Frutos-Vivar, Fernando; Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Arroliga, Alejandro C.] Scott & White Mem Hosp & Clin, Temple, TX USA. [Arroliga, Alejandro C.] Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA. [Frutos-Vivar, Fernando; Esteban, Andres] CIBER Enfermedades Resp, Madrid, Spain. [Raymondos, Konstantinos] Hannover Med Sch, D-30623 Hannover, Germany. [Putensen, Christian] Univ Bonn, Dept Anesthesiol & Intens Care Med, D-5300 Bonn, Germany. [Apezteguia, Carlos] Hosp Prof A Posadas, Buenos Aires, DF, Argentina. [Hurtado, Javier] Hosp Clin Montevideo, Montevideo, Uruguay. [Desmery, Pablo] Sanatorio Mitre, Buenos Aires, DF, Argentina. [Tomicic, Vinko] Clin Alemana Santiago, Santiago, Chile. [Elizalde, Jose] Hosp ABC, Mexico City, DF, Mexico. [Abroug, Fekri] Fattouma Bourguiba Monastir, Monastir, Tunisia. [Arabi, Yaseen] King Abdul Aziz Med City, Riyadh, Saudi Arabia. [Moreno, Rui] Hosp Santo Antonio dos Capuchos, Lisbon, Portugal. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ferguson, Niall D.] Univ Toronto, Dept Med, Interdept Div Crit Care Med, Div Respirol,Univ Hlth Network, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Carretera Toledo,Km 12-500, Madrid 28905, Spain. EM aesteban@ucigetafe.com OI Frutos-Vivar, Fernando/0000-0002-4648-9636; Ferguson, Niall/0000-0002-6213-5264 FU Canadian Institutes of Health Research (Ottawa, Canada) FX Dr. Ferguson is supported by a New Investigator Award from the Canadian Institutes of Health Research (Ottawa, Canada). NR 13 TC 27 Z9 30 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAY PY 2010 VL 36 IS 5 BP 817 EP 827 DI 10.1007/s00134-010-1837-1 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 580EE UT WOS:000276429200012 PM 20229042 ER PT J AU Jubran, A Lawm, G Kelly, J Duffner, LA Gungor, G Collins, EG Lanuza, DM Hoffman, LA Tobin, MJ AF Jubran, Amal Lawm, Gerald Kelly, Joanne Duffner, Lisa A. Gungor, Gokay Collins, Eileen G. Lanuza, Dorothy M. Hoffman, Leslie A. Tobin, Martin J. TI Depressive disorders during weaning from prolonged mechanical ventilation SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Weaning; Depressive disorders ID INTENSIVE-CARE-UNIT; QUALITY-OF-LIFE; CRITICALLY-ILL PATIENTS; DELIRIUM SCREENING CHECKLIST; CONTROLLED-TRIAL; TERM; OUTCOMES; ILLNESS; ICU; INTERVENTION AB Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality. Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death. C1 [Jubran, Amal; Gungor, Gokay; Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Jubran, Amal; Gungor, Gokay; Tobin, Martin J.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Lawm, Gerald; Kelly, Joanne; Duffner, Lisa A.] RML Specialty Hosp, Hinsdale, IL USA. [Collins, Eileen G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Collins, Eileen G.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Lanuza, Dorothy M.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Hoffman, Leslie A.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Jubran, A (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM ajubran@lumc.edu; mtobin2@lumc.edu OI Gungor, Gokay/0000-0003-2294-489X FU National Institute of Health [RO1 NR008782]; Veterans Administration Research Service FX This paper was supported by funding from the National Institute of Health (RO1 NR008782) and a Merit Review grant from the Veterans Administration Research Service NR 39 TC 60 Z9 62 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAY PY 2010 VL 36 IS 5 BP 828 EP 835 DI 10.1007/s00134-010-1842-4 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 580EE UT WOS:000276429200013 PM 20232042 ER PT J AU Landeck, L Gonzalez, E Baden, L Neumann, K Schalock, P AF Landeck, Lilla Gonzalez, Ernesto Baden, Lynn Neumann, Konrad Schalock, Peter TI Positive concomitant test reactions to allergens in the standard patch test series SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID DERMATITIS AB Background Patch testing is performed to evaluate suspected allergic contact dermatitis. Common wisdom suggests that various allergens cross-react but only a few larger studies have published confirmations of this. The purpose of our study was to identify significant correlations between positive test reactions in a screening series. Methods A total of 1235 patients undergoing patch testing to the Hermal standard series at the Massachusetts General Hospital, Contact Dermatitis Clinic between 1990 and 2006 were investigated. Results Two or more positive reactions were seen in 411 patients (33.3%). Sensitizations to eight pairs of allergens were found to have significant correlation (P < 0.0001). A strong association was observed for cross reactions between formaldehyde and its releasers quaternium 15 and imidazolidinyl urea and between balsam of Peru and fragrance mix. Moreover, significant co-sensitization was identified for potassium dichromate and colophony. Three significant pairings in our study were associations between fragrances and metals. Our data confirm the previously published cross-reactions in the literature between fragrance components, and formaldehyde and formaldehyde-releasing preservatives. The increased numbers of patients with metal and fragrance sensitization can be considered as a random finding due to independent sensitization. Conclusion Being aware of cross-reacting allergens is essential to success in resolving allergic dermatitis when counseling patients. C1 [Landeck, Lilla; Gonzalez, Ernesto; Schalock, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Baden, Lynn] Ctr Dermatol & Aesthet Med, Newton, MA USA. [Neumann, Konrad] Charite, Dept Biometry & Clin Epidemiol, D-13353 Berlin, Germany. RP Schalock, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, BAR622,55 Fruit St, Boston, MA 02114 USA. EM schalock@gmail.com NR 6 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 2010 VL 49 IS 5 BP 517 EP 519 PG 3 WC Dermatology SC Dermatology GA 586TF UT WOS:000276935400007 PM 20534085 ER PT J AU Kelly, JF Westerhoff, CM AF Kelly, John F. Westerhoff, Cassandra M. TI Does it matter how we refer to individuals with substance-related conditions? A randomized study of two commonly used terms SO INTERNATIONAL JOURNAL OF DRUG POLICY LA English DT Article DE Policy; Substance use disorder; Substance abuser; Terminology; Stigma; Treatment access ID HEPATITIS-C; ALCOHOL; DISCRIMINATION; STIGMATIZATION; DEPENDENCE; ADDICTION; DISEASE; STIGMA AB Objective: Stigma is a frequently cited barrier to help-seeking for many with substance-related conditions. Common ways of describing individuals with such problems may perpetuate or diminish stigmatizing attitudes yet little research exists to inform this debate. We sought to determine whether referring to an individual as "a substance abuser" vs. "having a substance use disorder" evokes different judgments about behavioral self-regulation, social threat, and treatment vs. punishment. Method: A randomized, between-subjects, cross-sectional design was utilized. Participants were asked to read a vignette containing one of the two terms and to rate their agreement with a number of related statements. Clinicians (N = 516) attending two mental health conferences (63% female, 81% white, M age 51; 65% doctoral-level) completed the study (71% response rate). A Likert-scaled questionnaire with three subscales ["perpetrator-punishment" (alpha =.80); "social threat" (alpha = .86); "victim-treatment" (alpha = .64)] assessed the perceived causes of the problem, whether the character was a social threat, able to regulate substance use, and should receive therapeutic vs. punitive action. Results: No differences were detected between groups on the social threat or victim-treatment subscales. However, a difference was detected on the perpetrator-punishment scale. Compared to those in the "substance use disorder" condition, those in the "substance abuser" condition agreed more with the notion that the character was personally culpable and that punitive measures should be taken. Conclusions: Even among highly trained mental health professionals, exposure to these two commonly used terms evokes systematically different judgments. The commonly used "substance abuser" term may perpetuate stigmatizing attitudes. (C) 2009 Elsevier B.V. All rights reserved. C1 [Kelly, John F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, Boston, MA 02114 USA. RP Kelly, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med,Dept Psychiat, 60 Staniford St,Suite 120, Boston, MA 02114 USA. EM jkelly11@partners.org NR 43 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0955-3959 J9 INT J DRUG POLICY JI Int. J. Drug Policy PD MAY PY 2010 VL 21 IS 3 BP 202 EP 207 DI 10.1016/j.drugpo.2009.10.010 PG 6 WC Substance Abuse SC Substance Abuse GA 592NH UT WOS:000277385600011 PM 20005692 ER PT J AU Katon, WJ Russo, JE Heckbert, SR Lin, EHB Ciechanowski, P Ludman, E Young, B Von Korff, M AF Katon, Wayne J. Russo, Joan E. Heckbert, Susan R. Lin, Elizabeth H. B. Ciechanowski, Paul Ludman, Evette Young, Bessie Von Korff, Michael TI The relationship between changes in depression symptoms and changes in health risk behaviors in patients with diabetes SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; behavior; health risk; symptom ID SELF-CARE; CARDIOVASCULAR EVENTS; PHYSICAL-ACTIVITY; OUTCOMES; MORTALITY; ADJUDICATION; POPULATION; ADHERENCE; SMOKING; COHORT AB Background: This longitudinal study of patients with diabetes examined the relationship between changes in depressive symptoms and changes in diabetes self-care behaviors over 5 years. Design, Patients and Measurements: A total of 2759 patients with diabetes enrolled in a large HMO were followed over a 5-year period. Patients filled out a baseline mail survey and participated in a telephone interview 5 years later. Depression was measured with the Patient Health Questionnaire (PHQ-9) and diabetes self-care was measured with the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire. Baseline and longitudinal evidence of diabetes and medical disease severity and complications were measured using ICD-9 and CPT codes and verified by chart review. Results: At the 5-year follow-up, patients with diabetes with either persistent or worsening depressive symptoms compared to those in the no depression group had significantly fewer days per week of following a healthy diet or participating in >= 30 mm of exercise. At 5-year follow-up, patients with clinical improvement in depression symptoms showed no differences compared to the no depression group on number of days per week of adherence to diet but showed deterioration in adherence to exercise on some, but not all, measures. Conclusions: Patients with diabetes with persistent or worsening depressive symptoms over 5 years had significantly worse adherence to dietary and exercise regimens than patients in the no depression group. These results emphasize the need to further develop and test interventions to improve both quality of care for depression and self-care in diabetes patients. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Katon, Wayne J.; Russo, Joan E.; Ciechanowski, Paul] Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. [Heckbert, Susan R.; Lin, Elizabeth H. B.; Ludman, Evette; Von Korff, Michael] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98195 USA. [Young, Bessie] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Young, Bessie] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Katon, WJ (reprint author), Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. EM wkaton@u.washington.edu FU National Institute of Mental Health [K24 MH067587, MH 073686] FX This study was supported by grants from the National Institute of Mental Health to Dr Katon (K24 MH067587) and Dr Von Korff (MH 073686). NR 27 TC 40 Z9 40 U1 2 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAY PY 2010 VL 25 IS 5 BP 466 EP 475 DI 10.1002/gps.2363 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 591XN UT WOS:000277338900005 PM 19711303 ER PT J AU McNamara, P Stavitsky, K Harris, E Szent-Imrey, O Durso, R AF McNamara, Patrick Stavitsky, Karina Harris, Erica Szent-Imrey, Orsolya Durso, Raymon TI Mood, side of motor symptom onset and pain complaints in Parkinson's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE McGill Pain Questionnaire; mood dysfunction; Parkinson's disease; pain ID STRESS SCALES DASS; SENSORY SYMPTOMS; SUBSTANTIA NIGRA; DEPRESSION; ASYMMETRY; SYSTEM AB Objective: Patients with Parkinson's disease (PD) present with a variety of non-motor symptoms including sensory complaints and mood disturbances. In the current pilot study, we aimed to explore pain complaints and the association between mood and pain in PD. We hypothesized that pain ratings would be elevated in patients with PD relative to controls. As PD is lateralized at onset and studies have found lateralization of some non-motor symptoms in PD, we also hypothesized that PD patients would exhibit differing pain profiles depending on side of onset of the disease. Methods: Twenty-three PD patients (11 right-onset (RPD), 12 left-onset (LPD) disease), and 11 control participants (CS) completed a mood questionnaire (Depression Anxiety Stress Scale; DASS) as well as the short form of the McGill Pain Questionnaire. Results: Both PD groups reported higher present pain intensity scores (p = 0.001), more evaluative pain intensity (p = 0.02), and more overall pain (p = 0.02) than control participants. There was a significant association between mood and all of the McGill pain ratings in the LPD patients, with those reporting more mood symptoms rating higher on all pain scales (all p-values < 0.001). This association was not found in the RPD group. Conclusions: Our results suggest an association between mood and pain in patients with PD that may be related to the differential contribution of right-hemispheric neural networks in processing of mood and pain states. These findings merit further investigation into the relation between mood and pain in patients with PD. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [McNamara, Patrick; Harris, Erica; Szent-Imrey, Orsolya; Durso, Raymon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McNamara, Patrick; Harris, Erica; Durso, Raymon] VA Boston Healthcare Syst, Dept Neurol 127, Boston, MA USA. [Stavitsky, Karina] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP McNamara, P (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM mcnamar@bu.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Federal grant [5R01DC007956-03] FX This study is based upon work supported, in part, by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and Federal grant No. 5R01DC007956-03 to the first author. NR 30 TC 20 Z9 20 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAY PY 2010 VL 25 IS 5 BP 519 EP 524 DI 10.1002/gps.2374 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 591XN UT WOS:000277338900012 PM 19711336 ER PT J AU Mitsis, EM Jacobs, D Luo, XD Andrews, H Andrews, K Sano, M AF Mitsis, Effie M. Jacobs, Diane Luo, Xiaodong Andrews, Howard Andrews, Karen Sano, Mary TI Evaluating cognition in an elderly cohort via telephone assessment SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE telephone assessment; aging; cognition ID IMPAIRMENT; VALIDATION; DEMENTIA; BATTERY; POPULATION; DISEASE; MEMORY AB Objective: Longitudinal neuropsychological assessment provides the opportunity to observe the earliest transition to cognitive impairment in healthy, elderly individuals. We examined the feasibility, and its comparability to in-person assessment, of a telephone administered battery of established neuropsychological measures of cognitive functioning in healthy, elderly women. Methods: Fifty-four women (age = 79+/-7.7; education = 15.4+/-3.3) who were in self-reported good health were recruited from senior centers and other community sources. A two-way cross-over design was used in which participants were randomly assigned to receive either (1) in-person neuropsychological assessment followed by telephone assessment and (2) telephone assessment followed by in-person assessment, separated by approximately 4 weeks. Linear regression models were used to determine whether there were performance differences by method (in-person vs. telephone), and equivalence testing assessed comparability of the two methods. Results: There were no statistically significant differences in performance between in-person and telephone assessments on most neuropsychological tests, with the exception of digit span backward, Oral Trail Making Test Part A, and delayed recall on the SRT, the latter likely related to non-comparable exposure (6-trials in-person vs. 3-trials telephone). Equivalence testing differences fell in the pre-specified clinical equivalence zones, providing evidence of comparability of the two methods. Conclusions: These pilot data support telephone administration of a neuropsychological battery that yields comparable performance to in-person assessment with respect to most instruments. Significant differences in scores on some measures suggest care should be taken in selecting specific measures used in a neuropsychological battery administered by telephone. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Mitsis, Effie M.; Luo, Xiaodong; Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Mitsis, Effie M.; Luo, Xiaodong; Sano, Mary] James J Peters VA Med Ctr, Bronx, NY USA. [Andrews, Howard; Andrews, Karen] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Mitsis, EM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Alzheimers Dis Res Ctr, New York, NY 10029 USA. EM effie.mitsis@mssm.edu FU [R01 AG15922] FX The authors wish to thank the directors of the community centers in the New York metropolitan area who provided us with the opportunity to recruit within their midst. This study was supported by R01 AG15922 (Dr. Sano). NR 19 TC 5 Z9 5 U1 0 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAY PY 2010 VL 25 IS 5 BP 531 EP 539 DI 10.1002/gps.2373 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 591XN UT WOS:000277338900014 PM 19697298 ER PT J AU Staats, PN Coutts, MA Young, RH AF Staats, Paul N. Coutts, Michael A. Young, Robert H. TI Primary Ovarian Mucinous Cystic Tumor With Prominent Theca Cell Proliferation and Focal Granulosa Cell Tumor in its Stroma: Case Report, Literature Review, and Comparison With Sertoli-Leydig Cell Tumor With Heterologous Elements SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Review DE Mucinous tumor; Theca cell proliferation; Granulosa cell tumor ID SEX-CORD ELEMENTS; CYSTADENOMA; NEOPLASM; TERATOMA AB A 73-year-old woman was found to have a 22 cm unilateral multilocular mucinous cystic tumor of the ovary. Microscopic examination showed a routine appearance of the epithelial component, which ranged from benign to borderline to low-grade carcinoma. The stromal component was unusual because of a striking cellular theca cell component in the stroma, which, in turn, merged with a component of adult granulosa cell tumor. The "parent'' neoplasm in this case and 3 other similar cases in the literature appears to be the mucinous neoplasm, in contrast with the other example of mucinous neoplasia associated with sex cord neoplasia, the Sertoli-Leydig cell tumor with heterologous elements, in which the "parent'' neoplasm is likely the Sertoli-Leydig cell tumor. C1 [Staats, Paul N.] Univ Maryland, Sch Med, Med Ctr, Dept Pathol, Baltimore, MD 21201 USA. [Coutts, Michael A.] Maidstone & Tunbridge Wells NHS Trust, Dept Cellular Pathol, Maidstone, Kent, England. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Staats, PN (reprint author), Univ Maryland, Sch Med, Med Ctr, Dept Pathol, 22 S Greene St, Baltimore, MD 21201 USA. EM pstaats@umm.edu NR 18 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAY PY 2010 VL 29 IS 3 BP 228 EP 233 DI 10.1097/PGP.0b013e3181c04007 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 586KO UT WOS:000276907300003 PM 20407320 ER PT J AU Imai, Y Shimaoka, M Kurokawa, M AF Imai, Yoichi Shimaoka, Motomu Kurokawa, Mineo TI Essential roles of VLA-4 in the hematopoietic system SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Review DE Integrin; VLA-4; Hematopoiesis; Chemotherapy sensitivity; Mobilization ID ACUTE MYELOID-LEUKEMIA; HUMAN BONE-MARROW; CELL-ADHESION; PROGENITOR CELLS; STEM/PROGENITOR CELLS; ALPHA(4) INTEGRINS; CD34(+) CELLS; FETAL LIVER; STEM-CELLS; EXPRESSION AB Integrins are one of the major families of adhesion molecules and make various kinds of biological effects by mediating cell-cell and cell-matrix interactions. Among integrins, VLA-4 is expressed on many types of hematopoietic cells including stem/progenitor cells and it is considered as a critical regulator of adult hematopoiesis. Recent studies revealed that VLA-4 is not necessarily required for the development or maintenance of adult hematopoietic cells. On the other hand, it was proved that VLA-4 is essential for homeostasis of distribution of hematopoietic stem/progenitor cells (HSPCs) and mature lymphocytes in the body. The dynamic regulation of VLA-4 function is mediated by its conformational change, which is strictly linked to the interaction between alpha and beta cytoplasmic domains. The study using knockin mice showed that GFFKR sequence, a well-preserved motif in the alpha cytoplasmic domain of VLA-4, is critical for binding of alpha and beta cytoplasmic domains as well as regulation of hematopoietic cell distribution. Small molecules targeting this cytoplasmic interaction or ligand-VLA-4 interaction may become good candidates of new drugs for mobilization of hematopoietic stem cells. Several studies have suggested the impact of VLA-4 on chemotherapy sensitivity and prognosis in hematological malignancies, which awaits further investigations. C1 [Imai, Yoichi; Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan. [Shimaoka, Motomu] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. RP Kurokawa, M (reprint author), Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kurokawa-tky@umin.ac.jp NR 38 TC 17 Z9 17 U1 0 U2 7 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD MAY PY 2010 VL 91 IS 4 BP 569 EP 575 DI 10.1007/s12185-010-0555-3 PG 7 WC Hematology SC Hematology GA 593OS UT WOS:000277469000002 PM 20352381 ER PT J AU Osawa, R Singh, N AF Osawa, Ryosuke Singh, Nina TI Colitis as a manifestation of infliximab-associated disseminated cryptococcosis SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Cryptococcosis; Cryptococcus; Gastrointestinal diseases; Crohn's disease; Tumor necrosis factor-alpha inhibitors ID TUMOR-NECROSIS-FACTOR; ORGAN TRANSPLANT RECIPIENTS; INFECTION JOBS SYNDROME; HIV-NEGATIVE PATIENT; IMMUNE RECONSTITUTION; GASTROINTESTINAL CRYPTOCOCCOSIS; ESOPHAGEAL CRYPTOCOCCOSIS; ANTIRETROVIRAL THERAPY; RHEUMATOID-ARTHRITIS; NEOFORMANS INFECTION AB The ability of tumor necrosis factor (TNF)-alpha inhibitors to impair pivotal pro-inflammatory host defenses may facilitate the development of disseminated cryptococcosis. Gastrointestinal (GI) tract disease is an unusual presentation of this yeast infection. We describe a unique case of disseminated cryptococcosis presenting as colitis that mimicked an exacerbation of Crohn's disease in a TNF-alpha inhibitor recipient. Review of existing literature shows that in immunocompromised patients, GI cryptococcosis invariably coexists with disseminated cryptococcosis, often lacks prominent GI symptomatology, and is primarily diagnosed postmortem. In cases with opportunistic infections, discontinuation of TNF-alpha inhibitors is a common practice, however rapid rebound of inflammatory responses may incur the risk of immune reconstitution syndrome. (C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Singh, Nina] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA 15240 USA. RP Singh, N (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu FU Pfizer; Schering-Plough; Enzon Inc. FX Conflict of interest: Dr Singh has received research support from Pfizer, Schering-Plough, and Enzon Inc. Dr Osawa has no interests to declare. There was no source of support for this study. NR 52 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD MAY PY 2010 VL 14 IS 5 BP E436 EP E440 DI 10.1016/j.ijid.2009.05.019 PG 5 WC Infectious Diseases SC Infectious Diseases GA 587IG UT WOS:000276983400015 PM 19660974 ER PT J AU Ernst, C Morton, CC Gusella, JF AF Ernst, Carl Morton, Cynthia C. Gusella, James F. TI Self-injurious behaviours in people with and without intellectual delay: implications for the genetics of suicide SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Genetics; suicide; self-injury ID PREVALENCE AB Self-injurious behaviours (SIBs) occur in both people at risk of suicide and in people with intellectual delay, and it may be that the underlying pathologies are shared, at least in part. Genes identified as causative in people with intellectual delay that show SIBs may be the same genes that have an effect on suicide outcome in people without intellectual delay that self-injure. C1 [Ernst, Carl; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Morton, Cynthia C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ernst, C (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM ernst@chgr.mgh.harvard.edu FU Canadian Institute for Health Research FX C.E. is funded by a Canadian Institute for Health Research fellowship. NR 5 TC 2 Z9 2 U1 0 U2 4 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 MAY PY 2010 VL 13 IS 4 BP 527 EP 528 DI 10.1017/S1461145709990885 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604KU UT WOS:000278278700011 PM 19887018 ER PT J AU Haymond, M Anderson, B Bush, C Gunn, S Holden, H Jones, M Hwu, K McGirk, S Mckay, S Thamotharan, S Schreiner, B Zarate, M Cuttler, L Abrams, E Casey, T Dahms, W Drotar, D Huestis, S Ievers-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 Johnson, B 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 Hall, M 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 Floreen, A Kociela, V Whelan, T Wolff, B Weinstock, R Bowerman, D Bulger, J Duncan, K Franklin, R Hartsig, J Izquierdo, R Kanaley, J Kearns, J Meyer, S Saletsky, R Trief, P Zeitler, P Abramson, N Bradhurst, A Celona-Jacobs, N Glazner, J Higgins, J Hoe, F Klingensmith, G Nadeau, K Strike, H 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 Ibarra, C Lynch, J Morales, E Rivera, S Rupert, G Wauters, A White, N Arbelaez, A Jones, J Jones, T Sadler, M Tanner, M Timpson, A Welch, R Caprio, S Grey, M Guandalini, C Lavietes, S Mignosa, M 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 Wilfley, D Aldrich-Rasche, D Franklin, K Leibach, G Massmann, C Mills, M O'Brien, D Patterson, J Tibbs, T Van Buren, D Zhang, P Palmert, M Epstein, L Silverstein, J AF Haymond, M. Anderson, B. Bush, C. Gunn, S. Holden, H. Jones, M. Hwu, K. McGirk, S. McKay, S. Thamotharan, S. Schreiner, B. Zarate, M. Cuttler, L. Abrams, E. Casey, T. Dahms, W. Drotar, D. Huestis, S. Ievers-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. Johnson, B. 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. Hall, M. 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. Floreen, A. Kociela, V. Whelan, T. Wolff, B. Weinstock, R. Bowerman, D. Bulger, J. Duncan, K. Franklin, R. Hartsig, J. Izquierdo, R. Kanaley, J. Kearns, J. Meyer, S. Saletsky, R. Trief, P. Zeitler, P. Abramson, N. Bradhurst, A. Celona-Jacobs, N. Glazner, J. Higgins, J. Hoe, F. Klingensmith, G. Nadeau, K. Strike, H. 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. Ibarra, C. Lynch, J. Morales, E. Rivera, S. Rupert, G. Wauters, A. White, N. Arbelaez, A. Jones, J. Jones, T. Sadler, M. Tanner, M. Timpson, A. Welch, R. Caprio, S. Grey, M. Guandalini, C. Lavietes, S. Mignosa, M. 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. Wilfley, D. Aldrich-Rasche, D. Franklin, K. Leibach, G. Massmann, C. Mills, M. 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 (vol 34, pg 946, 2010) SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Correction C1 [Haymond, M.; Anderson, B.; Bush, C.; Gunn, S.; Holden, H.; Jones, M.; Hwu, K.; McGirk, S.; McKay, S.; Thamotharan, S.; Schreiner, B.; Zarate, M.] Baylor Coll Med, Houston, TX 77030 USA. [Cuttler, L.; Abrams, E.; Casey, T.; Dahms, W.; Drotar, D.; Huestis, S.; Ievers-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.; Johnson, B.; 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.; Floreen, A.; Kociela, V.; Whelan, T.; Wolff, B.] St Louis Univ, St Louis, MO 63103 USA. [Weinstock, R.; Bowerman, D.; Bulger, J.; 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.; Celona-Jacobs, N.; Glazner, J.; Higgins, J.; Hoe, F.; Klingensmith, G.; Nadeau, K.; Strike, H.; 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.; Ibarra, C.; Lynch, J.; Morales, E.; Rivera, S.; Rupert, G.; Wauters, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [White, N.; Arbelaez, A.; Jones, J.; Jones, T.; Sadler, M.; Tanner, M.; Timpson, A.; Welch, R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Caprio, S.; Grey, M.; Guandalini, C.; Lavietes, S.; Mignosa, M.; 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.] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. [Linder, B.] NIDDK, Bethesda, MD 20892 USA. [Marcovina, S.; Chmielewski, J.; Ramirez, M.; Strylewicz, G.] Washington Univ, NW Lipid Res Labs, Cent Blood Lab, St Louis, MO 63130 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.; Aldrich-Rasche, D.; Franklin, K.; Leibach, G.; Massmann, C.; Mills, M.; O'Brien, D.; Patterson, J.; Tibbs, T.; Van Buren, D.] Washington Univ, Lifestyle Program Core, St Louis, MO 63130 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. [Zhang, P.] CDC, Atlanta, GA 30333 USA. RP Haymond, M (reprint author), Baylor Coll Med, Houston, TX 77030 USA. NR 1 TC 1 Z9 1 U1 1 U2 4 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 MAY PY 2010 VL 34 IS 5 BP 946 EP 946 DI 10.1038/ijo.2009.247 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 593EP UT WOS:000277435700020 ER PT J AU Vaid, M Katiyar, SK AF Vaid, Mudit Katiyar, Santosh K. TI Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE antioxidant; oxidative stress; inflammation; silymarin; photocarcinogenesis; interleukins; ultraviolet radiation; contact hypersensitivity ID TEA POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE; RANDOMIZED CONTROLLED-TRIAL; INDUCED OXIDATIVE STRESS; NONMELANOMA SKIN-CANCER; ULTRAVIOLET-RADIATION; CONTACT HYPERSENSITIVITY; MOUSE SKIN; IMMUNE SUPPRESSION; DNA-REPAIR; IN-VIVO AB Changes in life style over the past several decades including much of the time spent outdoors and the use of tanning devices for cosmetic purposes by individuals have led to an increase in the incidence of solar ultraviolet (UV) radiation-induced skin diseases including the risk of skin cancers. Solar UV radiations are considered as the most prevalent environmental carcinogens, and chronic exposure of the skin to UV leads to squamous and basal cell carcinoma and melanoma in human population A wide variety of phytochemicals have been reported to have substantial anti-carcinogenic activity because of their antioxidant and anti-inflammatory properties Silymarin is one of them and extensively studied for its skin photoprotective capabilities. Silymarin. a flavanolignan, is extracted from the fruits and seeds of milk thistle (Silybum marianum L Gaertn), and has been shown to have chemopreventive effects against photocarcinogenesis in mouse tumor models. Topical treatment of silymarin inhibited photocarcinogenesis in mice in terms of tumor incidence, tumor multiplicity and growth of the tumors Wide range of in vivo mechanistic studies conducted in a variety of mouse models indicated that silymarin has anti-oxidant, anti-inflammatory and immunomodulatory properties which led to the prevention of photocarcinogenesis in mice. This review summarizes and updates the photo protective potential of silymarin with the particular emphasis on its in vivo mechanism of actions It is suggested that silymarin may favorably supplement sunscreen protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and immunomodulatory effects. C1 [Vaid, Mudit; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. 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 USPHS [CA 105368]; Veterans Administration Merit Review Award FX The original work reported from Dr Katiyar's laboratory was supported from the funds from USPHS Grant, CA 105368 (S.K.K.) and Veterans Administration Merit Review Award (S.K.K.). NR 91 TC 31 Z9 31 U1 5 U2 18 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 MAY PY 2010 VL 36 IS 5 BP 1053 EP 1060 DI 10.3892/ijo_00000586 PG 8 WC Oncology SC Oncology GA 589EQ UT WOS:000277129600002 PM 20372777 ER PT J AU Friedlander, AH AF Friedlander, Arthur H. TI Amoxicillin prophylaxis is not associated with anaphylaxis SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Letter ID ENDOCARDITIS C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Ronald Reagan Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD MAY PY 2010 VL 39 IS 5 BP 520 EP 520 DI 10.1016/j.ijom.2010.01.020 PG 1 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 608LA UT WOS:000278584400022 PM 20189771 ER PT J AU McGowan, DG Hunt, D Jones, CU Amin, M Leibenhaut, MH Husian, SM Rotman, M Souhami, L Sandler, H Shipley, WU AF McGowan, D. G. Hunt, D. Jones, C. U. Amin, M. Leibenhaut, M. H. Husian, S. M. Rotman, M. Souhami, L. Sandler, H. Shipley, W. U. TI Short-term Endocrine Therapy Prior to and during Radiation Therapy Improves Overall Survival in Patients with T1b-T2b Adenocarcinoma of the Prostate and PSA <= 20: Initial Results of RTOG 94-08 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY OCT 31-NOV 05, 2009 CL Chicago, IL SP Amer Soc Therapeut Radiol & Oncol C1 [McGowan, D. G.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Hunt, D.] Amer Coll Radiol, Philadelphia, PA USA. [Jones, C. U.; Leibenhaut, M. H.] Radiol Associates Sacramento, Sacramento, CA USA. [Amin, M.; Sandler, H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Husian, S. M.] Tom Baker Canc Clin, Calgary, AB, Canada. [Rotman, M.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Souhami, L.] McGill Univ, Montreal, PQ, Canada. [Shipley, W. U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 9 Z9 10 U1 0 U2 1 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 MAY 1 PY 2010 VL 77 IS 1 MA LB1 BP 1 EP 1 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 588XC UT WOS:000277106900002 ER PT J AU Nanda, A Chen, MH Moran, BJ Braccioforte, MH Dosoretz, D Salenius, S Katin, M Ross, R D'Amico, AV AF Nanda, Akash Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel Salenius, Sharon Katin, Michael Ross, Rudi D'Amico, Anthony V. TI PREDICTORS OF PROSTATE CANCER SPECIFIC MORTALITY IN ELDERLY MEN WITH INTERMEDIATE-RISK PROSTATE CANCER TREATED WITH BRACHYTHERAPY WITH OR WITHOUT EXTERNAL BEAM RADIATION THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostate cancer; Prostate cancer-specific mortality; Radiation therapy; Prognostic factors; Cardiovascular disease ID DOSE-RATE BRACHYTHERAPY; PHASE-II; ANDROGEN SUPPRESSION; COMPETING RISK; RADIOTHERAPY; MONOTHERAPY; EXPERIENCE; TOXICITY; SURVIVAL; DISEASE AB Purpose: To identify clinical factors associated with prostate cancer specific mortality (PCSM), adjusting for comorbidity, in elderly men with intermediate-risk prostate cancer treated with brachytherapy alone or in conjunction with external beam radiation therapy. Methods and Materials: The study cohort comprised 1,978 men of median age 71 (interquartile range, 66-75) years with intermediate-risk disease (Gleason score 7, prostate-specific antigen (PSA) 20 ng/ml or less, tumor category T2c or less). Fine and Gray's multivariable competing risks regression was used to assess whether prevalent cardiovascular disease (CVD), age, treatment, year of brachytherapy, PSA level, or tumor category was associated with the risk of PCSM. Results: After a median follow-up of 3.2 (interquartile range, 1.7-5.4) years, the presence of CVD was significantly associated with a decreased risk of PCSM (adjusted hazard ratio, 0.20; 95% CI 0.04-0.99; p = 0.05), whereas an increasing PSA level was significantly associated with an increased risk of PCSM (adjusted hazard ratio 1.14; 95% CI 1.02-1.27; p = 0.02). In the absence of CVD, cumulative incidence estimates of PCSM were higher (p = 0.03) in men with PSA levels above as compared with the median PSA level (7.3 ng/mL) or less; however, in the setting of CVD there was no difference (p = 0.27) in these estimates stratified by the median PSA level (6.9 ng/mL). Conclusions: In elderly men with intermediate-risk prostate cancer, CVD status is a negative predictor of PCSM and affects the prognostic capacity of pretreatment PSA level. These observations support the potential utility of prerandomization stratification by comorbidity to more accurately assess prognostic factors and treatment effects within this population. (C) 2010 Elsevier Inc. C1 [Nanda, Akash] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP Nanda, A (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dana Farber Canc Inst, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM ananda@partners.org NR 33 TC 4 Z9 4 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 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2010 VL 77 IS 1 BP 147 EP 152 DI 10.1016/j.ijrobp.2009.04.085 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 588XC UT WOS:000277106900025 PM 19744800 ER PT J AU Wo, JY Taghian, AG Nguyen, PL Raad, RA Sreedhara, M Bellon, JR Wong, JS Gadd, MA Smith, BL Harris, JR AF Wo, Jennifer Y. Taghian, Alphonse G. Nguyen, Paul L. Raad, Rita Abi Sreedhara, Meera Bellon, Jennifer R. Wong, Julia S. Gadd, Michele A. Smith, Barbara L. Harris, Jay R. TI THE ASSOCIATION BETWEEN BIOLOGICAL SUBTYPE AND ISOLATED REGIONAL NODAL FAILURE AFTER BREAST-CONSERVING THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast cancer; Biological subtype; Regional nodal failure ID CANCER-COOPERATIVE-GROUP; ESTROGEN-RECEPTOR; ADJUVANT CHEMOTHERAPY; CONSERVATIVE SURGERY; POSTOPERATIVE RADIOTHERAPY; PROGESTERONE-RECEPTOR; PREMENOPAUSAL WOMEN; MOLECULAR PORTRAITS; RANDOMIZED-TRIAL; TUMOR SUBTYPES AB Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status, progesterone receptor status, and HER-2 status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients. (C) 2010 Elsevier Inc. C1 [Sreedhara, Meera; Bellon, Jennifer R.; Wong, Julia S.; Harris, Jay R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wo, Jennifer Y.; Nguyen, Paul L.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Taghian, Alphonse G.; Raad, Rita Abi; Gadd, Michele A.; Smith, Barbara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Harris, JR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jharris@lroc.harvard.edu NR 38 TC 25 Z9 31 U1 0 U2 1 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 MAY 1 PY 2010 VL 77 IS 1 BP 188 EP 196 DI 10.1016/j.ijrobp.2009.04.059 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 588XC UT WOS:000277106900031 PM 20171798 ER PT J AU Morina, N Rudari, V Bleichhardt, G Prigerson, HG AF Morina, Nexhmedin Rudari, Visar Bleichhardt, Gaby Prigerson, Holly G. TI PROLONGED GRIEF DISORDER, DEPRESSION, AND POSTTRAUMATIC STRESS DISORDER AMONG BEREAVED KOSOVAR CIVILIAN WAR SURVIVORS: A PRELIMINARY INVESTIGATION SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY LA English DT Article DE bereavement; civilian war survivors; depression; post-traumatic stress disorder; prolonged grief disorder ID COMPLICATED GRIEF; TRAUMATIC GRIEF; RISK; VALIDATION; REFUGEES; DISTINCT; ANXIETY; TORTURE AB Background: This study aimed at examining diagnostic concordance between Prolonged Grief Disorder (PGD), Major Depressive Disorder (MDD), and Posttraumatic Stress Disorder (PTSD) among bereaved war survivors who had lost relatives due to war-related violence. Method: We investigated the rates of PGD and its association with PTSD and MDD among 60 bereaved people who had lost first-degree relatives due to war-related violence seven years ago and had also experienced other war-related events. Results: The results indicated that 38.3% of the sample fulfilled the criteria for PGD, 55.0% for PTSD, and 38.3% for MDD. Thirty per cent of the participants without PTSD and 21.6% of those without MDD met criteria for PGD. Women were more likely to have PGD than men. The immediate threat to life was significantly associated with an elevated risk for PTSD and MDD, but not PGD. Conclusion: The findings suggest that many cases of PGD would be missed by an exclusive focus on PTSD among bereaved war survivors. C1 [Morina, Nexhmedin] Goethe Univ Frankfurt, Dept Psychol, D-60486 Frankfurt, Germany. [Rudari, Visar] Johannes Gutenberg Univ Mainz, Dept Psychol, D-6500 Mainz, Germany. [Bleichhardt, Gaby] Univ Marburg, Dept Psychol, D-35032 Marburg, Germany. [Prigerson, Holly G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Morina, N (reprint author), Goethe Univ Frankfurt, Dept Psychol, Varrentrappstr 40-42, D-60486 Frankfurt, Germany. EM n.morina@uva.nl RI Morina, Nexhmedin/D-4976-2012 OI Morina, Nexhmedin/0000-0002-2331-9140 NR 26 TC 36 Z9 38 U1 3 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7640 J9 INT J SOC PSYCHIATR JI Int. J. Soc. Psychiatr. PD MAY PY 2010 VL 56 IS 3 BP 288 EP 297 DI 10.1177/0020764008101638 PG 10 WC Psychiatry SC Psychiatry GA 591QE UT WOS:000277316000009 PM 19592437 ER PT J AU Tong, J Liu, CX Summanen, PH Xu, HX Finegold, SM AF Tong, Jia Liu, Chengxu Summanen, Paula H. Xu, Huaxi Finegold, Sydney M. TI Corynebacterium pyruviciproducens sp nov., a pyruvic acid producer SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DEOXYRIBONUCLEIC-ACID; CORYNEFORM BACTERIA; CLINICAL MATERIAL; IDENTIFICATION; SEQUENCE; STRAINS; INFECTIONS; GENE; HYBRIDIZATION AB A coryneform strain, 06-1773O(T) (=WAL 19168(T)), derived from a groin abscess sample was characterized using phenotypic and molecular taxonomic methods. Comparative analyses revealed more than 3% divergence of the 16S rRNA gene sequence and about 10% divergence of the partial rpoB gene sequence from the type strain of Corynebacterium glucuronolyticum. The strain could also be differentiated from C. glucuronolyticum by a set of phenotypic properties. A DNA-DNA relatedness study between strain WAL 19168(T) and C. glucuronolyticum CCUG 35055(T) showed a relatedness value of 13.3% (13.7% on repeat analysis). The genotypic and phenotypic data show that the strain merits classification within a novel species of Corynebacterium. We propose the name Corynebacterium pyruviciproducens sp. nov. for the novel species. The type strain is 06-1773O(T) (=WAL 19168(T) =CCUG 57046(T) =ATCC BAA-1742(T)). C1 [Tong, Jia; Finegold, Sydney M.] Univ Calif Los Angeles, Dept Med, Los Angeles Sch Med, Los Angeles, CA 90024 USA. [Tong, Jia; Liu, Chengxu; Summanen, Paula H.] W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. [Tong, Jia; Xu, Huaxi] Jiangsu Univ, Sch Food Sci & Engn, Zhenjiang, Peoples R China. [Tong, Jia; Xu, Huaxi] Jiangsu Univ, Sch Med Technol, Zhenjiang, Peoples R China. [Finegold, Sydney M.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles Sch Med, Los Angeles, CA USA. [Finegold, Sydney M.] W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. RP Finegold, SM (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles Sch Med, Los Angeles, CA 90024 USA. EM sidfinegol@aol.com FU DOD [W81XWH-0510134]; VA FX This work has been supported in part by DOD grant # W81XWH-0510134 and VA Merit Review funds. NR 30 TC 6 Z9 8 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAY PY 2010 VL 60 BP 1135 EP 1140 DI 10.1099/ijs.0.011783-0 PN 5 PG 6 WC Microbiology SC Microbiology GA 603UK UT WOS:000278233400022 PM 19666798 ER PT J AU Dastjerdi, MH Saban, DR Okanobo, A Nallasamy, N Sadrai, Z Chauhan, SK Hajrasouliha, AR Dana, R AF Dastjerdi, Mohammad H. Saban, Daniel R. Okanobo, Andre Nallasamy, Nambi Sadrai, Zahra Chauhan, Sunil K. Hajrasouliha, Amir R. Dana, Reza TI Effects of Topical and Subconjunctival Bevacizumab in High-Risk Corneal Transplant Survival SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GRAFT-SURVIVAL; ALLOGRAFT-REJECTION; INFLAMMATORY NEOVASCULARIZATION; VEGF-A; LYMPHANGIOGENESIS; ANGIOGENESIS; INHIBITION; HEMANGIOGENESIS; MORPHOMETRY AB PURPOSE. To investigate whether corneal graft survival could be improved by topical or subconjunctival bevacizumab in a murine model of vascularized high-risk corneal transplantation. METHODS. Before corneal transplantation, intrastromal sutures were placed for 2 weeks in the corneas of BALB/c mice, inducing intense angiogenesis. Allogeneic corneal transplantation was performed using C57BL/6 donor mice. Topical bevacizumab (2.5%) was delivered 3 times a day for 3 weeks in one treatment group, and 0.02 mL (0.5 mg) bevacizumab was injected subconjunctivally at days 0, 4, 8, and 15 after transplantation in the other treatment group. The control group received no treatment. Grafts were examined twice a week for 8 weeks by slit-lamp microscopy and were photographed once a week by slit-lamp digital camera and scored for opacity. For assessment of corneal neovascularization (NV), a quantitative method was used to measure three primary metrics including neovascular area, vessel caliber, and neovessel invasion area. RESULTS. Both topical and subconjunctival bevacizumab treatment reduced neovascular area and vessel caliber; however, the regression of corneal NV was more profound when treated subconjunctivally. The mean percentage reduction of neovascular area was 55% (P < 0.05) by week 8 in the subconjunctival treatment group and 33% (P = 0.15) in the topical group. Only subconjunctival bevacizumab treatment resulted in significant regression of neovessel invasion area (P < 0.05). All corneal transplants in both the control and the topical groups were rejected by 4 weeks after transplantation. However, in the subconjunctival treatment group, 33% of corneal grafts survived (P < 0.01). CONCLUSIONS. Subconjunctival bevacizumab may offer an adjunctive measure to conventional therapies in preventing graft rejection in high-risk corneal transplantation. (Invest Ophthalmol Vis Sci. 2010;51:2411-2417) DOI: 10.1167/iovs.09-3745 C1 [Dastjerdi, Mohammad H.; Saban, Daniel R.; Okanobo, Andre; Nallasamy, Nambi; Sadrai, Zahra; Chauhan, Sunil K.; Hajrasouliha, Amir R.; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA. [Dastjerdi, Mohammad H.; Saban, Daniel R.; Okanobo, Andre; Nallasamy, Nambi; Sadrai, Zahra; Chauhan, Sunil K.; Hajrasouliha, Amir R.; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Dastjerdi, Mohammad H.; Okanobo, Andre; Dana, Reza] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health/National Eye Institute [K24 EY019098, RO1 EY12963]; Eye Bank Association of America Scientific Research Grant FX Supported by National Institutes of Health/National Eye Institute Grants K24 EY019098 and RO1 EY12963 and by an Eye Bank Association of America Scientific Research Grant. NR 43 TC 36 Z9 39 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2010 VL 51 IS 5 BP 2411 EP 2417 DI 10.1167/iovs.09-3715 PG 7 WC Ophthalmology SC Ophthalmology GA 589UU UT WOS:000277180500018 PM 19892863 ER PT J AU Schacker, TW Bosch, RJ Bennett, K Pollard, R Robbins, GK Collier, AC Gulick, RM Spritzler, J Mildvan, D AF Schacker, Timothy W. Bosch, Ronald J. Bennett, Kara Pollard, Richard Robbins, Gregory K. Collier, Ann C. Gulick, Roy M. Spritzler, John Mildvan, Donna CA ACTG TI Measurement of Naive CD4 Cells Reliably Predicts Potential for Immune Reconstitution in HIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE early therapy; immune reconstitution; naive CD4 T cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; 4-DRUG ANTIRETROVIRAL REGIMENS; SEQUENTIAL 3-DRUG REGIMENS; LYMPHATIC TISSUE FIBROSIS; COLLAGEN DEPOSITION; INITIAL TREATMENT; TYPE-1 INFECTION; T-CELLS; THERAPY; HOMEOSTASIS AB Background: Pathogenesis studies show that naive CD4 cells are preferentially depleted in lymphoid tissues during HIV infection, and studies of advanced patients suggest levels of naive CD4 cells in blood correlate to total CD4 cells after starting antiretroviral therapy (ARV). We hypothesized that measuring naive CD4 cells in blood in people at earlier stages of disease would identify those at highest risk for poor CD4 reconstitution who may benefit from earlier initiation of ARV. Methods and Findings: We identified 348 patients from multiple AIDS Clinical Trials Group studies who were ARV naive, had a CD4 count between 200 and 500 cells per microliter, a measure of pretreatment-naive CD4 percent, and serial follow-up measures of CD4 count and plasma HIV RNA after starting ARV. We used logistic regression to model the ability of naive CD4 percent to predict 100 and 200 CD4 cell increases after 24 months of therapy. After controlling for baseline viral load and demographic variables, baseline naive but not total CD4 cell count strongly predicted CD4 cell increases. Lower baseline naive CD4 percent was associated with greater time spent at lower CD4 T-cell counts after initiating ARV. Conclusions: Measurement of naive CD4 percent in patients can identify those least likely to reconstitute immunity, who may benefit from earlier ARV treatment. C1 [Schacker, Timothy W.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Bosch, Ronald J.; Bennett, Kara; Spritzler, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pollard, Richard] Univ Calif, Div Infect Dis, Sacramento, CA USA. [Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Collier, Ann C.] Univ Washington, Dept Med, Seattle, WA USA. [Gulick, Roy M.] Weill Cornell Med Coll, Div Infect Dis, New York, NY USA. [Mildvan, Donna] Beth Israel Deaconess Med Ctr, Div Infect Dis, New York, NY 10003 USA. RP Schacker, TW (reprint author), Univ Minnesota, Dept Med, MMC 250 516 Delaware St SE, Minneapolis, MN 55455 USA. EM schacker@umn.edu RI Robbins, Gregory/F-7988-2011 FU AIDS Clinical Trials Group [AI68636, AI38858, AI68634, AI38885, AI54232, AI46370, AI28246] FX Supported by AIDS Clinical Trials Group, AI68636, AI38858, AI68634, AI38885, AI54232, AI46370, and AI28246. NR 21 TC 14 Z9 15 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 MAY 1 PY 2010 VL 54 IS 1 BP 59 EP 62 DI 10.1097/QAI.0b013e3181c96520 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 587OG UT WOS:000277001500008 PM 20182359 ER PT J AU Chen, JY Ogwu, AC Svab, P Lockman, S Moffat, HJ Gaolathe, T Moilwa, S Stordal, K Dryden-Peterson, S Moffat, C Makhema, J Essex, M Shapiro, RL AF Chen, Jennifer Y. Ogwu, Anthony C. Svab, Petr Lockman, Shahin Moffat, Howard J. Gaolathe, Tendani Moilwa, Shana Stordal, Ketil Dryden-Peterson, Scott Moffat, Claire Makhema, Joseph Essex, M. Shapiro, Roger L. TI Antiretroviral Treatment Initiation Among HIV-Infected Pregnant Women with Low CD4(+) Cell Counts in Gaborone, Botswana SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE Botswana; CD4(+) cell count testing; HAART initiation; pregnancy ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; SINGLE-DOSE NEVIRAPINE; RANDOMIZED-TRIAL; ZIDOVUDINE; PREVENTION; EFFICACY; RISK AB Background: Botswana has the most comprehensive public program in Africa for providing antiretroviral therapy to treat HIV and prevent mother-to-child transmission (PMTCT). Botswana guidelines prioritize CD4(+) cell count testing during pregnancy and initiation of highly active antiretroviral treatment (HAART) for women who qualify for treatment. We analyzed rates of HIV testing, CD4(+) cell count testing, and HAART initiation during pregnancy. Methods: From October 2007 through June 2008, we reviewed obstetric and laboratory records of women at Princess Marina Hospital in Gaborone, Botswana. Results: We recorded information from 3056 women. Of 2675 women eligible for the PMTCT program, 2623 (98%) had a documented HIV status, of whom 793 (30%) were HIV infected. Among women who were treatment naive at pregnancy conception, 397 (59%) had recorded CD4(+) cell counts, of whom 62 (16%) had a CD4(+) cell count <200 cells per cubic millimeter. Among this subset, 23 (37%) initiated HAART during pregnancy, 26 (42%) received zidovudine prophylaxis, and 13 (21%) received no therapy. Conclusions: We observed low rates of CD4(+) cell count testing and HAART initiation during pregnancy. Antenatal clinics should prioritize CD4(+) cell count testing and referral of women who qualify for HAART to maximize benefits of maternal treatment and PMTCT. C1 [Chen, Jennifer Y.] Harvard Univ, Sch Med, Boston, MA USA. [Ogwu, Anthony C.; Dryden-Peterson, Scott; Moffat, Claire; Makhema, Joseph] Botswana Harvard AIDS Inst, Gaborone, Botswana. [Svab, Petr; Moilwa, Shana; Stordal, Ketil] Princess Marina Hosp, Gaborone, Botswana. [Lockman, Shahin] Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA. [Lockman, Shahin; Essex, M.; Shapiro, Roger L.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Moffat, Howard J.] Hlth Inspectorate, Botswana Minist Hlth, Gaborone, Botswana. [Gaolathe, Tendani] Botswana Harvard PEPFAR Master Trainer Program, Gaborone, Botswana. [Dryden-Peterson, Scott] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA. EM rshapiro@hsph.harvard.edu FU Doris Duke Charitable Research Foundation FX Supported by Funding from the Doris Duke Charitable Research Foundation, through a Clinical Research Fellowship awarded to J.Y.C. NR 24 TC 14 Z9 14 U1 0 U2 0 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 MAY 1 PY 2010 VL 54 IS 1 BP 102 EP 106 DI 10.1097/QAI.0b013e3181c080bf PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 587OG UT WOS:000277001500014 PM 19864957 ER PT J AU Wolf, EJ Miller, MW Krueger, RF Lyons, MJ Tsuang, MT Koenen, KC AF Wolf, Erika J. Miller, Mark W. Krueger, Robert F. Lyons, Michael J. Tsuang, Ming T. Koenen, Karestan C. TI Posttraumatic Stress Disorder and the Genetic Structure of Comorbidity SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; structure of comorbidity; behavioral genetics; structural equation modeling ID COMMON MENTAL-DISORDERS; DEFICIT HYPERACTIVITY DISORDER; ENVIRONMENTAL RISK-FACTORS; LONGITUDINAL BIRTH COHORT; PROPOSED META-STRUCTURE; ERA TWIN REGISTRY; DSM-IV ANXIETY; EXTERNALIZING SPECTRUM; COMBAT EXPOSURE; BEHAVIORAL DISINHIBITION AB This study used structural equation modeling to examine the genetic and environmental architecture of latent dimensions of internalizing and externalizing psychiatric comorbidity and explored structural associations between posttraumatic stress disorder (PTSD) and these dimensions. Data were drawn from the Vietnam Era Twin Registry and included lifetime diagnoses for PTSD and a range of other psychiatric disorders for 3,372 male male twin pairs. Examination of the phenotypic structure of these disorders revealed that PTSD cross-loaded on both Internalizing and Externalizing common factors. Biometric analyses suggested largely distinct genetic risk factors for the latent internalizing and externalizing comorbidity dimensions, with the total heritability of the Externalizing factor (69%) estimated to be significantly stronger than that for Internalizing (41%). Nonshared environment explained the majority of the remaining variance in the Internalizing (58%) and Externalizing (20%) factors. Shared genetic variance across the 2 dimensions explained 67% of their phenotypic correlation (r = .52). These findings have implications for conceptualizations of the etiology of PTSD and its location in an empirically based nosology. C1 [Miller, Mark W.] Boston Univ, Dept Psychol, Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Miller, Mark W.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Krueger, Robert F.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Krueger, Robert F.] Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Lyons, Michael/B-6119-2011; Miller, Mark/G-7322-2011; Koenen, Karestan/K-5402-2014; OI Miller, Mark/0000-0001-6393-8563; Lyons, Michael/0000-0001-6516-9219; Koenen, Karestan/0000-0003-3293-4281; Wolf, Erika/0000-0003-2666-2435 FU CSRD VA [I01 CX000431]; NIMH NIH HHS [K08 MH070627-06, 5F31MH074267, F31 MH074267, K08 MH070627, K08MH070627, MH78928, R01 MH078928, R01 MH078928-04, R01 MH079806] NR 60 TC 49 Z9 49 U1 2 U2 7 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 MAY PY 2010 VL 119 IS 2 BP 320 EP 330 DI 10.1037/a0019035 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 596FU UT WOS:000277671200008 PM 20455605 ER PT J AU Thomas, SY Chyung, YH Luster, AD AF Thomas, Seddon Y. Chyung, Yung H. Luster, Andrew D. TI Natural killer T cells are not the predominant T cell in asthma and likely modulate, not cause, asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Natural killer T cell; asthma; CD1d; T(H)2 cells; airway hyperresponsiveness ID INDUCED AIRWAY HYPERREACTIVITY; NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; BRONCHOALVEOLAR LAVAGE; MONOCLONAL-ANTIBODY; BRONCHIAL-ASTHMA; DENDRITIC CELLS; ALLERGIC-ASTHMA; ATOPIC ASTHMA; MOUSE MODEL AB Asthma is a multifactorial disease of the airways characterized by airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Conventional MHC class II-restricted CD4(+) T cells are considered a key cell in asthma pathogenesis because they have a broad T-cell receptor repertoire, providing specificity and reactivity to diverse protein allergens. This notion was challenged when a study found that invariant Natural Killer (NK) T cells were the predominant T cells in the lung and bronchoalveolar lavage fluid of all asthmatic subjects studied. This finding was provocative because invariant NKT cells have a very limited T-cell receptor repertoire and are specific for a restricted set of lipid antigens that bind to CD1d, a nonpolymorphic MHC-like molecule. However, multiple subsequent studies failed to replicate the initial study and instead found that invariant NKT cells are present as a small fraction of the total T cells in the asthmatic lung. Thus, we believe that although CD1d-restricted NKT cells might play a role in modulating the asthmatic phenotype, they are not the critical drivers of the asthmatic response, a role we believe is still held by conventional MHC class II-restricted CD4(+) T cells. (J Allergy Clin Immunol 2010;125:980-4.) C1 [Chyung, Yung H.; Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Chyung, Yung H.; Luster, Andrew D.] Harvard Univ, Sch Med, Boston, MA USA. [Thomas, Seddon Y.] Univ Chicago, Dept Pathol, Howard Hughes Med Inst, Comm Immunol, Chicago, IL 60637 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU National Institute of Health [R37-AI040618]; American Academy of Allergy, Asthma Immunology FX Supported by grant R37-AI040618 from the National Institute of Health to A.D.L.; Disclosure of potential conflict of interest: Y. H. Chyung receives research support from the American Academy of Allergy, Asthma & Immunology. The rest of the authors have declared that they have no conflict of interest. NR 54 TC 28 Z9 30 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 MAY PY 2010 VL 125 IS 5 BP 980 EP 984 DI 10.1016/j.jaci.2010.01.032 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 596LO UT WOS:000277686700004 PM 20304475 ER PT J AU Dougherty, RH Sidhu, SS Raman, K Solon, M Solberg, OD Caughey, GH Woodruff, PG Fahy, JV AF Dougherty, Ryan H. Sidhu, Sukhvinder S. Raman, Kavita Solon, Margaret Solberg, Owen D. Caughey, George H. Woodruff, Prescott G. Fahy, John V. TI Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; mast cells; tryptase; chymase; carboxypeptidase A3; stem cell factor ID EPITHELIAL-CELLS; CARBOXYPEPTIDASE-A; ATOPIC ASTHMATICS; ANGIOTENSIN-II; HUMAN AIRWAY; EXPRESSION; CHYMASE; INFLAMMATION; BASOPHILS; ADHESION AB Background: Previously, we found that mast cell tryptases and carboxypeptidase A3 (CPA3) are differentially expressed in the airway epithelium in asthmatic subjects. We also found that asthmatic subjects can be divided into 2 subgroups ("T(H)2 high" and "T(H)2 low" asthma) based on epithelial cell gene signatures for the activity of T(H)2 cytokines. Objectives: We sought to characterize intraepithelial mast cells (IEMCs) in asthma. Methods: We performed gene expression profiling in epithelial brushings and stereology-based quantification of mast cell numbers in endobronchial biopsy specimens from healthy control and asthmatic subjects before and after treatment with inhaled corticosteroids (ICSs). We also performed gene expression and protein quantification studies in cultured airway epithelial cells and mast cells. Results: By means of unsupervised clustering, mast cell gene expression in the airway epithelium related closely to the expression of IL-13 signature genes. The levels of expression of mast cell genes correlate positively with lung function improvements with ICSs. IEMC density was 2-fold higher than normal in subjects with T(H)2-high asthma compared with that seen in subjects with T(H)2-low asthma or healthy control subjects (P = .015 for both comparisons), and these cells were characterized by expression of tryptases and CPA3 but not chymase. IL-13 induced expression of stem cell factor in cultured airway epithelial cells, and mast cells exposed to conditioned media from IL-13 activated epithelial cells showed downregulation of chymase but no change in tryptase or CPA3 expression. Conclusion: IEMC numbers are increased in subjects with T(H)2-high asthma, have an unusual protease phenotype (tryptase and CPA3 high and chymase low), and predict responsiveness to ICSs. IL-13 stimulated production of stem cell factor by epithelial cells potentially explains mast cell accumulation in TH2-high asthmatic epithelium. (J Allergy Clin Immunol 2010;125:1046-53.) C1 [Dougherty, Ryan H.; Sidhu, Sukhvinder S.; Solon, Margaret; Solberg, Owen D.; Caughey, George H.; Woodruff, Prescott G.; Fahy, John V.] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. [Dougherty, Ryan H.; Solon, Margaret; Solberg, Owen D.; Caughey, George H.; Woodruff, Prescott G.; Fahy, John V.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Dougherty, Ryan H.] Calif Pacific Med Ctr, San Francisco Crit Care Med Grp, San Francisco, CA USA. [Raman, Kavita; Caughey, George H.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Fahy, JV (reprint author), 513 Parnassus Ave,Box 0130, San Francisco, CA 94143 USA. EM john.fahy@ucsf.edu FU National Institutes of Health [F32HL093999-01, A1077439-025, R01 HL080414, R01 HL095372, P01 HL024136] FX Supported by the National Institutes of Health National Research Service Award F32HL093999-01 (R.H.D.), A1077439-025 and R01 HL080414 (J.V.F.), R01 HL095372 (P.G.W.), and P01 HL024136 (G.H.C.). NR 43 TC 95 Z9 96 U1 0 U2 2 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 MAY PY 2010 VL 125 IS 5 BP 1046 EP 1053 DI 10.1016/j.jaci.2010.03.003 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 596LO UT WOS:000277686700013 PM 20451039 ER PT J AU O'Connor, RD Bleecker, ER Long, AD Tashkin, D Peters, S Klingman, D Gutierrez, B AF O'Connor, Richard D. Bleecker, Eugene R. Long, Aidan Tashkin, Donald Peters, Stephen Klingman, David Gutierrez, Benjamin TI Subacute Lack of Asthma Control and Acute Asthma Exacerbation History as Predictors of Subsequent Acute Asthma Exacerbations: Evidence From Managed Care Data SO JOURNAL OF ASTHMA LA English DT Article DE asthma; asthma control; exacerbations; managed care; asthma morbidity ID INHALED CORTICOSTEROIDS; EMERGENCY-DEPARTMENT; ADULTS; VARIABILITY; REGIMENS; PATTERNS; THERAPY; PROGRAM; CLAIMS AB Background. Monitoring indicators of subacute lack of asthma control (SALAC) may help to reduce asthma morbidity. Objective. To determine whether SALAC, independent of current asthma exacerbations, is associated with subsequent acute asthma exacerbations. Methods. Administrative claims data from PharMetrics/IMS Health were used to identify patients 12 years or older continuously enrolled in a participating U. S. health plan from 2001 to 2004 with >= 1 asthma claim (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x), no chronic obstructive pulmonary disease or cystic fibrosis claims, and >= 1 prescription for an asthma medication during 2001-2004. SALAC was defined as more than 4 asthma-related physician visits (or >= 2/quarter) or more than 5 short-acting beta(2)-adrenergic agonist prescriptions during 2001. Effect of asthma control category (Exacerbation Only [EO], SALAC Only [SO], Both Exacerbation and SALAC [Both], Neither Exacerbation nor SALAC [Neither]) in 2001 on acute asthma exacerbations (hospitalization, emergency department visit, or short-term oral corticosteroid use) during 2002-2004 was assessed using logistic regression, adjusting for gender, age, health plan type, and region. Results. Of 11,779 patients, 8% were assigned to the EO group, 26% to SO, 12% to Both, and 54% to Neither in 2001. The incidence of exacerbations in 2002-2004 was higher for Both (61.8%) versus EO (55.0%) and for SO (37.3%) versus Neither (31.9%). The risk of exacerbation in 2002-2004 was increased significantly (p < .0001) for Both (3.394; 95% confidence interval [CI] = 3.009, 3.827), EO (2.503; 95% CI = 2.176, 2.879), and SO (1.277; 95% CI = 1.166, 1.399) versus Neither. Conclusion. In this study, the risk of subsequent exacerbation was greatest in patients with both SALAC and acute asthma exacerbations, followed by those with exacerbations only and those with SALAC only. SO identified an additional 26% of asthma patients at increased risk for subsequent exacerbation. The results from this study demonstrate that SALAC indicators and a history of acute asthma exacerbations are independent predictors of future acute asthma exacerbations and highlight the important role of subacute asthma worsening in predicting and preventing future asthma exacerbations. C1 [O'Connor, Richard D.] Sharp Rees Stealy Med Grp, Dept Qual Management, San Diego, CA 92101 USA. [O'Connor, Richard D.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Bleecker, Eugene R.; Peters, Stephen] Wake Forest Univ, Bowman Gray Sch Med, Translat Sci Inst, Winston Salem, NC USA. [Bleecker, Eugene R.; Peters, Stephen] Wake Forest Univ, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Long, Aidan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tashkin, Donald] Univ Calif Los Angeles, David Geffen Sch Med Pulm & Crit Care, Los Angeles, CA 92103 USA. [Klingman, David] IMS Hlth US Hlth Econ & Outcomes Res, Falls Church, VA USA. [Gutierrez, Benjamin] AstraZeneca LP, Wilmington, DE USA. RP O'Connor, RD (reprint author), Sharp Rees Stealy Med Grp, Dept Qual Management, 2001 4th Ave, San Diego, CA 92101 USA. EM roconnor1@cox.net FU AstraZeneca LP, Wilmington, DE; Wake Forest University Health Sciences; Aerovance; Amgen; AstraZeneca; Boehringer-Ingelheim; Centocor; Ception; Genentech; GlaxoSmithKline; Novartis; Pfizer; Wyeth; IMS for Abbott; Medtronic; Forest; Merck; Novo Nordisk; sanofiaventis; Shire; Vertex FX Funding for the study was provided by AstraZeneca LP, Wilmington, DE. The authors thank Keith Brown from the University of North Carolina-General Administration, Chapel Hill, NC; Chakkarin Burudpakdee, Jonothan Tierce, and Julie Munakata from IMS Heath, Inc., Falls Church, VA; Bhash Parasuraman from AstraZeneca LP, Wilmington, DE; and Robert Boggs from Wyeth, Collegeville, PA (formerly of AstraZeneca LP), for their contributions to this study.; Richard O'Connor has no relevant financial interests in this manuscript. Eugene Bleecker has served as a consultant for AstraZeneca, Boehringer-Ingelheim, Centocor, Genentech, GalxoSmithKline, Novartis, Pfizer, Wyeth, and Merck and has received research grants for clinical trials during the last 5 years through Wake Forest University Health Sciences, Aerovance, Amgen, AstraZeneca, Boehringer-Ingelheim, Centocor, Ception, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Wyeth. Aidan Long has received a research grant from Genentech, has served as a consultant for sanofi-aventis, was PST for Genentech, and is on the Board of Directors for Asthma and Allergy Foundation of America - New England Chapter. Donald Tashkin has served as consultant and speaker for and has received research grants from AstraZeneca. Stephen Peters has served as consultant and speaker for AstraZeneca. David Klingman has had contracts with IMS for Abbott, Amgen, Forest, GlaxoSmithKline, Medtronic, Merck, Novo Nordisk, Pfizer, sanofiaventis, Shire, Vertex, and Wyeth. Benjamin Gutierrez was an employee of AstraZeneca at the time of the manuscript authorship. NR 21 TC 16 Z9 16 U1 0 U2 0 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 MAY PY 2010 VL 47 IS 4 BP 422 EP 428 DI 10.3109/02770901003605332 PG 7 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 658VI UT WOS:000282517500012 PM 20528597 ER PT J AU Tomer, Y AF Tomer, Yaron TI Hepatitis C and interferon induced thyroiditis SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 7th International Congress on Autoimmunity CY MAY 05-09, 2010 CL Ljubljana, SLOVENIA DE Interferon; Thyroiditis; Autoimmunity ID AUTOIMMUNE ENDOCRINE DISEASE; HUMAN THYROCYTE CULTURES; CHRONIC VIRAL-HEPATITIS; HIV ENVELOPE PROTEINS; HCV CHRONIC HEPATITIS; GRAVES-DISEASE; ALPHA THERAPY; VIRUS-INFECTION; YERSINIA-ENTEROCOLITICA; GENETIC SUSCEPTIBILITY AB Autoimmune thyroid diseases (AITDs) are complex diseases that develop as a result of interactions between genetic, epigenetic, and environmental factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. The major environmental triggers of AITD include iodine, smoking, medications, pregnancy, and possibly stress. In this review we will focus on two well-documented environmental triggers of AITD, hepatitis C virus (HCV) infection and interferon alpha (IFNa) therapy. Chronic HCV infection has been shown to be associated with increased incidence of clinical and subclinical autoimmune thyroiditis (i.e. the presence of thyroid antibodies in euthyroid subjects). Moreover, IFNa therapy of chronic HCV infection is associated with subclinical or clinical thyroiditis in up to 40% of cases which can be autoimmune, or non-autoimmune thyroiditis. In some cases interferon induced thyroiditis (IIT) in chronic HCV patients may result in severe symptomatology necessitating discontinuation of therapy. While the epidemiology and clinical presentation of HCV and interferon induced thyroiditis have been well characterized, the mechanisms causing these conditions are still poorly understood. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, New York, NY USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, Box 1118,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU NIDDK NIH HHS [DK61659, R01 DK061659, R01 DK061659-08] NR 82 TC 58 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2010 VL 34 IS 3 SI SI BP J322 EP J326 DI 10.1016/j.jaut.2009.11.008 PG 5 WC Immunology SC Immunology GA 585IJ UT WOS:000276818300016 PM 20022216 ER PT J AU Funakoshi, T Martin, SD Wolf, BT Schmid, TM Thornhill, TS Spector, M AF Funakoshi, Tadanao Martin, Scott D. Wolf, Bryce T. Schmid, Thomas M. Thornhill, Thomas S. Spector, Myron TI alpha-Smooth muscle actin-expressing cells and lubricin in periprosthetic tissue SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE periprosthetic tissue; lubricin; smooth muscle actin; prosthesis ID SUPERFICIAL ZONE PROTEIN; TOTAL HIP-ARTHROPLASTY; BONE-CEMENT INTERFACE; POLYETHYLENE WEAR DEBRIS; MARROW STROMAL CELLS; ARTICULAR-CARTILAGE; CONNECTIVE-TISSUE; GROWTH-FACTORS; MOLECULAR-STRUCTURE; GENE-EXPRESSION AB The objective of the study was to evaluate the distributions of (1) cells expressing the contractile actin isoform, alpha-smooth muscle actin (alpha-SMA) and (2) a lubricating and antiadhesion glycoprotein, lubricin, in the tissue around loose joint replacement prostheses in human subjects. Periprostehtic tissue resected at revision arthroplasty of noncemented glenoid components of total shoulder arthroplasties was obtained from 10 patients. Samples of periprosthetic tissue were stained with monoclonal antibodies to alpha-SMA and lubricin. alpha-SMA was found in cells, principally of fibroblast morphology, in many of the fields of view (FOVs) in samples from all patients. Moderate correlations were observed between the percentage of FOVs containing alpha-SMA-expressing cells and the percentages of FOVs containing polyethylene (R(2) = 0.79) and metallic (R(2) = 0.75) particles. Lubricin was identified (1) as a discrete layer on the surface, (2) within the extracellular matrix, and (3) intracellularly. These lubricin-positive features were found in samples from all patients. Strong correlations were noted between the percentages of FOVs with matrix and intracellular lubricin staining (R(2) = 0.97) and between the percentages of FOVs with surface and matrix staining for lubricin (R(2) = 0.96). Having established the presence of alpha-SMA and lubricin in periprosthetic tissue, hypotheses regarding their role in the development and persistence of periprosthetic tissue can be synthesized for future study: for example, alpha-SMA-enabled contracture of the fibrous periprosthetic tissue results in its densification, and lubricin-coated surfaces interfere with integrative repair processes necessary for resorption and remodeling. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 93A: 515-527, 2010 C1 [Funakoshi, Tadanao; Martin, Scott D.; Wolf, Bryce T.; Thornhill, Thomas S.; Spector, Myron] Harvard Univ, Sch Med, Dept Orthopaed Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Funakoshi, Tadanao; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Schmid, Thomas M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu FU Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs FX This material is based on the work supported by the Office of Research and Development, Rehabilitation Research and Development Service, Department of Veterans Affairs. M.S. is a VA Research Career Scientist. The authors thank Alix Weaver and Karthik Sugumaran for assistance with immunohistochemistry. NR 68 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAY PY 2010 VL 93A IS 2 BP 515 EP 527 DI 10.1002/jbm.a.32522 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 579ET UT WOS:000276351300012 PM 19585565 ER PT J AU Luo, Y Kobler, JB Heaton, JT Jia, XQ Zeitels, SM Langer, R AF Luo, Ying Kobler, James B. Heaton, James T. Jia, Xinqiao Zeitels, Steven M. Langer, Robert TI Injectable Hyaluronic Acid-Dextran Hydrogels and Effects of Implantation in Ferret Vocal Fold SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE hydrogel; vocal fold; hyaluronic acid; dextran; tissue restoration ID POLY(ALDEHYDE GULURONATE) HYDROGELS; SYNTHETIC EXTRACELLULAR-MATRIX; VISCOELASTIC SHEAR PROPERTIES; SEALING CORNEAL INCISIONS; FUNCTIONALIZED DERIVATIVES; TISSUE ADHESIVES; GROWTH-FACTOR; BIOMATERIALS; REPAIR; MODEL AB Injectable hydrogels may potentially be used for augmentation/regeneration of the lamina propria of vocal fold tissue In this study, hyaluronic acid (HA) and dextran were chemically modified and subsequently crosslinked via formation of hydrazone bonds in phosphate buffer. Swelling ratios, degradation, and compressive moduli of the resulting hydrogels were investigated. It was found that the properties of HA-dextran hydrogels were variable and the trend of variation could be correlated with the hydrogel composition The biocompatibility of three injectable HA-dextran hydrogels with different crosslinking density was assessed in the vocal fold region using a ferret model It was found that HA-dextran hydrogels implanted for three weeks stimulated mild foreign-body reactions Distinct tissue-material interactions were also observed for hydrogels made from different formulations the hydrogel with the lowest crosslinking density was completely degraded in vivo, while material residues were visible for other types of hydrogel injections, with or without cell penetration into the implantation depending on the hydrogel composition The in vivo results suggest that the HA-dextran hydrogel matrices can be further developed for applications of vocal fold tissue restoration (C) 2010 Wiley Periodicals, Inc J Biomed Mater Res Part B Appl Biomater 93B 386-393, 2010 C1 [Luo, Ying] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China. [Kobler, James B.; Heaton, James T.; Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Kobler, James B.; Heaton, James T.; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Jia, Xinqiao] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Luo, Y (reprint author), Peking Univ, Coll Engn, Dept Biomed Engn, 60 Yan Nan Yuan, Beijing 100871, Peoples R China. RI Luo, Ying/A-9920-2012 OI Luo, Ying/0000-0001-9834-9419 FU Eugene B Casey Foundation; Advisory Board Foundation; Institute of Laryngology and Voice Restoration [DE013023] FX Contract grant sponsors The Eugene B Casey Foundation, the Advisory Board Foundation, Contract grant sponsor the Institute of Laryngology and Voice Restoration, contract grant number DE013023 NR 44 TC 16 Z9 18 U1 1 U2 23 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2010 VL 93B IS 2 BP 386 EP 393 DI 10.1002/jbm.b.31593 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 583YG UT WOS:000276715800012 PM 20151459 ER PT J AU Deliolanis, NC Dunham, J Wurdinger, T Figueiredo, JL Tannous, BA Ntziachristos, V AF Deliolanis, Nikolaos C. Dunham, Joshua Wurdinger, Thomas Figueiredo, Jose-Luiz Tannous, Bakhos A. Ntziachristos, Vasilis TI In-vivo imaging of murine tumors using complete-angle projection fluorescence molecular tomography (vol 14, 030509, 2009) SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Correction C1 [Deliolanis, Nikolaos C.; Dunham, Joshua; Wurdinger, Thomas; Figueiredo, Jose-Luiz; Tannous, Bakhos A.; Ntziachristos, Vasilis] Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. [Deliolanis, Nikolaos C.; Ntziachristos, Vasilis] Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany. RP Deliolanis, NC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St, Charlestown, MA 02129 USA. OI Deliolanis, Nikolaos/0000-0002-6392-3035 NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2010 VL 15 IS 3 AR 039801 DI 10.1117/1.3449540 PG 1 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 635GF UT WOS:000280642900063 ER PT J AU Pogue, BW Samkoe, KS Hextrum, S O'Hara, JA Jermyn, M Srinivasan, S Hasan, T AF Pogue, Brian W. Samkoe, Kimberley S. Hextrum, Shannon O'Hara, Julia A. Jermyn, Michael Srinivasan, Subhadra Hasan, Tayyaba TI Imaging targeted-agent binding in vivo with two probes SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence; imaging; image processing; molecules; fluorescence spectroscopy; image analysis ID CANCER; THERAPY AB An approach to quantitatively image targeted-agent binding rate in vivo is demonstrated with dual-probe injection of both targeted and nontargeted fluorescent dyes. Images of a binding rate constant are created that reveal lower than expected uptake of epidermal growth factor in an orthotopic xenograft pancreas tumor (2.3 x 10(-5) s(-1)), as compared to the normal pancreas (3.4 x 10(-5) s(-1)). This approach allows noninvasive assessment of tumor receptor targeting in vivo to determine the expected contrast, spatial localization, and efficacy in therapeutic agent delivery. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3449109] C1 [Pogue, Brian W.; Samkoe, Kimberley S.; Hextrum, Shannon; O'Hara, Julia A.; Jermyn, Michael; Srinivasan, Subhadra] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Pogue, Brian W.; O'Hara, Julia A.] Dartmouth Med Sch, Dept Surg, Dept Diagnost Radiol, Lebanon, NH 03756 USA. [Pogue, Brian W.; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM brian.w.pogue@dartmouth.edu FU NIH [P01CA84203, R01CA109558] FX The authors are very grateful for stimulating discussions with Adnan Abu-Yousif and Prakash Rai from the Wellman Center for Photomedicine at MGH during the model studies of this work. This work has been funded by NIH grants P01CA84203 and R01CA109558. NR 7 TC 24 Z9 24 U1 0 U2 3 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2010 VL 15 IS 3 AR 030513 DI 10.1117/1.3449109 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 635GF UT WOS:000280642900009 PM 20614996 ER PT J AU de Boer, PG Buckley, R Schmidt, P Fox, R Jupiter, J AF de Boer, Peter G. Buckley, Rick Schmidt, Pascal Fox, Robert Jupiter, Jesse TI Learning Assessment Toolkit SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID CONTINUING MEDICAL-EDUCATION; SELF-ASSESSMENT; PERFORMANCE; INFORMATION; PHYSICIANS; COMPETENCE C1 [de Boer, Peter G.; Schmidt, Pascal] AO Educ, CH-8600 Dubendorf, Switzerland. [Buckley, Rick] Foothills Med Ctr, Calgary, AB T2N 2T9, Canada. [Jupiter, Jesse] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP de Boer, PG (reprint author), AO Educ, Stettbachstr 6, CH-8600 Dubendorf, Switzerland. EM Piet.deboer@aofoundation.org; buckclin@ucalgary.ca; Pascal.schmidt@aofoundation.org; drrdfox@me.com; jjupiter1@partners.org RI AOCID, AO Foundation/R-6455-2016 NR 19 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2010 VL 92A IS 5 BP 1325 EP 1329 DI 10.2106/JBJS.I.00775 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 591WH UT WOS:000277335400052 PM 20439698 ER PT J AU Roodman, GD AF Roodman, G. David TI Targeting the bone microenvironment in multiple myeloma SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Review DE Multiple myeloma; Bone microenvironment; Bisphosphonates; Osteoclast; Cytokines ID HIGH-DOSE PAMIDRONATE; MARROW STROMAL CELLS; B LIGAND RANKL; OSTEOBLAST DIFFERENTIATION; RECEPTOR ACTIVATOR; PLASMA-CELLS; OSTEOCLAST FORMATION; OSTEOLYTIC LESIONS; TUMOR PROGRESSION; POTENTIAL ROLE AB Multiple myeloma (MM) is a plasma cell malignancy characterized by the frequent development of osteolytic lesions, osteopenia, pathological fractures, and/or severe bone pain. In the past few years several potential factors involved in this process have been identified and, with the increased knowledge of the signaling pathways involved in the regulation of normal osteoblast and osteoclast function, have provided us with a better understanding of the contributions of the marrow microenvironment to MM bone disease. These studies have identified several potential novel targets for treating MM bone disease in addition to the current standard treatment of bisphosphonates. In this article, we discuss several potential targets for treating MM bone disease as well as novel therapies that are in clinical trials for these patients. C1 Univ Pittsburgh, Dept Med Hematol Oncol, Vet Affairs Pittsburgh Healthcare Syst, Sch Med, Pittsburgh, PA 15240 USA. RP Roodman, GD (reprint author), Univ Pittsburgh, Dept Med Hematol Oncol, Vet Affairs Pittsburgh Healthcare Syst, Sch Med, Res & Dev 151-U Univ Dr C,Rm 2E113, Pittsburgh, PA 15240 USA. EM Roodmangd@upmc.edu NR 55 TC 20 Z9 21 U1 0 U2 4 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0914-8779 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PD MAY PY 2010 VL 28 IS 3 BP 244 EP 250 DI 10.1007/s00774-009-0154-7 PG 7 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 593OU UT WOS:000277469200002 PM 20127498 ER PT J AU Bonewald, LF Roodman, GD Boyce, BF Gutierrez, GE Yoneda, T Guise, TA Martin, TJ AF Bonewald, Lynda F. Roodman, G. David Boyce, Brendan F. Gutierrez, Gloria E. Yoneda, Toshiyuki Guise, Theresa A. Martin, T. John TI Gregory Robert Mundy 1942-2010 IN MEMORIAM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Biographical-Item C1 [Bonewald, Lynda F.] Univ Missouri, Kansas City, MO 64110 USA. [Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Boyce, Brendan F.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Gutierrez, Gloria E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Yoneda, Toshiyuki] Osaka Univ, Grad Sch Dent, Suita, Osaka, Japan. [Guise, Theresa A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Martin, T. John] St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. RP Bonewald, LF (reprint author), Univ Missouri, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2010 VL 25 IS 5 BP 931 EP 933 DI 10.1002/jbmr.109 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 604PX UT WOS:000278292100001 ER PT J AU Li, YC Samuvel, DJ Sundararaj, KP Lopes-Virella, MF Huang, Y AF Li, Yanchun Samuvel, Devadoss J. Sundararaj, Kamala P. Lopes-Virella, Maria F. Huang, Yan TI IL-6 and High Glucose Synergistically Upregulate MMP-1 Expression by U937 Mononuclear Phagocytes via ERK1/2 and JNK Pathways and c-Jun SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE MATRIX METALLOPROTEINASES; INTERLEUKIN 6; DIABETES; MITOGEN-ACTIVATED PROTEIN KINASES ID FACTOR-KAPPA-B; MATRIX METALLOPROTEINASES; GENE-EXPRESSION; CELL-DIFFERENTIATION; BACTERIAL-MENINGITIS; INFLAMMATORY MARKERS; PERIODONTAL-DISEASE; REACTIVE PROTEIN; INTERLEUKIN-6; RECEPTOR AB Matrix metalloproteinases (MMPs) play a pivotal role in tissue remodeling and destruction in inflammation-associated diseases such as cardiovascular disease and periodontal disease. Although it is known that interleukin (IL)-6 is a key proinflamatory cytokine, it remains unclear how IL-6 regulates MMP expression by mononuclear phagocytes. Furthermore, it remains undetermined how IL-6 in combination with hyperglycemia affects MMP expression. In the present study, we investigated the regulatory effect of IL-6 alone or in combination with high glucose on MMP-1 expression by U937 mononuclear phagocytes. We found that IL-6 is a powerful stimulator for MMP-1 expression and high glucose further augmented IL-6-stimulated MMP-1 expression. We also found that high glucose, IL-6, and lipopolysaccharide act in concert to stimulate MMP-1 expression. In the studies to elucidate underlying mechanisms, the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were found to be required for stimulation of MMP-1 by IL-6 and high glucose. We also observed that IL-6 and high glucose stimulated the expression of c-Jun, a key subunit of AP-1 known to be essential for MMP-1 transcription. The role of c-Jun in MMP-1 expression was confirmed by the finding that suppression of c-Jun expression by RNA interference significantly inhibited MMP-1 expression. Finally, we demonstrated that similarly to U937 mononuclear phagocytes, IL-6 and high glucose also stimulated MMP-1 secretion from human primary monocytes. In conclusion, this study demonstrated that IL-6 anti high glucose synergistically stimulated MMP-1 expression in mononuclear phagocytes via ERK and JNK cascades and c-Jun upregulation. J. Cell. Biochem. 110: 248-259, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Lopes-Virella, Maria F.; Huang, Yan] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Li, Yanchun; Samuvel, Devadoss J.; Sundararaj, Kamala P.; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@muse.edu FU Department of Veterans Affairs; NIH [DE16353] FX Grant sponsor: Department of Veterans Affairs; Grant sponsor: NIH; Grant number: DE16353. NR 50 TC 26 Z9 28 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2010 VL 110 IS 1 BP 248 EP 259 DI 10.1002/jcb.22532 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 593CO UT WOS:000277429700027 PM 20225236 ER PT J AU Mahmood, A Berry, J Wenger, DA Escolar, M Sobeih, M Raymond, G Eichler, FS AF Mahmood, Asif Berry, Jay Wenger, David A. Escolar, Maria Sobeih, Magdi Raymond, Gerald Eichler, Florian S. TI Metachromatic Leukodystrophy: A Case of Triplets With the Late Infantile Variant and a Systematic Review of the Literature SO JOURNAL OF CHILD NEUROLOGY LA English DT Review DE metachromatic leukodystrophy; demyelination; lysosome; arylsulfatase A ID BONE-MARROW-TRANSPLANTATION; ARYLSULFATASE-A GENE; ISOLATED PERIPHERAL NEUROPATHY; LATE-ONSET FORMS; COMPUTED-TOMOGRAPHY; COMPOUND HETEROZYGOTE; CLINICAL COURSE; JUVENILE TYPE; ADULT FORM; FOLLOW-UP AB Metachromatic leukodystrophy is a rare disorder with great clinical variability. We report the first case of triplets with the late infantile form of the disease and their systematic progression of symptoms. We reviewed the literature and identified all human studies that reported new cases since 1921. We analyzed survival by decade to assess the impact of historical changes in the management of care. Mean age at death and the 5-year survival from onset of symptoms for late infantile, juvenile, and adult phenotypes were 4.2 years and 24.9%, 17.4 years and 70.3%, and 43.1 years and 88.6%, respectively. The 5-year survival of cases reported after 1990 was significantly better than cases reported before 1970 in all subtypes of metachromatic leukodystrophy (late infantile: 52% vs 14%, juvenile: 100% vs 46%, adult: 95% vs 67%). Survival in the late infantile subtype was worse than that in other subtypes. Survival significantly improved over time in all subtypes. C1 [Eichler, Florian S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Mahmood, Asif] Univ Texas Galveston, Med Branch, Dept Internal Med, Galveston, TX 77550 USA. [Berry, Jay] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Wenger, David A.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurol, Philadelphia, PA 19107 USA. [Escolar, Maria] Univ N Carolina, Program Neurodevelopmental Funct Rare Disorders, Chapel Hill, NC USA. [Sobeih, Magdi] Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Raymond, Gerald] Kennedy Krieger Inst, Dept Neurogenet, Baltimore, MD USA. RP Eichler, FS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM feichler@partners.org RI Escolar, Maria/J-3721-2016 FU NIH [1K08NS52550-01A1, DK08795] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: Support for FE by NIH grant 1K08NS52550-01A1, and partial support for DAW was from NIH grant DK08795. NR 147 TC 8 Z9 8 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2010 VL 25 IS 5 BP 572 EP 580 DI 10.1177/0883073809341669 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 586YF UT WOS:000276950800007 PM 20038527 ER PT J AU Helfand, M AF Helfand, Mark TI AHRQ Series Editorial: Public involvement improves methods development in comparative effectiveness reviews SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Editorial Material ID STRENGTH; QUALITY; TRIALS; WORLD C1 Portland VA Med Ctr, Oregon Evidence Based Practice Ctr Hosp & Special, Portland, OR 97219 USA. RP Helfand, M (reprint author), Portland VA Med Ctr, Oregon Evidence Based Practice Ctr Hosp & Special, P3MED, Portland, OR 97219 USA. EM helfand@ohsu.edu NR 17 TC 4 Z9 4 U1 1 U2 3 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 MAY PY 2010 VL 63 IS 5 BP 471 EP 473 DI 10.1016/j.jclinepi.2009.11.018 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581OY UT WOS:000276534800001 PM 20346860 ER PT J AU Helfand, M Balshem, H AF Helfand, Mark Balshem, Howard TI AHRQ Series Paper 2: Principles for developing guidance: AHRQ and the Effective Health-Care Program SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Comparative effectiveness reviews; Stakeholders; Hierarchy of evidence; Patient-centered care; Avoiding bias; Evidence-based medicine ID PRACTICAL CLINICAL-TRIALS; SERVICES-TASK-FORCE; SYSTEMATIC REVIEWS; DECISION-MAKING; CHALLENGES; INTERVENTIONS; METAANALYSES; HIERARCHY; MEDICINE; DELIVERY AB Objective: This article describes some of the fundamental principles that have been developed to guide the work of producing comparative effectiveness reviews (CERs). Study Design and Setting: We briefly describe the role stakeholders play in providing important insights that inform the evidence-gathering process, and discuss the critical role of analytic frameworks in illuminating the relationship between surrogate measures and health outcomes, providing an understanding of the context in which clinical decisions are made and the uncertainties that underlie clinical controversies. Results: We describe the Effective Health Care program conceptual model for considering different types of evidence that emphasizes minimizing the risk of bias, but places high-quality, highly applicable evidence about effectiveness at the top of the hierarchy. Finally; we briefly describe areas of future methodological research. Conclusion: CERs have become a foundation for decision-making in clinical practice and health policy. To be useful, CERs must approach the evidence from a patient-centered perspective; explore the clinical logic underlying the rationale for a service; cast a broad net with respect to types of evidence, placing a high value on effectiveness and applicability, in addition to internal validity; and, present benefits and harms for treatments and tests in a consistent way. (C) 2010 Elsevier Inc. All rights reserved. C1 [Helfand, Mark; Balshem, Howard] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Oregon Evidence Based Practice Ctr, Portland, OR 97239 USA. [Helfand, Mark] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. RP Balshem, H (reprint author), Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Oregon Evidence Based Practice Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM balshemh@ohsu.edu NR 47 TC 28 Z9 28 U1 0 U2 2 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 MAY PY 2010 VL 63 IS 5 BP 484 EP 490 DI 10.1016/j.jclinepi.2009.05.005 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581OY UT WOS:000276534800006 PM 19716268 ER PT J AU Whitlock, EP Lopez, SA Chang, S Helfand, M Eder, M Floyd, N AF Whitlock, Evelyn P. Lopez, Sarah A. Chang, Stephanie Helfand, Mark Eder, Michelle Floyd, Nicole TI AHRQ Series Paper 3: Identifying, selecting, and refining topics for comparative effectiveness systematic reviews: AHRQ and the Effective Health-Care program SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Comparative effectiveness; Evidence-based practice; Systematic review; Priority setting; Methods; Decision making ID CLINICAL-PRACTICE GUIDELINES; SETTING PRIORITIES; CHALLENGES AB Objective: This article discusses the identification, selection, and refinement of topics for comparative effectiveness systematic reviews within the Agency for Healthcare Research and Quality's Effective Health Care (EHC) program. Study Design and Setting: The EHC program seeks to align its research topic selection with the overall goals of the program, impartially and consistently apply predefined criteria to potential topics, involve stakeholders to identify high-priority topics, be transparent and accountable, and continually evaluate and improve processes. Results: A topic prioritization group representing stakeholder and scientific perspectives evaluates topic nominations that fit within the EHC program (are "appropriate") to determine how "important" topics are as considered against seven criteria. The group then judges whether a new comparative effectiveness systematic review would be a duplication of existing research syntheses, and if not duplicative, if there is adequate type and volume of research to conduct a new systematic review. Finally, the group considers the "potential value and impact" of a comparative effectiveness systematic review. Conclusion: As the EHC program develops, ongoing challenges include ensuring the program addresses truly unmet needs for synthesized research because national and international efforts in this arena are uncoordinated, as well as engaging a range of stakeholders in program decisions while also achieving efficiency and timeliness. (C) 2010 Elsevier Inc. All rights reserved. C1 [Whitlock, Evelyn P.; Helfand, Mark; Eder, Michelle; Floyd, Nicole] Oregon Evidence Based Practice Ctr, Portland, OR 97227 USA. [Whitlock, Evelyn P.; Eder, Michelle] Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. [Lopez, Sarah A.; Floyd, Nicole] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Chang, Stephanie] Agcy Healthcare Res & Qual, Dept Hlth & Human Serv, Rockville, MD 20850 USA. [Helfand, Mark] Portland VA Med Ctr, Portland, OR 97239 USA. RP Whitlock, EP (reprint author), Oregon Evidence Based Practice Ctr, Portland, OR 97227 USA. EM evelyn.whitlock@kpchr.org NR 23 TC 45 Z9 46 U1 2 U2 5 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 MAY PY 2010 VL 63 IS 5 BP 491 EP 501 DI 10.1016/j.jclinepi.2009.03.008 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581OY UT WOS:000276534800007 PM 19540721 ER PT J AU Owens, DK Lohr, KN Atkins, D Treadwell, JR Reston, JT Bass, EB Chang, S Helfand, M AF Owens, Douglas K. Lohr, Kathleen N. Atkins, David Treadwell, Jonathan R. Reston, James T. Bass, Eric B. Chang, Stephanie Helfand, Mark TI AHRQ Series Paper 5: Grading the strength of a body of evidence when comparing medical interventions-Agency for Healthcare Research and Quality and the Effective Health-Care Program SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Comparative effectiveness; Evidence-based medicine; Methods; Strength of evidence; Systematic reviews ID RECOMMENDATIONS AB Objective: To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality. Study Design and Setting: Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. Results: The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence. Conclusion: EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence. (C) 2010 Elsevier Inc. All rights reserved. C1 [Owens, Douglas K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford UCSF Evidence Based Practice Ctr, Stanford, CA 94305 USA. [Owens, Douglas K.] VA Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA. [Owens, Douglas K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. [Lohr, Kathleen N.] RTI Int, Res Triangle Pk, NC 27709 USA. [Atkins, David] Dept Vet Affairs, Hlth Serv Res & Dev Serv, Qual Enhancement Res Initiat, Washington, DC 20420 USA. [Treadwell, Jonathan R.; Reston, James T.] ECRI Inst, Evidence Based Practice Ctr, Plymouth Meeting, PA 19462 USA. [Bass, Eric B.] Johns Hopkins Univ, Evidence Based Practice Ctr, Baltimore, MD 21287 USA. [Chang, Stephanie] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD 20850 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Evidence Based Practice Ctr, Portland, OR 97207 USA. [Helfand, Mark] Portland VA Med Ctr, Portland, OR 97207 USA. RP Owens, DK (reprint author), Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford UCSF Evidence Based Practice Ctr, 117 Encina Commons, Stanford, CA 94305 USA. EM owens@stanford.edu FU AHRQ FX This research was funded through contracts from the AHRQ to the following EPCs: ECRI Institute (290-02-0019); Johns Hopkins University (290-02-0018), Oregon Health & Science University (290-02-0009); RTI International (290-02-0016); and Stanford University (290-02-0017). The opinions expressed here are those of the authors and do not necessarily represent the views of the AHRQ, the Department of Health and Human Services, or the Department of Veterans Affairs. The authors thank Valerie King, MD, MPH, of the John M. Eisenberg Center at Oregon Health & Science University for her insightful comments on an earlier draft; and Loraine Monroe, of RTI International, for superior assistance with manuscript preparation. We thank Gordon Guyatt, Holger Schunemann, and the members of the GRADE working group for their work on rating quality of evidence, for very helpful discussions about our approach, and for comments on the manuscript. NR 15 TC 232 Z9 235 U1 0 U2 10 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 MAY PY 2010 VL 63 IS 5 BP 513 EP 523 DI 10.1016/j.jclinepi.2009.03.009 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581OY UT WOS:000276534800009 PM 19595577 ER PT J AU Boutin, SR Shen, Z Roesch, PL Stiefel, SM Sanderson, AE Multari, HM Pridhoko, EA Smith, JC Taylor, NS Lohmiller, JJ Dewhirst, FE Klein, HJ Fox, JG AF Boutin, S. R. Shen, Z. Roesch, P. L. Stiefel, S. M. Sanderson, A. E. Multari, H. M. Pridhoko, E. A. Smith, J. C. Taylor, N. S. Lohmiller, J. J. Dewhirst, F. E. Klein, H. J. Fox, J. G. TI Helicobacter pullorum Outbreak in C57BL/6NTac and C3H/HeNTac Barrier-Maintained Mice SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CYTOLETHAL DISTENDING TOXIN; SP-NOV; GASTROENTERITIS; IDENTIFICATION; CHICKENS; POULTRY; DISEASE; TISSUE AB Helicobacter pullorum is a bacterial pathogen in humans. By using microaerobic culture techniques, H. pullorum was isolated from the feces of barrier-maintained mice and identified, on the basis of biochemical, restriction fragment length polymorphism, and 16S rRNA gene sequence analyses. This finding presents an opportunity to study H. pullorum pathogenesis in mice. C1 [Shen, Z.; Taylor, N. S.; Fox, J. G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Boutin, S. R.; Roesch, P. L.; Stiefel, S. M.; Sanderson, A. E.; Multari, H. M.; Pridhoko, E. A.; Smith, J. C.; Lohmiller, J. J.; Klein, H. J.] Taconic Inc, Hudson, NY 12534 USA. [Dewhirst, F. E.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,16-825C, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NIH [R01 CA-067529, R01 DK-052413, P30 ES-02109] FX This work was supported by the NIH grants R01 CA-067529, R01 DK-052413 (F. E. Dewhirst), and P30 ES-02109 (J. G. Fox). NR 18 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2010 VL 48 IS 5 BP 1908 EP 1910 DI 10.1128/JCM.02531-09 PG 3 WC Microbiology SC Microbiology GA 592DV UT WOS:000277356600064 PM 20220161 ER PT J AU Koo, S Bryar, JM Baden, LR Marty, FM AF Koo, Sophia Bryar, Julie M. Baden, Lindsey R. Marty, Francisco M. TI Prognostic Features of Galactomannan Antigenemia in Galactomannan-Positive Invasive Aspergillosis (vol 48, pg 1255, 2010) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction C1 [Koo, Sophia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2010 VL 48 IS 5 BP 1994 EP 1994 DI 10.1128/JCM.00680-10 PG 1 WC Microbiology SC Microbiology GA 592DV UT WOS:000277356600095 ER PT J AU Yurkovetsky, Z Skates, S Lomakin, A Nolen, B Pulsipher, T Modugno, F Marks, J Godwin, A Gorelik, E Jacobs, I Menon, U Lu, K Badgwell, D Bast, RC Lokshin, AE AF Yurkovetsky, Zoya Skates, Steven Lomakin, Aleksey Nolen, Brian Pulsipher, Trenton Modugno, Francesmary Marks, Jeffrey Godwin, Andrew Gorelik, Elieser Jacobs, Ian Menon, Usha Lu, Karen Badgwell, Donna Bast, Robert C., Jr. Lokshin, Anna E. TI Development of a Multimarker Assay for Early Detection of Ovarian Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; HUMAN CHORIONIC-GONADOTROPIN; COLONY-STIMULATING FACTOR; TISSUE KALLIKREIN FAMILY; SERUM TUMOR-MARKERS; GROWTH-FACTOR-I; ENDOMETRIAL CANCER; PROGNOSTIC-FACTOR; POOR-PROGNOSIS; CYST FLUIDS AB Purpose Early detection of ovarian cancer has great promise to improve clinical outcome. Patients and Methods Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data. Results A training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer. Conclusion A panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer. C1 [Lokshin, Anna E.] Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. MIT, Dept Phys, Cambridge, MA 02139 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. UCL, Dept Gynecol Oncol, Inst Womens Hlth, London, England. RP Lokshin, AE (reprint author), Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM lokshina@pitt.edu RI Menon, Usha/C-4716-2008; Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013 OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624 FU National Institutes of Health NIH [RO1 CA098642, R01 CA108990, P50 CA083639, CA086381, CA105009]; Avon (NIH/National Cancer Institute); University of Pittsburgh Cancer Institute Hillman Fellows Award; Frieda G. and Saul F. Shapira BRCA Cancer Research Program Award FX Supported by an Early Detection Research Network Associate Member Award and Grants No. RO1 CA098642, R01 CA108990, P50 CA083639, CA086381, and CA105009 from the National Institutes of Health NIH; Avon (NIH/National Cancer Institute); University of Pittsburgh Cancer Institute Hillman Fellows Award; and The Frieda G. and Saul F. Shapira BRCA Cancer Research Program Award (A. E. L.). NR 96 TC 130 Z9 138 U1 2 U2 25 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 MAY 1 PY 2010 VL 28 IS 13 BP 2159 EP 2166 DI 10.1200/JCO.2008.19.2484 PG 8 WC Oncology SC Oncology GA 589US UT WOS:000277180300008 PM 20368574 ER PT J AU Mateos, MV Richardson, PG Schlag, R Khuageva, NK Dimopoulos, MA Shpilberg, O Kropff, M Spicka, I Petrucci, MT Palumbo, A Samoilova, OS Dmoszynska, A Abdulkadyrov, KM Schots, R Jiang, B Esseltine, DL Liu, K Cakana, A van de Velde, H San Miguel, JF AF Mateos, Maria-Victoria Richardson, Paul G. Schlag, Rudolf Khuageva, Nuriet K. Dimopoulos, Meletios A. Shpilberg, Ofer Kropff, Martin Spicka, Ivan Petrucci, Maria T. Palumbo, Antonio Samoilova, Olga S. Dmoszynska, Anna Abdulkadyrov, Kudrat M. Schots, Rik Jiang, Bin Esseltine, Dixie L. Liu, Kevin Cakana, Andrew van de Velde, Helgi San Miguel, Jesus F. TI Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERNATIONAL STAGING SYSTEM; STEM-CELL TRANSPLANTATION; NEWLY-DIAGNOSED MYELOMA; ELDERLY-PATIENTS; PERIPHERAL NEUROPATHY; IMPROVED SURVIVAL; PROGRESSION-FREE; YOUNGER PATIENTS; THALIDOMIDE; EFFICACY AB Purpose The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies. Patients and Methods Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338). Results With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide( 41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months. Conclusion VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse. C1 [San Miguel, Jesus F.] Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc,CSIC, Inst Biol Mol & Celular Canc, Salamanca 37007, Spain. Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Praxisklin Dr Schlag, Wurzburg, Germany. Univ Munster, Munster, Germany. St Petersburg Botkin Moscow City Clin Hosp, Moscow, Russia. Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia. Univ Athens, Sch Med, GR-11527 Athens, Greece. Rabin Med Ctr, Petah Tiqwa, Israel. Univ Hosp, Prague, Czech Republic. Univ Roma La Sapienza, Rome, Italy. Univ Turin, Turin, Italy. Med Univ Lublin, Lublin, Poland. Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. RP San Miguel, JF (reprint author), Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc,CSIC, Inst Biol Mol & Celular Canc, Paseo San Vicente 58-182, Salamanca 37007, Spain. EM sanmigiz@usal.es RI IBSAL, Secretaria/H-3719-2011; OI SAN MIGUEL, JESUS/0000-0002-9183-4857; abdulkadyrov, kudrat/0000-0002-3771-909X FU Johnson & Johnson Pharmaceutical Research Development; Millennium Pharmaceuticals FX Supported by Johnson & Johnson Pharmaceutical Research & Development and Millennium Pharmaceuticals. NR 32 TC 197 Z9 207 U1 1 U2 5 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 MAY 1 PY 2010 VL 28 IS 13 BP 2259 EP 2266 DI 10.1200/JCO.2009.26.0638 PG 8 WC Oncology SC Oncology GA 589US UT WOS:000277180300022 PM 20368561 ER PT J AU Choueiri, TK Schutz, FAB Je, YJ Rosenberg, JE Bellmunt, J AF Choueiri, Toni K. Schutz, Fabio A. B. Je, Youjin Rosenberg, Jonathan E. Bellmunt, Joaquim TI Risk of Arterial Thromboembolic Events With Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID RENAL-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; CANCER-PATIENTS; BEVACIZUMAB; MECHANISMS; INHIBITOR; THERAPY; HYPERTENSION; 1ST-LINE; PATHWAY AB Purpose Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib. Patients and Methods PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. Results A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed. Conclusion Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs. C1 [Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Univ Hosp del Mar, Inst Municipal Invest Med, Barcelona, Spain. RP Choueiri, TK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lank Ctr Genitourinary Oncol,Dana Farber Canc Ins, 44 Binney St Dana 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU Trust Family Research Fund for Kidney Cancer FX Supported by the Trust Family Research Fund for Kidney Cancer. NR 42 TC 182 Z9 183 U1 1 U2 3 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 MAY 1 PY 2010 VL 28 IS 13 BP 2280 EP 2285 DI 10.1200/JCO.2009.27.2757 PG 6 WC Oncology SC Oncology GA 589US UT WOS:000277180300025 PM 20351323 ER PT J AU Grewal, J Zhou, HD Factor, R Kesari, S AF Grewal, Jai Zhou, Huadong Factor, Rachel Kesari, Santosh TI Isolated Loss of Hormonal Receptors in Leptomeningeal Metastasis From Estrogen Receptor- and Progesterone Receptor-Positive Lobular Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 [Grewal, Jai] Long Isl Brain Tumor Ctr Neurol Surg, Great Neck, NY USA. [Zhou, Huadong] Daping Hosp, Dept Neurol, Chongqing, Peoples R China. [Zhou, Huadong] Third Mil Med Univ, Field Surg Res Inst, Chongqing, Peoples R China. [Factor, Rachel] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores Canc Ctr, San Diego, CA 92103 USA. [Kesari, Santosh] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grewal, J (reprint author), Long Isl Brain Tumor Ctr Neurol Surg, Great Neck, NY USA. RI Kesari, Santosh/E-8461-2013 FU Novartis Expert Testimony FX Employment or Leadership Position: None Consultant or Advisory Role: Santosh Kesari, Enzon Pharmaceuticals Stock Ownership: None Honoraria: None Research Funding: Jai Grewal, Novartis Expert Testimony: None Other Remuneration: None NR 3 TC 3 Z9 3 U1 0 U2 2 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 MAY 1 PY 2010 VL 28 IS 13 BP E200 EP E202 DI 10.1200/JCO.2009.25.3518 PG 3 WC Oncology SC Oncology GA 589US UT WOS:000277180300033 PM 20124173 ER PT J AU Sonpavde, G Rosenberg, JE Hahn, NM Galsky, MD Bangs, R Sternberg, CN Vogelzang, NJ AF Sonpavde, Guru Rosenberg, Jonathan E. Hahn, Noah M. Galsky, Matthew D. Bangs, Rick Sternberg, Cora N. Vogelzang, Nicholas J. TI Suggestions for Regulatory Agency Approval of Second-Line Systemic Therapy for Metastatic Transitional Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID COOPERATIVE-ONCOLOGY-GROUP; PHASE-II TRIAL; ADVANCED UROTHELIAL CARCINOMA; PLATINUM-CONTAINING REGIMEN; LUNG-CANCER; SUPPORTIVE CARE; CHEMOTHERAPY; PACLITAXEL; GEMCITABINE; VINFLUNINE C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Rosenberg, Jonathan E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rosenberg, Jonathan E.] Harvard Univ, Sch Med, Boston, MA USA. [Hahn, Noah M.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. [Galsky, Matthew D.; Vogelzang, Nicholas J.] Compehens Canc Ctr Nevada, Las Vegas, NV USA. [Bangs, Rick] SW Oncol Grp, Rochester Hills, MI USA. [Sternberg, Cora N.] San Camillo Forlanini Hosp, Rome, Italy. [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Sonpavde, G (reprint author), Texas Oncol, Houston, TX USA. NR 24 TC 7 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 MAY 1 PY 2010 VL 28 IS 13 BP E205 EP E207 DI 10.1200/JCO.2009.27.1114 PG 3 WC Oncology SC Oncology GA 589US UT WOS:000277180300035 PM 20159797 ER PT J AU Wilens, TE Hammerness, P Martelon, M Brodziak, K Utzinger, L Wong, P AF Wilens, Timothy E. Hammerness, Paul Martelon, MaryKate Brodziak, Kerry Utzinger, Linsey Wong, Patricia TI A Controlled Trial of the Methylphenidate Transdermal System on Before-School Functioning in Children With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BEHAVIOR RATING INVENTORY; EXECUTIVE FUNCTION; HYPERACTIVE-CHILDREN; DOUBLE-BLIND; ADHD; VALIDITY; MOTHERS; TIME AB Objective: Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest behavioral difficulties in the morning prior to school. Our aim was to examine the effects of the methylphenidate transdermal system (MTS) on before-school ADHD symptoms and functioning in children with ADHD. Method: In this randomized crossover study, conducted from May 2007 until December 2008, 6- to 12-year-old subjects with DSM-IV-defined ADHD received either MTS or a placebo transdermal system (PTS) at 10 mg for 1 week and then 20 mg for 1 week. Subjects were then crossed over directly to the other treatment for the remaining 2 weeks. The primary efficacy measure was the ADHD Rating Scale. All analyses were intent to treat, with the last observation carried forward. Results: Thirty subjects completed at least 1 week of treatment, and 26 subjects completed the entire protocol. The sample was primarily male, with a mean +/- SD age of 9.17 +/- 1.84 years. Compared to PTS, there were significant reductions with MTS in the ADHD Rating Scale score (P<.001). Adverse effects of MTS during the active (versus PTS) phase were similar to those seen in other controlled trials of MTS. Conclusions: These results show that MTS is effective not only for morning ADHD symptoms, but also in improving associated activities and functioning that occur before school in children with ADHD. C1 [Wilens, Timothy E.; Hammerness, Paul; Martelon, MaryKate; Brodziak, Kerry; Utzinger, Linsey; Wong, Patricia] Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.; Hammerness, Paul] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. EM twilens@partners.org FU Abbott; McNeil; Eli Lilly; NIH (NIDA); Merck; Shire; Forest; Elminda; Bristol-Myers Squibb; Cephalon; GlaxoSmithKline; Johnson Johnson; New River; Organon; Pfizer; Takeda; Shire Pharmaceutical Company FX Potential conflicts of interest: Dr Wilens receives or has received grant support from Abbott, McNeil, Eli Lilly, NIH (NIDA), Merck, and Shire; has been a speaker for Eli Lilly, McNeil, Novartis, and Shire; has been a consultant for Abbott, AstraZeneca, McNeil, Eli Lilly, NIH (NIDA), Novartis, Merck, and Shire; and has a published book with Guilford Press, Straight Talk About Psychiatric Medications for Kids. Dr Hammerness has received research support from or participated in CME activities/professional talks supported by Abbott, Eli Lilly, Forest, McNeil, Shire, and Elminda; has participated in speaker training with Shire; has participated as an investigator in research studies funded by Abbott, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, McNeil, Merck, New River, Organon, Pfizer, Shire, and Takeda; and has received honoraria from Reed Medical Education (logistics collaborator for MGH Psychiatry Academy)-educational programs are supported through Independent Medical Education grants from pharmaceutical companies along with participant tuition. Mss Martelon, Brodziak, Utzinger, and Wong report no conflict of interest.; Funding/support: This study and medication/placebo were funded by an investigator-initiated grant through Shire Pharmaceutical Company. NR 36 TC 7 Z9 7 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2010 VL 71 IS 5 BP 548 EP 556 DI 10.4088/JCP.09m05779pur PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599XC UT WOS:000277946400006 PM 20492851 ER PT J AU Perlis, RH Adams, DH Fijal, B Sutton, VK Farmen, M Breier, A Houston, JP AF Perlis, Roy H. Adams, David H. Fijal, Bonnie Sutton, Virginia K. Farmen, Mark Breier, Alan Houston, John P. TI Genetic Association Study of Treatment Response With Olanzapine/Fluoxetine Combination or Lamotrigine in Bipolar I Depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RECEPTOR MESSENGER-RNA; GLUCOCORTICOID-RECEPTOR; MOOD DISORDERS; DOUBLE-BLIND; OLANZAPINE; SCHIZOPHRENIA; PHARMACOGENETICS; POLYMORPHISMS; TRIAL; ANKK1 AB Objective: To evaluate common genetic variations for association with symptomatic improvement in bipolar I depression following treatment with olanzapine/fluoxetine combination (OFC) or lamotrigine. Method: Symptom improvement was assessed in 88 OFC-treated and 85 lamotrigine-treated white patients with bipolar I depression in the 7-week acute period of a randomized, double-blind study comparing OFC (6/25, 6/50, 12/25, or 12/50 mg/d [olanzapine/fluoxetine]) with lamotrigine (titrated to 200 mg/d). The original study was conducted from November 2003 to August 2004. Single nucleotide polymorphisms (SNPs) were genotyped in a set of 19 candidate genes corresponding to known sites of activity for olanzapine and fluoxetine or previously associated with antidepressant or antipsychotic response. Primary outcome was the reduction in Montgomery-Asberg Depression Rating Scale (MADRS) total score as assessed by the difference by genotype from baseline to week 7 from a mixed-effects repeated measures analysis with terms for visit, genotype, genotype-by-visit interaction, and baseline MADRS score as a covariate. Results: SNPs within the dopamine D, receptor and histamine H, receptor (HRH1) genes were significantly associated with response to OFC. SNPs within the dopamine D, receptor, HRH1, dopamine beta-hydroxylase, glucocorticoid receptor, and melanocortin 2 receptor genes were significantly associated with response to lamotrigine. Conclusions: SNPs in specific candidate genes were associated with symptomatic improvement in a treatment-specific fashion. These results suggest the importance of dopaminergic effects in the treatment of patients with bipolar I depression and the potential utility of genotyping in selection of pharmacologic treatments for bipolar depression. J Clin Psychiatry 2010;71(5):599-605 (C) Copyright 2009 Physicians Postgraduate Press, Inc. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA USA. [Adams, David H.; Sutton, Virginia K.; Farmen, Mark; Breier, Alan] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Fijal, Bonnie; Houston, John P.] Lilly USA LLC, Indianapolis, IN USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Stanford St,5th Floor, Boston, MA 02114 USA. EM rperlis@partners.org FU Eli Lilly and Company FX Funding/support: Eli Lilly and Company supported this work. NR 32 TC 20 Z9 20 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2010 VL 71 IS 5 BP 599 EP 605 DI 10.4088/JCP.08m04632gre PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599XC UT WOS:000277946400011 PM 20021991 ER PT J AU Stahl, SM Fava, M Trivedi, MH Caputo, A Shah, A Post, A AF Stahl, Stephen M. Fava, Maurizio Trivedi, Madhukar H. Caputo, Angelika Shah, Amy Post, Anke TI Agomelatine in the Treatment of Major Depressive Disorder: An 8-Week, Multicenter, Randomized, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; ANTIDEPRESSANT ACTION; RHYTHM DISTURBANCES; CLINICAL-EFFICACY; DOUBLE-BLIND; SLEEP; RECEPTORS; AGONIST; SCALE; EPIDEMIOLOGY AB Objective: To evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with moderate-to-severe major depressive disorder (MDD) compared to placebo. Method: In this 8-week, multicenter, double-blind, parallel-group trial, patients with DSM-IV-defined MDD were randomly assigned (1:1:1) to receive a once-daily dose of agomelatine 25 mg, agomelatine 50 mg, or placebo. The primary efficacy measure was the change from baseline to week 8 in the clinician-rated 17-item Hamilton Depression Rating Scale (HDRS(17)); other efficacy measures were the clinical remission and response rates (measured by HDRS(17)), Clinical Global Impressions scales, Hospital Anxiety and Depression Scale (HADS) score, subjective measures on sleep, and the overall quality of life. The study was conducted between December 2006 and January 2008. Results: Agomelatine 25 mg/d was more efficacious based on the HDRS(17) total score (P = .01) compared to placebo throughout the treatment period, whereas for agomelatine 50 mg/d, statistically significant reduction in HDRS(17) total score could be observed from weeks 2 to 6 but not at week 8 (P = .144). A higher proportion of patients receiving agomelatine 25 mg/d showed clinical response (P = .013), clinical remission (P = .07), and improvement according to the Clinical Global Impressions-Improvement scale (P = .065) compared to those receiving placebo. No statistically significant difference between patients receiving agomelatine 50 mg/d compared to placebo on clinical response (P = .116) or clinical remission (P = .457) was observed. HADS score, quality of sleep, and quality of life significantly improved with agomelatine 25 mg/d compared to placebo. Both agomelatine doses were safe and well tolerated, although clinically notable aminotransferase elevations were observed transiently in the agomelatine 50 mg/d group. Conclusions: Agomelatine 25 mg/d was effective in the treatment of patients with moderate-to-severe MDD and was safe and well tolerated. Agomelatine 50 mg/d provided evidence for its antidepressant efficacy until week 6 and was also safe and well tolerated. C1 [Stahl, Stephen M.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Caputo, Angelika; Post, Anke] Novartis Pharma AG, Basel, Switzerland. [Shah, Amy] Novartis Pharmaceutical Corp, E Hanover, NJ USA. RP Stahl, SM (reprint author), 1930 Palomar Point Way,Ste 103, Carlsbad, CA 92008 USA. EM smstahl@neiglobal.com FU Forest; Johnson Johnson; Novartis; Organon; Pamlab; Pfizer; Sepracor; Shire; Takeda; Vanda; Wyeth; Abbott; Alkermes; Aspect Medical Systems; Bio Research; BrainCells; Bristol-Myers Squibb; Cephalon; Clinical Trial Solutions; Eli Lilly; Ganeden; GlaxoSmithKline; Lichtwer Pharma; Lorex; NARSAD; NCCAM; NIDA; NIMH; Pharmavite; Roche; Sanofi-Aventis; Solvay; Synthelabo; Wyeth-Ayerst; Agency for Healthcare Research and Quality; Targacept; Fabre-; Fabre-Kramer; Janssen; Neuronetics; Otsuka FX Potential conflicts of interest: Dr Stahl, over the past 12 months (April 2008-May 2009), has served as a consultant to Arena, Azur, Bionevia, Boehringer Ingelheim, Bristol-Myers Squibb, CeNeRx, Dainippon Sumitomo, Eli Lilly, Endo, Forest, Janssen, Jazz, Johnson & Johnson, Labopharm, Lundbeck, Marinus, Neuronetics, Novartis, Noven, Pamlab, Pfizer, Pierre Fabre, Sanofi, Sepracor, Servier, Shire, SK Corporation, Solvay, Somaxon, Tetragenex, and Vanda; has served on speakers bureaus for Wyeth, Pfizer, and Eli Lilly; and has received grant support from Forest, Johnson & Johnson, Novartis, Organon, Pamlab, Pfizer, Sepracor, Shire, Takeda, Vanda, and Wyeth. Dr Fava has received research grants from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bio Research, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, Forest, Ganeden, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma, Lorex, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has served as a consultant or advisor for Abbott, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer, Best Practice Project Management, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Dov, Eli Lilly, EPIX, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmBH, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, Transcept, Vanda, and Wyeth-Ayerst; and has had speaking/publishing-related affiliations with Advanced Meeting Partners, American Psychiatric Association, AstraZeneca, Belvoir,Boehringer, Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, Pharmastar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, and UBC, and Wyeth-Ayerst; has equity holdings in Compellis; has patent applications for SPCD and for a combination of azapirones and bupropion in MDD; and has received copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER. In the last 12 months, Dr Trivedi has received research support from Agency for Healthcare Research and Quality, National Institute of Mental Health, National Institute on Drug Abuse, and Targacept; consulting fees from AstraZeneca, Cephalon, Fabre-Kramer, GlaxoSmithKline, Janssen, Johnson & Johnson, Eli Lilly, Neuronetics, Otsuka, and Pfizer; and consulting fees/honoraria from Bristol-Myers Squibb, Forest, and Wyeth-Ayerst. Drs Shah, Caputo, and Post are fulltime employees of Novartis.; Funding/support: This study was fully supported by Novartis Pharma AG, Basel, Switzerland. NR 52 TC 63 Z9 68 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2010 VL 71 IS 5 BP 616 EP 626 DI 10.4088/JCP.09m05471blu PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599XC UT WOS:000277946400013 PM 20361916 ER PT J AU Stein, MB Ravindran, LN Simon, NM Liebowitz, MR Khan, A Brawman-Mintzer, O Lydiard, RB Pollack, MH AF Stein, Murray B. Ravindran, Lakshmi N. Simon, Naomi M. Liebowitz, Michael R. Khan, Arifulla Brawman-Mintzer, Olga Lydiard, R. Bruce Pollack, Mark H. TI Levetiracetam in Generalized Social Anxiety Disorder: A Double-Blind, Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OPEN-LABEL; DSM-IV; PHOBIA; PREGABALIN; EFFICACY; SCALE AB Objective: This multicenter, double-blind, placebo-controlled, 2-arm, parallel-group study was carried out to determine the effectiveness and safety of the novel anticonvulsant levetiracetam for the treatment of generalized social anxiety disorder (GSAD). Method: After a 1-week, single-blind, placebo run-in period, 217 adult outpatients meeting DSM-IV criteria for social anxiety disorder, generalized type, were randomly assigned (1:1) to 12 weeks of double-blind treatment with either levetiracetam (n = 111) or placebo (n = 106). Participants were required to have scores of >= 60 on the Liebowitz Social Anxiety Scale (LSAS) and a total score of <= 17 on the 17-item Hamilton Depression Rating Scale (HDRS). The primary outcome measure was mean change from baseline on LSAS total score. Levetiracetam was initiated at 250 mg/d and flexibly titrated up to a maximum dose of 3,000 mg/d (1,500 mg bid). Dosage was held stable for the last 6 weeks of treatment. The study was conducted from September 2003 to June 2004. Results: No statistically significant difference was found between the adjusted mean changes in LSAS score for levetiracetam (-24.4) and placebo (-28.7) using an efficacy intent-to-treat, last-observation-carried-forward analysis. Rates of response (>= 30% reduction in LSAS score) were similar with 41.3% (levetiracetam) and 46.6% (placebo). No significant between-group differences were found on secondary outcome measures, which included changes in Sheehan Disability Scale, Clinical Global Impression of Change, and HDRS scores. Conclusions: Although well-tolerated, levetiracetam failed to separate from placebo in this trial for the treatment of moderate to severe GSAD. J Clin Psychiatry 2010;71(5):627-631 (C) Copyright 2009 Physicians Postgraduate Press, Inc. C1 [Stein, Murray B.] Univ Calif San Diego, Anxiety & Traumat Stress Disorders Res Program, La Jolla, CA 92037 USA. [Ravindran, Lakshmi N.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Simon, Naomi M.; Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorder, Boston, MA 02114 USA. [Simon, Naomi M.; Pollack, Mark H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Liebowitz, Michael R.] New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA. [Liebowitz, Michael R.] Columbia Univ, New York, NY USA. [Khan, Arifulla] NW Clin Res Ctr, Dept Psychiat, Bellevue, WA USA. [Brawman-Mintzer, Olga] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Lydiard, R. Bruce] SE Hlth Consultants LLC, Charleston, SC USA. RP Stein, MB (reprint author), Univ Calif San Diego, Anxiety & Traumat Stress Disorders Res Program, 8939 Villa La Jolla Dr,Suite 200, La Jolla, CA 92037 USA. EM mstein@ucsd.edu FU Eli Lilly; GlaxoSmithKline; AstraZeneca; Bristol-Myers Squibb; Cephalon; Forest; Janssen; NARSAD; National Institute of Mental Health (NIMH); Pfizer; UCB Pharma; Sepracor; Takeda; Sanofi-Aventis; Novartis; UCB; Wyeth; Cyberonics; National Institute on Drug Abuse; Roche FX Potential conflicts of interest: Dr Stein has received research support in the past 3 years from Eli Lilly and GlaxoSmithKline and has been a consultant for BrainCells, Bristol-Myers Squibb, Eli Lilly, EPI-Q, Forest, Hoffman-La Roche Pharmaceuticals, Integral Health Decisions, Jazz, Johnson & Johnson, Mindsite, Pfizer, Sanofi-Aventis, Sepracor, Transcept Pharmaceuticals, and Virtual Reality Medical Center. Dr Simon has received grant/research support from AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, National Institute of Mental Health (NIMH), Pfizer, UCB Pharma, and Sepracor; has served on advisory/consultation boards for American Foundation for Suicide Prevention, Paramount Biosciences, Pfizer, Sepracor, and Solvay; and has participated in speaking/CME activities for AstraZeneca, Forest, MGH Psychiatry Academy, Janssen, Eli Lilly, Pfizer, and UCB Pharma. Dr Liebowitz has been a consultant for AstraZeneca, Wyeth, Eli Lilly, Jazz, Tikvah, and Pherin; has served on the speakers/advisory boards for AstraZeneca, Wyeth, Bristol-Myers Squibb, and Jazz; has equity ownership in ChiMatrix LLC and Liebowitz Social Anxiety Scale (LSAS); has licensing software or LSAS with GlaxoSmithKline, Pfizer, Avera, Tikvah, Eli Lilly, Indevus, and Servier; and has had recent or has current clinical trial contracts with Pfizer, GlaxoSmithKline, AstraZeneca, Forest, Tilcvah, Avera, Eli Lilly, Novartis, Sepracor, Horizon, Johnson & Johnson, Pherin, PGX Health, Abbott, Jazz, MAP, Takeda, Wyeth, and Cephalon. Dr Khan, principal investigator of over 330 clinical trials sponsored by over 55 pharmaceutical companies and 30 clinical research organizations, has done no compensated consulting or speaking on their behalf. Dr Brawman-Mintzer has been a consultant to and has served on speakers/advisory boards for Janssen and AstraZeneca; has received honoraria from AstraZeneca; and, more than twelve months ago, received grant/research support from Takeda, AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Forest, Eli Lilly, and UCB.. Dr Brawman-Mintzer's spouse, Dr Jacobo Mintzer, is the Director of the Division of Translational Research at the Medical University of South Carolina. He receives grant support from multiple pharmaceutical companies to perform double-blind, randomized clinical trials in Alzheimer's disease. Dr Mintzer has not received any funding or support from UCB Pharma, maker of levetiracetam. Dr Mintzer is majority owner of a privately held company, BioPharma Connex. This company conducts business with pharmaceutical companies in the commercialization of different compounds in Latin America. None of the business of BioPharma Connex is related to UCB Pharma. Dr Lydiard has received grant/research support from Sanofi-Aventis, Eli Lilly, UCB Pharma, AstraZeneca, Wyeth, Bristol-Myers Squibb, and Forest and has served on speakers or advisory boards for Eli Lilly and Takeda.; Dr Pollack has served on advisory boards for and provides consultation to AstraZeneca, BrainCells, Bristol-Myers Squibb, Cephalon, Dov Pharmaceuticals, Forest, GlaxoSmithKline, Janssen, Jazz, Labopharm, Eli Lilly, Medavante, Neurocrine, Neurogen, Novartis, Otsuka, Pfizer, Predix, Roche, Sanofi, Sepracor, Solvay, Tikvah Therapeutics, Transcept, UCB Pharma, and Wyeth; has received grant support from AstraZeneca, Bristol-Myers Squibb, Cephalon, Cyberonics, Forest, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, National Institute on Drug Abuse, NIMH, Pfizer, Roche, Sepracor, UCB Pharma, and Wyeth; has served on speakers boards for Brstol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Solvay, and Wyeth; has equity in Medavante and Mensante; and has received royalties/patents for the SIGH-A and SAFER. Dr Ravindran reports no financial or other relationships relevant to the subject of this article.; Funding/support: This study was funded in its entirety by UCB Pharma, USA. NR 22 TC 15 Z9 16 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2010 VL 71 IS 5 BP 627 EP 631 DI 10.4088/JCP.08m04949gre PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599XC UT WOS:000277946400014 PM 20021997 ER PT J AU Gershon, AA Gershon, MD Breuer, J Levin, MJ Oaklander, AL Griffiths, PD AF Gershon, Anne A. Gershon, Michael D. Breuer, Judith Levin, Myron J. Oaklander, Anne Louise Griffiths, Paul D. TI Advances in the understanding of the pathogenesis and epidemiology of herpes zoster SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT Global-Virology-Foundation Zoster Workshop CY APR 17-19, 2009 CL Fdn Merieux, Annecy, FRANCE SP Global Virol Fdn HO Fdn Merieux DE Zoster; VZV; Epidemiology; Pathogenesis ID VARICELLA-ZOSTER; POSTHERPETIC NEURALGIA; VIRUS-INFECTIONS; RISK-FACTORS; PHYLOGENETIC ANALYSIS; IMMUNE EVASION; UNITED-KINGDOM; VACCINE; GENOTYPES; RECOMBINATION AB The primary varicella zoster virus (VZV) infection results in chickenpox (varicella), which is transmitted via the airborne route. VZV is highly infectious, but in the USA the incidence of varicella has been reduced by 76-87% as a result of the varicella vaccine. The virus establishes latency in the dorsal root ganglia during varicella and, when reactivated, travels along the sensory nerve axons to cause shingles (herpes zoster [HZ]). There are over 1 million cases of HZ in the USA each year, with an estimated lifetime attack rate of 30%. The incidence of HZ, which causes significant morbidity, increases with age and reaches approximately 10 cases per 1,000 patient-years by age 80. Cell-mediated immunity (CMI) is known to decline with age as part of immunosenescence, and decreased CMI is associated with reactivation of VZV. This article provides an overview of our emerging understanding of the epidemiology and pathogenesis of varicella and HZ, in addition to exploring the current theories on latency and reactivation. Understanding the risk factors for developing HZ and the complications associated with infection, particularly in older people, is important for prompt diagnosis and management of HZ in primary care, and they are therefore also reviewed. (c) 2010 Elsevier B.V. All rights reserved. C1 [Griffiths, Paul D.] Univ Coll Med Sch, Ctr Virol, London NW3 2PF, England. [Gershon, Anne A.] Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. [Gershon, Michael D.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Breuer, Judith] Ctr Infect Dis, London E1 2AT, England. [Levin, Myron J.] Univ Colorado Denver, Aurora, CO 80045 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nerve Injury Unit, Boston, MA 02214 USA. RP Griffiths, PD (reprint author), Univ Coll Med Sch, Ctr Virol, Rowland Hill St, London NW3 2PF, England. EM p.griffiths@medsch.ucl.ac.uk FU NIDDK NIH HHS [R01 DK093094] NR 52 TC 90 Z9 93 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD MAY PY 2010 VL 48 SU 1 BP S2 EP S7 PG 6 WC Virology SC Virology GA 601AZ UT WOS:000278031700002 PM 20510263 ER PT J AU Opstelten, W McElhaney, J Weinberger, B Oaklander, AL Johnson, RW AF Opstelten, Wim McElhaney, Janet Weinberger, Birgit Oaklander, Anne Louise Johnson, Robert W. TI The impact of varicella zoster virus: Chronic pain SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT Global-Virology-Foundation Zoster Workshop CY APR 17-19, 2009 CL Fdn Merieux, Annecy, FRANCE SP Global Virol Fdn HO Fdn Merieux DE Pain; Zoster; VZV; PHN ID ACUTE HERPES-ZOSTER; POSTHERPETIC NEURALGIA; GENERAL-PRACTICE; ELDERLY PERSONS; HUMAN SKIN; ITCH; INFECTION; SHINGLES; CD8(+); CELLS AB Herpes zoster (HZ) is a common condition that affects all age groups and both immunocompetent and immunocompromised individuals. However, it mainly impacts elderly and immunocompromised people and is associated with important and sometimes permanent detriment to quality of life and activities of daily living. Age-related decline in cell-mediated immunity (CMI) permits reactivation of varicella zoster virus (VZV) from latency. The risk of developing post-herpetic neuralgia (PHN) can be predicted using epidemiologically identified risk factors, thus indicating which patients may benefit most from protection by appropriate means, including vaccination. Despite increasing knowledge of the pathology causing PHN, the management modalities for acute HZ pain and PHN remain inadequate. Public, and probably physician, understanding of HZ and its complications is poor, potentially leading to low utilisation of HZ vaccination and delayed presentation for treatment. (c) 2010 Elsevier B.V. All rights reserved. C1 [Johnson, Robert W.] Univ Bristol, Bristol BS41 9EX, Avon, England. [Opstelten, Wim] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [McElhaney, Janet] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [McElhaney, Janet] Univ Connecticut, Sch Med, Ctr Immunotherapy Canc & Infect Dis, Storrs, CT 06269 USA. [Weinberger, Birgit] Austrian Acad Sci, Inst Biomed Aging Res, Innsbruck, Austria. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nerve Injury Unit, Boston, MA 02214 USA. RP Johnson, RW (reprint author), Univ Bristol, 9 Ridgeway Rd, Bristol BS41 9EX, Avon, England. EM r.w.johnson@bris.ac.uk NR 49 TC 14 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD MAY PY 2010 VL 48 SU 1 BP S8 EP S13 PG 6 WC Virology SC Virology GA 601AZ UT WOS:000278031700003 PM 20510265 ER PT J AU Whitley, RJ Volpi, A McKendrick, M van Wijck, A Oaklander, AL AF Whitley, Richard J. Volpi, Antonio McKendrick, Mike van Wijck, Albert Oaklander, Anne Louise TI Management of herpes zoster and post-herpetic neuralgia now and in the future SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT Global-Virology-Foundation Zoster Workshop CY APR 17-19, 2009 CL Fdn Merieux, Annecy, FRANCE SP Global Virol Fdn HO Fdn Merieux DE Zoster; VZV; Antivirals; Management ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; IMMUNOCOMPETENT PATIENTS; ORAL ACYCLOVIR; NUCLEOSIDE ANALOGS; ANTIVIRAL ACTIVITY; NEUROPATHIC PAIN; IMPROVED THERAPY; CLINICAL-TRIAL AB Herpes zoster (HZ; shingles) - a reactivation of the latent varicella zoster virus (VZV) - can cause significant morbidity. Its major complication is pain, particularly post-herpetic neuralgia (PHN). We will review the current management strategies available for the treatment of both acute HZ and PHN, including antiviral drugs, analgesic agents, anticonvulsants, tricyclic antidepressants and topical therapies. New molecules in development that show improved activity against VZV are also covered, and new drug targets are outlined. The role of translational neuroscience in moving towards a goal of finding disease-modifying treatments will be examined. (c) 2010 Elsevier B.V. All rights reserved. C1 [Whitley, Richard J.] Univ Alabama, Birmingham, AL 35233 USA. [Volpi, Antonio] Univ Roma Tor Vergata, Dept Publ Hlth, I-00133 Rome, Italy. [McKendrick, Mike] Royal Hallamshire Hosp, S Yorkshire Reg Dept Infect & Trop Med, Sheffield S10 2JF, S Yorkshire, England. [van Wijck, Albert] Univ Med Ctr Utrecht, Dept Anaesthesiol, Pain Clin, NL-3508 GA Utrecht, Netherlands. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nerve Injury Unit, Boston, MA 02214 USA. RP Whitley, RJ (reprint author), Univ Alabama, CHB 303,1600 7th Ave S, Birmingham, AL 35233 USA. EM rwhitley@peds.uab.edu NR 86 TC 34 Z9 37 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD MAY PY 2010 VL 48 SU 1 BP S20 EP S28 PG 9 WC Virology SC Virology GA 601AZ UT WOS:000278031700005 PM 20510264 ER PT J AU Bredella, MA Ghomi, RH Thomas, BJ Ouellette, HA Sahani, DV Miller, KK Torriani, M AF Bredella, Miriam A. Ghomi, Reza Hosseini Thomas, Bijoy J. Ouellette, Hugue A. Sahani, Dushyant V. Miller, Karen K. Torriani, Martin TI Breath-Hold 1H-Magnetic Resonance Spectroscopy for Intrahepatic Lipid Quantification at 3 Tesla SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE MR spectroscopy; liver; lipids ID PROTON MR SPECTROSCOPY; FATTY LIVER-DISEASE; HEPATIC TRIGLYCERIDE CONTENT; IN-VIVO; NONALCOHOLIC STEATOHEPATITIS; NATURAL-HISTORY; STEATOSIS; REPRODUCIBILITY; PREVALENCE; ADIPOSITY AB Objective: To compare breath-hold 1H-magnetic resonance spectroscopy (1H-MRS) with respiratory-gated 1H-MRS and computed tomography (CT) for quantification of hepatic lipid content. Methods: Twenty-three premenopausal women underwent breath-hold point-resolved single-voxel 1H-MRS of the liver followed by respiratory-gated 1H-MRS at 3 Tesla and CT slice through the liver. Interscan variability for 1H-MRS was assessed in 6 volunteers. Pearson correlation coefficients, Bland-Altman 95% limit of agreement, and concordance correlation coefficients were calculated. Results: There was a strong correlation between breath-hold and respiratory-gated 1H-MRS (r = 0.94, P < 0.0001; concordance correlation coefficient, 0.75). Using Bland-Altman analysis, all but 2 data points were within the limits of agreement. Both 1H-MRS techniques had low interscan variability. There was an inverse correlation of both 1H-MRS techniques with CT attenuation values of the liver. Conclusions: Breath-hold 1H-MRS is a reliable method to measure hepatic lipid content at 3 Tesla. Breath-hold 1H-MRS of the liver provides data that closely correlates with that obtained from longer-duration respiratory-gated technique. C1 [Bredella, Miriam A.; Ghomi, Reza Hosseini; Thomas, Bijoy J.; Ouellette, Hugue A.; Sahani, Dushyant V.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU National Institutes of Health [RO1 HL-077674, UL1 RR025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants RO1 HL-077674, UL1 RR025758, and K23 RR-23090. NR 36 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2010 VL 34 IS 3 BP 372 EP 376 DI 10.1097/RCT.0b013e3181cefb89 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 607GX UT WOS:000278488200009 PM 20498538 ER PT J AU Gaibani, P Vocale, C Ambretti, S Cavrini, F Izard, J Miragliotta, L Pellegrino, MT Sambri, V AF Gaibani, P. Vocale, C. Ambretti, S. Cavrini, F. Izard, J. Miragliotta, L. Pellegrino, M. T. Sambri, V. TI Killing of Treponema denticola by Mouse Peritoneal Macrophages SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE treponemes; phagocytosis; innate immunity; dissemination; immune response; periodontitis ID POLYMERASE-CHAIN-REACTION; PALLIDUM SUBSP PALLIDUM; PERIODONTAL-DISEASE; ENDODONTIC INFECTIONS; SURFACE PROTEIN; MUTANT; INACTIVATION; ASSOCIATION; ACTIVATION; NONSMOKERS AB Treponema denticola has been identified as an important cause of periodontal disease and hypothesized to be involved in extra-oral infections. The objective of this study was to investigate the role of T. denticola cell length and motility during mouse peritoneal macrophages in vitro uptake. Macrophages, incubated under aerobic and anaerobic conditions, produced a similar amount of TNF-alpha when stimulated with Escherichia coli LPS. The uptake of FlgE-and CfpA-deficient mutants of T. denticola was significantly increased compared with the wild-type strain, due to cell size or lack of motility. Opsonization with specific antibodies considerably improved the treponemes' uptake. These results suggest that macrophages, in addition to other phagocytes, could play an important role in the control of T. denticola infection, and that the raising of specific antibodies could improve the efficacy of the immune response toward T. denticola, either at an oral site or during dissemination. C1 [Gaibani, P.; Vocale, C.; Ambretti, S.; Sambri, V.] Univ Bologna, Dept Haematol & Oncol L & A Seragnoli, Microbiol Sect, St Orsola Hosp, I-40138 Bologna, Italy. [Sambri, V.] Natl Inst Biostruct & Biosyst, Bologna, Italy. [Izard, J.] Harvard Univ, Forsyth Inst, Boston, MA 02115 USA. [Izard, J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Sambri, V (reprint author), Univ Bologna, Dept Haematol & Oncol L & A Seragnoli, Microbiol Sect, St Orsola Hosp, 9 Via G Massarenti, I-40138 Bologna, Italy. EM vittorio.sambri@unibo.it RI Izard, Jacques/A-6074-2012; gaibani, paolo/K-7690-2016; OI Izard, Jacques/0000-0002-5904-5436; gaibani, paolo/0000-0003-3791-8635; SAMBRI, VITTORIO/0000-0002-5012-7355 FU FdM; National Institutes of Health, Bethesda, MD [DE017106] FX This work was supported by a grant from "FdM" to VS, and by grant DE017106 from the National Institutes of Health, Bethesda, MD, to JI. NR 26 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2010 VL 89 IS 5 BP 521 EP 526 DI 10.1177/0022034510363105 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 583OA UT WOS:000276685900015 PM 20200417 ER PT J AU Misra, R Patel, T Kotha, P Raji, A Ganda, O Banerji, M Shah, V Vijay, K Mudaliar, S Iyer, D Balasubramanyam, A AF Misra, Ranjita Patel, Thakor Kotha, Purushotham Raji, Annaswamy Ganda, Om Banerji, MaryAnn Shah, Viral Vijay, Kris Mudaliar, Sundar Iyer, Dinakar Balasubramanyam, Ashok TI Prevalence of diabetes, metabolic syndrome, and cardiovascular risk factors in US Asian Indians: results from a national study SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Diabetes prevalence; Asian Indian; CVD risk factors; Metabolic syndrome ID BODY-FAT PATTERN; UNITED-STATES; INSULIN-RESISTANCE; GLUCOSE-INTOLERANCE; ASSOCIATION; DISEASE; OBESITY; MEN; HYPERINSULINEMIA; HEMOGLOBIN AB Background: Although studies of immigrant Asian Indians in other countries show high rates of diabetes (DM), metabolic syndrome (MetS), and cardiovascular disease (CVD), no randomized, population-based studies of this rapidly growing ethnic group exist in the US. Methods: The sample comprised 1038 randomly selected Asian Indian immigrants, aged 18 years and older at seven US sites. Prevalence of diabetes and MetS (age-adjusted and sex-adjusted means) was estimated and ANOVA was used to calculate gender and group differences (normoglycemia/impaired fasting glucose/diabetes) for CVD risk factors. Results: The mean age was 48.2 years. The majority of respondents were male, married, educated, and with some form of health insurance. Prevalence of diabetes was 17.4%, and 33% of the respondents had prediabetes. Cardiovascular risk factors, especially high levels of triglycerides, total cholesterol, LDL cholesterol, homocysteine, and C-reactive protein, and low levels of HDL cholesterol, were also prevalent; elevated lipoprotein(a) was not observed. The age-adjusted prevalence of MetS was 26.9% by the original NCEP/ATP III criteria, 32.7% by the modified NCEP/ATP III criteria, and 38.2% by the IDF criteria. The MetS rates for women, but not for men, increased with age using all three criteria. There was a progressive worsening of all metabolic parameters as individuals progressed from normal to IFG to diabetes. Conclusion: The prevalence rates of diabetes and MetS among US Asian Indians are higher than reported in earlier, nonrandomized, smaller surveys. These data provide a firm basis for future mechanistic and interventional studies. Published by Elsevier Inc. C1 [Misra, Ranjita] Texas A&M Univ, College Stn, TX 77843 USA. [Patel, Thakor] USUHS, Bethesda, MD USA. [Kotha, Purushotham; Mudaliar, Sundar] UC San Diego, San Diego, CA USA. [Raji, Annaswamy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ganda, Om] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Banerji, MaryAnn; Shah, Viral] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Vijay, Kris] Scottsdale Heart Inst, Scottsdale, AZ USA. [Iyer, Dinakar; Balasubramanyam, Ashok] Baylor Coll Med, Houston, TX 77030 USA. RP Misra, R (reprint author), Texas A&M Univ, College Stn, TX 77843 USA. EM misra@hlkn.tamu.edu OI Misra, Ranjita/0000-0001-7314-0184 NR 36 TC 49 Z9 49 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2010 VL 24 IS 3 BP 145 EP 153 DI 10.1016/j.jdiacomp.2009.01.003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 595DL UT WOS:000277590800001 PM 19303333 ER PT J AU Muth, CM Shank, E Hauser, B Radermacher, P Groger, M Ehrmann, U AF Muth, Claus-Martin Shank, Erik Hauser, Balazs Radermacher, Peter Groger, Michael Ehrmann, Ulrich TI INFRARED EAR THERMOMETRY IN WATER-RELATED ACCIDENTS-NOT A GOOD CHOICE SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE drowning; hypothermia; temperature; monitoring; ambulance ID TYMPANIC THERMOMETER; CARDIOPULMONARY BYPASS; CARDIAC-ARREST; TEMPERATURE; HYPOTHERMIA; SUBMERSION; ESOPHAGEAL; ACCURACY; CHILDREN; BRAIN AB Hypothermia in near-drowning victims is a serious problem that impacts clinical decision-making. The purpose of this trial was to determine the reliability of tympanic temperature measurements compared to oral temperature measurements after immersion in water. After ethical approval was obtained, we studied oral and tympanic temperature in 25 volunteer swimmers (aged 18-49 years). Sublingual (Fixotherm; Tradesell Europe, Eglharting, Germany) and tympanic (First Temp Genius; Sherwood Medical, Sulzbach, Germany) temperature measurements were performed before entering the water, after 45 min of immersion in water, and 15 min after leaving the water. During the immersion phase, the ears were temporarily immersed. A control group (the same 25 volunteers) had to swim for the same amount of time without ever immersing their heads in the water. The trial was performed in an indoor swimming pool at 28 degrees C water and 30 degrees C air temperature. The oral temperature did not change over time in either group. The tympanic temperature was significantly lower after immersion compared to baseline in the "immersed" group (33.7 degrees C vs. 37.5 degrees C, p < 0.001), increased significantly in the recovery period, but remained significantly lower than baseline (36.0 degrees C vs. 37.5 degrees C, p < 0.001). At baseline, the oral temperature was lower compared to the tympanic temperature. This relationship reversed after immersion and remained reversed until the end of the trial in the immersion group. The control group maintained oral temperatures lower than tympanic throughout the study; furthermore, the control group had no clinically relevant change in oral or tympanic temperature over the time (tympanic temperature: 37.4 degrees C vs. 37.2 degrees C, p = 0.06). Our data suggest that in water-related accidents such as near drowning, the values of body (core) temperature obtained via use of infrared ear thermometry are unreliable, and should not be used for clinical decision-making. (C) 2010 Elsevier Inc. C1 [Muth, Claus-Martin; Hauser, Balazs; Radermacher, Peter; Groger, Michael; Ehrmann, Ulrich] Univ Ulm Klinikum, Sekt Anaesthesiol Pathophysiol & Verfahrensentwic, Ulm, Germany. [Shank, Erik] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Hauser, Balazs] Semmelweis Egyet, Aneszteziol & Intenziv Terapias Klin, Budapest, Hungary. RP Ehrmann, U (reprint author), Univ Ulm, Univ Klin Anaesthesiol, Sekt Anaesthesiol Pathophysiol & Verfahrensentwic, Pk Str 11, D-89073 Ulm, Germany. NR 29 TC 3 Z9 3 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 MAY PY 2010 VL 38 IS 4 BP 417 EP 421 DI 10.1016/j.jemermed.2007.10.061 PG 5 WC Emergency Medicine SC Emergency Medicine GA 597ZZ UT WOS:000277802600001 PM 18439786 ER PT J AU Perkins, AM Liteplo, A Noble, VE AF Perkins, Alisha M. Liteplo, Andrew Noble, Vicki E. TI ULTRASOUND DIAGNOSIS OF TYPE A AORTIC DISSECTION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE aortic dissection; ultrasound; thoracic aortic dissection; type A dissection; intimal flap ID ECHOCARDIOGRAPHY; ACCURACY AB Background: An aortic dissection is a life-threatening process that must be diagnosed and treated expeditiously. Imaging modalities used for diagnosis in the emergency department include computed tomography, magnetic resonance imaging, and trans-esophageal echocardiography. There are significant limitations to these studies, including patient contraindications (intravenous contrast dye allergies, renal insufficiency, metal-containing implants, hemodynamic instability) and the length of time required for study completion and interpretation by a radiologist or cardiologist. Objectives: A case is presented that demonstrates how emergency physicians can use transthoracic and abdominal bedside ultrasound to diagnose a type A aortic dissection. Case Report: A 72-year-old woman presented with chest pain radiating to her neck and back that was concerning for aortic dissection. This was subsequently confirmed and further classified as a type A dissection by bedside emergency physician-performed ultrasound. The images showed a clear intimal flap in the abdominal aorta, a dilatated aortic root, and extension of the intimal flap into the left common carotid artery. With prompt diagnosis, the patient was able to have emergent surgical consultation, confirmatory imaging, and intervention before further complication occurred. Conclusion: This case provides an example of how emergency transthoracic and abdominal ultrasound can be used to promptly diagnose a type A aortic dissection and expedite further consultation and prompt management. (C) 2010 Elsevier Inc. C1 [Perkins, Alisha M.; Liteplo, Andrew; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Perkins, AM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2010 VL 38 IS 4 BP 490 EP 493 DI 10.1016/j.jemermed.2008.05.013 PG 4 WC Emergency Medicine SC Emergency Medicine GA 597ZZ UT WOS:000277802600016 PM 19038520 ER PT J AU Sullivan, AF Clark, S Pallin, DJ Camargo, CA AF Sullivan, Ashley F. Clark, Sunday Pallin, Daniel J. Camargo, Carlos A., Jr. TI FOOD SECURITY, HEALTH, AND MEDICATION EXPENDITURES OF EMERGENCY DEPARTMENT PATIENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE food insecurity; hunger; Emergency Department ID INSECURITY; OVERWEIGHT; CHILDREN; OBESITY; HUNGER; WOMEN AB Background: In the United States, 35 million people live in food-insecure households. Although food insecurity and hunger are undesirable in their own right, they also are potential precursors to nutritional, health, and developmental problems. Study Objectives: To examine the prevalence of household food insecurity and its association with health problems and medication expenditures among Emergency Department (ED) patients. Methods: We conducted a cross-sectional study in four Boston-area EDs and enrolled consecutive adult patients during two 24-h periods at each site. Food security status was measured using the validated 18-item US Household Food Security Survey Module. Results: Overall, 66 (13%; 95% confidence interval [CI] 10-17%) of 520 ED patients screened positive for food insecurity. Among these 66 patients, 32 (48%; 95% CI 36-61%) reported food insecurity with hunger. Patients from food-insecure households differed from food-secure patients with respect to sociodemographic factors. Food-insecure patients were more likely than food-secure patients to report a variety of chronic and mental health problems (all p < 0.05), including obesity. Food-insecure patients, compared to food-secure patients, also were more likely (all p < 0.001) to put off paying for medication to have money for food (27% vs. 4%, respectively), to take medication less often because they couldn't afford more (32% vs. 4%, respectively), to report needing to make a choice between buying medication and food (27% vs. 2%, respectively), and to report getting sick because they couldn't afford to take medication (27% vs. 1%, respectively). Conclusions: ED patients from food-insecure households report more chronic and mental health problems, and difficulty purchasing medication. (C) 2010 Elsevier Inc. C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Sullivan, Ashley F.] Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Sullivan, AF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Harvard Clinical Nutrition Research Center, (Boston, MA) [P30-DK040561] FX This work was supported by the Harvard Clinical Nutrition Research Center (P30-DK040561) (Boston, MA). NR 20 TC 22 Z9 25 U1 1 U2 7 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 MAY PY 2010 VL 38 IS 4 BP 524 EP 528 DI 10.1016/j.jemermed.2008.11.027 PG 5 WC Emergency Medicine SC Emergency Medicine GA 597ZZ UT WOS:000277802600026 PM 19272731 ER PT J AU Eisner, BH Kurtz, MP Harisinghani, MG AF Eisner, Brian H. Kurtz, Michael P. Harisinghani, Mukesh G. TI Evolving Role of Magnetic Resonance Imaging in Renal Cancer Imaging SO JOURNAL OF ENDOUROLOGY LA English DT Article ID RADIO-FREQUENCY ABLATION; CELL CARCINOMA; RADIOFREQUENCY ABLATION; ANTIANGIOGENIC THERAPY; TUMORS; INVASION; MRI; CT; CLASSIFICATION; CRYOABLATION AB MRI is an imaging modality that is used in the evaluation and treatment of renal cancer. Although less frequently used than CT, MRI is useful in several aspects of renal cancer evaluation and may have some advantages. MRI has shown promising results for renal cancer staging (especially determination of vascular invasion by tumor), in differentiating malignant from benign complex cystic renal lesions, and in the treatment and follow-up of minimally invasive ablative therapies for renal cancer. In addition, new research shows promise for novel applications of MRI. Herein we review the evolving of MRI in renal cancer imaging. C1 [Eisner, Brian H.; Kurtz, Michael P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Harisinghani, Mukesh G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 35 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 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAY PY 2010 VL 24 IS 5 SI SI BP 707 EP 711 DI 10.1089/end.2009.0507 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 596ZA UT WOS:000277723400009 PM 20433369 ER PT J AU de la Rosette, J Ahmed, H Barentsz, J Johansen, TB Brausi, M Emberton, M Frauscher, F Greene, D Harisinghani, M Haustermans, K Heidenreich, A Kovacs, G Mason, M Montironi, R Mouraviev, V de Reijke, T Taneja, S Thuroff, S Tombal, B Trachtenberg, J Wijkstra, H Polascik, T AF de la Rosette, J. Ahmed, H. Barentsz, J. Johansen, T. Bjerklund Brausi, M. Emberton, M. Frauscher, F. Greene, D. Harisinghani, M. Haustermans, K. Heidenreich, A. Kovacs, G. Mason, M. Montironi, R. Mouraviev, V. de Reijke, T. Taneja, S. Thuroff, S. Tombal, B. Trachtenberg, J. Wijkstra, H. Polascik, T. TI Focal Therapy in Prostate Cancer-Report from a Consensus Panel SO JOURNAL OF ENDOUROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; MAPPING BIOPSY; ULTRASOUND AB Purpose: To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. Material and Methods: Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and Europe participated in a consensus workshop on focal therapy for prostate cancer. The consensus process was face to face within a structured meeting, in which pertinent clinical issues were raised, discussed, and agreement sought. Where no agreement was possible, this was acknowledged, and the nature of the disagreement noted. Results: Candidates for focal treatment should have unilateral low-to intermediate-risk disease with clinical stage <= cT(2a). Prostate size and both tumor volume and tumor topography are important case selection criteria that depend on the ablative technology used. Currently, the best method to ascertain the key characteristics for men who are considering focal therapy is exposure to transperineal template mapping biopsies. MRI of the prostate using novel techniques such as dynamic contrast enhancement and diffusion weighed imaging are increasingly being used to diagnose and stage primary prostate cancer with excellent results. For general use, however, these new techniques require validation in prospective clinical trials. Until such are performed, MRI will, in most centers, continue to be an investigative tool in assessing eligibility of patients for focal therapy. Conclusions: Consensus was derived for most of the key aspects of case selection, conduct of treatment, and outcome measures for men who are undergoing focal therapy for localized prostate cancer. The level of agreement achieved will pave the way for future collaborative trials. C1 [de la Rosette, J.; de Reijke, T.; Wijkstra, H.] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands. [Ahmed, H.; Emberton, M.] UCLH UCL Comprehens Biomed Ctr, Div Surg & Intervent Sci, London, England. [Barentsz, J.] Radboud Univ Nijmegen Med Ctr, Dept Radiol, Nijmegen, Netherlands. [Johansen, T. Bjerklund] Arhus Univ Hosp, Dept Urol, Aarhus, Denmark. [Brausi, M.] AUSL Modena, Dept Urol, Modena, Italy. [Frauscher, F.] Med Univ Innsbruck, Dept Radiol, Innsbruck, Austria. [Greene, D.] Sunderland Royal Univ Hosp, Dept Urol, Sunderland, England. [Harisinghani, M.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Haustermans, K.] Univ Hosp Gasthuisberg, Leuven Canc Inst, Dept Radiat Oncol, Louvain, Belgium. [Heidenreich, A.] Rhein Westfal TH Aachen, Dept Urol, Aachen, Germany. [Kovacs, G.] Univ Lubeck, Interdisciplinary Brachytherapy Unit, Lubeck, Germany. [Mason, M.] Cardiff Univ, Sch Med, Sect Oncol & Palliat Med, Cardiff, S Glam, Wales. [Montironi, R.] Polytech Univ Marche Reg, Sch Med, United Hosp, Sect Pathol Anat, Ancona, Italy. [Mouraviev, V.; Polascik, T.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. [Taneja, S.] NYU, Div Urol Oncol, Dept Urol, Langone Med Ctr, New York, NY USA. [Thuroff, S.] Harlaching Klinikum Munich, Dept Urol, Munich, Germany. [Tombal, B.] Clin Univ St Luc, Dept Urol, B-1200 Brussels, Belgium. [Trachtenberg, J.] Princess Margaret Hosp, Dept Urol, Toronto, ON M4X 1K9, Canada. RP de la Rosette, J (reprint author), AMC Univ Hosp, Dept Urol G4 105, Amsterdam, Netherlands. EM j.j.delarosette@amc.uva.nl RI Ahmed, Hashim/C-5744-2008; Barentsz, Jelle/D-3515-2009; OI TOMBAL, Bertrand/0000-0002-0093-8408; bjerklund johansen, truls erik/0000-0003-3490-6460 FU UCLH/UCL Comprehensive Biomedical Research Centre, London, United Kingdom; Medical Research Council UK FX Mark Emberton is funded by UCLH/UCL Comprehensive Biomedical Research Centre, London, United Kingdom; Hashim Ahmed holds a Medical Research Council UK Fellowship. NR 31 TC 76 Z9 77 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD MAY PY 2010 VL 24 IS 5 SI SI BP 775 EP 780 DI 10.1089/end.2009.0596 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 596ZA UT WOS:000277723400019 PM 20477543 ER PT J AU Riley, EH Wright, RJ Jun, HJ Hibert, EN Rich-Edwards, JW AF Riley, E. H. Wright, R. J. Jun, H. J. Hibert, E. N. Rich-Edwards, J. W. TI Hypertension in adult survivors of child abuse: observations from the Nurses' Health Study II SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID BLOOD-PRESSURE; PHYSICAL ABUSE; SEXUAL-ABUSE; RISK-FACTORS; WOMEN; STRESS; MALTREATMENT; DEPRESSION; VIOLENCE; ASSOCIATION AB Background Limited research has shown a possible association between exposure to physical or sexual abuse prior to age 18 and the risk of developing hypertension as an adult. The factors mediating this relationship are unknown. Methods Questionnaire data from 68 505 female participants in the Nurses' Health Study II were analysed regarding exposure to physical and sexual abuse prior to age 18. Cox proportional hazards regression was used to assess the relationship between abuse exposure and hypertension. Results 64% of the participants (n = 41 792) reported physical and/or sexual abuse prior to age 18; 17% reported hypertension. All forms of abuse had a dose-response relationship with hypertension. Adjustments for smoking, alcohol, family history of hypertension, exercise and oral contraceptives did not alter risk estimates. Adjustment for body mass index (BMI) significantly attenuated the associations between abuse and risk of hypertension and accounted for approximately 50% of the observed association between abuse exposure and hypertension. Women experiencing forced sexual activity as a child and as an adolescent had a 20% increased risk for developing hypertension (95% CI 8% to 32%) that was independent of BMI. Similarly, women reporting severe physical abuse in childhood and/or adolescence had risk estimates ranging from 14% (95% CI 5% to 24%) to 22% (95% CI 11% to 33%). Conclusion Early interpersonal violence may be a widespread risk factor for the development of hypertension in women. BMI is a significant mediator in the relationship between early abuse and adult hypertension. C1 [Riley, E. H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wright, R. J.; Jun, H. J.; Hibert, E. N.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Wright, R. J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Rich-Edwards, J. W.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Rich-Edwards, J. W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Riley, EH (reprint author), 165 Cambridge St,Suite 501, Boston, MA 02114 USA. EM ehriley@partners.org FU National Institute of Health [HL081557, CA50385, HL64108] FX Funding This work was funded by National Institute of Health grants HL081557, CA50385, and HL64108. The study sponsors had no role in the study design, collection, analysis and interpretation of data, writing or editing of the manuscript, or in the decision to submit for publication. NR 50 TC 41 Z9 41 U1 1 U2 11 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD MAY PY 2010 VL 64 IS 5 BP 413 EP 418 DI 10.1136/jech.2009.095109 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 591SK UT WOS:000277323700008 PM 20445210 ER PT J AU Bliss-Moreau, E Owren, MJ Barrett, LF AF Bliss-Moreau, Eliza Owren, Michael J. Barrett, Lisa Feldman TI I like the sound of your voice: Affective learning about vocal signals SO JOURNAL OF EXPERIMENTAL SOCIAL PSYCHOLOGY LA English DT Article DE Affect; Value; Learning; Vocalization ID AUTOMATIC ATTITUDE ACTIVATION; TALKER IDENTITY; SPEECH; COMMUNICATION; INFORMATION; EMOTION; CONTEXT; VOWELS AB This paper provides the first demonstration that the content of a talker's speech is sufficient to imbue the acoustics of his voice with affective meaning. In two studies, participants listened to male talkers utter positive, negative, or neutral words. Next, participants completed a sequential evaluative priming task where a neutral word spoken by one of talkers was presented before each target word to be evaluated. We predicted, and found, that voices served as evaluative primes influencing the speed with which participants evaluated the target words. These two experiments demonstrate that the human voice can take on affective meaning merely based on the positive or negative value words it has spoken. Implications for affective processing, the pragmatics of communication, and person perception are discussed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Bliss-Moreau, Eliza] Univ Calif Davis, Calif Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Sch Med, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Boston Coll, Chestnut Hill, MA 02167 USA. [Owren, Michael J.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RP Bliss-Moreau, E (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, Dept Psychiat & Behav Sci, 1 Shields Ave, Davis, CA 95616 USA. EM eblissmoreau@ucdavis.edu FU NIH HHS [DP1 OD003312, DP1 OD003312-01, DP1 OD003312-03]; NIMH NIH HHS [K02 MH001981-03, R01 MH065317-01A2, K02 MH001981-05, K02 MH001981, R01 MH065317] NR 28 TC 3 Z9 4 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 0022-1031 J9 J EXP SOC PSYCHOL JI J. Exp. Soc. Psychol. PD MAY PY 2010 VL 46 IS 3 BP 557 EP 563 DI 10.1016/j.jesp.2009.12.017 PG 7 WC Psychology, Social SC Psychology GA 590IE UT WOS:000277218000009 PM 20495619 ER PT J AU Leykum, L Mortensen, E AF Leykum, Luci Mortensen, Eric TI Exploring the Potential Causes of the Emergence of Hospitalists: Chicken vs. Egg SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; CARE; MOVEMENT; GROWTH C1 [Leykum, Luci; Mortensen, Eric] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Leykum, Luci] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, San Antonio, TX 78229 USA. RP Mortensen, E (reprint author), Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2010 VL 25 IS 5 BP 378 EP 379 DI 10.1007/s11606-010-1320-2 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 584AH UT WOS:000276721900002 PM 20309739 ER PT J AU Katon, WJ Lin, EHB Williams, LH Ciechanowski, P Heckbert, SR Ludman, E Rutter, C Crane, PK Oliver, M Von Korff, M AF Katon, Wayne J. Lin, Elizabeth H. B. Williams, Lisa H. Ciechanowski, Paul Heckbert, Susan R. Ludman, Evette Rutter, Carolyn Crane, Paul K. Oliver, Malia Von Korff, Michael TI Comorbid Depression Is Associated with an Increased Risk of Dementia Diagnosis in Patients with Diabetes: A Prospective Cohort Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE depression; dementia; diabetes ID ALZHEIMERS-DISEASE; MAJOR DEPRESSION; HIPPOCAMPAL VOLUME; COGNITIVE DECLINE; EPSILON-4 ALLELE; OLDER-ADULTS; SELF-CARE; SYMPTOMS; HEALTH; WOMEN AB Both depression and diabetes have been found to be risk factors for dementia. This study examined whether comorbid depression in patients with diabetes increases the risk for dementia compared to those with diabetes alone. We conducted a prospective cohort study of 3,837 primary care patients with diabetes (mean age 63.2 +/- 13.2 years) enrolled in an HMO in Washington State. The Patient Health Questionnaire (PHQ-9) was used to assess depression at baseline, and ICD-9 diagnoses for dementia were used to identify cases of dementia. Cohort members with no previous ICD-9 diagnosis of dementia prior to baseline were followed for a 5-year period. The risk of dementia for patients with both major depression and diabetes at baseline relative to patients with diabetes alone was estimated using cause-specific Cox proportional hazard regression models that adjusted for age, gender, education, race/ethnicity, diabetes duration, treatment with insulin, diabetes complications, nondiabetes-related medical comorbidity, hypertension, BMI, physical inactivity, smoking, HbA(1c), and number of primary care visits per month. Over the 5-year period, 36 of 455 (7.9%) patients with major depression and diabetes (incidence rate of 21.5 per 1,000 person-years) versus 163 of 3,382 (4.8%) patients with diabetes alone (incidence rate of 11.8 per 1,000 person-years) had one or more ICD-9 diagnoses of dementia. Patients with comorbid major depression had an increased risk of dementia (fully adjusted hazard ratio 2.69, 95% CI 1.77, 4.07). Patients with major depression and diabetes had an increased risk of development of dementia compared to those with diabetes alone. These data add to recent findings showing that depression was associated with an increased risk of macrovascular and microvascular complications in patients with diabetes. C1 [Katon, Wayne J.; Ciechanowski, Paul] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lin, Elizabeth H. B.; Ludman, Evette; Rutter, Carolyn; Oliver, Malia; Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Williams, Lisa H.; Crane, Paul K.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Williams, Lisa H.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Heckbert, Susan R.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. RP Katon, WJ (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM wkaton@u.washington.edu RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU NIMH [R01 MH073686, K24 MH069741] FX This study was supported by NIMH R01 MH073686 (Von Korff) and NIMH K24 MH069741 (Katon). The authors would like to acknowledge Jurgen Unutzer, MD, MPH, for providing critiques for this manuscript. NR 55 TC 52 Z9 53 U1 2 U2 13 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 MAY PY 2010 VL 25 IS 5 BP 423 EP 429 DI 10.1007/s11606-009-1248-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 584AH UT WOS:000276721900012 PM 20108126 ER PT J AU Jacobs, EA Beach, MC Saha, S AF Jacobs, Elizabeth A. Beach, Mary Catherine Saha, Somnath TI What Matters in Health Disparities Education-Changing Hearts or Minds? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID ATTITUDES C1 [Jacobs, Elizabeth A.] John H Stroger Jr Hosp Cook Cty, Div Gen Med, Chicago, IL 60612 USA. [Jacobs, Elizabeth A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Div Gen Internal Med, Chicago, IL USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR USA. RP Jacobs, EA (reprint author), John H Stroger Jr Hosp Cook Cty, Div Gen Med, 1900 W Polk St,16th Floor, Chicago, IL 60612 USA. EM ejacobs@rush.edu NR 14 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2010 VL 25 SU 2 BP S198 EP S199 DI 10.1007/s11606-010-1297-x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591AQ UT WOS:000277270300025 PM 20352521 ER PT J AU Wakeman, SE Rich, JD AF Wakeman, Sarah E. Rich, Josiah D. TI Fulfilling the Mission of Academic Medicine: Training Residents in the Health Needs of Prisoners SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE academic; residency; prison; incarceration; training ID DISEASE; INFECTION; EDUCATION; INMATES AB The single mission of academic medicine is the pursuit of health for all. This mandate serves as a reminder to focus care on vulnerable and underserved populations. The 12 million Americans who cycle through correctional facilities each year are arguably among the most vulnerable populations in this country; predominantly black, with a high burden of disease and many barriers to care after release. Medical training programs should provide exposure to the health needs of prisoners. Residents could establish care with inmates prior to release and arrange follow-up in the community. This addition to training would not only provide care to this underserved group, but also would train residents in the myriad problems prisoners face, and foster social responsibility. C1 [Rich, Josiah D.] Miriam Hosp, Dept Med, Div Infect Dis, Providence, RI 02906 USA. [Wakeman, Sarah E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rich, Josiah D.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Rich, Josiah D.] Ctr Prisoner Hlth & Human Rights, Providence, RI USA. RP Rich, JD (reprint author), Miriam Hosp, Dept Med, Div Infect Dis, Providence, RI 02906 USA. EM JRich@lifespan.org FU National Institute on Drug Abuse, National Institutes of Health [1K24DA022112-01A]; (NIDA/NIH); National Institutes of Health; Center for AIDS Research (NIH/CFAR); NIDA [P30DA013868] FX This work was supported in part by grant number 1K24DA022112-01A from the National Institute on Drug Abuse, National Institutes of Health; (NIDA/NIH) to Dr Rich and by grant number P30-AI-42853 from the National; Institutes of Health, Center for AIDS Research (NIH/CFAR), and by grant number P30DA013868 from the NIDA funded Center for Drug Abuse and AIDS Research (CDAAR). We would like to thank Dr. Charles C. J. Carpenter for his ongoing inspiration, mentorship and careful review of this manuscript. NR 26 TC 3 Z9 3 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2010 VL 25 SU 2 BP S186 EP S188 DI 10.1007/s11606-010-1258-4 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 591AQ UT WOS:000277270300022 PM 20352517 ER PT J AU Jung, SR Hille, B Nguyen, TD Koh, DS AF Jung, Seung-Ryoung Hille, Bertil Nguyen, Toan D. Koh, Duk-Su TI Cyclic AMP potentiates Ca2+-dependent exocytosis in pancreatic duct epithelial cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID PAROTID ACINAR-CELLS; PROTEIN-KINASE-A; REGULATED EXOCYTOSIS; CHROMAFFIN CELLS; ACTIVATED RECEPTOR-2; TRANSMITTER RELEASE; SECRETORY GRANULES; VESICLE DYNAMICS; ION CHANNELS; SYNAPSIN-I AB Exocytosis is evoked by intracellular signals, including Ca2+ and protein kinases. We determined how such signals interact to promote exocytosis in exocrine pancreatic duct epithelial cells (PDECs). Exocytosis, detected using carbon-fiber microamperometry, was stimulated by [Ca2+](i) increases induced either through Ca2+ influx using ionomycin or by activation of P2Y2 or protease-activated receptor 2 receptors. In each case, the exocytosis was strongly potentiated when cyclic AMP (cAMP) was elevated either by activating adenylyl cyclase with forskolin or by activating the endogenous vasoactive intestinal peptide receptor. This potentiation was completely inhibited by H-89 and partially blocked by Rp-8-Br-cAMPS, inhibitors of protein kinase A. Optical monitoring of fluorescently labeled secretory granules showed slow migration toward the plasma membrane during Ca2+ elevations. Neither this Ca2+-dependent granule movement nor the number of granules found near the plasma membrane were detectably changed by raising cAMP, suggesting that cAMP potentiates Ca2+-dependent exocytosis at a later stage. A kinetic model was made of the exocytosis stimulated by UTP, trypsin, and Ca2+ ionophores with and without cAMP increase. In the model, without a cAMP rise, receptor activation stimulates exocytosis both by Ca2+ elevation and by the action of another messenger(s). With cAMP elevation the docking/priming step for secretory granules was accelerated, augmenting the releasable granule pool size, and the Ca2+ sensitivity of the final fusion step was increased, augmenting the rate of exocytosis. Presumably both cAMP actions require cAMP-dependent phosphorylation of target proteins. cAMP-dependent potentiation of Ca2+-induced exocytosis has physiological implications for mucin secretion and, possibly, for membrane protein insertion in the pancreatic duct. In addition, mechanisms underlying this potentiation of slow exocytosis may also exist in other cell systems. C1 [Jung, Seung-Ryoung; Hille, Bertil; Koh, Duk-Su] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. [Nguyen, Toan D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Nguyen, Toan D.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Jung, Seung-Ryoung; Koh, Duk-Su] POSTECH, Dept Phys, Pohang 790784, Kyungbuk, South Korea. RP Koh, DS (reprint author), Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. EM koh@u.washington.edu FU Korea Science and Engineering Foundation [M7-2004-000-10106-0]; R&D Program of Advanced Technologies; National Institutes of Health [GM083913]; Department of Veterans Affairs FX This work was supported by the International Research Internship Program of the Korea Science and Engineering Foundation (to S.-R. Jung, M7-2004-000-10106-0), grants from R&D Program of Advanced Technologies (to D.-S. Koh), the National Institutes of Health (GM083913 to B. Hille), and the Department of Veterans Affairs (Merit Review to T. D. Nguyen). NR 54 TC 8 Z9 8 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAY PY 2010 VL 135 IS 5 BP 527 EP 543 DI 10.1085/jgp.200910355 PG 17 WC Physiology SC Physiology GA 587ZM UT WOS:000277035500011 PM 20421376 ER PT J AU Yusim, K Fischer, W Yoon, H Thurmond, J Fenimore, PW Lauer, G Korber, B Kuiken, C AF Yusim, Karina Fischer, William Yoon, Hyejin Thurmond, James Fenimore, Paul W. Lauer, Georg Korber, Bette Kuiken, Carla TI Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage of genetic diversity SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC LIVER-DISEASE; IMMUNE-RESPONSES; VIRAL CLEARANCE; HIV-1 VACCINE; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; RHESUS-MONKEYS; UNITED-STATES; BLOOD-DONORS AB Immunological control of hepatitis C virus (HCV) is possible and is probably mediated by host T-cell responses, but the genetic diversity of the virus poses a major challenge to vaccine development. We considered monovalent and polyvalent candidates for an HCV vaccine, including natural, consensus and synthetic 'mosaic' sequence cocktails. Mosaic vaccine reagents were designed using a computational approach first applied to and demonstrated experimentally for human immunodeficiency virus type 1 (HIV-Delta). Mosaic proteins resemble natural proteins, but are assembled from fragments of natural sequences via a genetic algorithm and optimized to maximize the coverage of potential T-cell epitopes (all 9-mers) found in natural sequences and to minimize the inclusion of rare 9-mers to avoid vaccine-specific responses. Genotype 1-specific and global vaccine cocktails were evaluated. Among vaccine candidates considered, polyvalent mosaic sequences provided the best coverage of both known and potential epitopes and had the fewest rare epitopes. A global vaccine based on conserved proteins across genotypes may be feasible, as a five-antigen mosaic cocktail provided 90, 77 and 70% coverage of the Core, NS3 and NS4 proteins, respectively; protein coverage diminished with increased protein variability, dropping to 38% for NS2. For the genotype 1-specific vaccine, the H77 prototype vaccine sequence matched only 50% of the potential epitopes in the population, whilst a polyprotein three-antigen mosaic cocktail increased potential epitope coverage to 83%. More than 75% coverage of all HCV proteins was achieved with a three-antigen mosaic cocktail, suggesting that genotype-specific vaccines could also include the more variable proteins. C1 [Yusim, Karina; Fischer, William; Yoon, Hyejin; Thurmond, James; Fenimore, Paul W.; Korber, Bette; Kuiken, Carla] Los Alamos Natl Lab, Div Theory, Los Alamos, NM 87545 USA. [Lauer, Georg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Yusim, K (reprint author), Los Alamos Natl Lab, Div Theory, Los Alamos, NM 87545 USA. EM kyusim@lanl.gov OI Fischer, Will/0000-0003-4579-4062; Korber, Bette/0000-0002-2026-5757 FU Los Alamos National Laboratory [LDRD 20050155DR] FX Funding for this work was provided by the Los Alamos National Laboratory Directed Research Program (LDRD 20050155DR, 'Rational Vaccine Design'). We thank Jennifer Macke for assistance in editing the manuscript. NR 51 TC 21 Z9 21 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 2010 VL 91 BP 1194 EP 1206 DI 10.1099/vir.0.017491-0 PN 5 PG 13 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 597MH UT WOS:000277761100012 PM 20053820 ER PT J AU Ring, D AF Ring, David TI Commentary: Terms That Accurately Reflect Current Best Evidence SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkee Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 1 TC 1 Z9 1 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 MAY PY 2010 VL 35A IS 5 BP 718 EP 718 DI 10.1016/j.jhsa.2010.02.014 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 592GT UT WOS:000277367100002 PM 20438991 ER PT J AU Vranceanu, AM Kadzielski, J Hwang, R Ring, D AF Vranceanu, Ana-Maria Kadzielski, John Hwang, Ray Ring, David TI A Patient-Specific Version of the Disabilities of the Arm, Shoulder, and Hand Questionnaire SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Disability; Disabilities of the Arm; Shoulder; Hand questionnaire; carpal tunnel syndrome ID INDEX; PAIN; VALIDATION; OUTCOMES; SCALE AB Purpose We modified the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire to be weighted according to a patient's priorities (patient-specific [PS-DASH]) and compared it with the DASH in terms of its mean and variance and its relationship with coping styles (pain avoidance, pain catastrophizing, anxiety sensitivity, and hypochondriasis), depression, and overall stress. Methods Ninety-eight patients with carpal tunnel syndrome completed questionnaires measuring depression, pain catastrophizing, avoidance, hypochondriasis, anxiety sensitivity, and ordinal measures of self-reported stress and disability. They also completed the DASH and a modification of the DASH that weighted each item according to personal priorities. Results The DASH scores had a significantly higher mean and greater standard deviation than the PS-DASH (mean +/- standard deviation, 54.1 +/- 16.8 vs 32.7 +/- 11.0). Health anxiety (r = 0.355), anxiety sensitivity (r = 0.258), and pain catastrophizing (r = 0.421) were significantly related to PS-DASH; health anxiety (r = 0.298), depression (r = 0.225), and pain catastrophizing (r = .350) were significantly related to DASH. Multivariable regression analyses were statistically significant, but accounted for only 35% of the variance in PS-DASH and 17% of the variance in DASH. Pain catastrophizing and gender were the sole significant predictors for PS-DASH (B = 0.290, B = 0.384), whereas only pain catastrophizing predicted DASH (B = 0.251). Conclusions A version of the DASH weighted according to patient priorities narrowed the variability in DASH scores but did not appear to have sufficient advantage over DASH to warrant this much more cumbersome questionnaire. (J Hand Surg 2010;35A:824-826. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Ring, David] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthoped Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Combined Orthopaed Residency, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Acuried; LLC; Biomet; Smith Nephew; Tornier FX D.R. received support from Acuried, LLC, Biomet, Smith & Nephew, and Tornier. NR 18 TC 5 Z9 7 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 MAY PY 2010 VL 35A IS 5 BP 824 EP 826 DI 10.1016/j.jhsa.2010.02.029 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 592GT UT WOS:000277367100020 PM 20438997 ER PT J AU Ring, D AF Ring, David TI Effectiveness of Magnetic Resonance Imaging in Detecting Partial and Complete Distal Biceps Tendon Rupture SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 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 MAY PY 2010 VL 35A IS 5 BP 865 EP 865 DI 10.1016/j.jhsa.2010.01.026 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 592GT UT WOS:000277367100033 PM 20439006 ER PT J AU Hasnain-Wynia, R Kang, R Landrum, MB Vogeli, C Baker, DW Weissman, JS AF Hasnain-Wynia, Romana Kang, Raymond Landrum, Mary Beth Vogeli, Christine Baker, David W. Weissman, Joel S. TI Racial and Ethnic Disparities within and between Hospitals for Inpatient Quality of Care: An Examination of Patient-Level Hospital Quality Alliance Measures SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Disparities; quality of care; Hospital Quality Alliance; inpatient ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; US HOSPITALS; PERFORMANCE-MEASURES; MORTALITY-RATES; BLACK PATIENTS; HEART-FAILURE; OUTCOMES; ASSOCIATION; PHYSICIANS AB Background. Little is known about whether disparities occur within or between hospitals for national Hospital Quality Alliance (HQA) measures. Methods. We examined patient-level data from 4,450 non-federal hospitals in the U.S. for over 2.3 million Black, Hispanic, Asian, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander patients who received care for acute myocardial infarction, heart failure, or pneumonia in 2005. Results. There were 37 out of 95 findings of disparities after adjusting for patient characteristics. Eleven of the disparities were explained entirely by where minorities received care and the magnitude for 25 of the others was substantially reduced after adjusting for site of care. Discussion. Adjusting for between-hospital quality differences accounted for a large proportion of the disparities. Where disparities exist, the primary cause may be that minorities are more likely to receive care in lower-performing hospitals. Policies to reduce disparities should include targeting resources to facilities serving a high percentage of minority patients. C1 [Hasnain-Wynia, Romana] Northwestern Univ, Ctr Healthcare Equ, Inst Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Landrum, Mary Beth] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Vogeli, Christine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Hasnain-Wynia, R (reprint author), Northwestern Univ, Ctr Healthcare Equ, Inst Healthcare Studies, Feinberg Sch Med, 750 Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM r-hasnainwynia@northwestern.edu RI Schiaffino, Melody/E-9629-2011 NR 47 TC 19 Z9 19 U1 2 U2 11 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 MAY PY 2010 VL 21 IS 2 BP 629 EP 648 PG 20 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 594GC UT WOS:000277523200018 PM 20453362 ER PT J AU Lakdawalla, DN Sun, EC Jena, AB Reyes, CM Goldman, DP Philipson, TJ AF Lakdawalla, Darius N. Sun, Eric C. Jena, Anupam B. Reyes, Carolina M. Goldman, Dana P. Philipson, Tomas J. TI An economic evaluation of the war on cancer SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE Cancer; Economic gains; Life expectancy ID HEALTH; DRUGS; PRICE; LIFE; COMPETITION; MORTALITY; COSTS AB For decades, the US public and private sectors have committed substantial resources towards cancer research, but the societal payoff has not been well-understood. We quantify the value of recent gains in cancer survival, and analyze the distribution of value among various stakeholders. Between 1988 and 2000, life expectancy for cancer patients increased by roughly four years, and the average willingness-to-pay for these survival gains was roughly $322,000. Improvements in cancer survival during this period created 23 million additional life-years and roughly $1.9 trillion of additional social value, implying that the average life-year was worth approximately $82,000 to its recipient. Health care providers and pharmaceutical companies appropriated 5-19% of this total, with the rest accruing to patients. The share of value flowing to patients has been rising over time. In terms of economic rates of return, R&D investments against cancer have been a success, particularly from the patient's point of view. (C) 2010 Published by Elsevier B.V. C1 [Sun, Eric C.; Philipson, Tomas J.] Univ Chicago, Chicago, IL 60637 USA. [Lakdawalla, Darius N.; Sun, Eric C.; Goldman, Dana P.] RAND Corp, Santa Monica, CA 90406 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lakdawalla, Darius N.; Goldman, Dana P.] Univ So Calif, Los Angeles, CA 90089 USA. [Reyes, Carolina M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Philipson, TJ (reprint author), Univ Chicago, Chicago, IL 60637 USA. EM t-philipson@uchicago.edu RI Lakdawalla, Darius/B-4409-2011; OI Lakdawalla, Darius/0000-0001-5934-8042 FU Genentech, Inc.; RAND Corporation's Bing Center for Health Economics FX The authors wish to thank Genentech, Inc., and the RAND Corporation's Bing Center for Health Economics for financial support. The opinions expressed herein are solely those of the authors. NR 38 TC 28 Z9 28 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD MAY PY 2010 VL 29 IS 3 BP 333 EP 346 DI 10.1016/j.jhealeco.2010.02.006 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 604RW UT WOS:000278297200001 PM 20363520 ER PT J AU Filen, S Ylikoski, E Tripathi, S West, A Bjorkman, M Nystrom, J Ahlfors, H Coffey, E Rao, KVS Rasool, O Lahesmaa, R AF Filen, Sanna Ylikoski, Emmi Tripathi, Subhash West, Anne Bjorkman, Mari Nystrom, Joel Ahlfors, Helena Coffey, Eleanor Rao, Kanury V. S. Rasool, Omid Lahesmaa, Riitta TI Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER-CELL-DIFFERENTIATION; CD4(+) T-CELLS; TH2 CELLS; C-JUN; GAMMA PRODUCTION; SELECTIVE EXPRESSION; LINEAGE COMMITMENT; NEGATIVE REGULATOR; STAT4 ACTIVATION; ATF3 GENE AB IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-alpha in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation. The Journal of Immunology, 2010, 184: 4990-4999. C1 [Filen, Sanna; Ylikoski, Emmi; Tripathi, Subhash; West, Anne; Bjorkman, Mari; Nystrom, Joel; Ahlfors, Helena; Coffey, Eleanor; Rasool, Omid; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland. [Ahlfors, Helena] Abo Akad Univ, Natl Sch Informat & Struct Biol, Turku, Finland. [Filen, Sanna] Univ Turku, Drug Discovery Grad Sch, FI-20521 Turku, Finland. [Ylikoski, Emmi] Univ Turku, Turku Grad Sch Biomed Sci, FI-20521 Turku, Finland. [Rao, Kanury V. S.] Int Ctr Genet Engn & Biotechnol, New Delhi, India. [Lahesmaa, Riitta] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Lahesmaa, R (reprint author), Univ Turku, Turku Ctr Biotechnol, POB 123, FI-20521 Turku, Finland. EM riitta.lahesmaa@btk.fi FU National Technology Agency of Finland; Academy of Finland; Turku University Hospital Fund; Turku University Foundation; Ida Montin Foundation; Oskar Oflund Foundation; Hengityssairauksien Tutkimussaatio FX This work was supported by the National Technology Agency of Finland, the Academy of Finland, Turku University Hospital Fund, Turku University Foundation, Ida Montin Foundation, Oskar Oflund Foundation, and Hengityssairauksien Tutkimussaatio. NR 64 TC 23 Z9 23 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 MAY 1 PY 2010 VL 184 IS 9 BP 4990 EP 4999 DI 10.4049/jimmunol.0903106 PG 10 WC Immunology SC Immunology GA 588SD UT WOS:000277093000051 PM 20304822 ER PT J AU Zhao, H Leu, SW Shi, LY Dedaj, R Zhao, GF Garg, HG Shen, LJ Lien, E Fitzgerald, KA Shiedlin, A Shen, HH Quinn, DA Hales, CA AF Zhao, Hang Leu, Shaw-Wei Shi, Liyun Dedaj, Rejmon Zhao, Gaofeng Garg, Hari G. Shen, Lianjun Lien, Egil Fitzgerald, Katherine A. Shiedlin, Aviva Shen, Huahao Quinn, Deborah A. Hales, Charles A. TI TLR4 Is a Negative Regulator in Noninfectious Lung Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY INFLAMMATION; HYALURONIC-ACID; PATHOGEN RECOGNITION; SIGNALING PATHWAY; DANGER SIGNAL; INJURY; INTERLEUKIN-1; GENE AB Low m.w. hyaluronan (LMW HA) has been shown to elicit the expression of proinflammatory cytokines and chemokines in various cells in vitro. However, the effects of this molecule in vivo are unknown. In this study, we report that intratracheal administration of LMW HA (200 kDa) causes inflammation in mouse lung. A lack of TLR4 is associated with even stronger inflammatory response in the lung as shown by increased neutrophil counts and elevated cytokine and chemokine concentrations. We also demonstrate that TLR4 anti-inflammatory signaling is dependent upon a MyD88-independent pathway. TLR4-mediated IL-1R antagonist production plays a negative regulatory role in LMW HA (200 kDa) induced lung inflammation. These data provide a molecular level explanation for the function of TLR4 in LMW HA (200 kDa)-induced lung inflammation, as inhibition of the 13 form of pro IL-1 promotes an anti-inflammatory response. The Journal of Immunology, 2010, 184: 5308-5314. C1 [Zhao, Hang; Leu, Shaw-Wei; Shi, Liyun; Dedaj, Rejmon; Zhao, Gaofeng; Garg, Hari G.; Quinn, Deborah A.; Hales, Charles A.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Zhao, Hang; Leu, Shaw-Wei; Shi, Liyun; Dedaj, Rejmon; Zhao, Gaofeng; Garg, Hari G.; Quinn, Deborah A.; Hales, Charles A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shen, Lianjun] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Lien, Egil; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Infect Dis & Immunol, Worcester, MA 01605 USA. [Shiedlin, Aviva] Genzyme Corp, Framingham, MA 01701 USA. [Leu, Shaw-Wei] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan. [Shi, Liyun] Hangzhou Normal Univ, Dept Immunol, Hangzhou, Zhejiang, Peoples R China. [Shen, Huahao] Zhejiang Univ, Sch Med, Hosp 2,Inst Resp Dis, Dept Resp Med, Hangzhou 310003, Zhejiang, Peoples R China. RP Zhao, H (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM hzhao5@partners.org FU Genzyme Corporation [HL007874, HL039150]; Susannah Wood Fund FX This work was supported by HL007874, HL039150, an unrestricted grant from the Genzyme Corporation, and the Susannah Wood Fund. NR 36 TC 21 Z9 24 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2010 VL 184 IS 9 BP 5308 EP 5314 DI 10.4049/jimmunol.1000009 PG 7 WC Immunology SC Immunology GA 588SD UT WOS:000277093000085 PM 20357263 ER PT J AU Seaman, MS Wilck, MB Baden, LR Walsh, SR Grandpre, LE Devoy, C Giri, A Noble, LC Kleinjan, JA Stevenson, KE Kim, HT Dolin, R AF Seaman, Michael S. Wilck, Marissa B. Baden, Lindsey R. Walsh, Stephen R. Grandpre, Lauren E. Devoy, Colleen Giri, Ayush Noble, Lizanne C. Kleinjan, Jane A. Stevenson, Kristen E. Kim, Haesook T. Dolin, Raphael TI Effect of Vaccination with Modified Vaccinia Ankara (ACAM3000) on Subsequent Challenge with Dryvax SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SMALLPOX VACCINATION; MONOCLONAL-ANTIBODIES; LETHAL MONKEYPOX; VIRUS; PROTECTION; MICE; MYOPERICARDITIS; IMMUNOGENICITY; COMPLICATIONS; REGRESSION AB Background. Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax). Methods. Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization. Subjects were followed up for clinical take, viral shedding, and immune responses. Results. MVA administration attenuated clinical takes in 21 (72%) of 29 subjects, compared with 0 of 7 placebo recipients (P = .001). Attenuation was most significant in MVA groups that received 1 x 10(7) median tissue culture infective doses (TCID(50)) intradermally (P = .001) and 1 x 10(7) TCID(50) intramuscularly (P = .001). Both duration and peak titer of viral shedding were reduced in MVA recipients. Peak neutralizing antibody responses to vaccinia virus or MVA previously induced by MVA immunization were associated with attenuated takes (P = .02) and reduced duration (P < .001) and titer (P = .005) of viral shedding. Conclusions. MVA immunization results in clinical and virologic protection against Dryvax challenge. Protection is associated with prior induction of neutralizing antibodies to MVA or vaccinia virus. MVA administered intradermally has protective and immunologic responses similar to those of a 10-fold-higher dose given subcutaneously. C1 [Seaman, Michael S.; Grandpre, Lauren E.; Devoy, Colleen; Giri, Ayush; Dolin, Raphael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Wilck, Marissa B.; Baden, Lindsey R.; Noble, Lizanne C.; Kleinjan, Jane A.; Dolin, Raphael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02215 USA. [Walsh, Stephen R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02215 USA. [Stevenson, Kristen E.; Kim, Haesook T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Seaman, Michael S.; Wilck, Marissa B.; Baden, Lindsey R.; Walsh, Stephen R.; Dolin, Raphael] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Dolin, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave,E CLS 1003, Boston, MA 02215 USA. EM rdolin@bidmc.harvard.edu FU National Institute of Allergy and Infectious Diseases (US Public Health Service) [U54 AI057159, U19 AI057330] FX National Institute of Allergy and Infectious Diseases (US Public Health Service grants U54 AI057159 and U19 AI057330). NR 33 TC 13 Z9 13 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2010 VL 201 IS 9 BP 1353 EP 1360 DI 10.1086/651560 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UB UT WOS:000276248400012 PM 20350190 ER PT J AU Wilck, MB Seaman, MS Baden, LR Walsh, SR Grandpre, LE Devoy, C Giri, A Kleinjan, JA Noble, LC Stevenson, KE Kim, HT Dolin, R AF Wilck, Marissa B. Seaman, Michael S. Baden, Lindsey R. Walsh, Stephen R. Grandpre, Lauren E. Devoy, Colleen Giri, Ayush Kleinjan, Jane A. Noble, Lizanne C. Stevenson, Kristen E. Kim, Haesook T. Dolin, Raphael TI Safety and Immunogenicity of Modified Vaccinia Ankara (ACAM3000): Effect of Dose and Route of Administration SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SMALLPOX VACCINATION; DRYVAX(R) CHALLENGE; ANTIBODY-RESPONSES; VIRUS PROPAGATION; INFLUENZA VACCINE; STRAIN; MICE; MVA; PROTEINS; PROTECTS AB Background. We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration. Methods. Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart. Results. MVA was generally well tolerated at all dose levels and by all routes. More pronounced local reactogenicity was seen with the intradermal and subcutaneous routes than with intramuscular administration. Binding antibodies to whole virus and neutralizing antibodies to the intracellular mature virion and extracellular enveloped virion forms of vaccinia virus were elicited by all routes of MVA administration and were greater for the higher dose by each route. Similar levels of neutralizing antibodies were seen at a 10-fold-lower dose given intradermally (1 x 10(7) median tissue culture infective doses [TCID(50)]), compared with responses after TCID(50) given intramuscularly or subcutaneously. T cell immune responses to vaccinia virus were detected by an interferon g enzyme-linked immunospot assay but had no clear relationship to dose or route. Conclusions. These data suggest that intradermal immunization with MVA provides a dose-sparing effect by eliciting antibody responses similar in magnitude and kinetics to those elicited by the intramuscular or subcutaneous routes but at a 10-fold-lower dose. C1 [Seaman, Michael S.; Grandpre, Lauren E.; Devoy, Colleen; Giri, Ayush; Dolin, Raphael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Wilck, Marissa B.; Baden, Lindsey R.; Kleinjan, Jane A.; Noble, Lizanne C.; Dolin, Raphael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02215 USA. [Walsh, Stephen R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02215 USA. [Stevenson, Kristen E.; Kim, Haesook T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wilck, Marissa B.; Seaman, Michael S.; Baden, Lindsey R.; Walsh, Stephen R.; Dolin, Raphael] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Dolin, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave,E CLS 1003, Boston, MA 02215 USA. EM rdolin@bidmc.harvard.edu FU National Institute of Allergy and Infectious Diseases (US Public Health Service) [U54 AI057159, U19 AI057330] FX National Institute of Allergy and Infectious Diseases (US Public Health Service grants U54 AI057159 and U19 AI057330). NR 34 TC 28 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2010 VL 201 IS 9 BP 1361 EP 1370 DI 10.1086/651561 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 577UB UT WOS:000276248400013 PM 20350191 ER PT J AU Chren, MM AF Chren, Mary-Margaret TI Interpretation of Quality-of-Life Scores SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material AB Patients' reports of their experience with illness are a key health outcome, but scores that measure these reports can be difficult to interpret. Skindex-29 measures skin-related quality of life reliably and validly. In this issue, Prinsen and colleagues compare patients' responses to "anchor" questions with their Skindex scores to derive clinically meaningful scores for the subscales of Skindex-29. The cutoff scores identify patients whose skin diseases severely affect their quality of life. C1 [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco VAMC 151R,4150 Clement St, San Francisco, CA 94121 USA. EM chrenm@derm.ucsf.edu FU NIAMS NIH HHS [K24 AR052667-07, K24 AR052667] NR 12 TC 8 Z9 9 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2010 VL 130 IS 5 BP 1207 EP 1209 DI 10.1038/jid.2010.51 PG 4 WC Dermatology SC Dermatology GA 587EL UT WOS:000276972300005 PM 20393476 ER PT J AU Asgari, MM Tang, J Warton, ME Chren, MM Quesenberry, CP Bikle, D Horst, RL Orentreich, N Vogelman, JH Friedman, GD AF Asgari, Maryam M. Tang, Jean Warton, Margaret E. Chren, Mary-Margaret Quesenberry, Charles P., Jr. Bikle, Dan Horst, Ronald L. Orentreich, Norman Vogelman, Joseph H. Friedman, Gary D. TI Association of Prediagnostic Serum Vitamin D Levels with the Development of Basal Cell Carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SKIN-CANCER; PROSTATE-CANCER; UNITED-STATES; SUN EXPOSURE; D SYSTEM; POPULATION; RISK; RECEPTOR; MEN AB We investigated the association between serum 25-hydroxyvitamin D (25(OH) D) levels and basal cell carcinoma (BCC) risk in a nested case-control study at Kaiser Permanente Northern California (KPNC). A total of 220 case patients with BCC diagnosed after serum collection were matched to 220 control subjects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression. Fully adjusted models included body mass index (BMI), smoking, education, sun-exposure variables, X-ray exposure, and personal history of cancer. For each measure of serum 25(OH) D (continuous, clinically relevant tertiles, quintiles), we found an increased risk of BCC in unadjusted models (OR = 1.03, 95% CI 1.00-1.05, P<0.05; OR = 3.98, 95% CI: 1.31-12.31, deficient vs. sufficient, test for trend P-value <0.01; OR = 2.32, 95% CI: 1.20-4.50, 1st vs. 5th quintile, test for trend P-value 0.03). In fully adjusted models, the values attenuated slightly (OR = 1.02, 95% CI 1.00-1.05, P<0.05; OR = 3.61, 95% CI: 1.00-13.10, deficient vs. sufficient, t-trend P = 0.03; OR = 2.09 1st vs. 5th quintile, 95% CI: 0.95-4.58, t-trend P = 0.11). Our findings suggest that higher prediagnostic serum 25(OH) D levels may be associated with increased risk of subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and serum 25(OH) D levels may be warranted. C1 [Asgari, Maryam M.] Kaiser Permanente No Calif, Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Asgari, Maryam M.; Chren, Mary-Margaret; Bikle, Dan] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Tang, Jean] Stanford Univ, Dept Dermatol, Sch Med, Stanford, CA 94305 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, San Francisco, CA USA. [Horst, Ronald L.] Heartland Assays, Ames, IA USA. [Orentreich, Norman; Vogelman, Joseph H.] Orentreich Fdn Adv Sci Inc, Cold Spring On Hudson, NY USA. [Friedman, Gary D.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Asgari, MM (reprint author), Kaiser Permanente No Calif, Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Maryam.m.asgari@kp.org RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23 AR 051037, RO1AR05003, K24 AR05266]; Kaiser Foundation Research Institute [9601]; American Institute of Cancer Research [07A140]; Veterans Administration FX We thank Nancy P Durr of OFAS for editorial assistance. This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23 AR 051037, MA; RO1AR05003, DB; K24 AR05266, MC), Kaiser Foundation Research Institute (Community Benefits Grant 9601, MA), American Institute of Cancer Research (07A140, DB), and Veterans Administration Merit Review (DB). NR 32 TC 33 Z9 35 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2010 VL 130 IS 5 BP 1438 EP 1443 DI 10.1038/jid.2009.402 PG 6 WC Dermatology SC Dermatology GA 587EL UT WOS:000276972300031 PM 20043012 ER PT J AU Reddy, VB Shimada, SG Sikand, P LaMotte, RH Lerner, EA AF Reddy, Vemuri B. Shimada, Steven G. Sikand, Parul LaMotte, Robert H. Lerner, Ethan A. TI Cathepsin S Elicits Itch and Signals via Protease-Activated Receptors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID CYSTEINE PROTEASE; MECHANISM; PATHWAYS; PRURITUS; MICE C1 [Reddy, Vemuri B.; Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Shimada, Steven G.; Sikand, Parul; LaMotte, Robert H.] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp E, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM elerner@partners.org RI Silva, Mariana/B-9530-2012 FU NCRR NIH HHS [UL1 RR024139, UL1 RR0249139, UL1 RR024139-04]; NIAID NIH HHS [U01 AI061420-01, U01 AI061420]; NIAMS NIH HHS [R01 AR057744]; NINDS NIH HHS [P01 NS047399-06, K25 NS047300, P01 NS047399, P01 NS047300] NR 17 TC 41 Z9 41 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2010 VL 130 IS 5 BP 1468 EP 1470 DI 10.1038/jid.2009.430 PG 4 WC Dermatology SC Dermatology GA 587EL UT WOS:000276972300037 PM 20072136 ER PT J AU Ramadan, S Ratai, EM Wald, LL Mountford, CE AF Ramadan, Saadallah Ratai, Eva-Maria Wald, Lawrence L. Mountford, Carolyn E. TI In vivo 1D and 2D correlation MR spectroscopy of the soleus muscle at 7T SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE MR spectroscopy; L-COSY; 7 Tesla; Soleus muscle; In vivo; Human; Intra-myocellular and extramyocellular lipids ID MAGNETIC-RESONANCE SPECTROSCOPY; LOCALIZED PROTON SPECTROSCOPY; MALIGNANT COLORECTAL CELLS; TWO-DIMENSIONAL NMR; SKELETAL-MUSCLE; RELAXATION-TIMES; HUMAN-BRAIN; INTRAMYOCELLULAR LIPIDS; PROGRESSIVE-SATURATION; STIMULATED ECHOES AB Aim: This study aims to (1) undertake and analyse 1D and 2D MR correlation spectroscopy from human soleus muscle in vivo at 7T, and (2) determine T1 and T2 relaxation time constants at 7T field strength due to their importance in sequence design and spectral quantitation. Method: Six healthy, male volunteers were consented and scanned on a 7T whole-body scanner (Siemens AG, Erlangen, Germany). Experiments were undertaken using a 28 cm diameter detunable birdcage coil for signal excitation and an 8.5 cm diameter surface coil for signal reception. The relaxation time constants, T1 and T2 were recorded using a STEAM sequence, using the 'progressive saturation' method for the T1 and multiple echo times for T2. The 2D L-Correlated SpectroscopY (L-COSY) method was employed with 64 increments (0.4 ms increment size) and eight averages per scan, with a total time of 17 min. Results: T1 and T2 values for the metabolites of interest were determined. The L-COSY spectra obtained from the soleus muscle provided information on lipid content and chemical structure not available, in vivo, at lower field strengths. All molecular fragments within multiple lipid compartments were chemically shifted by 0.20-0.26 ppm at this field strength. 1D and 2D L-COSY spectra were assigned and proton connectivities were confirmed with the 2D method. Conclusion: In vivo 1D and 2D spectroscopic examination of muscle can be successfully recorded at 7T and is now available to assess lipid alterations as well as other metabolites present with disease. T1 and T2 values were also determined in soleus muscle of male healthy volunteers. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ramadan, Saadallah; Mountford, Carolyn E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Spect,Dept Radiol, Boston, MA 02115 USA. [Ratai, Eva-Maria; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Ramadan, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Spect,Dept Radiol, 4 Blackfan St,HIM 8th Floor, Boston, MA 02115 USA. EM saad.ramadan@gmail.com RI Wald, Lawrence/D-4151-2009 FU Australian Research Council [DP0663987]; NIH [R21NS059331, R01NS050041]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute FX This work was supported by a grant from the Australian Research Council Grant DP0663987 and NIH Grants R21NS059331 and R01NS050041. The MGH A.A. Martinos Center for Biomedical Imaging is also supported by National Center for Research ResourcesGrant No. P41RR14075 and the Mental Illness and Neuroscience Discovery (MIND) Institute. NR 51 TC 21 Z9 22 U1 0 U2 8 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 MAY PY 2010 VL 204 IS 1 BP 91 EP 98 DI 10.1016/j.jmr.2010.02.008 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 584WT UT WOS:000276785300011 PM 20206561 ER PT J AU Jelin, AC Cheng, YW Shaffer, BL Kaimal, AJ Little, SE Caughey, AB AF Jelin, Angie C. Cheng, Yvonne W. Shaffer, Brian L. Kaimal, Anjali J. Little, Sarah E. Caughey, Aaron B. TI Early-onset preeclampsia and neonatal outcomes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Early-onset preeclampsia; neonatal outcomes; preterm delivery ID RANDOMIZED CONTROLLED-TRIAL; 32 WEEKS GESTATION; EXPECTANT MANAGEMENT; PRETERM BIRTH; DELIVERY; TERM; PREGNANCIES; PREVENTION; ECLAMPSIA; REMOTE AB Study design. This is a retrospective cohort of 1709 infants delivered at 24 0/7 to 29 6/7 weeks gestation was examined. Neonatal outcomes of 235 infants delivered prematurely because of preeclampsia were compared with 1474 infants delivered preterm because of other etiologies. Primary outcomes examined included: small for gestational age (SGA), respiratory distress syndrome (RDS), and neonatal death (NND). Multivariable logistic regression was used to analyze the association between preeclampsia and the neonatal outcomes, controlling for potential confounders. Results. Infants of women with preeclampsia were more likely to be SGA (17.8% vs. 5.6%, AOR 3.9, CI 2.5-6.2) and have RDS (70.6% vs. 60.7%, AOR 1.5, 95% CI 1.1-2.2); however, they were less likely to suffer a NND (11.1% vs. 18.1%, AOR 0.6, 95% CI 0.4-0.9). Conclusion. Compared with neonates delivered prematurely because of other etiologies, neonates born to preeclamptic mothers were more likely to be SGA and have RDS, but had a decrease in mortality. This may be a reflection of the differences in the underlying pathophysiology behind indicated preterm birth due to preeclampsia. C1 [Jelin, Angie C.; Cheng, Yvonne W.; Shaffer, Brian L.; Kaimal, Anjali J.; Caughey, Aaron B.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Div Perinatal Med & Genet, San Francisco, CA 94143 USA. [Little, Sarah E.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Caughey, AB (reprint author), Univ Calif San Francisco, Dept Obstet & Gynecol, 505 Parnassus Ave,Box 0132, San Francisco, CA 94143 USA. EM abcmd@berkeley.edu FU Robert Wood Johnson Foundation FX Aaron B. Caughey is supported by the Robert Wood Johnson Foundation as a Physician Faculty Scholar. NR 23 TC 15 Z9 15 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2010 VL 23 IS 5 BP 389 EP 392 DI 10.3109/14767050903168416 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 580PX UT WOS:000276462500006 PM 19670045 ER PT J AU Yang, XF Dai, G Li, G Yang, ES AF Yang, Xifei Dai, George Li, Geng Yang, Edward S. TI Coenzyme Q10 Reduces beta-Amyloid Plaque in an APP/PS1 Transgenic Mouse Model of Alzheimer's Disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; Coenzyme Q10; A beta; Plaque; MR imaging ID Q(10); MICE; PATHOLOGY; PROTEIN AB We previously reported that coenzyme Q10 (CoQ10) could reduce intracellular deposition in an aged transgenic mouse model. Here, we further tested the effect of CoQ10 on amyloid plaque in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease (AD). By using immunohistochemistry and magnetic resonance imaging to determine the burden of amyloid plaque, we found that oral administration of CoQ10 can efficiently reduce the burden of the plaques in this mouse model. These data demonstrate that in addition to reducing intracellular deposition of A beta, CoQ10 can also reduce plaque pathology. Our study further supports the use of CoQ10 as a therapeutic candidate for AD. C1 [Yang, Xifei; Li, Geng; Yang, Edward S.] Hong Kong Appl Sci & Technol Res Inst Co Ltd, Hong Kong, Hong Kong, Peoples R China. [Yang, Xifei] Huazhong Univ Sci & Technol, Dept Pathophysiol, Tongji Med Coll, Wuhan 430074, Peoples R China. [Dai, George] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Li, G (reprint author), Hong Kong Appl Sci & Technol Res Inst Co Ltd, Hong Kong, Hong Kong, Peoples R China. EM ligenggeng@gmail.com FU Rejuvenis, Hong Kong Jockey Club Charities Trust FX This study was supported by a grant from Rejuvenis, Hong Kong Jockey Club Charities Trust. NR 17 TC 32 Z9 33 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD MAY PY 2010 VL 41 IS 1 BP 110 EP 113 DI 10.1007/s12031-009-9297-1 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 573IH UT WOS:000275905400015 PM 19834824 ER PT J AU Li, WJ Wu, SS Ahmad, M Jiang, JF Liu, H Nagayama, T Rose, ME Tyurin, VA Tyurina, YY Borisenko, GG Belikova, N Chen, J Kagan, VE Graham, SH AF Li, Wenjin Wu, Shasha Ahmad, Muzamil Jiang, Jianfei Liu, Hao Nagayama, Tetsuya Rose, Marie E. Tyurin, Vladimir A. Tyurina, Yulia Y. Borisenko, Grigory G. Belikova, Natalia Chen, Jun Kagan, Valerian E. Graham, Steven H. TI The cyclooxygenase site, but not the peroxidase site of cyclooxygenase-2 is required for neurotoxicity in hypoxic and ischemic injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cell death; cyclooxygenase-2; hypoxia; ischemia; prostaglandin ID PROSTAGLANDIN-H-SYNTHASE; TRAUMATIC BRAIN-INJURY; CEREBRAL-ISCHEMIA; ASCORBIC-ACID; CELL-DEATH; ENDOPEROXIDE SYNTHASE; REACTION-MECHANISM; SUPEROXIDE ANION; GENE-EXPRESSION; MOUSE MODEL AB P>Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of ischemic injury, but the exact mechanisms responsible for its toxicity remain unclear. Infection of primary neurons with an adenovirus expressing wild type (WT) COX-2 increased the susceptibility of neurons to hypoxia. Infection with an adenoviral vector expressing COX-2 with a mutation at the cyclooxygenase site did not increase susceptibility to hypoxia, whereas over-expression of COX-2 with a mutation in the peroxidase site produced similar susceptibility to hypoxia as WT COX-2. Primary neuronal cultures obtained from transgenic mice bearing a mutation in the COX-2 cylooxygenase site were protected from hypoxia. Mice with a mutation in the cyclooxygenase site had smaller infarctions 24 h after 70 min of middle cerebral artery occlusion than WT control mice. COX-2 activity had no effect on the formation of protein carbonyls. Ascorbate radicals were detected by electron paramagnetic resonance as a product of recombinant COX-2 activity and were blocked by COX-2 inhibitors. Similarly, formation of ascorbate radicals was inhibited in the presence of COX-2 inhibitors and in homogenates obtained from COX-2 null mice. Taken together, these results indicate that the cyclooxygenase activity of COX-2 is necessary to exacerbate neuronal hypoxia/ischemia injury rather than the peroxidase activity of the enzyme. C1 [Li, Wenjin; Wu, Shasha; Ahmad, Muzamil; Liu, Hao; Nagayama, Tetsuya; Rose, Marie E.; Chen, Jun; Graham, Steven H.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Li, Wenjin; Wu, Shasha; Ahmad, Muzamil; Liu, Hao; Nagayama, Tetsuya; Rose, Marie E.; Chen, Jun; Graham, Steven H.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Jiang, Jianfei; Tyurin, Vladimir A.; Tyurina, Yulia Y.; Borisenko, Grigory G.; Belikova, Natalia; Kagan, Valerian E.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare, Geriatr Res Educ & Clin Ctr 00GRH, Highland Dr, Pittsburgh, PA 15205 USA. EM sgra@pitt.edu OI Tyurin, Vladimir/0000-0002-3474-1697 FU NIH [NS37549, HL70755, R03TW007320]; VA Merit Review program (SHG); Pennsylvania Department of Health [SAP 4100027294] FX The authors thank Pat Strickler for secretarial support. The Y371F mouse model was provided by Dr. Colin Funk of Queen's University, Kingston, Ontario. WT COX-2, H374Y COX-2 and Y371F COX-2 cDNAs were a gift of Dr. L.J. Marnett (Vanderbilt University, Nashville, TN). SC58125 and recombinant COX-2 were a gift of Peter Isakson (Monsanto-Searle, Saint Louis, MO.). This work was supported by NIH NS37549 and the VA Merit Review program (SHG), and by NIH Grants HL70755, R03TW007320 and the Pennsylvania Department of Health SAP 4100027294 (VEK). The authors declare no conflict of interest. NR 52 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2010 VL 113 IS 4 BP 965 EP 977 DI 10.1111/j.1471-4159.2010.06674.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 583EM UT WOS:000276656100015 PM 20236388 ER EF