FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Murshid, A Gong, JL Calderwood, S AF Murshid, Ayesha Gong, Jianlin Calderwood, Stuart TI Scavenger Receptor, SRECI activates dsRNA-mediated TLR3 innate immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Murshid, Ayesha; Gong, Jianlin; Calderwood, Stuart] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700599 ER PT J AU Oyoshi, M He, R Li, YT Yoon, JH Afshar, R Chen, M Lee, D Luo, HB Luster, A Larson, A Murphy, G Geha, R AF Oyoshi, Michiko He, Rui Li, Yitang Yoon, Juhan Afshar, Roshi Chen, Mei Lee, David Luo, Hongbo Luster, Andrew Larson, Allison Murphy, George Geha, Raif TI LTB4 driven neutrophil recruitment to the skin is essential for allergic skin inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Li, Yitang; Luo, Hongbo] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Afshar, Roshi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Murphy, George] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dermatopathol Program Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701362 ER PT J AU Paintlia, M Paintlia, A Singh, A Singh, I AF Paintlia, Manjeet Paintlia, Ajaib Singh, Avtar Singh, Inderjit TI Endogenous S-Nitrosothiol Induced hypertrophic Astrogliosis has potential to maintain CNS homeostasis under pathological Conditions SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Paintlia, Manjeet; Paintlia, Ajaib; Singh, Avtar; Singh, Inderjit] MUSC, Charleston, SC USA. [Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700556 ER PT J AU Paust, S Flynn, M Wang, BZ Dougan, S Ploegh, H Telenti, A Compans, R von Andrian, U AF Paust, Silke Flynn, Michael Wang, Baozhong Dougan, Stephanie Ploegh, Hidde Telenti, Amalio Compans, Richard von Andrian, Ulrich TI Adaptive immunity mediated by Natural Killer cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Paust, Silke; Flynn, Michael; von Andrian, Ulrich] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [von Andrian, Ulrich] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Paust, Silke; von Andrian, Ulrich] Ragon Inst MIT MGH & Harvard, Dept Immunol, Boston, MA USA. [Wang, Baozhong; Compans, Richard] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Wang, Baozhong; Compans, Richard] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Telenti, Amalio] Univ Lausanne, Inst Microbiol, Univ Hosp, Lausanne, Switzerland. [Dougan, Stephanie; Ploegh, Hidde] Whitehead Inst, Boston, MA USA. RI Compans, Richard/I-4087-2013 OI Compans, Richard/0000-0003-2360-335X NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700136 ER PT J AU Platzer, B Baker, K Schopoff, S Turley, S Blumberg, R Fiebiger, E AF Platzer, Barbara Baker, Kristi Schopoff, Sandy Turley, Shannon Blumberg, Richard Fiebiger, Edda TI Sensing of low-dose soluble antigen via Immunoglobulin E SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Platzer, Barbara; Schopoff, Sandy; Fiebiger, Edda] Childrens Hosp, Boston, MA 02115 USA. [Baker, Kristi; Blumberg, Richard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turley, Shannon] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Platzer, Barbara; Fiebiger, Edda] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700601 ER PT J AU Politikos, I Kim, H Cutler, C McDonough, S Antin, J Ballen, K Ritz, J Boussiotis, V AF Politikos, Ioannis Kim, Haesook Cutler, Corey McDonough, Sean Antin, Joseph Ballen, Karen Ritz, Jerome Boussiotis, Vassiliki TI Recovery of thymic epithelial cells and immune reconstitution after cord blood transplantation depends on angiogenesis and neovascularization SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Politikos, Ioannis; Boussiotis, Vassiliki] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kim, Haesook; Cutler, Corey; McDonough, Sean; Antin, Joseph; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701400 ER PT J AU Porichis, F Kwon, D Jennifer, Z Hart, M McMullen, A Freeman, G Kavanagh, D Kaufmann, D AF Porichis, Filippos Kwon, Douglas Jennifer, Zupkosky Hart, Meghan McMullen, Ashley Freeman, Gordon Kavanagh, Daniel Kaufmann, Daniel TI PD-1, IL-10 and IFN-gamma form a network to regulate HIV-specific CD4 T cell dysfunction SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Porichis, Filippos; Kwon, Douglas; Jennifer, Zupkosky; Hart, Meghan; McMullen, Ashley; Kavanagh, Daniel; Kaufmann, Daniel] Harvard Univ, Ragon Inst MGH & Harvard, Massachusetts Gen Hosp, Charlestown, MA USA. [Freeman, Gordon] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700012 ER PT J AU Seung, E Dudek, T Dugast, AS Mattoo, H Vrbanac, V Tivey, T Cariappa, A Pillai, S Luster, A Tager, A AF Seung, Edward Dudek, Timothy Dugast, Anne-Sophie Mattoo, Hamid Vrbanac, Vladimir Tivey, Trevor Cariappa, Annaiah Pillai, Shiv Luster, Andrew Tager, Andrew TI Neutralizing anti-HIV antibodies develop in a humanized mouse model of HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Seung, Edward; Vrbanac, Vladimir; Tivey, Trevor; Luster, Andrew; Tager, Andrew] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Dudek, Timothy; Dugast, Anne-Sophie] Harvard Univ, Ragon Inst, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Mattoo, Hamid; Cariappa, Annaiah; Pillai, Shiv] Harvard Univ, Canc Ctr, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RI Dugast, AnneSophie/L-9541-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700002 ER PT J AU Shamri, R Young, K Weller, P AF Shamri, Revital Young, Kristen Weller, Peter TI p38 MAPK but not ERK is required for eosinophil migration and degranulation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Shamri, Revital; Young, Kristen; Weller, Peter] Beth Isreal Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702118 ER PT J AU Sharma, A Chen, QH Nguyen, T Yu, Q Sen, J AF Sharma, Archna Chen, Qinghua Trang Nguyen Yu, Qing Sen, Jyoti TI T Cell Factor-1 and beta-catenin regulate the development of memory-like CD8 thymocytes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Sharma, Archna; Chen, Qinghua; Trang Nguyen; Sen, Jyoti] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. [Yu, Qing] Forsyth Inst, Dept Immunol, Cambridge, MA USA. RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700679 ER PT J AU Shibata, Y Kogiso, M Huang, CJ Nouri-Shirazi, M Mizoguchi, E Dorey, CK AF Shibata, Yoshimi Kogiso, Mari Huang, Chun-Jung Nouri-Shirazi, Mahyar Mizoguchi, Emiko Dorey, C. Kathleen TI Macrophage chitin binding proteins in phagocytosis and M1 activation in response to chitin microparticles SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Shibata, Yoshimi; Kogiso, Mari; Huang, Chun-Jung; Nouri-Shirazi, Mahyar] Florida Atlantic Univ, Boca Raton, FL 33431 USA. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Dorey, C. Kathleen] Virginia Tech, Carilion Sch Med & Res Inst, Basic Sci, Roanoke, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702120 ER PT J AU Sholukh, A Mukhtar, M Humbert, M Essono, S Watkins, J Shanmuganathan, V Hemashettar, G Hu, SL Montefiori, D Polonis, V Schur, P Ruprecht, R AF Sholukh, Anton Mukhtar, Muhammad Humbert, Michael Essono, Sosthene Watkins, Jennifer Shanmuganathan, Vivekanandan Hemashettar, Girish Hu, Shiu-Lok Montefiori, David Polonis, Victoria Schur, Peter Ruprecht, Ruth TI Isolation of neutralizing monoclonal antibodies against HIV-1 with predetermined conformational epitope specificity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Sholukh, Anton; Mukhtar, Muhammad; Humbert, Michael; Essono, Sosthene; Watkins, Jennifer; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Ruprecht, Ruth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sholukh, Anton; Mukhtar, Muhammad; Humbert, Michael; Essono, Sosthene; Watkins, Jennifer; Ruprecht, Ruth] Harvard Univ, Sch Med, Boston, MA USA. [Hu, Shiu-Lok] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Montefiori, David] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Polonis, Victoria] Walter Reed Army Inst Res, Mil HIV Res Program, Rockville, MD USA. [Schur, Peter] Brigham & Womens Hosp, Dept Rheumatol Immunol & Allergy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700597 ER PT J AU Song, JH Change, SY Guleng, B Cotoner, C Arihiro, S Karp, C Kweon, MN Sharpe, A Bhan, A Terhors, C Reinecker, HC AF Song, Joo Hye Change, Sun Young Guleng, Bayasi Cotoner, Carmen Arihiro, Seiji Karp, Christopher Kweon, Mi-Na Sharpe, Arlene Bhan, Atul Terhors, Cox Reinecker, Hans-Christian TI Intestinal dendritic cells survey circulatory antigens prior to induction of regulatory CD8 alpha/beta T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Song, Joo Hye; Change, Sun Young; Guleng, Bayasi; Cotoner, Carmen; Arihiro, Seiji; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Div Gastroenterol, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Karp, Christopher] Univ Cincinnati, Coll Med, Div Mol Immunol, Cincinnati, OH USA. [Kweon, Mi-Na] Int Vaccine Inst, Mucosal Immunol Sect, Seoul, South Korea. [Sharpe, Arlene] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA USA. [Bhan, Atul] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Terhors, Cox] Beth Israel Deaconess Med Ctr, Div Immunol, Ctr Study Inflammatory Bowel Dis, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700602 ER PT J AU Stelekati, E Shin, H Doering, T Dolfi, D Ziegler, C Beiting, D Liboon, J Wolski, D Katsikis, P Shen, H Roos, D Haining, W Lauer, G Wherry, E AF Stelekati, Erietta Shin, Haina Doering, Travis Dolfi, Douglas Ziegler, Carly Beiting, Daniel Liboon, Jennifer Wolski, David Katsikis, Peter Shen, Hao Roos, David Haining, W. Lauer, Georg Wherry, E. TI Bystander chronic infection negatively impacts the development of CD8 T cell memory SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Stelekati, Erietta; Shin, Haina; Doering, Travis; Dolfi, Douglas; Ziegler, Carly; Liboon, Jennifer; Shen, Hao; Wherry, E.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Stelekati, Erietta; Shin, Haina; Doering, Travis; Dolfi, Douglas; Ziegler, Carly; Wherry, E.] Univ Penn, Inst Immunol, Philadelphia, PA 19104 USA. [Beiting, Daniel; Roos, David] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Wolski, David; Lauer, Georg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Katsikis, Peter] Drexel Univ, Dept Microbiol & Immunol, Coll Med, Philadelphia, PA 19104 USA. [Haining, W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Haining, W.] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700595 ER PT J AU Tam, J Tanne, A Khan, N Mansour, M Becker, C Sokolovska, A Stuart, L Xavier, R Vyas, J AF Tam, Jenny Tanne, Antoine Khan, Nida Mansour, Michael Becker, Christine Sokolovska, Anna Stuart, Lynda Xavier, Ramnik Vyas, Jatin TI Dectin-1 Signaling Recruits Elements of the Autophagic Machinery to Candida albicans-containing Phagosomes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Tam, Jenny; Khan, Nida; Mansour, Michael; Vyas, Jatin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Havard Med Sch, Ctr Computat & Integrat Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700358 ER PT J AU Touma, M Saito, I Reinherz, E Clayton, L AF Touma, Maki Saito, Ibuki Reinherz, Ellis Clayton, Linda TI B cell development and immunoglobulin production are altered in the absence of I kappa BNS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Touma, Maki; Saito, Ibuki] Niigata Univ, Grad Sch Sci & Technol, Niigata 95021, Japan. [Reinherz, Ellis; Clayton, Linda] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reinherz, Ellis; Clayton, Linda] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700666 ER PT J AU Tuzova, M Richmond, J Wolpowitz, D Curiel-Levandrowsk, C Kupper, T Cruikshank, W AF Tuzova, Marina Richmond, Jillian Wolpowitz, Deon Curiel-Levandrowsk, Clara Kupper, Thomas Cruikshank, William TI Potential role of TSLP and IL-16 for migration and proliferation in Mycosis Fungoides T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Wolpowitz, Deon] Boston Univ, Sch Med, Boston, MA 02118 USA. [Curiel-Levandrowsk, Clara] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Kupper, Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701499 ER PT J AU Vaine, C Primo, V Nikolic, B Calderone, N Nigrovic, P Soberman, R AF Vaine, Christine Primo, Valeria Nikolic, Boris Calderone, Nicholas Nigrovic, Peter Soberman, Roy TI CD200R1 regulates synovial inflammation through neutrophil LTB4 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Vaine, Christine; Primo, Valeria; Nikolic, Boris; Soberman, Roy] Massachusetts Gen Hosp, Charlestown, MA USA. [Calderone, Nicholas; Nigrovic, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700494 ER PT J AU van Driel, B Liao, GX Romero, J Faubion, W Wang, GX Berger, S O'Keeffe, M Magelky, E Manocha, M Azcutia, V Malefyt, RD Grisham, M Luscinskas, F Mizoguchi, E Bhan, A Wang, NH Terhorst, C AF van Driel, Boaz Liao, Gongxian Romero, Javier Faubion, William Wang, Guoxing Berger, Scott O'Keeffe, Michael Magelky, Erica Manocha, Monika Azcutia, Veronica Malefyt, Rene de Waal Grisham, Matthew Luscinskas, F. Mizoguchi, Emiko Bhan, Atul Wang, Ninghai Terhorst, Cox TI Slamf1 controls monocyte/macrophage migration in experimental colitis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [van Driel, Boaz; Liao, Gongxian; Romero, Javier; Wang, Guoxing; Berger, Scott; O'Keeffe, Michael; Magelky, Erica; Manocha, Monika; Wang, Ninghai; Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Faubion, William] Mayo Clin, Rochester, ME USA. [Azcutia, Veronica; Luscinskas, F.] Brigham & Womens Hosp, Div Vasc Res, Boston, MA 02115 USA. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. [Malefyt, Rene de Waal] Merck Res Labs, Boston, MA USA. [Grisham, Matthew] LSU Hlth Sci Ctr, Shreveport, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701160 ER PT J AU Vannier, E Silver, Z Wilson, C Su, JS Chiam, J Laurie, S Telford, S Gelfand, J Krause, P Wortis, H AF Vannier, Edouard Silver, Zachary Wilson, Carrie Su, Jia-Shyuan Chiam, Jake Laurie, Sonia Telford, Sam Gelfand, Jeffrey Krause, Peter Wortis, Henry TI Cellular basis for clearance of the protozoan parasite Babesia microti in immunocompromised hosts SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Vannier, Edouard; Silver, Zachary; Wilson, Carrie; Su, Jia-Shyuan; Chiam, Jake] Tufts Med Ctr, Boston, MA USA. [Laurie, Sonia; Wortis, Henry] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Telford, Sam] Tufts Univ, Sch Vet Med, Grafton, MA USA. [Gelfand, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Krause, Peter] Yale Univ, Sch Publ Hlth, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700086 ER PT J AU Villablanca, E Torregrosa-Paredes, P Cassani, B Wagers, A Mora, R AF Villablanca, Eduardo Torregrosa-Paredes, Patricia Cassani, Barbara Wagers, Amy Mora, Rodrigo TI Gut-tropic DC precursors contribute to intestinal immune tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Villablanca, Eduardo; Torregrosa-Paredes, Patricia; Cassani, Barbara; Mora, Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701215 ER PT J AU Vollmann, E von Andrian, U AF Vollmann, Elisabeth von Andrian, Ulrich TI Specialized role of thymic transendothelial dendritic cells in antigen acquisition SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Vollmann, Elisabeth; von Andrian, Ulrich] Immune Dis Inst, Boston, MA USA. [von Andrian, Ulrich] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701035 ER PT J AU Wang, YH Scadden, D AF Wang, Ying-Hua Scadden, David TI Pyruvate kinase M2 plays distinct roles in hematopoietic stem cells and leukemia SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Wang, Ying-Hua; Scadden, David] Massachussetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA. [Wang, Ying-Hua; Scadden, David] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701039 ER PT J AU Woodruff, M Carroll, M AF Woodruff, Matthew Carroll, Michael TI Rapid activation and migration of lymph node resident dendritic cells in response to Influenza vaccination SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Woodruff, Matthew; Carroll, Michael] Harvard Univ, Immune Dis Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700138 ER PT J AU Wroblewska, J Iweala, O Kline, A Urban, J Nagler, C AF Wroblewska, Joanna Iweala, Onyinye Kline, Austin Urban, Joseph Nagler, Cathryn TI Infection with the helminthic parasite Heligmosomoides bakeri alters B cell function and impairs vaccine induced antibody responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Wroblewska, Joanna; Kline, Austin; Nagler, Cathryn] Univ Chicago, Chicago, IL 60637 USA. [Iweala, Onyinye] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Urban, Joseph] ARS, Diet Genom Immunol Lab, USDA, BHNRC, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659701624 ER PT J AU Yang, H Levine, J Katz, D Lu, B Scheinerman, J Dancho, M Ochani, M Li, JH Chavan, S Warren, S Tracey, K AF Yang, Huan Levine, Jacob Katz, David Lu, Ben Scheinerman, Josh Dancho, Meghan Ochani, Mahendar Li, Jianhua Chavan, Sangeeta Warren, Shaw Tracey, Kevin TI Haptoglobin inhibits the pro-inflammatory activity of HMGB1 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Yang, Huan; Levine, Jacob; Katz, David; Lu, Ben; Scheinerman, Josh; Dancho, Meghan; Ochani, Mahendar; Li, Jianhua; Chavan, Sangeeta; Tracey, Kevin] Feinstein Inst, Manhasset, NY USA. [Warren, Shaw] Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702094 ER PT J AU Zhang, X Suzuki, E Karam, E Williams, S Gikeson, G AF Zhang, Xian Suzuki, Eiji Karam, Eva Williams, Sarah Gikeson, Gary TI Fli-1 transcription factor directly regulates expression of inflammatory chemokine MCP-1 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Zhang, Xian; Suzuki, Eiji; Karam, Eva; Williams, Sarah; Gikeson, Gary] Med Univ S Carolina, Charleston, SC 29425 USA. [Zhang, Xian; Gikeson, Gary] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659700113 ER PT J AU Zhao, Y Song, JH Ajami, AM Reinecker, HC AF Zhao, Yun Song, Joo Hye Ajami, Alfred M. Reinecker, Hans-Christian TI A New Rip2 Kinase Inhibitor for the Treatment of Intestinal Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Zhao, Yun; Song, Joo Hye; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ajami, Alfred M.] DCAM Pharma Inc, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702007 ER PT J AU Zhu, M Van Dyke, T Gyurko, R AF Zhu, Min Van Dyke, Thomas Gyurko, Robert TI Inflammation-resolving mediator resolvin E1 inhibits osteoclast fusion. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 99th Annual Meeting of the American-Association-of-Immunologists CY MAY 04-08, 2012 CL Boston, MA SP Amer Assoc Immunol C1 [Zhu, Min; Gyurko, Robert] Boston Univ, Boston, MA 02215 USA. [Van Dyke, Thomas] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2012 VL 188 PG 1 WC Immunology SC Immunology GA 950OX UT WOS:000304659702006 ER PT J AU Yoon, JH Di Vito, L Moses, JW Fearon, WF Yeung, AC Zhang, SS Bezerra, HG Costa, MA Jang, IK AF Yoon, Joo Heung Di Vito, Luca Moses, Jeffrey W. Fearon, William F. Yeung, Alan C. Zhang, Shaosong Bezerra, Hiram G. Costa, Marco A. Jang, Ik-Kyung TI Feasibility and Safety of the Second-Generation, Frequency Domain Optical Coherence Tomography (FD-OCT): A Multicenter Study SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE frequency domain OCT; FD-OCT; feasibility; safety ID INTRAVASCULAR ULTRASOUND AB Objectives. This study sought to assess the effectiveness and safety of the second-generation frequency-domain optical coherence tomography (FD-OCT) system. Background. The second-generation FD-OCT was recently developed, with simplified imaging technique and faster acquisition time compared to the first-generation time-domain OCT. However, the safety and effectiveness of the FD-OCT has not been evaluated, and this study was conceived as a pre-approval study for Food and Drug Administration clearance for clinical use in the United States. Methods. A total of 50 patients were enrolled from 3 institutions. Following stent implantation, the FD-OCT was performed with contrast injection through the guiding catheter to acquire pullback images with the pressure-triggered automatic pullback device. The primary endpoint was to achieve a median clear image length of more than 24 mm. Serious procedure-related or postprocedural adverse events (death, myocardial infarction, or ventricular arrhythmia) were recorded to assess safety of the device. Results. The primary endpoint of obtaining >24 mm of median clear image length (CIL) was achieved in 94% of the subjects (47 out of 50), with measured CIL of 43.2 mm. In 5 patients (10.6 %), a second attempt was necessary due to suboptimal image quality of the first pullback. In 36 patients (76.6%), a full stent length was obtained during the first attempt. There were no serious procedure-related or postprocedural adverse events. Conclusions. The new second-generation FD-OCT system provides fast and reliable resolution images of the coronary artery. The pullback can be safely performed over long segments of the artery without serious adverse events. C1 [Yoon, Joo Heung; Di Vito, Luca; Jang, Ik-Kyung] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA. [Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA. [Fearon, William F.; Yeung, Alan C.] Stanford Univ, Med Ctr, Div Cardiovasc Med, Stanford, CA 94305 USA. [Zhang, Shaosong] LightLab Imaging St Jude Med, Westford, MA USA. [Bezerra, Hiram G.; Costa, Marco A.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. RP Jang, IK (reprint author), Harvard Univ, Med Sch Cardiol, Massachusetts Gen Hosp, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM ijang@partners.org FU Core Laboratories Analysis Grant; St Jude Medical FX This study was funded by a Core Laboratories Analysis Grant.; The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Jang holds a research grant and is a consultant for St Jude Medical. Dr Bezzera is a consultant for St Jude Medical. Dr Zhang is an employee of St Jude Medical. Dr Costa is a consultant for Abbott and St Jude Medical and has received honoraria from Daiichi Sankyo, Cordis, Scitech, Sanofi, and Medtronic. NR 9 TC 9 Z9 9 U1 0 U2 4 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD MAY PY 2012 VL 24 IS 5 BP 206 EP 209 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 950SN UT WOS:000304669300011 PM 22562913 ER PT J AU Li, X Priest, RA Woodward, WJ Siddiqui, F Beer, TM Garzotto, MG Rooney, WD Springer, CS AF Li, Xin Priest, Ryan A. Woodward, William J. Siddiqui, Faisal Beer, Tomasz M. Garzotto, Mark G. Rooney, William D. Springer, Charles S., Jr. TI Cell membrane water exchange effects in prostate DCE-MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Dynamic-Contrast-Enhanced; Water exchange; Contrast reagent; Prostate cancer ID CONTRAST-ENHANCED-MRI; CR BOLUS-TRACKING; SHUTTER-SPEED; IN-VIVO; CANCER; BENIGN; DIFFERENTIATION; TISSUES; MUSCLE; NMR AB Prostate Dynamic-Contrast-Enhanced (DCE) MRI often exhibits fast and extensive global contrast reagent (CR) extravasation - measured by K-trans, a pharmacokinetic parameter proportional to its rate. This implies that the CR concentration [CR] is high in the extracellular, extravascular space (EES) during a large portion of the DCE-MRI study. Since CR is detected indirectly, through water proton signal change, the effects of equilibrium transcytolemmal water exchange may be significant in the data and thus should be admitted in DCE-MRI pharmacokinetic modeling. The implications for parameter values were investigated through simulations, and analyses of actual prostate data, with different models. Model parameter correlation and precision were also explored. A near-optimal version of the exchange-sensitized model was found. Our results indicate that Delta K-trans (the K-trans difference returned by this version and a model assuming exchange to be effectively infinitely fast) may be a very useful biomarker for discriminating malignant from benign prostate tissue. Using an exchange-sensitized model, we find that the mean intracellular water lifetime (tau(i)) - an exchange measure - can be meaningfully mapped for the prostate. Our results show prostate glandular zone differences in tau(i) values. (C) 2012 Elsevier Inc. All rights reserved. C1 [Li, Xin; Woodward, William J.; Rooney, William D.; Springer, Charles S., Jr.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn High Field MRI Lab, Portland, OR 97239 USA. [Priest, Ryan A.; Siddiqui, Faisal] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97239 USA. [Priest, Ryan A.; Siddiqui, Faisal] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Dept Hematol Oncol, Portland, OR 97239 USA. [Garzotto, Mark G.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA. [Beer, Tomasz M.; Springer, Charles S., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Garzotto, Mark G.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Li, X (reprint author), Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, WM Keck Fdn High Field MRI Lab, Mail Code L452, Portland, OR 97239 USA. EM lxin@ohsu.edu OI Springer, Charles/0000-0002-5966-2135 FU Medical Research Foundation of Oregon; NIH [R01-EB00422, R01-NS40801, UL1RR024140-04S1] FX Grant Support: Medical Research Foundation of Oregon (XL), NIH: R01-EB00422 (CSS), R01-NS40801 (CSS,WDR), computational support provided by an administrative supplement NIH UL1RR024140-04S1, and RSNA Research and Education Foundation: Research Medical Student Grant #RMS0801 (FS). We thank Dr. Charles Thomas for continued support and encouragement. NR 32 TC 10 Z9 10 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2012 VL 218 BP 77 EP 85 DI 10.1016/j.jmr.2012.03.019 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 948GK UT WOS:000304491400012 PM 22578558 ER PT J AU Houtrow, AJ Yock, TI Delahaye, J Kuhlthau, K AF Houtrow, Amy J. Yock, Torunn I. Delahaye, Jennifer Kuhlthau, Karen TI The Family Impacts of Proton Radiation Therapy for Children With Brain Tumors SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING LA English DT Article DE family impact; brain tumors; proton radiation; quality of life ID QUALITY-OF-LIFE; POSTTRAUMATIC STRESS SYMPTOMS; GENERIC CORE SCALES; CHILDHOOD-CANCER; PEDIATRIC CANCER; PARENTS; SURVIVORS; VALIDITY; RELIABILITY; EPIDEMIOLOGY AB Children with brain tumors experience significant alterations to their health and well-being due to the tumors themselves and oncologic treatment. Caring for children with brain tumors can have significant impacts on families, especially during and shortly after treatment. In this study of the impacts on families caring for children undergoing proton radiation therapy for brain tumors, the authors found that families experienced a broad array of negative impacts. Families reported feeling like they were living on a roller coaster, feeling that others treated them differently, and having to give up things as a family. In the multivariable linear regression model, older age of the child and higher reported child health-related quality of life were associated with less family impact. The presence of concurrent chemotherapy was associated with increased family impact. This is the first study to specifically evaluate the families of children being treated with proton radiation therapy. The findings in this study are consistent with the findings in other studies of children treated with standard therapy that show that families experience a variety of stressors and negative impacts while their children are receiving treatment. Health care providers should be aware of the potential impacts on families of children with brain tumors and their treatment to provide robust services to meet the health, psychological, and social needs of such children and their families. C1 [Houtrow, Amy J.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15224 USA. [Yock, Torunn I.; Kuhlthau, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Yock, Torunn I.; Delahaye, Jennifer; Kuhlthau, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Houtrow, AJ (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 4401 Penn Ave, Pittsburgh, PA 15224 USA. EM houtrow@upmc.edu FU National Cancer Institute [P01 CA021239]; Susan McDaniel Brain Tumor Fund; MGH Marathon Fund for Pediatric Cancer; Rehabilitation Medicine Scientist Training Program [K12: 2K12H001097-12] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project was supported by Award Number P01 CA021239 from the National Cancer Institute. The project was also supported in part by the Susan McDaniel Brain Tumor Fund and the MGH Marathon Fund for Pediatric Cancer. Dr Amy J. Houtrow is supported by a Rehabilitation Medicine Scientist Training Program K12: 2K12H001097-12. NR 37 TC 4 Z9 4 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-4542 J9 J PEDIATR ONCOL NURS JI J. Pediatr. Oncol. Nurs. PD MAY-JUN PY 2012 VL 29 IS 3 BP 171 EP 179 DI 10.1177/1043454212446345 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 951KN UT WOS:000304719500006 PM 22647729 ER PT J AU Giannino, K McCarthy, MW Berry, L AF Giannino, Kerri McCarthy, Maureen W. Berry, Laura TI NPWT TO A COMPLEX PERIRECTAL WOUND: A UNIQUE MANAGEMENT APPROACH SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [Giannino, Kerri; McCarthy, Maureen W.; Berry, Laura] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM KinGiannino@partners.org; mmccarthy29@partners.org; lberry1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2012 VL 39 IS 3 SU S MA 6138 BP S21 EP S21 PG 1 WC Nursing SC Nursing GA 948MP UT WOS:000304507600057 ER PT J AU McCarthy, MW Giannino, K Berry, L AF McCarthy, Maureen W. Giannino, Kerri Berry, Laura TI STARTING AN OSTOMY SUPPORT GROUP SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Meeting Abstract C1 [McCarthy, Maureen W.; Giannino, Kerri; Berry, Laura] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mmccarthy29@partners.org; KmGiannino@partners.org; lberry1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD MAY-JUN PY 2012 VL 39 IS 3 SU S MA 6279 BP S54 EP S54 PG 1 WC Nursing SC Nursing GA 948MP UT WOS:000304507600159 ER PT J AU Prabhakaran, V Nair, VA Austin, BP La, C Gallagher, TA Wu, YJ McLaren, DG Xu, GF Turski, P Rowley, H AF Prabhakaran, Vivek Nair, Veena A. Austin, Benjamin P. La, Christian Gallagher, Thomas A. Wu, Yijing McLaren, Donald G. Xu, Guofan Turski, Patrick Rowley, Howard TI Current Status and Future Perspectives of Magnetic Resonance High-Field Imaging: A Summary SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Magnetic resonance imaging; High-field MR imaging; Current status; Future perspectives ID WHITE-MATTER HYPERINTENSITIES; MILD COGNITIVE IMPAIRMENT; VISUAL RATING-SCALES; CEREBRAL-BLOOD-FLOW; NEPHROGENIC SYSTEMIC FIBROSIS; ANISOTROPIC WATER DIFFUSION; SUPPLEMENTARY MOTOR AREA; CENTRAL-NERVOUS-SYSTEM; SURFACE-BASED ANALYSES; SILENT BRAIN INFARCTS AB There are several magnetic resonance (MR) imaging techniques that benefit from high-field MR imaging. This article describes a range of novel techniques that are currently being used clinically or will be used in the future for clinical purposes as they gain popularity. These techniques include functional MR imaging, diffusion tensor imaging, cortical thickness assessment, arterial spin labeling perfusion, white matter hyperintensity lesion assessment, and advanced MR angiography. C1 [Prabhakaran, Vivek; Rowley, Howard] Univ Wisconsin, Dept Radiol, Div Neuroradiol, Madison, WI 53792 USA. [Austin, Benjamin P.] Univ Wisconsin, Dept Med, UW Cardiovasc Res Ctr, Madison, WI 53705 USA. [Austin, Benjamin P.] Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Madison, WI 53705 USA. [La, Christian] Univ Wisconsin, Wisconsin Inst Med Res, Neurosci Training Program, Madison, WI 53705 USA. [Gallagher, Thomas A.] Northwestern Univ, NW Mem Hosp, Dept Radiol, Div Neuroradiol, Chicago, IL 60611 USA. [Wu, Yijing] Univ Wisconsin, Wisconsin Inst Med Res, Dept Med Phys, Madison, WI 53705 USA. [McLaren, Donald G.] ENRM VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [McLaren, Donald G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Xu, Guofan] Univ Wisconsin, UW Hosp & Clin, Nucl Med Program, Madison, WI 53792 USA. [Turski, Patrick] Univ Wisconsin, Wisconsin Inst Med Res, Div Neuroradiol, Dept Radiol, Madison, WI 53705 USA. RP Prabhakaran, V (reprint author), Univ Wisconsin, Dept Radiol, Div Neuroradiol, 600 Highland Ave, Madison, WI 53792 USA. EM vprabhakaran@uwhealth.org RI Nair, Veena/E-4037-2013; OI NAIR, VEENA/0000-0002-5666-3239; McLaren, Donald/0000-0002-0566-4610 FU National Institutes of Health [1RC1MH090912-01, KL2 RR025012, R21 EB009441, 5 T32 HL007936-10] FX This work was supported by Grant No. 1RC1MH090912-01, KL2 RR025012, R21 EB009441, 5 T32 HL007936-10, from the National Institutes of Health. NR 182 TC 6 Z9 6 U1 2 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2012 VL 22 IS 2 BP 373 EP + DI 10.1016/j.nic.2012.02.012 PG 26 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 950DE UT WOS:000304628700017 PM 22548938 ER PT J AU Xing, CH Hayakawa, K Lok, J Arai, K Lo, EH AF Xing, Changhong Hayakawa, Kazuhide Lok, Josephine Arai, Ken Lo, Eng H. TI Injury and repair in the neurovascular unit SO NEUROLOGICAL RESEARCH LA English DT Review DE Neuron; Astrocyte; Pericyte; Microglia; Endothelium; Plasticity; Stroke; Traumatic brain injury; Neurodegeneration ID OLIGODENDROCYTE PRECURSOR CELLS; BLOOD-BRAIN-BARRIER; CEREBRAL ENDOTHELIAL-CELLS; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; SUBVENTRICULAR ZONE; AMYLOID-BETA; FUNCTIONAL RECOVERY; DENTATE GYRUS; SPINAL-CORD AB The neurovascular unit provides a conceptual framework for investigating the pathophysiology of how brain cells die after stroke, brain injury, and neurodegeneration. Emerging data now suggest that this concept can be further extended. Cell-cell signaling between neuronal, glial, and vascular elements in the brain not only mediates the mechanisms of acute injury, but integrated responses in these same elements may also be required for recovery as the entire neurovascular unit attempts to reorganize and remodel. Understanding the common signals and substrates of this transition between acute injury and delayed repair in the neurovascular unit may reveal useful paradigms for augmenting neuronal, glial, and vascular plasticity in damaged and diseased brain. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Lo, EH (reprint author), MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU American Heart Association; NINDS FX This work is supported by grants from the American Heart Association and NINDS. Some concepts discussed here are based in part on data and ideas presented in previous reviews (Lok et al., Neurochem Res. 2007; Lo, Br J Pharmacol. 2008; Lo, Nat Med. 2008; Arai et al, FEBS J. 2009; Hayakawa et al., Ann New York Acad Sci. 2010; Lo, Nat Med. 2010; Moskowitz et al., Neuron. 2010). NR 82 TC 36 Z9 37 U1 0 U2 14 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD MAY PY 2012 VL 34 IS 4 BP 325 EP 330 DI 10.1179/1743132812Y.0000000019 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 948XJ UT WOS:000304536600002 PM 22643075 ER PT J AU Gennatas, ED Cholfin, JA Zhou, J Crawford, RK Sasaki, DA Karydas, A Boxer, AL Bonasera, SJ Rankin, KP Gorno-Tempini, ML Rosen, HJ Kramer, JH Weiner, M Miller, BL Seeley, WW AF Gennatas, E. D. Cholfin, J. A. Zhou, J. Crawford, R. K. Sasaki, D. A. Karydas, A. Boxer, A. L. Bonasera, S. J. Rankin, K. P. Gorno-Tempini, M. L. Rosen, H. J. Kramer, J. H. Weiner, M. Miller, B. L. Seeley, W. W. TI COMT Val(158)Met genotype influences neurodegeneration within dopamine-innervated brain structures SO NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; ALZHEIMERS-DISEASE; MESSENGER-RNA; DEMENTIA; SCHIZOPHRENIA; ATROPHY; POLYMORPHISM; PATTERNS; RISK AB Objective: We sought to determine whether the Val(158)Met polymorphism in the catechol-O-methyltransferase (COMT) gene influences neurodegeneration within dopamine-innervated brain regions. Methods: A total of 252 subjects, including healthy controls and patients with Alzheimer disease, behavioral variant frontotemporal dementia, and semantic dementia, underwent COMT genotyping and structural MRI. Results: Whole-brain voxel-wise regression analyses revealed that COMT Val(158)Met Val allele dosage, known to produce a dose-dependent decrease in synaptic dopamine (DA) availability, correlated with decreased gray matter in the region of the ventral tegmental area (VTA), ventromedial prefrontal cortex, bilateral dorsal midinsula, left dorsolateral prefrontal cortex, and right ventral striatum. Unexpectedly, patients carrying a Met allele showed greater VTA volumes than age-matched controls. Gray matter intensities within COMT-related brain regions correlated with cognitive and behavioral deficits. Conclusions: The results are consistent with the hypothesis that increased synaptic DA catabolism promotes neurodegeneration within DA-innervated brain regions. Neurology (R) 2012;78:1663-1669 C1 [Gennatas, E. D.; Cholfin, J. A.; Zhou, J.; Crawford, R. K.; Sasaki, D. A.; Karydas, A.; Boxer, A. L.; Rankin, K. P.; Gorno-Tempini, M. L.; Rosen, H. J.; Kramer, J. H.; Miller, B. L.; Seeley, W. W.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94122 USA. [Bonasera, S. J.] Univ Nebraska Med Ctr, Dept Internal Med, Div Geriatr, Omaha, NE USA. [Weiner, M.] San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Seeley, WW (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94122 USA. EM wseeley@memory.ucsf.edu RI Gorno-Tempini, Maria Luisa/E-7203-2012; OI Bonasera, Stephen/0000-0001-6808-2821 FU National Institute of Aging [AG19724, AG1657303]; Larry L. Hillblom Foundation [2005/2T]; National Institute of Mental Health (NIMH) [K08 MH065938]; Stephen D. Bechtel Foundation FX Supported by grants from the National Institute of Aging (AG19724 and AG1657303 to B. L. M.), the Larry L. Hillblom Foundation (grant 2005/2T to W. W. S.), National Institute of Mental Health (NIMH grant K08 MH065938 to S.J.B.), and the Stephen D. Bechtel Foundation to S.J.B. NR 25 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 21 BP 1663 EP 1669 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 948UB UT WOS:000304527000011 PM 22573634 ER PT J AU Hernandez-Diaz, S Smith, CR Shen, A Mittendorf, R Hauser, WA Yerby, M Holmes, LB AF Hernandez-Diaz, S. Smith, C. R. Shen, A. Mittendorf, R. Hauser, W. A. Yerby, M. Holmes, L. B. CA N Amer AED Pregnancy Registry TI Comparative safety of antiepileptic drugs during pregnancy SO NEUROLOGY LA English DT Article ID MAJOR BIRTH-DEFECTS; CONGENITAL-MALFORMATIONS; ANTICONVULSANT DRUGS; VALPROIC ACID; UK-EPILEPSY; PRELIMINARY EXPERIENCE; PARENTAL EPILEPSY; FETAL EXPOSURE; IN-UTERO; REGISTER AB Objective: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. Methods: The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. Results: The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0-8.5) for valproate, 2.9 (1.4-5.8) for phenobarbital, and 2.2 (1.2-4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. Conclusions: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population. Neurology (R) 2012;78:1692-1699 C1 [Hernandez-Diaz, S.; Smith, C. R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Shen, A.; Holmes, L. B.] MassGen Hosp Children, N Amer AED Pregnancy Registry, Boston, MA USA. [Mittendorf, R.] Loyola Univ Hlth Syst, Chicago, IL USA. [Hauser, W. A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Hauser, W. A.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Yerby, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Hernandez-Diaz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM shernan@hsph.harvard.edu FU Abbott; Eisai; Novartis; Ortho-McNeil; Pfizer; Sunovian Pharmaceuticals FX The North American AED Pregnancy Registry has been supported by funds provided by Abbott, Eisai, Novartis, Ortho-McNeil, Pfizer, and Sunovian Pharmaceuticals. Contributors to the North American AED Pregnancy Registry include Aurobindo Pharma, Dr. Reddy's laboratories, GlaxoSmithKline, Sandoz, and Teva. NR 40 TC 147 Z9 151 U1 1 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 21 BP 1692 EP 1699 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 948UB UT WOS:000304527000015 PM 22551726 ER PT J AU Van den Stock, J Vandenbulcke, M Zhu, Q Hadjikhani, N de Gelder, B AF Van den Stock, J. Vandenbulcke, M. Zhu, Q. Hadjikhani, N. de Gelder, B. TI DEVELOPMENTAL PROSOPAGNOSIA IN A PATIENT WITH HYPOPLASIA OF THE VERMIS CEREBELLI SO NEUROLOGY LA English DT Editorial Material ID FMRI C1 [Van den Stock, J.; Vandenbulcke, M.; de Gelder, B.] Katholieke Univ Leuven, Dept Neurosci, BELL, Div Psychiat, Louvain, Belgium. [Zhu, Q.] Katholieke Univ Leuven, Dept Neurosci, Lab Neuro & Psychophysiol, Louvain, Belgium. [Van den Stock, J.; de Gelder, B.] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [Hadjikhani, N.] Swiss Fed Inst Technol, Brain Mind Inst, CH-1015 Lausanne, Switzerland. [Hadjikhani, N.; de Gelder, B.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Van den Stock, J (reprint author), Katholieke Univ Leuven, Dept Neurosci, BELL, Div Psychiat, Louvain, Belgium. EM jan.vandenstock@med.kuleuven.be RI Hadjikhani, Nouchine/C-2018-2008; Van den Stock, Jan/F-1906-2014 OI Hadjikhani, Nouchine/0000-0003-4075-3106; Van den Stock, Jan/0000-0001-5756-3195 NR 7 TC 7 Z9 7 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 21 BP 1700 EP 1702 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 948UB UT WOS:000304527000016 PM 22573630 ER PT J AU Okonkwo, OC Xu, G Dowling, NM Bendlin, BB LaRue, A Hermann, BP Koscik, R Jonaitis, E Rowley, HA Carlsson, CM Asthana, S Sager, MA Johnson, SC AF Okonkwo, O. C. Xu, G. Dowling, N. M. Bendlin, B. B. LaRue, A. Hermann, B. P. Koscik, R. Jonaitis, E. Rowley, H. A. Carlsson, C. M. Asthana, S. Sager, M. A. Johnson, S. C. TI Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults SO NEUROLOGY LA English DT Article ID NORMAL INDIVIDUALS; MATERNAL HISTORY; TEMPORAL-LOBE; APOLIPOPROTEIN-E; GRAY-MATTER; BASE-LINE; VOLUME; CHILDREN; STATISTICS; TRIALS AB Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E epsilon 4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. Methods: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. Results: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH x APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. Conclusion: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade. Neurology (R) 2012;78:1769-1776 C1 [Okonkwo, O. C.; Xu, G.; Bendlin, B. B.; Carlsson, C. M.; Asthana, S.; Johnson, S. C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Okonkwo, O. C.; Xu, G.; Dowling, N. M.; Bendlin, B. B.; LaRue, A.; Hermann, B. P.; Koscik, R.; Jonaitis, E.; Rowley, H. A.; Carlsson, C. M.; Asthana, S.; Sager, M. A.; Johnson, S. C.] Univ Wisconsin, Sch Med, Alzheimers Dis Res Ctr, Madison, WI 53706 USA. [Okonkwo, O. C.; Xu, G.; Dowling, N. M.; Bendlin, B. B.; LaRue, A.; Hermann, B. P.; Koscik, R.; Jonaitis, E.; Rowley, H. A.; Carlsson, C. M.; Asthana, S.; Sager, M. A.; Johnson, S. C.] Univ Wisconsin, Sch Med, Wisconsin Alzheimers Inst, Madison, WI 53706 USA. [Dowling, N. M.] Univ Wisconsin, Sch Med, Dept Biostat & Med Informat, Madison, WI 53706 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU NIA [AG021155, AG027161, P50-AG033514]; Veterans Administration [I01CX000165]; Clinical and Translational Science Award [UL1-RR025011]; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. FX Supported by NIA grants AG021155 (S.C.J.), AG027161 (M.A.S.), and P50-AG033514 (S.A.); by Veterans Administration Merit Review grant I01CX000165 (S.C.J.); and by a Clinical and Translational Science Award (UL1-RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 39 TC 15 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 22 BP 1769 EP 1776 DI 10.1212/WNL.0b013e3182583047 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 948UZ UT WOS:000304529600017 PM 22592366 ER PT J AU McAllister, TW Flashman, LA Maerlender, A Greenwald, RM Beckwith, JG Tosteson, TD Crisco, JJ Brolinson, PG Duma, SM Duhaime, AC Grove, MR Turco, JH AF McAllister, T. W. Flashman, L. A. Maerlender, A. Greenwald, R. M. Beckwith, J. G. Tosteson, T. D. Crisco, J. J. Brolinson, P. G. Duma, S. M. Duhaime, A. -C. Grove, M. R. Turco, J. H. TI Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes SO NEUROLOGY LA English DT Article ID TRAUMATIC BRAIN-INJURY; FOOTBALL PLAYERS; DESCRIPTIVE EPIDEMIOLOGY; SURVEILLANCE SYSTEM; FUNCTIONAL MRI; CONCUSSION; MILD; LOCATION; RECOVERY; ENCEPHALOPATHY AB Objective: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes. Methods: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery. Results: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics. Conclusion: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent. Neurology (R) 2012;78:1777-1784 C1 [McAllister, T. W.; Flashman, L. A.; Maerlender, A.; Grove, M. R.] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. [Tosteson, T. D.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Turco, J. H.] Dartmouth Med Sch, Dept Med, Lebanon, NH USA. [Greenwald, R. M.; Beckwith, J. G.] Simbex, Lebanon, NH USA. [Greenwald, R. M.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Crisco, J. J.] Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Bioengn Lab, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI USA. [Brolinson, P. G.] Edward Via Virginia Coll Osteopath Med, Blacksburg, VA USA. [Duma, S. M.] Virginia Tech Wake Forest, Ctr Injury Biomech, Blacksburg, VA USA. [Duhaime, A. -C.] Dartmouth Hitchcock Med Ctr, Childrens Hosp Dartmouth, Hanover, NH USA. [Duhaime, A. -C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McAllister, TW (reprint author), Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. EM thomas.w.mcallister@dartmouth.edu RI Duma, Stefan/A-8368-2012 FU NIH [R01HD048638, RO1NS055020]; National Operating Committee on Standards for Athletic Equipment (NOCSAE) [04-07] FX NIH R01HD048638 and RO1NS055020 and the National Operating Committee on Standards for Athletic Equipment (NOCSAE 04-07). NR 37 TC 61 Z9 62 U1 0 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 22 BP 1777 EP 1784 DI 10.1212/WNL.0b013e3182582fe7 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 948UZ UT WOS:000304529600018 PM 22592370 ER PT J AU Khaled, S Gupta, KB Kucik, DF AF Khaled, Saman Gupta, Kiran B. Kucik, Dennis F. TI Ionizing Radiation Increases Adhesiveness of Human Aortic Endothelial Cells via a Chemokine-Dependent Mechanism SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; ADHESION MOLECULES; LEUKOCYTE ADHESION; AVIDITY REGULATION; P-SELECTIN; ATHEROSCLEROSIS; INFLAMMATION; MICE; DISEASE; EXPRESSION AB Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved. (C) 2012 by Radiation Research Society C1 [Khaled, Saman; Gupta, Kiran B.; Kucik, Dennis F.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Kucik, DF (reprint author), Univ Alabama Birmingham, Dept Pathol, 640A Kaul Bldg,720 S 20th St, Birmingham, AL 35294 USA. EM Kucik@uab.edu FU National Space Biomedical Research Institute through NASA [NCC 9-58] FX This work was supported by the National Space Biomedical Research Institute through NASA NCC 9-58. NR 37 TC 16 Z9 18 U1 0 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2012 VL 177 IS 5 BP 594 EP 601 DI 10.1667/RR2557.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 948JD UT WOS:000304498600008 PM 22087741 ER PT J AU Perez-Johnston, R Sainani, NI Sahani, DV AF Perez-Johnston, Rocio Sainani, Nisha I. Sahani, Dushyant V. TI Imaging of Chronic Pancreatitis (Including Groove and Autoimmune Pancreatitis) SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Chronic pancreatitis; Calcifying; Autoimmune; Groove ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; MR CHOLANGIOPANCREATOGRAPHY; HEREDITARY PANCREATITIS; ALCOHOLIC PANCREATITIS; TROPICAL PANCREATITIS; SECRETIN STIMULATION; VILLOUS TUMORS; CT; CARCINOMA; FEATURES AB Multiple disorders may cause chronic pancreatitis (CP) through recurrent inflammation of the pancreatic parenchyma. Chronic calcifying pancreatitis caused by excessive alcohol intake accounts for most cases of CP. However, there are multiple other causes of CP, including obstructive chronic pancreatitis, autoimmune pancreatitis, groove pancreatitis, tropical, and hereditary pancreatitis. This article reviews the multiple imaging techniques, some of which are accepted as first-line modalities in patients with suspected CP, and the imaging features associated with the different causes of CP. C1 [Perez-Johnston, Rocio; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Sainani, Nisha I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 74 TC 15 Z9 17 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2012 VL 50 IS 3 BP 447 EP + DI 10.1016/j.rcl.2012.03.005 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 949KR UT WOS:000304575600007 PM 22560691 ER PT J AU Cortot, CF Sheehan, WJ Permaul, P Baxi, SN Gaffin, JM Dioun, AF Hoffman, EB Schneider, LC Phipatanakul, W AF Cortot, Catherine F. Sheehan, William J. Permaul, Perdita Baxi, Sachin N. Gaffin, Jonathan M. Dioun, Anahita F. Hoffman, Elaine B. Schneider, Lynda C. Phipatanakul, Wanda TI Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID ALLERGY; CHILDREN; WHITE AB Previous studies suggest that children with egg allergy may be able to tolerate baked egg. Reliable predictors of a successful baked egg challenge are not well established. We examined egg white specific IgE levels, skin-prick test (SPY) results, and age as predictors of baked egg oral food challenge (OFC) outcomes. We conducted a retrospective chart review of children, aged 2-18 years, receiving an egg white specific IgE level, SPY, and OFC to baked egg from 2008 to 2010. Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT wheal size was 12 mm (range, 0-35 mm) for passed challenges and 17 mm (range, 10-30 mm) for failed challenges (p = 0.091). The negative predictive value for passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white specific IgE was 2.02 kU/L (range, <0.35-13.00 kU/L) for passed challenges and 1.52 kU/L (range, 0.51-6.10 kU/L) for failed challenges (p = 0.660). Receiver operating characteristic (ROC) curve analysis for SPY revealed an area under the curve (AUC) of 0.64. ROC curve analysis for egg white specific IgE revealed an AUC of 0.63. There was no significant difference in age between patients who failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721). Based on our sample, SPT, egg white specific IgE and age are not good predictors of passing a baked egg challenge. However, there was a trend for more predictability with SPT wheal size. (Allergy Asthma Proc 33:275-281, 2012; doi: 10.2500/aap.2012.33.3544) C1 [Cortot, Catherine F.; Sheehan, William J.; Baxi, Sachin N.; Dioun, Anahita F.; Schneider, Lynda C.; Phipatanakul, Wanda] Childrens Hosp, Dept Med, Div Allergy & Immunol, Boston, MA 02115 USA. [Cortot, Catherine F.; Sheehan, William J.; Permaul, Perdita; Baxi, Sachin N.; Gaffin, Jonathan M.; Dioun, Anahita F.; Schneider, Lynda C.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Dept Pediat, Div Pulm Allergy & Immunol, Boston, MA 02114 USA. [Gaffin, Jonathan M.] Childrens Hosp, Dept Med, Div Pulm & Resp Dis, Boston, MA 02115 USA. [Hoffman, Elaine B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Phipatanakul, W (reprint author), Childrens Hosp, Dept Med, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU National Institutes of Health [R01 AI 073964, R01 AI 073964-02S1] FX W Phipatanakul is funded by grants R01 AI 073964 and R01 AI 073964-02S1 from the National Institutes of Health. The remaining authors have no conflicts of interest to declare pertaining to this article NR 13 TC 21 Z9 22 U1 0 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAY-JUN PY 2012 VL 33 IS 3 BP 275 EP 281 DI 10.2500/aap.2012.33.3544 PG 7 WC Allergy SC Allergy GA 946UA UT WOS:000304381800009 PM 22584194 ER PT J AU Leonardi, S Mahaffey, KW White, HD Gibson, CM Stone, GW Steg, PGW Hamm, CW Price, MJ Todd, M Dietrich, M Gallup, D Liu, TP Skerjanec, S Harrington, RA Bhatt, DL AF Leonardi, Sergio Mahaffey, Kenneth W. White, Harvey D. Gibson, C. Michael Stone, Gregg W. Steg, Ph Gabriel W. Hamm, Christian W. Price, Matthew J. Todd, Meredith Dietrich, Markus Gallup, Dianne Liu, Tiepu Skerjanec, Simona Harrington, Robert A. Bhatt, Deepak L. TI Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ELEVATION MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; GLYCOPROTEIN IIB/IIIA INHIBITORS; ASSOCIATION TASK-FORCE; CLINICAL-TRIALS; UNIVERSAL DEFINITION; RECEPTOR ANTAGONIST; PRACTICE GUIDELINES; CLOPIDOGREL AB Background Despite robust efficacy in the reduction of ischemic events in patients who require percutaneous coronary intervention (PCI), current P2Y(12) inhibitors have limitations. In particular, they require hours to be effective, and they can only be administered orally. Cangrelor is an intravenous, potent, and reversible P2Y12 inhibitor with fast onset and offset of action. We designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in patients with atherosclerosis undergoing PCI. Trial Design The CHAMPION PHOENIX is a randomized, double-blind, double-dummy, superiority trial comparing cangrelor with clopidogrel standard of care in approximately 10,900 patients who have not previously received a P2Y12 inhibitor and who require PCI, including patients with stable angina and with acute coronary syndromes (with or without ST-segment elevation). The primary objective of the study is to demonstrate that cangrelor will reduce the incidence of the composite of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48 hours after randomization compared with clopidogrel without excessive periprocedural bleeding. The key secondary objective is to demonstrate that cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction will be defined according to the universal MI definition, adapting the definition of PCI-related (type 4a) MI. Bleeding will be assessed according to the thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research Consortium (BARC) scales. Conclusion The CHAMPION PHOENIX may establish the role of cangrelor in the care of patients who require PCI across the spectrum of stable and unstable coronary diseases in the setting of current treatment strategies. (Am Heart J 2012;163:768-776.e2.) C1 [Leonardi, Sergio; Mahaffey, Kenneth W.; Gallup, Dianne; Harrington, Robert A.] Duke Clin Res Inst, Durham, NC USA. [Leonardi, Sergio] Fdn IRCCS Policlin S Matteo, Pavia, Italy. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. [Stone, Gregg W.] Cardiovasc Res Fdn, New York, NY USA. [Steg, Ph Gabriel W.] INSERM, U698, Paris, France. [Steg, Ph Gabriel W.] Univ Paris Diderot, Paris, France. [Steg, Ph Gabriel W.] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Hamm, Christian W.] Kerckhoff Heart & Thorax Ctr, Bad Nauheim, Germany. [Price, Matthew J.] Scripps Clin, La Jolla, CA USA. [Price, Matthew J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Todd, Meredith; Dietrich, Markus; Liu, Tiepu; Skerjanec, Simona] Medicines Co, Parsippany, NJ USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), 1400 VFW Pkwy, Boston, MA 02132 USA. EM DLBHATTMD@post.harvard.edu OI Leonardi, Sergio/0000-0002-4800-6132 FU Medicines Company; Bayer; Sanofi-Aventis; Boehringer Ingleheim; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Johnson and Johnson; Merck; Novartis; Portola Pharmaceuticals; Pozen; Regado; GSK; Astra Zeneca; Merck Sharpe Dohme; Schering Plough; Roche; Pfizer; NIH; NYU School of Medicine; Sanofi; Servier; Ablynx; Amarin; Amgen; Astellas; Boehringer-Ingelheim; Daiichi-Sankyo/Eli Lilly alliance; Eisai; Medtronic; Otsuka; BMS/Sanofi Aventis; Accumetrics; AstraZeneca; Ethicon; Significant; BMS; Portola FX The CHAMPION PHOENIX trial is funded by The Medicines Company. K. W. Mahaffey: Research Grant for Bayer, Sanofi-Aventis, Boehringer Ingleheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson and Johnson, Merck, Novartis, Portola Pharmaceuticals, Pozen, Regado. Consultant/Advisory Board for Bayer, Merck, Johnson and Johnson, Boehringer Ingleheim, GlaxoSmithKline, Eli Lilly, Bristol-Myers Squibb, Ortho/McNeill, Sanofi-Aventis. Consultant/Advisory Board for Astra Zeneca. Complete disclosures at https://www.dcri.org/about-us/conflict-of-interest. H. White: Research Grant from Bristol-Myers Squibb, Sanofi-Aventis, Daiichi Sankyo, GSK, Astra Zeneca, Merck Sharpe & Dohme, Schering Plough, Johnson & Johnson, Roche, Pfizer, NIH, The Medicines Company, Eli Lilly. Consultant/Advisory Board for Regado. C. M. Gibson: Research Grant for The Medicines Company. Honoraria for The Medicines Company. Consultant/Advisory Board for The Medicines Company. G. W. Stone: Consultant/Advisory Board for The Medicines Company. Ph. G. Steg: Research grants from NYU School of Medicine, Sanofi, Servier; fees for consultancy or participation in advisory board meetings from Ablynx, Amarin, Amgen, Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly alliance, Eisai, GlaxoSmithKline, Medtronic, Merck Sharpe and Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier and The Medicines Company; and has equity ownership in Aterovax. Meredith Todd, Tiepu Liu, Simona Skerjanec and Markus Dietricht are employees of The Medicines Company. C. W. Hamm: Consultant/advisory board and speaker honorarium: The Medicines Company, AstraZeneca, Sanofi-Aventis, Lilly, Daiichi Sankyo, GSK, BMS. M. J. Price: Research Grants - BMS/Sanofi Aventis, Accumetrics, Quest Diagnostics Consulting/Advisory Boards - BMS/Sanofi-Aventis, DSI/Lilly&Company, Accumetrics, Merck, Medicure, AstraZeneca, The Medicines Company, Johnson & Johnson Speaking Honoraria - DSI/Lilly & Company, AstraZeneca. R. A. Harrington: Research Grant; Significant; The Medicines Company, BMS, Merck, Sanofi-Aventis, Portola, Novartis. Consultant/Advisory Board; Modest; Merck, Astra Zeneca. Consultant/Advisory Board; Significant; BMS, Sanofi-Aventis. Complete disclosures at https://www.dcri.org/about-us/conflict-of-interest. D. L. Bhatt: Research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. NR 38 TC 32 Z9 32 U1 0 U2 1 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 2012 VL 163 IS 5 BP 768 EP + DI 10.1016/j.ahj.2012.02.018 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 945GL UT WOS:000304261000011 PM 22607853 ER PT J AU Lev, MH AF Lev, M. H. TI Acute Stroke Imaging: What Is Sufficient for Triage to Endovascular Therapies? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; CEREBRAL-BLOOD-FLOW; DIFFUSION; BRAIN; MRI C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Lev, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2012 VL 33 IS 5 BP 790 EP 792 DI 10.3174/ajnr.A3098 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 944VI UT WOS:000304231500002 PM 22460336 ER PT J AU Chou, YH Panych, LP Dickey, CC Petrella, JR Chen, NK AF Chou, Y. -h. Panych, L. P. Dickey, C. C. Petrella, J. R. Chen, N. -k. TI Investigation of Long-Term Reproducibility of Intrinsic Connectivity Network Mapping: A Resting-State fMRI Study SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID WORLD BRAIN NETWORKS; FUNCTIONAL CONNECTIVITY; DEFAULT-MODE; MENSTRUAL-CYCLE; CEREBRAL-CORTEX; BOLD SIGNAL; MRI; FLUCTUATIONS; ORGANIZATION; SCHIZOPHRENIA AB BACKGROUND AND PURPOSE: Connectivity mapping based on resting-state fMRI is rapidly developing, and this methodology has great potential for clinical applications. However, before resting-state fMRI can be applied for diagnosis, prognosis, and monitoring treatment for an individual patient with neurologic or psychiatric diseases, it is essential to assess its long-term reproducibility and between-subject variations among healthy individuals. The purpose of the study was to quantify the long-term test-retest reproducibility of ICN measures derived from resting-state fMRI and to assess the between-subject variation of ICN measures across the whole brain. MATERIALS AND METHODS: Longitudinal resting-state fMRI data of 6 healthy volunteers were acquired from 9 scan sessions during > 1 year. The within-subject reproducibility and between-subject variation of ICN measures, across the whole brain and major nodes of the DMN, were quantified with the ICC and COV. RESULTS: Our data show that the long-term test-retest reproducibility of ICN measures is outstanding, with > 70% of the connectivity networks showing an ICC > 0.60. The COV across 6 healthy volunteers in this sample was > 0.2, suggesting significant between-subject variation. CONCLUSIONS: Our data indicate that resting-state ICN measures (eg, the correlation coefficients between fMRI signal-intensity profiles from 2 different brain regions) are potentially suitable as biomarkers for monitoring disease progression and treatment effects in clinical trials and individual patients. Because between-subject variation is significant, it may be difficult to use quantitative ICN measures in their current state as a diagnostic tool. C1 [Chen, N. -k.] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Chou, Y. -h.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. [Petrella, J. R.; Chen, N. -k.] Duke Univ, Dept Radiol, Durham, NC 27710 USA. [Panych, L. P.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Dickey, C. C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Chen, NK (reprint author), Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC 27710 USA. EM Nankuei@gmail.com RI Chen, Nan-kuei/E-7791-2016 OI Chen, Nan-kuei/0000-0001-6564-4219 FU NIH [R01NS37992]; National Institute on Aging [5T32 AG-000029-35] FX This study was supported by NIH grant R01NS37992 awarded to Lawrence P. Panych, PhD; partial funding for Dr. Chou was provided by the National Institute on Aging (5T32 AG-000029-35).; Jeffrey Petrella-UNRELATED: Board Membership Janssen Pharmaceuticals (2010),* Comments: Alzheimer's Disease Neuroradiologist Advisory Board. Consultancy, Draftfcb Healthcare (2011);* Expert Testimony Wilson & Elser (2010),* Comments: medicolegal consultation, Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Portuguese Society of Neuroradiology (2011). Nan-kuei Chen-UNRELATED: Grants/Grants Pending: NIH. * Money paid to institution. NR 50 TC 33 Z9 35 U1 0 U2 12 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 2012 VL 33 IS 5 BP 833 EP 838 DI 10.3174/ajnr.A2894 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 944VI UT WOS:000304231500009 PM 22268094 ER PT J AU Brown, D Bouley, R Paunescu, TG Breton, S Lu, HAJ AF Brown, Dennis Bouley, Richard Paunescu, Teodor G. Breton, Sylvie Lu, Hua A. J. TI New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE aquaporin 2; vacuolar ATPase; intercalated cell; principal cell; kidney; epididymis ID NEPHROGENIC DIABETES-INSIPIDUS; VACUOLAR H+-ATPASE; KIDNEY COLLECTING DUCT; SOLUBLE ADENYLYL-CYCLASE; PROTEIN-KINASE-A; MALE REPRODUCTIVE-TRACT; EPIDIDYMAL CLEAR CELLS; V2 RECEPTOR MUTANTS; INTERCALATED CELLS; RAT-KIDNEY AB Brown D, Bouley R, Paunescu TG, Breton S, Lu HA. New insights into the dynamic regulation of water and acid/base balance by renal epithelial cells. Am J Physiol Cell Physiol 302: C1421-C1433, 2012. First published March 28, 2012; doi:10.1152/ajpcell.00085.2012.-Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes. C1 [Brown, Dennis] Massachusetts Gen Hosp, Simches Res Ctr, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, MGH Ctr Syst Biol, Program Membrane Biol, Simches Res Bldg,185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU NIH [DK-38452, DK-42956, DK-HD40793, DK-73266, DK-075940]; National Kidney Foundation; MGH FX The authors acknowledge the important contributions of all of their past and present lab members in the MGH Program in Membrane Biology/Division of Nephrology. They also thank the NIH for continuous funding of these projects over the years, currently via NIH Grants DK-38452 (to D. Brown and S. Breton), DK-42956 (to D. Brown), DK-HD40793 (to S. Breton), DK-73266 (to T. G. Paunescu), DK-075940 (to H. A. J. Lu), and an Investigator Award from the National Kidney Foundation (to R. Bouley). S. Breton is the recipient of an MGH Scholars Award and H. A. J. Lu is an MGH Claflin Distinguished Fellow. We thank Yechuan Sharon Ruan from the Breton lab for preparing the illustration shown in Fig. 2. Finally, we are grateful for our continued interactions with many other labs throughout the world whose invaluable insights and collegiality make research so rich and rewarding. NR 148 TC 26 Z9 26 U1 5 U2 23 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 2012 VL 302 IS 10 BP C1421 EP C1433 DI 10.1152/ajpcell.00085.2012 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 946OG UT WOS:000304361300001 PM 22460710 ER PT J AU Duerr, EM Mizukami, Y Moriichi, K Gala, M Jo, WS Kikuchi, H Xavier, RJ Chung, DC AF Duerr, Eva-Maria Mizukami, Yusuke Moriichi, Kentaro Gala, Manish Jo, Won-Seok Kikuchi, Hirotoshi Xavier, Ramnik J. Chung, Daniel C. TI Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bone morphogenetic protein 4; GATA2; colon cancer; extracellular signal-regulated kinase; phosphatidylinositol 3-kinase ID BONE-MORPHOGENETIC PROTEIN; GROWTH-FACTOR-BETA; JUVENILE POLYPOSIS; SIGNALING PATHWAYS; GERMLINE MUTATIONS; DIRECT BINDING; TGF-BETA; RAS; SUPPRESSION; INHIBITION AB Duerr EM, Mizukami Y, Moriichi K, Gala M, Jo WS, Kikuchi H, Xavier RJ, Chung DC. Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines. Am J Physiol Gastrointest Liver Physiol 302: G1223-G1230, 2012. First published March 1, 2012; doi:10.1152/ajpgi.00047.2011.-Activating mutations in the KRAS oncogene are common in colorectal cancer. However, the complete spectrum of KRAS targets that mediate its tumorigenic effect has not yet been fully delineated. We identified bone morphogenetic protein 4 (Bmp4), a transforming growth factor-beta family member that regulates development and tissue homeostasis, as a new target of KRAS. In SW480, Hela, and 293 cells, oncogenic KRAS(V12) downregulated BMP4 RNA levels, a BMP4 promoter luciferase construct, and Bmp4 protein levels. The MEK inhibitor PD98059 but not the phosphatidylinositol 3-kinase inhibitor LY294002 blocked this downregulation of BMP4. To identify the region of the BMP4 promoter that mediated this regulation by KRAS, serial 5'-deletions of the promoter were generated. An inhibitory region was identified between -3,285 and -3,258 bp in the Bmp4 promoter. In summary, oncogenic KRAS can downregulate Bmp4 through a transcriptional pathway that depends on ERK. These findings point to a unique link between two pathways that are frequently altered in colon cancer. C1 [Duerr, Eva-Maria; Mizukami, Yusuke; Moriichi, Kentaro; Gala, Manish; Jo, Won-Seok; Kikuchi, Hirotoshi; Xavier, Ramnik J.; Chung, Daniel C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Duerr, Eva-Maria] Univ Munich, Klinikum Grosshadern, Dept Gastroenterol, D-8000 Munich, Germany. [Mizukami, Yusuke] Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Sapporo, Hokkaido, Japan. RP Chung, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM dchung@partners.org FU German Research Foundation (Deutsche Forschungsgemeinschaft); National Cancer Institute [CA-92594] FX E.-M. Duerr was the recipient of a research grant from the German Research Foundation (Deutsche Forschungsgemeinschaft). This work was supported in part by National Cancer Institute Grant CA-92594 (to D. C. Chung). NR 38 TC 1 Z9 1 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 2012 VL 302 IS 10 BP G1223 EP G1230 DI 10.1152/ajpgi.00047.2011 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 946KJ UT WOS:000304350200015 PM 22383492 ER PT J AU Zeitels, SM Wain, JC Barbu, AM Bryson, PC Burns, JA AF Zeitels, Steven M. Wain, John C. Barbu, Anca M. Bryson, Paul C. Burns, James A. TI Aortic Homograft Reconstruction of Partial Laryngectomy Defects: A New Technique SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 18-19, 2012 CL San Diego, CA SP Amer Broncho Esophagol Assoc DE aortic homograft; glottic cancer; larynx cancer; larynx chondrosarcoma; partial laryngectomy; subglottic cancer ID TRACHEAL REPLACEMENT; LASER TREATMENT; SURGERY; CANCER; CARCINOMA; REPAIR AB Objectives: Wide-field transcervical partial laryngectomy often precludes tracheotomy decannulation. It is done infrequently today, primarily because of the popularity of chemotherapy-radiotherapy treatment regimens and limited enthusiasm for using transcervical partial laryngectomy after failed radiotherapy. We sought to identify a new reconstructive technique that would provide an alternative to total laryngectomy in as many patients as possible. Methods: We performed a retrospective examination of 15 patients who underwent single-stage wide-field transcervical partial laryngectomy with cryopreserved aortic homograft reconstruction. Eight of the 15 patients had previously undergone failed radiotherapy. At least 40% of the cricoid circumference was resected in 8 patients. Results: All 15 patients had their tracheotomy tube removed and have laryngeal phonation, and 14 of the 15 resumed oral intake. There were no major surgical complications. Conclusions: Use of aortic homografts is a new, reliable, and versatile reconstructive option for performing conservation laryngeal cancer surgery that allows for airway, swallowing, and voice preservation. C1 [Zeitels, Steven M.; Barbu, Anca M.; Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Zeitels, Steven M.; Wain, John C.; Barbu, Anca M.; Bryson, Paul C.; Burns, James A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Wain, John C.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq, Boston, MA 02114 USA. NR 27 TC 10 Z9 10 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2012 VL 121 IS 5 BP 301 EP 306 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 946FE UT WOS:000304336100004 PM 22724275 ER PT J AU Mehta, DD Zeitels, SM Burns, JA Friedman, AD Deliyski, DD Hillman, RE AF Mehta, Daryush D. Zeitels, Steven M. Burns, James A. Friedman, Aaron D. Deliyski, Dimitar D. Hillman, Robert E. TI High-Speed Videoendoscopic Analysis of Relationships Between Cepstral-Based Acoustic Measures and Voice Production Mechanisms in Patients Undergoing Phonomicrosurgery SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE acoustics; cepstrum; high-speed videoendoscopy; laryngology; phonosurgery ID PHONOSURGICAL TREATMENT; PEAK PROMINENCE; DYSPHONIA; SIGNALS AB Objectives: There is increased interest in using cepstral-based acoustic measures for objective clinical voice assessment because of their apparent advantages over more time-honored methods, but there is a paucity of information about how these newer measures relate to underlying phonatory mechanisms. Methods: We investigated the relationships between the acoustic cepstral peak magnitude (CPM) and high-speed videoendoscopy (HSV)-based measures of vocal fold phonatory function in 20 subjects who underwent phonomicrosurgery for vocal fold lesions. Acoustic and imaging data were acquired during sustained vowel phonation before and after surgery. Results: The changes in the measures between presurgical and postsurgical assessments showed that the CPM correlated significantly with an HSV-based measure combining fundamental frequency deviation and average speed quotient (r = 0.70; p < 0.001) in a multiple linear regression, and that the variation in the CPM could also be attributed to trading relationships between the HSV-based measures of vibratory phase asymmetry and glottal closure. Conclusions: These initial results demonstrate that the clinical utility of cepstral-based measures can be enhanced by a better understanding of how these acoustic measures relate to underlying phonatory mechanisms. The CPM seems to integrate information about aperiodicity in vocal fold vibration, the relative speed of glottal closure, and estimates of glottal noise generation. C1 [Mehta, Daryush D.; Zeitels, Steven M.; Burns, James A.; Friedman, Aaron D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Zeitels, Steven M.; Burns, James A.; Friedman, Aaron D.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Deliyski, Dimitar D.] Cincinnati Childrens Hosp Med Ctr, Commun Sci Res Ctr, Cincinnati, OH USA. [Deliyski, Dimitar D.] Univ Cincinnati, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. RP Hillman, RE (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. FU Eugene B. Casey Foundation; Institute of Laryngology and Voice Restoration; NIH [R01 DC007640] FX From the Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital (Mehta, Zeitels, Burns, Friedman, Hillman), and the Department of Surgery, Harvard Medical School (Zeitels, Burns, Friedman, Hillman), Boston, Massachusetts, and the Communication Sciences Research Center, Cincinnati Children's Hospital Medical Center (Deliyski), and the Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati (Deliyski), Cincinnati, Ohio. This work was supported in part by the Eugene B. Casey Foundation, the Institute of Laryngology and Voice Restoration, and NIH grant R01 DC007640. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 19 TC 12 Z9 12 U1 0 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2012 VL 121 IS 5 BP 341 EP 347 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 946FE UT WOS:000304336100010 PM 22724281 ER PT J AU Taneja, C Papakostas, GI Jing, YH Baker, RA Forbes, RA Oster, G AF Taneja, Charu Papakostas, George I. Jing, Yonghua Baker, Ross A. Forbes, Robert A. Oster, Gerry TI Cost-Effectiveness of Adjunctive Therapy with Atypical Antipsychotics for Acute Treatment of Major Depressive Disorder SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE atypical antipsychotics; cost-effectiveness; major depressive disorder ID EXTENDED-RELEASE QUETIAPINE; DOUBLE-BLIND; INADEQUATE-RESPONSE; ARIPIPRAZOLE; MULTICENTER; ANTIDEPRESSANTS; EPIDEMIOLOGY; EFFICACY; SAFETY AB BACKGROUND: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. OBJECTIVE: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. METHODS: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. RESULTS: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. CONCLUSIONS: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine. C1 [Taneja, Charu; Oster, Gerry] Policy Anal Inc, Brookline, MA USA. [Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA USA. [Papakostas, George I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jing, Yonghua] Bristol Myers Squibb Co, Hlth Serv, Plainsboro, NJ USA. [Forbes, Robert A.] Otsuka Pharmaceut Dev & Commercializat Inc, CNS Global Med Affairs, Neurosci, Princeton, NJ USA. RP Oster, G (reprint author), Policy Anal Inc, Brookline, MA USA. EM goster@pai2.com RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics; Bristol-Myers Squibb Company (Plainsboro, NJ); Otsuka Pharmaceutical Co., Ltd. (Rockville, MD) FX Ms. Taneja and Dr. Oster are employees of Policy Analysis Inc., which has received research funding from Bristol-Myers Squibb Company. Dr. Papakostas has served as a consultant and received honoraria for Abbott Laboratories, AstraZeneca PLC, Brainsway Ltd., Bristol-Myers Squibb Company, Cephalon Inc., Eli Lilly Co., GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, and Wyeth, Inc. He has also received honoraria from Titan Pharmaceuticals, received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics, and served On the past, but not currently) on the speaker's bureau for Bristol-Myers Squibb Company and Pfizer, Inc.; This study was supported by Bristol-Myers Squibb Company (Plainsboro, NJ) and Otsuka Pharmaceutical Co., Ltd. (Rockville, MD). NR 22 TC 7 Z9 7 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 2012 VL 46 IS 5 BP 642 EP 649 DI 10.1345/aph.1Q326 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945QQ UT WOS:000304291500003 PM 22550279 ER PT J AU van der Wilden, GM Velmahos, GC Emhoff, T Brancato, S Adams, C Georgakis, G Jacobs, L Gross, R Agarwal, S Burke, P Maung, AA Johnson, DC Winchell, R Gates, J Cholewczynski, W Rosenblatt, M Chang, YC AF van der Wilden, Gwendolyn M. Velmahos, George C. Emhoff, Timothy Brancato, Samielle Adams, Charles Georgakis, Georgios Jacobs, Lenworth Gross, Ronald Agarwal, Suresh Burke, Peter Maung, Adrian A. Johnson, Dirk C. Winchell, Robert Gates, Jonathan Cholewczynski, Walter Rosenblatt, Michael Chang, Yuchiao TI Successful Nonoperative Management of the Most Severe Blunt Liver Injuries A Multicenter Study of the Research Consortium of New England Centers for Trauma SO ARCHIVES OF SURGERY LA English DT Article ID HEPATIC INJURIES; ANGIOGRAPHIC EMBOLIZATION; EXPERIENCE; MORBIDITY; MORTALITY; RECONECT; OUTCOMES; SPLEEN; ORGAN AB Hypothesis: Grade 4 and grade 5 blunt liver injuries can be safely treated by nonoperative management (NOM). Design: Retrospective case series. Setting: Eleven level I and level II trauma centers in New England. Patients: Three hundred ninety-three adult patients with grade 4 or grade 5 blunt liver injury who were admitted between January 1, 2000, and January 31, 2010. Main Outcome Measure: Failure of NOM (f-NOM), defined as the need for a delayed operation. Results: One hundred thirty-one patients (33.3%) were operated on immediately, typically because of hemodynamic instability. Among 262 patients (66.7%) who were offered a trial of NOM, treatment failed in 23 patients (8.8%) (attributed to the liver in 17, with recurrent liver bleeding in 7 patients and biliary peritonitis in 10 patients). Multivariate analysis identified the following 2 independent predictors of f-NOM: systolic blood pressure on admission of 100 mm Hg or less and the presence of other abdominal organ injury. Failure of NOM was observed in 23% of patients with both independent predictors and in 4% of those with neither of the 2 independent predictors. No patients in the f-NOM group experienced life-threatening events because of f-NOM, and mortality was similar between patients with successful NOM( 5.4%) and patients with f-NOM (8.7%) (P=.52). Among patients with successful NOM, liver-specific complications developed in 10.0% and were managed definitively without major sequelae. Conclusions: Nonoperative management was offered safely in two-thirds of grade 4 and grade 5 blunt liver injuries, with a 91.3% success rate. Only 6.5% of patients with NOM required a delayed operation because of liver-specific issues, and none experienced life-threatening complications because of the delay. C1 [van der Wilden, Gwendolyn M.; Velmahos, George C.; Gates, Jonathan; Chang, Yuchiao] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [van der Wilden, Gwendolyn M.; Velmahos, George C.; Gates, Jonathan; Chang, Yuchiao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Agarwal, Suresh; Burke, Peter] Boston Med Ctr, Boston, MA USA. [Agarwal, Suresh; Burke, Peter] Boston Univ, Boston, MA 02215 USA. [Emhoff, Timothy] Univ Massachusetts Mem Hosp, Dept Surg, Div Trauma Surg & Surg Crit Care, Worcester, MA USA. [Gross, Ronald] Baystate Med Ctr, Dept Surg, Div Trauma Surg & Surg Crit Care, Springfield, MA 01107 USA. [Rosenblatt, Michael] Lahey Clin Fdn, Burlington, MA USA. [Brancato, Samielle; Adams, Charles] Rhode Isl Hosp, Dept Surg, Div Trauma Surg & Surg Crit Care, Providence, RI USA. [Brancato, Samielle; Adams, Charles] Brown Univ, Providence, RI 02912 USA. [Georgakis, Georgios; Jacobs, Lenworth] Univ Connecticut, Sch Med, Hartford Hosp, Hartford, CT 06112 USA. [Maung, Adrian A.; Johnson, Dirk C.] Yale Univ, Sch Med, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, New Haven, CT 06510 USA. [Maung, Adrian A.; Johnson, Dirk C.] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Cholewczynski, Walter] Bridgeport Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Bridgeport, CT USA. [Winchell, Robert] Maine Med Ctr, Portland, ME USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 25 TC 27 Z9 27 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2012 VL 147 IS 5 BP 423 EP 428 PG 6 WC Surgery SC Surgery GA 945JY UT WOS:000304270300006 PM 22785635 ER PT J AU McCormick, F Kadzielski, J Landrigan, CP Evans, B Herndon, JH Rubash, HE AF McCormick, Frank Kadzielski, John Landrigan, Christopher P. Evans, Brady Herndon, James H. Rubash, Harry E. TI Surgeon Fatigue A Prospective Analysis of the Incidence, Risk, and Intervals of Predicted Fatigue-Related Impairment in Residents SO ARCHIVES OF SURGERY LA English DT Article ID ADVERSE EVENTS; PRACTICE PARAMETERS; SLEEP DISORDERS; MEDICAL ERRORS; DUTY HOURS; PERFORMANCE; ACTIGRAPHY; ALCOHOL; INTERNS; COMPLICATIONS AB Hypothesis: A novel approach to identify at-risk periods among orthopedic surgical residents may direct fatigue risk mitigation and facilitate targeted interventions. Design: A prospective cohort study with a minimum 2-week continuous assessment period. Data on sleep and awake periods were processed using the sleep, activity, fatigue, and task effectiveness model. Setting: Rotations at 2 academic tertiary care centers. Participants: Twenty-seven of 33 volunteer orthopedic surgical residents (82%) completed the study, representing 65% (33 of 51) of the orthopedic residency program. Intervention: Residents' sleep and awake periods were continuously recorded via actigraphy, and a daily questionnaire was used to analyze mental fatigue. Main Outcome Measures: Percentage of time at less than 80% mental effectiveness (correlating with an in-creased risk of error), percentage of time at less than 70% mental effectiveness (correlating with a blood alcohol level of 0.08%), the mean amount of daily sleep, and the relative risk of medical error compared with chance. Results: Residents were fatigued during 48% and impaired during 27% of their time awake. Among all residents, the mean amount of daily sleep was 5.3 hours. Overall, residents' fatigue levels were predicted to increase the risk of medical error by 22% compared with well-rested historical control subjects. Night-float residents were more impaired (P=.02), with an increased risk of medical error (P=.045). Conclusions: Resident fatigue is prevalent, pervasive, and variable. To guide targeted interventions, fatigue modeling can be conducted in hospitals to identify periods, rotations, and individuals at risk of medical error. C1 [McCormick, Frank; Kadzielski, John] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02494 USA. [Herndon, James H.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02494 USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02494 USA. [Landrigan, Christopher P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Landrigan, Christopher P.] Childrens Hosp Boston, Div Gen Pediat, Boston, MA USA. [Herndon, James H.] Harvard Univ, Sch Med, Dept Orthoped, Cambridge, MA 02138 USA. RP McCormick, F (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 300 2nd Ave,Unit 4123, Boston, MA 02494 USA. EM Fmccormick@partners.org NR 44 TC 23 Z9 23 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0004-0010 EI 1538-3644 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2012 VL 147 IS 5 BP 430 EP 435 PG 6 WC Surgery SC Surgery GA 945JY UT WOS:000304270300008 PM 22785637 ER PT J AU Geller, AC Swetter, SM AF Geller, A. C. Swetter, S. M. TI Reporting and registering nonmelanoma skin cancers: a compelling public health need SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID BASAL-CELL; RISK; COST C1 [Geller, A. C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Geller, A. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Swetter, S. M.] Vet Affairs Palo Alto Hlth Care Syst, Dermatol Serv, Palo Alto, CA USA. [Swetter, S. M.] Stanford Univ, Med Ctr, Dept Dermatol, Pigmented Les & Melanoma Program, Stanford, CA 94305 USA. [Swetter, S. M.] Inst Canc Res, Stanford, CA USA. RP Geller, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM ageller@hsph.harvard.edu NR 15 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2012 VL 166 IS 5 BP 913 EP 915 DI 10.1111/j.1365-2133.2012.10911.x PG 4 WC Dermatology SC Dermatology GA 950PQ UT WOS:000304661600004 PM 22524396 ER PT J AU Braunstein, I Klein, R Okawa, J Werth, VP AF Braunstein, I. Klein, R. Okawa, J. Werth, V. P. TI The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID DISEASE-ACTIVITY; EXPRESSION; RECRUITMENT; ASSOCIATION; LESIONS; CELLS AB Background There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN-regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0 01 with SLE and P < 0 05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman's rho = 0 55, P = 0 0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE. C1 [Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Dermatol Sect, Philadelphia, PA 19104 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Philadelphia Vet Affairs Med Ctr, Dermatol Sect, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health (NIH) [K24-AR 02207] FX The study was supported by a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development and by the National Institutes of Health (NIH K24-AR 02207) to V.P.W. NR 13 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAY PY 2012 VL 166 IS 5 BP 971 EP 975 DI 10.1111/j.1365-2133.2012.10825.x PG 5 WC Dermatology SC Dermatology GA 950PQ UT WOS:000304661600012 PM 22242767 ER PT J AU Garcia-Garcia, C Ibrahim, YH Serra, V Calvo, MT Guzman, M Grueso, J Aura, C Perez, J Jessen, K Liu, Y Rommel, C Tabernero, J Baselga, J Scaltriti, M AF Garcia-Garcia, Celina Ibrahim, Yasir H. Serra, Violeta Teresa Calvo, Maria Guzman, Marta Grueso, Judit Aura, Claudia Perez, Jose Jessen, Katti Liu, Yi Rommel, Christian Tabernero, Josep Baselga, Jose Scaltriti, Maurizio TI Dual mTORC1/2 and HER2 Blockade Results in Antitumor Activity in Preclinical Models of Breast Cancer Resistant to Anti-HER2 Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID TRASTUZUMAB RESISTANCE; ADJUVANT CHEMOTHERAPY; PATHWAY ACTIVATION; PI3K PATHWAY; LAPATINIB; INHIBITION; RECEPTOR; CELLS; PLUS; AMPLIFICATION AB Purpose: The PI3K/Akt/mTOR pathway is an attractive target in HER2-positive breast cancer that is refractory to anti-HER2 therapy. The hypothesis is that the suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance. Experimental Design: We analyzed in vitro cell viability and induction of apoptosis in five different cell lines resistant to trastuzumab and lapatinib. Inhibition of HER2/HER3 phosphorylation, PI3K/Akt/mTOR, and extracellular signal-regulated kinase (ERK) signaling pathways was evaluated by Western blotting. Tumor growth inhibition after treatment with lapatinib, INK-128, or the combination of both agents was evaluated in three different animal models: two cell-based xenograft models refractory to both trastuzumab and lapatinib and a xenograft derived from a patient who relapsed on trastuzumab-based therapy. Results: The addition of lapatinib to INK-128 prevented both HER2 and HER3 phosphorylation induced by INK-128, resulting in inhibition of both PI3K/Akt/mTOR and ERK pathways. This dual blockade produced synergistic induction of cell death in five different HER2-positive cell lines resistant to trastuzumab and lapatinib. In vivo, both cell line-based and patient-derived xenografts showed exquisite sensitivity to the antitumor activity of the combination of lapatinib and INK-128, which resulted in durable tumor shrinkage and exhibited no signs of toxicity in these models. Conclusions: The simultaneous blockade of both PI3K/Akt/mTOR and ERK pathways obtained by combining lapatinib with INK-128 acts synergistically in inducing cell death and tumor regression in breast cancer models refractory to anti-HER2 therapy. Clin Cancer Res; 18(9); 2603-12. (C) 2012 AACR. C1 [Garcia-Garcia, Celina; Ibrahim, Yasir H.; Serra, Violeta; Teresa Calvo, Maria; Guzman, Marta; Grueso, Judit; Perez, Jose; Tabernero, Josep] Vall dHebron Inst Oncol VHIO, Dept Expt Therapeut Lab, Barcelona, Spain. [Aura, Claudia] Vall dHebron Inst Oncol VHIO, Dept Mol Pathol, Barcelona, Spain. [Scaltriti, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Jessen, Katti; Liu, Yi; Rommel, Christian] Intellikine, La Jolla, CA USA. [Baselga, Jose; Scaltriti, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. RP Scaltriti, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, CNY 149,13th St, Charlestown, MA 02129 USA. EM mscaltriti@partners.org FU Breast Cancer Research Foundation; European Research Council [AdG09 250244] FX This work was supported by Breast Cancer Research Foundation and European Research Council (AdG09 250244). NR 56 TC 71 Z9 72 U1 1 U2 4 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 2012 VL 18 IS 9 BP 2603 EP 2612 DI 10.1158/1078-0432.CCR-11-2750 PG 10 WC Oncology SC Oncology GA 945CA UT WOS:000304249200020 PM 22407832 ER PT J AU Nay, SL Lee, DH Bates, SE O'Connor, TR AF Nay, Stephanie L. Lee, Dong-Hyun Bates, Steven E. O'Connor, Timothy R. TI Alkbh2 protects against lethality and mutation in primary mouse embryonic fibroblasts SO DNA REPAIR LA English DT Article DE DNA repair; AlkB homologs; Fe(II)/alpha-ketoglutarate-dependent dioxygenases; Mutagenesis ID DNA ALKYLATION DAMAGE; REPAIR ENZYME ALKB; ESCHERICHIA-COLI; OXIDATIVE DEMETHYLATION; MOLECULAR-CLONING; RNA; BACTERIAL; 3-METHYLTHYMINE; DIOXYGENASES; PROTEINS AB Alkylating agents modify DNA and RNA forming adducts that disrupt replication and transcription, trigger cell cycle checkpoints and/or initiate apoptosis. If left unrepaired, some of the damage can be cytotoxic and/or mutagenic. In Escherichia coli, the alkylation repair protein B (AlkB) provides one form of resistance to alkylating agents by eliminating mainly 1-methyladenine and 3-methylcytosine, thereby increasing survival and preventing mutation. To examine the biological role of the mammalian AlkB homologs Alkbh2 and Alkbh3, which both have similar enzymatic activities to that of AlkB, we evaluated the survival and mutagenesis of primary Big Blue mouse embryonic fibroblasts (MEFs) that had targeted deletions in the Alkbh2 or Alkbh3 genes. Both Alkbh2- and Alkbh3-deficient MEFs were similar to 2-fold more sensitive to methyl methanesulfonate (MMS) induced cytotoxicity compared to the wild type control cells. Spontaneous mutant frequencies were similar for the wild type. Alkbh2(-/-) and Alkbh3(-/-) MEFs (average - 1.3 x 10(-5)). However, despite the similar survival of the two mutant MEFs after MMS treatment, only the Alkbh2-deficient MEFs showed a statistically significant increase in mutant frequency compared to wild type MEFs after MMS treatment. Therefore, although both Alkbh2 and Alkbh3 can protect against MMS-induced cell death, only Alkbh2 shows statistically significant protection of MEF DNA against mutations following treatment with this exogenous methylating agent. (C) 2012 Elsevier B.V. All rights reserved. C1 [Nay, Stephanie L.; Bates, Steven E.; O'Connor, Timothy R.] City Hope Natl Med Ctr, Div Biol, Duarte, CA 91010 USA. [Nay, Stephanie L.; Lee, Dong-Hyun] City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA. [Lee, Dong-Hyun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP O'Connor, TR (reprint author), City Hope Natl Med Ctr, Div Biol, 1450 E Duarte Rd, Duarte, CA 91010 USA. EM toconnor@coh.org FU City of Hope; City of Hope Cancer Center; Payson Foundation; TRDRP FX We thank the City of Hope, Payson Foundation, TRDRP, and City of Hope Cancer Center for funding and Drs. Walter Tsark, Seung-Gi Jin, and Margaret Morgan for their scientific expertise and help with manuscript preparation. Dr. Jeffrey Longmate is gratefully acknowledged for his assistance with the statistical analysis of the mutation spectra and maps. NR 42 TC 13 Z9 13 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD MAY 1 PY 2012 VL 11 IS 5 BP 502 EP 510 DI 10.1016/j.dnarep.2012.02.005 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 948HP UT WOS:000304494500006 PM 22429847 ER PT J AU Toogood, A Brabant, G Maiter, D Jonsson, B Feldt-Rasmussen, U Koltowska-Haggstrom, M Rasmussen, AK Buchfelder, M Saller, B Biller, BMK AF Toogood, Andrew Brabant, Georg Maiter, Dominique Jonsson, Bjorn Feldt-Rasmussen, Ulla Koltowska-Haggstrom, Maria Rasmussen, Ase Krogh Buchfelder, Michael Saller, Bernhard Biller, Beverly M. K. TI SIMILAR CLINICAL FEATURES AMONG PATIENTS WITH SEVERE ADULT GROWTH HORMONE DEFICIENCY DIAGNOSED WITH INSULIN TOLERANCE TEST OR ARGININE OR GLUCAGON STIMULATION TESTS SO ENDOCRINE PRACTICE LA English DT Article ID QUALITY-OF-LIFE; GH DEFICIENCY; (GH)-RELEASING HORMONE; HYPOPITUITARY ADULTS; CONSENSUS GUIDELINES; PREMATURE MORTALITY; ENDOCRINE-SOCIETY; PROVOCATIVE TESTS; BODY-COMPOSITION; CHILDREN AB Objective: To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 mu g/L is used. Methods: Data were obtained from the KIMS database (Pfizer International. Metabolic Database). Comparisons were made between patients who underwent ITT, AST, or GST for GH peak, body mass index, lipids, waist circumference, waist-to-hip ratio, and quality of life. Results: A total of 5453 tests were available from 4867 patients registered in the database (ITT = 3111, AST = 1390, GST = 952). Significant (P<.001) intraindividual correlations were observed between the GH peaks for ITT vs AST (r = 0.655), ITT vs GST (r = 0.445), and AST vs GST (r = 0.632). GH peaks in response to all tests were negatively correlated to the number of additional pituitary hormone deficiencies and positively correlated to the insulinlike growth factor 1 standard deviation score. Body mass index had a negative influence on all 3 tests. Most clinical variables did not differ between the groups when comparing GH-deficient patients according to the diagnostic test used. The only exceptions that showed any difference were body mass index (slightly higher in the AST and GST groups), triglyceride levels (increased in the GST group), and insulinlike: growth factor I (standard deviation score) (lower in the ITT and AST groups than in the GST group). Waist circumference was greater and quality of life was worse in the GST group than in the other groups. Conclusions: The ITT, AST, and GST produce similar GH peaks, are influenced by similar clinical factors, and identify patients with similar features of GH deficiency at a diagnostic threshold of 3 mu g/L. (Endocr Pract. 2012;18:325-334) C1 [Toogood, Andrew] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Dept Endocrinol, Birmingham B15 2TH, W Midlands, England. [Brabant, Georg] Med Klin 1, Lubeck, Germany. [Maiter, Dominique] Clin Univ St Luc, Dept Endocrinol, B-1200 Brussels, Belgium. [Jonsson, Bjorn] Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden. [Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh] Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. [Koltowska-Haggstrom, Maria] Pfizer Hlth AB, Specialty Business Unit, KIMS Pfizer Endocrine Care, Sollentuna, Sweden. [Buchfelder, Michael] Univ Erlangen Nurnberg, Dept Neurosurg, D-91054 Erlangen, Germany. [Saller, Bernhard] Pfizer Endocrine Care Europe, Tadworth, Surrey, England. [Biller, Beverly M. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. RP Toogood, A (reprint author), Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Dept Endocrinol, Birmingham B15 2TH, W Midlands, England. EM andrew.toogood@uhb.nhs.uk FU Eli Lilly and Company; Pfizer; NovoNordisk A/S; Arvid Nilsson's Foundation FX Dr. Andrew Toogood has received research grants from NovoNordisk A/S and Eli Lilly and Company, has received honoraria from NovoNordisk A/S and Pfizer, and is a member of the International KIMS Board. Dr. Georg Brabant is a member of the KIMS board in Germany and has received honoraria from Pfizer. Dr. Dominique Maiter has received honoraria from Pfizer. Dr. Bjorn Jonsson is a consultant for Pfizer. Dr. Ulla Feldt-Rasmussen has received honoraria and research grants from Pfizer, NovoNordisk A/S, and Arvid Nilsson's Foundation and is a member of the International KIMS Board. Dr. Maria Koltowska-Haggstroni is a full-time employee of Pfizer. Dr. Ase Krogh Rasmussen has received honoraria from Pfizer. Dr. Michael Buchfelder is a member of the KIMS Strategic Advisory Board and has received honoraria from Pfizer. Dr. Bernhard Seller is a full-time employee of Pfizer. Dr. Beverly M. K. Biller has received research grants from Eli Lilly and Company, NovoNordisk A/S, and Pfizer and consulting honoraria from NovoNordisk A/S and Pfizer. NR 30 TC 10 Z9 10 U1 0 U2 5 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2012 VL 18 IS 3 BP 325 EP 334 DI 10.4158/EP11146.OR PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 944WI UT WOS:000304234100003 PM 22068248 ER PT J AU Lee, SL Peterfreund, RA AF Lee, Stephanie L. Peterfreund, Robert A. TI Case Presentation SO ENDOCRINE PRACTICE LA English DT Editorial Material ID SUBGLOTTIC STENOSIS C1 [Lee, Stephanie L.] Boston Med Ctr, Dept Med, Sect Endocrinol Diabet & Metab, Boston, MA USA. [Peterfreund, Robert A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lee, SL (reprint author), 88 E Newton St,Evans 201, Boston, MA 02118 USA. EM stlee@bmc.org NR 3 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD MAY-JUN PY 2012 VL 18 IS 3 BP 428 EP 428 DI 10.4158/EP11381VV PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 944WI UT WOS:000304234100021 PM 22592054 ER PT J AU Borger, DR Zhu, AX AF Borger, Darrell R. Zhu, Andrew X. TI IDH mutations: new genetic signatures in cholangiocarcinoma and therapeutic implications SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE 2-hydroxyglutarate; bile duct; cholangiocarcinoma; differentiation; hypermethylation; IDH1; IDH2; methyltransferase inhibitors; mutation; targeted therapy ID PROMOTER METHYLATION; ONCOMETABOLITE 2-HYDROXYGLUTARATE; EXTRAHEPATIC CHOLANGIOCARCINOMA; PROFILES; GLIOMAS; CANCER C1 [Borger, Darrell R.] Massachusetts Gen Hosp, Dept Med, Translat Res Lab, Boston, MA 02114 USA. RP Borger, DR (reprint author), Massachusetts Gen Hosp, Dept Med, Translat Res Lab, GRJ 1008A,55 Fruit St, Boston, MA 02114 USA. EM dborger@partners.org NR 20 TC 8 Z9 8 U1 0 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAY PY 2012 VL 12 IS 5 BP 543 EP 546 DI 10.1586/ERA.12.32 PG 4 WC Oncology SC Oncology GA 944WS UT WOS:000304235100001 PM 22594888 ER PT J AU Osborn, CY Egede, LE AF Osborn, Chandra Y. Egede, Leonard E. TI The relationship between depressive symptoms and medication nonadherence in type 2 diabetes: the role of social support SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; GLYCEMIC CONTROL; RANDOMIZED-TRIAL; CARE MANAGEMENT; DOUBLE-BLIND; ADHERENCE; METAANALYSIS; MEDIATION; ASSOCIATION AB Objective: Medication adherence promotion interventions are needed that target modifiable behavioral factors contributing to the link between depressive symptoms and poor adherence to diabetes self-care behaviors. In an effort to identify what factors contribute to this link, we examined the role of social support as a mediator of the relationship between depressive symptoms and medication nonadherence. Method: We recruited 139 subjects with type 2 diabetes. Using an indirect effect test with bias-corrected (BC) bootstrapping, we tested whether depressive symptoms had an indirect effect on medication nonadherence through a lack of social support. Results: More depressive symptoms were associated with medication nonadherence (total effect=.06, P<.001), more depressive symptoms were associated with less social support (direct effect of the predictor on the mediator=.96, P=.02), and less social support was associated with medication nonadherence (direct effect of the mediator on the outcome=-.01, P<.01). While the relationship between more depressive symptoms and medication nonadherence persisted with social support in the predicted pathway, the degree of this relationship was partially explained by a relationship between more depressive symptoms and less social support (indirect effect=.01, 95% BC bootstrapped confidence interval of .0005 to .0325). Conclusion: Providing social support to patients with diabetes who have symptoms of depression may ameliorate some of the deleterious effects of depressive symptoms on medication nonadherence, but social support alone is not enough. (C) 2012 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Dept Biomed Informat, Sch Med, Nashville, TN 37232 USA. [Osborn, Chandra Y.] Vanderbilt Univ, Vanderbilt Diabet Res & Training Ctr, Sch Med, Nashville, TN 37232 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29401 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institutes of Health (NIH) [NIDDK K01 DK087894]; NTH [NIDDK K24 DK093699] FX Dr. Osborn is supported by a National Institutes of Health (NIH) Career Development Award (NIDDK K01 DK087894). Dr. Egede is supported by an NTH Career Development Award (NIDDK K24 DK093699). NR 41 TC 22 Z9 24 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2012 VL 34 IS 3 BP 249 EP 253 DI 10.1016/j.genhosppsych.2012.01.015 PG 5 WC Psychiatry SC Psychiatry GA 944XR UT WOS:000304237600006 PM 22401705 ER PT J AU Sher, L AF Sher, Leo TI Bipolar Psychopharmacotherapy: Caring for the Patient SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), Mt Sinai Sch Med, New York, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 2012 VL 200 IS 5 BP 454 EP 454 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 946ET UT WOS:000304335000014 ER PT J AU Shelton, L Pendse, G Maleki, N Moulton, EA Lebel, A Becerra, L Borsook, D AF Shelton, L. Pendse, G. Maleki, N. Moulton, E. A. Lebel, A. Becerra, L. Borsook, D. TI Mapping pain activation and connectivity of the human habenula SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE diffusion tensor imaging; efferent; functional connectivity; afferent ID NEGATIVE REWARD SIGNALS; LATERAL HABENULA; PERIAQUEDUCTAL GRAY; MEDIAL HABENULA; ELECTRICAL-STIMULATION; EFFERENT PROJECTIONS; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; DOPAMINE NEURONS; BASAL GANGLIA AB Shelton L, Pendse G, Maleki N, Moulton EA, Lebel A, Becerra L, Borsook D. Mapping pain activation and connectivity of the human habenula. J Neurophysiol 107: 2633-2648, 2012. First published February 8, 2012; doi:10.1152/jn.00012.2012.-The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e. g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e. g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain. C1 [Shelton, L.; Maleki, N.; Becerra, L.; Borsook, D.] Childrens Hosp Boston, PAIN Grp, Dept Radiol, Waltham, MA 02453 USA. [Lebel, A.; Becerra, L.] Childrens Hosp Boston, Dept Anesthesiol, Waltham, MA USA. [Pendse, G.; Moulton, E. A.; Becerra, L.; Borsook, D.] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Borsook, D (reprint author), Childrens Hosp Boston, PAIN Grp, Dept Radiol, Waltham, MA 02453 USA. EM david.borsook@childrens.harvard.edu FU National Institute of Neurological Disorders and Stroke [1R01 NS-065051, K24 NS-64050]; NIDA [K01 DA-024289] FX This work was supported by National Institute of Neurological Disorders and Stroke Grants 1R01 NS-065051 and K24 NS-64050 and NIDA Grant K01 DA-024289. NR 79 TC 29 Z9 30 U1 2 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2012 VL 107 IS 10 BP 2633 EP 2648 DI 10.1152/jn.00012.2012 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 947HZ UT WOS:000304422300006 PM 22323632 ER PT J AU Tan, CS Broge, T Seung, E Vrbanac, V Viscidi, R Gordon, J Tager, A Koralnik, I AF Tan, Chen Sabrina Broge, Thomas, Jr. Seung, Edward Vrbanac, Vlad Viscidi, Raphael Gordon, Jennifer Tager, Andrew Koralnik, Igor TI JC Virus Infection in a Humanized Mouse Model SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Tan, Chen Sabrina; Broge, Thomas, Jr.; Koralnik, Igor] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Seung, Edward; Vrbanac, Vlad; Tager, Andrew] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Viscidi, Raphael] Johns Hopkins Med Ctr, Baltimore, MD USA. [Gordon, Jennifer] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. EM ctan@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2012 VL 18 SU 1 MA P222 BP 108 EP 109 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 948FA UT WOS:000304487800223 ER PT J AU Bush, AL Patel, AB Allen, JG Teal, C Latini, DM Ellis, TE Herrera, S Frueh, BC AF Bush, Amber L. Patel, Amee B. Allen, Jon G. Teal, Cayla Latini, David M. Ellis, Thomas E. Herrera, Steven Frueh, B. Christopher TI Factor Structure and Convergent Validity of the Inventory of Interpersonal Problems in an Inpatient Setting SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE Inventory of Interpersonal Problems; interpersonal processes; psychometric evaluation; inpatient population; clinical utility ID PERSONALITY-DISORDERS; COGNITIVE THERAPY; SOCIAL SUPPORT; PSYCHOTHERAPY; DEPRESSION; VERSION; STYLES; SCALES; LONG; CARE AB The Inventory of Interpersonal Problems (IIP-32) is a self-report measure designed to be used in clinical settings to assess interpersonal difficulties. However, it has been exclusively used in either outpatient or non-clinical settings, and psychometric data concerning its use in inpatients are limited. The current study examined the factor structure and construct validity of the IIP-32, and ways to optimally use this measure with inpatients at a private hospital providing intensive treatment. The original eight-factor structure was a poor fit to the data, whereas a five-factor structure provided a somewhat better fit. Although the five factors (Nonassertive, Detached, Intrusive, Self-Sacrificing, and Socially Inhibited) demonstrated adequate internal consistency, reliability, and limited convergent validity, the IIP is ultimately useful insofar as it engages patients in collaborative self-awareness during intensive psychotherapeutically oriented treatment. (Journal of Psychiatric Practice 2012;18:145-158) C1 [Bush, Amber L.] VA Hlth Serv Res & Dev Houston Ctr Excellence, Houston, TX 77030 USA. [Bush, Amber L.; Latini, David M.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Bush, Amber L.; Allen, Jon G.; Teal, Cayla; Latini, David M.; Ellis, Thomas E.; Herrera, Steven; Frueh, B. Christopher] Baylor Coll Med, Houston, TX 77030 USA. [Patel, Amee B.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Patel, Amee B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. RP Bush, AL (reprint author), VA Hlth Serv Res & Dev Houston Ctr Excellence, 2002 Holcombe Blvd,MEDVAMC 152, Houston, TX 77030 USA. EM amspoker@bcm.tmc.edu OI Latini, David/0000-0002-6161-4861; Ellis, Thomas/0000-0002-4496-5280 FU Houston VA HSR&D Center of Excellence [HFP90-020]; Menninger Foundation FX This work was supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020) and the Menninger Foundation. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs /Baylor College of Medicine. NR 37 TC 1 Z9 1 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2012 VL 18 IS 3 BP 145 EP 158 DI 10.1097/01.pra.0000415072.36121.2d PG 14 WC Psychiatry SC Psychiatry GA 946MV UT WOS:000304356900002 PM 22617080 ER PT J AU Lipsky, BA Kuss, M Edmonds, M Reyzelman, A Sigal, F AF Lipsky, Benjamin A. Kuss, Michael Edmonds, Michael Reyzelman, Alexander Sigal, Felix TI Topical Application of a Gentamicin-Collagen Sponge Combined with Systemic Antibiotic Therapy for the Treatment of Diabetic Foot Infections of Moderate Severity A Randomized, Controlled, Multicenter Clinical Trial SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID IN-VITRO ACTIVITY; RESISTANT STAPHYLOCOCCUS-AUREUS; CALCIUM-SULFATE PELLETS; ANTIMICROBIAL AGENTS; FLUOROQUINOLONES; MANAGEMENT; SYNERGY AB Background: The aim of this pilot study was to determine the safety and potential benefit of adding a topical gentamicin-collagen sponge to standard of care (systemic antibiotic therapy plus standard diabetic wound management) for treating diabetic foot infections of moderate severity. Methods: We randomized 56 patients with moderately infected diabetic foot ulcers in a 2:1 ratio to receive standard of care plus the gentamicin-collagen sponge (treatment group, n=38) or standard of care only (control group, n = 18) for up to 28 days of treatment. Investigators performed clinical, microbiological, and safety assessments at regularly scheduled intervals and collected pharmacokinetic samples from patients treated with the gentamicin-collagen sponge. Test of cure was clinically assessed 14 days after all antibiotic therapy was stopped. Results: On treatment day 7, we noted clinical cure in no treatment patients and three control patients (P=.017). However, for evaluable patients at the test-of-cure visit, the treatment group had a significantly higher proportion of patients with clinical cure than did the control group (22 of 22 [100.0%] versus 7 of 10 [70.0%]; P=.024). Patients in the treatment group also had a higher rate of eradication of baseline pathogens at all visits (P <=.038) and a reduced time to pathogen eradication (P<.001). Safety data were similar for both groups. Conclusions: Topical application of the gentamicin-collagen sponge seems safe and may improve clinical and microbiological outcomes of diabetic foot infections of moderate severity when combined with standard of care. These pilot data suggest that a larger trial of this treatment is warranted. (J Am Podiatr Med Assoc 102(3): 223-232, 2012) C1 [Lipsky, Benjamin A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, Seattle, WA 98116 USA. [Kuss, Michael] Premier Res Grp Ltd, Austin, TX USA. [Edmonds, Michael] Kings Coll Hosp London, London, England. [Reyzelman, Alexander] Clin Res Ctr, Castro Valley, CA USA. [Sigal, Felix] Pacific Clin Ctr, Los Angeles, CA USA. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Sch Med, S-111-PCC,1660 S Columbian Way, Seattle, WA 98116 USA. EM balipsky@uw.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU Innocoll Technologies Ltd. FX This study was funded in whole by Innocoll Technologies Ltd. NR 21 TC 16 Z9 19 U1 0 U2 7 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAY-JUN PY 2012 VL 102 IS 3 BP 223 EP 232 PG 10 WC Orthopedics SC Orthopedics GA 945OW UT WOS:000304286900007 PM 22659765 ER PT J AU Briggs, SM AF Briggs, Susan Miller TI EDITORIAL CRITIQUE SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Briggs, SM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAY PY 2012 VL 72 IS 5 BP 1334 EP 1334 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 944JD UT WOS:000304195100041 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Charles F. Kettering-Medical Philanthropist and Inventor SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN USA. OI Steensma, David/0000-0001-5130-9284 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2012 VL 87 IS 5 BP E35 EP E35 DI 10.1016/j.mayocp.2012.01.014 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 944IX UT WOS:000304194300002 PM 22560533 ER PT J AU Stahl, EA Wegmann, D Trynka, G Gutierrez-Achury, J Do, R Voight, BF Kraft, P Chen, R Kallberg, HJ Kurreeman, FAS Kathiresan, S Wijmenga, C Gregersen, PK Alfredsson, L Siminovitch, KA Worthington, J de Bakker, PIW Raychaudhuri, S Plenge, RM AF Stahl, Eli A. Wegmann, Daniel Trynka, Gosia Gutierrez-Achury, Javier Do, Ron Voight, Benjamin F. Kraft, Peter Chen, Robert Kallberg, Henrik J. Kurreeman, Fina A. S. Kathiresan, Sekar Wijmenga, Cisca Gregersen, Peter K. Alfredsson, Lars Siminovitch, Katherine A. Worthington, Jane de Bakker, Paul I. W. Raychaudhuri, Soumya Plenge, Robert M. CA Diabet Genetics Replication Metaan Myocardial Infarction Genetics Con TI Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CELIAC-DISEASE; GENETIC SUSCEPTIBILITY; MISSING HERITABILITY; HEART-DISEASE; HUMAN HEIGHT; COMMON SNPS; RISK LOCI; VARIANTS AB The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases. C1 [Stahl, Eli A.; Chen, Robert; Kurreeman, Fina A. S.; Raychaudhuri, Soumya; Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Stahl, Eli A.; Do, Ron; Chen, Robert; Kurreeman, Fina A. S.; Kathiresan, Sekar; de Bakker, Paul I. W.; Raychaudhuri, Soumya; Plenge, Robert M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Stahl, Eli A.; Chen, Robert; Kurreeman, Fina A. S.; de Bakker, Paul I. W.; Raychaudhuri, Soumya; Plenge, Robert M.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Wegmann, Daniel] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Trynka, Gosia; Gutierrez-Achury, Javier; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Trynka, Gosia; Gutierrez-Achury, Javier; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Do, Ron; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Do, Ron; Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Voight, Benjamin F.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Kallberg, Henrik J.; Alfredsson, Lars] Karolinska Inst Hosp Solna, Inst Environm Med, Stockholm, Sweden. [Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Siminovitch, Katherine A.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. [Siminovitch, Katherine A.] Univ Hlth Network, Toronto, ON, Canada. [Worthington, Jane] Univ Manchester, Arthrit Res UK Epidemiol Unit, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. RP Stahl, EA (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM estahl@rics.bwh.harvard.edu; rplenge@partners.org RI Elliott, Amanda/G-5120-2012; Rudan, Igor/I-1467-2012; Wegmann, Daniel/K-2199-2012; de Bakker, Paul/B-8730-2009; Wijmenga, Cisca/D-2173-2009; Siminovitch, Katherine/K-1475-2013; Duga, Stefano/F-8173-2014; Worthington, Jane/M-9770-2014; Boehm, Bernhard/F-8750-2015; Meitinger, Thomas/O-1318-2015; Ramos , Rafel/D-9627-2016; OI van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Asselta, Rosanna/0000-0001-5351-0619; Ramos , Rafel/0000-0001-7970-5537; Hide, Winston/0000-0002-8621-3271; Alfredsson, Lars/0000-0003-1688-6697; Wijmenga, Cisca/0000-0002-5635-1614; Jorgensen, Torben/0000-0001-9453-2830; Marrugat, Jaume/0000-0003-3320-554X; Rudan, Igor/0000-0001-6993-6884; Wegmann, Daniel/0000-0003-2866-6739; de Bakker, Paul/0000-0001-7735-7858; Worthington, Jane/0000-0003-0544-042X; Ramos , Rafel/0000-0001-8146-5288; Zeggini, Eleftheria/0000-0003-4238-659X; Trynka, Gosia/0000-0002-6955-9529 FU US National Institutes of Health (NIH) [R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648]; NIH [K08AR055688-01A1, NO1-AR-2-2263, RO1-AR44422]; Crescendo and Biogen-Idec; National Institute of Arthritis, Musculoskeletal and Skin Diseases of the NIH; Canada Research Chair; Canadian Institutes for Health Research [MOP79321, IIN-84042]; Ontario Research Fund [RE01061] FX R.M.P. is supported by grants from the US National Institutes of Health (NIH) (R01-AR057108, R01-AR056768, U01-GM092691 and R01-AR059648) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. S. R. is supported by an NIH Career Development Award (K08AR055688-01A1). The Brigham Rheumatoid Arthritis Sequential Study Registry is supported by a grant from Crescendo and Biogen-Idec. The North American Rheumatoid Arthritis Consortium is supported by the NIH (NO1-AR-2-2263 and RO1-AR44422). This research was also supported in part by the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the NIH and by a Canada Research Chair and grants to K. A. S. from the Canadian Institutes for Health Research (MOP79321 and IIN-84042) and the Ontario Research Fund (RE01061). We acknowledge S. Purcell, A. Price and N. Zaitlen for help with the design and implementation of the study and analysis. NR 59 TC 187 Z9 187 U1 3 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2012 VL 44 IS 5 BP 483 EP + DI 10.1038/ng.2232 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 934BW UT WOS:000303416300006 PM 22446960 ER PT J AU Stein, JL Medland, SE Vasquez, AA Hibar, DP Senstad, RE Winkler, AM Toro, R Appel, K Bartecek, R Bergmann, O Bernard, M Brown, AA Cannon, DM Chakravarty, MM Christoforou, A Domin, M Grimm, O Hollinshead, M Holmes, AJ Homuth, G Hottenga, JJ Langan, C Lopez, LM Hansell, NK Hwang, KS Kim, S Laje, G Lee, PH Liu, XM Loth, E Lourdusamy, A Mattingsdal, M Mohnke, S Maniega, SM Nho, K Nugent, AC O'Brien, C Papmeyer, M Putz, B Ramasamy, A Rasmussen, J Rijpkema, M Risacher, SL Roddey, JC Rose, EJ Ryten, M Shen, L Sprooten, E Strengman, E Teumer, A Trabzuni, D Turner, J van Eijk, K van Erp, TGM van Tol, MJ Wittfeld, K Wolf, C Woudstra, S Aleman, A Alhusaini, S Almasy, L Binder, EB Brohawn, DG Cantor, RM Carless, MA Corvin, A Czisch, M Curran, JE Davies, G de Almeida, MAA Delanty, N Depondt, C Duggirala, R Dyer, TD Erk, S Fagerness, J Fox, PT Freimer, NB Gill, M Goring, HHH Hagler, DJ Hoehn, D Holsboer, F Hoogman, M Hosten, N Jahanshad, N Johnson, MP Kasperaviciute, D Kent, JW Kochunov, P Lancaster, JL Lawrie, SM Liewald, DC Mandl, R Matarin, M Mattheisen, M Meisenzahl, E Melle, I Moses, EK Muhleisen, TW Nauck, M Nothen, MM Olvera, RL Pandolfo, M Pike, GB Puls, R Reinvang, I Renteria, ME Rietschel, M Roffman, JL Royle, NA Rujescu, D Savitz, J Schnack, HG Schnell, K Seiferth, N Smith, C Steen, VM Hernandez, MCV Van den Heuvel, M van der Wee, NJ Van Haren, NEM Veltman, JA Volzke, H Walker, R Westlye, LT Whelan, CD Agartz, I Boomsma, DI Cavalleri, GL Dale, AM Djurovic, S Drevets, WC Hagoort, P Hall, J Heinz, A Jack, CR Foroud, TM Le Hellard, S Macciardi, F Montgomery, GW Poline, JB Porteous, DJ Sisodiya, SM Starr, JM Sussmann, J Toga, AW Veltman, DJ Walter, H Weiner, MW Bis, JC Ikram, MA Smith, AV Gudnason, V Tzourio, C Vernooij, MW Launer, LJ DeCarli, C Seshadri, S Andreassen, OA Apostolova, LG Bastin, ME Blangero, J Brunner, HG Buckner, RL Cichon, S Coppola, G de Zubicaray, GI Deary, IJ Donohoe, G de Geus, EJC Espeseth, T Fernandez, G Glahn, DC Grabe, HJ Hardy, J Pol, HEH Jenkinson, M Kahn, RS McDonald, C McIntosh, AM McMahon, FJ McMahon, KL Meyer-Lindenberg, A Morris, DW Muller-Myhsok, B Nichols, TE Ophoff, RA Paus, T Pausova, Z Penninx, BW Potkin, SG Samann, PG Saykin, AJ Schumann, G Smoller, JW Wardlaw, JM Weale, ME Martin, NG Franke, B Wright, MJ Thompson, PM AF Stein, Jason L. Medland, Sarah E. Vasquez, Alejandro Arias Hibar, Derrek P. Senstad, Rudy E. Winkler, Anderson M. Toro, Roberto Appel, Katja Bartecek, Richard Bergmann, Orjan Bernard, Manon Brown, Andrew A. Cannon, Dara M. Chakravarty, M. Mallar Christoforou, Andrea Domin, Martin Grimm, Oliver Hollinshead, Marisa Holmes, Avram J. Homuth, Georg Hottenga, Jouke-Jan Langan, Camilla Lopez, Lorna M. Hansell, Narelle K. Hwang, Kristy S. Kim, Sungeun Laje, Gonzalo Lee, Phil H. Liu, Xinmin Loth, Eva Lourdusamy, Anbarasu Mattingsdal, Morten Mohnke, Sebastian Maniega, Susana Munoz Nho, Kwangsik Nugent, Allison C. O'Brien, Carol Papmeyer, Martina Putz, Benno Ramasamy, Adaikalavan Rasmussen, Jerod Rijpkema, Mark Risacher, Shannon L. Roddey, J. Cooper Rose, Emma J. Ryten, Mina Shen, Li Sprooten, Emma Strengman, Eric Teumer, Alexander Trabzuni, Daniah Turner, Jessica van Eijk, Kristel van Erp, Theo G. M. van Tol, Marie-Jose Wittfeld, Katharina Wolf, Christiane Woudstra, Saskia Aleman, Andre Alhusaini, Saud Almasy, Laura Binder, Elisabeth B. Brohawn, David G. Cantor, Rita M. Carless, Melanie A. Corvin, Aiden Czisch, Michael Curran, Joanne E. Davies, Gail de Almeida, Marcio A. A. Delanty, Norman Depondt, Chantal Duggirala, Ravi Dyer, Thomas D. Erk, Susanne Fagerness, Jesen Fox, Peter T. Freimer, Nelson B. Gill, Michael Goering, Harald H. H. Hagler, Donald J. Hoehn, David Holsboer, Florian Hoogman, Martine Hosten, Norbert Jahanshad, Neda Johnson, Matthew P. Kasperaviciute, Dalia Kent, Jack W., Jr. Kochunov, Peter Lancaster, Jack L. Lawrie, Stephen M. Liewald, David C. Mandl, Rene Matarin, Mar Mattheisen, Manuel Meisenzahl, Eva Melle, Ingrid Moses, Eric K. Muehleisen, Thomas W. Nauck, Matthias Noethen, Markus M. Olvera, Rene L. Pandolfo, Massimo Pike, G. Bruce Puls, Ralf Reinvang, Ivar Renteria, Miguel E. Rietschel, Marcella Roffman, Joshua L. Royle, Natalie A. Rujescu, Dan Savitz, Jonathan Schnack, Hugo G. Schnell, Knut Seiferth, Nina Smith, Colin Steen, Vidar M. Hernandez, Maria C. Valdes Van den Heuvel, Martijn van der Wee, Nic J. Van Haren, Neeltje E. M. Veltman, Joris A. Voelzke, Henry Walker, Robert Westlye, Lars T. Whelan, Christopher D. Agartz, Ingrid Boomsma, Dorret I. Cavalleri, Gianpiero L. Dale, Anders M. Djurovic, Srdjan Drevets, Wayne C. Hagoort, Peter Hall, Jeremy Heinz, Andreas Jack, Clifford R., Jr. Foroud, Tatiana M. Le Hellard, Stephanie Macciardi, Fabio Montgomery, Grant W. Poline, Jean Baptiste Porteous, David J. Sisodiya, Sanjay M. Starr, John M. Sussmann, Jessika Toga, Arthur W. Veltman, Dick J. Walter, Henrik Weiner, Michael W. Bis, Joshua C. Ikram, M. Arfan Smith, Albert V. Gudnason, Vilmundur Tzourio, Christophe Vernooij, Meike W. Launer, Lenore J. DeCarli, Charles Seshadri, Sudha Andreassen, Ole A. Apostolova, Liana G. Bastin, Mark E. Blangero, John Brunner, Han G. Buckner, Randy L. Cichon, Sven Coppola, Giovanni de Zubicaray, Greig I. Deary, Ian J. Donohoe, Gary de Geus, Eco J. C. Espeseth, Thomas Fernandez, Guillen Glahn, David C. Grabe, Hans J. Hardy, John Pol, Hilleke E. Hulshoff Jenkinson, Mark Kahn, Rene S. McDonald, Colm McIntosh, Andrew M. McMahon, Francis J. McMahon, Katie L. Meyer-Lindenberg, Andreas Morris, Derek W. Mueller-Myhsok, Bertram Nichols, Thomas E. Ophoff, Roel A. Paus, Tomas Pausova, Zdenka Penninx, Brenda W. Potkin, Steven G. Saemann, Philipp G. Saykin, Andrew J. Schumann, Gunter Smoller, Jordan W. Wardlaw, Joanna M. Weale, Michael E. Martin, Nicholas G. Franke, Barbara Wright, Margaret J. Thompson, Paul M. CA ADNI EPIGEN Consortium IMAGEN Consortium Saguenay Youth Study Grp SYS Cohorts Heart Aging Res Genomic Ep Enhancing Neuro Imaging Genetics M TI Identification of common variants associated with human hippocampal and intracranial volumes SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; TEMPORAL-LOBE EPILEPSY; AUTOMATED SEGMENTATION; GENOTYPE IMPUTATION; ALZHEIMERS-DISEASE; BRAIN VOLUME; HUMAN HEIGHT; FUNCTIONAL IMPLICATIONS; NA+/H+ EXCHANGER; UNIFIED APPROACH AB Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and mesial temporal lobe epilepsy(5). Whereas many brain imaging phenotypes are highly heritable(6,7), identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)). 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[Vasquez, Alejandro Arias; Rijpkema, Mark; Hoogman, Martine; Hagoort, Peter; Fernandez, Guillen; Franke, Barbara] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Winkler, Anderson M.; Glahn, David C.] Hartford Hosp, Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT 06115 USA. [Winkler, Anderson M.; Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Toro, Roberto] Inst Pasteur, Lab Human Genet & Cognit Funct, Paris, France. [Toro, Roberto] Inst Pasteur, CNRS, URA Genes Synapses & Cognit 2182, Paris, France. [Toro, Roberto] Univ Paris Diderot, Dept Neurosci, Paris, France. [Appel, Katja; Wittfeld, Katharina; Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Appel, Katja] Univ Heidelberg, Inst Psychol, Dept Clin Psychol & Psychotherapy, Heidelberg, Germany. [Bartecek, Richard; Mandl, Rene; Schnack, Hugo G.; Van den Heuvel, Martijn; Van Haren, Neeltje E. 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Valdes; Porteous, David J.; Starr, John M.; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Hwang, Kristy S.; Apostolova, Liana G.; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Shen, Li; Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Neuroimaging, Dept Radiol & Imaging Sci, Indianapolis, IN USA. [Kim, Sungeun; Shen, Li; Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA. [Laje, Gonzalo; Liu, Xinmin; McMahon, Francis J.] NIMH, Mood & Anxiety Disorders Sect, Human Genet Branch,US Dept HHS, Intramural Res Program,US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. 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[Jack, Clifford R., Jr.] Mayo Clin & Mayo Fdn, Aging & Dementia Imaging Res Lab, Dept Radiol, Rochester, MN USA. [Foroud, Tatiana M.; Saykin, Andrew J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Poline, Jean Baptiste] Commissariat Energie Atom, Inst Imagerie Biomed I2BM, Gif Sur Yvette, France. [Porteous, David J.] Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Mol Med Ctr,Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Royal Victoria Hosp, Geriatr Med Unit, Edinburgh, Midlothian, Scotland. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr, Erasmus Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr, Erasmus Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan; Vernooij, Meike W.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Tzourio, Christophe] Univ Bordeaux, U708, Bordeaux, France. [Tzourio, Christophe] INSERM, U708, Bordeaux, France. [Launer, Lenore J.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Seshadri, Sudha] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Bastin, Mark E.] Univ Edinburgh, Div Hlth Sci Med Phys, Edinburgh, Midlothian, Scotland. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Espeseth, Thomas] Univ Bergen, Dept Biol & Med Psychol, Fac Psychol, Bergen, Norway. [Grabe, Hans J.] German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany. [Jenkinson, Mark; Nichols, Thomas E.] Univ Oxford, FMRIB, Oxford, England. [McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. RP Thompson, PM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuro Imaging, Los Angeles, CA 90095 USA. EM thompson@loni.ucla.edu RI Cavalleri, Gianpiero/A-6632-2010; Weale, Michael/F-2587-2010; McIntosh, Andrew/B-9379-2008; Potkin, Steven/A-2021-2013; Muller-Myhsok, Bertram/A-3289-2013; Jack, Clifford/F-2508-2010; Hardy, John/C-2451-2009; Rijpkema, Mark/D-1974-2010; Kowall, Neil/G-6364-2012; Rose, Emma/A-9960-2010; Cavalieri, Margherita/G-8053-2012; Ramasamy, Adaikalavan/G-2632-2010; Lopez, Lorna/F-7265-2010; Trabzuni, Daniah/C-4034-2012; Meyer-Lindenberg, Andreas/H-1076-2011; Poustka, Luise/D-9299-2017; Moreno, Margarita/K-9869-2014; Wright, Margaret/A-4560-2016; Vollstadt-Klein, Sabine/C-6744-2012; Arias Vasquez, Alejandro/E-4762-2012; McMahon, Katie/C-6440-2009; Vernooij, Meike/E-4061-2016; Macciardi, Fabio/N-3768-2014; Smith, Albert/K-5150-2015; Matarin, Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Finsterbusch, Jurgen/M-2969-2016; Putz, Benno/P-2630-2016; Winkler, Anderson/P-7773-2016; Lourdusamy, Anbarasu/P-6606-2014; lambert, jean-charles/F-8787-2013; LICEND, CEMND/F-1296-2015; de Zubicaray, Greig/B-1763-2008; 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McIntosh, Andrew/0000-0002-0198-4588; Jack, Clifford/0000-0001-7916-622X; Rijpkema, Mark/0000-0002-8495-4703; Kowall, Neil/0000-0002-6624-0213; Rose, Emma/0000-0001-5365-4794; Ramasamy, Adaikalavan/0000-0002-7598-2892; Andreassen, Ole A./0000-0002-4461-3568; Flor, Herta/0000-0003-4809-5398; Shen, Li/0000-0002-5443-0503; Beiser, Alexa/0000-0001-8551-7778; Nugent, Allison/0000-0003-2569-2480; Becker, James/0000-0003-4425-4726; Trabzuni, Daniah/0000-0003-4826-9570; Cavalleri, Gianpiero/0000-0002-9802-0506; Agartz, Ingrid/0000-0002-9839-5391; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Morris, Derek/0000-0002-3413-570X; Delaney, Norman/0000-0002-3953-9842; Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Gill, Michael/0000-0003-0206-5337; Ikram, Mohammad Arfan/0000-0003-0372-8585; van den Heuvel, Martijn/0000-0003-1570-1195; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Moreno, Margarita/0000-0001-7336-6167; Stein, Jason/0000-0003-4829-0513; Nichols, Thomas/0000-0002-4516-5103; Lemaitre, Herve/0000-0002-5952-076X; Walker, Robert/0000-0001-7383-7846; Toro, Roberto/0000-0002-6671-858X; Whelan, Christopher/0000-0003-0308-5583; Wright, Margaret/0000-0001-7133-4970; Vollstadt-Klein, Sabine/0000-0002-6210-672X; Arias Vasquez, Alejandro/0000-0002-4786-0169; McMahon, Katie/0000-0002-6357-615X; Macciardi, Fabio/0000-0003-0537-4266; Smith, Albert/0000-0003-1942-5845; Matarin, Mar/0000-0002-4717-5735; Melle, Ingrid /0000-0002-9783-548X; Putz, Benno/0000-0002-2208-209X; Winkler, Anderson/0000-0002-4169-9781; de Zubicaray, Greig/0000-0003-4506-0579; Hoogman, Martine/0000-0002-1261-7628; Turner, Jessica/0000-0003-0076-8434; Gudnason, Vilmundur/0000-0001-5696-0084; Veltman, Joris/0000-0002-3218-8250; de Geus, Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Hansell, Narelle/0000-0002-8229-9741; Saykin, Andrew/0000-0002-1376-8532; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Fernandez, Guillen/0000-0002-5522-0604; Desrivieres, Sylvane/0000-0002-9120-7060; Hulshoff Pol, Hilleke/0000-0002-2038-5281; Munoz Maniega, Susana/0000-0001-5185-6384; Pike, Bruce/0000-0001-8924-683X; Laje, Gonzalo/0000-0003-2763-3329; Tzourio, christophe/0000-0002-6517-2984; Porteous, David/0000-0003-1249-6106; Medland, Sarah/0000-0003-1382-380X; Franke, Barbara/0000-0003-4375-6572; Savitz, Jonathan/0000-0001-8143-182X; Fox, Peter/0000-0002-0465-2028; Preda, Adrian /0000-0003-3373-2438; Cannon, Dara/0000-0001-7378-3411; Smolka, Michael/0000-0001-5398-5569; Jenkinson, Mark/0000-0001-6043-0166; Seshadri, Sudha/0000-0001-6135-2622; McMahon, Francis/0000-0002-9469-305X; Corvin, Aiden/0000-0001-6717-4089; Kent, Jack/0000-0002-0758-7639; Lourdusamy, Anbarasu/0000-0002-1978-6301; Westlye, Lars T./0000-0001-8644-956X; Martin, Nicholas/0000-0003-4069-8020 FU Eli Lilly Company; Wyeth; Bristol-Myers Squibb; AstraZeneca; GlaxoSmithKline; German Research Foundation; Federal Ministry of Education and Research Germany; Janssen-Cilag; Novartis; Lundbeck; SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health; Federal Ministry of Education and Research, Germany; BioRad Laboratories; Siemens AG; Zeitschrift fur Laboratoriumsmedizin; Bruker Daltronics; Abbott; Jurilab Kuopio; Roche Diagnostics; Instand; Becton Dickinson; Hofmann La Roche; Humboldt Foundation; Araclon; Medivation/Pfizer; Ipsen; TauRx Therapeutics; Bayer Healthcare; Biogen Idec; Exonhit Therapeutics; SA; Servier; Synarc; Pfizer; Janssen; Merck; Avid; DoD; VA; Alzheimer's Disease Neuroimaging Initiative; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Anonymous Foundation; BioClinica (ADNI 2); Cure Alzheimer's Fund; Eisai; Elan; Gene Network Sciences; Genentech; GE Healthcare; Innogenetics; Johnson Johnson; Medpace; Roche; Schering Plough; US NIH [U01 AG024904, U24 RR21992, MH0708143, MH083824, MH078111, MH59490, C06 RR13556, C06 RR017515, R01D0042157-01A, MH079799]; Foundation for the NIH; NIH [U01 AG024904, RC2 AG036535-01, P30 AG010129, K01 AG030514, EB006395, AG040060, EB008432, P41 RR013642, HD050735, AG036535, AG020098, EB008281]; NIA [R01 AG019771-09]; NCRAD [U24AG021886]; ADNI (NIH) [U01 AG024904]; NIA; National Institute of Biomedical Imaging and Bioengineering (NIBIB); Dana Foundation; Biobanking and Biomolecular Resources Research Infrastructure Netherlands (BBMRI-NL); Netherlands Organisation for Scientific Research (NWO) [93511010]; National Alliance for Research on Schizophrenia and Depression (NARSAD); Health Foundation; Italian Ministry of University and Research [RBIN04SWHR]; European Commission [PL037286]; UK Department of Health National Institute of Health Research (NIHR)-Biomedical Research Centre; MRC [93558]; NIA at the University of California, Los Angeles [AG16570]; Age UK's Disconnected Mind programme; Research Into Ageing [251, 285]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1]; UK MRC [G1001401, 8200, G0901254]; Engineering and Physical Sciences Research Council (EPSRC); Economic and Social Research Council (ESRC); Scottish Funding Council through the SINAPSE Collaboration; AXA; German Federal Ministry of Education and Research (BMBF); Exzellenz-Stiftung of the Max Planck Society; BMBF in the framework of the National Genome Research Network (NGFN) [FKZ 01GS0481]; Research Council of Norway [154313/ V50, 177458/V50, 167153/V50, 163070/V50, 183782/V50]; Bergen Research Foundation; University of Bergen; Research Council of Norway (FUGE; Psykisk Helse), Helse Vest Regionalt Helseforetak (RHF); Dr Einar Martens Fund; NWO (MagW/ZonMW) [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, SPI 56-464-14192, 10-000-1002]; Center for Medical Systems Biology (CMSB; NWO Genomics); Biobanking and Biomolecular Resources Research Infrastructure; VU University; EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam; European Science Foundation [EU/QLRT-2001-01254]; European Community [HEALTH-F4-2007-201413]; European Science Council (ERC) Genetics of Mental Illness [230374]; Rutgers University Cell; DNA Repository (NIMH) [U24 MH068457-06]; Genetic Association Information Network (a public-private partnership between the NIH and Pfizer, Affymetrix and Abbott Laboratories); National Institute of Mental Health (NIMH) from NIH; US Department of Health and Human Services [K99 MH085098, 1ZIA MH002810, 1ZIA MH002790]; US National Institute of Child Health and Human Development [R01 HD050735]; Australian National Health and Medical Research Council (NHMRC) [496682]; NHMRC [389891, 613667]; Australian Research Council (ARC) [FT0991634, FT110100548]; Achievement Rewards for College Scientists foundation; US NIMH [F31 MH087061, MH078075]; National Science Foundation (NSF) [DGE-0707424]; Canadian Institutes of Health Research; Heart and Stroke Foundation of Quebec; Canadian Foundation for Innovation; German Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; German Research Foundation (DFG) [GR 1912/5-1]; Federal Ministry of Education and Research [03ZIK012, 03IS2061A]; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; German Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Simons Foundation; Howard Hughes Medical Institute; Oslo University Hospital-Ulleval; Eastern Norway Health Authority [2004-123]; Wellcome Trust [072894/z/03/z-Gill, 084730]; Science Foundation Ireland [08/IN.1/B1916_Corvin, 08/RFP/GEN1538]; University College London (UCL)/University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre/Specialist Biomedical Research Centres (CBRC/SBRC) [114]; European Union Marie Curie Reintegration; UK NIHR [08-08-SCC]; Comprehensive Local Research Network (CLRN) [CEL1300]; The Big Lottery Fund; Wolfson Trust; Epilepsy Society; UK Department of Health's NIHR Biomedical Research Centres; Brainwave-the Irish Epilepsy Association; Fonds National de la Recherche Scientifique [FC 63574 / 3.4.620.06 F]; Fonds Erasme pour la Recherche Medicale at the Universite Libre de Bruxelles; MRC Sudden Death Brain and Tissue Bank; Sun Health Research Institute Brain Bank; Netherlands Organization for Health Research and Development ZonMw [917.46.370]; [NBIC/BioAssist/RK/2008.024] FX Some authors received commercial funding unrelated to the topic of this paper. N.J.v.d. W. received speaking fees from Eli Lilly & Company and Wyeth and served on advisory panels of Eli Lilly & Company, Pfizer, Wyeth and Servier. A. A. received an investigator-initiated unrestricted research grant from Bristol-Myers Squibb and speaker's fees from AstraZeneca, Bristol-Myers Squibb and GlaxoSmithKline. H.J.G. received external research support from the German Research Foundation, the Federal Ministry of Education and Research Germany, speaker's honoraria from Bristol-Myers Squibb, Eli Lilly & Company, Novartis, Eisai, Boehringer Ingelheim and Servier and travel funds from Janssen-Cilag, Eli Lilly & Company, Novartis, AstraZeneca, Lundbeck and the SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health. M.N. received research grants from the Federal Ministry of Education and Research, Germany, the German Research Foundation, BioRad Laboratories, Siemens AG, Zeitschrift fur Laboratoriumsmedizin, Bruker Daltronics, Abbott, Jurilab Kuopio, Roche Diagnostics, Instand and Becton Dickinson. H. V. received external research support via research grants from Hofmann La Roche, the Humboldt Foundation, the Federal Ministry of Education and Research (Germany) and the German Research Foundation. M. W. is on the following scientific advisory boards: Lilly, Araclon and Institut Catala de Neurociencies Aplicades, the Gulf War Veterans Illnesses Advisory Committee, VACO, Biogen Idec and Pfizer. M. W. received funding for consulting from Astra Zeneca, Araclon, Medivation/Pfizer, Ipsen, TauRx Therapeutics, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, SA, Servier, Synarc, Pfizer and Janssen; for travel from NeuroVigil, CHRU-Hopital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, the University of California, San Diego-ADNI, Paris University, Institut Catala de Neurociencies Aplicades, the University of New Mexico School of Medicine, Ipsen, Clinical Trials on Alzheimer's Disease (CTAD), Pfizer, AD PD Meeting, Paul Sabatier University, Novartis and Tohoku University; and research support from: Merck, Avid, DoD, VA. M. W. received honoraria from PMDA/the Japanese Ministry of Health, Labour, and Welfare, Tohoku University, Neuro Vigil, Insitut Catala de Neurociencies Aplicades. M. W. owns stock options for Synarc, Elan. Organizations contributing to the Foundation for the US NIH and thus to the National Institute on Aging (NIA)-funded Alzheimer's Disease Neuroimaging Initiative included Abbott, the Alzheimer's Association, the Alzheimer's Drug Discovery Foundation, Anonymous Foundation, AstraZeneca, Bayer Healthcare, BioClinica (ADNI 2), Bristol-Myers Squibb, the Cure Alzheimer's Fund, Eisai, Elan, Gene Network Sciences, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck, Novartis, Pfizer, Roche, Schering Plough, Synarc and Wyeth.; ADNI: The ADNI study was supported by the US NIH (U01 AG024904) and the Foundation for the NIH for genotype and phenotype data collection, the NIH (RC2 AG036535-01) for data analysis, the NIA (R01 AG019771-09) for additional data analysis and NCRAD (U24AG021886) for DNA used in part for the GWAS. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (see URLs). As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. The ADNI sample wishes to acknowledge the investigators who contributed to the design and implementation of ADNI (see URLs). Data collection and sharing for this project were funded by ADNI (NIH grant U01 AG024904). ADNI is funded by the NIA, the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and through generous contributions from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck and Cocpany, Novartis AG, Pfizer, F. Hoffman-La Roche, Schering-Plough and Synarc, as well as from nonprofit partners at the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration (FDA). Private sector contributions to ADNI are facilitated by the Foundation for the NIH (see URLs). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants (P30 AG010129 and K01 AG030514) and by the Dana Foundation. ADNI was launched in 2003 by the NIA, the NIBIB, the FDA, private pharmaceutical companies and nonprofit organizations as a 5-year public-private partnership. The primary goal of ADNI has been to test whether serial MRI), positron emission tomography (PET), other biological markers and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease. Determination of sensitive and specific markers of very early Alzheimer's disease progression is intended to aid researchers and clinicians in developing new treatments and monitoring their effectiveness, as well as lessening the time and cost of clinical trials. The Principal Investigator of this initiative is M. W. Weiner. ADNI is the result of efforts of many coinvestigators from a broad range of academic institutions and private corporations, and subjects have been recruited from over 50 sites across the United States and Canada. The initial goal of ADNI was to recruit 800 adults ages 55 to 90 to participate in the research-approximately 200 cognitively normal older individuals to be followed for 3 years, 400 people with MCI to be followed for 3 years and 200 people with early Alzheimer's disease to be followed for 2 years. For up-to-date information, please visit the ADNI website (see URLs).; BIG: The BIG study wishes to acknowledge S. Kooijman for coordination of sample collection and A. Heister, M. Naber, R. Makkinje, M. Hakobjan and M. Steehouwer for genotyping. The BIG study was supported by a Biobanking and Biomolecular Resources Research Infrastructure Netherlands (BBMRI-NL) complementation grant for brain segmentation and the Netherlands Organisation for Scientific Research (NWO) Horizon Breakthrough grant (grant number 93511010 (to A. A. V.).; Bipolar Family Study: The Bipolar Family Study wishes to thank the Scottish Mental Health Research Network for research assistant support, the Brain Research Imaging Centre Edinburgh (see URLs), a center in the Scottish Funding Council Scottish Imaging Network-A Platform for Scientific Excellence (SINAPSE) Collaboration (see URLs), for image acquisition and the Wellcome Trust Clinical Research Facility for genotyping. Genotyping was supported by the National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award (to A. M. M.), and data collection was supported by the Health Foundation Clinician Scientist Fellowship.; fBIRN: fBIRN wishes to acknowledge D. B. Keator for leading fBIRN neuroinformatics development, B. A. Mueller for image calibration and quality assurance and A. Belger, V. D. Calhoun, G. G. Brown, J. M. Ford, G. H. Glover, R. Kikinis, K. Lim, J. Laurriello, J. Bustillo, G. McCarthy, D. S. O'Leary, B. Rosen, A. W. T. and J. T. Voyvodic for their leadership contributions to fBIRN scanner and sequence calibration, tool development and data collection efforts. The fBIRN study was supported by the US NIH (U24 RR21992) for phenotypic data collection. Genotyping was performed with the support of the grant RBIN04SWHR to F. M. from the Italian Ministry of University and Research.; GOBS: The GOBS study was supported by the US NIH (MH0708143 and MH083824 to D. C. G., MH078111 and MH59490 to J. B., C06 RR13556 and C06 RR017515). P. K. was also supported by an NIH grant (EB006395).; IMAGEN: IMAGEN is funded by the European Commission Framework Programme 6 (FP-6) Integrated Project IMAGEN (PL037286), the European Commission Framework Programme 7 (FP-7) Project Alzheimer's Disease, Alcoholism, Memory, Schizophrenia (ADAMS), the FP-7 Innovative Medicine Initiative Project European Autism Interventions (AIMS), the UK Department of Health National Institute of Health Research (NIHR)-Biomedical Research Centre Mental Health program and the MRC programme grant Developmental Pathways into Adolescent Substance Abuse (93558).; ImaGene: ImaGene wishes to acknowledge J. Lee and J. Lane for processing the blood samples, The Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarker Development and the Alzheimer's Disease Research Center (ADRC) funded by the NIA at the University of California, Los Angeles (AG16570).; LBC1936: We thank the participants in LBC1936. We thank C. Murray, A. J. Gow, S. E. Harris, M. Luciano, P. Redmond, E. Sandeman, I. Gerrish, J. Boyd-Ellison, N. Leslie, A. Howden and C. Scott for data collection and preparation. This project is funded by the Age UK's Disconnected Mind programme and also by Research Into Ageing (251 and 285). The entire genome association part of the study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F019394/1). Analysis of brain images was funded by UK MRC grants (G1001401 and 8200). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/ 84698). Imaging was performed at the Brain Research Imaging Centre, Edinburgh, a center in the SINAPSE Collaboration. Funding from BBSRC, the Engineering and Physical Sciences Research Council (EPSRC), the Economic and Social Research Council (ESRC) and the MRC and Scottish Funding Council through the SINAPSE Collaboration is gratefully acknowledged. L. M. L. is the beneficiary of a postdoctoral grant from the AXA Research Fund.; MooDS: This work was funded by the German Federal Ministry of Education and Research (BMBF) in the National Genome Research Network (NGFN-plus) through the MooDs grant Molecular Causes of Major Mood Disorders and Schizophrenia (coordinator M. M. N.). Additional funding for genotyping was provided by a NARSAD Distinguished Investigator award to A. M.-L.; MPIP: The MPIP Munich Morphometry Sample comprises images acquired as part of the Munich Antidepressant Response Signature Study and the Recurrent Unipolar Depression (RUD) Case-Control Study performed at the MPIP and control subjects acquired at the Department of Psychiatry at the Ludwig-Maximilians-University. We wish to acknowledge A. Olynyik and radiographers R. Schirmer, E. Schreiter and R. Borschke for image acquisition and data preparation. We thank D. P. Auer for local study management in the initial phase of the RUD study. We are grateful to GlaxoSmithKline for providing the genotypes of the RUD Case-Control Sample. We thank the staff of the Center of Applied Genotyping (CAGT) for generating the genotypes of the MARS cohort. The study is supported by a grant from the Exzellenz-Stiftung of the Max Planck Society. This work has also been funded by the BMBF in the framework of the National Genome Research Network (NGFN) (FKZ 01GS0481).; NCNG: We would like to thank the personnel involved in recruitment and data collection and, in particular, P. Due-Tonnessen for clinical assessment of the MRI images. The NCNG study was supported by Research Council of Norway grants (154313/ V50 and 177458/V50). The NCNG GWAS was financed by grants from the Bergen Research Foundation, the University of Bergen, the Research Council of Norway (FUGE; Psykisk Helse), Helse Vest Regionalt Helseforetak (RHF) and the Dr Einar Martens Fund.; NESDA-NTR: Funding was obtained from the NWO (MagW/ZonMW 904-61-090; 985-10-002; 904-61-193; 480-04-004; 400-05-717, Addiction-31160008; 911-09-032; SPI 56-464-14192 and Geestkracht Program, 10-000-1002), the Center for Medical Systems Biology (CMSB; NWO Genomics), NBIC/BioAssist/RK/2008.024, BBMRI-NL, Biobanking and Biomolecular Resources Research Infrastructure, the VU University, the EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, the European Science Foundation (EU/QLRT-2001-01254), the European Community's FP7 (HEALTH-F4-2007-201413), the European Science Council (ERC) Genetics of Mental Illness (230374), Rutgers University Cell and DNA Repository (cooperative agreement NIMH U24 MH068457-06), the US NIH (R01D0042157-01A) and the Genetic Association Information Network (a public-private partnership between the NIH and Pfizer, Affymetrix and Abbott Laboratories).; NIMH-IRP: This study was supported by funding from the Intramural Research Program of the National Institute of Mental Health (NIMH) from the NIH and the US Department of Health and Human Services (K99 MH085098 to G. L., 1ZIA MH002810 to F. J. M. and 1ZIA MH002790 to W. C. D.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government.; QTIM: We are extremely grateful to the twins for their participation, the radiographers at the Centre for Advanced Imaging at the University of Queensland for image acquisition and the many research assistants and support staff at the Queensland Institute of Medical Research for twin recruitment and daily management, and we especially thank K. Johnson for MRI scanning and processing, A. Henders for DNA processing and preparation and S. Gordon for quality control and management of the genotypes. Phenotyping was funded by the US National Institute of Child Health and Human Development (R01 HD050735) and the Australian National Health and Medical Research Council (NHMRC) (project grant 496682). Genotyping was funded by the NHMRC (Medical Bioinformatics Genomics Proteomics Program, 389891). G. M. was supported by an NHMRC Fellowship (613667), and G.Z. was supported by Australian Research Council (ARC) Future Fellowship (FT0991634). S. E. M. is funded by an ARC Future Fellowship (FT110100548). J.L.S. was supported by the Achievement Rewards for College Scientists foundation and the US NIMH (F31 MH087061). D. P. H. is partially supported by a National Science Foundation (NSF) Graduate Research Fellowhip Program (GRFP) grant (DGE-0707424). P. T. was also supported by the NIH (grants U01 AG024904, AG040060, EB008432, P41 RR013642, HD050735, AG036535, AG020098 and EB008281).; SYS: The Saguenay Youth Study Group wishes to thank the following individuals for their contribution in acquiring and analyzing the data: N. Arbour, M.-E. Bouchard, A. Houde, A. Gauthier and H. Simard for the recruitment and assessment of participating families, M. Berube, S. Masson, S. Castonguay and M.-J. Morin for MRI acquisition and E. Ding and N. Qiu for MR data management. We thank J. Mathieu for the medical follow up of participants in whom we detected any medically relevant abnormalities. We are grateful to all families for participating in the study. The Saguenay Youth Study Group is supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Quebec and the Canadian Foundation for Innovation. For more information, please see the study website (see URLs).; SHIP: The Study of Health in Pomerania (SHIP) is supported by the German Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103 and 01ZZ0403) and the German Research Foundation (DFG; GR 1912/5-1). Genome-wide data and MRI scans were supported by the Federal Ministry of Education and Research (grant 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the Center of Knowledge Interchange program of the Siemens AG. We thank all staff members and participants of the SHIP study, as well as all of the genotyping staff for generating the SHIP SNP data set. The genetic data analysis workflow was created using the Software InforSense. Genetic data were stored using the database Cache (InterSystems).; SHIP-TREND: The authors from SHIP are grateful to M. Stanke for the opportunity to use his Server Cluster for SNP Imputation. This cohort is part of the Community Medicine Research net (CMR) of the University of Greifswald, which is funded by the German Federal Ministry of Education and Research and the German Ministry of Cultural Affairs, as well as by the Social Ministry of the Federal State of Mecklenburg-West Pomerania. CMR encompasses several research projects that share data from the population-based Study of Health in Pomerania (SHIP; see URLs). The work is also supported by the German Research Foundation (DFG; GR 1912/5-1) and the Greifswald Approach to Individualized Medicine (GANI_MED) network funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data and MRI scans were supported by the Federal Ministry of Education and Research (grant 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The University of Greifswald is a member of the Center of Knowledge Interchange program of the Siemens AG.; Superstruct: We thank the investigators and participants who contributed to the brain genomics data collection for Superstruct at Massachusetts General Hospital and Harvard University, with funding from the Simons Foundation, the Howard Hughes Medical Institute and the US NIH (grant MH079799).; TOP: We thank the study participants of TOP and the personnel involved in data collection and logistics, especially T. D. Bjella. This work was supported by the Oslo University Hospital-Ulleval, the Eastern Norway Health Authority (2004-123), the Research Council of Norway (167153/V50, 163070/V50 and 183782/V50), and by Eli Lilly & Company (who covered part of the genotyping costs).; TCD: We wish to express our sincere thanks to all participants and to clinical staff who facilitated patients' involvement. In particular, we acknowledge colleagues from the Trinity College Institute of Neuroscience A. Bodke, J. McGrath, F. Newell, H. Garavan, and J. O'Doherty for their support in sample collection. Collection and analysis of these samples were funded by the Wellcome Trust (072894/z/03/z-Gill) and the Science Foundation Ireland (08/IN.1/B1916_Corvin).; EPIGEN: Work from the London Cohort was supported by research grants from the Wellcome Trust (grant 084730 to S. M. S.), University College London (UCL)/University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre/Specialist Biomedical Research Centres (CBRC/SBRC) (grant 114 to S. M. S.), the European Union Marie Curie Reintegration (to M. Matarin and S. M. S.), the UK NIHR (08-08-SCC), the Comprehensive Local Research Network (CLRN) Flexibility and Sustainability Funding (FSF) (grant CEL1300 to S. M. S.), The Big Lottery Fund, the Wolfson Trust and the Epilepsy Society. This work was undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health's NIHR Biomedical Research Centres funding scheme. Work from the Royal College of Surgeons in Ireland was supported by research grants from the Science Foundation Ireland (Research Frontiers Programme award 08/RFP/GEN1538) and Brainwave-the Irish Epilepsy Association. The collection of Belgian subjects was supported by the Fonds National de la Recherche Scientifique (grant FC 63574 / 3.4.620.06 F) and the Fonds Erasme pour la Recherche Medicale at the Universite Libre de Bruxelles.; UCL Institute of Neurology Control Brain Tissue Collection: Funding was provided by the UK MRC (grant G0901254), the MRC Sudden Death Brain and Tissue Bank and the Sun Health Research Institute Brain Bank.; UMCU: The UMCU study was supported by the Netherlands Organization for Health Research and Development ZonMw (917.46.370 to H. E. H.) and the US NIMH (MH078075 to R.A.O.). NR 68 TC 247 Z9 250 U1 10 U2 122 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2012 VL 44 IS 5 BP 552 EP + DI 10.1038/ng.2250 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 934BW UT WOS:000303416300016 PM 22504417 ER PT J AU Burger, RA Brady, MF Bookman, MA Fleming, GF Monk, BJ Huang, H Mannel, RS Homesley, HD Fowler, J Greer, BE Boente, M Birrer, MJ Liang, SRX AF Burger, Robert A. Brady, Mark F. Bookman, Michael A. Fleming, Gini F. Monk, Bradley J. Huang, Helen Mannel, Robert S. Homesley, Howard D. Fowler, Jeffrey Greer, Benjamin E. Boente, Matthew Birrer, Michael J. Liang, Sharon X. TI Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Burger, Robert A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ Chicago, Chicago, IL 60637 USA. Creighton Univ, Sch Med, St Josephs Hosp & Med Ctr, Phoenix, AZ USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Ohio State Univ, James Canc Hosp, Hilliard, OH USA. Seattle Canc Care Alliance, Seattle, WA USA. Minnesota Oncol & Hematol, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA. RP Burger, RA (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 1 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2012 VL 67 IS 5 BP 289 EP 290 DI 10.1097/OGX.0b013e3182547170 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 946NA UT WOS:000304357400015 ER PT J AU Clare, CA Yeh, J AF Clare, Camille A. Yeh, John TI Postpartum Depression in Special Populations: A Review SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Review ID PERINATAL DEPRESSION; POSTNATAL DEPRESSION; PREGNANCY; MOTHERS; SYMPTOMS; FATHERS; ASSOCIATION; IMMIGRANT; ANXIETY; WOMEN AB This review article aims to define and characterize postpartum depression; to discuss the social, financial, regulatory and legal implications of the disorder; and to elucidate its impact on special groups, namely adolescents, immigrants, fathers, and those of different racial and ethnic groups. A MEDLINE review of the current literature was run on postpartum depression, using the key words postpartum depression, depression, pregnancy, peripartum, or postpartum, from the years 2000 to 2011. Postpartum depressive syndromes place women and their children at risk of suicide and infanticide if not appropriately diagnosed and treated. Screening should occur within 4 to 6 weeks postpartum. Women with a history of depression before or during pregnancy, adolescents, those with low incomes and poor social support, or with a history of substance abuse, are especially at high risk. Treatments include antidepressants and psychotherapy. The unique populations of adolescents, fathers, immigrants, and certain racial and ethnic groups require special consideration in terms of diagnosis, screening modalities, and treatment. Collaboration between obstetrical providers and behavioral health professionals can ensure improved outcomes. It was found that postpartum depression is a challenging diagnosis and may be difficult to treat. A multidisciplinary approach is warranted to prevent life-threatening consequences in mothers and their children. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to diagnose postpartum depression and to analyze the social, financial, regulatory and legal implications of the disorder; and to evaluate its impact on special groups, namely adolescents, immigrants, fathers, and those of different racial and ethnic groups. C1 [Yeh, John] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Clare, Camille A.] New York Med Coll, Dept Obstet & Gynecol, Valhalla, NY 10595 USA. RP Yeh, J (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM john.yeh.md@gmail.com NR 43 TC 16 Z9 17 U1 4 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2012 VL 67 IS 5 BP 313 EP 323 DI 10.1097/OGX.0b013e318259cb52 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 946NA UT WOS:000304357400018 PM 22624779 ER PT J AU Schalock, PC Thyssen, JP Dinulos, JGH AF Schalock, Peter C. Thyssen, Jacob P. Dinulos, James G. H. TI Epidemic of Tinea Corporis Due to Trichophyton Mentagrophytes of Rabbit Origin SO PEDIATRIC DERMATOLOGY LA English DT Letter ID DERMATOPHYTOSES; KERION; FARMS C1 [Schalock, Peter C.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Thyssen, Jacob P.] Univ Copenhagen, Gentofte Hosp, Dept Dermatoallergol, Natl Allergy Res Ctr, Copenhagen, Denmark. [Dinulos, James G. H.] Univ Connecticut, Dept Dermatol, Farmington, CT USA. RP Schalock, PC (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM schalock.prof@gmail.com NR 6 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAY-JUN PY 2012 VL 29 IS 3 BP 392 EP 392 DI 10.1111/j.1525-1470.2012.01782.x PG 1 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 943QM UT WOS:000304139900044 PM 22594340 ER PT J AU Panda, A Gallardo, S Sidbury, R AF Panda, Angela Gallardo, Steven Sidbury, Robert TI Delineating Capillary Malformations in the Operating Suite Using White Eyeliner Pencil SO PEDIATRIC DERMATOLOGY LA English DT Letter C1 [Panda, Angela; Gallardo, Steven] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sidbury, Robert] Seattle Childrens Hosp, Seattle, WA USA. RP Panda, A (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM robert.sidbury@seattlechildrens.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAY-JUN PY 2012 VL 29 IS 3 BP 393 EP 393 DI 10.1111/j.1525-1470.2012.01752.x PG 1 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 943QM UT WOS:000304139900046 PM 22594341 ER PT J AU Barabino, S Chen, YH Chauhan, S Dana, R AF Barabino, Stefano Chen, Yihe Chauhan, Sunil Dana, Reza TI Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article DE Ocular surface; Dry eye disease; Autoimmunity; Inflammation; Anti-inflammatory agents ID CORNEAL EPITHELIAL-CELLS; HORMONE REPLACEMENT THERAPY; REGULATORY T-CELLS; MATRIX-METALLOPROTEINASE ACTIVITY; DELAYED TEAR CLEARANCE; IN-SITU KERATOMILEUSIS; TOLL-LIKE RECEPTORS; LIGAND 1 PD-L1; KERATOCONJUNCTIVITIS SICCA; SJOGRENS-SYNDROME AB The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Chen, Yihe; Chauhan, Sunil; Dana, Reza] Harvard Univ, Dept Ophthalmol, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02114 USA. [Barabino, Stefano] Univ Genoa, Clin Oculist, Dept Neurosci Ophthalmol & Genet, I-16132 Genoa, Italy. RP Dana, R (reprint author), Harvard Univ, Dept Ophthalmol, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Sch Med, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [EY019098, EY20889] FX This work was supported in part by National Institutes of Health Grants EY019098 and EY20889. NR 177 TC 51 Z9 54 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAY PY 2012 VL 31 IS 3 BP 271 EP 285 DI 10.1016/j.preteyeres.2012.02.003 PG 15 WC Ophthalmology SC Ophthalmology GA 944XB UT WOS:000304236000005 PM 22426080 ER PT J AU Derose, SF Gabayan, GZ Chiu, VY Sun, BC AF Derose, Stephen F. Gabayan, Gelareh Z. Chiu, Vicki Y. Sun, Benjamin C. TI Patterns and Preexisting Risk Factors of 30-Day Mortality After a Primary Discharge Diagnosis of Syncope or Near Syncope SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID EMERGENCY ROOM PATIENTS; SHORT-TERM; PROSPECTIVE VALIDATION; EXTERNAL VALIDATION; SERIOUS OUTCOMES; PREDICT PATIENTS; FOLLOW-UP; RULE; STRATIFICATION; POPULATION AB Objectives: The risk of short-term mortality after an emergency department (ED) visit for syncope is poorly understood, resulting in prognostic uncertainty and frequent hospital admission. The authors determined patterns and risk factors for short-term mortality after a diagnosis of syncope or near syncope to aid in medical decision-making. Methods: A retrospective cohort study was performed of adult members of Kaiser Permanente Southern California seen at 11 EDs from 2002 to 2006 with a primary discharge diagnosis of syncope or near syncope (International Classification of Diseases, Ninth Revision [ICD-9] 780.2). The outcome was 30-day mortality. Proportional hazards time-to-event regression models were used to identify risk factors. Results: There were 22,189 participants with 23,951 ED visits, resulting in 307 deaths by 30 days. A relatively lower risk of death was reached within 2 weeks for ages 18 to 59 years, but not until 3 months or more for ages 60 and older. Preexisting comorbidities associated with increased mortality included heart failure (hazard ratio [HR] = 14.3 in ages 18 to 59 years, HR = 3.09 in ages 60 to 79 years, HR = 2.34 in ages 80 years plus; all p < 0.001), diabetes (HR = 1.49, p = 0.002), seizure (HR = 1.65, p = 0.016), and dementia (HR = 1.41, p = 0.034). If the index visit followed one or more visits for syncope in the previous 30 days, it was associated with increased mortality (HR = 1.86, p = 0.024). Absolute risk of death at 30 days was under 0.2% in those under 60 years without heart failure and more than 2.5% across all ages in those with heart failure. Conclusions: The low risk of death after an ED visit for syncope or near syncope in patients younger than 60 years old without heart failure may be helpful when deciding who to admit for inpatient evaluation. The presence of one or more comorbidities that predict death and a prior visit for syncope should be considered in clinical decisions and risk stratification tools for patients with syncope. Close clinical follow-up seems advisable in patients 60 years and older due to a prolonged risk of death. ACADEMIC EMERGENCY MEDICINE 2012; 19: 488-496 (C) 2012 by the Society for Academic Emergency Medicine C1 [Derose, Stephen F.; Chiu, Vicki Y.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Gabayan, Gelareh Z.; Sun, Benjamin C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sun, Benjamin C.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Derose, SF (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. EM stephen.f.derose@kp.org FU American Geriatrics Society [20051687]; University of California, Los Angeles, National Institutes of Aging [AG 02-004]; UCLA Older Americans Independence Center, NIH/NIA [P30-AG028748]; Greater Los Angeles Veteran's Affairs Health Services Research and Development Fellowship FX This research was supported by grants from American Geriatrics Society Dennis Jahnigen Career Development Award (20051687, BCS) and University of California, Los Angeles, National Institutes of Aging K12 Mentored Clinical Scientist Development Program in Geriatrics (AG 02-004, BCS). Dr. Sun received support from the UCLA Older Americans Independence Center, NIH/NIA Grant P30-AG028748, and the content does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.; We thank the Greater Los Angeles Veteran's Affairs Health Services Research and Development Fellowship for their support of Dr. Gabayan. We thank Robert Weiss, UCLA School of Public Health Professor of Biostatistics, for his helpful manuscript review. NR 47 TC 5 Z9 5 U1 0 U2 2 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 2012 VL 19 IS 5 BP 488 EP 496 DI 10.1111/j.1553-2712.2012.01336.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 943OI UT WOS:000304133300002 PM 22594351 ER PT J AU Neuman, MI Ting, SA Meydani, A Mansbach, JM Camargo, CA AF Neuman, Mark I. Ting, Sarah A. Meydani, Ahou Mansbach, Jonathan M. Camargo, Carlos A., Jr. TI National Study of Antibiotic Use in Emergency Department Visits for Pneumonia, 1993 Through 2008 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID OUTCOMES; INTERVENTIONS; PATTERNS AB Objectives: The Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) developed guidelines for the management of community-acquired pneumonia (CAP); however, there are sparse data on actual rates of antibiotic use in the emergency department (ED) setting. Methods: Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) for ED visits during 1993 through 2008 for adults with a diagnosis of pneumonia. Results: During the study period there were an estimated 23,252,000 pneumonia visits, representing 1.8% of all ED visits. The visit rate for pneumonia during this 16-year period may have increased (p trend = 0.055). Overall, 66% of adult patients with a primary diagnosis of pneumonia had documentation of an antibiotic administered while in the ED. There was an increase in antibiotic administration for adults with pneumonia from 1993 through 2008 (49% to 80%; p trend < 0.001). Specifically, there was an increase in use of macrolides from 1993 to 2006 (20% to 30%, p trend < 0.001) and a marked increase in use of quinolones from 0% to 39% from 1993 through 2008 (p trend < 0.001). Penicillin and cephalosporin use remained stable. Use of an antibiotic consistent with 2007 IDSA/ATS guidelines increased from 22% (95% confidence interval [CI] = 16% to 27%) of cases in 1993-1994 to 68% (95% CI = 63% to 73%) of cases in 2007-2008 (p trend < 0.001). Conclusions: ED visit rates for pneumonia increased slightly from 1993 through 2008. Although antibiotic administration in the ED has increased for adults with CAP, guideline-concordant antibiotics may not be consistently administered. ACADEMIC EMERGENCY MEDICINE 2012; 19: 562-568 (C) 2012 by the Society for Academic Emergency Medicine C1 [Neuman, Mark I.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Mansbach, Jonathan M.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Ting, Sarah A.; Meydani, Ahou; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Neuman, MI (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM mark.neuman@childrens.harvard.edu FU NIH (Bethesda, MD) [R01, AI-93723] FX Dr. Camargo was funded, in part, by NIH grant R01 [grant AI-93723] (Bethesda, MD). NR 30 TC 6 Z9 6 U1 0 U2 0 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 2012 VL 19 IS 5 BP 562 EP 568 DI 10.1111/j.1553-2712.2012.01342.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 943OI UT WOS:000304133300011 PM 22594360 ER PT J AU Eneriz-Wiemer, M Nelson, BD Bruce, J Chamberlain, LJ AF Eneriz-Wiemer, Monica Nelson, Brett D. Bruce, Janine Chamberlain, Lisa J. TI Global Health Training in Pediatric Residency: A Qualitative Analysis of Faculty Director Insights SO ACADEMIC PEDIATRICS LA English DT Article DE global child health; international child health; resident education/training ID INTERNATIONAL HEALTH; MEDICAL-STUDENTS; CHILD HEALTH; EXPERIENCE; EDUCATION; ELECTIVES; OPPORTUNITIES; COMPETENCE; CURRICULUM; PHYSICIAN AB OBJECTIVE: Interest and participation in global health (GH) has been growing rapidly among pediatric residents. Residency programs are responding by establishing formal GH programs. We sought to define key insights in GH education from pediatric residency programs with formal OH tracks. METHODS: Seven model pediatric residency programs with formal OH training were identified in 2007. Faculty directors representing 6 of these programs participated in expert interviews assessing 6 categories of questions about GH tracks: understanding how GH tracks establish partnerships with global sites; defining organizational and financing structure of OH tracks; describing resident curriculum and pre-trip preparation; describing clinical experiences of residents in OH tracks; defining evaluation of residents and GH tracks; and defining factors that affect development and ongoing implementation of OH tracks. Data were analyzed using qualitative methodology. RESULTS: All programs relied on faculty relationships to establish dynamic partnerships with global sites. All programs acknowledged resident burden on GH partners. Strategies to alleviate burden included improving resident supervision and providing varying models of GH curricula and pre-trip preparation, generally based on core residency training competencies. Support and funding for GH programs are minimal and variable. Resident experiences included volunteer patient care, teaching, and research. Commitment of experienced faculty and support from institutional leadership facilitated implementation of GH programs. CONCLUSIONS: Directors of 6 model GH programs within pediatric residencies provided insights that inform others who want to establish successful GH partnerships and resident training that will prepare trainees to meet global child health needs. C1 [Eneriz-Wiemer, Monica; Chamberlain, Lisa J.] Stanford Sch Med, Div Gen Pediat, Palo Alto, CA 94304 USA. [Bruce, Janine] Stanford Sch Med, Pediat Advocacy Program, Palo Alto, CA 94304 USA. [Nelson, Brett D.] Harvard Univ, Sch Med, Dept Pediat, Div Global Hlth,MassGen Hosp Children, Boston, MA 02115 USA. RP Eneriz-Wiemer, M (reprint author), Stanford Sch Med, Div Gen Pediat, 770 Welch Rd,Suite 100, Palo Alto, CA 94304 USA. EM meneriz@stanford.edu RI yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 FU Lucile Packard Children's Hospital FX Project support was received from the Lucile Packard Children's Hospital Community Partnerships Grant. NR 50 TC 14 Z9 14 U1 0 U2 5 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 2012 VL 12 IS 3 BP 238 EP 244 PG 7 WC Pediatrics SC Pediatrics GA 944NZ UT WOS:000304212400014 PM 22503444 ER PT J AU Wu, HJ De Boer, JF Chen, TC AF Wu, Huijuan De Boer, Johannes F. Chen, Teresa C. TI Diagnostic Capability of Spectral-Domain Optical Coherence Tomography for Glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NERVE-FIBER LAYER; MACULAR THICKNESS MEASUREMENTS; SCANNING LASER POLARIMETER; STRATUS OCT; FIELD LOSS; HIGH-SPEED; CIRRUS HD; ABILITY; EYES; PARAMETERS AB PURPOSE: To determine the diagnostic capability of spectral-domain optical coherence tomography in glaucoma patients with visual field defects. DESIGN: Prospective, cross-sectional study. METHODS: SETTINGS: Participants were recruited from a university hospital clinic. STUDY POPULATION: One eye of 85 normal subjects and 61 glaucoma patients with average visual field mean deviation of -9.61 +/- 8.76 dB was selected randomly for the study. A subgroup of the glaucoma patients with early visual field defects was calculated separately. OBSERVATION PROCEDURES: Spectralis optical coherence tomography (Heidelberg Engineering, Inc) circular scans were performed to obtain peripapillary retinal nerve fiber layer (RNFL) thicknesses. The RNFL diagnostic parameters based on the normative database were used alone or in combination for identifying glaucomatous RNFL thinning. MAIN OUTCOME MEASURES: To evaluate diagnostic performance, calculations included areas under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: Overall RNFL thickness had the highest area under the receiver operating characteristic curve values: 0.952 for all patients and 0.895 for the early glaucoma subgroup. For all patients, the highest sensitivity (98.4%; 95% confidence interval, 96.3% to 100%) was achieved by using 2 criteria: >= 1 RNFL sectors being abnormal at the < 5% level and overall classification of borderline or outside normal limits, with specificities of 88.9% (95% confidence interval, 84.0% to 94.0%) and 87.1% (95% confidence interval, 81.6% to 92.5%), respectively, for these 2 criteria. CONCLUSIONS: Statistical parameters for evaluating the diagnostic performance of the Spectralis spectral-domain optical coherence tomography were good for early perimetric glaucoma and were excellent for moderately advanced perimetric glaucoma. (Am J Ophthalmol 2012;153:815-826. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Wu, Huijuan; Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. [De Boer, Johannes F.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02115 USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NATIONAL INSTITUTES OF Health, Bethesda, Maryland [R01 EY14975-01]; NIDEK Co Ltd (Gamagori, Japan); Massachusetts Eye and Ear Infirmary FX PUBLICATION OF THIS ARTICLE WAS SUPPORTED IN PART BY GRANT R01 EY14975-01 FROM THE NATIONAL INSTITUTES OF Health, Bethesda, Maryland. Dr de Boer holds patents in spectral-domain optical coherence tomography technology, and NIDEK Co Ltd (Gamagori, Japan) has supported his research. Drs Wu and Chen indicate no financial conflicts of interest in the design or conduct of the study. Involved in the Design and conduct of study (H.W., T.C.C.); Procurement of research funds (T.C.C., J.F.d.D); Collection and management of data (H.W., T.C.C.); Data analysis (H.W.); and Preparation, review, and approval of manuscript (H.W., J.F.d.D, T.C.C.). The Massachusetts Eye and Ear Infirmary Institutional Review Board approved all protocols, which adhered to the Declaration of Helsinki and which complied with the Health Insurance Portability and Accountability Act. The authors thank Baojian Fan, PhD, Department of Ophthalmology, Harvard Medical School, for statistical consultation and the Peking University People's Hospital for permitting Dr Wu to take a sabbatical for her research fellowship at the Massachusetts Eye and Ear Infirmary. NR 38 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2012 VL 153 IS 5 BP 815 EP 826 DI 10.1016/j.ajo.2011.09.032 PG 12 WC Ophthalmology SC Ophthalmology GA 941LN UT WOS:000303964800004 PM 22265147 ER PT J AU Andreoli, MT Andreoli, CM AF Andreoli, Michael T. Andreoli, Christopher M. TI Surgical Rehabilitation of the Open Globe Injury Patient SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROGNOSTIC-FACTORS AB PURPOSE: To describe the long-term surgical course of patients with open globe injury. DESIGN: Retrospective case series. METHODS: Patients with open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between 2000 and 2009 were retrospectively reviewed. Data from presentation, initial repair, and follow-up surgery were analyzed. RESULTS: Among 848 injuries, 1415 surgical procedures were performed. The mean follow-up time was 19.7 months, including 6017 visits. On average, patients required 1.7 surgeries and 7.1 follow-up visits. Factors predicting follow-up surgery included more severe ocular trauma score, worse prerepair visual acuity, retinal hemorrhage, anterior vitrectomy at primary repair, pars plana vitrectomy at primary repair, and lensectomy at primary repair. Patients with zone II injury, hemorrhagic choroidal detachment, and a history of previous ocular surgery tended to require follow-up surgery less frequently. Patients requiring a second surgery tended to have worse visual acuity at presentation and postrepair. Postoperative visual outcomes were worse for patients who underwent vitreoretinal follow-up surgery, likely because of mechanism of injury. Variables associated with inferior visual outcome were worse prerepair visual acuity, postoperative afferent pupillary defect (APD), old age, scleral laceration, and retinal detachment. CONCLUSION: Open globe injuries require significant surgical follow-up. Patients requiring multiple operations tended to have worse postoperative visual acuity. Patients who underwent vitreoretinal surgery had overall worse visual outcomes. While the first year of surveillance appears to be pivotal in the course of an open globe injury, these patients can expect long-term care from comprehensive and subspecialty ophthalmologists. (Am J Ophthalmol 2012;153:856-860. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Andreoli, Christopher M.] Harvard Univ, Vanguard Med Associates, Visual Serv, Boston, MA 02115 USA. [Andreoli, Michael T.; Andreoli, Christopher M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Vanguard Med Associates, Boston, MA 02114 USA. [Andreoli, Christopher M.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Andreoli, CM (reprint author), Harvard Univ, Vanguard Med Associates, Visual Serv, 133 Brookline Ave, Boston, MA 02115 USA. EM christopher_andreoli@meei.harvard.edu NR 14 TC 21 Z9 22 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2012 VL 153 IS 5 BP 856 EP 860 DI 10.1016/j.ajo.2011.10.013 PG 5 WC Ophthalmology SC Ophthalmology GA 941LN UT WOS:000303964800009 PM 22265150 ER PT J AU Kovacs, K Wagley, S Quirk, MT Ceron, OM Silva, PA Singh, RJ Gukasyan, HJ Arroyo, JG AF Kovacs, Kyle Wagley, Sushant Quirk, Matthew T. Ceron, Olga M. Silva, Paolo A. Singh, Ravinder J. Gukasyan, Hovhannes J. Arroyo, Jorge G. TI Pharmacokinetic Study of Vitreous and Serum Concentrations of Triamcinolone Acetonide After Posterior Sub-Tenon's Injection SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DIABETIC MACULAR EDEMA; INTRAVITREAL TRIAMCINOLONE; SUBTENON INJECTION; HUMAN EYES; UVEITIS; DELIVERY; SAFETY AB PURPOSE: To compare a theoretical pharmacokinetic model of triamcinolone acetonide after posterior sub-Tenon's injection with experimental serum and undiluted vitreous triamcinolone acetonide concentrations obtained during pars plana vitrectomy. DESIGN: Clinical-practice, prospective, interventional case series study. METHODS: This study compared computer-modeled triamcinolone acetonide diffusion after posterior sub-Tenon's injection with triamcinolone acetonide levels in experimental undiluted vitreous and serum samples from 57 patients undergoing vitrectomy assessed via mass spectrometry and high-pressure liquid chromatography. At least 5 pairs of samples were collected at each of 7 time points (1 day, 3 days, and 1, 2, 3, 4, and 8 weeks) after triamcinolone acetonide injection, with 6 controls without injection. Cortisol levels were measured in 31 sets of samples. RESULTS: The theoretical model predicted that triamcinolone acetonide levels in systemic blood, vitreous, and choroidal extracellular matrix would plateau after 3 days at 15 ng/mL, 227 ng/mL and 2230 ng/mL, respectively. Experimental vitreous levels of triamcinolone peaked at 111 ng/mL at day 1, then reached a plateau in the range 15 to 25 ng/mL, while serum triamcinolone levels peaked at day 3 near 35 ng/mL and plateaued near 2 to 8 ng/mL. Serum triamcinolone and cortisol levels were inversely correlated (Spearman -0.42, P = .02). CONCLUSIONS: The theoretical model predicts efficient delivery of triamcinolone acetonide from the posterior sub-Tenon's space to the extracellular choroidal matrix. The experimental findings demonstrate low levels of serum triamcinolone that alter systemic cortisol levels and higher vitreous levels lasting at least 1 month. Both assessments support trans-scleral delivery of posterior sub-Tenon's triamcinolone. (Am J Ophthalmol 2012; 153:939-948. (C) 2012 by Elsevier Inc. All rights reserved.) C1 [Arroyo, Jorge G.] Beth Israel Deaconess Med Ctr, Retina Serv, Div Ophthalmol, Boston, MA 02215 USA. [Silva, Paolo A.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Silva, Paolo A.; Arroyo, Jorge G.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Singh, Ravinder J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MI USA. [Gukasyan, Hovhannes J.] La Jolla Labs, Pfizer Global Res & Dev, San Diego, CA USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Retina Serv, Div Ophthalmol, 330 Brookline Ave,Shapiro 5th Floor, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu FU Mills and Margaret Cox Endowment Funds; Grimshaw-Gudewicz Charitable Foundation (Fall River, Massachusetts); Macula Society from the Retina Research Foundation (Cleveland, Ohio) FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF Interest. Publication of this article was supported by the Mills and Margaret Cox Endowment Funds, by the Grimshaw-Gudewicz Charitable Foundation (Fall River, Massachusetts), and by the Macula Society Award from the Retina Research Foundation (Cleveland, Ohio). The ocular simulation software was developed by Bend Research Inc (Bend, Oregon, USA) under contract with Pfizer. The authors report no proprietary interests in the results of the study. Involved in design and conduct of study (K.K., M.Q., H.G., P.S., J.A.); collection, management, analysis, and interpretation of data (K.K., S.W., M.Q., O.C., H.G., R.S., J.A.); and preparation, review, or approval of manuscript (K.K., S.W., P.S., J.A.). Prospective Institutional Review Board approval was obtained from the Beth Israel Deaconess Medical Center and an informed consent form was approved by the IRB and signed by all study participants before involvement in the study. Patient information was maintained in a locked room on a password-protected computer with all subjects de-identified to ensure HIPAA compliance. There is no Clinical Trials registration number for this study. NR 40 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2012 VL 153 IS 5 BP 939 EP 948 DI 10.1016/j.ajo.2011.10.021 PG 10 WC Ophthalmology SC Ophthalmology GA 941LN UT WOS:000303964800020 PM 22310078 ER PT J AU Walcott, BP Kahle, KT Butler, WE AF Walcott, Brian P. Kahle, Kristopher T. Butler, William E. TI Endoscopic Treatment of Hydrocephalus SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID CHOROID-PLEXUS CAUTERIZATION; 3RD VENTRICULOSTOMY; INFANTS C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2012 VL 69 IS 5 BP 664 EP 664 DI 10.1001/archneurol.2011.1766 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 941ZO UT WOS:000304009100018 PM 22271236 ER PT J AU Craft, S AF Craft, Suzanne TI Insulin and Alzheimer Disease reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 [Craft, Suzanne] Univ Washington, Sch Med, Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. RP Craft, S (reprint author), Univ Washington, Sch Med S GRECC 182, Vet Affairs Puget Sound Healthcare Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@uw.edu NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2012 VL 69 IS 5 BP 671 EP 671 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 941ZO UT WOS:000304009100022 ER PT J AU Sher, L AF Sher, Leo TI Educating health care professionals about suicide prevention SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Sher, Leo] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 5 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAY PY 2012 VL 46 IS 5 BP 481 EP 482 DI 10.1177/0004867411434722 PG 2 WC Psychiatry SC Psychiatry GA 944EI UT WOS:000304181700015 PM 22535300 ER PT J AU Lansdorp-Vogelaar, I Kuntz, KM Knudsen, AB van Ballegooijen, M Zauber, AG Jemal, A AF Lansdorp-Vogelaar, Iris Kuntz, Karen M. Knudsen, Amy B. van Ballegooijen, Marjolein Zauber, Ann G. Jemal, Ahmedin TI Contribution of Screening and Survival Differences to Racial Disparities in Colorectal Cancer Rates SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FECAL-OCCULT-BLOOD; LARGE-INTESTINE; RISK-FACTORS; LARGE-BOWEL; FLEXIBLE SIGMOIDOSCOPY; RECTAL-CANCER; TASK-FORCE; POLYPS; MORTALITY; AUTOPSY AB Background: Considerable disparities exist in colorectal cancer (CRC) incidence and mortality rates between blacks and whites in the United States. We estimated how much of these disparities could be explained by differences in CRC screening and stage-specific relative CRC survival. Methods: We used the MISCAN-Colon microsimulation model to estimate CRC incidence and mortality rates in blacks, aged 50 years and older, from 1975 to 2007 assuming they had: (i) the same trends in screening rates as whites instead of observed screening rates (incidence and mortality); (ii) the same trends in stage-specific relative CRC survival rates as whites instead of observed (mortality only); and (iii) a combination of both. The racial disparities in CRC incidence and mortality rates attributable to differences in screening and/or stage-specific relative CRC survival were then calculated by comparing rates from these scenarios to the observed black rates. Results: Differences in screening accounted for 42% of disparity in CRC incidence and 19% of disparity in CRC mortality between blacks and whites. Thirty-six percent of the disparity in CRC mortality could be attributed to differences in stage-specific relative CRC survival. Together screening and survival explained a little more than 50% of the disparity in CRC mortality between blacks and whites. Conclusion: Differences in screening and relative CRC survival are responsible for a considerable proportion of the observed disparities in CRC incidence and mortality rates between blacks and whites. Impact: Enabling blacks to achieve equal access to care as whites could substantially reduce the racial disparities in CRC burden. Cancer Epidemiol Biomarkers Prey; 21(5); 728-36. (C)2012 AACR. C1 [Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30329 USA. RP Lansdorp-Vogelaar, I (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM i.vogelaar@erasmusmc.nl FU National Cancer Institute at the NIH [U01-CA-088204, U01-CA-097426, U01-CA-115953, U01-CA-152959] FX This work was supported by the National Cancer Institute at the NIH (U01-CA-088204, U01-CA-097426, U01-CA-115953, and U01-CA-152959). NR 61 TC 39 Z9 39 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2012 VL 21 IS 5 BP 728 EP 736 DI 10.1158/1055-9965.EPI-12-0023 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 940QN UT WOS:000303908200006 PM 22514249 ER PT J AU Forrester, MT Foster, MW AF Forrester, Michael T. Foster, Matthew W. TI Protection from nitrosative stress: A central role for microbial flavohemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Nitric oxide; Flavohemoglobin; Nitrosative stress; Redox; S-nitrosylation; Oxidoreductase; Bacteria; Fungi; Oxidative stress; Dioxygenase; Free radicals ID NITRIC-OXIDE DIOXYGENASE; UROPATHOGENIC ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS HEMOGLOBIN; SENSITIVE TRANSCRIPTIONAL REGULATOR; MUCOID PSEUDOMONAS-AERUGINOSA; ENTERICA SEROVAR TYPHIMURIUM; OXIDATIVE DNA-DAMAGE; DISTAL HEME POCKET; SACCHAROMYCES-CEREVISIAE; BACILLUS-SUBTILIS AB Nitric oxide (NO) is an inevitable product of life in an oxygen- and nitrogen-rich environment. This reactive diatomic molecule exhibits microbial cytotoxicity, in large part by facilitating nitrosative stress and inhibiting heme-containing proteins within the aerobic respiratory chain. Metabolism of NO is therefore essential for microbial life. In many bacteria, fungi, and protozoa, the evolutionarily ancient Flavohemoglobin (FlavoHb) converts NO and O-2 to inert nitrate (NO3-) and undergoes catalytic regeneration via Flavin-dependent reduction. Since its identification, widespread efforts have characterized roles for FlavoHb in microbial nitrosative stress protection. Subsequent genomic studies focused on flavoHb have elucidated the transcriptional machinery necessary for inducible NO protection, such as NsrR in Escherichia coli, as well as additional proteins that constitute a nitrosative stress protection program. As an alternative strategy, FlavoHb has been heterologously employed in higher eukaryotic organisms such as plants and human tumors to probe the function(s) of endogenous NO signaling. Such an approach may also provide a therapeutic route to in vivo NO depletion. Here we focus on the molecular features of FlavoHb, the hitherto characterized NO-sensitive transcriptional machinery responsible for its induction, the roles of flavoHb in resisting mammalian host defense systems, and heterologous applications of FlavoHb in plant/mammalian systems (including human tumors), as well as unresolved questions surrounding this paradigmatic NO-consuming enzyme. (c) 2012 Elsevier Inc. All rights reserved. C1 [Forrester, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Foster, Matthew W.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. RP Forrester, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. EM mtforrester@partners.org; mwfoster@duke.edu NR 178 TC 40 Z9 42 U1 3 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2012 VL 52 IS 9 BP 1620 EP 1633 DI 10.1016/j.freeradbiomed.2012.01.028 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 944DB UT WOS:000304177500013 PM 22343413 ER PT J AU Yoo, SE Chen, LJ Na, R Liu, YH Rios, C Van Remmen, H Richardson, A Ran, QT AF Yoo, Si-Eun Chen, Liuji Na, Ren Liu, Yuhong Rios, Carmen Van Remmen, Holly Richardson, Arlan Ran, Qitao TI Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Gpx4; Knockout mice; Lipid peroxidation; Mitochondria; Neurodegeneration; Apoptosis; Oxidative stress ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; CYTOCHROME-C; SUPEROXIDE-PRODUCTION; LIPID-PEROXIDATION; INDUCED APOPTOSIS; CELL-DEATH; MOUSE; GLUTATHIONE-PEROXIDASE-4 AB Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme important in reducing hydroperoxides in membrane lipids and lipoproteins. Gpx4 is essential for survival of embryos and neonatal mice; however, whether Gpx4 is required for adult animals remains unclear. In this study, we generated a floxed Gpx4 mouse (Gpx4(f/f)) in which exons 2-4 of Gpx4 gene are flanked by loxP sites. We then cross-bred the Gpx4(f/f) mice with a tamoxifen (tam)-inducible Cre transgenic mouse (R26CreER mice) to obtain mice in which the Gpx4 gene could be ablated by tam administration (Gpx4(f/f)/Cre mice). After treatment with tam, adult Gpx4(f/f)/Cre mice (6-9 months of age) showed a significant reduction of Gpx4 levels (a 75-85% decrease) in tissues such as brain, liver, lung, and kidney. Tam-treated Gpx4(f/f)/Cre mice lost body weight and died within 2 weeks, indicating that Gpx4 is essential for survival of adult animals. Tam-treated Gpx4(f/f)/Cre mice exhibited increased mitochondrial damage, as evidenced by the elevated 4-hydroxylnonenal (4-HNE) level, decreased activities of electron transport chain complexes I and IV, and reduced ATP production in liver. Tam treatment also significantly elevated apoptosis in Gpx4(f/f)/Cre mice. Moreover, tam-treated Gpx4(f/f)/Cre mice showed neuronal loss in the hippocampus region and had increased astrogliosis. These data indicate that Gpx4 is essential for mitochondria integrity and survival of neurons in adult animals. Published by Elsevier Inc. C1 [Yoo, Si-Eun; Chen, Liuji; Na, Ren; Liu, Yuhong; Rios, Carmen; Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Yoo, Si-Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Chen, Liuji; Rios, Carmen; Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly; Richardson, Arlan; Ran, Qitao] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. RP Ran, QT (reprint author), 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu FU NIH [P01 AG19316, P01AG020591]; San Antonio Nathan Shock Aging Center [1P30-AG13319]; Department of Veteran Affairs FX This work was supported by NIH Grants P01 AG19316 and P01AG020591, the San Antonio Nathan Shock Aging Center (1P30-AG13319), and a Merit Review grant (Q.R.) from the Department of Veteran Affairs. NR 34 TC 18 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2012 VL 52 IS 9 BP 1820 EP 1827 DI 10.1016/j.freeradbiomed.2012.02.043 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 944DB UT WOS:000304177500034 PM 22401858 ER PT J AU Oreskovic, NM Blossom, J Field, AE Chiang, SR Winickoff, JP Kleinman, RE AF Oreskovic, Nicolas M. Blossom, Jeff Field, Alison E. Chiang, Sylvia R. Winickoff, Jonathan P. Kleinman, Ronald E. TI Combining global positioning system and accelerometer data to determine the locations of physical activity in children SO GEOSPATIAL HEALTH LA English DT Article DE physical activity; built environment; adolescence; global positioning system; geographical information system; USA ID BUILT ENVIRONMENT; UNITED-STATES; SCHOOL; CALIBRATION; OBESITY; YOUTH AB National trends indicate that children and adolescents are not achieving sufficient levels of physical activity. Combining global positioning system (GPS) technology with accelerometers has the potential to provide an objective determination in locations where youth engage in physical activity. The aim of this study was to identify the optimal methods for collecting combined accelerometer and GPS data in youth, to best locate where children spend time and are physically active. A convenience sample of 24 mid-school children in Massachusetts was included. Accelerometers and GPS units were used to quantify and locate childhood physical activity over 5 weekdays and 2 weekend days. Accelerometer and GPS data were joined by time and mapped with a geographical information system (GIS) using ArcGIS software. Data were collected in winter, spring, summer in 2009-2010, collecting a total of 26,406 matched datapoints overall. Matched data yield was low (19.1% total), regardless of season (winter, 12.8%; spring, 30.1%; summer, 14.3%). Teacher-provided, pre-charged equipment yielded the most matched (30.1%; range: 10.1-52.3%) and greatest average days (6.1 days) of data. Across all seasons, children spent most of their time at home. Outdoor use patterns appeared to vary by season, with street use increasing in spring, and park and playground use increasing in summer. Children spent equal amounts of physical activity time at home and walking in the streets. Overall, the various methods for combining GPS and accelerometer data provided similarly low amounts of combined data. No combined GPS and accelerometer data collection method proved superior in every data return category, but use of GIS to map joined accelerometer and GPS data can demarcate childhood physical activity locations. C1 [Oreskovic, Nicolas M.; Winickoff, Jonathan P.] MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Chiang, Sylvia R.; Winickoff, Jonathan P.; Kleinman, Ronald E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oreskovic, Nicolas M.; Field, Alison E.; Winickoff, Jonathan P.; Kleinman, Ronald E.] Harvard Univ, Sch Med, Boston, MA USA. [Blossom, Jeff] Harvard Ctr Geog Anal, Cambridge, MA USA. [Field, Alison E.] Childrens Hosp Boston, Boston, MA USA. RP Oreskovic, NM (reprint author), MGH Ctr Child & Adolescent Hlth Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM noreskovic@partners.org OI Oreskovic, Nicolas/0000-0001-8702-8636 FU Department of Pediatrics, Massachusetts General Hospital FX Supported in part by the Department of Pediatrics, Massachusetts General Hospital. We thank the Revere Food and Fitness collaboration and Revere CARES for their input and guidance throughout the study, as well as Daniel Rodriguez, PhD, for his kind guidance and assistance in conceptualizing and developing this study. NR 20 TC 27 Z9 27 U1 2 U2 20 PU UNIV NAPLES FEDERICO II PI NAPLES PA FAC VET MED, DEP PATHOLOGY & ANIMAL HEALTH, VET PARASITOLOGY, VIA DELLA VETERINARIA 1, NAPLES, 80137, ITALY SN 1827-1987 J9 GEOSPATIAL HEALTH JI Geospatial Health PD MAY PY 2012 VL 6 IS 2 BP 263 EP 272 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 942GO UT WOS:000304032300014 PM 22639128 ER PT J AU Thakuria, JV Zaranek, AW Church, GM Berry, GT AF Thakuria, Joseph V. Zaranek, Alexander W. Church, George M. Berry, Gerard T. TI Back to the Future: From Genome to Metabolome SO HUMAN MUTATION LA English DT Article DE genomics; metabolomics; nutritional therapy; pharmacological therapy AB In the traditional medical genetics setting, metabolic disorders, identified either clinically or through biochemical screening, undergo subsequent single gene testing to molecularly confirm diagnosis, provide further insight on natural disease history, and inform on disease management, treatment, familial testing, and reproductive options. For decades now, this process has been responsible for saving many lives worldwide. Only recently, though, has it become possible to move in the opposite direction by starting with an individual's whole genome or exome, and, guided by this data, study more minor perturbations in the absolute values and substrate ratios of clinically important biochemical analytes. Genomic individuality can also be used to guide more detailed phenotyping aimed at uncovering milder manifestations of known metabolic diseases. Metabolomic phenotyping in the Personal Genome Project for our first 200+ participants-all of whom are scheduled to have full genome sequence at more than 40x coverage available by May 2012-is aimed at uncovering potential subclinical and preclinical disease states in carriers of known pathogenic mutations and in lesser known rare variants that are protein predicted to be pathogenic. Our initial focus targets 88 genes involved in 68 metabolic disturbances with established evidence-based nutritional and/or pharmacological therapy as part of standard medical care. Hum Mutat 33: 809-812, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Thakuria, Joseph V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Genet, Boston, MA 02114 USA. [Thakuria, Joseph V.; Zaranek, Alexander W.; Church, George M.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. [Berry, Gerard T.] Childrens Hosp Boston, Dept Med, Div Genet, Boston, MA USA. RP Thakuria, JV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Genet, Boston, MA 02114 USA. EM jthakuria@genetics.med.harvard.edu OI Berry, Gerard/0000-0001-5299-3313 NR 8 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2012 VL 33 IS 5 SI SI BP 809 EP 812 DI 10.1002/humu.22073 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 941ZK UT WOS:000304008400006 PM 22431014 ER PT J AU Bast, RC Skates, S Lokshin, A Moore, RG AF Bast, Robert C., Jr. Skates, Steven Lokshin, Anna Moore, Richard G. TI Differential Diagnosis of a Pelvic Mass Improved Algorithms and Novel Biomarkers SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Pelvic mass; Gynecologic oncologists; CA 125; HE4; ROMA; OVA1 ID EPITHELIAL OVARIAN-CANCER; MULTIVARIATE INDEX ASSAY; MALIGNANCY INDEX; GYNECOLOGIC ONCOLOGISTS; ADNEXAL MASS; CYTOREDUCTIVE SURGERY; RISK; HE-4; CARCINOMA; CARE AB More than 200,000 women undergo exploratory surgery for a pelvic mass in the United States each year and 13%-21% of pelvic lesions are found to be malignant. Individual reports and meta-analysis indicate better outcomes when cancer surgery is performed by gynecologic oncologists. Despite the advantages provided by more thorough staging and cytoreductive surgery, only 30%-50% of women with ovarian cancer are referred to surgeons with specialized training in the United States. Imaging, menopausal status and biomarkers can aid in distinguishing malignant from benign pelvic masses to inform decisions regarding appropriate referral. The risk of malignancy index (RMI) uses ultrasound, menopausal status and CA125 and has been utilized in the United Kingdom for two decades, providing sensitivity that has ranged from 71%-88% and specificity it from 97%-74% for identifying patients with malignant disease. Criteria have been established by the Society of Gynecology Oncology and American College of Obstetrics and Gynecology for referral to a gynecologic oncologist, but these have lower sensitivity and specificity than the RMI. Recently, two new algorithms have been developed to identify women at sufficiently high risk to prompt referral to a specialized surgeon. The OVA1 multivariate index incorporates imaging, menopausal status, CA125 and four other proteomic biomarkers. Use of OVA1 provides 85%-96% sensitivity at 28%-40% specificity depending upon menopausal status. The negative predictive value for women judged to be at low risk is 94%-96%. The risk of malignancy algorithm (ROMA) includes CA125, human epididymal protein 4 and menopausal status, but not imaging results. The ROMA has yielded 93%-94% sensitivity at 75% specificity with a negative predictive value of 93%-98%. In a direct comparison, ROMA has achieved greater sensitivity (94%) than the RMI (75%) at 75% specificity. OVA1 has not been compared directly to ROMA, but is likely to be as sensitive, but substantially less specific. Both algorithms have high negative predictive values 94%-98%. Although a difference in specificity should not affect patient outcomes, it could affect distribution of medical resources. C1 [Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Skates, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lokshin, Anna] Pittsburgh Canc Ctr, Pittsburgh, PA USA. [Moore, Richard G.] Brown Univ, Women & Infants Hosp, Providence, RI USA. RP Bast, RC (reprint author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM rbast@mdanderson.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU Ovarian Cancer NCI [P50 CA83639]; CCSG NCI [P30 CA16672, NCI 1 R01 CA136491-01]; National Foundation for Cancer Research; Golfers Against Cancer; Tracey Jo Wilson Foundation; Mossy Foundation; Zarrow Foundation; Stuart and Gaye Lynn Zarrow; Fujirebio Diagnostics, Inc; Abbott Diagnostics, Inc FX This work was supported by funds from the MD Anderson SPORE in Ovarian Cancer NCI P50 CA83639, the MD Anderson CCSG NCI P30 CA16672, NCI 1 R01 CA136491-01, the National Foundation for Cancer Research, the Ovarian Cancer Research Fund and philanthropic support from Golfers Against Cancer, the Tracey Jo Wilson Foundation, the Mossy Foundation, the Zarrow Foundation, and Stuart and Gaye Lynn Zarrow.; Dr Robert C. Bast Jr receives royalties for the discovery of CA 125 and serves on scientific advisory boards for Fujirebio Diagnostics, Inc, Vermillion, Inc, and Illumina, Inc.; Dr Richard G. Moore receives research support from Fujirebio Diagnostics, Inc and Abbott Diagnostics, Inc, and consults with Fujirebio Diagnostics, Inc. NR 39 TC 23 Z9 24 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2012 VL 22 SU 1 BP S5 EP S8 DI 10.1097/IGC.0b013e318251c97d PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 942VN UT WOS:000304078200003 PM 22543921 ER PT J AU Skates, SJ AF Skates, Steven J. TI Ovarian Cancer Screening: Development of the Risk of Ovarian Cancer Algorithm (ROCA) and ROCA Screening Trials SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Longitudinal CA125; ROCA; Early detection; Ovarian cancer ID WOMEN; MARKERS AB Ovarian cancer is most often detected in late stage when prognosis is poor; in contrast, prognosis is excellent when detection occurs in early stage. Early detection with regular biomarker tests may reduce disease-specific mortality. Two screening trials with annual CA125 greater than 35 U/mL demonstrated promise. Before undertaking larger trials, statistical analyses of serial CA125 levels showed each woman has her own baseline level; and in ovarian cancer cases, CA125 rose rapidly from her baseline after a change point. Improved early detection of ovarian cancer may result if each woman were tested for the presence of a change-point CA125 profile. Using the serial CA125 from the completed trials, a statistical method was developed to measure the probability a change-point had occurred. Subsequent screening trials implemented the risk of ovarian cancer algorithm (ROCA) in which screening decisions are made based on the risk of having a change point. Development of ROCA is described, and ROCA trials are listed. C1 [Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, Suite 560,50 Staniford St, Boston, MA 02114 USA. EM sskates@gmail.com FU NCI's Early Detection Research Network [U01-CA152990]; Massachusetts General Hospital FX Dr. Skates was supported by NCI's Early Detection Research Network grant U01-CA152990, USPTO patent, and by the Julie Fund at the Massachusetts General Hospital. NR 9 TC 17 Z9 17 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2012 VL 22 SU 1 BP S24 EP S26 DI 10.1097/IGC.0b013e318256488a PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 942VN UT WOS:000304078200009 PM 22543916 ER PT J AU Lee, DJ AF Lee, Daniel J. TI Response to Letter to the Editor by Saburi et al., IJPORL-D-11-00699, entitled "Letter to the Editor regarding review of cochlear implantation outcome in a case of Waardenburg syndrome." SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Letter ID HEARING-LOSS; CHILDREN C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Otol & Neurotol, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Otol & Neurotol, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAY PY 2012 VL 76 IS 5 BP 761 EP 762 DI 10.1016/j.ijporl.2012.01.027 PG 2 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 940NX UT WOS:000303901400032 ER PT J AU Condray, R Siegle, GJ Keshavan, MS Steinhauer, SR AF Condray, Ruth Siegle, Greg J. Keshavan, Matcheri S. Steinhauer, Stuart R. TI Effects of word frequency on semantic memory in schizophrenia: Electrophysiological evidence for a deficit in linguistic access (vol 75, pg 141, 2010) SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Correction C1 [Condray, Ruth] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Condray, R (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, 3811 OHara St, Pittsburgh, PA 15213 USA. EM condrayr@upmc.com NR 1 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD MAY PY 2012 VL 84 IS 2 BP 226 EP 231 DI 10.1016/j.ijpsycho.2011.05.011 PG 6 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 941JW UT WOS:000303960500016 ER PT J AU Perez, VB Ford, JM Roach, BJ Woods, SW McGlashan, TH Srihari, VH Loewy, RL Vinogradov, S Mathalon, DH AF Perez, Veronica B. Ford, Judith M. Roach, Brian J. Woods, Scott W. McGlashan, Thomas H. Srihari, Vinod H. Loewy, Rachel L. Vinogradov, Sophia Mathalon, Daniel H. TI Error Monitoring Dysfunction Across the Illness Course of Schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; prodrome; at-risk; error-related negativity; performance monitoring ID ANTERIOR CINGULATE CORTEX; CROSSMODAL DIVIDED ATTENTION; MEDIAL FRONTAL-CORTEX; CHOICE REACTION TASKS; LATE ERP COMPONENTS; EVENT-RELATED FMRI; BRAIN ACTIVITY; INTERRATER RELIABILITY; PREDICTIVE-VALIDITY; PRODROMAL SYNDROMES AB Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word matching task yielded error-related negativity (ERN), correct-response negativity (CRN), and error positivity (Pe) from 84 schizophrenia patients (SZ), 48 clinical high risk patients (CHR), and their age-matched healthy controls (HC; n = 110 and 88, respectively). A sub-sample of 35 early illness schizophrenia patients (ESZ) was compared to 93 age-matched HC and the CHR patients (after statistically removing the effects of normal aging). Relative to HC, 1) SZ, ESZ, and CHR had smaller ERNs, and 2) SZ and ESZ had larger CRNs and smaller Pes. Within the SZ, longer illness duration was associated with larger CRNs but was unrelated to ERN or Pe. CHR and ESZ did not differ on ERN or CRN, although Pe was smaller in ESZ than CHR. These results indicate that while ERN, CRN, and Pe abnormalities are present early in the illness, only the ERN abnormality is evident prior to psychosis onset, and only the CRN abnormality appears to worsen progressively over the illness course. Brain regions subserving response monitoring may be compromised early in the illness and possibly during its clinical prodrome. C1 [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Loewy, Rachel L.; Vinogradov, Sophia; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Vinogradov, Sophia; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Woods, Scott W.; McGlashan, Thomas H.; Srihari, Vinod H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Mathalon, DH (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM daniel.mathalon@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Srihari, Vinod/0000-0003-1556-2332 FU NIMH NIH HHS [T32 MH089920, T32 MH089920-01, K02 MH067967, R01 MH076989, R01 MH058262, RC1 MH088971] NR 98 TC 21 Z9 21 U1 5 U2 14 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 2012 VL 121 IS 2 BP 372 EP 387 DI 10.1037/a0025487 PG 16 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 943NQ UT WOS:000304131400008 PM 22060947 ER PT J AU Goldstein, DJ Maybaum, S MacGillivray, TE Moore, SA Bogaev, R Farrar, DJ Frazier, OH AF Goldstein, Daniel J. Maybaum, Simon MacGillivray, Thomas E. Moore, Stephanie A. Bogaev, Roberta Farrar, David J. Frazier, O. Howard CA Heartmate II Clinical TI Young Patients With Nonischemic Cardiomyopathy Have Higher Likelihood of Left Ventricular Recovery During Left Ventricular Assist Device Support SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; LVAD; myocardial recovery ID MECHANICAL CIRCULATORY SUPPORT; CHRONIC HEART-FAILURE; MYOCARDIAL RECOVERY; TO-RECOVERY; TRANSPLANTATION; BRIDGE; THERAPY; SYSTEM AB Background: Recovery of ventricular function during left ventricular assist device (LVAD) support allowing device explantation occurs infrequently. We explored the hypothesis that certain patient profiles are more likely to exhibit LV recovery during LVAD support. Methods and Results: A retrospective analysis of data from the Heart Mate II bridge to transplant (BTT) and destination therapy (DT) trials was conducted, including 490 BTT, 600 DT, and 18 compassionate-use patients. Of the 1,108 patients, 20 (1.8%; 10 BIT, 10 DT) were explanted owing to LV recovery. The median age was 33 years, and 12 patients (60%) were <40 years of age. History of heart failure was <1 year for 11 patients (61%), and the primary etiology was nonischemic (90%). Of the patients with nonischemic etiologies and <1-year history of heart failure, 13% were explained. Three patients required LVAD reimplantation; of the remaining 17, 16 remain alive. At follow-up (median 510 days), the mean ejection fraction was 42% (20%-67%) and the mean left ventricular end-diastolic diameter was 55 +/- 8 mm. At the 2-year follow-up (n = 13), patients were New York Heart Association functional class I or II and overall survival rate was 85 +/- 11%. Conclusions: The results of this study suggest that LV recovery is most likely to occur in young patients (<40 years) with nonischemic cardiomyopathy of <1 year duration. Two-year postexplant survival was excellent. (J Cardiac Fail 2012;18:392-395) C1 [Goldstein, Daniel J.; Maybaum, Simon] Montefiore Med Ctr, Bronx, NY 10467 USA. [MacGillivray, Thomas E.; Moore, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bogaev, Roberta; Frazier, O. Howard] Texas Heart Inst, Houston, TX 77025 USA. [Farrar, David J.] Thoratec Corp, Pleasanton, CA USA. RP Goldstein, DJ (reprint author), Dept Cardiovasc & Thorac Surg, 3400 Bainbridge Ave,MAP Bldg,5th Floor, Bronx, NY 10467 USA. EM dgoldste@montefiore.org FU Thoratec; Heartware FX Simon Maybaum: Thoratec, modest, research grant.; O.H. Frazier: Thoratec, significant, research grant; Heartware, significant, research grant. NR 26 TC 22 Z9 22 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAY PY 2012 VL 18 IS 5 BP 392 EP 395 DI 10.1016/j.cardfail.2012.01.020 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 942VS UT WOS:000304078700008 PM 22555270 ER PT J AU Beinart, R Heist, EK Ruskin, J Mansour, M AF Beinart, Roy Heist, E. Kevin Ruskin, Jeremy Mansour, Moussa TI Is the Pulmonary Vein Isolated? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID ATRIAL-FIBRILLATION; ABLATION C1 [Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2012 VL 23 IS 5 BP 564 EP 566 DI 10.1111/j.1540-8167.2011.02139.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 937MH UT WOS:000303662100022 PM 21806699 ER PT J AU van der Lely, AJ Biller, BMK Brue, T Buchfelder, M Ghigo, E Gomez, R Hey-Hadavi, J Lundgren, F Rajicic, N Strasburger, CJ Webb, SM Koltowska-Haggstrom, M AF van der Lely, A. J. Biller, Beverly M. K. Brue, Thierry Buchfelder, Michael Ghigo, Ezio Gomez, Roy Hey-Hadavi, Judith Lundgren, Frida Rajicic, Natasa Strasburger, Christian J. Webb, Susan M. Koltowska-Haggstrom, Maria TI Long-Term Safety of Pegvisomant in Patients with Acromegaly: Comprehensive Review of 1288 Subjects in ACROSTUDY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR ANTAGONIST PEGVISOMANT; SOMATOSTATIN ANALOGS; COMBINATION THERAPY; EFFICACY; MULTICENTER; EXPERIENCE AB Context: Pegvisomant is a GH receptor antagonist. The ACROSTUDY is a global safety surveillance study of long-term treatment of acromegaly with pegvisomant. Objective: The objective of the study was to monitor long-term safety and treatment outcomes. Design: ACROSTUDY is open to all patients with acromegaly who are treated with pegvisomant. We report an interim analysis of data captured from 1288 subjects enrolled before a database freeze of December 31, 2009. Setting: This was a global noninterventional surveillance study. Main Outcome Measure(s): Long-term monitoring of safety, including central magnetic resonance imaging (MRI) reading and treatment outcomes, was measured. Results: Subjects (n = 1288) were treated with pegvisomant for a mean of 3.7 yr and followed up in ACROSTUDY for a mean of 2.1 yr. A total of 1147 adverse events (AE) were recorded in 477 subjects (37%), among which 192 AE in 124 subjects (9.6%) were considered to be related to pegvisomant. Serious AE were recorded in 159 subjects (12.3%), whereas pegvisomant-related Serious AE were recorded in 26 subjects (2%). No deaths (15 subjects; 1.2%) were attributed to pegvisomant use. The incidence of increase in pituitary tumor size in the subset with confirmed MRI increases on central reading represented 3.2% of the overall cohort with at least two available MRI (n = 936). Injection-site reactions were reported in 28 cases (2.2%). In 30 patients (2.5%), an elevated aspartate aminotransferase or alanine aminotransferase of more than 3 times the upper level of normality was reported. There were no reports of liver failure. After 5 yr of pegvisomant treatment, 63.2% of subjects had normal IGF-I levels at a mean dose of 18 mg/d. Conclusions: Data entered and evaluated in ACROSTUDY indicate that pegvisomant is an effective and safe medical treatment in patients with acromegaly. The reported low incidence of pituitary tumor size increase, liver enzyme elevations, and lipodystrophy at the injection site are reassuring. (J Clin Endocrinol Metab 97: 1589-1597, 2012) C1 [van der Lely, A. J.] Erasmus Univ, Dept Med, Med Ctr, NL-3000 CA Rotterdam, Netherlands. [Biller, Beverly M. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brue, Thierry] Aix Marseille Univ, Dept Endocrinol, Ctr Reference Malad Rares Origine Hypophysaire, Hop La Timone,Assistance Publ Hop Marseille, F-13331 Marseille, France. Aix Marseille Univ, Fac Med Marseille, F-13331 Marseille, France. [Buchfelder, Michael] Neurochirurg Klin, Dept Neurosurg, D-91054 Erlangen, Germany. [Ghigo, Ezio] Univ Turin, Dept Endocrinol, I-10126 Turin, Italy. [Gomez, Roy] Pfizer, European Med Affairs, B-1050 Brussels, Belgium. [Hey-Hadavi, Judith; Rajicic, Natasa] Pfizer Inc, Med Dev Grp, Clin Affairs, New York, NY 10017 USA. [Lundgren, Frida; Koltowska-Haggstrom, Maria] Pfizer Hlth AB, ACROSTUDY, S-19190 Sollentuna, Sweden. [Strasburger, Christian J.] Dept Med, Div Clin Endocrinol, D-10117 Berlin, Germany. Univ Autonoma Barcelona, Barcelona 08025, Spain. [Webb, Susan M.] Inst Salud Carlos III, Dept Endocrinol, Hosp St Pau, IIB St Pau,Ctr Invest Biomed Red Enfermedades Rar, Barcelona 08025, Spain. [Webb, Susan M.] Inst Salud Carlos III, Dept Med, Hosp St Pau, IIB St Pau,Ctr Invest Biomed Red Enfermedades Rar, Barcelona 08025, Spain. RP van der Lely, AJ (reprint author), Erasmus Univ, Dept Internal Med, Med Ctr, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.vanderlelij@erasmusmc.nl RI Webb, Susan/C-7294-2008; Eric, Ghigo/N-9427-2016; OI Brue, Thierry/0000-0001-8482-6691 FU Pfizer Inc. FX We thank all of the investigators, subinvestigators, nurses, and study coordinators involved in ACROSTUDY and the patients who allowed their data to be captured. ACROSTUDY is sponsored by Pfizer Inc. We also thank Dr. Pia Burman for her significant contribution to the design of the ACROSTUDY and for her valuable help with evaluating the data. NR 24 TC 86 Z9 86 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2012 VL 97 IS 5 BP 1589 EP 1597 DI 10.1210/jc.2011-2508 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940TL UT WOS:000303915900050 PM 22362824 ER PT J AU Bergman, BC Howard, D Schauer, IE Maahs, DM Snell-Bergeon, JK Eckel, RH Perreault, L Rewers, M AF Bergman, Bryan C. Howard, David Schauer, Irene E. Maahs, David M. Snell-Bergeon, Janet K. Eckel, Robert H. Perreault, Leigh Rewers, Marian TI Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-ARTERY CALCIFICATION; GLUCOSE-METABOLISM; CARDIOVASCULAR-DISEASE; MELLITUS; COMPLICATIONS; MECHANISMS; DISPOSAL; DEFECT; WOMEN; LIVER AB Context: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control. Objective: We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration. Design, Patients, and Methods: Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 +/- 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2).min. Glucose metabolism was quantified using an infusion of [6,6-H-2(2)] glucose. Hepatic insulin sensitivity was measured using the insulin IC50 for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose. Results: Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8-and 40-mU/m(2).min stages. Conclusion: Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia. (J Clin Endocrinol Metab 97: 1663-1672, 2012) C1 [Bergman, Bryan C.; Howard, David; Schauer, Irene E.; Eckel, Robert H.; Perreault, Leigh] Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Aurora, CO 80045 USA. [Snell-Bergeon, Janet K.; Rewers, Marian] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Schauer, Irene E.] Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Bergman, BC (reprint author), Univ Colorado, Div Endocrinol Metab & Diabet, Dept Med, Anschutz Med Campus,POB 6511,MS 8106, Aurora, CO 80045 USA. EM bryan.bergman@ucdenver.edu OI Bergman, Bryan/0000-0002-9561-1052 FU National Institutes of Health's National Heart, Lung, and Blood Institute [R01 HL-61753, R01 HL-079611]; Clinical Translational Research Center at the University of Colorado Denver [M01 RR000051, RR-00036]; Barbara Davis Center for Childhood Diabetes (Denver, CO); National Institutes of Health Diabetes Endocrinology Research Center [P30 DK57516]; National Institute for Diabetes and Digestive and Kidney Diseases [K01 DK066219, K23 DK075360]; American Diabetes Association [1-10-JF-50] FX This work was supported by the National Institutes of Health's National Heart, Lung, and Blood Institute Grants R01 HL-61753 and R01 HL-079611, and Clinical Translational Research Center at the University of Colorado Denver Grants M01 RR000051 and RR-00036 as well as the Barbara Davis Center for Childhood Diabetes (Denver, CO). Support was also provided by the National Institutes of Health Diabetes Endocrinology Research Center Clinical Investigation Core Grant P30 DK57516; National Institute for Diabetes and Digestive and Kidney Diseases Grants K01 DK066219 (to B.C.B.) and K23 DK075360 (to D.M.M.); and the American Diabetes Association Junior Faculty Award 1-10-JF-50 (to J.K.S.-B.). NR 42 TC 29 Z9 29 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2012 VL 97 IS 5 BP 1663 EP 1672 DI 10.1210/jc.2011-3172 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940TL UT WOS:000303915900059 PM 22362823 ER PT J AU Burney, BO Hayes, TG Smiechowska, J Cardwell, G Papusha, V Bhargava, P Konda, B Auchus, RJ Garcia, JM AF Burney, Basil O. Hayes, Teresa G. Smiechowska, Joanna Cardwell, Gina Papusha, Victor Bhargava, Peeyush Konda, Bhavana Auchus, Richard J. Garcia, Jose M. TI Low Testosterone Levels and Increased Inflammatory Markers in Patients with Cancer and Relationship with Cachexia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW SERUM TESTOSTERONE; ERECTILE DYSFUNCTION; HYPOGONADAL MEN; GRIP STRENGTH; OLDER MEN; SURVIVORS; ANOREXIA; MASS; INTERLEUKIN-6; ASSOCIATIONS AB Context: Male cancer patients suffer from fatigue, sexual dysfunction, and decreased functional performance and muscle mass. These symptoms are seen in men with hypogonadism and/or inflammatory conditions. However, the relative contribution of testosterone and inflammation to symptom burden in cancer has not been well-established. Objective: The aim of this study was to measure testosterone levels in male cancer patients and determine the relationship between testosterone, inflammation, and symptom burden. Design/Setting: This cross-sectional study enrolled patients from a tertiary-care center. Subjects/Outcome Measures: Subjects included males with cancer-cachexia (CC; n = 45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO; n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein (CRP), and IL-6 were measured in plasma. Functional performance was assessed by the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance Scales), and sexual function was assessed by the IIEF (International Index of Erectile Function). Results: Low testosterone levels were seen in more than 70% of CC cases. TT was lower in CC compared to CNC(P < 0.05). Also, CC had lower bioavailable testosterone, grip strength, IIEF scores, appendicular lean body mass, and fat mass and higher IL-6 and CRP compared to controls (P <= 0.05). ECOG and KPS were lower in CC and CNC compared to controls (P <= 0.05). On multiple regression analysis, TT, albumin, and CRP predicted symptoms differentially in cancer patients. Conclusions: CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients. (J Clin Endocrinol Metab 97: E700-E709, 2012) C1 [Garcia, Jose M.] Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hayes, Teresa G.] Michael E DeBakey VA Med Ctr, Div Hematol & Oncol, Houston, TX 77030 USA. [Smiechowska, Joanna] Michael E DeBakey VA Med Ctr, Div Geriatr, Houston, TX 77030 USA. [Konda, Bhavana] Univ Miami, Miller Sch Med, Dept Med, Atlantis, FL 33136 USA. [Auchus, Richard J.] Univ Michigan, Div Metab Endocrinol & Diabet, Dept Internal Med, Ann Arbor, MI 48109 USA. [Smiechowska, Joanna; Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Bhargava, Peeyush] Michael E DeBakey VA Med Ctr, Dept Radiol, Houston, TX 77030 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA. EM jgarcia1@bcm.edu FU Abbott; MERIT from the Department of Veterans Affairs [I01-BX000507]; Clinical Scientist Award in Translational Research from the Burroughs-Welcome Fund [1005954] FX This work was supported by an unrestricted grant from Abbott and a MERIT grant from the Department of Veterans Affairs (to J.M.G.; I01-BX000507). R.J.A. is supported by a Clinical Scientist Award in Translational Research (no. 1005954) from the Burroughs-Welcome Fund. NR 47 TC 23 Z9 25 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2012 VL 97 IS 5 BP E700 EP E709 DI 10.1210/jc.2011-2387 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940TL UT WOS:000303915900001 PM 22419719 ER PT J AU Wang, S Wong, ML Hamilton, N Ben Davoren, J Jahan, TM Walter, LC AF Wang, Sunny Wong, Melisa L. Hamilton, Nathan Ben Davoren, J. Jahan, Thierry M. Walter, Louise C. TI Impact of Age and Comorbidity on Non-Small-Cell Lung Cancer Treatment in Older Veterans SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINED-MODALITY THERAPY; HEALTH-CARE UTILIZATION; QUALITY-OF-LIFE; ELDERLY-PATIENTS; PHASE-III; MEDICARE BENEFICIARIES; CHEMOTHERAPY REGIMENS; VINORELBINE; CISPLATIN; ONCOLOGY AB Purpose Because comorbidity affects cancer treatment outcomes, guidelines recommend considering comorbidity when making treatment decisions in older patients with lung cancer. Yet, it is unclear whether treatment is targeted to healthier older adults who might reasonably benefit. Patients and Methods Receipt of first-line guideline-recommended treatment was assessed for 20,511 veterans age >= 65 years with non-small-cell lung cancer (NSCLC) in the Veterans Affairs (VA) Central Cancer Registry from 2003 to 2008. Patients were stratified by age (65 to 74, 75 to 84, >= 85 years), Charlson comorbidity index score (0, 1 to 3, >= 4), and American Joint Committee on Cancer stage (I to II, IIIA to IIIB, IIIB with malignant effusion to IV). Comorbidity and patient characteristics were obtained from VA claims and registry data. Multivariate analysis identified predictors of receipt of guideline-recommended treatment. Results In all, 51% of patients with local, 35% with regional, and 27% with metastatic disease received guideline-recommended treatment. Treatment rates decreased more with advancing age than with worsening comorbidity for all stages, such that older patients with no comorbidity had lower rates than younger patients with severe comorbidity. For example, 50% of patients with local disease age 75 to 84 years with no comorbidity received surgery compared with 57% of patients age 65 to 74 years with severe comorbidity (P < .001). In multivariate analysis, age and histology remained strong negative predictors of treatment for all stages, whereas comorbidity and nonclinical factors had a minor effect. Conclusion Advancing age is a much stronger negative predictor of treatment receipt among older veterans with NSCLC than comorbidity. Individualized decisions that go beyond age and include comorbidity are needed to better target NSCLC treatments to older patients who may reasonably benefit. C1 [Wang, Sunny; Hamilton, Nathan; Ben Davoren, J.; Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wang, Sunny; Jahan, Thierry M.] Univ Calif San Francisco, Thorac Oncol Program, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Wang, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111H1, San Francisco, CA 94121 USA. EM sunny.wang@ucsf.edu FU San Francisco Veterans Affairs (VA) Medical Center; University of California at San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center; Division of Hematology/Oncology, Department of Medicine at USCF; USCF Pathways Funding Agency; Philip R. Lee Program; Department of General Internal Medicine, UCSF; San Francisco VA Medical Center; National Cancer Institute, National Institutes of Health [R01 CA134425]; Eli Lilly; Genentech/OSI Pharmaceuticals; ImClone Systems; Morphotek; Pfizer FX Supported by the San Francisco Veterans Affairs (VA) Medical Center (S. W.); the Thoracic Oncology Program, University of California at San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, and the Division of Hematology/Oncology, Department of Medicine at USCF (S. W. and T.M.J.); the USCF Pathways Funding Agency, the Philip R. Lee Program, and the Department of General Internal Medicine, UCSF (M. L. W.); San Francisco VA Medical Center (J.B.D.); and by Grant No. R01 CA134425 from the National Cancer Institute, National Institutes of Health, and the San Francisco VA Medical Center (L. C. W.).; Sunny Wang, Eli Lilly, Genentech/OSI Pharmaceuticals, ImClone Systems, Morphotek, Pfizer; Thierry M. Jahan, Eli Lilly, Genentech/OSI Pharmaceuticals, ImClone Systems, Morphotek, Pfizer NR 61 TC 52 Z9 54 U1 0 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 2012 VL 30 IS 13 BP 1447 EP 1455 DI 10.1200/JCO.2011.39.5269 PG 9 WC Oncology SC Oncology GA 939ZJ UT WOS:000303859400013 PM 22454424 ER PT J AU Baselga, J Segalla, JGM Roche, H del Giglio, A Pinczowski, H Ciruelos, EM Cabral, S Gomez, P Van Eyll, B Bermejo, B Llombart, A Garicochea, B Duran, MAC Hoff, PMG Espie, M de Moraes, AAJG Ribeiro, RA Mathias, C Gil, MG Ojeda, B Morales, J Ro, SK Li, S Costa, F AF Baselga, Jose Martins Segalla, Jose Getulio Roche, Henri del Giglio, Auro Pinczowski, Helio Ciruelos, Eva M. Cabral Filho, Sebastiao Gomez, Patricia Van Eyll, Brigitte Bermejo, Begona Llombart, Antonio Garicochea, Bernardo Climent Duran, Miguel Angel Gehm Hoff, Paulo Marcelo Espie, Marc Junior Gemeinder de Moraes, Andre Augusto Ribeiro, Ronaldo Albuquerque Mathias, Clarissa Gil Gil, Miguel Ojeda, Belen Morales, Josefa Ro, Sunhee Kwon Li, Shell Costa, Frederico TI Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; TUMOR ANGIOGENESIS; SOLID TUMORS; MULTIKINASE INHIBITOR; THERAPY; BEVACIZUMAB; GROWTH; CARCINOMA; ANTIBODY; PROGRESSION AB Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose. C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Martins Segalla, Jose Getulio] Fundacao Dr Amaral Carvalho, Jau, Brazil. [del Giglio, Auro; Pinczowski, Helio] Ctr Estudos & Pesquisas Hematol & Oncol, Fac Med ABC, Santo Andre, Brazil. [Cabral Filho, Sebastiao] Clin Santa Casa Belo Horizonte, Belo Horizonte, MG, Brazil. [Gehm Hoff, Paulo Marcelo] Univ Sao Paulo, Fac Med, Hosp Clin, BR-05508 Sao Paulo, Brazil. [Junior Gemeinder de Moraes, Andre Augusto] Ctr Canc Santa Casa Piracicaba Sao Paulo, Sao Paulo, Brazil. [Costa, Frederico] Inst Brasileiro Pesquisaem Canc, Sao Paulo, Brazil. [Garicochea, Bernardo] Pontificia Univ Rio Grande Sul, Hosp Sao Lucas, Porto Alegre, RS, Brazil. [Ribeiro, Ronaldo Albuquerque] Hosp Canc Ceara, Inst Canc Ceara, Fortaleza, Ceara, Brazil. [Mathias, Clarissa] Hosp Portugues Bahia, Salvador, BA, Brazil. [Espie, Marc] Hop St Louis, Assistance Publ Hop Paris, Ctr Malad Sein, Paris, France. [Roche, Henri] Inst Claudius Regaud, Toulouse, France. [Ciruelos, Eva M.] Hosp Univ 12 Octubre, Madrid, Spain. [Gomez, Patricia] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [Gil Gil, Miguel] Inst Invest Biomed Bellvitge, Inst Catalan Oncol, Barcelona, Spain. [Ojeda, Belen] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Morales, Josefa] Spanish Breast Canc Res Grp, Grp Espanol Estudio Tratamiento & Otras Estrategi, Sabadell, Spain. [Bermejo, Begona] Univ Valencia, Hosp Clin, Valencia, Spain. [Climent Duran, Miguel Angel] Inst Valenciano Oncol, Valencia, Spain. [Llombart, Antonio] Hosp Univ Arnau de Vilanova Lleida, Lleida, Spain. [Ro, Sunhee Kwon; Li, Shell] Onyx Pharmaceut, San Francisco, CA USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA. EM jbaselga@partners.org RI Roche, Henri/O-9211-2014; OI Roche, Henri/0000-0001-7463-205X; Ciruelos, Eva /0000-0002-2796-1042 FU Roche; SOLTI Group; Onyx Pharmaceuticals; Bayer HealthCare Pharmaceuticals FX Marc Espie, Roche; Supported by the SOLTI Group and in part by Onyx Pharmaceuticals and Bayer HealthCare Pharmaceuticals. Onyx Pharmaceuticals and Bayer HealthCare Pharmaceuticals also provided sorafenib free of charge and editorial support. NR 42 TC 87 Z9 90 U1 1 U2 9 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 2012 VL 30 IS 13 BP 1484 EP 1491 DI 10.1200/JCO.2011.36.7771 PG 8 WC Oncology SC Oncology GA 939ZJ UT WOS:000303859400018 PM 22412143 ER PT J AU Kelly, WK Halabi, S Carducci, M George, D Mahoney, JF Stadler, WM Morris, M Kantoff, P Monk, JP Kaplan, E Vogelzang, NJ Small, EJ AF Kelly, William Kevin Halabi, Susan Carducci, Michael George, Daniel Mahoney, John F. Stadler, Walter M. Morris, Michael Kantoff, Philip Monk, J. Paul Kaplan, Ellen Vogelzang, Nicholas J. Small, Eric J. TI Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LEUKEMIA GROUP-B; COLORECTAL-CANCER; RECOMMENDATIONS; EXPRESSION; CARCINOMA; SURVIVAL; OUTCOMES AB Purpose A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status <= 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m(2) intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. Results In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P <= .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). Conclusion Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity. C1 [Kelly, William Kevin] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Halabi, Susan; Kaplan, Ellen] Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. [Mahoney, John F.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Carducci, Michael] Johns Hopkins Univ, Baltimore, MD USA. [Stadler, Walter M.] Univ Chicago, Chicago, IL 60637 USA. [Morris, Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kantoff, Philip] Dana Farber Canc Inst, Boston, MA 02115 USA. [Monk, J. Paul] Ohio State Univ, Columbus, OH 43210 USA. [Vogelzang, Nicholas J.] US Oncol Res, Comprehens Canc Ctr Nevada, Las Vegas, NV USA. [Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kelly, WK (reprint author), 834 Chestnut St,Ben Franklin House,Suite 314, Philadelphia, PA 19017 USA. EM wm.kevin.kelly@jefferson.edu OI Morris, Michael J./0000-0002-9454-0096 FU National Cancer Institute [CA31946, CA33601]; Roche-Genentech; sanofi-aventis; Genentech; Algeta; Genta; Johnson Johnson; Agensys; GlaxoSmithKline; Hollis-Eden Pharmaceuticals; Bristol-Myers Squibb; Tokai Pharmaceuticals; Progenix; Bayer Pharmaceuticals FX Supported in part by Grants No. CA31946 from the National Cancer Institute to the Cancer and Leukemia Group B (CALGB) and No. CA33601 to the CALGB Statistical Center and by Roche-Genentech.; William Kevin Kelly, sanofi-aventis, Genentech; Susan Halabi, sanofi-aventis; Walter M. Stadler, Genentech; Michael Morris, sanofi-aventis, Algeta, Genta, Johnson & Johnson, Agensys, GlaxoSmithKline, Hollis-Eden Pharmaceuticals, Bristol-Myers Squibb; Nicholas J. Vogelzang, Tokai Pharmaceuticals, Progenix, Algeta, Bayer Pharmaceuticals NR 21 TC 219 Z9 227 U1 0 U2 12 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 2012 VL 30 IS 13 BP 1534 EP 1540 DI 10.1200/JCO.2011.39.4767 PG 7 WC Oncology SC Oncology GA 939ZJ UT WOS:000303859400025 PM 22454414 ER PT J AU Brastianos, P AF Brastianos, Priscilla TI Kairos SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brastianos, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 1537, Boston, MA 02115 USA. EM pbrastianos@partners.org OI Brastianos, Priscilla/0000-0003-4470-8425 NR 0 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 1 PY 2012 VL 30 IS 13 BP 1562 EP 1562 DI 10.1200/JCO.2012.42.0208 PG 1 WC Oncology SC Oncology GA 939ZJ UT WOS:000303859400038 PM 22473164 ER PT J AU Kalra, MK Woisetschlager, M Dahlstrom, N Singh, S Lindblom, M Choy, G Quick, P Schmidt, B Sedlmair, M Blake, MA Persson, A AF Kalra, Mannudeep K. Woisetschlager, Mischa Dahlstrom, Nils Singh, Sarabjeet Lindblom, Maria Choy, Garry Quick, Petter Schmidt, Bernhard Sedlmair, Martin Blake, Michael A. Persson, Anders TI Radiation Dose Reduction With Sinogram Affirmed Iterative Reconstruction Technique for Abdominal Computed Tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE multiYdetector-row CT; radiation dose; iterative reconstruction; filtered back-projection ID IMAGE QUALITY; CT; ALGORITHM; FILTERS; PHANTOM AB Purpose: The objective of this study was to assess the effect of Sinogram Affirmed Iterative Reconstruction (SAFIRE) and filtered back-projection (FBP) techniques on abdominal computed tomography (CT) performed with 50% and 75% radiation dose reductions. Methods: Twenty-four patients (mean age, 64 +/- 14 years; male-female ratio, 10: 14) gave informed consent for an institutional review board- approved prospective study involving acquisition of additional research images through the abdomen on 128-slice multi-detector-row CT (SOMATOM Definition Flash) at quality reference mAs of 100 (50% lower dose) and 50 (75% lower dose) over a scan length of 10 cm using combined modulation (CARE Dose 4D). Standard-of-care abdominal CT was performed at 200 quality reference mAs, with remaining parameters held constant. The 50- and 100-mAs data sets were reconstructed with FBP and at 4 SAFIRE settings (S1, S2, S3, S4). Higher number of SAFIRE settings denotes increased strength of the algorithm resulting in lower image noise. Two abdominal radiologists independently compared the FBP and SAFIRE images for lesion number, location, size and conspicuity, and visibility of small structures, image noise, and diagnostic confidence. Objective noise and Hounsfield units (HU) were measured in the liver and the descending aorta. Results: All 43 lesions were detected on both FBP and SAFIRE images. Minor blocky, pixelated appearance of 50% and 75% reduced dose images was noted at S3 and S4 SAFIRE but not at S1 and S2 settings. Subjective noise was suboptimal in both 50% and 75% lower-dose FBP images but was deemed acceptable on all SAFIRE settings. Sinogram Affirmed Iterative Reconstruction images were deemed acceptable in all patients at 50% lower dose and in 22 of 24 patients at 75% lower dose. As compared with 75% reduced dose FBP, objective noise was lower by 22.8% (22.9/29.7), 35% (19.3/29.7), 44.3% (16.7/29.3), and 54.8% (13.4/29.7) on S1 to S4 settings, respectively (P < 0.001). Conclusions: Sinogram Affirmed Iterative Reconstruction-enabled reconstruction provides abdominal CT images without loss in diagnostic value at 50% reduced dose and in some patients also at 75% reduced dose. C1 [Kalra, Mannudeep K.; Singh, Sarabjeet; Choy, Garry; Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Woisetschlager, Mischa; Dahlstrom, Nils; Lindblom, Maria; Quick, Petter; Persson, Anders] Linkoping Univ Hosp, Ctr Med Image Sci & Visualizat, S-58185 Linkoping, Sweden. [Schmidt, Bernhard; Sedlmair, Martin] Siemens Healthcare, Forchheim, Germany. RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders Room 202, Boston, MA 02114 USA. EM ssingh6@partners.org RI Persson, Anders/L-1004-2013 OI Persson, Anders/0000-0002-9446-6981 NR 13 TC 92 Z9 102 U1 1 U2 14 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 2012 VL 36 IS 3 BP 339 EP 346 DI 10.1097/RCT.0b013e31825586c0 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 944KU UT WOS:000304201200013 PM 22592621 ER PT J AU Singh, S Kalra, MK Do, S Thibault, JB Pien, H Connor, OOJ Blake, MA AF Singh, Sarabjeet Kalra, Mannudeep K. Do, Synho Thibault, Jean Baptiste Pien, Homer Connor, Owen O. J. Blake, Michael A. TI Comparison of Hybrid and Pure Iterative Reconstruction Techniques With Conventional Filtered Back Projection: Dose Reduction Potential in the Abdomen SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT image reconstruction; fully iterative reconstruction; radiation dose reduction ID IMAGE-QUALITY; CT; TOMOGRAPHY; ALGORITHMS; SPECT AB Purpose: Assess the effect of filtered back projection (FBP) and hybrid (adaptive statistical iterative reconstruction [ASIR]) and pure (model-based iterative reconstruction [MBIR]) iterative reconstructions on abdominal computed tomography (CT) acquired with 75% radiation dose reduction. Materials and Methods: In an institutional review board-approved prospective study, 10 patients (mean [standard deviation] age, 60 (8) years; 4 men and 6 women) gave informed consent for acquisition of additional abdominal images on 64-slice multidetector-row CT (GE 750HD, GE Healthcare). Scanning was repeated over a 10-cm scan length at 200 and 50 milliampere second (mA s), with remaining parameters held constant at 120 kilovolt (peak), 0.984:1 pitch, and standard reconstruction kernel. Projection data were deidentified, exported, and reconstructed to obtain 4 data sets (200-mA s FBP, 50-mA s FBP, 50-mA s ASIR, 50-mA s MBIR), which were evaluated by 2 abdominal radiologists for lesions and subjective image quality. Objective noise and noise spectral density were measured for each image series. Results: Among the 10 patients, the maximum weight recorded was 123 kg, with maximum transverse diameter measured as 43.7 cm. Lesion conspicuity at 50-mA s MBIR was better than on 50-mA s FBP and ASIR images (P < 0.01). Image noise was rated as suboptimal on low-dose FBP and ASIR but deemed acceptable in MBIR images. Objective noise with 50-mA s MBIR was 2 to 3 folds lower compared to 50-mA s ASIR, 50-mA s FBP, and 200-mA s FBP (P < 0.0001).Noise spectral density analyses demonstrated that ASIR retains the noise spectrum signature of FBP, whereas MBIR has much lower noise with a more regularized noise spectrum pattern. Conclusion: Model-based iterative reconstruction renders acceptable image quality and diagnostic confidence in 50-mA s abdominal CT images, whereas FBP and ASIR images are associated with suboptimal image quality at this radiation dose level. C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Do, Synho; Pien, Homer; Connor, Owen O. J.; Blake, Michael A.] Massachusetts Gen Hosp, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. [Thibault, Jean Baptiste] GE Healthcare, Waukesha, WI USA. RP Singh, S (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. EM ssingh6@partners.org FU GE Healthcare; Siemens; Philips FX MKK has received research grant from GE Healthcare. JBT is an employee of GE Healthcare.; Two other coauthors (HP and SD) have received research grants from Siemens and Philips within the past 12 months. The remaining coauthors have no pertinent financial disclosures and had complete and unrestricted access to the study data and manuscript. NR 20 TC 79 Z9 85 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2012 VL 36 IS 3 BP 347 EP 353 DI 10.1097/RCT.0b013e31824e639e PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 944KU UT WOS:000304201200014 PM 22592622 ER PT J AU Hwang, DY Silva, GS Furie, KL Greer, DM AF Hwang, David Y. Silva, Gisele S. Furie, Karen L. Greer, David M. TI COMPARATIVE SENSITIVITY OF COMPUTED TOMOGRAPHY VS. MAGNETIC RESONANCE IMAGING FOR DETECTING ACUTE POSTERIOR FOSSA INFARCT SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE computed tomography scanners; X-ray; cranial fossa; posterior; stroke; sensitivity; magnetic resonance imaging ID ACUTE ISCHEMIC-STROKE; BASILAR ARTERY-OCCLUSION; OF-HEALTH STROKE; CEREBELLAR INFARCTION; CIRCULATION REGISTRY; SOURCE IMAGES; MANAGEMENT; HYPOATTENUATION; PROGNOSIS; DIAGNOSIS AB Background: Posterior fossa strokes, particularly those related to basilar occlusion, pose a high risk for progression and poor neurological outcomes. The clinical history and examination are often not adequately sensitive or specific for detection. Study Objectives: Because this population stands to benefit from acute interventions such as intravenous and intra-arterial tissue plasminogen activator, mechanical thrombectomy, and intensive monitoring for neurologic deterioration, this study examined the sensitivity of non-contrast head computed tomography (NCCT) for diagnosing posterior fossa strokes in the emergency department. Methods: This study analyzed a prospectively collected database of acute ischemic stroke patients who underwent head NCCT within 30 h of symptom onset and who were subsequently found to have a posterior fossa infarct on brain magnetic resonance imaging (MRI) performed within 6 h of the NCCT. Results: There were 67 patients identified who had restricted diffusion on MRI in the posterior fossa. The National Institutes of Health Stroke Scale (NIHSS) scores ranged from 0 to 36, median 3. Only 28 patients had evidence of infarction on the initial NCCT scan. The timing of NCCT scans ranged from 1.2 to 28.9 h after symptom onset. The sensitivity of NCCT was 41.8% (95% confidence interval 30.1-54.4). The longest period of time between symptom onset and a negative NCCT with a subsequent positive diffusion-weighted imaging MRI was 26.7 h. Conclusions: Head NCCT imaging is frequently insensitive for detecting posterior fossa infarction. Temporal evolution of strokes in this distribution, coupled with beam-hardening artifact, may contribute to this limitation. When a posterior fossa stroke is suspected and the NCCT is non-diagnostic, MRI is the preferred imaging modality to exclude posterior fossa infarction. (C) 2012 Elsevier Inc. C1 [Hwang, David Y.; Silva, Gisele S.; Furie, Karen L.; Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hwang, David Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Hwang, David Y.; Furie, Karen L.; Greer, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Hwang, DY (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. FU Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; National Institutes of Health [K23 NS42720, P50NS051343] FX supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392 and National Institutes of Health grants K23 NS42720 and P50NS051343. The authors gratefully acknowledge the support of the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation. This work was made possible by the generous support of the Esther U. Sharp Fund, Conway Fellowship Fund, Lakeside Fund, and Levitt Fund. NR 35 TC 18 Z9 18 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 2012 VL 42 IS 5 BP 559 EP 565 DI 10.1016/j.jemermed.2011.05.101 PG 7 WC Emergency Medicine SC Emergency Medicine GA 944DW UT WOS:000304179600012 PM 22305149 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NIGRA PARS RETICULATA; SUBSTANTIA-NIGRA; NUCLEUS NEURONS; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; BASAL GANGLIA; IN-VITRO; CEREBRAL-CORTEX; MESSENGER-RNA; LOCALIZATION AB Dopamine depletion in experimental models of Parkinson's disease promotes burst firing of neurons in the subthalamic nucleus (STN) and substantia nigra zona reticulata (SNR). A synaptically generated form of burst firing has been shown to arise from complex excitatory postsynaptic currents (EPSCs) that are evoked in SNR neurons by STN stimulation. The present experiments were designed to characterize actions of dopamine on complex EPSCs in slices of rat brain. Using patch pipettes to record whole-cell currents under voltage clamp, dopamine (30 mu M) caused a reversible 64% reduction in complex EPSC charge. This effect was partially mimicked by D2, D3 and D4 receptor agonists, and the action of dopamine could be nearly completely blocked by the combined effects of the D2/3 antagonist sulpiride and the D4 antagonist L-745,870. Local application of dopamine to the STN caused a larger inhibition of the complex EPSC (55% reduction) than did dopamine application to the SNR (15% reduction). Simple, monophasic EPSCs, which were evoked in SNR neurons by stimulating the SNR close to the recording pipette, were inhibited to a smaller extent compared to complex EPSCs. Bursts of action potentials evoked in SNR neurons by STN stimulation were inhibited by dopamine to a greater extent than was spontaneous firing. These results show that dopamine D2-like receptors inhibit complex EPSCs and burst discharges in the SNR by acting within the STN to suppress transmission in the subthalamonigral pathway. Dopamine receptor-mediated inhibition of polysynaptic connections in the STN might be beneficial in the treatment of Parkinson's disease. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU United States Public Health Service [NS38715, NS060662]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by United States Public Health Service grants NS38715 and NS060662, and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 38 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 2012 VL 590 IS 10 BP 2273 EP 2284 DI 10.1113/jphysiol.2011.225672 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 942ZK UT WOS:000304090000014 PM 22371474 ER PT J AU Fisher, MC Hochberg, MC El-Taha, M Kremer, JM Peng, C Greenberg, JD AF Fisher, Mark C. Hochberg, Marc C. El-Taha, Muhammad Kremer, Joel M. Peng, Cheng Greenberg, Jeffrey D. CA CORRONA Investigators TI Smoking, Smoking Cessation, and Disease Activity in a Large Cohort of Patients with Rheumatoid Arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; SMOKING; DISEASE ACTIVITY ID CIGARETTE-SMOKING; SEVERITY; EXPRESSION; REGISTER AB Objective. While cigarette smoking is the best-studied environmental factor contributing to rheumatoid arthritis (RA), no study to date has examined the influence of smoking cessation on disease activity. We examined this relationship in an observational cohort of patients with RA in the United States. Methods. Patients enrolled in the Consortium of Rheumatology Researchers of North America registry (CORRONA) were stratified into never, former, and current smokers at enrollment. Current smokers were further stratified into continued and ceased smoking groups during their followup in the registry. The primary outcome was change in Clinical Disease Activity Index (CDAI) at last visit in a multivariate, random-effects regression model accounting for multiple timepoints. Results. At last visit, there was no significant change in CDAI between ceased smokers and continued smokers (coefficient -0.00091, SE 0.0033, p = 0.7834). The study did confirm prior cross-sectional studies that current smokers have worse disease activity than former or never smokers. Conclusion. In the short term, smoking cessation did not appear to influence change in disease activity over time. (First Release March 152012; J Rheumatol 2012;39:904-9; doi:10.3899/jrheum.110852) C1 [Fisher, Mark C.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Hochberg, Marc C.] Univ Maryland, Div Rheumatol & Clin Immunol, Baltimore, MD 21201 USA. [El-Taha, Muhammad; Peng, Cheng] Univ So Maine, Dept Math & Stat, Portland, ME 04103 USA. [Kremer, Joel M.] Albany Med Coll, Div Rheumatol, Albany, NY 12208 USA. [Greenberg, Jeffrey D.] New York Univ Hosp Joint Dis, Dept Rheumatol, New York, NY USA. RP Fisher, MC (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Yavvkey 2100,55 Fruit St, Boston, MA 02114 USA. EM mfisher6@partners.org FU US National Institutes of Health (NIH) [K23AR054412]; Arthritis Foundation; Bristol Myers Squibb; Amgen; Abbott; Centocor; Roche; Genentech; Lilly FX Dr. Greenberg is supported by research grants from the US National Institutes of Health (NIH; K23AR054412), the Arthritis Foundation, and Bristol Myers Squibb and has served on advisory boards for BMS, Centocor, Genentech, Roche, and UCB. Research support was provided to Dr. Kremer by Amgen, Abbott, Centocor, BMS, Roche, and Genentech, and honoraria from Abbott, Centocor, BMS, Roche, and Genentech. Dr. Hochberg served as a consultant for Amgen, Bristol Meyers Squibb, Roche, and UCB. CORRONA has received support from Abbott, Amgen, BMS, Centocor, Genentech, Lilly, and Roche. NR 18 TC 10 Z9 10 U1 1 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2012 VL 39 IS 5 BP 904 EP 909 DI 10.3899/jrheum.110852 PG 6 WC Rheumatology SC Rheumatology GA 941PO UT WOS:000303975300007 PM 22422494 ER PT J AU Streit, JJ Lenarz, CJ Shishani, Y McCrum, C Wanner, JP Nowinski, RJ Warner, JJP Gobezie, R AF Streit, Jonathan J. Lenarz, Christopher J. Shishani, Yousef McCrum, Christopher Wanner, J. P. Nowinski, R. J. Warner, Jon J. P. Gobezie, Reuben TI Pectoralis major tendon transfer for the treatment of scapular winging due to long thoracic nerve palsy SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Scapular winging; long thoracic nerve palsy; pectoralis major tendon transfer ID DYNAMIC STABILIZATION; WINGED SCAPULA; PARALYSIS; MUSCLE AB Background: Painful scapular winging due to chronic long thoracic nerve (LTN) palsy is a relatively rare disorder that can be difficult to treat. Pectoralis major tendon (PMT) transfer has been shown to be effective in relieving pain, improving cosmesis, and restoring function. However, the available body of literature consists of few, small-cohort studies, and more outcomes data are needed. Materials and methods: Outcomes of 26 consecutive patients with electromyelogram-confirmed LTN palsy who underwent direct (n = 4) or indirect transfer (n = 22) of the PMT for dynamic stabilization of the scapula were reviewed. All patients were followed up clinically for an average of 21.8 months (range, 3-62 months) with evaluations of active forward flexion, active external rotation, American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) pain score, and observation of scapular winging. Results: Preoperative to postoperative results included increases in the mean active forward flexion from 112 degrees to 149 degrees (P < .001) an in mean active external rotation from 53.8 degrees to 62.8 degrees (P = .045), an improvement in the mean ASES score from 28 to 67.0 (P < .001), and an improvement in the mean VAS pain score from 7.7 to 3.0 (P < .001). Recurrent scapular winging occurred in 5 patients. There was no difference in outcome by length of follow-up. Conclusions: PMT transfer is an effective treatment for painful scapular winging resulting from LTN palsy. This is the largest reported series of consecutive patients treated with PMT transfer for the correction of scapular winging. (c) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Streit, Jonathan J.; Lenarz, Christopher J.; Shishani, Yousef; McCrum, Christopher; Wanner, J. P.; Gobezie, Reuben] Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Case Shoulder & Elbow Serv, Cleveland, OH 44106 USA. [Nowinski, R. J.] Orthopaed & Neurol Consultants Inc, Columbus, OH USA. [Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Shoulder Surg,Dept Orthopaed Surg, Boston, MA USA. RP Gobezie, R (reprint author), 11100 Euclid Ave,HH5043, Cleveland, OH 44106 USA. EM clevelandshoulder@gmail.com FU NCRR NIH HHS [UL1 RR024989] NR 15 TC 11 Z9 11 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY PY 2012 VL 21 IS 5 BP 685 EP 690 DI 10.1016/j.jse.2011.03.025 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 944HU UT WOS:000304190700023 PM 21723148 ER PT J AU Niederman, R Richards, D Brands, W AF Niederman, Richard Richards, Derek Brands, Wolter TI The changing standard of care SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material ID DENTAL-CARIES; RECOMMENDATIONS; SEALANTS C1 [Niederman, Richard] Forsyth Inst, Ctr Evidence Based Dent, Cambridge, MA 02115 USA. [Richards, Derek] Ctr Evidence Based Dent, Oxford, England. [Richards, Derek] Univ Dundee, Hlth Serv & Res Unit, Dundee DD1 4HN, Scotland. [Brands, Wolter] Radboud Univ Nijmegen, Nijmegen Med Ctr, Nijmegen Dent Sch, Dept Prevent & Restorat Dent, Nijmegen, Netherlands. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, 245 1st St, Cambridge, MA 02115 USA. EM rniederman@forsyth.org FU NIDCR NIH HHS [R34 DE 022272]; NIMHD NIH HHS [U24 MD006964] NR 14 TC 8 Z9 8 U1 0 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2012 VL 143 IS 5 BP 434 EP 437 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 944FS UT WOS:000304185300001 PM 22547707 ER PT J AU Lakey, SL LaCroix, AZ Gray, SL Borson, S Williams, CD Calhoun, D Goveas, JS Smoller, JW Ockene, JK Masaki, KH Coday, M Rosal, MC Woods, NF AF Lakey, Susan L. LaCroix, Andrea Z. Gray, Shelly L. Borson, Soo Williams, Carla D. Calhoun, Darren Goveas, Joseph S. Smoller, Jordan W. Ockene, Judith K. Masaki, Kamal H. Coday, Mace Rosal, Milagros C. Woods, Nancy F. TI Antidepressant Use, Depressive Symptoms, and Incident Frailty in Women Aged 65 and Older from the Women's Health Initiative Observational Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE antidepressant use; frailty; depression; Women's Health Initiative ID PRIMARY-CARE PATIENTS; SUBSYNDROMAL DEPRESSION; POSTMENOPAUSAL WOMEN; RISK-FACTORS; LATER LIFE; MORTALITY; COMMUNITY; ADULTS; FALLS; DISABILITY AB OBJECTIVES To examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older. DESIGN Secondary analysis of the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort study. SETTING WHI-OS was conducted in 40 U.S. clinical centers. PARTICIPANTS Women aged 65 to 79, not frail at baseline. MEASUREMENTS Antidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 01, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self-report and physical measurements at baseline and Year 3. RESULTS Of 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios (ORs) ranged from 1.73 (95% confidence interval (CI) = 1.412.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.375.55). All durations of use were associated with incident frailty (<1 year OR = 1.95, 95% CI = 1.412.68; 13 years OR = 1.99, 95% CI = 1.452.74; >3 years OR = 1.60, 95% CI = 1.202.14). CONCLUSION In older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow-up. J Am Geriatr Soc 60:854-861, 2012. C1 [Lakey, Susan L.] Univ Washington, Sch Pharm, Dept Pharm, Seattle, WA 98195 USA. [Lakey, Susan L.] Fred Hutchinson Canc Res Ctr, Grp Hlth Res Inst, Seattle, WA 98104 USA. [LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98104 USA. [Calhoun, Darren] MedStar Res Inst, Phoenix, AZ USA. [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ockene, Judith K.; Rosal, Milagros C.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Masaki, Kamal H.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. [Coday, Mace] Univ Tennessee, Hlth Sci Ctr, Dept Preventat Med & Psychiat, Memphis, TN USA. [Woods, Nancy F.] Univ Washington, Sch Nursing, Dept Biobehav Nursing, Seattle, WA 98195 USA. [Williams, Carla D.] Howard Univ, Ctr Canc, Washington, DC 20059 USA. [Borson, Soo] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Lakey, SL (reprint author), Univ Washington, Sch Pharm, Dept Pharm, Box 357630, Seattle, WA 98195 USA. EM slakey@uw.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Institute of Aging [T32 AG027677] FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through Contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107 -26, 42129-32, and 44221. This work was supported by the T32 AG027677 fellowship sponsored by the National Institute of Aging. NR 47 TC 22 Z9 22 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 854 EP 861 DI 10.1111/j.1532-5415.2012.03940.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900006 PM 22568404 ER PT J AU Butler, D Kowall, NW Lawler, E Gaziano, J Driver, JA AF Butler, Daniel Kowall, Neil W. Lawler, Elizabeth Michael Gaziano, J. Driver, Jane A. TI Underuse of Diagnostic Codes for Specific Dementias in the Veterans Affairs New England Healthcare System SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; coding; dementia; diagnosis; veterans ID ALZHEIMERS-DISEASE; MANAGEMENT; PREVALENCE; CRITERIA; POPULATION AB OBJECTIVES To examine the specificity of dementia coding in large populations. DESIGN Retrospective cohort and chart review study of dementia diagnosis. SETTING U.S. Department of Veterans Affairs (VA) New England healthcare system. PARTICIPANTS Veterans aged 50 and older given outpatient visit codes for dementia between January 1, 2000, and December 31, 2009. MEASUREMENTS The frequency of the code dementia not otherwise specified (DNOS) as a first and final diagnosis was determined. DNOS use was examined according to provider type and geographic location. The medical records of 100 individuals with unspecified dementia were reviewed to determine their underlying diagnoses and describe their examination. RESULTS Twenty-two thousand fifty veterans diagnosed with dementia were identified over 10 years of follow-up. One-third of all cases had no specific dementia code (n = 6,659). DNOS was the most commonly used code as a first dementia diagnosis (42.5%) and was second only to Alzheimer's type dementia (35.8%) as a final diagnosis. Individuals who saw geriatricians and neurologists were most likely to have a specific dementia diagnosis, and DNOS use was lowest in centers with the most dementia specialists. Only 12% of primary care physicians performed cognitive testing the first time they used the DNOS code, compared with 98% of specialists. Nearly half of individuals with a persistent diagnosis of DNOS met criteria for a specific dementia. CONCLUSION Substantial overuse was found of nonspecific dementia codes in the VA New England healthcare system, leading to an underestimation of the prevalence of Alzheimer's disease and other dementias. System-based changes in dementia coding and greater access to dementia specialists may help improve diagnostic specificity. J Am Geriatr Soc 60:910-915, 2012. C1 [Butler, Daniel] Univ Arizona, Coll Med, Tucson, AZ USA. [Kowall, Neil W.] Dept Neurol, Boston, MA USA. [Kowall, Neil W.; Lawler, Elizabeth; Michael Gaziano, J.; Driver, Jane A.] New England Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Kowall, Neil W.] Sch Med, Dept Neurol, Boston, MA USA. [Kowall, Neil W.] Sch Med, Alzheimers Dis Ctr, Boston, MA USA. [Lawler, Elizabeth; Michael Gaziano, J.; Driver, Jane A.] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Lawler, Elizabeth] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lawler, Elizabeth; Michael Gaziano, J.; Driver, Jane A.] Harvard Univ, Sch Med, Dept Med, Div Aging,Brigham & Womens Hosp, Boston, MA USA. RP Driver, JA (reprint author), VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM jdriver@partners.org RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU VA Career Development award; American Federation for Aging Research MSTAR; VA Cooperative Studies Program FX This research was funded by a VA Career Development award (JAD), and an American Federation for Aging Research MSTAR grant (DB). The Massachusetts Veteran's Research and Information Center is supported by the VA Cooperative Studies Program. NR 25 TC 8 Z9 8 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 910 EP 915 DI 10.1111/j.1532-5415.2012.03933.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900013 PM 22587853 ER PT J AU Xu, HP Covinsky, KE Stallard, E Thomas, J Sands, LP AF Xu, Huiping Covinsky, Kenneth E. Stallard, Eric Thomas, Joseph, III Sands, Laura P. TI Insufficient Help for Activity of Daily Living Disabilities and Risk of All-Cause Hospitalization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE activities of daily living; disability; hospitalization; insufficient help ID UNMET NEED; OLDER-ADULTS; PERSONAL ASSISTANCE; ELDERLY-PATIENTS; CARE; SERVICES; HOME; CONSEQUENCES; VALIDATION; CAREGIVERS AB OBJECTIVES To determine whether insufficient help for activity of daily living (ADL) disability, a potentially modifiable condition, significantly increases disabled older adults risk of future hospital admissions. DESIGN Prospective study. SETTING Community-living participants with ADL disabilities in the 1994, 1999, and 2004 National Long-Term Care Survey (NLTCS). PARTICIPANTS Medicare recipients with one or more ADL disabilities completed 5,884 surveys. MEASUREMENTS Times to hospital admission in the year after the NLTCS community survey were obtained from linked Medicare claims. Insufficient ADL help for each ADL limitation was determined from a series of questions common to the three NLTCS community surveys. RESULTS Insufficient help for one or more ADL limitations was reported in 22% of surveys. Respondents to 3,629 surveys did not experience a hospital admission in the year after the survey. Of the remaining 2,255 surveys, one admission occurred for 382 surveys, two admissions for 525 surveys, three admissions for 193 surveys, and four or more admissions for 155 surveys. Participants reporting insufficient help were 14% (hazard ratio = 1.14, 95% confidence interval = 1.011.28) more likely to experience one or more hospitalizations than those who did not report insufficient help after controlling for demographic characteristics, comorbidities, prior hospitalizations, and level of ADL disability. CONCLUSION Self-reports of insufficient help provide prognostic information beyond what typical health assessments can capture. Greater recognition and referral for insufficient help for ADL disability may result in lower rates of hospitalization in a population that is at high risk of hospitalization. J Am Geriatr Soc 60:927-933, 2012. C1 [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. [Xu, Huiping] Indiana Univ, Sch Med, Indianapolis, IN USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Stallard, Eric] Duke Univ, Ctr Populat Hlth & Aging, Durham, NC USA. [Thomas, Joseph, III] Purdue Univ, Ctr Aging & Life Course, Ctr Hlth Outcomes Res & Policy, Regenstrief Ctr Healthcare Engn,Coll Pharm, W Lafayette, IN 47907 USA. RP Sands, LP (reprint author), Purdue Univ, Sch Nursing, 502 N Univ St, W Lafayette, IN 47907 USA. EM lsands@purdue.edu RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU National Institutes of Health [R01AG034160] FX This research was supported by Grant R01AG034160 from the National Institutes of Health to Dr. Sands. Drs. Xu, Covinsky, Thomas, and Sands and Prof. Stallard do not have any financial interest or personal conflicts with the methodologies discussed in this manuscript. NR 31 TC 9 Z9 10 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 927 EP 933 DI 10.1111/j.1532-5415.2012.03926.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900016 PM 22587855 ER PT J AU Finlayson, E Zhao, SJ Boscardin, WJ Fries, BE Landefeld, CS Dudley, RA AF Finlayson, Emily Zhao, Shoujun Boscardin, W. John Fries, Brant E. Landefeld, C. Seth Dudley, R. Adams TI Functional Status After Colon Cancer Surgery in Elderly Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE functional decline; nursing home residents; surgery ID CARE; COMORBIDITY; ADULTS; MDS AB OBJECTIVES To determine functional status and mortality rates after colon cancer surgery in older nursing home residents. DESIGN Retrospective cohort study. SETTING Nursing homes in the United States. PARTICIPANTS Six thousand eight hundred twenty-two nursing home residents aged 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005. MEASUREMENTS Changes in functional status were assessed before and after surgery using the Minimum Data Set Activity of Daily Living (MDS-ADL) summary scale, a 28-point scale in which score increases as functional dependence increases. Regression techniques were used to identify patient characteristics associated with mortality and functional decline 1 year after surgery. RESULTS On average, residents who underwent colectomy had a 3.9-point worsening in MDS-ADL score at 1 year. One year after surgery, rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (=80 vs 6569, adjusted relative risk (ARR) = 1.53, 95% confidence interval (CI) = 1.152.04, P < .001), readmission after surgical hospitalization (ARR = 1.15, 95% CI = 1.031.29, P = .02), surgical complications (ARR = 1.11, 95% CI = 1.021.21, P = .01), and functional decline before surgery (ARR = 1.21, 95% CI = 1.111.32, P < .001) were associated with functional decline at 1 year. CONCLUSION Mortality and sustained functional decline are common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population. J Am Geriatr Soc 60:967-973, 2012. C1 [Finlayson, Emily; Dudley, R. Adams] Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94118 USA. [Finlayson, Emily; Zhao, Shoujun] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Boscardin, W. John; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Boscardin, W. John; Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. [Fries, Brant E.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. [Fries, Brant E.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Dudley, R. Adams] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Finlayson, E (reprint author), Philip R Lee Inst Hlth Policy Studies, 3333 Calif St, San Francisco, CA 94118 USA. EM emily.finlayson@ucsfmedctr.org FU National Institute on Aging [K08AG028965] FX Dr. Finlayson was supported by a National Institute on Aging/Paul B. Beeson Clinical Scientist Development Award in Aging (K08AG028965). NR 19 TC 27 Z9 27 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2012 VL 60 IS 5 BP 967 EP 973 DI 10.1111/j.1532-5415.2012.03915.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 942HE UT WOS:000304033900023 PM 22428583 ER PT J AU Rosen, RC Connor, MK Miyasato, G Link, C Shifren, JL Fisher, WA Derogatis, LR Schobelock, MJ AF Rosen, Raymond C. Connor, Megan K. Miyasato, Gavin Link, Carol Shifren, Jan L. Fisher, William A. Derogatis, Leonard R. Schobelock, Michael J. TI Sexual Desire Problems in Women Seeking Healthcare: A Novel Study Design for Ascertaining Prevalence of Hypoactive Sexual Desire Disorder in Clinic-Based Samples of US Women SO JOURNAL OF WOMENS HEALTH LA English DT Article ID FUNCTION INDEX FSFI; UNITED-STATES; DISTRESS; VALIDATION; DYSFUNCTION; INSTRUMENT; HSDD AB Background: Hypoactive sexual desire disorder (HSDD) has been estimated to occur in 10%-15% of adult women in large population-representative and community-based studies. However, none of these studies have used in-person diagnostic interview assessment to rule out alternative diagnoses, nor has the impact of other health conditions or help-seeking experiences been investigated. The current study aimed to determine the prevalence of generalized acquired HSDD in women aged >= 18 who attended primary care or obstetrics and gynecology clinics for nonurgent clinic visits in the United States. Methods: A total of 701 women were enrolled at 20 clinical sites across the United States between June 11, 2010, and October 15, 2010. Participants completed a two-part self-administered questionnaire, and a validated, structured, in-person diagnostic interview, conducted by a trained health professional was used for diagnosing HSDD according to DSM-IV-TR criteria. Results: Fifty-two women (7.4%) were assigned a diagnosis of generalized acquired HSDD. Prevalence was lower in minority and postmenopausal women. Level of education and other sociodemographic factors did not appear to differentiate between women with and without HSDD. A marked increase in HSDD prevalence was noted in the perimenopausal (i.e., 40-49 years) and immediate postmenopausal (i.e., 50-59) age groups. Of the women diagnosed with HSDD, 53% had sought care from a health professional for HSDD. Conclusions: In this sample of women recruited in the clinical care setting, we observed an overall prevalence rate of 7.4% of acquired, generalized HSDD, with markedly increased prevalence in midlife women. C1 [Rosen, Raymond C.; Connor, Megan K.; Miyasato, Gavin; Link, Carol] New England Res Inst Inc, Dept Epidemiol, Watertown, MA 02472 USA. [Shifren, Jan L.] Massachusetts Gen Hosp, Vincent OB GYN Serv, Boston, MA 02114 USA. [Fisher, William A.] Univ Western Ontario, Dept Psychol, London, ON N6A 3K7, Canada. [Fisher, William A.] Univ Western Ontario, Dept Obstet & Gynaecol, London, ON N6A 3K7, Canada. [Derogatis, Leonard R.] Sheppard Pratt Johns Hopkins Dept Psychiat & Beha, Ctr Sexual Med, Baltimore, MD USA. [Schobelock, Michael J.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Rosen, RC (reprint author), New England Res Inst Inc, Dept Epidemiol, 9 Galen St, Watertown, MA 02472 USA. EM rrosen@neriscience.com FU Boehringer Ingelheim Pharmaceuticals, Inc. FX We gratefully acknowledge the contributions of Heather Cochran, M.A.T., Jennifer Yee, Blandyna Williams, and Max Krauthamer from New England Research Institutes, Inc., and Saeeduddin Ahmed, M.D., Michael Sand, Ph.D., M.P.H., and Robert Pyke, M.D., Ph.D., from Boehringer Ingelheim Pharmaceuticals, Inc. Funding for the study was provided by Boehringer Ingelheim Pharmaceuticals, Inc.; R.C.R. is a consultant to Boehringer Ingelheim Pharmaceuticals, Inc., Palatin Technologies, and Johnson and Johnson. M.K.C., G.M., C.L., and L.R.G. have no conflicts of interest to declare. W.A.F. has served as a consultant and advisory board member for Boehringer Ingelheim Pharmaceuticals, Inc., Bayer, and Merck. J.L.S. is a consultant for New England Research Institutes, Inc., and has research support from Boehringer Ingelheim Pharmaceuticals, Inc. M.J.S. is an employee of Boehringer Ingelheim Pharmaceuticals, Inc. NR 27 TC 5 Z9 5 U1 0 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2012 VL 21 IS 5 BP 505 EP 515 DI 10.1089/jwh.2011.3002 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 942OO UT WOS:000304054900006 PM 22229714 ER PT J AU Weisberg, E Azab, AK Manley, PW Kung, AL Christie, AL Bronson, R Ghobrial, IM Griffin, JD AF Weisberg, E. Azab, A. K. Manley, P. W. Kung, A. L. Christie, A. L. Bronson, R. Ghobrial, I. M. Griffin, J. D. TI Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib SO LEUKEMIA LA English DT Article DE plerixafor; nilotinib; stem cell mobilization; chronic myeloid leukemia; stromal-mediated chemoresistance; bone marrow microenvironment ID CHRONIC MYELOID-LEUKEMIA; ELM ERYTHROLEUKEMIA-CELLS; MULTIPLE-MYELOMA; STROMAL CELLS; BCR-ABL; INDUCED PROLIFERATION; PREVENT APOPTOSIS; UP-REGULATION; IMATINIB; SURVIVAL AB Drug resistance is a growing area of concern. It has been shown that a small, residual pool of leukemic CD34+ progenitor cells can survive in the marrow microenvironment of chronic myeloid leukemia (CML) patients after years of kinase inhibitor treatment. Bone marrow (BM) stroma has been implicated in the long-term survival of leukemic cells, and contributes to the expansion and proliferation of both transformed and normal hematopoietic cells. Mechanistically, we found that CML cells expressed CXCR4, and that plerixafor diminished BCR-ABL-positive cell migration and reduced adhesion of these cells to extra cellular-matrix components and to BM stromal cells in vitro. Moreover, plerixafor decreased the drug resistance of CML cells induced by co-culture with BM stromal cells in vitro. Using a functional mouse model of progressive and residual disease, we demonstrated the ability of the CXCR4 inhibitor, plerixafor, to mobilize leukemic cells in vivo, such that a plerixafor-nilotinib combination reduced the leukemia burden in mice significantly below the baseline level suppression exhibited by a moderate-to-high dose of nilotinib as single agent. These results support the idea of using CXCR4 inhibition in conjunction with targeted tyrosine kinase inhibition to override drug resistance in CML and suppress or eradicate residual disease. C1 [Weisberg, E.; Azab, A. K.; Ghobrial, I. M.; Griffin, J. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Manley, P. W.] Novartis Pharma AG, Basel, Switzerland. [Kung, A. L.; Christie, A. L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kung, A. L.; Christie, A. L.] Childrens Hosp, Boston, MA 02115 USA. [Bronson, R.] Harvard Univ, Sch Med, Dept Pathol, Rodent Histopathol Core, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mailstop Mayer 540, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu; james_griffin@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NIH [CA66996] FX JDG is supported by NIH grant CA66996. JDG has a financial interest with Novartis Pharma AG. JDG and ALK have a financial interest with Novartis Pharma AG. PWM is an employee of Novartis. NR 42 TC 53 Z9 55 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2012 VL 26 IS 5 BP 985 EP 990 DI 10.1038/leu.2011.360 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 940IP UT WOS:000303883500017 PM 22182920 ER PT J AU Mahindra, A Kalaycio, ME Vela-Ojeda, J Vesole, DH Zhang, MJ Li, P Berenson, JR Bird, JM Dispenzieri, A Gajewski, JL Gale, RP Holmberg, L Kumar, S Kyle, RA Lazarus, HM Lonial, S Mikhael, J Milone, GA Munker, R Nath, R Saccaro, S To, LB Vogl, DT Wirk, B Hari, P AF Mahindra, A. Kalaycio, M. E. Vela-Ojeda, J. Vesole, D. H. Zhang, M-J Li, P. Berenson, J. R. Bird, J. M. Dispenzieri, A. Gajewski, J. L. Gale, R. P. Holmberg, L. Kumar, S. Kyle, R. A. Lazarus, H. M. Lonial, S. Mikhael, J. Milone, G. A. Munker, R. Nath, R. Saccaro, S. To, L. Bik Vogl, D. T. Wirk, B. Hari, P. TI Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research SO LEUKEMIA LA English DT Article DE primary plasma cell leukemia; stem cell transplant; overall survival ID MULTIPLE-MYELOMA; BORTEZOMIB; DEXAMETHASONE; THERAPY; LENALIDOMIDE; INDUCTION; MELPHALAN; GVHD AB There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n = 97) or allogeneic (n = 50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit. C1 [Li, P.; Hari, P.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Mahindra, A.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Kalaycio, M. E.] Cleveland Clin Fdn, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA. [Vela-Ojeda, J.] Hosp Especialidades CMN La RAZA IMSS, Dept Hematol & Internal Med, Mexico City, DF, Mexico. [Vesole, D. H.] Hackensack Univ, Med Ctr, Dept Med, Hackensack, NJ USA. [Zhang, M-J] Med Coll Wisconsin, Dept Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Berenson, J. R.] Inst Myeloma & Bone Canc Res, Dept Med, Los Angeles, CA USA. [Bird, J. M.] Bristol Childrens Hosp, Dept Haematol, Bristol, Avon, England. [Dispenzieri, A.; Kumar, S.; Kyle, R. A.] Mayo Clin Rochester, Dept Hematol, Rochester, MN USA. [Gajewski, J. L.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Gale, R. P.] Celgene Corp, Dept Hematol & Oncol, Summit, NJ USA. [Holmberg, L.] Fred Hutchinson Canc Res Ctr, Dept Hematol, Seattle, WA 98104 USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [Lonial, S.] Emory Univ Hosp, Dept Med, Atlanta, GA 30322 USA. [Mikhael, J.] Mayo Clin Arizona, Dept Hematol & Oncol, Scottsdale, AZ USA. [Milone, G. A.] FUNDALEU, Dept Oncohematol, Buenos Aires, DF, Argentina. [Munker, R.] LSU Hlth Sci Ctr, Dept Hematol & Oncol, Shreveport, LA USA. [Nath, R.] Univ Massachusetts, Med Ctr, Dept Hematol & Oncol, Worcester, MA USA. [Saccaro, S.] St Frances Cabrini Ctr Canc Care, Dept Med, Alexandria, LA USA. [To, L. Bik] Royal Adelaide Hosp, Dept Haematol, Adelaide, SA 5000, Australia. [Vogl, D. T.] Univ Penn, Dept Hematol & Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Wirk, B.] Univ Florida, Shands Hosp, Dept Hematol & Oncol, Gainesville, FL USA. RP Hari, P (reprint author), Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU Public Health Service from National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) [U24-CA76518]; National Institute of Allergy and Infectious Diseases (NIAID) [U24-CA76518]; NHLBI [5U01HL069294]; NCI [5U01HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos, Inc.; Amgen, Inc FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Allos, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Eisai, Inc.; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Vidacare Corporation; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. NR 18 TC 18 Z9 19 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2012 VL 26 IS 5 BP 1091 EP 1097 DI 10.1038/leu.2011.312 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 940IP UT WOS:000303883500029 PM 22042147 ER PT J AU Sukhdeo, K Mani, M Hideshima, T Takada, K Pena-Cruz, V Mendez, G Ito, S Anderson, KC Carrasco, DR AF Sukhdeo, K. Mani, M. Hideshima, T. Takada, K. Pena-Cruz, V. Mendez, G. Ito, S. Anderson, K. C. Carrasco, D. R. TI beta-catenin is dynamically stored and cleared in multiple myeloma by the proteasome-aggresome-autophagosome-lysosome pathway SO LEUKEMIA LA English DT Letter ID CELLS C1 [Sukhdeo, K.] Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA. [Mani, M.; Hideshima, T.; Takada, K.; Pena-Cruz, V.; Anderson, K. C.; Carrasco, D. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hideshima, T.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Mendez, G.; Carrasco, D. R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ito, S.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Sukhdeo, K (reprint author), Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44106 USA. EM ruben_carrasco@dfci.harvard.edu OI Sukhdeo, Kumar /0000-0001-8725-6081 FU NCI NIH HHS [R01 CA151391, P50 CA100707, R01CA151391-01] NR 15 TC 14 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2012 VL 26 IS 5 BP 1116 EP 1119 DI 10.1038/leu.2011.303 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 940IP UT WOS:000303883500035 PM 22051532 ER PT J AU MacMahon, PJ Palmer, WE AF MacMahon, Peter J. Palmer, William E. TI Magnetic Resonance Imaging in Glenohumeral Instability SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE Shoulder; Glenohumeral instability; MR Imaging; MR arthrography; Labrum; Glenohumeral ligaments; Bankart ID ANTERIOR SHOULDER INSTABILITY; INFERIOR CAPSULAR SHIFT; HILL-SACHS LESION; ARTHROSCOPIC CAPSULOLABRAL REPAIR; ARTICULAR-CARTILAGE LESIONS; ROTATOR INTERVAL CAPSULE; SLEEVE AVULSION LESION; MR ARTHROGRAPHY; MULTIDIRECTIONAL INSTABILITY; POSTERIOR INSTABILITY AB The glenohumeral joint enables tremendous range of motion at the expense of stability. Functional stability is maintained by the synchronous coordination of complex static and dynamic structures. Symptomatic glenohumeral instability most often results from injury to the inferior labral-ligamentous complex, the primary passive stabilizer of the shoulder. This article reviews the structures important in glenohumeral stabilization and illustrates their normal appearances and the abnormalities associated with anterior, posterior, and multidirectional instability. These lesions are discussed in the context of therapeutic decision making. C1 [MacMahon, Peter J.; Palmer, William E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP MacMahon, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6030, Boston, MA 02114 USA. EM petermacmahon@yahoo.com NR 145 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD MAY PY 2012 VL 20 IS 2 BP 295 EP + DI 10.1016/j.mric.2012.01.003 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 941IL UT WOS:000303956800012 PM 22469405 ER PT J AU Lindsay, AC Sussner, KM Greaney, M Wang, ML Davis, R Peterson, KE AF Lindsay, Ana Cristina Sussner, Katrina Mucha Greaney, Mary Wang, Monica L. Davis, Rachel Peterson, Karen E. TI Using Qualitative Methods to Design a Culturally Appropriate Child Feeding Questionnaire for Low-Income, Latina Mothers SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Childhood overweight and obesity; Latina; Child feeding practices ID PHYSICAL-ACTIVITY; POSTPARTUM WOMEN; SOCIAL-CONTEXT; HEALTH; FAMILY; OBESITY; ACCULTURATION; OVERWEIGHT; BELIEFS; PERSPECTIVES AB Obesity rates remain high among children in the United States (US), but children of low-income, minority families are at particularly high risk. Latinos are the largest and most rapidly growing US population group. Effective strategies will require attention to a wide array of culturally mediated variables that influence child feeding practices through the social contexts in which behaviors take place. This paper presents the design and implementation of a qualitative study examining low-income, Latina mothers' perceptions of child weight status and feeding practices, and their associations with the development of overweight in children. Guided by the social ecologic model and social contextual model on the role of the family in mediating health behavior, the Latina Mother Child Feeding Practices (LMCFP) study provided a systematic exploration of the influence of social class, culture, and environmental factors associated with mothers' perceptions of child overweight on feeding practices and behaviors. The design for this qualitative study consisted of three sequential phases: focus groups, in-depth interviews and cognitive interviews with Latina mothers conducted by Spanish-speaking researchers. Results showed the important role of socio-cultural factors in influencing Latina mothers' child feeding practices. In the short-term, this research yielded information to develop a child-feeding questionnaire appropriate for low-income, Latina mothers. Findings have important implications in developing nutrition education strategies for child health promotion that account for the social and cultural context of minority, low-income caregivers. C1 [Lindsay, Ana Cristina] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Sussner, Katrina Mucha] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Greaney, Mary] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Wang, Monica L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Davis, Rachel] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth, Ann Arbor, MI 48109 USA. RP Lindsay, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM alindsay@hsph.harvard.edu; katarina.sussner@mssm.edu; Mary_Greaney@DFCI.HARVARD.EDU; mlwang@hsph.harvard.edu; reda@umich.edu FU NCI NIH HHS [R03 CA108347-02, R03 CA108347, R03 CA108347-01] NR 36 TC 5 Z9 7 U1 1 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD MAY PY 2012 VL 16 IS 4 BP 860 EP 866 DI 10.1007/s10995-011-0804-y PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 934GY UT WOS:000303433400016 PM 21512780 ER PT J AU Pennock, S Kazlauskas, A AF Pennock, Steven Kazlauskas, Andrius TI Vascular Endothelial Growth Factor A Competitively Inhibits Platelet-Derived Growth Factor (PDGF)-Dependent Activation of PDGF Receptor and Subsequent Signaling Events and Cellular Responses SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY; RETINAL-DETACHMENT; IN-VIVO; DIABETIC-RETINOPATHY; CRYSTAL-STRUCTURE; ALPHA RECEPTOR; VITREOUS-HUMOR; EPH RECEPTORS; CELLS; EXPRESSION AB Certain platelet-derived growth factor (PDGF) isoforms are associated with proliferative vitreoretinopathy (PVR), a sight-threatening complication that develops in a subset of patients recovering from retinal reattachment surgery. Although these PDGF isoforms are abundant in the vitreous of patients and experimental animals with PVR, they make only a minor contribution to activating PDGF receptor alpha (PDGFR alpha) and driving experimental PVR. Rather, growth factors outside of the PDGF family are the primary (and indirect) agonists of PDGFR alpha. These observations beg the question of why vitreal PDGFs fail to activate PDGFR alpha. We report here that vitreous contains an inhibitor of PDGF-dependent activation of PDGFR alpha and that a major portion of this inhibitory activity is due to vascular endothelial cell growth factor A (VEGF-A). Furthermore, recombinant VEGF-A competitively blocks PDGF-dependent binding and activation of PDGFR, signaling events, and cellular responses. These findings unveil a previously unappreciated relationship between distant members of the PDGF/VEGF family that may contribute to pathogenesis of a blinding eye disease. C1 [Pennock, Steven; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02115 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02115 USA. EM ak@eri.harvard.edu FU U.S. Department of Defense [WB1XWH-10-1-0392]; National Institutes of Health [EY012509] FX Funding for this research was provided by grants from the U.S. Department of Defense (WB1XWH-10-1-0392) and the National Institutes of Health (EY012509) to A.K. NR 61 TC 27 Z9 28 U1 0 U2 4 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 PY 2012 VL 32 IS 10 BP 1955 EP 1966 DI 10.1128/MCB.06668-11 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 939TP UT WOS:000303840100016 PM 22431518 ER PT J AU Cannuscio, CC Alley, DE Pagan, JA Soldo, B Krasny, S Shardell, M Asch, DA Lipman, TH AF Cannuscio, Carolyn C. Alley, Dawn E. Pagan, Jose A. Soldo, Beth Krasny, Sarah Shardell, Michelle Asch, David A. Lipman, Terri H. TI Housing strain, mortgage foreclosure, and health SO NURSING OUTLOOK LA English DT Article DE Housing security; Housing strain; Material resources; Housing policy; Economic strain; Health disparities AB Background: Foreclosure rates have risen rapidly since 2005, reaching historically high levels. The purpose of this study was to examine the health implications of the current housing crisis. Methods: We conducted a cross-sectional online consumer panel survey including residents of California, Arizona, Nevada, and Florida (n = 798) to determine the feasibility of contacting distressed homeowners via the Internet and to assess mental and physical health among respondents across the spectrum from those having no housing strain to those in loan default or home foreclosure. Results: Homeowners in default or foreclosure exhibited poorer mental health and more physical symptoms than renters, homeowners with moderate strain, and homeowners with no strainofollowing a gradient that was consistent across multiple health indicators. Conclusions: Internet panel sampling was an efficient method of contacting distressed homeowners. Record-high foreclosure rates may have broad implications for nursing and public health. Homeowners in default or foreclosure represent an identifiable high-risk group that may benefit from coordinated, affordable health and social services. Cite this article: Cannuscio, C. C., Alley, D. E., Pagan, J. A., Soldo, B., Krasny, S., Shardell, M., Asch, D. A., & Lipman, T. H. (2012, JUNE). Housing strain, mortgage foreclosure, and health. Nursing Outlook, 60(3), 134-142. doi:10.1016/j.outlook.2011.08.004. C1 [Lipman, Terri H.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Lipman, Terri H.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Shardell, Michelle; Asch, David A.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Cannuscio, Carolyn C.; Shardell, Michelle] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol Publ Hlth, Baltimore, MD 21201 USA. [Pagan, Jose A.] Univ N Texas Hlth Sci Ctr, Dept Hlth Management & Policy, Ft Worth, TX USA. [Soldo, Beth] Univ Penn, Populat Aging Res Ctr, Ctr Populat Studies, Philadelphia, PA 19104 USA. [Krasny, Sarah] Univ Penn, Huntsman Program Int Studies & Business, Sch Arts & Sci, Philadelphia, PA 19104 USA. [Krasny, Sarah] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Lipman, TH (reprint author), Univ Penn, Sch Nursing, Room 224,Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM lipman@nursing.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation Health Society; University of Pennsylvania Center for Public Health Initiatives; Office of Practice and Community Affairs, University of Pennsylvania School of Nursing; Department of Veterans Affairs, Office of Health Services Research and Development, Center for Health Equity Research and Promotion FX We gratefully acknowledge the support provided by Jeannette Schroeder, as well as funding support from the Robert Wood Johnson Foundation Health & Society Scholars Program, University of Pennsylvania Center for Public Health Initiatives, and the Office of Practice and Community Affairs, University of Pennsylvania School of Nursing, Investment for the Future Funds. Drs. Asch and Cannusio are supported by the Department of Veterans Affairs, Office of Health Services Research and Development, Center for Health Equity Research and Promotion. The contents of this article do not represent the views of the Department of Veteran Affairs or the United States government. NR 0 TC 21 Z9 22 U1 1 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAY-JUN PY 2012 VL 60 IS 3 BP 134 EP 142 DI 10.1016/j.outlook.2011.08.004 PG 9 WC Nursing SC Nursing GA 944DK UT WOS:000304178400006 PM 22000689 ER PT J AU Ward, PS Cross, JR Lu, C Weigert, O Abel-Wahab, O Levine, RL Weinstock, DM Sharp, KA Thompson, CB AF Ward, P. S. Cross, J. R. Lu, C. Weigert, O. Abel-Wahab, O. Levine, R. L. Weinstock, D. M. Sharp, K. A. Thompson, C. B. TI Identification of additional IDH mutations associated with oncometabolite R(-)-2-hydroxyglutarate production SO ONCOGENE LA English DT Article DE IDH1; IDH2; 2-hydroxyglutarate; oncometabolite; NADPH ID ACUTE MYELOID-LEUKEMIA; HIGH-GRADE GLIOMAS; ISOCITRATE; MECHANISM; DISEASE AB Mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) or its mitochondrial homolog IDH2 can lead to R(-)-2-hydroxyglutarate (2HG) production. To date, mutations in three active site arginine residues, IDH1 R132, IDH2 R172 and IDH2 R140, have been shown to result in the neomorphic production of 2HG. Here we report on three additional 2HG-producing IDH1 mutations: IDH1 R100, which is affected in adult glioma, IDH1 G97, which is mutated in colon cancer cell lines and pediatric glioblastoma, and IDH1 Y139. All these new mutants stereospecifically produced 2HG's (R) enantiomer. In contrast, we find that the IDH1 SNPs V71I and V178I, as well as a number of other single-sample reports of IDH non-synonymous mutation, did not elevate cellular 2HG levels in cells and retained the wild-type ability for isocitrate-dependent NADPH production. Finally, we report the existence of additional rare, but recurring mutations found in lymphoma and thyroid cancer, which while failing to elevate 2HG nonetheless displayed loss of function, indicating a possible tumorigenic mechanism for a non-2HG-producing subset of IDH mutations in some malignancies. These data broaden our understanding of how IDH mutations may contribute to cancer through either neomorphic R(-)-2HG production or reduced wildtype enzymatic activity, and highlight the potential value of metabolite screening in identifying IDH-mutated tumors associated with elevated oncometabolite levels. Oncogene (2012) 31, 2491-2498; doi: 10.1038/onc.2011.416; published online 26 September 2011 C1 [Ward, P. S.; Cross, J. R.; Lu, C.; Thompson, C. B.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. [Ward, P. S.; Lu, C.] Univ Penn, Abramson Canc Ctr, Dept Canc Biol, Philadelphia, PA 19104 USA. [Weigert, O.; Weinstock, D. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Abel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. [Sharp, K. A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Thompson, CB (reprint author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave,Room M110, New York, NY 10065 USA. EM thompsonc@mskcc.org RI Lu, Chao/E-8047-2012; Ward, Patrick/H-2361-2014; OI Ward, Patrick/0000-0001-6437-8174; Abdel-Wahab, Omar/0000-0002-3907-6171; Cross, Justin/0000-0002-6356-057X FU NCI; NIH; HHMI; Stand Up To Cancer Innovative Research Grant; American Cancer Society FX This work was supported in part by grants from the NCI and NIH. RL Levine is a HHMI Early Career Award Recipient and Geoffrey Beene Junior Faculty Chair at MSKCC. DM Weinstock is supported by a Stand Up To Cancer Innovative Research Grant and American Cancer Society Research Scholar Grant. NR 27 TC 76 Z9 77 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2012 VL 31 IS 19 BP 2491 EP 2498 DI 10.1038/onc.2011.416 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 941SP UT WOS:000303985300011 PM 21996744 ER PT J AU Wang, Y Sheng, Q Spillman, MA Behbakht, K Gu, H AF Wang, Y. Sheng, Q. Spillman, M. A. Behbakht, K. Gu, H. TI Gab2 regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells SO ONCOGENE LA English DT Article DE Gab2; PI3K; Zeb1; E-cadherin; EMT; ovarian cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER; SIGNAL-TRANSDUCTION; DOCKING PROTEIN; HIGH-FREQUENCY; PIK3CA GENE; METASTASIS; PROLIFERATION; TUMORIGENESIS; AMPLIFICATION AB Ovarian cancer, the most deadly gynecologic malignancy, is often diagnosed late and at the advanced stage when the cancer cells have already migrated and invaded into other tissues and organs. Better understanding of the mechanism of metastasis in ovarian cancer cells is essential to the design of effective therapy. In this study, we investigated the function of scaffolding adaptor protein Gab2 in ovarian cancer cells. Gab2 is found to be overexpressed in a subset of ovarian tumors and cancer cell lines. Gab2 expression mainly regulates the migratory behaviors of ovarian cancer cells. Overexpression of Gab2 promotes the migration and invasion, and downregulates E-cadherin expression in ovarian cancer cells with low-Gab2 expression. Conversely, knockdown of Gab2 expression inhibits the migration and invasion, and promotes E-cadherin expression in ovarian cancer cells with high-Gab2 expression. By expressing Gab2 wild-type and Gab2 mutants that are defective in activation of the PI3K and Shp2-Erk pathways, we find that Gab2 inhibits E-cadherin expression and enhances the expression of Zeb1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), and cell migration and invasion through the activation of the PI3K pathway. Knockdown of Zeb1 expression blocks Gab2-induced suppression of E-cadherin expression and increase in cell invasion. LY294002 and GDC-0941, inhibitors of PI3K, or Rapamycin, an inhibitor of PI3K downstream target mTOR, can reverse the effects of Gab2 on migration and invasion. Overall, our studies reveal that Gab2 overexpression, via activation of the PI3K-Zeb1 pathway, promotes characteristics of EMT in ovarian cancer cells. Oncogene (2012) 31, 2512-2520; doi:10.1038/onc.2011.435; published online 26 September 2011 C1 [Wang, Y.; Gu, H.] Univ Colorado Denver, Dept Pathol, Aurora, CO 80045 USA. [Sheng, Q.] Univ Colorado Denver, Div Bas Reprod Sci & Gynecol Oncol, Dept Obstet & Gynecol, Aurora, CO 80045 USA. [Spillman, M. A.; Behbakht, K.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Spillman, M. A.; Behbakht, K.] Harvard Univ, Sch Med, Boston, MA USA. RP Gu, H (reprint author), Univ Colorado Denver, Dept Pathol, Anschutz Med Campus,Mail Stop 8104,POB 6511, Aurora, CO 80045 USA. EM haihua.gu@ucdenver.edu OI Behbakht, Kian/0000-0003-4793-9958 FU Department of Pathology, University of Colorado, Anschutz Medical Campus; National Institutes of Health [R01-AI51612] FX We thank Dr Sam Mok for the HOSE lines. This work is supported by the Department of Pathology, University of Colorado, Anschutz Medical Campus and in part by the National Institutes of Health grant R01-AI51612 (to HG). NR 40 TC 31 Z9 39 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2012 VL 31 IS 20 BP 2512 EP 2520 DI 10.1038/onc.2011.435 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 944ID UT WOS:000304191800002 PM 21996746 ER PT J AU Chen, BB Glasser, JR Coon, TA Mallampalli, RK AF Chen, B. B. Glasser, J. R. Coon, T. A. Mallampalli, R. K. TI F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest SO ONCOGENE LA English DT Article DE ubiquitin; camodulin; lung ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; D1 DEGRADATION; CALCIUM-CONCENTRATION; REGULATORY ENZYME; CALMODULIN; CANCER; PHOSPHORYLATION; EXPRESSION; KINASE; IDENTIFICATION AB Dysregulated behavior of cell cycle proteins and their control by ubiquitin E3 ligases is an emerging theme in human lung cancer. Here, we identified and characterized the activity of a novel F-box protein, termed FBXL2, belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family. Ectopically expressed FBXL2 triggered G2/M-phase arrest, induced chromosomal anomalies and increased apoptosis of transformed lung epithelia by mediating polyubiquitination and degradation of the mitotic regulator, cyclin D3. Unlike other F-box proteins that target phosphodegrons within substrates, FBXL2 uniquely recognizes a canonical calmodulin (CaM)-binding motif within cyclin D3 to facilitate its polyubiquitination. CaM bound and protected cyclin D3 from FBXL2 by direct intermolecular competition with the F-box protein for access within this motif. The chemotherapeutic agent vinorelbine increased apoptosis of human lung carcinoma cells by inducing FBXL2 expression and cyclin D3 degradation, an effect accentuated by CaM knockdown. Depletion of endogenous FBXL2 stabilized cyclin D3 levels, accelerated cancer cell growth and increased cell viability after vinorelbine treatment. Last, ectopic expression of FBXL2 significantly inhibited the growth and migration of tumorogenic cells and tumor formation in athymic nude mice. These observations implicate SCFFBXL2 as an indispensible regulator of mitosis that serves as a tumor suppressor. Oncogene (2012) 31, 2566-2579; doi:10.1038/onc.2011.432; published online 24 October 2011 C1 [Mallampalli, R. K.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, UPMC Montefiore,Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, R. K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, UPMC Montefiore,Acute Lung Injury Ctr Excellence, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX We thank AF Stewart for critical review of the manuscript and helpful suggestions. This material is based upon work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376 and HL098174 (to RKM). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 56 TC 30 Z9 32 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2012 VL 31 IS 20 BP 2566 EP 2579 DI 10.1038/onc.2011.432 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 944ID UT WOS:000304191800007 PM 22020328 ER PT J AU Conner, TS Barrett, LF AF Conner, Tamlin S. Barrett, Lisa Feldman TI Trends in Ambulatory Self-Report: The Role of Momentary Experience in Psychosomatic Medicine SO PSYCHOSOMATIC MEDICINE LA English DT Article DE ecological momentary assessment; Positive and Negative Affect Schedule; emotion; memory bias; stress; questionnaires ID POSITIVE AFFECT; NEGATIVE AFFECT; DAILY-LIFE; RETROSPECTIVE EVALUATIONS; POLYMORPHISM 5-HTTLPR; SALIVARY CORTISOL; EMOTIONAL STYLE; DEFAULT NETWORK; DAILY MOOD; REAL-TIME AB In this article, we review the differences between momentary, retrospective, and trait self-report techniques and discuss the unique role that ambulatory reports of momentary experience play in psychosomatic medicine. After a brief historical review of self-report techniques, we discuss the latest perspective that links ambulatory self-reports to a qualitatively, different conscious self the "experiencing self"-which is functionally and neuroanatomically different from the "remembering" and "believing" selves measured through retrospective and trait questionnaires. The experiencing self functions to navigate current environments and is relatively more tied to the salience network and corporeal information from the body that regulates autonomic processes. As evidence, we review research showing that experiences measured through ambulatory assessment have stronger associations with cardiovascular reactivity, cortisol response, immune system function, and threat/reward biomarkers compared with memories or beliefs. By contrast, memories and beliefs play important roles in decision making and long-term planning, but they are less tied to bodily processes and more tied to default/long-term memory networks, which minimizes their sensitivity for certain research questions. We conclude with specific recommendations for using self-report questionnaires in psychosomatic medicine and suggest that intensive ambulatory assessment of experiences may provide greater sensitivity for connecting psychological with biologic processes. C1 [Conner, Tamlin S.] Univ Otago, Dept Psychol, Dunedin 9054, New Zealand. [Barrett, Lisa Feldman] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Northeastern Univ, Boston, MA USA. RP Conner, TS (reprint author), Univ Otago, Dept Psychol, POB 56, Dunedin 9054, New Zealand. EM tconner@psy.otago.ac.nz FU National Institutes of Health [DP1OD003312] FX Preparation of this article was supported by a National Institutes of Health Director's Pioneer Award (DP1OD003312) to Dr. Barrett. NR 129 TC 54 Z9 54 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY PY 2012 VL 74 IS 4 SI SI BP 327 EP 337 DI 10.1097/PSY.0b013e3182546f18 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 943MW UT WOS:000304128700002 PM 22582330 ER PT J AU Wagner, J Tennen, H Wolpert, H AF Wagner, Julie Tennen, Howard Wolpert, Howard TI Continuous Glucose Monitoring: A Review for Behavioral Researchers SO PSYCHOSOMATIC MEDICINE LA English DT Article DE continuous glucose monitoring; ambulatory monitoring; diabetes; glycemic; behavioral; glucose ID TYPE-1 DIABETIC-PATIENTS; BLOOD-GLUCOSE; SELF-CONTROL; CHILDREN; MOMENTARY; COMPLICATIONS; HYPERGLYCEMIA; HYPOGLYCEMIA; INDIVIDUALS; VARIABILITY AB Objective: Continuous glucose monitoring (CGM) systems collect and store glucose data in an ongoing fashion for several days at a time. The main advantage of CGM is that it can help identify fluctuations and trends that would otherwise go unnoticed with other glucose measures. Here, we provide a review of CGM for behavioral researchers. Methods: We begin with a brief review of diabetes and glucose measurement and then describe what CGM is and reference the commercial CGM systems currently available. We discuss the challenges involved in using CGM in behavioral research. We then present a broad overview of CGM in behavioral research, including data from ours and others' research programs. Finally, we cover some practical issues to be considered when using CGM, suggest reporting guidelines for the behavioral researcher, and offer suggestions for future research. Results: Only a handful of behavioral researchers are using CGM, although its use is increasing. The main ways that CGM is being used in behavioral research is to investigate basic biobehavioral processes, to assess the effects of behavioral interventions on diabetes control, and to use CGM itself as a behavior modification and teaching tool in diabetes self-management interventions. Conclusions: Continuous glucose monitoring holds promise to help behavioral researchers unravel the complex relationships among glucose and intrapersonal, interpersonal, and contextual factors. However, the uptake of CGM for this purpose is limited, and the possibilities for its use are largely unmet. We encourage behavioral researchers to implement CGM in their protocols and to do so in a way that maximizes its explanatory power. C1 [Wagner, Julie] Univ Connecticut, Ctr Hlth, Div Behav Sci & Community Hlth, Farmington, CT 06405 USA. [Tennen, Howard] Univ Connecticut, Ctr Hlth, Dept Community Med, Farmington, CT 06405 USA. [Wolpert, Howard] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Wagner, J (reprint author), Univ Connecticut, Ctr Hlth, Div Behav Sci & Community Hlth, Farmington, CT 06405 USA. EM juwagner@uchc.edu FU NIDDK NIH HHS [R21 DK074468] NR 65 TC 8 Z9 8 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY PY 2012 VL 74 IS 4 SI SI BP 356 EP 365 DI 10.1097/PSY.0b013e31825769ac PG 10 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 943MW UT WOS:000304128700005 PM 22582333 ER PT J AU McDermott, S Oei, TN Iyer, VR Lee, SI AF McDermott, Shaunagh Oei, Tamara N. Iyer, Veena R. Lee, Susanna I. TI MR Imaging of Malignancies Arising in Endometriomas and Extraovarian Endometriosis SO RADIOGRAPHICS LA English DT Article ID ABDOMINAL-WALL ENDOMETRIOSIS; MUCINOUS BORDERLINE TUMORS; DEEP PELVIC ENDOMETRIOSIS; OVARIAN-CANCER; MIMICKING MALIGNANCY; DIAGNOSTIC-ACCURACY; CARCINOMA; FEATURES; DISEASE; MASSES AB Cancers that arise in ovarian or extraovarian endometriosis are a distinct disease category with a histologic profile different from that of the more common epithelial ovarian cancers and with a better prognosis. Because the malignant transformation of endometriomas is rarely associated with lymphadenopathy or peritoneal carcinomatosis, a high index of suspicion on the part of the radiologist is necessary to establish a timely diagnosis of endometriosis-related ovarian cancers and allow appropriate oncologic management. Although imaging is not currently performed for surveillance of endometriosis, magnetic resonance (MR) imaging is often performed when surgical treatment is under consideration. An optimal MR imaging protocol for the detection of cancer arising in an endometrioma includes a review of subtraction images derived from unenhanced and contrast material-enhanced T1-weighted datasets. Subtraction images provide improved conspicuity of enhancing mural nodules-which are the most sensitive MR imaging sign of malignancy in ovarian endometriosis- against the background of the high-signal-intensity endometriotic cyst. Cancers arising in extraovarian endometriosis typically manifest as solid lesions with intermediate signal intensity on T1-and T2-weighted images, enhancement after the intravenous administration of a gadolinium- based contrast material, and restricted diffusion on diffusion-weighted images and apparent diffusion coefficient (ADC) maps. The signal intensity of myometrium, or, if the uterus is absent, that of the small bowel wall, is used as an internal reference standard for lesion signal intensity. Lesions are considered to have restricted diffusion if they show signal hyperintensity relative to the reference structure on diffusion-weighted images and hypointensity or isointensity relative to that structure on ADC maps. For definitive diagnosis, histopathologic analysis is required. (C) RSNA, 2012 . radiographics.rsna.org C1 [McDermott, Shaunagh; Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Oei, Tamara N.] Midatlantic Permanente Med Grp, Dept Radiol, Kensington, NSW, Australia. [Iyer, Veena R.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. RP McDermott, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mcdermottshaunagh@gmail.com RI Oei, Tian/K-4870-2012 NR 61 TC 15 Z9 16 U1 0 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2012 VL 32 IS 3 BP 845 EP 863 DI 10.1148/rg.323115736 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 942OG UT WOS:000304054000018 PM 22582363 ER PT J AU Kacmarek, RM Barnes, TA Durbin, CG AF Kacmarek, Robert M. Barnes, Thomas A. Durbin, Charles G., Jr. TI Survey of Directors of Respiratory Therapy Departments Regarding the Future Education and Credentialing of Respiratory Care Students and Staff SO RESPIRATORY CARE LA English DT Article DE respiratory care; respiratory therapist; survey; education; credentials; accreditation AB OBJECTIVE: Information and opinions were sought on the need for graduating and practicing respiratory therapists to obtain 66 competencies necessary for practice in 2015 and beyond, the required length of respiratory care programs, the educational needs of practicing therapists, current and future workforce positions, and the appropriate credential needed by graduating therapists. METHODS: Survey responses from respiratory therapy department directors or managers are the basis of this report. After pilot testing and refining the questions, a self-administered, Internet based, American Association for Respiratory Care (AARC) endorsed survey was used to gather information from 2,368 individuals designated as respiratory therapy department directors or managers in the AARC membership list as of May 2010. RESULTS: A total of 663 valid survey responses (28.0%) were received. On average, the vacancy rate of surveyed hospitals was only 0.81 full-time equivalents (FTEs). Responses by directors on 66 competencies described in the second 2015 conference as needed by graduate and practicing respiratory therapists indicated 90% agreement on 37, between 50% and 90% agreement on 25, and < 50% agreement on 4 competencies. There was no consensus among directors on the academic preparation of new graduates, with 245 (36.8%) indicating a preference for a baccalaureate or master's degree, 243 (36.7%) indicating a preference for an associate degree, and 176 (26.5%) indicating no preference. There were 270 (41.8%) respondents who indicated that a baccalaureate or master's degree in respiratory therapy should be required to qualify for a license to deliver respiratory care. The survey indicated that 523 (81.2%) of directors are in favor of the RRT credential being required to practice in 2015 and beyond. CONCLUSIONS: There was good agreement that graduate and practicing therapists should obtain the vast majority of the 66 competencies surveyed and that the entry level credential should be the RRT. Similar numbers of managers favored an entry level baccalaureate degree as favored an associate degree. C1 [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 01460 USA. [Barnes, Thomas A.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Durbin, Charles G., Jr.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Warren 1225,55 Fruit St, Boston, MA 01460 USA. EM rkacmarek@partners.org NR 10 TC 4 Z9 4 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2012 VL 57 IS 5 BP 710 EP 720 DI 10.4187/respcare.01360 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 943NN UT WOS:000304131100005 PM 22153135 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, Robert M. Villar, Jesus TI Acute Application of Noninvasive Ventilation Outside the ICU: When Is It Safe? SO RESPIRATORY CARE LA English DT Editorial Material ID ACUTE RESPIRATORY-FAILURE; INTENSIVE-CARE-UNIT; MANAGEMENT; DISEASE C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 01460 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Villar, Jesus] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Warren 1225,55 Fruit St, Boston, MA 01460 USA. EM rkacmarek@partners.org NR 14 TC 4 Z9 4 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD MAY PY 2012 VL 57 IS 5 BP 815 EP 816 DI 10.4187/respcare.01869 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 943NN UT WOS:000304131100022 PM 22546302 ER PT J AU Messamore, E AF Messamore, Erik TI Niacin subsensitivity is associated with functional impairment in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Niacin; Schizophrenia; Niacin; Laser Doppler flowmetry; Psychiatric status rating scales ID SKIN-FLUSH RESPONSE; CATALEPTIC BEHAVIOR; NICOTINIC-ACID; FATTY-ACIDS; CYCLOOXYGENASE INHIBITORS; POSSIBLE INVOLVEMENT; HEALTHY CONTROLS; ABSENT RESPONSE; EARLY PSYCHOSIS; CHALLENGE TEST AB Objective: Sensitivity to the skin flush effect of niacin is reduced in a portion of patients with schizophrenia. Though this peripheral physiological abnormality has been widely replicated, its relevance to neuropsychiatric manifestations of the illness has been unclear. The goal of this study was to determine if the niacin response abnormality in schizophrenia is associated with functional impairment. Methods: Following psychiatric assessment, a Global Assessment of Functioning (GAF) score was assigned to each of 40 volunteers with schizophrenia. For each subject, the blood flow responses to several concentrations of topical methylnicotinate were recorded. Blood flow was measured objectively, using laser Doppler flowmetry. From the dose-response data, EC50 values were derived. GAF scores were assigned without knowledge of the participants' niacin response data. Results: There was a significant negative correlation between GAF scores and EC50 values for methylnicotinate (Pearson r=-0.42; p=0.007). Conclusions: Reduced niacin sensitivity is associated with greater functional impairment among patients with schizophrenia. These findings raise the possibility that a subset of schizophrenia patients possesses a biochemical abnormality that reduces niacin sensitivity in the skin and contributes to functional impairment from the disease. Published by Elsevier B.V. C1 [Messamore, Erik] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Messamore, Erik] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Messamore, E (reprint author), Portland VA Med Ctr, Div Mental Hlth, P35C,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Erik.Messamore@va.gov FU NIMH [R03 MH070434]; VA Career Development Award FX Funding for this study was provided by NIMH grant R03 MH070434 and by a VA Career Development Award (to the author). Neither the NIMH nor VA funding sources had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 47 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 180 EP 184 DI 10.1016/j.schres.2012.03.001 PG 5 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800029 PM 22445461 ER PT J AU Smith, MJ Horan, WP Karpouzian, TM Abram, SV Cobia, DJ Csernansky, JG AF Smith, Matthew J. Horan, William P. Karpouzian, Tatiana M. Abram, Samantha V. Cobia, Derin J. Csernansky, John G. TI Self-reported empathy deficits are uniquely associated with poor functioning in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Social cognition; Community functioning; Functional capacity ID SOCIAL COGNITION; NEUROCOGNITIVE DEFICITS; MIND; NEUROSCIENCE; DISORDER; OPPORTUNITIES; METAANALYSIS; WORKSHOP; RECOVERY; CNTRICS AB Background: Social cognitive deficits have been proposed to be among the causes of poor functional outcome in schizophrenia. Empathy, or sharing and understanding the unique emotions and experiences of other people, is one of the key elements of social cognition, and prior studies suggest that empathic processes are impaired in schizophrenia. The current study examined whether impairments in self-reported empathy were associated with poor functioning, above and beyond the influences of neurocognitive deficits and psychopathology. Methods: Individuals with schizophrenia (n=46) and healthy controls (n=37) completed the Interpersonal Reactivity Index (IRI), a measure of emotional and cognitive empathy. Participants also completed a neuropsychological test battery, clinical ratings of psychopathology, and functional outcome measures assessing both functional capacity and community functioning. After testing for between-group differences, we assessed the relationships between self-reported empathy and the measures of functioning, neurocognition, and psychopathology. Regression analyses examined whether empathic variables predicted functional outcomes. Results: Individuals with schizophrenia reported lower IRI scores for perspective-taking and empathic concern, and higher IRI scores for personal distress than controls. Among individuals with schizophrenia, lower perspective-taking, greater disorganized symptoms, and deficits in working memory and episodic memory were correlated with poorer functional capacity and community functioning. Lower scores for perspective-taking explained significant incremental variance in both functional capacity (Delta R-2=.09, p <.05) and community functioning (Delta R-2=.152, p <.01) after accounting for relevant neurocognitive and psychopathological variables. Conclusions: Impaired perspective-taking, a component of cognitive empathy, is associated with poor functioning even after taking into account the influences of neurocognitive deficits and psychopathology. These findings support further efforts to clarify the underlying causes of empathic disturbances and suggest that treatments for these disturbances may help functional recovery in schizophrenia. (C) 2012 Elsevier B.V. All rights reserved. C1 [Smith, Matthew J.; Karpouzian, Tatiana M.; Abram, Samantha V.; Cobia, Derin J.; Csernansky, John G.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Horan, William P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.] VISN22 MIRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Smith, MJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, 446 E Ontario St,Suite 1000, Chicago, IL 60611 USA. EM matthewsmith@northwestern.edu OI Smith, Matthew/0000-0002-0079-1477; Cobia, Derin/0000-0003-2339-958X FU Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine; Northwestern University Schizophrenia Research Group FX Sources of Support: Support for the preparation of this paper was provided by the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine and the Northwestern University Schizophrenia Research Group. NR 62 TC 37 Z9 39 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 196 EP 202 DI 10.1016/j.schres.2012.01.012 PG 7 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800032 PM 22321668 ER PT J AU Irani, F Seligman, S Kamath, V Kohler, C Gur, RC AF Irani, Farzin Seligman, Sarah Kamath, Vidyulata Kohler, Christian Gur, Ruben C. TI A meta-analysis of emotion perception and functional outcomes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Emotion perception; Social cognition; Schizophrenia; Functional outcome; Quality of life; Meta-analysis ID FACIAL-AFFECT RECOGNITION; SOCIAL COGNITION; TRAINING-PROGRAM; FLAT AFFECT; OTHER-RACE; REMEDIATION; DEFICITS; NEUROCOGNITION; EXPRESSIONS; COMPETENCE AB Introduction: Emotion perception (EP) is impaired in schizophrenia, is stable across clinical state, resistant to antipsychotic treatment and linked to symptom severity. Given its pervasive nature, there is a need to quantitatively examine whether this dysfunction impacts functional outcomes. We used a meta-analytic strategy to combine results from several studies and examine synthesized effect sizes. Methods: A Meta-analysis of Observational Studies in Epidemiology standard was used to extract data following a PubMed and PsychInfo search. Studies reporting correlations between measures of EP and functional outcomes in schizophrenia spectrum disorders were selected. The impact of potential methodological (task type), demographic (sex, age, race, education, marital status) and clinical (age of onset, duration of illness, setting, symptoms, anti-psychotic medication) moderators on effect sizes were examined. Results: Twenty-five studies met inclusion criteria and included 1306 patients who were 37 years old, with 12 years of education, 64% male and 63% Caucasian. There was a significant relationship between EP and functional outcomes in individuals with schizophrenia or schizoaffective disorder, with effect sizes in the medium range. Medium to large range positive correlations were observed between emotion identification and functional outcome domains involving social problem solving, social skills and community functioning. Significant moderators included task type (emotion identification tasks), sex (% male in sample), race (% Caucasian in sample) and clinical symptoms (negative and positive). Conclusions: Emotion identification deficits are associated with functional impairments in schizophrenia and moderated by sex, race and symptoms. This has implications for treatment efforts to improve outcomes. (C) 2012 Elsevier B.V. All rights reserved. C1 [Irani, Farzin; Seligman, Sarah; Kamath, Vidyulata; Kohler, Christian; Gur, Ruben C.] Univ Penn, Sch Med, Neuropsychiat Sect, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Ruben C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Irani, Farzin] Immaculata Univ, Dept Grad Psychol, Immaculata, PA USA. RP Irani, F (reprint author), Univ Penn, Sch Med, Neuropsychiat Sect, Dept Psychiat, 10th Floor,Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM firani@upenn.edu OI Rycroft, Sarah/0000-0002-9041-0825 FU NIMH [T32MH019112] FX FI is supported by a training grant from NIMH (T32MH019112); the NIMH had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 70 TC 44 Z9 47 U1 3 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2012 VL 137 IS 1-3 BP 203 EP 211 DI 10.1016/j.schres.2012.01.023 PG 9 WC Psychiatry SC Psychiatry GA 941AI UT WOS:000303933800033 PM 22341200 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Treatment Center Characteristics Associated with Better Outcomes: A Role for the Medical Director? SO SEMINARS IN DIALYSIS LA English DT Article ID DIALYSIS; MORTALITY; HEMODIALYSIS; ADEQUACY; PROGRAM; QUALITY C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 12 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2012 VL 25 IS 3 BP 296 EP 298 DI 10.1111/j.1525-139X.2012.01077.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 944HP UT WOS:000304190200011 PM 22607212 ER PT J AU Yeh, DD Schecter, WP AF Yeh, Daniel Dante Schecter, William P. TI Primary Blast Injuries-An Updated Concise Review SO WORLD JOURNAL OF SURGERY LA English DT Article ID TRAUMATIC BRAIN-INJURY; TYMPANIC-MEMBRANE PERFORATION; LUNG INJURY; EXPLOSIVE BLAST; CIVILIAN BUS; SURVIVORS; MANAGEMENT; DIAGNOSIS; PATHOLOGY; BOMBINGS AB Blast injuries have been increasing in the civilian setting and clinicians need to understand the spectrum of injury and management strategies. Multisystem trauma associated with combined blunt and penetrating injuries is the rule. Explosions in closed spaces increase the likelihood of primary blast injury. Rupture of tympanic membranes is an inaccurate marker for severe primary blast injury. Blast lung injury manifests early and should be managed with lung-protective ventilation. Blast brain injury is more common than previously appreciated. C1 [Yeh, Daniel Dante] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Schecter, William P.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Surg, San Francisco, CA 94143 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St 810, Boston, MA 02114 USA. EM dyeh2@partners.org NR 39 TC 16 Z9 19 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAY PY 2012 VL 36 IS 5 BP 966 EP 972 DI 10.1007/s00268-012-1500-9 PG 7 WC Surgery SC Surgery GA 943BZ UT WOS:000304096700006 PM 22411082 ER PT J AU Yee, HS Chang, MF Pocha, C Lim, J Ross, D Morgan, TR Monto, A AF Yee, Helen S. Chang, Michael F. Pocha, Christine Lim, Joseph Ross, David Morgan, Timothy R. Monto, Alexander TI Update on the Management and Treatment of Hepatitis C Virus Infection: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID SUSTAINED VIROLOGICAL RESPONSE; TREATMENT-NAIVE PATIENTS; GENOTYPE 1 INFECTION; CHRONIC HCV INFECTION; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; LIVER FIBROSIS; RANDOMIZED-TRIAL; TRANSIENT ELASTOGRAPHY; PEGYLATED INTERFERON AB Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the United States population and 4% of veterans who use Department of Veterans Affairs medical services. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring liver transplantation in the United States. Management of chronic HCV is aimed at halting disease progression, preventing cirrhosis decompensation, reducing the risk of HCC, and treating extrahepatic complications of the infection. As part of a comprehensive HCV management strategy, peginterferon alfa and ribavirin, along with the addition of a hepatitis C protease inhibitor therapy for many genotype 1-infected patients, are the current standard of care. Antiviral therapy should be provided to those individuals who are clinically stable, have moderate liver disease or compensated cirrhosis, and are motivated to pursue therapy. Many patients have comorbid medical and psychiatric conditions, which may affect their adherence to antiviral therapy or worsen while on antiviral therapy. To optimally manage hepatitis C and associated comorbidities, patients benefit from multidisciplinary teams that can provide HCV-specific care and treatment. Sustained virologic response is associated with "cure" of chronic HCV, and results in improved liver disease outcomes and prolonged survival. C1 [Yee, Helen S.; Chang, Michael F.; Pocha, Christine; Lim, Joseph; Monto, Alexander] US Dept Vet Affairs, Hepatitis Resource Ctr Program C, Washington, DC USA. [Yee, Helen S.; Monto, Alexander] US Dept Vet Affairs, Med Ctr, San Francisco, CA USA. [Chang, Michael F.] US Dept Vet Affairs, Med Ctr, Portland, OR USA. [Pocha, Christine] US Dept Vet Affairs, Med Ctr, Minneapolis, MN USA. [Lim, Joseph] US Dept Vet Affairs, Med Ctr, West Haven, CT USA. [Ross, David] Vet Hlth Adm, Off Publ Hlth Clin Publ Hlth, Washington, DC USA. [Morgan, Timothy R.] US Dept Vet Affairs, Med Ctr, Long Beach, CA USA. RP Monto, A (reprint author), 4150 Clement St,111B, San Francisco, CA 94121 USA. EM Alexander.monto@va.gov NR 93 TC 59 Z9 63 U1 1 U2 7 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 2012 VL 107 IS 5 BP 669 EP 689 DI 10.1038/ajg.2012.48 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700005 PM 22525303 ER PT J AU McFarland, LV AF McFarland, Lynne V. TI The Role of Compassion in the Practice of Evidence-Based Medicine SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID DIFFICILE-ASSOCIATED DISEASE AB Patients with diseases having a high failure rate with standard treatments typically enroll in randomized clinical trials of new investigational treatments. Not all potential therapies are amenable to these types of designs and thus may be offered compassionately; however, claims of efficacy are thus viewed with caution. In a paper in this issue, 43 patients with recurrent Clostridium difficile infections were treated with fecal microbiota transplants using a compassionate use protocol. By using standardized healthy donor stool preparations and following standardized protocols, the 92% response rate can be viewed with more confidence than other case series reports. C1 [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Dept Vet Affairs, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov NR 10 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2012 VL 107 IS 5 BP 768 EP 769 DI 10.1038/ajg.2011.489 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700016 PM 22552243 ER PT J AU Boardman, CR Sonnenberg, A AF Boardman, Charles R. Sonnenberg, Amnon TI A Watched Pot Can Boil: Interval Cancer in Tightly Surveyed Barrett's Esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID ADENOCARCINOMA; SURVEILLANCE; PREVALENCE C1 [Boardman, Charles R.; Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Boardman, Charles R.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2012 VL 107 IS 5 BP 793 EP 794 DI 10.1038/ajg.2012.27 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937SU UT WOS:000303679700024 PM 22552249 ER PT J AU Behr, S Weinstein, S Aslam, R Jung, A Sebro, R Yee, J AF Behr, S. Weinstein, S. Aslam, R. Jung, A. Sebro, R. Yee, J. TI Can CT Performed for Nonspecific Abdominal Pain Reliably Exclude Acute Cholecystitis? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Behr, S.; Weinstein, S.; Aslam, R.; Jung, A.; Sebro, R.; Yee, J.] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Weinstein, S.; Aslam, R.; Jung, A.; Yee, J.] San Francisco VA Med Ctr, San Francisco, CA USA. EM stefage00@yahoo.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 2012 VL 198 IS 5 SU S PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400468 ER PT J AU Braschi, M Ramaiya, N Sainani, N Lee, S AF Braschi, M. Ramaiya, N. Sainani, N. Lee, S. TI Seven Steps to an Effective Oncologic Imaging Report SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Braschi, M.; Ramaiya, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sainani, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM martabraschi@yahoo.it 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400341 ER PT J AU Cao, K Hedgire, S Nadkarni, N Elmi, A McDermott, S Harisinghani, M AF Cao, K. Hedgire, S. Nadkarni, N. Elmi, A. McDermott, S. Harisinghani, M. TI Imaging Characteristics of Hepatic Metastases From Primary Pancreatic Neuroendocrine Tumors on Triple-Phase Contrast CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Cao, K.; Hedgire, S.; Nadkarni, N.; Elmi, A.; McDermott, S.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kcao1@partners.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400071 ER PT J AU Chikarmane, S Khurana, B Krajewski, K Shinagare, A Sodickson, A Jagannathan, J Ramaiya, N AF Chikarmane, S. Khurana, B. Krajewski, K. Shinagare, A. Sodickson, A. Jagannathan, J. Ramaiya, N. TI Conventional Chemotherapeutic and Newer Molecular Targeted Therapy Treatment-Related Complications in Oncology Patients Presenting to the Emergency Department SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Chikarmane, S.; Khurana, B.; Sodickson, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Krajewski, K.; Shinagare, A.; Jagannathan, J.; Ramaiya, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM schikarmane@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400503 ER PT J AU Conley, H Patel, M Caruso, P Yousuf, N Curtin, H AF Conley, H. Patel, M. Caruso, P. Yousuf, N. Curtin, H. TI The Pterygopalatine Fossa Revisited: The Piccadilly Circus of the Head and Neck SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Conley, H.; Patel, M.] Santa Clara Valley Med Ctr, Mountain View, CA USA. [Caruso, P.; Curtin, H.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Yousuf, N.] Bloomington Radiol, Normal, IL USA. EM nelsonconley@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400611 ER PT J AU Covarrubias, D Bronzo, B Uppot, R Arellano, R Kalva, S AF Covarrubias, D. Bronzo, B. Uppot, R. Arellano, R. Kalva, S. TI Interventional Treatment of Hepatic Tumors: Review of Ablative and Embolic Therapies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Covarrubias, D.; Bronzo, B.; Uppot, R.; Arellano, R.; Kalva, S.] Massachusetts Gen Hosp, Cambridge, MA USA. EM dacovarrubias@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 2012 VL 198 IS 5 SU S PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400780 ER PT J AU Czuczman, G Huang, A AF Czuczman, G. Huang, A. TI Improving Quality of Image Processing and Display: A Model for Reducing Errors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Czuczman, G.; Huang, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM gregchooch@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400009 ER PT J AU Gee, M Quencer, K Nimkin, K Mino-Kenudson, M AF Gee, M. Quencer, K. Nimkin, K. Mino-Kenudson, M. TI Prospective Comparison of MR Enterography (MR-E) and CT Enterography (CT-E) in the Evaluation of Crohn Disease in Pediatric Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Gee, M.; Quencer, K.; Nimkin, K.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kquencer@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400015 ER PT J AU Gupta, S Schultz, T Choy, G Dreyer, K AF Gupta, S. Schultz, T. Choy, G. Dreyer, K. TI Assessing Correlation Between Decision Scores and Report Findings for CT Chest Examinations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Gupta, S.; Schultz, T.; Choy, G.; Dreyer, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgupta11@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400059 ER PT J AU Gupta, S Saini, S Schultz, T Boland, G Choy, G Dreyer, K AF Gupta, S. Saini, S. Schultz, T. Boland, G. Choy, G. Dreyer, K. TI Assessing the Yield of Radiologists' Recommendations for Additional Imaging Following Equivocal Abdominal Ultrasound SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Gupta, S.; Saini, S.; Schultz, T.; Boland, G.; Choy, G.; Dreyer, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgupta11@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400047 ER PT J AU Hedgire, S McDermott, S Elmi, A Cao, K Blake, M Harisinghani, M AF Hedgire, S. McDermott, S. Elmi, A. Cao, K. Blake, M. Harisinghani, M. TI Matrix Unplugged: Multimodality Imaging of Alloderm in the Abdomen and Pelvis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Hedgire, S.; McDermott, S.; Elmi, A.; Cao, K.; Blake, M.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Hedgire.Sandeep@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400462 ER PT J AU Hedgire, S McDermott, S Cao, K Elmi, A Saini, S Harisinghani, M AF Hedgire, S. McDermott, S. Cao, K. Elmi, A. Saini, S. Harisinghani, M. TI Spectrum of IgG4-Related Disease of Abdomen and Pelvis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Hedgire, S.; McDermott, S.; Cao, K.; Elmi, A.; Saini, S.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Hedgire.Sandeep@mgh.harvard.edu NR 1 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400459 ER PT J AU Hedgire, S Elmi, A Nadkarni, N Cao, K McDermott, S Harisinghani, M AF Hedgire, S. Elmi, A. Nadkarni, N. Cao, K. McDermott, S. Harisinghani, M. TI Preoperative Evaluation of Perinephric Fat Invasion in Patients With Renal Cell Carcinoma: Correlation With Pathologic Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Hedgire, S.; Elmi, A.; Nadkarni, N.; Cao, K.; McDermott, S.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Hedgire.Sandeep@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400220 ER PT J AU Humphrey, K Salazar, G Gilman, M Shepard, J Wu, C AF Humphrey, K. Salazar, G. Gilman, M. Shepard, J. Wu, C. TI Not So Fake: Pseudoaneurysms of the Pulmonary Arteries SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Humphrey, K.; Salazar, G.; Gilman, M.; Shepard, J.; Wu, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM klhumphrey@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400299 ER PT J AU Kraeft, J Uppot, R Heffess, A AF Kraeft, J. Uppot, R. Heffess, A. TI Review of Imaging Findings in Eating Disorders SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Kraeft, J.; Heffess, A.] Mt Auburn Hosp, Cambridge, MA USA. [Uppot, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jkraeft@mah.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400482 ER PT J AU Kraeft, J Harisinghani, M Gervais, D Wu, C AF Kraeft, J. Harisinghani, M. Gervais, D. Wu, C. TI Gastric Fistulas: A Pictorial Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Kraeft, J.] Mt Auburn Hosp, Cambridge, MA USA. [Harisinghani, M.; Gervais, D.; Wu, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jkraeft@mah.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400393 ER PT J AU Lalwani, N Bhargava, P Moshiri, M Lee, J Wang, C Bastawrous, S Vaidya, S Dighe, M AF Lalwani, N. Bhargava, P. Moshiri, M. Lee, J. Wang, C. Bastawrous, S. Vaidya, S. Dighe, M. TI Abdominal Oncologic Emergencies: Imaging Appearances and Therapeutic Options SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Lalwani, N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bhargava, P.; Moshiri, M.; Lee, J.; Wang, C.; Bastawrous, S.; Vaidya, S.; Dighe, M.] Univ Washington, Shoreline, WA USA. [Bhargava, P.; Bastawrous, S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM bhargp@uw.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400465 ER PT J AU Lalwani, N Bhargava, P Dighe, M Shanbhogue, A Nagar, A AF Lalwani, N. Bhargava, P. Dighe, M. Shanbhogue, A. Nagar, A. TI Primary and Secondary Sclerosing Cholangitis: Current Update and Role of Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Lalwani, N.; Shanbhogue, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Bhargava, P.; Dighe, M.] Univ Washington, Seattle, WA 98195 USA. [Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Nagar, A.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. EM neerajlalwani@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400367 ER PT J AU Lee, A Engel, L Hui, G Ghoshhajra, B AF Lee, A. Engel, L. Hui, G. Ghoshhajra, B. TI Coronary CT Angiography at 140 kV vs 120 kV: Assessment of Image Quality and Effective Dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Lee, A.; Engel, L.; Hui, G.; Ghoshhajra, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM amlee@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400279 ER PT J AU MacMahon, P Alkasab, T Singh, A Nazarian, R Avery, L Novelline, R Abujudeh, H AF MacMahon, P. Alkasab, T. Singh, A. Nazarian, R. Avery, L. Novelline, R. Abujudeh, H. TI Indeterminate CT Appendicitis Examinations: Correlating Patient Outcome With Imaging Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [MacMahon, P.; Alkasab, T.; Singh, A.; Nazarian, R.; Avery, L.; Novelline, R.; Abujudeh, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM petermacmahon@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400065 ER PT J AU McDermott, S O'Connor, O Cao, K Harisinghani, M AF McDermott, S. O'Connor, O. Cao, K. Harisinghani, M. TI Radiology Publications in the 21st Century: Trend of Contribution From Different Countries SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [McDermott, S.; O'Connor, O.; Cao, K.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM smcdermott1@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400362 ER PT J AU McDermott, S Shelly, M Hahn, P Gervais, D Harisinghani, M AF McDermott, S. Shelly, M. Hahn, P. Gervais, D. Harisinghani, M. TI Imaging-Guided Percutaneous Biopsy of Abdominal and Pelvic Lymph Nodes in the Diagnosis of Lymphoma: Comparison of Techniques SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [McDermott, S.; Shelly, M.; Hahn, P.; Gervais, D.; Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM smcdermott1@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400017 ER PT J AU Reddy, S Jati, A AF Reddy, S. Jati, A. TI Extratesticular Scrotal Abnormalities: Clinical and Surgical Impact of Imaging Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Reddy, S.] Boston Univ, Med Ctr, Boston, MA USA. [Jati, A.] VA Boston Healthcare Syst, Boston, MA USA. EM susmitha.reddy@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400736 ER PT J AU Reddy, S Jati, A AF Reddy, S. Jati, A. TI Extranodal Lymphoma: A Comprehensive Imaging Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Reddy, S.] Boston Univ, Med Ctr, Boston, MA USA. [Jati, A.] VA Boston Healthcare Syst, Boston, MA USA. EM susmitha.reddy@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 2012 VL 198 IS 5 SU S PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400467 ER PT J AU Ridge, C Chan, V McDermott, S Eisenberg, R Heffernan, E AF Ridge, C. Chan, V McDermott, S. Eisenberg, R. Heffernan, E. TI Skeletons in the Closet SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Ridge, C.] Mem Sloan Kettering, New York, NY USA. [Ridge, C.; Eisenberg, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Chan, V; Heffernan, E.] St Vincents Univ Hosp, Dublin 4, Ireland. [McDermott, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM caroleridge@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 2012 VL 198 IS 5 SU S PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400470 ER PT J AU Rosenthal, P Massoglia, D Lundy, K Gebregziabher, M Gilbert, G AF Rosenthal, P. Massoglia, D. Lundy, K. Gebregziabher, M. Gilbert, G. TI Under Our Noses: A Reformulation of Our Understanding of Incidental Paranasal Sinusitis and Its Application in Interpreting Routine Sinus Imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Rosenthal, P.; Massoglia, D.; Lundy, K.; Gebregziabher, M.; Gilbert, G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM peter.rosenthal@va.gov 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400604 ER PT J AU Sebro, R Aparici, CM Pampaloni, MH AF Sebro, R. Aparici, Mari C. Pampaloni, Hernandez M. TI Comparison Between True Whole-Body and Limited Whole-Body FDG PET/CT Studies in Oncology Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Sebro, R.; Aparici, Mari C.; Pampaloni, Hernandez M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Aparici, Mari C.] San Francisco VA Med Ctr, San Francisco, CA USA. EM ronnie.sebro@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400684 ER PT J AU Shinagare, A Krajewski, K Souza, D Howard, S Jagannathan, I Ramaiya, N AF Shinagare, A. Krajewski, K. Souza, D. Howard, S. Jagannathan, J. Ramaiya, N. TI Role of Imaging in Management of Advanced RCC in the Era of Molecular Targeted Therapy: A Decade of Change SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Shinagare, A.; Krajewski, K.; Souza, D.; Howard, S.; Jagannathan, J.; Ramaiya, N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Brookline, MA USA. EM ashinagare@partners.org NR 1 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 2012 VL 198 IS 5 SU S PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400765 ER PT J AU Shinagare, A Howard, S Souza, D Krajewski, K Jagannathan, J Ramaiya, N AF Shinagare, A. Howard, S. Souza, D. Krajewski, K. Jagannathan, J. Ramaiya, N. TI Liver Metastases in the Era of Molecular Targeted Therapy: New Faces of Treatment Response SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Shinagare, A.; Howard, S.; Souza, D.; Krajewski, K.; Jagannathan, J.; Ramaiya, N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Brookline, MA USA. EM ashinagare@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400411 ER PT J AU Shinagare, A Shyn, P Sadow, C Wasser, E Catalano, P AF Shinagare, A. Shyn, P. Sadow, C. Wasser, E. Catalano, P. TI Incidence, Appropriateness, and Clinical Impact of Recommendations for Additional Imaging Tests in Oncologic PET/CT Reports SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Shinagare, A.; Catalano, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shinagare, A.; Shyn, P.; Sadow, C.; Wasser, E.] Brigham & Womens Hosp, 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400212 ER PT J AU Shinagare, A Zukotynski, K Krajewski, K Jagannathan, J Hornick, J Ramaiya, N AF Shinagare, A. Zukotynski, K. Krajewski, K. Jagannathan, J. Hornick, J. Ramaiya, N. TI Role of CT, MRI, and PET/CT in Management of Myeloid Sarcoma With Clinical and Pathologic Correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Shinagare, A.; Zukotynski, K.; Krajewski, K.; Jagannathan, J.; Ramaiya, N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Brookline, MA USA. [Hornick, J.] Brigham & Womens Hosp, 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400129 ER PT J AU Singh, A Cai, W Deshpande, V Hornicek, F Chen, Y DeLaney, T Nielsen, G Harmon, D AF Singh, A. Cai, W. Deshpande, V Hornicek, F. Chen, Y. DeLaney, T. Nielsen, G. Harmon, D. TI Targeted Correlation of Tissue-Stained Pathologic Tumor Viability Scores With Corresponding MRI Estimates: Comparison of Postprocessing Estimates Obtained by Dynamic and Nondynamic MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Singh, A.; Cai, W.; Deshpande, V; Hornicek, F.; Chen, Y.; DeLaney, T.; Nielsen, G.; Harmon, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400139 ER PT J AU Singh, A Cai, W Harris, G Sahani, D AF Singh, A. Cai, W. Harris, G. Sahani, D. TI Comparing Survival Curve Estimates Produced by Defining Various Limits for Stable Disease by Total Tumor Volumetry Criteria for Evaluating Therapy Response in Hepatocellular Carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Singh, A.; Cai, W.; Harris, G.; Sahani, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400073 ER PT J AU Souza, D Krajewski, K Shinagare, A Howard, S Ramaiya, N Jagannathan, J AF Souza, D. Krajewski, K. Shinagare, A. Howard, S. Ramaiya, N. Jagannathan, J. TI Emerging Applications of Gadoxetate Disodium in Oncology: When, Why, and How SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Souza, D.; Krajewski, K.; Shinagare, A.; Howard, S.; Ramaiya, N.; Jagannathan, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Souza, D.; Shinagare, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM dasouza@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400420 ER PT J AU Souza, F Araujo, C Roda, M Jagannathan, J Ramayia, N AF Souza, F. Araujo, C. Roda, M. Jagannathan, J. Ramayia, N. TI Imaging Findings on Secondary Nonepithelial Neoplasms: Sarcomatosis and Lymphomatosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Souza, F.; Araujo, C.; Roda, M.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Jagannathan, J.; Ramayia, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM fsouza@umc.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400447 ER PT J AU Weinstein, S Osei-Bonsu, S Sajewicz, A Yee, J AF Weinstein, S. Osei-Bonsu, S. Sajewicz, A. Yee, J. TI MDCT of the Postoperative Colon: Normal Findings and Common Complications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Weinstein, S.; Yee, J.] Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. [Weinstein, S.; Yee, J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Osei-Bonsu, S.] Chicago Med Sch, N Chicago, IL USA. [Sajewicz, A.] Redwood Reg Med Grp, Santa Rosa, CA USA. EM stefage00@yahoo.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400466 ER PT J AU Wilbur, S Wandtke, J Wilbur, D AF Wilbur, S. Wandtke, J. Wilbur, D. TI Radiologic-Pathologic Education: How We Do It SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Wilbur, S.; Wandtke, J.] Univ Rochester, Rochester, NY USA. [Wilbur, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM scott_wilbur@urmc.rochester.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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400343 ER PT J AU Zondervan, R Hahn, P Sadow, C Liu, B Lee, S AF Zondervan, R. Hahn, P. Sadow, C. Liu, B. Lee, S. TI Radiation From CT Scanning Young Adults - What Are the Real Risks? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2012 CL Vancouver, CANADA SP Amer Roentgen Ray Soc C1 [Zondervan, R.; Hahn, P.; Liu, B.; Lee, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sadow, C.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM robert.zondervan@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 2012 VL 198 IS 5 SU S PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937OI UT WOS:000303667400057 ER PT J AU Tariq, Z Ghose, A Sofi, A Mohamed, I Harmon, D AF Tariq, Zeeshan Ghose, Abhimanyu Sofi, Aijaz Mohamed, Iman Harmon, David TI Metastatic Renal Extraskeletal Ewing Sarcoma in Complete Remission for the Last 8 Years SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE Ewing sarcoma; metastases; remission; chemotherapy; recurrence ID KIDNEY; TUMOR AB Primary renal extraskeletal Ewing sarcoma (EES) is rare but well known to be aggressive, less responsive to the treatment, and has early predilection for metastases. Metastases at the time of diagnosis to the lungs or bones are associated with poor outcome. We present a case of primary renal EES in 57-year-old woman with multiple metastases to the lungs at the time of diagnosis with complete remission of the disease for the last 8 years following multimodality treatment Multidisciplinary approach for the management of EES has definitely improved the quality of life and the survival of the patients. C1 [Tariq, Zeeshan; Ghose, Abhimanyu; Sofi, Aijaz] Univ Toledo, Dept Med, Toledo, OH 43614 USA. [Mohamed, Iman] Univ Toledo, Dept Hematol Oncol, Toledo, OH 43614 USA. [Harmon, David] Harvard Univ, Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02115 USA. RP Tariq, Z (reprint author), Univ Toledo, Dept Med, 3000 Arlington Ave, Toledo, OH 43614 USA. EM zeeshan.tariq@utoledo.edu RI Sofi, Aijaz/H-9519-2013 OI Sofi, Aijaz/0000-0002-4415-7056 NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD MAY PY 2012 VL 19 IS 3 BP E120 EP E121 DI 10.1097/MJT.0b013e3181dcf613 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 939QM UT WOS:000303828200004 ER PT J AU Joffe, H Chang, YC Dhaliwal, S Hess, R Thurston, R Gold, E Matthews, KA Bromberger, JT AF Joffe, Hadine Chang, Yuefang Dhaliwal, Sammy Hess, Rachel Thurston, Rebecca Gold, Ellen Matthews, Karen A. Bromberger, Joyce T. TI Lifetime History of Depression and Anxiety Disorders as a Predictor of Quality of Life in Midlife Women in the Absence of Current Illness Episodes SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID STRUCTURED CLINICAL INTERVIEW; NATIONAL-COMORBIDITY-SURVEY; HEALTH SURVEY SF-36; MIDDLE-AGED WOMEN; MENOPAUSAL TRANSITION; SYMPTOMS; INSOMNIA; ASSOCIATION; RELIABILITY; IMPAIRMENT AB Context: It is unknown whether a history of depression, anxiety disorders, or comorbid depression and anxiety affects subsequent health-related quality of life (HRQOL) during midlife in women when vasomotor symptoms (VMS) and sleep disturbance commonly disrupt QOL. Objectives: To evaluate whether previous affective illness is associated with low HRQOL during midlife in the absence of current illness episodes and whether low HRQOL is explained by VMS or sleep disruption. Design: Longitudinal, community-based study. Setting: Western Pennsylvania. Participants: A total of 425 midlife women in the Study of Women's Health Across the Nation who completed the Structured Clinical Interview for DSM-IV (SCID) and the 36-Item Short Form Health Survey (SF-36) annually during 6 years of follow-up. Main Outcome Measures: Scores on the SF-36 scales of social functioning (SF), role-emotional (RE), rolephysical (RP), body pain (BP), and vitality. Results: Ninety-seven women (22.8%) had comorbid affective illness histories, 162 (38.1%) had previous depression only, and 21 (4.9%) had previous anxiety only. Those with comorbid illness histories and depression alone were more likely to report low HRQOL on the SF, RE, RP, and BP domains (odds ratio [OR]=2.31-3.54 and 1.59-2.28, respectively) than were women with neither disorder. After adjustment for VMS and sleep disturbance, the comorbid group continued to have low HRQOL on these domains (OR=2.13-3.07), whereas the association was significant on SF and BP only for the depression-alone group(OR=2.08 and 1.95, respectively). Compared with women with neither disorder, the anxiety-only group had low HRQOL on the RP domain (OR=2.60). Sleep disturbance, but not VMS, was independently associated with low HRQOL on all the domains except RE. Conclusions: A history of both depression and anxiety has the most robust negative effect on HRQOL in women during midlife, an association not explained by VMS or sleep disturbance. For the depression-alone group, sleep disturbance may partially explain the negative impact of previous affective illness on HRQOL. Sleep disturbance remains an independent correlate of low HRQOL. C1 [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Dept Psychiat,Med Sch, Boston, MA 02114 USA. [Chang, Yuefang] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. [Thurston, Rebecca; Matthews, Karen A.; Bromberger, Joyce T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Dhaliwal, Sammy; Hess, Rachel; Thurston, Rebecca; Matthews, Karen A.; Bromberger, Joyce T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Gold, Ellen] Univ Calif Davis, Div Epidemiol, Dept Publ Hlth Sci, Sch Med, Davis, CA 95616 USA. RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Dept Psychiat,Med Sch, Simches Res Bldg,185 Cambridge St,Ste 2000, Boston, MA 02114 USA. EM hjoffe@partners.org FU Bayer Healthcare Pharmaceuticals; National Institutes of Health (NIH), Department of Health and Human Services through the National Institute on Aging; National Institutes of Health (NIH), Department of Health and Human Services through National Institute of Nursing Research; National Institutes of Health (NIH), Department of Health and Human Services through Office of Research on Women's Health [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; National Institute of Mental Health [MH59689, 5R01MH082922] FX Dr Joffe has received research support from Bayer Healthcare Pharmaceuticals and has served as a consultant to JDS-Noven Pharmaceutical, Pfizer Inc, and Sunovion.; The SWAN has received grant support from the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the Office of Research on Women's Health (grants NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495) and from the National Institute of Mental Health (grant MH59689). Support for this research was also provided in part by grant 5R01MH082922 from the National Institute of Mental Health (Dr Joffe). NR 27 TC 16 Z9 16 U1 0 U2 4 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 2012 VL 69 IS 5 BP 484 EP 492 PG 9 WC Psychiatry SC Psychiatry GA 937QB UT WOS:000303672000007 PM 22566580 ER PT J AU Barnes, DE Yaffe, K Byers, AL McCormick, M Schaefer, C Whitmer, RA AF Barnes, Deborah E. Yaffe, Kristine Byers, Amy L. McCormick, Mark Schaefer, Catherine Whitmer, Rachel A. TI Midlife vs Late-Life Depressive Symptoms and Risk of Dementia Differential Effects for Alzheimer Disease and Vascular Dementia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; MILD COGNITIVE IMPAIRMENT; TEMPORAL RELATIONSHIP; PREVALENCE; POPULATION; METAANALYSIS; ASSOCIATION; HYPOTHESIS; DECLINE AB Context: Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia. Objective: To clarify the timing and nature of the association between depression and dementia. Design: We examined depressive symptoms assessed in midlife (1964-1973) and late life (1994-2000) and the risks of dementia, Alzheimer disease (AD), and vascular dementia (VaD) (2003-2009) in a retrospective cohort study. Depressive symptoms were categorized as none, midlife only, late life only, or both. Cox proportional hazards models (age as timescale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD, or VaD. Setting: Kaiser Permanente Medical Care Program of Northern California. Participants: Thirteen thousand five hundred thirty-five long-term Kaiser Permanente members. Main Outcome Measure: Any medical record diagnosis of dementia or neurology clinic diagnosis of AD or VaD. Results: Subjects had a mean (SD) age of 81.1 (4.5) years in 2003, 57.9% were women, and 24.2% were non-white. Depressive symptoms were present in 14.1% of subjects in midlife only, 9.2% in late life only, and 4.2% in both. During 6 years of follow-up, 22.5% were diagnosed with dementia (5.5% with AD and 2.3% with VaD). The adjusted hazard of dementia was increased by approximately 20% for midlife depressive symptoms only (hazard ratio, 1.19 [95% CI, 1.07-1.32]), 70% for latelife symptoms only (1.72 [1.54-1.92]), and 80% for both (1.77 [1.52-2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a 2-fold increase in AD risk (hazard ratio, 2.06 [95% CI, 1.67-2.55]), whereas subjects with midlife and latelife symptoms had more than a 3-fold increase in VaD risk (3.51 [2.44-5.05]). Conclusions: Depressive symptoms in midlife or in late life are associated with an increased risk of developing dementia. Depression that begins in late life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD. C1 [Barnes, Deborah E.; Yaffe, Kristine; Byers, Amy L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine; Byers, Amy L.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [McCormick, Mark; Schaefer, Catherine; Whitmer, Rachel A.] Kaiser Div Res, Oakland, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,151R, San Francisco, CA 94121 USA. EM deborah.barnes@ucsf.edu FU Brain and Behavior Research Foundation; National Institutes of Health [K24 AG031155, R01 MH086498]; Kaiser Permanente Community Benefits FX This study was supported by the Brain and Behavior Research Foundation (formerly the National Alliance for Research on Schizophrenia and Depression) (Dr Barnes), grants K24 AG031155 and R01 MH086498 from the National Institutes of Health (Dr Yaffe), and Kaiser Permanente Community Benefits (Dr Whitmer). NR 38 TC 87 Z9 91 U1 5 U2 27 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 2012 VL 69 IS 5 BP 493 EP 498 PG 6 WC Psychiatry SC Psychiatry GA 937QB UT WOS:000303672000008 PM 22566581 ER PT J AU Choi, W Baumann, B Liu, JJ Clermont, AC Feener, EP Duker, JS Fujimoto, JG AF Choi, WooJhon Baumann, Bernhard Liu, Jonathan J. Clermont, Allen C. Feener, Edward P. Duker, Jay S. Fujimoto, James G. TI Measurement of pulsatile total blood flow in the human and rat retina with ultrahigh speed spectral/Fourier domain OCT SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC-RETINOPATHY; MACULAR DEGENERATION; GLAUCOMA AB We present an approach to measure pulsatile total retinal arterial blood flow in humans and rats using ultrahigh speed Doppler OCT. The axial blood velocity is measured in an en face plane by raster scanning and the flow is calculated by integrating over the vessel area, without the need to measure the Doppler angle. By measuring flow at the central retinal artery, the scan area can be very small. Combined with ultrahigh speed, this approach enables high volume acquisition rates necessary for pulsatile total flow measurement without modification in the OCT system optics. A spectral domain OCT system at 840nm with an axial scan rate of 244kHz was used for this study. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/- 37.7mm/s. By repeatedly scanning a small area centered at the central retinal artery with high volume acquisition rates, pulsatile flow characteristics, such as systolic, diastolic, and mean total flow values, were measured. Real-time Doppler C-scan preview is proposed as a guidance tool to enable quick and easy alignment necessary for large scale studies. Data processing for flow calculation can be entirely automatic using this approach because of the simple and robust algorithm. Due to the rapid volume acquisition rate and the fact that the measurement is independent of Doppler angle, this approach is inherently less sensitive to involuntary eye motion. This method should be useful for investigation of small animal models of ocular diseases as well as total blood flow measurements in human patients in the clinic. (c) 2012 Optical Society of America C1 [Choi, WooJhon; Baumann, Bernhard; Liu, Jonathan J.; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Choi, WooJhon; Baumann, Bernhard; Liu, Jonathan J.; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Baumann, Bernhard; Duker, Jay S.] Tufts Univ, New England Eye Ctr, Boston, MA 02116 USA. [Baumann, Bernhard; Duker, Jay S.] Tufts Univ, Tufts Med Ctr, Boston, MA 02116 USA. [Clermont, Allen C.; Feener, Edward P.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Choi, W (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM jgfuji@mit.edu OI Baumann, Bernhard/0000-0001-6419-1932 FU National Institutes of Health (NIH) [R01-EY011289-26, R01-EY013516-09, R01-EY019029-04, R01-EY013178-12, R01-HL095717-03, R01-CA075289-14]; Air Force Office of Scientific Research (AFOSR) [FA9550-10-1-0551, FA9550-10-1-0063]; Samsung Scholarship FX The authors thank Dr. Alison Hayward and Wayne Au at Division of Comparative Medicine, Massachusetts Institute of Technology, for their helpful advice for animal handling. This work was supported by the National Institutes of Health (NIH R01-EY011289-26, R01-EY013516-09, R01-EY019029-04, R01-EY013178-12, R01-HL095717-03, R01-CA075289-14), the Air Force Office of Scientific Research (AFOSR FA9550-10-1-0551 and FA9550-10-1-0063) and a Samsung Scholarship. Dr. Bernhard Baumann was visiting from the Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria. NR 28 TC 42 Z9 43 U1 2 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAY 1 PY 2012 VL 3 IS 5 BP 1047 EP 1061 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 935RH UT WOS:000303537400019 PM 22567595 ER PT J AU Thomas, C Kveraga, K Huberle, E Karnath, HO Bar, M AF Thomas, Cibu Kveraga, Kestutis Huberle, Elisabeth Karnath, Hans-Otto Bar, Moshe TI Enabling global processing in simultanagnosia by psychophysical biasing of visual pathways SO BRAIN LA English DT Article DE brain circuits; cerebral ischaemia; visual system; dorsal stream; neurological disorders ID SPATIAL-FREQUENCY CHANNELS; LATERAL GENICULATE-NUCLEUS; MACAQUE STRIATE CORTEX; TOP-DOWN FACILITATION; FUNCTIONAL-ANATOMY; PARVOCELLULAR CONTRIBUTIONS; DORSAL SIMULTANAGNOSIA; GANGLION-CELLS; EYE-MOVEMENTS; PERCEPTION AB A fundamental aspect of visual cognition is our disposition to see the 'forest before the trees'. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the 'forest' but not the 'trees' (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventral visual pathway, the primary recognition pathway, is intact in these patients. Here, we enabled global processing in patients with simultanagnosia using a psychophysical technique, which allowed us to bias stimuli such that they are processed predominantly by the intact ventral visual pathway. Our findings reveal that the impairment in global processing that characterizes simultanagnosia stems from a disruption in the processing of low-spatial frequencies through the dorsal pathway. These findings advance our understanding of the relationship between visuospatial attention and perception and reveal the neural mechanism mediating the disposition to see the 'forest before the trees'. C1 [Thomas, Cibu; Kveraga, Kestutis; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Thomas, Cibu; Kveraga, Kestutis; Bar, Moshe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Huberle, Elisabeth; Karnath, Hans-Otto] Univ Tubingen, Hertie Inst Clin Brain Res, Ctr Neurol, Div Neuropsychol, D-72074 Tubingen, Germany. [Huberle, Elisabeth] Cty Hosp Lucerne, Dept Neurol, CH-6000 Luzern, Switzerland. [Karnath, Hans-Otto] Georgia Inst Technol, Ctr Adv Brain Imaging, Atlanta, GA 30332 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. RP Thomas, C (reprint author), NIH, 10 Ctr Dr,MSC 1240,Bldg 10,Room 3N228, Bethesda, MD 20892 USA. EM cibu.thomas@nih.gov FU Bundesministerium fur Bildung und Forschung (BMBF-Verbund) [01GW0654]; National Institutes of Health [R01EY019477] FX Bundesministerium fur Bildung und Forschung (BMBF-Verbund Grant Number 01GW0654 to H-O.K.) and by the National Institutes of Health (Grant Number R01EY019477 to M.B.). NR 54 TC 12 Z9 12 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2012 VL 135 BP 1578 EP 1585 DI 10.1093/brain/aws066 PN 5 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 937JE UT WOS:000303654000022 PM 22418740 ER PT J AU Goss, PE Qi, SL Hu, HQ Gediya, LK Purushottamachar, P Godbole, AM Njar, VCO AF Goss, Paul E. Qi, Shangle Hu, Haiqing Gediya, Lalji K. Purushottamachar, Puranik Godbole, Abhijit M. Njar, Vincent C. O. TI Anti-tumor effects of a novel retinoic acid metabolism blocking agent VN/14-1 in the N-methyl-N-nitrosourea-induced rat mammary carcinoma model and its effects on the uterus SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Retinoic acid metabolism blocking agent (RAMBA); VN/14-1; Anti-tumor efficacy; Blockage of estrogenic stimulation on uterus ID LIAROZOLE FUMARATE R85246; METASTATIC BREAST-CANCER; MECHANICAL-PROPERTIES; UTEROTROPHIC ASSAY; GROWTH; CELLS; ESTROGEN; INHIBITOR; RECEPTORS; LETROZOLE AB VN/14-1 [4-(+/-)-(1H-Imidazol-1-yl)-(E)-retinoic acid], a novel retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of all-trans-retinoic acid. The purpose of this study was to evaluate the anti-tumor effects of VN/14-1 on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, and peripheral organ effects on the uteri of immature ovariectomized (OVX) rats. In tumor burden experiments, after 56 days of administration of VN/14-1 5, 10, and 20 mg/kg/day, significant tumor reductions in mean tumor weight of 19.1, 34.4, and 44.3%, compared to tumors in control animals occurred. Cumulative tumor growth was also significantly slower in a dose-dependent manner in groups receiving 5, 10, and 20 mg/kg/day of VN/14-1 compared to growth rates in the control group. Tumor apoptosis was significant increases in animals treated with 5, 10, and 20 mg/kg/day of VN/14-1. In uterotrophic experiments, immature OVX rats given VN/14-1 significantly reduced uterine weight and blocked endometrial stimulation induced by unopposed beta-estradiol (E2). In both rat models, adverse toxicities included weakness, anorexia, and reduction in body weight in the groups given the highest dose of 20 mg/kg/day. In summary, VN/14-1 inhibited tumor growth in the MNU-induced estrogen receptor (ER)-positive rat mammary tumor model, and antagonized the stimulatory effect of estrogens on the uterus. The studies suggest that VN/14-1 may be a useful novel therapy for ER-positive breast cancer. C1 [Goss, Paul E.; Qi, Shangle; Hu, Haiqing] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Massachusetts Gen Hosp,Canc Ctr,Breast Canc Dis P, Boston, MA 02114 USA. [Gediya, Lalji K.; Purushottamachar, Puranik; Godbole, Abhijit M.; Njar, Vincent C. O.] Thomas Jefferson Univ, Dept Pharmaceut Sci, Jefferson Sch Pharm, Philadelphia, PA 19107 USA. [Gediya, Lalji K.; Purushottamachar, Puranik; Godbole, Abhijit M.; Njar, Vincent C. O.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Goss, PE (reprint author), Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Massachusetts Gen Hosp,Canc Ctr,Breast Canc Dis P, Boston, MA 02114 USA. EM pgoss@partners.org FU US Department of Defense [W81XW-04-1-0101]; US National Institutes of Health and National Cancer Institute (NIH/NCI) [1R01CA12379-01A2]; Golfers against Cancer FX We thank Endocrine Unit and Dr. Ernestina Schipani laboratory, Massachusetts General Hospital and Harvard Medical School for friendly providing the equipment for the bone densitometry. The study was supported in part by grants from the US Department of Defense under the Peer Reviewed Medical Research Program (PRMRP, W81XW-04-1-0101, Njar, VCO), and US National Institutes of Health and National Cancer Institute (NIH/NCI, 1R01CA12379-01A2, Njar VCO) and by Golfers against Cancer. NR 30 TC 1 Z9 1 U1 0 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 2012 VL 133 IS 1 BP 137 EP 144 DI 10.1007/s10549-011-1724-7 PG 8 WC Oncology SC Oncology GA 935HH UT WOS:000303509200013 PM 21842418 ER PT J AU Kuter, I Gee, JMW Hegg, R Singer, CF Badwe, RA Lowe, ES Emeribe, UA Anderson, E Sapunar, F Finlay, P Nicholson, RI Bines, J Harbeck, N AF Kuter, Irene Gee, Julia M. W. Hegg, Roberto Singer, Christian F. Badwe, Rajendra A. Lowe, Elizabeth S. Emeribe, Ugochi A. Anderson, Elizabeth Sapunar, Francisco Finlay, Pauline Nicholson, Robert I. Bines, Jose Harbeck, Nadia TI Dose-dependent change in biomarkers during neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase II study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Estrogen receptor-positive breast cancer; Fulvestrant 500 mg; Faslodex (R); Neoadjuvant; Biomarkers ID ADVANCED BREAST-CANCER; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; MULTICENTER; TRIAL; ANASTROZOLE; TAMOXIFEN AB NEWEST (Neoadjuvant Endocrine Therapy for Women with Estrogen-Sensitive Tumors) is the first study to compare biological and clinical activity of fulvestrant 500 versus 250 mg in the neoadjuvant breast cancer setting. We hypothesized that fulvestrant 500 mg may be superior to 250 mg in blocking estrogen receptor (ER) signaling and growth. A multicenter, randomized, open-label, Phase II study was performed to compare fulvestrant 500 mg (500 mg/month plus 500 mg on day 14 of month 1) versus fulvestrant 250 mg/month for 16 weeks prior to surgery in postmenopausal women with ER+ locally advanced breast cancer. Core biopsies at baseline, week 4, and surgery were assessed for biomarker changes. Primary endpoint: change in Ki67 labeling index (LI) from baseline to week 4 determined by automated computer imaging system (ACIS). Secondary endpoints: ER protein expression and function; progesterone receptor (PgR) expression; tumor response; tolerability. ER and PgR were examined retrospectively using the H score method. A total of 211 patients were randomized (fulvestrant 500 mg: n = 109; 250 mg: n = 102). At week 4, fulvestrant 500 mg resulted in greater reduction of Ki67 LI and ER expression versus 250 mg (-78.8 vs. -47.4% [p < 0.0001] and -25.0 vs. -13.5% [p = 0.0002], respectively [ACIS]); PgR suppression was not significantly different (-22.7 vs. -17.6; p = 0.5677). However, H score detected even greater suppression of ER (-50.3 vs. -13.7%; p < 0.0001) and greater PgR suppression (-80.5 vs. -46.3%; p = 0.0018) for fulvestrant 500 versus 250 mg. At week 16, tumor response rates were 22.9 and 20.6% for fulvestrant 500 and 250 mg, respectively, with considerable decline in all markers by both ACIS and H score. No detrimental effects on endometrial thickness or bone markers and no new safety concerns were identified. This provides the first evidence of greater biological activity for fulvestrant 500 versus 250 mg in depleting ER expression, function, and growth. C1 [Kuter, Irene] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gee, Julia M. W.; Finlay, Pauline; Nicholson, Robert I.] Cardiff Univ, Welsh Sch Pharm, Tenovus Ctr Canc Res, Cardiff, S Glam, Wales. [Hegg, Roberto] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Hegg, Roberto] Hosp Perola Byington, Sao Paulo, Brazil. [Singer, Christian F.] Med Univ Vienna, Div Special Gynaecol, Vienna, Austria. [Badwe, Rajendra A.] Tata Mem Hosp, Bombay 400012, Maharashtra, India. [Lowe, Elizabeth S.; Emeribe, Ugochi A.] AstraZeneca, Wilmington, DE USA. [Anderson, Elizabeth; Sapunar, Francisco] AstraZeneca, Macclesfield, Cheshire, England. [Bines, Jose] Inst Canc Res, Rio De Janeiro, Brazil. [Harbeck, Nadia] Tech Univ Munich, Frauenklin, Munich, Germany. RP Kuter, I (reprint author), Massachusetts Gen Hosp, Profess Off Bldg 228,55 Fruit St, Boston, MA 02114 USA. EM ikuter@partners.org RI Gee, Julia /N-3995-2014 OI Gee, Julia /0000-0001-6483-2015 FU AstraZeneca FX The authors gratefully acknowledge the collaboration of the Munich Study Centre, Munich, Germany, and would like to thank Sandra Cusco, PhD, from Complete Medical Communications, who provided medical writing support funded by AstraZeneca. Final approval of the manuscript lay solely with the authors. The NEWEST study was funded by AstraZeneca. NR 17 TC 27 Z9 28 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2012 VL 133 IS 1 BP 237 EP 246 DI 10.1007/s10549-011-1947-7 PG 10 WC Oncology SC Oncology GA 935HH UT WOS:000303509200022 PM 22286314 ER PT J AU Biswas, S Tankhiwale, N Blackford, A Barrera, AMG Ready, K Lu, K Amos, CI Parmigiani, G Arun, B AF Biswas, Swati Tankhiwale, Neelam Blackford, Amanda Barrera, Angelica M. Gutierrez Ready, Kaylene Lu, Karen Amos, Christopher I. Parmigiani, Giovanni Arun, Banu TI Assessing the added value of breast tumor markers in genetic risk prediction model BRCAPRO SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BRCA2; BRCAPRO; BayesMendel; CancerGene; ER; Her-2/neu; Genetic risk; PR; Validation ID CARRIER PROBABILITY ESTIMATION; IMMUNOHISTOCHEMICAL MARKERS; ESTROGEN-RECEPTOR; CANCER; MUTATIONS; PATHOLOGY AB The BRCAPRO model estimates carrier probabilities for the BRCA1 and BRCA2 genes, and was recently enhanced to use estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. No independent assessment of the added value of these markers exists. Moreover, earlier versions of BRCAPRO did not use human epidermal growth factor receptor 2 (Her-2/neu) status of breast cancer. Here, we incorporate Her-2/neu in BRCAPRO and validate all the markers. We trained the enhanced model on 406 germline tested individuals, and validated on a separate clinical cohort of 796 individuals for whom test results and family history are available. For model-building, we estimated joint probabilities of ER, PR, and Her-2/neu status for carriers and non-carriers of BRCA1/2 mutations. For validation, we obtained BRCAPRO predictions with and without markers. We calculated area under the receiver operating characteristic curve (AUC), sensitivity, specificity, predictive values, and correct reclassification rates. The AUC for predicting BRCA1 status among individuals who are carriers of at least one mutation improved when ER and PR were used. The AUC for predicting the presence of either mutation improved when Her-2/neu was added. Use of markers also produced highly significant correct reclassification improvements in both cases. Breast tumor markers are useful for prediction of BRCA1/2 mutation status. ER and PR improve discrimination between BRCA1 and BRCA2 mutation carriers while Her-2/neu helps discriminate between carriers and non-carriers, particularly among women who are ER positive and Her-2/neu negative. These results support the use of the enhanced version of BRCAPRO in clinical settings. C1 [Biswas, Swati; Tankhiwale, Neelam] Univ N Texas, Hlth Sci Ctr, Dept Biostat, Sch Publ Hlth, Ft Worth, TX 76107 USA. [Blackford, Amanda] Johns Hopkins Sch Med, Div Biostat, Dept Oncol, Baltimore, MD USA. [Barrera, Angelica M. Gutierrez; Ready, Kaylene; Arun, Banu] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol & Clin Canc Genet, Houston, TX 77030 USA. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Clin Canc Genet, Houston, TX 77030 USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Biswas, S (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Biostat, Sch Publ Hlth, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM swati.biswas@unthsc.edu FU University of North Texas Health Science Center [KG081303]; MDACC FX This study was supported in part by the Susan G Komen for the Cure Grant KG081303, an Intramural Seed Grant from the University of North Texas Health Science Center, and the Program in Human and Computational Genomics at MDACC. NR 25 TC 13 Z9 13 U1 0 U2 7 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 2012 VL 133 IS 1 BP 347 EP 355 DI 10.1007/s10549-012-1958-z PG 9 WC Oncology SC Oncology GA 935HH UT WOS:000303509200033 PM 22270937 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Not so fast: the use of incomplete data to devalue the role of mammography screening SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Breast Imaging Div, Boston, MA 02115 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Breast Imaging Div, Boston, MA 02115 USA. EM dkopans@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 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 2012 VL 133 IS 1 BP 399 EP 399 DI 10.1007/s10549-012-1966-z PG 1 WC Oncology SC Oncology GA 935HH UT WOS:000303509200039 PM 22331480 ER PT J AU Saslow, D Solomon, D Lawson, HW Killackey, M Kulasingam, SL Cain, J Garcia, FAR Moriarty, AT Waxman, AG Wilbur, DC Wentzensen, N Downs, LS Spitzer, M Moscicki, AB Franco, EL Stoler, MH Schiffman, M Castle, PE Myers, ER Comm, AAACCG AF Saslow, Debbie Solomon, Diane Lawson, Herschel W. Killackey, Maureen Kulasingam, Shalini L. Cain, Joanna Garcia, Francisco A. R. Moriarty, Ann T. Waxman, Alan G. Wilbur, David C. Wentzensen, Nicolas Downs, Levi S., Jr. Spitzer, Mark Moscicki, Anna-Barbara Franco, Eduardo L. Stoler, Mark H. Schiffman, Mark Castle, Philip E. Myers, Evan R. Comm, Acs-Asccp-Ascp Cervical Canc Guideline TI American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY; LONG-TERM RISK; WOMEN 30 YEARS; COST-EFFECTIVENESS AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012. (C) 2012 American Cancer Society. C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA. [Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30322 USA. [Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, Reg Network, New York, NY 10021 USA. [Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Cain, Joanna] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. [Garcia, Francisco A. R.] Univ Arizona, Ctr Excellence Womens Hlth, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA. [Waxman, Alan G.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Masonic Canc Ctr, Dept Obstet Gynecol & Womens Hlth,Div Gynecol Onc, Minneapolis, MN 55455 USA. [Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Castle, Philip E.] Amer Soc, Clin Pathol Inst, Washington, DC USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Comm, Acs-Asccp-Ascp Cervical Canc Guideline] Steering Comm, Data Grp, Working Grp 1 2 3A 3B 4 5 6, Valdosta, GA USA. [Saslow, Debbie; Castle, Philip E.; Comm, Acs-Asccp-Ascp Cervical Canc Guideline] Writing Comm, New York, NY USA. [Cain, Joanna] Working Grp 2, Stanford, CA USA. [Waxman, Alan G.] Working Grp 3A, Menlo Pk, CA USA. [Garcia, Francisco A. R.; Moriarty, Ann T.] Working Grp 6, Atlanta, GA USA. RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA. EM debbie.saslow@cancer.org RI Colgan, Terence/J-2339-2016; OI Franco, Eduardo/0000-0002-4409-8084 FU Qiagen; Roche; Gen-Probe, Inc; BD; Abbott Laboratories; Roche Molecular Systems; Merck, Inc; GlaxoSmithKline (GSK), Inc.; National Institute of Allergy and Infectious Diseases FX The following reported no financial relationships or potential conflicts of interest to disclose: D. Saslow, E. Partridge, B. Holladay, W. Kinney, H. Lawson, K. Noller, K. Poole, R. Smith, P. Fontaine, A. Herzig, M. Killackey, S. Kulasingam, D. McCoy, W. Brewster, J. Cain, D. Chelmow, V. King, R. Pretorius, B. Winkler, I. Eltoum, J. Kim, N. Wentzensen, L. Downs, S. Greening, H. Haefner, L. Zephyrin, M. Chevarie-Davis, D. Ekwueme, T. Colgan, M. Henry, S. Massad, K. Simon. P. Castle receives payment for service on the Data Monitoring and Safety Board for Merck Sharp & Dohme and has received free or discounted human papillomavirus tests for research from Qiagen and Roche. C. Cohen serves as a speaker for Merck, Inc, and receives honoraria. M. Edelson's spouse is employed by and receives a salary from Merck and Company. F. Garcia is employed by the University of Arizona, which holds contracts for the performance of research with Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company (BD); and MediSpectra/LUMA. He also serves on the Speakers' Bureau for Qiagen and receives honoraria. J. Cuzick serves on advisory boards and as an ad hoc consultant for Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories, with research funds provided to his institution from Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories. P. Gravitt has acted as a member of the Women's Health Advisory Board for Qiagen Corporation and has received research funding from Roche Molecular Systems and Merck, Inc within the last 5 years. E. Myers received research support for investigations for Gen-Probe, Inc, and from GlaxoSmithKline (GSK), Inc. He served as a speaker for and received honoraria from Gen-Probe, Inc, and has served as a consultant for and received honoraria from Gen-Probe, Inc; Merck and Company; and GSK. M. Schiffman holds a research agreement to serve as a medical monitor in the National Cancer Institute (NCI) vaccine trial through GSK; he also receives research support from Qiagen for careHPV research in Nigeria. D. Solomon serves as a medical monitor for the NCI's Costa Rica HPV Vaccine Trial; the trial receives vaccine from GSK. M. Stoler received fees for serving as a consultant to Merck Research Laboratories; Roche; Ventana Medical Systems, Inc; BD; Hologic; MTM Laboratories; and Gen-Probe, Inc. D. Mody conducted lectures and workshops for the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Cytopathology (ASC), for which she received honoraria and/or travel expenses. G. Birdsong's employer receives funding for contracted research performed by him for BD Diagnostics. C. Wheeler is an employee of University of New Mexico, which is contracted by GSK for its vaccine trials and receives equipment/reagents from Roche Molecular Systems, Inc, for human papillomavirus genotyping. D. Wilbur serves on the scientific advisory board for Corista, LLC. T. Darragh received ThinPrep supplies for research from Hologic. She also serves on an advisory board for OncoHealth Corporation and has received stock options as payment and serves on the advisory board of Arbor Vita Corporation. E. Mayeaux serves on the speakers' advisory board for both Merck, Inc, and PharmaDerm and receives honoraria from both companies for his service. M. Spitzer serves as a speaker for both Merck, Inc, and Qiagen and receives honoraria. K.; Ault received clinical research grants from the National Institute of Allergy and Infectious Diseases; Gen-Probe, Inc; Merck, Inc; and Roche and served as a site principal investigator for the research. All grants were provided to his employer, Emory University. E. Franco received honorarium as a Study Steering Committee member for GSK; he also serves on the advisory boards of Merck, Inc; Roche; and Gen-Probe, Inc, from which he receives honoraria and has acted as an ad hoc consultant for Merck, Inc; Roche; Gen-Probe, Inc; and Qiagen, for which honoraria were paid to compensate for time away and work performed. M. Gold received honorarium for serving as a speaker and consultant for Hologic. W. Huh serves as a consultant to Roche; Qiagen; Merck, Inc; and Inovio Pharmaceuticals, Inc and receives honoraria from all 4 companies. A-B. Moscicki received honorarium for serving as a consultant to an advisory board for Merck, Inc. M. Einstein has advised or participated in educational speaking activities, but does not receive an honorarium from any companies. His employer, Montefiore Medical Center, has received payment for his time spent on activities for Merck, Inc; GSK; Roche; Bristol-Myers Squibb; Hologic; Advaxis, Inc; Aura Biosciences, Inc; Inovio Pharmaceuticals, Inc; Photocure ASA; NeoDiagnostix, Inc; and PDS Biotechnology Corporation. Montefiore has received grant funding for research related to the costs of those Merck, GSK, Roche, Advaxis, and Hologic clinical trials for which Dr. Einstein served as the Montefiore principal investigator. A. Moriarty received honorarium as a speaker for ASC. R. Guido has acted as the local principal investigator for a multicenter study (contracted research) for IKONOsys. A. Waxman receives honoraria and expenses for teaching related to the subject matter in this article from nonprofit professional organizations and governmental agencies and contractors. He is on the executive committee of the board of directors of the American Society for Colposcopy and Cervical Pathology; he lectures for them and codirects some of their courses and receives honoraria and expenses for these functions. He also lectures and directs courses for the American College/Congress of Obstetricians and Gynecologists on subjects related to this article and receives honoraria from them. Both organizations are nonprofit professional organizations. He has also received honoraria and expenses from the State of Alaska Department of Health and Social Services and several Alaska Native corporations (Southcentral Foundation, SouthEast Alaska Regional Health Corporation, Arctic Slope Regional Corporation, and Yukon-Kuskokwim Health Corporation) and the Breast Cancer Detection Center of Alaska for lecturing on material related to this article. He also received honoraria from the Center for Health Training, a contractor to Title X agencies for lecturing for the Texas Department of State Health Services. He also received a $200 honorarium from Quadrant HealthCom, Inc for writing an article related to cervical cancer screening for the journal OBG Management. NR 156 TC 357 Z9 378 U1 13 U2 53 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2012 VL 62 IS 3 BP 147 EP 172 DI 10.3322/caac.21139 PG 26 WC Oncology SC Oncology GA 937NO UT WOS:000303665400003 PM 22422631 ER PT J AU Partridge, AH Elmore, JG Saslow, D McCaskill-Stevens, W Schnitt, SJ AF Partridge, Ann H. Elmore, Joann G. Saslow, Debbie McCaskill-Stevens, Worta Schnitt, Stuart J. TI Challenges in ductal carcinoma in situ risk communication and decision-making Report From an American Cancer Society and National Cancer Institute Workshop SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID INVASIVE BREAST-CANCER; QUALITY-OF-LIFE; THE-SCIENCE CONFERENCE; PSYCHOLOGICAL MORBIDITY; INFORMED DECISION; RETHINKING TNM; PERCEIVED RISK; NORTH-AMERICA; WOMEN; DIAGNOSIS AB In September 2010, the American Cancer Society and National Cancer Institute convened a conference to review current issues in ductal carcinoma in situ (DCIS) risk communication and decision-making and to identify directions for future research. Specific topics included patient and health care provider knowledge and attitudes about DCIS and its treatment, how to explain DCIS to patients given the heterogeneity of the disease, consideration of nomenclature changes, and the usefulness of decision tools/aids. This report describes the proceedings of the workshop in the context of the current literature and discusses future directions. Evidence suggests that there is a lack of clarity about the implications and risks of a diagnosis of DCIS among patients, providers, and researchers. Research is needed to understand better the biology and mechanisms of the progression of DCIS to invasive breast cancer and the factors that predict those subtypes of DCIS that do not progress, as well as efforts to improve the communication and informed decision-making surrounding DCIS. CA Cancer J Clin 2012. (C) 2012 American Cancer Society. C1 [Partridge, Ann H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med, Boston, MA 02215 USA. [Elmore, Joann G.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Saslow, Debbie] Amer Canc Soc, Atlanta, GA 30329 USA. [McCaskill-Stevens, Worta] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Schnitt, Stuart J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu FU NCATS NIH HHS [UL1 TR000423] NR 63 TC 15 Z9 17 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2012 VL 62 IS 3 BP 203 EP 210 DI 10.3322/caac.21140 PG 8 WC Oncology SC Oncology GA 937NO UT WOS:000303665400005 PM 22488610 ER PT J AU Krodel, DJ Eikermann, M AF Krodel, David J. Eikermann, Matthias TI Negative Pressure Pulmonary Edema Consider Undiagnosed Obstructive Sleep Apnea Too Response SO CHEST LA English DT Letter ID POSTOPERATIVE COMPLICATIONS; ASSOCIATION C1 [Krodel, David J.; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Krodel, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM dkrodel@partners.org NR 6 TC 0 Z9 0 U1 0 U2 1 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 2012 VL 141 IS 5 BP 1365 EP 1366 DI 10.1378/chest.11-3316 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 940PO UT WOS:000303905700046 ER PT J AU Bansilal, S Bhatt, DL AF Bansilal, Sameer Bhatt, Deepak L. TI Declining Coronary Artery Bypass-Related Mortality: More Than Meets the Eye? SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; INTERVENTION; SURGEONS; OUTCOMES; DISEASE; TRENDS AB Dr. Bhatt receives research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. The authors have no other funding, financial relationships, or conflicts of interest to disclose. C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, TIMI Study Grp, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, TIMI Study Grp, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2012 VL 35 IS 5 BP 261 EP 262 DI 10.1002/clc.21990 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 938UT UT WOS:000303759300003 PM 22528147 ER PT J AU Hagmann, H Thadhani, R Benzing, T Karumanchi, SA Stepan, H AF Hagmann, Henning Thadhani, Ravi Benzing, Thomas Karumanchi, S. Ananth Stepan, Holger TI The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia SO CLINICAL CHEMISTRY LA English DT Review ID PLACENTAL GROWTH-FACTOR; UTERINE ARTERY DOPPLER; CIRCULATING ANTIANGIOGENIC FACTORS; MATERNAL PLASMA-CONCENTRATIONS; LATE-ONSET PREECLAMPSIA; TYROSINE KINASE-1; FACTOR RECEPTOR-1; SOLUBLE ENDOGLIN; EARLY-PREGNANCY; HYPERTENSIVE DISORDERS AB BACKGROUND: An imbalance in circulating factors that regulate blood vessel formation and health, referred to as angiogenic factors, plays a central role in the pathogenesis of preeclampsia. CONTENT: Several studies have demonstrated a strong association between altered circulating angiogenic factors and preeclampsia. These factors include circulating antiangiogenic proteins such as soluble fms-like tyrosine kinase 1 and soluble endoglin and proangiogenic protein such as placental growth factor. Abnormalities in these circulating angiogenic factors are not only present during clinical disease, but also antedate clinical signs and symptoms by several weeks. These alterations are particularly prominent in patients who present with preeclamptic signs and symptoms prematurely and/or in patients with severe preeclampsia. The availability of automated platforms for the rapid measurement of circulating angiogenic proteins in blood samples has now allowed researchers and clinicians to evaluate the utility of these assays in the diagnosis of the disease, in the stratification of patients in clinical trials, or in the monitoring of therapies. In this review we highlight the various studies that have been performed, with a focus on large validation studies. SUMMARY: Measurement of circulating angiogenic proteins for the diagnosis and prediction of preeclampsia is still at an early stage but is rapidly evolving. Standardization across the various automated platforms and prospective studies that demonstrate clinical utility are needed. (C) 2012 American Association for Clinical Chemistry C1 [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Dept Med, Boston, MA 02215 USA. [Hagmann, Henning; Benzing, Thomas] Univ Cologne, Div Renal, Dept Med, D-50931 Cologne, Germany. [Hagmann, Henning; Benzing, Thomas] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Dept Med,Med Sch, Boston, MA USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Stepan, Holger] Univ Hosp Leipzig, Dept Obstet, Leipzig, Germany. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU Howard Hughes Medical Institute; NIEHS NIH HHS [P30 ES002109] NR 84 TC 39 Z9 40 U1 0 U2 0 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 2012 VL 58 IS 5 BP 837 EP 845 DI 10.1373/clinchem.2011.169094 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 937YZ UT WOS:000303701400012 PM 22431894 ER PT J AU Ix, JH Katz, R de Boer, IH Kestenbaurn, BR Peralta, CA Jenny, NS Budoff, M Allison, MA Criqui, MH Siscovick, D Shlipak, MG AF Ix, Joachim H. Katz, Ronit de Boer, Ian H. Kestenbaurn, Bryan R. Peralta, Carmen A. Jenny, Nancy S. Budoff, Matthew Allison, Matthew A. Criqui, Michael H. Siscovick, David Shlipak, Michael G. TI Fetuin-A Is Inversely Associated with Coronary Artery Calcification in Community-Living Persons: The Multi-Ethnic Study of Atherosclerosis SO CLINICAL CHEMISTRY LA English DT Article ID ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; SUBCLINICAL CARDIOVASCULAR-DISEASE; MAINTENANCE HEMODIALYSIS-PATIENTS; ELEVATION MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; TYROSINE KINASE; VASCULAR CALCIFICATION; KIDNEY-FUNCTION; OLDER PERSONS; SERUM AB BACKGROUND: Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain. METHODS: Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC incidence and progression. RESULTS: The mean age was 62 (SD 10) years, and the mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline, there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence. In models adjusted for demographics, traditional cardiovascular disease (CVD) risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%-13%; P = 0.04) greater CAC prevalence compared with quartiles 2-4. Similar associations were observed with CAC severity at baseline, but the association was more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI 3%-21%; P = 0.01) greater CAC severity in adjusted models. There was no significant association of fetuin-A with CAC incidence or progression. CONCLUSIONS: Fetuin-A is inversely associated with CAC severity among community-living individuals without CVD. Whether fetuin-A concentrations are associated with incident CVD event in the general population requires future study. (C) 2012 American Association for Clinical Chemistry C1 [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego, CA 92161 USA. [Criqui, Michael H.] Univ Calif San Diego, Div Cardiol, Dept Med, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.; Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92161 USA. [Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaurn, Bryan R.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.; Kestenbaurn, Bryan R.] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Peralta, Carmen A.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92161 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Jenny, Nancy S.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Budoff, Matthew] Harbor UCLA Med Ctr, Div Cardiol, Dept Med, Los Angeles BioMed Res Inst, Torrance, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Med Sect, San Francisco, CA USA. RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu OI Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute (NHLBI) [R21HL091217, N01-HC-95159, N01-HC-95169]; VA San Diego Healthcare System FX J.H. Ix (principal investigator), National Heart, Lung, and Blood Institute (NHLBI) grants R21HL091217 and contracts N01-HC-95159 through N01-HC-95169 with the NHLBI, to the VA San Diego Healthcare System; R. Katz, NHLBI grants R21HL091217 and contracts N01-HC-95159 through N01-HC-95169 with the NHLBI; D. Sisovick, NHLBI grants R21HL091217 and contracts N01-HC-95159 through N01-HC-95169 with the NHLBI; M. Shlipak, NHLBI grants R21HL091217 and contracts N01-HC-95159 through N01-HC-95169 with the NHLBI.; The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This material is the result of work supported with resources of the VA San Diego Healthcare System. We thank Clydene Nee for administrative review and assistance with this manuscript. NR 43 TC 21 Z9 23 U1 1 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2012 VL 58 IS 5 BP 887 EP 895 DI 10.1373/clinchem.2011.177725 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 937YZ UT WOS:000303701400017 PM 22377528 ER PT J AU Akber, A Portale, AA Johansen, KL AF Akber, Aalia Portale, Anthony A. Johansen, Kirsten L. TI Pedometer-Assessed Physical Activity in Children and Young Adults with CKD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; QUALITY-OF-LIFE; EXERCISE CAPACITY; ACTIVITY RECOMMENDATIONS; ADOLESCENTS; HEMODIALYSIS; OVERWEIGHT; PATTERNS; DIALYSIS; PREVALENCE AB Background and objectives Data on physical activity are limited in children with CKD. The objectives of this study were to measure the level and correlates of physical activity in children and young adults with CKD and to determine the association of physical activity with physical performance and physical functioning. Design, setting, participants, & measurements Physical activity was measured for 7 days using pedometers; physical performance was measured by the 6-minute walk distance (6MWD) and physical functioning with the PedsQL 4.0. Results Study participants were 44 patients 7-20 years of age who had CKD stage 1-4 (n=12), had ESRD and were undergoing dialysis (n=7), or had undergone kidney transplantation (n=25). Participants were very sedentary; they walked 6218 (interquartile range, 3637, 9829) steps per day, considerably less than recommended. Physical activity did not differ among participants in the CKD stage 1-4, ESRD, and transplant groups. Females were less active than males (P < 0.01), and physical activity was 44% lower among young adults (18-20 years) than younger participants (P < 0.05). Physical activity was associated positively with maternal education and hemoglobin concentration and inversely with body mass index. Respective 6MWD in males and females was 2 and approximately 4 SDs below expected. Low levels of physical activity were associated with poor physical performance and physical functioning, after adjustment for age, sex, and body mass index. Conclusions In most participants with CKD, physical activity was considerably below recommended levels. Future studies are needed to determine whether increasing physical activity can improve physical performance and physical functioning. Clin J Ant Soc Nephrol 7: 720-726, 2012. doi: 10.2215/CJN.06330611 C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. [Akber, Aalia; Portale, Anthony A.] Univ Calif San Francisco, Dept Pediat, Div Pediat Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect 111J, 4150 Clement St, San Francisco, CA 94121 USA. EM Kirsten.johansen@Ucsf.edu FU University of California, San Francisco, Nephrology Division [K24DK085153]; National Institutes of Health/National Center for Research Resources University of California, San Francisco-Clinical & Translational Science Institute [UL1 RR024131]; Amgen, Inc.; Abbott Laboratories; Genzyme Corp. FX This project was supported by the University of California, San Francisco, Nephrology Division T32 fellowship training grants (A.A.) and grant K24DK085153 (K.L.J.). This project was also supported by National Institutes of Health/National Center for Research Resources University of California, San Francisco-Clinical & Translational Science Institute grant UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.; K.L.J. also receives research support from Amgen, Inc., and Abbott Laboratories and serves on the National Nephrology Advisory Board of Amgen. A.A.P. receives research support from Genzyme Corp. and Abbott Laboratories. NR 40 TC 15 Z9 16 U1 1 U2 5 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 2012 VL 7 IS 5 BP 720 EP 726 DI 10.2215/CJN.06330611 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 937AZ UT WOS:000303632700006 PM 22422539 ER PT J AU Bomback, AS Smith, RJ Barile, GR Zhang, YZ Heher, EC Herlitz, L Stokes, MB Markowitz, GS D'Agati, VD Canetta, PA Radhakrishnan, J Appel, GB AF Bomback, Andrew S. Smith, Richard J. Barile, Gaetano R. Zhang, Yuzhou Heher, Eliot C. Herlitz, Leal Stokes, M. Barry Markowitz, Glen S. D'Agati, Vivette D. Canetta, Pietro A. Radhakrishnan, Jai Appel, Gerald B. TI Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; ALTERNATIVE PATHWAY; COMPLEMENT; GLOMERULOPATHY; MUTATION AB Background and objectives The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial. Design, setting, participants, & measurements In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria > 1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark. Results The subjects included three patients with dense deposit disease (including one patient with recurrent dense deposit disease in allograft) and three patients with C3 glomerulonephritis (including two patients with recurrent C3 glomerulonephritis in allograft). Genetic and complement function testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic factor in three subjects, and elevated levels of serum membrane attack complex in three subjects. After 12 months, two subjects showed significantly reduced serum creatinine, one subject achieved marked reduction in proteinuria, and one subject had stable laboratory parameters but histopathologic improvements. Elevated serum membrane attack complex levels normalized on therapy and paralleled improvements in creatinine and proteinuria. Conclusions Clinical and histopathologic data suggest a response to eculizumab in some but not all subjects with dense deposit disease and C3 glomerulonephritis. Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered. Clin J Am Soc Nephrol 7: 748-756, 2012. doi: 10.2215/CJN.12901211 C1 [Bomback, Andrew S.; Canetta, Pietro A.; Radhakrishnan, Jai; Appel, Gerald B.] Columbia Univ, Dept Med, Div Nephrol, Med Ctr, New York, NY USA. [Smith, Richard J.; Zhang, Yuzhou] Univ Iowa, Dept Med, Carver Coll Med, Div Nephrol & Mol Otolaryngol, Iowa City, IA 52242 USA. [Smith, Richard J.; Zhang, Yuzhou] Univ Iowa, Renal Res Labs, Carver Coll Med, Iowa City, IA USA. [Barile, Gaetano R.] Columbia Univ, Dept Ophthalmol, Med Ctr, New York, NY 10027 USA. [Heher, Eliot C.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Heher, Eliot C.] Massachusetts Gen Hosp, Transplantat Ctr, Boston, MA 02114 USA. [Herlitz, Leal; Stokes, M. Barry; Markowitz, Glen S.; D'Agati, Vivette D.] Columbia Univ, Med Ctr, Dept Pathol, New York, NY USA. RP Bomback, AS (reprint author), 622 W 168th St,PH 4-124, New York, NY 10032 USA. EM asb68@columbia.edu OI Herlitz, Leal/0000-0003-2665-8559; Stokes, Michael/0000-0003-0958-7672; Canetta, Pietro/0000-0003-1130-5486 FU National Institutes of Health [DK074409]; Center for Glomerular Diseases at Columbia University; Alexion Pharmaceuticals, the manufacturer of Soliris (eculizumab) FX This research was supported, in part, by the Center for Glomerular Diseases at Columbia University and National Institutes of Health Grant DK074409 (to R.J.S.).; This study was supported by an investigator-initiated study grant from Alexion Pharmaceuticals, the manufacturer of Soliris (eculizumab). The investigators were responsible for study design, implementation, data analysis, and manuscript preparation. G.B.A. has received consulting honoraria from Alexion Pharmaceuticals. NR 18 TC 114 Z9 126 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2012 VL 7 IS 5 BP 748 EP 756 DI 10.2215/CJN.12901211 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 937AZ UT WOS:000303632700010 PM 22403278 ER PT J AU Isakova, T Xie, HL Barchi-Chung, A Smith, K Sowden, N Epstein, M Collerone, G Keating, L Juppner, H Wolf, M AF Isakova, Tamara Xie, Huiliang Barchi-Chung, Allison Smith, Kelsey Sowden, Nicole Epstein, Michael Collerone, Gina Keating, Leigh Jueppner, Harald Wolf, Myles TI Daily Variability in Mineral Metabolites in CKD and Effects of Dietary Calcium and Calcitriol SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; FIBROBLAST GROWTH FACTOR-23; CHRONIC RENAL-INSUFFICIENCY; VITAMIN-D METABOLISM; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; PHOSPHATE; FGF23; HYPERCALCIURIA; REABSORPTION AB Background and objectives Primary prevention of disordered mineral metabolism in CKD necessitates knowledge of its early pathophysiology. This study evaluated daily fluctuations in mineral metabolites in patients with CKD stages 3 and 4 before and after short-term calcitriol treatment and tested the effects of dietary calcium and calcitriol supplementation on these parameters in the dynamic postprandial setting. Design, setting, participants, S, measurements Twelve CKD patients received calcitriol (0.25 mu g daily for 1 week) with hourly assessments of mineral metabolites made throughout the day and in the context of standardized meals before and after treatment. Calcium content (250 versus 500 mg) in the breakfasts constituted the dietary calcium intervention. Twelve healthy volunteers were used as controls. Results At baseline, compared with controls, fasting CKD subjects had higher parathyroid hormone and fibroblast growth factor 23 levels and greater fractional excretion of phosphate. After breakfast, urinary calcium excretion increased and parathyroid hormone levels dipped transiently in both groups, but they rose soon thereafter, reaching higher peaks in CKD. Calcitriol decreased fasting parathyroid hormone levels, and when combined with dietary calcium load, it normalized the postprandial parathyroid and calcemic responses. Daily variability in mineral metabolites was preserved in CKD before and after calcitriol. Fibroblast growth factor 23 levels increased after calcitriol, although the response was heterogeneous. Conclusions Short-term treatment with calcitriol and dietary calcium supplementation normalizes the parathyroid and calcemic postprandial responses in patients with CKD, in whom the diurnal rhythms of mineral metabolites are preserved. Future studies should investigate the variable fibroblast growth factor 23 response to calcitriol in CKD. Chit J Am Soc Nephrol 7: 820-828, 2012. doi: 10.2215/CJN.11721111 C1 [Isakova, Tamara; Barchi-Chung, Allison; Smith, Kelsey; Sowden, Nicole; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. [Xie, Huiliang] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Epstein, Michael; Collerone, Gina] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Keating, Leigh] Massachusetts Gen Hosp, Dept Med, Clin Res Ctr, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Nephrol, Boston, MA 02114 USA. RP Isakova, T (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, 1120 NW 14th St, Miami, FL 33136 USA. EM tisakova@med.miami.edu FU Harvard Clinical and Translational Science Center from the National Center for Research Resources [M01-RR-01066, 1 UL1 RR025758-03]; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK087858, R01DK076116, R01DK081374]; American Kidney Fund FX This study was supported by Harvard Clinical and Translational Science Center from the National Center for Research Resources Grants M01-RR-01066 and 1 UL1 RR025758-03, National Institute of Diabetes and Digestive and Kidney Diseases Grants K23DK087858 (to T.I.), R01DK076116 (to MW.), and R01DK081374 (to M.W.), and the American Kidney Fund (T.I.). NR 28 TC 20 Z9 20 U1 0 U2 21 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 2012 VL 7 IS 5 BP 820 EP 828 DI 10.2215/CJN.11721111 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 937AZ UT WOS:000303632700018 PM 22383746 ER PT J AU Molitoris, BA Okusa, MD Palevsky, PM Kimmel, PL Star, RA AF Molitoris, Bruce A. Okusa, Mark D. Palevsky, Paul M. Kimmel, Paul L. Star, Robert A. TI Designing Clinical Trials in Acute Kidney Injury SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID ACUTE-RENAL-FAILURE; MORTALITY C1 [Kimmel, Paul L.; Star, Robert A.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Molitoris, Bruce A.] Indiana Univ, Dept Med, Indianapolis, IN USA. [Molitoris, Bruce A.] Roudebush VA Med Ctr, Indianapolis, IN USA. [Okusa, Mark D.] Univ Virginia Hlth Syst, Div Nephrol, Charlottesville, VA USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Kimmel, PL (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM KimmelP@extra.niddk.nih.gov OI Palevsky, Paul/0000-0002-7334-5400 NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2012 VL 7 IS 5 BP 842 EP 843 DI 10.2215/CJN.12801211 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 937AZ UT WOS:000303632700021 PM 22442185 ER PT J AU Fang, SC Mehta, AJ Alexeeff, SE Gryparis, A Coull, B Vokonas, P Christiani, DC Schwartz, J AF Fang, Shona C. Mehta, Amar J. Alexeeff, Stacey E. Gryparis, Alexandros Coull, Brent Vokonas, Pantel Christiani, David C. Schwartz, Joel TI Residential Black Carbon Exposure and Circulating Markers of Systemic Inflammation in Elderly Males: The Normative Aging Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; black carbon; cardiovascular disease; coronary heart disease; diabetes; inflammation; land-use regression model; particulate matter; susceptible; traffic ID PARTICULATE AIR-POLLUTION; TYPE-2 DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; TNF-ALPHA; MYOCARDIAL-INFARCTION; HEART-DISEASE; ASSOCIATION; RISK; PARTICLES AB BACKGROUND: Traffic-related particles (TRPs) are associated with adverse cardiovascular events. The exact mechanisms are unclear, but systemic inflammatory responses likely play a role. OBJECTIVES: We conducted a repeated measures study among male participants of the Normative Aging Study in the greater Boston, Massachusetts, area to determine whether individual-level residential black carbon (BC), a marker of TRPs, is associated with systemic inflammation and whether coronary heart disease (CHD), diabetes, and obesity modify associations. METHODS: We quantified markers of inflammation in 1,163 serum samples from 580 men. Exposure to BC up to 4 weeks prior was predicted from a validated spatiotemporal land-use regression model. Linear mixed effects models estimated the effects of BC on each marker while adjusting for potential confounders. RESULTS: Associations between BC and blood markers were not observed in main effects models or when stratified by obesity status. However, BC was positively associated with markers of inflammation in men with CHD (particularly vascular endothelial growth factor) and in men with diabetes (particularly interleukin-1 beta and tumor necrosis factor-alpha). Significant exposure time windows varied by marker, although in general the strongest associations were observed with moving averages of 2-7 days after a lag of several days. CONCLUSIONS: In an elderly male population, estimated BC exposures were positively associated with markers of systemic inflammation but only in men with CHD or diabetes. C1 [Fang, Shona C.; Mehta, Amar J.; Alexeeff, Stacey E.; Christiani, David C.; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Mehta, Amar J.] Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol Unit, Basel, Switzerland. [Mehta, Amar J.] Univ Basel, Dept Publ Hlth, Basel, Switzerland. [Gryparis, Alexandros] Univ Crete, Dept Appl Math, Iraklion, Greece. [Coull, Brent] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Vokonas, Pantel] Vet Affairs Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fang, SC (reprint author), 665 Huntington Ave,Bldg 1,Room 1411, Boston, MA 02115 USA. EM sfang@hsph.harvard.edu FU National Institutes of Health [1R01 ES014663-01A2]; Harvard-National Institute for Occupational Safety and Health Education and Research Center [T42 OH008416-04]; Epidemiology Research and Information Center (ERIC) of the Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC); American Heart Association FX This research was supported by National Institutes of Health grant 1R01 ES014663-01A2 and Harvard-National Institute for Occupational Safety and Health Education and Research Center Pilot Project grant T42 OH008416-04. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center (ERIC) of the Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). S.C. Fang was supported by an award from the American Heart Association. NR 38 TC 14 Z9 15 U1 2 U2 10 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2012 VL 120 IS 5 BP 674 EP 680 DI 10.1289/ehp.1103982 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 935UF UT WOS:000303546000030 PM 22336131 ER PT J AU Poh, KK Lee, LC Shen, L Chong, E Tan, YL Chai, P Yeo, TC Wood, MJ AF Poh, Kian Keong Lee, Li Ching Shen, Liang Chong, Eric Tan, Yee Leng Chai, Ping Yeo, Tiong Cheng Wood, Malissa J. TI Left ventricular fluid dynamics in heart failure: echocardiographic measurement and utilities of vortex formation time SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING LA English DT Article DE Vortex formation time; Heart failure; Systolic; Preserved ejection fraction; Diastolic dysfunction; Myocardial performance index; Echocardiography; Tissue Doppler; Prognostic significance ID PRESERVED EJECTION FRACTION; TRANSMITRAL FLOW EFFICIENCY; PARTICLE IMAGE VELOCIMETRY; ACUTE MODERATE ELEVATION; DOPPLER-ECHOCARDIOGRAPHY; DIASTOLIC FUNCTION; CLINICAL CHARACTERISTICS; SYSTOLIC FUNCTION; TEI INDEX; DYSFUNCTION AB Background In clinical heart failure (HF), inefficient propagation of blood through the left ventricle (LV) may result from suboptimal vortex formation (VF) ability of the LV during early diastole. We aim to (i) validate echocardiographic-derived vortex formation time (adapted) (VFTa) in control subjects and (ii) examine its utility in both systolic and diastolic HF. Methods Transthoracic echocardiography was performed in 32 normal subjects and in 130 patients who were hospitalized with HF [91, reduced ejection fraction (rEF) and 39, preserved ejection fraction (pEF)]. In addition to biplane left ventricular ejection fraction (LVEF) and conventional parameters, the Tei index and tissue Doppler (TD) indices were measured. VFTa was obtained using the formula: 4 x (1 - beta)/pi x alpha(3) x LVEF, where beta is the fraction of total transmitral diastolic stroke volume contributed by atrial contraction (assessed by time velocity integral of the mitral E- and A-waves) and alpha is the biplane end-diastolic volume (EDV)(1/3) divided by mitral annular diameter during early diastole. VFTa was correlated with demographic, cardiac parameters, and a composite clinical endpoint comprising cardiac death and repeat hospitalization for HF. Results Mean VFTa was 2.67 +/- 0.8 in control subjects; reduced in HF, preserved EF HF, 2.21 +/- 0.8; HF with reduced EF, 1.25 +/- 0.6 (P < 0.001). It was not affected by age, gender, body surface area but was correlated positively with TD early diastolic myocardial velocities (E', septal, r = 0.46; lateral, r = 0.43), systolic myocardial velocities (S', septal, r = 0.47; lateral, r = 0.41), and inversely with the Tei index (r = -0.41); all Ps < 0.001. Sixty-two HF patients (49%) met the composite endpoint. VFTa of < 1.32 was associated with significantly reduced event-free survival (Kaplan Meier log rank = 16.3, P = 0.0001) and predicted the endpoint with a sensitivity and specificity of 65 and 72%, respectively. Conclusion VFTa, a dimensionless index, incorporating LV geometry, systolic and diastolic parameters, may be useful in the diagnosis and prognosis of HF. C1 [Poh, Kian Keong; Lee, Li Ching; Chong, Eric; Tan, Yee Leng; Chai, Ping; Yeo, Tiong Cheng] Natl Univ Heart Ctr, Dept Cardiac, Singapore 119228, Singapore. [Poh, Kian Keong; Shen, Liang] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Poh, Kian Keong; Wood, Malissa J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Poh, KK (reprint author), Natl Univ Heart Ctr, Dept Cardiac, 1E,Kent Ridge Rd,NUHS Tower Block,Level 9, Singapore 119228, Singapore. EM doctorpoh@yahoo.com NR 45 TC 17 Z9 19 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2047-2404 J9 EUR HEART J-CARD IMG JI Eur. Heart J.-Cardiovasc. Imaging PD MAY PY 2012 VL 13 IS 5 BP 385 EP 393 DI 10.1093/ejechocard/jer288 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 936ZH UT WOS:000303628300004 PM 22180464 ER PT J AU Satou, R Miyata, K Gonzalez-Villalobos, RA Ingelfinger, JR Navar, LG Kobori, H AF Satou, Ryousuke Miyata, Kayoko Gonzalez-Villalobos, Romer A. Ingelfinger, Julie R. Navar, L. Gabriel Kobori, Hiroyuki TI Interferon-gamma biphasically regulates angiotensinogen expression via a JAK-STAT pathway and suppressor of cytokine signaling 1 (SOCS1) in renal proximal tubular cells SO FASEB JOURNAL LA English DT Article DE kidney; inflammation; hypertension ID MESSENGER-RNA; INTRARENAL ANGIOTENSINOGEN; AUGMENTS ANGIOTENSINOGEN; DIABETIC-NEPHROPATHY; GENE; KIDNEY; TRANSCRIPTION; HYPERTENSION; ACTIVATION; RECEPTOR AB Renal inflammation modulates angiotensinogen (AGT) production in renal proximal tubular cells (RPTCs) via inflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and interferon-gamma (IFN-gamma). Among these, the effects of IFN-gamma on AGT regulation in RPTCs are incompletely delineated. This study aimed to elucidate mechanisms by which IFN-gamma regulates AGT expression in RPTCs. RPTCs were incubated with or without IFN-gamma up to 48 h. AGT expression, STAT1 and STAT3 activities, and SOCS1 expression were evaluated. RNA interference studies against STAT1, SOCS1, and STAT3 were performed to elucidate a signaling cascade. IFN-gamma decreased AGT expression at 6 h (0.61 +/- 0.05, ratio to control) and 12 h (0.47 +/- 0.03). In contrast, longer exposure for 24 and 48 h increased AGT expression (1.76 +/- 0.18, EC50 +/- 3.4 ng/ml, and 1.45 +/- 0.08, respectively). IFN-gamma treatment for 6 h strongly induced STAT1 phosphorylation and SOCS1 augmentation, and decreased STAT3 activity. However, STAT1 phosphorylation and SOCS1 augmentation waned at 24 h, while STAT3 activity increased. RNA interference studies revealed that activation of STAT1-SOCS1 axis decreased STAT3 activity. Thus, IFN-gamma biphasically regulates AGT expression in RPTCs via STAT3 activity modulated by STAT1-SOCS1 axis, suggesting the STAT1-SOCS1 axis is important in IFN-gamma-induced activation of the intrarenal renin-angiotensin system.-Satou, R., Miyata, K., Gonzalez-Villalobos, R. A., Ingelfinger, J. R., Navar, L. G., Kobori, H. Interferon-gamma biphasically regulates angiotensinogen expression via a JAK-STAT pathway and suppressor of cytokine signaling 1 (SOCS1) in renal proximal tubular cells. FASEB J. 26, 1821-1830 (2012). www.fasebj.org C1 [Satou, Ryousuke; Miyata, Kayoko; Navar, L. Gabriel; Kobori, Hiroyuki] Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. [Satou, Ryousuke; Miyata, Kayoko; Navar, L. Gabriel; Kobori, Hiroyuki] Tulane Univ, Hlth Sci Ctr, Hypertens & Renal Ctr Excellence, New Orleans, LA 70112 USA. [Gonzalez-Villalobos, Romer A.] Cedars Sinai Med Ctr, Dept Biomed Sci & Pathol, Los Angeles, CA 90048 USA. [Gonzalez-Villalobos, Romer A.] Cedars Sinai Med Ctr, Dept Lab Med, Los Angeles, CA 90048 USA. [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Satou, R (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Physiol, 1430 Tulane Ave,SL39-M720, New Orleans, LA 70112 USA. EM rsato@tulane.edu RI Kobori, Hiroyuki/F-1994-2014 OI Kobori, Hiroyuki/0000-0001-5128-5059 FU U.S. National Institute of Diabetes and Digestive and Kidney Diseases [R01DK072408, K99DK083455]; National Center for Research Resources [P20RR017659]; National Heart, Lung, and Blood Institute [R01HL026371] FX The authors acknowledge the valuable comments and excellent technical assistance of Dr. Maki Urushihara, Dr. Masumi Kamiyama, Dr. Daisuke Inui, Dr. Omar W. Acres, Ms. Akemi Katsurada, and Ms. Ayumi Kitano (Tulane University). This study was supported by grants from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072408 and K99DK083455), the National Center for Research Resources (P20RR017659), and the National Heart, Lung, and Blood Institute (R01HL026371). The authors declare no conflicts of interest. NR 44 TC 23 Z9 24 U1 2 U2 7 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 2012 VL 26 IS 5 BP 1821 EP 1830 DI 10.1096/fj.11-195198 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 937TD UT WOS:000303680800010 PM 22302831 ER PT J AU Townsend, KL Suzuki, R Huang, TL Jing, EX Schulz, TJ Lee, K Taniguchi, CM Espinoza, DO McDougall, LE Zhang, HB He, TC Kokkotou, E Tseng, YH AF Townsend, Kristy L. Suzuki, Ryo Huang, Tian Lian Jing, Enxuan Schulz, Tim J. Lee, Kevin Taniguchi, Cullen M. Espinoza, Daniel O. McDougall, Lindsay E. Zhang, Hongbin He, Tong-Chuan Kokkotou, Efi Tseng, Yu-Hua TI Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway SO FASEB JOURNAL LA English DT Article DE hypothalamus; p70S6K ID MESOLIMBIC DOPAMINE SYSTEM; NEUROTROPHIC FACTOR; MAMMALIAN TARGET; ENERGY-BALANCE; FOOD-INTAKE; STEM-CELLS; MELANOCORTIN-4 RECEPTOR; TRANSLATION MACHINERY; NERVOUS-SYSTEM; RAT MODEL AB Body weight is regulated by coordinating energy intake and energy expenditure. Transforming growth factor beta (TGF beta)/bone morphogenetic protein (BMP) signaling has been shown to regulate energy balance in lower organisms, but whether a similar pathway exists in mammals is unknown. We have previously demonstrated that BMP7 can regulate brown adipogenesis and energy expenditure. In the current study, we have uncovered a novel role for BMP7 in appetite regulation. Systemic treatment of diet-induced obese mice with BMP7 resulted in increased energy expenditure and decreased food intake, leading to a significant reduction in body weight and improvement of metabolic syndrome. Similar degrees of weight loss with reduced appetite were also observed in BMP7-treated ob/ob mice, suggesting a leptin-independent mechanism utilized by BMP7. Intracerebroventricular administration of BMP7 to mice led to an acute decrease in food intake, which was mediated, at least in part, by a central rapamycin-sensitive mTOR-p70S6 kinase pathway. Together, these results underscore the importance of BMP7 in regulating both food intake and energy expenditure, and suggest new therapeutic approaches for obesity and its comorbidities.-Townsend, K. L., Suzuki, R., Huang, T. L., Jing, E., Schulz, T. J., Lee, K., Taniguchi, C. M., Espinoza, D. O., McDougall, L. E., Zhang, H., He, T.-C., Kokkotou, E., Tseng, Y.-H. Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway. FASEB J. 26, 2187-2196 (2012). www.fasebj.org C1 [Townsend, Kristy L.; Suzuki, Ryo; Huang, Tian Lian; Jing, Enxuan; Schulz, Tim J.; Lee, Kevin; Taniguchi, Cullen M.; Espinoza, Daniel O.; McDougall, Lindsay E.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [He, Tong-Chuan] Univ Chicago, Med Ctr, Mol Oncol Lab, Chicago, IL 60637 USA. [Kokkotou, Efi] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM ekokkoto@caregroup.harvard.edu; yu-hua.tseng@joslin.harvard.edu RI Schulz, Tim/F-4842-2013 OI Schulz, Tim/0000-0002-8413-3972 FU U.S. National Institutes of Health (NIH) [NIH R01 DK077097, UL1 RR 025758-01]; Eli Lilly Research Foundation; Harvard Stem Cell Institute [NIH R01 DK080058]; NIH [T32-DK007260-33, F32-DK091996]; Joslin Diabetes and Endocrinology Center; National Institute of Diabetes and Digestive and Kidney Diseases [P30-DK036836] FX This work was supported in part by U.S. National Institutes of Health (NIH) grants NIH R01 DK077097 and UL1 RR 025758-01 (Harvard Catalyst/The Harvard Clinical and Translational Science Center) and research grants from the Eli Lilly Research Foundation and Harvard Stem Cell Institute (to Y.-H.T.) and NIH R01 DK080058 (to E.K.). K.L.T. was supported by NIH T32-DK007260-33 and F32-DK091996. The Joslin Physiology and Special Assay Cores were supported by the Joslin Diabetes and Endocrinology Center, grant P30-DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors thank C. R. Kahn (Joslin Diabetes Center) for helpful discussion, and Andre Kleinridders (Joslin Diabetes Center) for technical advice. The authors declare no conflicts of interest. K.L.T. wrote the manuscript and conducted several of the experiments. R.S. performed most of the i.c.v. experiments. T.L.H. performed several of the in vitro and in vivo experiments. E.J. did the immunohistochemical staining. T.J.S. performed some of the LacZ staining and assisted with some of the i.c.v. studies. K.L. did the in situ hybridization and part of the LacZ staining. D.O.E. performed some of the in vitro studies and assisted with some of the i.c.v. studies. C.M.T. did the adenovirus experiments. L.E.M. assisted with the animal studies and RNA extractions. T.-C.H. provided the adenovirus and technical expertise. E.K. and Y.-H.T. designed the studies, performed the key experiments, and wrote the manuscript. NR 60 TC 40 Z9 43 U1 0 U2 8 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 2012 VL 26 IS 5 BP 2187 EP 2196 DI 10.1096/fj.11-199067 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 937TD UT WOS:000303680800044 PM 22331196 ER PT J AU Maleki, N Becerra, L Brawn, J Bigal, M Burstein, R Borsook, D AF Maleki, N. Becerra, L. Brawn, J. Bigal, M. Burstein, R. Borsook, D. TI Functional and Structural Changes in Primary Somatosensory Cortex in Migraine SO HEADACHE LA English DT Meeting Abstract CT 54th Annual Scientific Meeting on American-Headache-Society CY JUN 21-24, 2012 CL Los Angeles, CA SP Amer Headache Soc C1 [Maleki, N.; Becerra, L.; Brawn, J.; Borsook, D.] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA. [Bigal, M.] Merck & Co Inc, Merck Res Labs, N Wales, PA USA. [Burstein, R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Becerra, L.; Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Becerra, L.; Borsook, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2012 VL 52 IS 5 BP 865 EP 865 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 936NA UT WOS:000303595900029 ER PT J AU Sommers, BD Tomasi, MR Swartz, K Epstein, AM AF Sommers, Benjamin D. Tomasi, Meredith Roberts Swartz, Katherine Epstein, Arnold M. TI Reasons For The Wide Variation In Medicaid Participation Rates Among States Hold Lessons For Coverage Expansion In 2014 SO HEALTH AFFAIRS LA English DT Article ID HEALTH-INSURANCE PROGRAM; TAKE-UP; PUBLIC INSURANCE; DROP-OUT; CARE; ACCESS; SCHIP; CHILDREN AB The Affordable Care Act will expand Medicaid eligibility in 2014 to adults with incomes of up to 133 percent of the federal poverty level. To maximize this opportunity, policy makers need to ensure that participation, or "take-up," among eligible adults exceeds current rates. Using the Current Population Survey 2005-10, we estimated that the nationwide Medicaid participation rate was 62.6 percent among eligible adults ages 19-64 without private insurance. Take-up varied widely by state, from 43.0 percent in Arkansas and Louisiana to 82.8 percent in Massachusetts, after adjusting for population demographics. Participation was highest among disabled adults, 75.8 percent, and lowest among childless adults, 38.3 percent. Factors linked to higher take-up rates included low cost sharing for beneficiaries; more generous benefits; and greater use of managed care programs for Medicaid populations. Factors associated with lower take-up rates included the existence of asset tests in some states. Massachusetts's health reform was associated with a major increase in Medicaid participation. Our results suggest that when Medicaid is expanded in 2014, take-up may be less than anticipated because new enrollees will be offered a more restrictive set of benefits-known as " benchmark coverage"-compared to those in traditional Medicaid, and the majority of newly eligible adults will be in groups with traditionally low take-up (primarily nondisabled adults). To encourage high participation in the expanded Medicaid program, states will need to offer comprehensive coverage of needed benefits; provide community-based outreach; and consider more dramatic changes to their enrollment processes, such as automatically enrolling people in Medicaid based on their participation in other public programs. C1 [Sommers, Benjamin D.; Epstein, Arnold M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Sommers, Benjamin D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sommers, Benjamin D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tomasi, Meredith Roberts] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sommers, BD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. EM bsommers@hsph.harvard.edu FU Agency for Healthcare Research and Quality [R03 HS19754-01] FX A preliminary version of this article was presented at the regional and national meetings of the Society for General Internal Medicine in Boston, Massachusetts, on March 4, 2011, and in Phoenix, Arizona, on May 5, 2011. This work was supported by funding from the Agency for Healthcare Research and Quality (R03 HS19754-01; principal investigator: Benjamin Sommers). The authors are grateful to Alan Weil and Anna Aizer for helpful feedback on earlier versions of this article. NR 42 TC 35 Z9 35 U1 0 U2 19 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 PY 2012 VL 31 IS 5 BP 909 EP 919 DI 10.1377/hlthaff.2011.0977 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 940EP UT WOS:000303873100004 PM 22566429 ER PT J AU Roysland, R Bonaca, MP Omland, T Sabatine, M Murphy, SA Scirica, BM Bjerre, M Flyvbjerg, A Braunwald, E Morrow, DA AF Roysland, Ragnhild Bonaca, Marc P. Omland, Torbjorn Sabatine, Marc Murphy, Sabina A. Scirica, Benjamin M. Bjerre, Mette Flyvbjerg, Allan Braunwald, Eugene Morrow, David A. TI Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes SO HEART LA English DT Article ID PROGNOSTIC VALUE; HEART-FAILURE; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; EARLY-ONSET; CALCIFICATION; OSTEOPOROSIS; POPULATION; DENOSUMAB; DISEASE AB Objective To assess the relationship between osteoprotegerin (OPG) and cardiovascular death, and the pathobiological mechanisms contributing to the association, in acute coronary syndromes (ACS). Design Prospective observational. Setting Biomarker substudy of MERLIN-TIMI 36, a randomised, placebo controlled trial of ranolazine in non-ST elevation (NSTE)-ACS. Patients 4463 patients with NSTE-ACS. Interventions Ranolazine or placebo. Main outcome measures Incidence of cardiovascular death (CV death); additionally, heart failure (HF), cardiac arrhythmias, inhospital ischaemia, severe recurrent ischaemia or recurrent myocardial infarction (MI). Results During a median follow-up of 341 days, 208 patients died of cardiovascular causes. The OPG baseline concentration was strongly associated with both 30 day and 1 year incidence of CV death. After adjustment for conventional risk markers, OPG concentrations (log transformed) remained a significant predictor of CV death by 30 days (HR (95% CI) 2.32 (1.30 to 4.17); p=0.005) and by 1 year (HR 1.85 (1.33 to 2.59); p<0.001). Baseline levels of OPG were also an independent predictor of new or worsening HF at 30 days (HR 2.25 (1.38 to 3.69); p=0.001) and 1 year (HR 1.81 (1.26 to 2.58) p=0.001). By univariable analysis, higher OPG was associated with both early ischaemic and arrhythmic events. Although OPG levels were associated with recurrent MI within 12 months, this association was attenuated and no longer significant after multivariable adjustment. Conclusions OPG is independently associated with 30 day and 1 year risk of cardiovascular mortality and HF development after NSTE-ACS. As no independent relationship between OPG levels and recurrent ischaemia or MI was observed, myocardial dysfunction may be a more important stimulus for OPG production than ischaemia in ACS. C1 [Roysland, Ragnhild; Omland, Torbjorn] Akershus Univ Hosp, Div Med, N-1478 Lorenskog, Norway. [Roysland, Ragnhild; Omland, Torbjorn] Univ Oslo, KG Jebsen Cardiac Res Ctr, Oslo, Norway. [Roysland, Ragnhild; Omland, Torbjorn] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway. [Bonaca, Marc P.; Sabatine, Marc; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bonaca, Marc P.; Sabatine, Marc; Scirica, Benjamin M.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Bjerre, Mette; Flyvbjerg, Allan] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Bjerre, Mette; Flyvbjerg, Allan] Aarhus Univ, Fac Hlth Sci, Dept Clin Med, Med Res Labs, Aarhus, Denmark. RP Omland, T (reprint author), Akershus Univ Hosp, Div Med, Sykehusveien 27, N-1478 Lorenskog, Norway. EM torbjorn.omland@medisin.uio.no FU Gilead Science Inc; Roche Diagnostics; Abbott Laboratories; Amarin; Eli Lilly; Novartis Pharmaceuticals Corporation; AstraZeneca Pharmaceuticals LP; Daiichi-Sankyo Inc; Merck Co Inc; Johnson and Johnson Pharmaceutical Research & Development LLC; Bayer HealthCare Pharmaceuticals; Bristol-Myers-Squibb Company; TIMI Study Group; Accumetrics; Amgen; AstraZeneca; Beckman Coulter; BG Medicine; BRAHMS; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Integrated Therapeutics; Merck and Co; Nanosphere; Novartis Pharmaceuticals; Nuvelo; Ortho-Clinical Diagnostics; Pfizer; Sanofi-Aventis; Sanofi-Synthelabo; Siemens; Singulex FX MERLIN-TIMI 36 was supported by CV Therapeutics (now Gilead Science Inc). The company had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.; TO has received speakers' honoraria and research support from Roche Diagnostics and Abbott Laboratories. MS has received grants for clinical research via the TIMI Study Group and Brigham and Women's Hospital from Nanosphere and served as a consultant for Singulex. SAM has received consultant fees from Amarin and Eli Lilly. BMS has received grants for clinical research via the TIMI Study Group and Brigham and Women's Hospital from CV Therapeutics, Novartis Pharmaceuticals Corporation, AstraZeneca Pharmaceuticals LP, Daiichi-Sankyo Inc, Merck & Co Inc, Johnson and Johnson Pharmaceutical Research & Development LLC, Bayer HealthCare Pharmaceuticals and Bristol-Myers-Squibb Company, and has served as a consultant for AstraZeneca Pharmaceuticals LP, Novartis Pharmaceuticals Corporation, CV Therapeutics, Cogentus, Shionogi and Co Ltd, Gilead Sciences Inc, Merck & Co Inc and Schering-Plough Corporation. DAM is an investigator and receives salary from the TIMI Study Group. He has received honoraria for educational presentations from Eli Lilly. He has received remuneration for consulting from Beckman-Coulter, Boehringher Ingelheim, Cardiokinetix, Critical Diagnostics, Gilead, Instrumentation Laboratory, Ikaria, Menarini, Merck, OrthoClinical Diagnostics, Servier, Roche Diagnostics and Siemens, and remuneration from AstraZeneca for adjudication as a member of a Clinical Events Committee. The TIMI Study Group has received research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Siemens and Singulex. NR 30 TC 16 Z9 16 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAY PY 2012 VL 98 IS 10 BP 786 EP 791 DI 10.1136/heartjnl-2011-301260 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 941UO UT WOS:000303992200007 PM 22373720 ER PT J AU Chen, DD Dong, YG Yuan, H Chen, AF AF Chen, Dan-Dan Dong, Yu-Gang Yuan, Hong Chen, Alex F. TI Endothelin 1 Activation of Endothelin A Receptor/NADPH Oxidase Pathway and Diminished Antioxidants Critically Contribute to Endothelial Progenitor Cell Reduction and Dysfunction in Salt-Sensitive Hypertension SO HYPERTENSION LA English DT Article DE endothelin 1; oxidative stress; NADPH oxidase; endothelial progenitor cell; hypertension ID MANGANESE SUPEROXIDE-DISMUTASE; CORONARY-ARTERY-DISEASE; OXIDATIVE STRESS; MINERALOCORTICOID HYPERTENSION; CARDIOVASCULAR DISORDERS; ETA-RECEPTOR; PROTEIN; RATS; SENESCENCE; EXPRESSION AB Circulating endothelial progenitor cells (EPCs) are reduced in hypertension, which inversely correlates with its mortality. Deoxycorticosterone acetate (DOCA)-salt hypertension features elevated endothelin (ET) 1 and oxidative stress. We tested the hypothesis that ET-1 induces EPC dysfunction by elevating oxidative stress through the ETA/NADPH oxidase pathway in salt-sensitive hypertension. Both ETA and ETB receptors were expressed in EPCs, but only ETA receptors were significantly increased in EPCs of DOCA-salt rats. EPC number and function were reduced in DOCA-salt rats compared with sham controls, and both were reversed by in vivo blockade of ETA receptors or NADPH oxidase. The enzymatic activities of NAPDH oxidase and its subunits gp91(phox), p22(phox), and Rac1 were augmented in EPCs of DOCA-salt rats, with concomitantly decreased antioxidant enzymes manganese superoxide dismutase, copper-zinc superoxide dismutase, and glutathione peroxidase 1. Reactive oxygen species level was elevated in EPCs from DOCA-salt rats, accompanied by increased EPC telomerase inactivation, senescence, and apoptosis, which were rescued by ETA or NADPH oxidase blockade. Cell therapy of normal or treated DOCA EPCs, but not untreated DOCA EPCs, significantly increased capillary density and blood perfusion in ischemic hindlimbs of DOCA-salt rats. p53 and Bax/Bcl-2 ratios were increased in EPCs of DOCA-salt rats, which were reversed by ETA antagonist, NADPH oxidase inhibitor, or polyethylene glycol-superoxide dismutase, Finally, in ETB-deficient rats, plasma ET-1 was elevated, and EPC number and telomerase activity were diminished. These results demonstrate, for the first time, that both ET-1 activation of ETA/NADPH oxidase pathway and diminished antioxidants critically contribute to EPC reduction and dysfunction via increased oxidative stress in salt-sensitive hypertension. (Hypertension. 2012;59:1037-1043.) circle Online Data Supplement C1 [Yuan, Hong; Chen, Alex F.] Cent S Univ, Xiangya Hosp 3, Dept Cardiol, Changsha 410013, Hunan, Peoples R China. [Yuan, Hong; Chen, Alex F.] Cent S Univ, Xiangya Hosp 3, Ctr Clin Pharmacol, Changsha, Hunan, Peoples R China. [Chen, Dan-Dan; Chen, Alex F.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Chen, Dan-Dan; Chen, Alex F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Chen, Dan-Dan; Dong, Yu-Gang] Sun Yat Sen Univ, Dept Cardiol, Affiliated Hosp 1, Guangzhou, Peoples R China. RP Chen, AF (reprint author), Cent S Univ, Xiangya Hosp 3, Dept Cardiol, 138 Tong Zi Bo Rd, Changsha 410013, Hunan, Peoples R China. EM afychen@yahoo.com FU National Institutes of Health [R01 GM077352]; American Heart Association [0855601G, 0720114Z]; National Science Foundation of China [30900519] FX This work was supported by National Institutes of Health grant R01 GM077352 and the American Heart Association Grant-in-Aid 0855601G (to A.F.C.). D.-D.C. is the receipt of the American Heart Association postdoctoral fellowship 0720114Z and the National Science Foundation of China grant 30900519. NR 42 TC 29 Z9 30 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2012 VL 59 IS 5 BP 1037 EP + DI 10.1161/HYPERTENSIONAHA.111.183368 PG 27 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 938VH UT WOS:000303760900035 PM 22431579 ER PT J AU Holsen, LM Savage, CR Martin, LE Bruce, AS Lepping, RJ Ko, E Brooks, WM Butler, MG Zarcone, JR Goldstein, JM AF Holsen, L. M. Savage, C. R. Martin, L. E. Bruce, A. S. Lepping, R. J. Ko, E. Brooks, W. M. Butler, M. G. Zarcone, J. R. Goldstein, J. M. TI Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE DLPFC; inhibition; motivation; fMRI; Prader-Willi syndrome ID HUMAN ORBITOFRONTAL CORTEX; HIGH-CALORIE FOODS; RESPONSE-INHIBITION; COGNITIVE CONTROL; NEURAL CIRCUITRY; BODY-COMPOSITION; HUMAN BRAIN; ACTIVATION; CHILDREN; MOTIVATION AB Background: The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. Objective: This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. Design and participants: A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. Results: Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. Conclusion: In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB. International Journal of Obesity (2012) 36, 638-647; doi:10.1038/ijo.2011.204; published online 25 October 2011 C1 [Holsen, L. M.; Ko, E.; Goldstein, J. M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, Boston, MA 02120 USA. [Holsen, L. M.; Goldstein, J. M.] Harvard Univ, Sch Med, Dept Psychiat & Med, Boston, MA USA. [Savage, C. R.] Univ Kansas, Med Ctr, Ctr Hlth Behav Neurosci, Kansas City, KS 66103 USA. [Savage, C. R.; Martin, L. E.; Lepping, R. J.; Brooks, W. M.] Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. [Savage, C. R.; Butler, M. G.] Univ Kansas, Med Ctr, Dept Psychiat, Kansas City, KS 66103 USA. [Martin, L. E.] Univ Kansas, Med Ctr, Dept Prevent Med & Publ Hlth, Kansas City, KS 66103 USA. [Bruce, A. S.] Univ Missouri Kansas City, Dept Psychol, Kansas City, MO USA. [Brooks, W. M.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. [Zarcone, J. R.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA. [Zarcone, J. R.] Univ Rochester, Med Ctr, Strong Ctr Dev Disabil, Rochester, NY 14642 USA. [Goldstein, J. M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Goldstein, J. M.] MIT, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Holsen, LM (reprint author), Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, BC-3,1620 Tremont St, Boston, MA 02120 USA. EM lholsen@partners.org OI brooks, william/0000-0001-6227-7636 FU Office for Research on Women's Health and National Institute of Child Health and Human Development [K12 HD051959]; National Institute for Child Health and Human Development [HD041672]; Hall Family Foundation; Heartland Genetics and Newborn Screening Collaborative [HRSA U22MC03962-02] FX This study was supported by a K12-award grant to Dr Holsen from the Office for Research on Women's Health and National Institute of Child Health and Human Development (K12 HD051959), the National Institute for Child Health and Human Development (HD041672), the Hall Family Foundation, and the Heartland Genetics and Newborn Screening Collaborative (HRSA U22MC03962-02). The Hoglund Brain Imaging Center is supported by the generosity of Forrest and Sally Hoglund. The authors are grateful to Phil Lee, Allan Schmitt, Muriel Williams and Pat Weber for technical assistance and Stacey Ward, Jean Reeves, and Jean Guadagnino for help in project coordination. NR 68 TC 34 Z9 35 U1 4 U2 23 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 2012 VL 36 IS 5 SI SI BP 638 EP 647 DI 10.1038/ijo.2011.204 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 938YZ UT WOS:000303771000003 PM 22024642 ER PT J AU Smith, RJ McCannel, CA Gordon, LK Hollander, DA Giaconi, JA Stelzner, SK Devgan, U Bartlett, J Mondino, BJ AF Smith, Ronald J. McCannel, Colin A. Gordon, Lynn K. Hollander, David A. Giaconi, JoAnn A. Stelzner, Sadiqa K. Devgan, Uday Bartlett, John Mondino, Bartly J. TI Evaluating teaching methods of cataract surgery: Validation of an evaluation tool for assessing surgical technique of capsulorhexis SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article AB PURPOSE: To develop and assess the validity of an evaluation tool to quantitatively assess the capsulorhexis portion of cataract surgery performed by residents. SETTING: University of California at Los Angeles (UCLA), Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, California, USA. DESIGN: Masked prospective case series. METHODS: Ophthalmology faculty members at UCLA were surveyed and literature was reviewed to develop a grading tool comprising 12 questions to evaluate surgical technique, including 4 from the Global Rating Assessment of Skills in Intraocular Surgery and 2 from the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric. Video clips of continuous curvilinear capsulorhexis (CCC) performed by 2 postgraduate year (PGY) 3 residents, 2 PGY 4 residents, and 2 advanced surgeons were independently graded in a masked fashion by a 7-member faculty panel. RESULTS: Four questions had low interobserver variability and a significant correlation with surgical skill level (intraclass correlation coefficient >0.75; P<.05, analysis of variance; 42 observations). The 4 questions were visual Likert-scale questions grading flow of operation, set up for regrasp, commencement of flap and formation, and circular completion of the CCC. CONCLUSIONS: Surgical performance can be validly measured using an evaluation tool. However, not all evaluation questions produced reliable results. The reliability and accuracy of the measurements appear to depend on the form and content of the question. Studies to optimize assessment tools identifying the best questions for evaluating each step of cataract surgery may help ophthalmic educators more precisely measure outcomes for improving teaching interventions. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles, Los Angeles, CA USA. RP Smith, RJ (reprint author), 7320 Hawthorn Ave,207, Los Angeles, CA 90046 USA. EM lasik@pacbell.net OI McCannel, Colin/0000-0003-0774-6414 FU American Society of Cataract and Refractive Surgery Foundation, Fairfax, Virginia, USA FX Supported by a grant from the American Society of Cataract and Refractive Surgery Foundation, Fairfax, Virginia, USA. NR 13 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAY PY 2012 VL 38 IS 5 BP 799 EP 806 DI 10.1016/j.jcrs.2011.11.046 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 939VD UT WOS:000303846300012 PM 22520304 ER PT J AU Dhanani, NM Jiang, YD AF Dhanani, Nadya M. Jiang, Yandong TI Anosmia and hypogeusia as a complication of general anesthesia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Anesthesia; General: complications; Anosmia; Hypogeusia ID MECHANISMS; PROPOFOL; TASTE AB A 57 year old woman with no previous history of any sensory deficits developed anosmia and hypogeusia after general anesthesia for laparoscopic cholecystcctomy, with complete recovery over 6 months. There were no other identifiable factors that may have contributed to her anosmia and hypogeusia after general anesthesia. As anosmia and hypogeusia related to anesthesia and surgery are not frequently reported, the incidence of these events related to anesthesia may be higher than expected. (C) 2012 Elsevier Inc. All rights reserved. C1 [Dhanani, Nadya M.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 422, Boston, MA 02114 USA. EM yjiang@partners.org NR 13 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY PY 2012 VL 24 IS 3 BP 231 EP 233 DI 10.1016/j.jclinane.2011.08.005 PG 3 WC Anesthesiology SC Anesthesiology GA 939EL UT WOS:000303790200011 PM 22495083 ER PT J AU Young, MJ Ehrenfeld, JM AF Young, Mark Jason Ehrenfeld, Jesse Menachem TI Knotting of an orogastric tube around an endotracheal tube SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter ID NASOGASTRIC TUBE C1 [Young, Mark Jason; Ehrenfeld, Jesse Menachem] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Young, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM MYoung14@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140 NR 6 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 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY PY 2012 VL 24 IS 3 BP 254 EP 255 DI 10.1016/j.jclinane.2011.04.019 PG 2 WC Anesthesiology SC Anesthesiology GA 939EL UT WOS:000303790200017 PM 22495088 ER PT J AU Boes, AD Grafft, A Espe-Pfeifer, P Rowe, J Stein, MT AF Boes, Aaron D. Grafft, Amanda Espe-Pfeifer, Patricia Rowe, Jeffrey Stein, Martin T. TI Manipulative and Antisocial Behavior in an 11-Year-Old Boy with Epilepsy SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material ID VENTROMEDIAL PREFRONTAL CORTEX; DAMAGE AB CASE: Brian is an 11-year-old boy who presented to the emergency room with suicidal ideation and hearing voices. In the preceding weeks, he had escalating symptoms of oppositional defiant disorder, attention-deficit hyperactivity disorder (ADHD), and bipolar disorder. His medical history was notable for complex partial epilepsy with onset at age 4 that had been well controlled with divalproate. He had several mental health diagnoses by various practitioners including oppositional defiant disorder, ADHD, and bipolar disorder. Brian's family and social history was notable for the absence of identifiable risk factors for seizures or psychiatric problems. Over the course of a week-long psychiatric hospitalization, his complaints of depression and hearing voices seemed incongruent with his behavior. His parents endorsed a long history of Brian manipulating family and friends, such as conning his friends into stealing money and giving it to him. There was increasing suspicion that Brian was contriving his presenting symptoms for secondary gains. When his parents visited, he consistently bargained for prized items such as a long sought after cell phone and his own bedroom to improve his mood. His prior diagnoses (ADHD, a mood disorder, and oppositional defiant disorder) did not capture what seemed to be his core problem-an ability and willingness to manipulate others for his own self-serving purposes. Three months later, he was seen in the pediatric neurology clinic for increased seizure frequency. In the interim, he had several very serious altercations including setting fire to his family church, an attempted break-in-and-entry, assaulting his principal and resisting the arresting officer, and a malicious planned attack on his father where he struck him in the head with a crescent wrench "in cold blood, without any emotion." (J Dev Behav Pediatr 33:365-368, 2012) C1 [Boes, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Neurol, Cambridge, MA 02138 USA. [Grafft, Amanda] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. [Espe-Pfeifer, Patricia] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Rowe, Jeffrey] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Stein, Martin T.] Hlth Univ Calif San Diego, Div Child Dev & Community, San Diego, CA USA. RP Boes, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Neurol, Cambridge, MA 02138 USA. NR 8 TC 0 Z9 0 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD MAY PY 2012 VL 33 IS 4 BP 365 EP 368 PG 4 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 939PQ UT WOS:000303825200010 PM 22566031 ER PT J AU Liu, ZG Stanojevic, V Brindamour, LJ Habener, JF AF Liu, Zhengu Stanojevic, Violeta Brindamour, Luke J. Habener, Joel F. TI GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic beta-cells from glucolipotoxicity SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; GLUCAGON-LIKE PEPTIDE-1; NEUTRAL ENDOPEPTIDASE-24.11; METABOLIC SYNDROME; OPIOID-PEPTIDES; AMIDE; ENZYME; GLP-1 AB Type 2 diabetes, often associated with obesity, results from a deficiency of insulin production and action manifested in increased blood levels of glucose and lipids that further promote insulin resistance and impair insulin secretion. Glucolipotoxicity caused by elevated plasma glucose and lipid levels is a major cause of impaired glucose-stimulated insulin secretion from pancreatic beta-cells, due to increased oxidative stress, and insulin resistance. Glucagon-like peptide-1 (GLP1), an insulinotropic glucoincretin hormone, is known to promote beta-cell survival via its actions on its G-protein-coupled receptor on beta-cells. Here, we report that a nonapeptide, GLP1(28-36)amide, derived from the C-terminal domain of the insulinotropic GLP1, exerts cytoprotective actions on INS-1 beta-cells and on dispersed human islet cells in vitro in conditions of glucolipotoxicity and increased oxidative stress independently of the GLP1 receptor. The nonapeptide appears to enter preferably stressed, glucolipotoxic cells compared with normal unstressed cells. It targets mitochondria and improves impaired mitochondrial membrane potential, increases cellular ATP levels, inhibits cytochrome c release, caspase activation, and apoptosis, and enhances the viability and survival of INS-1 beta-cells. We propose that GLP1(28-36) amide might be useful in alleviating beta-cell stress and might improve beta-cell functions and survival. Journal of Endocrinology (2012) 213, 143-154 C1 [Liu, Zhengu; Stanojevic, Violeta; Brindamour, Luke J.; Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Their 306, Boston, MA 02114 USA. EM jhabener@partners.org FU Charles A. Hood Foundation; Novo Nordisk FX The studies were supported in part by a grant from the Charles A. Hood Foundation to Z L and a Basic Science Grant from Novo Nordisk to J F H. NR 30 TC 37 Z9 39 U1 2 U2 17 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2012 VL 213 IS 2 BP 143 EP 154 DI 10.1530/JOE-11-0328 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940XC UT WOS:000303925400004 PM 22414687 ER PT J AU Neuhaus, V Wong, G Russo, KE Mudgal, CS AF Neuhaus, Valentin Wong, Grace Russo, Katherine E. Mudgal, Chaitanya S. TI Dynamic Splinting With Early Motion Following Zone IV/V and TI to TIII Extensor Tendon Repairs SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Dynamic; extensor; repair; splinting; tendon ID INJURIES AB Purpose To investigate the influence of a dynamic splinting protocol on outcomes of extensor tendon repairs. Methods All patients in a prospectively collected database underwent extensor tendon repair by a single surgeon between 2004 and 2008. The inclusion criterion was simple extensor tendon repairs in zone IV and V in the fingers and zones TI to TIII in the thumb. The tendon repairs used a 4-strand core technique and running epitendinous suture. Within 7 days, each subject began using a dynamic extension splint during the day and a static extension splint at night. The extension splint allowed the patient to passively extend and actively flex the digits. After 3 weeks, the dynamic splint was discontinued and the patients were started on active digital motion. Static night splinting was continued for the next 3 weeks, after which time splinting was discontinued and strengthening was instituted. A total of 17 patients with 19 tendon lacerations met the inclusion criterion. There were 5 patients with lacerations of the thumb extensors and 12 patients with zone IV/V finger extensor tendon lacerations. The average time from injury to surgery was 11 days (range, 2-39 d). The follow-up was 43 to 215 days, with an average of 96 days. Results A total of 16 patients achieved good or excellent results by 6 weeks according to our grading system. One patient had a fair result. There were no ruptures and no tenolysis surgeries performed. Conclusions Dynamic splinting resulted in generally good functional outcomes for extensor tendon laceration repairs in zone IV/V and TI to TIII, without complications. (J Hand Surg 2012; 37A:933-937. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 16 TC 3 Z9 5 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2012 VL 37A IS 5 BP 933 EP 937 DI 10.1016/j.jhsa.2012.01.039 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 937AX UT WOS:000303632500010 PM 22463924 ER PT J AU Neuhaus, V Alqueza, A Mudgal, CS AF Neuhaus, Valentin Alqueza, Arnold Mudgal, Chaitanya S. TI Open Reduction and Temporary Internal Fixation of a Subacute Elbow Dislocation SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Chronic; dislocation; elbow; fixation; internal AB We present the case of a 61-year-old woman with a subacute elbow dislocation, who was referred to our institution 4 weeks after a fall. She was treated with open reduction and temporary bridging internal fixation through a posterior approach with a limited contact dynamic compression plate. After 4 weeks, the hardware was removed. One year postoperatively, the patient had nearly pain-free motion of 200 short of full extension and full flexion. Her radiographs showed residual incongruity and degenerative arthritis of the elbow. (J Hand Surg 2012;37A:1011-1014. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 8 TC 2 Z9 2 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 2012 VL 37A IS 5 BP 1011 EP 1014 DI 10.1016/j.jhsa.2012.02.025 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 937AX UT WOS:000303632500023 PM 22480505 ER PT J AU Buijze, GA Ochtman, L Ring, D AF Buijze, Geert A. Ochtman, Lidewij Ring, David TI Management of Scaphoid Nonunion SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Bone graft; internal fixation; operative treatment; scaphoid fracture nonunion ID VASCULARIZED BONE-GRAFT; AVASCULAR NECROSIS; FRACTURE NONUNION; ILIAC CREST; SUPRARETINACULAR ARTERY; QUANTITATIVE-ANALYSIS; COMPUTED-TOMOGRAPHY; DISPLACED FRACTURES; SURGICAL-TREATMENT; NATURAL-HISTORY AB The primary risk factor for nonunion of the scaphoid is displacement/instability, but delayed or missed diagnosis, inadequate treatment, fracture location, and blood supply are also risk factors. Untreated nonunion leads to degenerative wrist arthritis-the so-called "scaphoid nonunion advanced collapse" wrist. However, the correlation of symptoms and disease is poor; the true "natural history" is debatable because we evaluate only symptomatic patients presenting for treatment. It is not clear that surgery can change the natural history, even if union is attained. The diagnosis of nonunion is made on radiographs, but computed tomography or magnetic resonance imaging scans can be useful to assess deformity and blood supply. Treatment options vary from percutaneous fixation to open reduction and internal fixation with vascularized or nonvascularized bone grafting to salvage procedures involving excision and/or arthrodesis of carpals. (J Hand Surg 2012;37A:1095-1100. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr,Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU Netherlands Organisation for Scientific Research (NWO); Skeletal Dynamics; Wright Medical; Biomet; AO North America FX G.A.B. is supported by the Netherlands Organisation for Scientific Research (NWO) as a PhD Research Fellow. D.R. receives study-specific grants from Skeletal Dynamics; is a consultant for Wright Medical, Skeletal Dynamics, and Biomet; receives honoraria from AO North America and AO International; receives royalties from Wright Medical, Biomet, and Skeletal Dynamic; receives stock options from Illuminos and Mimedex; receives funding for a hand surgery fellowship from AO North America; serves as deputy editor for Journal of Hand Surgery (American volume), review Journal of Orthopaedic Trauma hand and wrist articles; and serves as assistant editor for the Journal of Shoulder and Elbow Surgery. NR 57 TC 31 Z9 32 U1 1 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2012 VL 37A IS 5 BP 1095 EP 1101 DI 10.1016/j.jhsa.2012.03.002 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 937AX UT WOS:000303632500040 PM 22541157 ER PT J AU Smith, ZA Yang, I Gorgulho, A Raphael, D De Salles, AAF Khoo, LT AF Smith, Zachary A. Yang, Isaac Gorgulho, Alessandra Raphael, Dan De Salles, Antonio A. F. Khoo, Larry T. TI Emerging techniques in the minimally invasive treatment and management of thoracic spine tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Vertebroplasty; Minimally invasive spine; Spine surgery; Spinal radiosurgery; Lateral extracavitary; Lateral interbody ID LATERAL EXTRACAVITARY APPROACH; CORD COMPRESSION; LUMBAR SPINE; PERCUTANEOUS VERTEBROPLASTY; RADIATION TOLERANCE; RANDOMIZED-TRIAL; STEREOTACTIC RADIOSURGERY; ANTERIOR DECOMPRESSION; NONOPERATIVE TREATMENT; THORACOSCOPIC APPROACH AB Over the past decade, the development and refinement of minimally invasive spine surgery techniques has lead to procedures with the potential to minimize iatrogenic and post-operative sequelae that may occur during the surgical treatment of various pathologies. In a similar manner, parallel advances in other current treatment technologies have led to the development of other minimally invasive treatments of spinal malignancies. These advances include percutaneous techniques for vertebral reconstruction, including vertebroplasty and kyphoplasty, the development of safe and effective spinal radiosurgery, and minimal-access spinal surgical procedures that allow surgeons to safely decompress and reconstruct the anterior spinal column. The advent of these new techniques has given modern practitioners treatment options in situations where they previously were limited by the potentially significant morbidities of the available techniques. Here, the authors discuss the application of current minimally invasive technologies in the treatment of malignancies of the thoracic spine, focusing on vertebral kyphoplasty, spinal radiosurgery, and minimally invasive spinal decompression techniques. The author's describe how these emerging treatment options are significantly expanding the options open to clinicians in the treatment of thoracic spinal column malignancies. Specific illustrative case examples are provided. The development of these techniques has the potential to improve clinical outcomes, limit surgical morbidity, and also improve the safety and efficiency of treatment pathways. C1 [Smith, Zachary A.; Raphael, Dan; Khoo, Larry T.] Univ So Calif, Hosp Good Samaritan, Spine Clin Los Angeles, Los Angeles, CA 90017 USA. [Smith, Zachary A.] Northwestern Univ, Dept Neurol Surg, Chicago, IL 60601 USA. [Yang, Isaac; Gorgulho, Alessandra; De Salles, Antonio A. F.] David Geffen UCLA Sch Med, Ronald Reagan UCLA Med Ctr, Dept Neurosurg, Los Angeles, CA 90095 USA. [De Salles, Antonio A. F.] W Los Angeles Vet Adm Hosp, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Khoo, LT (reprint author), Univ So Calif, Hosp Good Samaritan, Spine Clin Los Angeles, 1245 Wilshire Ave,717, Los Angeles, CA 90017 USA. EM lkhoo@laspineclinic.com FU UCLA; AANS/CNS; CNS FX Dr. Isaac Yang, the second author, was partially support by a UCLA Stein Oppenheimer Grant. Dr. Larry T. Khoo is a consultant and member of the medical speaker's board for Globus Medical Inc.; Audubon, PA; Drs. Antonio A. F. De Salles and Alessandra Gorgulho have received honorarium from Brainlab Inc. for speaking engagements. Dr. Zachary A. Smith acknowledges the support of both the AANS/CNS Spine Section Apfelbaum Award as well as the CNS Spine Fellowship in aiding the production of this work. The other authors in this manuscript do not have disclosures. NR 90 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2012 VL 107 IS 3 BP 443 EP 455 DI 10.1007/s11060-011-0755-6 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TK UT WOS:000303469400001 PM 22094716 ER PT J AU Alexander, BM Pinnell, N Wen, PY D'Andrea, A AF Alexander, Brian M. Pinnell, Nancy Wen, Patrick Y. D'Andrea, Alan TI Targeting DNA repair and the cell cycle in glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE DNA repair; Cell cycle; Glioblastoma ID PHASE-I TRIAL; TEMOZOLOMIDE PLUS O-6-BENZYLGUANINE; ADVANCED SOLID TUMORS; DOUBLE-STRAND BREAKS; APURINIC/APYRIMIDINIC ENDONUCLEASE ACTIVITY; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; RECURRENT MALIGNANT GLIOMA; NUCLEOTIDE EXCISION-REPAIR; DEPENDENT KINASE INHIBITOR; FACTOR RECEPTOR COMMON AB Glioblastoma is a disease with poor outcomes despite standard therapy. Specific targeting of the DNA damage response is a strategy that is becoming increasingly employed in oncology and has intriguing potential for improving outcomes in glioblastoma. DNA damage targeting has implications for improving current therapy as well as the potential to leverage inherent differences in glioblastoma cells to widen the therapeutic window. C1 [Alexander, Brian M.; Pinnell, Nancy; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Neurol, Boston, MA 02115 USA. RP Alexander, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@partners.org NR 145 TC 18 Z9 18 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2012 VL 107 IS 3 BP 463 EP 477 DI 10.1007/s11060-011-0765-4 PG 15 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TK UT WOS:000303469400003 PM 22113697 ER PT J AU Das, RR Artsy, E Hurwitz, S Wen, PY Black, P Golby, A Dworetzky, B Lee, JW AF Das, Rohit R. Artsy, Elinor Hurwitz, Shelley Wen, Patrick Y. Black, Peter Golby, Alexandra Dworetzky, Barbara Lee, Jong Woo TI Outcomes after discontinuation of antiepileptic drugs after surgery in patients with low grade brain tumors and meningiomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Brain tumor; Seizures; Antiepileptic drug ID TOXIC EPIDERMAL NECROLYSIS; EPILEPSY; GLIOMAS; SEIZURES; CHEMOTHERAPY; THERAPY; RISK AB Low grade tumors are associated with a high risk of seizures. Prolonged use of antiepileptic drugs (AEDs) is associated with morbidity. Determining which patients can safely discontinue AEDs perioperatively is difficult. We examined patients with low grade supratentorial brain tumors to determine characteristics of patients who underwent AED withdrawal. A retrospective chart review was performed in patients who underwent resection between 1/1/2004 and 12/31/2005 at a single center. Data were collected regarding the use of postoperative AEDs, occurrence of postoperative seizures, and patient/tumor characteristics. We examined 169 patients with a median follow-up of 3.1 years. AEDs were withdrawn or never started in 111 patients; post-withdrawal seizures occurred in 11 (9.9%). The rate was similar between meningiomas and primary brain tumors. No independent risk factors for post-withdrawal seizures were found. Of 58 patients whose AEDs were not withdrawn, postoperative seizures occurred in 28 (48%). Predictors of AED continuation included existence of preoperative seizures, temporal tumor location, tumor recurrence, incomplete resection, and male sex. The decision to continue AEDs was predictive for postoperative seizures even after controlling for known risk factors. Although clinicians are able to identify patients at high risk for postoperative seizures, treatment with AEDs is ineffective in many patients. C1 [Das, Rohit R.; Artsy, Elinor; Black, Peter; Golby, Alexandra; Dworetzky, Barbara; Lee, Jong Woo] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Hurwitz, Shelley] Brigham & Womens Hosp, Dept Biostat, Boston, MA 02120 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Lee, JW (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM rohitdas@yahoo.com; elinor.artsy@gmail.com; Hurwitz@hms.harvard.edu; Patrick_wen@dfci.harvard.edu; pmblack@bics.bwh.harvard.edu; agolby@partners.org; bdworetzky@partners.org; jlee38@partners.org OI Dworetzky, Barbara/0000-0002-3364-2347 NR 24 TC 11 Z9 11 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2012 VL 107 IS 3 BP 565 EP 570 DI 10.1007/s11060-011-0779-y PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 934TK UT WOS:000303469400013 PM 22212850 ER PT J AU Wu, Y Zhao, JB Zhao, WD Pan, JP Bauman, WA Cardozo, CP AF Wu, Yong Zhao, Jingbo Zhao, Weidong Pan, Jiangping Bauman, William A. Cardozo, Christopher P. TI Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE muscle atrophy; nandrolone; oxidative metabolism; PGC-1 alpha; slow twitch muscle; spinal cord injury ID FOXO TRANSCRIPTION FACTORS; SKELETAL-MUSCLE; GENE-EXPRESSION; DENERVATION ATROPHY; SIGNALING PATHWAYS; TESTOSTERONE REPLACEMENT; UBIQUITIN LIGASES; OLDER MEN; STIMULATION; TIME AB Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1 alpha protein and PGC-1 alpha mRNA levels. For PGC-1 alpha target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1 alpha in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1 alpha target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation. C1 [Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A.; Cardozo, Christopher P.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Chris.cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B4616R, B3347K] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B4162C, B4616R, and B3347K). NR 49 TC 12 Z9 13 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD MAY PY 2012 VL 29 IS 8 BP 1663 EP 1675 DI 10.1089/neu.2011.2203 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 939NJ UT WOS:000303818000012 PM 22208735 ER PT J AU Majmudar, MD Nahrendorf, M AF Majmudar, Maulik D. Nahrendorf, Matthias TI Cardiovascular Molecular Imaging: The Road Ahead SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular imaging; cardiovascular; nuclear medicine; multimodality; MRI ID MATRIX-METALLOPROTEINASE ACTIVATION; MYOCARDIAL-INFARCTION; IN-VIVO; PET; ATHEROSCLEROSIS; INFLAMMATION; MODEL; EXPRESSION; RECEPTOR; PLAQUE AB Despite significant advancements in medical and device-based therapies, cardiovascular disease remains the number one cause of death in the United States. Early detection of atherosclerosis, prevention of myocardial infarction and sudden cardiac death, and modulation of adverse ventricular remodeling still remain elusive goals. Molecular imaging focuses on identifying critical cellular and molecular targets and therefore plays an integral role in understanding these biologic processes in vivo. Because many imaging targets are upregulated before irreversible tissue damage occurs, early detection could ultimately lead to development of novel, preventive therapeutic strategies. This review addresses recent work on radionuclide imaging of cardiovascular inflammation, infection, and infarct healing. We further discuss opportunities provided by multimodality approaches such as PET/MRI and PET/optical imaging. C1 [Majmudar, Maulik D.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Majmudar, Maulik D.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Majmudar, Maulik D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NIH [R01HL095629, R01HL096576]; Translational Program of Excellence in Nanotechnology [HHSN268201000044C] FX This work was funded in part by grants from the NIH (R01HL095629, R01HL096576, and Translational Program of Excellence in Nanotechnology HHSN268201000044C). We acknowledge fruitful discussions with Drs. Ralph Weissleder and Peter Libby. No other potential conflict of interest relevant to this article was reported. NR 25 TC 23 Z9 25 U1 1 U2 9 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2012 VL 53 IS 5 BP 673 EP 676 DI 10.2967/jnumed.111.099838 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 939BU UT WOS:000303782700006 PM 22492729 ER PT J AU Friedlander, AH Tajima, T Garrett, NR AF Friedlander, Arthur H. Tajima, Tracey Garrett, Neal R. TI Panoramic Radiographs of Head and Neck Cancer Patients Are Often Evidence of Carotid Artery Atherosclerotic Lesions: A Sign of High-Risk Comorbid Illness SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; CARDIOVASCULAR-DISEASE; DENSITY-LIPOPROTEINS; TOBACCO-SMOKE; HYPERTENSION; PROGRESSION; COMPLICATIONS; POPULATION; COMMUNITIES AB Purpose: The purpose of this study was to estimate the prevalence and identify the risk factors for calcified carotid artery plaque (CCAP) in patients with squamous cell carcinoma of the head and neck. Materials and Methods: Radiographs of 48 consecutive patients were evaluated for CCAP and their medical histories reviewed for the anatomic extent of cancer (staging) and atherogenic risk factors (age, extent of alcohol and tobacco use, body mass index, hypertension, dyslipidemia, and diabetes mellitus). Results: Unilateral or bilateral CCAPs were found in 52.1% of subjects (mean age, 61.5 years). Hypertension was seen in a larger percentage (60%; P = .049) of subjects with CCAP on their radiographs compared with those without CCAP (30.4%). No other atheroma risk factors or stage of cancer differed significantly between those with and those without CCAP. Conclusion: Panoramic radiographs of patients with squamous cell carcinoma of the head and neck show a very high rate of CCAP, a marker of comorbid vascular diseases that may cause treatment complications and affect overall survival. This is a US government work. There are no restrictions on its use. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 70: 1096-1101, 2012 C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. [Tajima, Tracey] Univ Calif Los Angeles, Sch Dent, Oral Med & Orofacial Pain Div, Los Angeles, CA 90024 USA. [Tajima, Tracey] VA Greater Los Angeles Healthcare Syst, Gen Practice Dent Residency, Los Angeles, CA 90073 USA. [Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 USA. [Garrett, Neal R.] VA Greater Los Angeles Healthcare Syst, Oral Biol Res Lab, Los Angeles, CA 90073 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Grad Med Educ, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthurfriedlander@med.va.gov FU Department of Veterans Affairs; University of California; National Center for Research Resources, National Institutes of Health [CO6 RR-14529-01] FX The financial support of this project was limited to the full-time salaries paid to the authors by the Department of Veterans Affairs and the University of California. Elements of this investigation were conducted in a facility constructed with support from Research Facilities Improvement Program Grant CO6 RR-14529-01 from the National Center for Research Resources, National Institutes of Health. NR 46 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2012 VL 70 IS 5 BP 1096 EP 1101 DI 10.1016/j.joms.2011.05.020 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 938IF UT WOS:000303726500023 PM 21855199 ER PT J AU Friedlander, AH Rosenbluth, SC Rubin, RT AF Friedlander, Arthur H. Rosenbluth, Susan C. Rubin, Robert T. TI The Adult Suicide-Prone Patient: A Review of the Medical Literature and Implications for Oral and Maxillofacial Surgeons SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; NESTED CASE-CONTROL; RISK-FACTORS; PSYCHIATRIC-DISORDERS; CANCER-PATIENTS; IDEATION; FREUD,SIGMUND; DEPRESSION; BEHAVIOR; ILLNESS AB Purpose: Suicide is the 11th most common cause of death among American adults. Some individuals who commit suicide may have been treated by oral and maxillofacial surgeons in the days preceding the event. Because suicide often is preventable, in this report we review methods that are useful in identifying individuals at risk of imminent suicide and give suggestions for obtaining interventional assistance. Methods: A Medline search using the key terms "suicide," "adult," and "oral surgery" was conducted. Articles selected were published in peer-reviewed journals. Results: Individuals who have told their surgeon they have no further reason to live, have developed a suicide plan, have secured a lethal device, and have previously made such an attempt are at extreme risk and require immediate intervention. Additional risk factors include being white, aged older than 45 years, and unemployed; living alone, with poor social supports; having a current mental illness or history of mental illness, including substance abuse; and having a family history of suicide. Specialty-specific patients at highest risk are those treated for oral cancer and cosmetic issues and those with adverse surgical outcomes. With regard to assessment of these individuals, the modified SAD PERSONS acronym can assist surgeons in documenting the presence of major risk factors associated with adult suicide and in facilitating communication with emergency personnel. Conclusions: Suicide is a potentially preventable public health problem. Oral and maxillofacial surgeons can be key in elucidating clinically significant suicide potential in their patients and referring them for timely intervention. This is a US government work. There are no restrictions on its use. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 70:1253-1260, 2012 C1 [Friedlander, Arthur H.; Rosenbluth, Susan C.] VA Greater Los Angeles Healthcare Syst, Mental Hlth Outpatient Addict Treatment Programs, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Rosenbluth, Susan C.; Rubin, Robert T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Hlth Outpatient Addict Treatment Programs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov RI Price, Katie/H-1931-2012 NR 72 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2012 VL 70 IS 5 BP 1253 EP 1260 DI 10.1016/j.joms.2011.02.024 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 938IF UT WOS:000303726500048 PM 21741743 ER PT J AU Pantilat, SZ Kerr, KM Billings, JA Bruno, KA O'Riordan, DL AF Pantilat, Steven Z. Kerr, Kathleen M. Billings, J. Andrew Bruno, Kelly A. O'Riordan, David L. TI Characteristics of Palliative Care Consultation Services in California Hospitals SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID LUNG-CANCER; PREVALENCE AB Background: Although hospital palliative care consultation services (PCCS) can improve a variety of clinical and nonclinical outcomes, little is known about how these services are structured. Methods: We surveyed all 351 acute care hospitals in California to examine the structure and characteristics of those hospitals with PCCS. Results: We achieved a 92% response rate. Thirty-one percent (n = 107) of hospitals reported having a PCCS. Teams commonly included physicians (87%), social workers (80%), spiritual care professionals (77%), and registered nurses (71%). Nearly all PCCS were available on-site during weekday business hours; 50% were available on-site or by phone in the weekday evenings and 54% were available during weekend daytime hours. The PCCS saw an average of 347 patients annually (median = 310, standard deviation [ SD] = 217), or 258 patients per clinical full-time equivalent (FTE; median = 250, SD = 150.3). Overall, 60% of consultation services reported they are struggling to cope with the workload. On average, patients were in the hospital 5.9 days (median = 5.5, SD = 3.3) prior to referral to PCCS, and remained in the hospital for 6 days (median = 4, SD = 7.9) following the initial consultation. Patient and family meetings were an aspect of the consultation in 74% of cases. Overall, 21% of consultation patients were discharged home with hospice services and 25% died in the hospital. Conclusions: There is variation in how PCCS in California hospitals are structured and in the ways they engage with patients. Ultimately, linking PCCS characteristics and practices to patient and family outcomes will identify best practices that PCCS can use to maximize quality. C1 [Pantilat, Steven Z.; Kerr, Kathleen M.; O'Riordan, David L.] Univ Calif San Francisco, Palliat Care Program, San Francisco, CA 94143 USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Billings, J. Andrew] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Bruno, Kelly A.] Natl Hlth Fdn, Los Angeles, CA USA. RP Pantilat, SZ (reprint author), Univ Calif San Francisco, Palliat Care Program, 521 Parnassus Ave,Suite C-126, San Francisco, CA 94143 USA. EM stevep@medicine.ucsf.edu FU California HealthCare Foundation FX No competing financial interests exist. The California HealthCare Foundation provided funding to support the administration of the survey and analysis of findings, as well as limited dissemination of results though the Foundation's communication venues. NR 13 TC 12 Z9 12 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAY PY 2012 VL 15 IS 5 BP 555 EP 560 DI 10.1089/jpm.2011.0390 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 941CM UT WOS:000303940500012 PM 22394365 ER PT J AU Branco-de-Almeida, LS Franco, GC Castro, ML dos Santos, JG Anbinder, AL Cortelli, SC Kajiya, M Kawai, T Rosalen, PL AF Branco-de-Almeida, Luciana S. Franco, Gilson C. Castro, Myrella L. dos Santos, Juliana G. Anbinder, Ana Lia Cortelli, Sheila C. Kajiya, Mikihito Kawai, Toshihisa Rosalen, Pedro L. TI Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature-Induced Periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Bone resorption; collagen; fluoxetine; inflammation; periodontitis ID NITRIC-OXIDE; HEALTHY-VOLUNTEERS; DISEASE; ANTIDEPRESSANTS; EXPRESSION; CELLS; ACID; MATRIX-METALLOPROTEINASE-2; METALLOPROTEINASES; DESIPRAMINE AB Background: Fluoxetine, a selective serotonin reuptake inhibitor, has been found recently to possess anti-inflammatory properties. The present study investigates the effects of fluoxetine on inflammatory tissue destruction in a rat model of ligature-induced periodontal disease. Methods: Thirty male Wistar rats were randomly assigned into three groups (n = 10 animals per group): 1) control rats (without ligature); 2) rats with ligature + placebo (saline; oral gavage); and 3) rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histologic analyses were performed on the furcation region and mesial aspect of mandibular first molars of rats sacrificed at 15 days after ligature-induced periodontal disease. Reverse transcription-polymerase chain reaction and zymography were performed to analyze the mRNA expression of interleukin (IL)-1 beta, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase and the MMP-9 activity, respectively, in gingival tissues samples. Results: Compared to the ligature + placebo group, alveolar bone loss was reduced in the fluoxetine group (P <0.05), and the amount of collagen fibers in the gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after ligature attachment, fluoxetine administration reduced IL-1 beta and COX-2 mRNA expression. Fluoxetine downregulated MMP-9 activity, without affecting MMP-9 mRNA expression induced by ligature, compared to the ligature + placebo group (P <0.05). These data suggest that fluoxetine suppressed proinflammatory responses, as well as proteolytic enzyme activity, induced by ligature. Conclusion: In the present study, fluoxetine suppresses the inflammatory response and protects against periodontal bone resorption and destruction of collagen fibers, suggesting that fluoxetine can constitute a promising therapeutic approach for periodontal diseases. J Periodontol 2012;83:664-671. C1 [Branco-de-Almeida, Luciana S.; Castro, Myrella L.; Rosalen, Pedro L.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Physiol Sci, BR-13414903 Piracicaba, SP, Brazil. [Franco, Gilson C.; dos Santos, Juliana G.; Cortelli, Sheila C.] Univ Taubate, Dept Oral Biol, Sao Paulo, Brazil. [Anbinder, Ana Lia] Univ Estadual Paulista UNESP, Sch Dent Sao Jose dos Campos, Dept Biosci & Oral Diag, Sao Paulo, Brazil. [Kajiya, Mikihito; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA USA. [Kajiya, Mikihito; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Rosalen, PL (reprint author), Univ Estadual Campinas, Piracicaba Dent Sch, Dept Physiol Sci, Ave Limeira,901,Areao,Caixa Postal 52, BR-13414903 Piracicaba, SP, Brazil. EM rosalen@fop.unicamp.br RI Franco, Gilson/F-9312-2012; Rosalen, Pedro/I-3718-2012; Branco-de-Almeida, Luciana /J-8946-2012; Anbinder, Ana Lia/B-8816-2012 OI Anbinder, Ana Lia/0000-0003-3930-4274 FU Sao Paulo Research Foundation (FAPESP) [2008/00566-6]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; Coordination for the Improvement of Higher Education Personnel) [4073/08-8]; National Institutes of Health/National Institute of Dental and Craniofacial Research [DE-018499, DE-019917] FX This study was supported by Sao Paulo Research Foundation (FAPESP) Grant #2008/00566-6 (LS Branco-de-Almeida-fellowship), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; Coordination for the Improvement of Higher Education Personnel) Grant #4073/08-8 (LS Branco-de-Almeida-fellowship), and National Institutes of Health/National Institute of Dental and Craniofacial Research Grants DE-018499 and DE-019917. The authors report no conflicts of interest related to this study. NR 40 TC 24 Z9 25 U1 1 U2 5 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 2012 VL 83 IS 5 BP 664 EP 671 DI 10.1902/jop.2011.110370 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 937EH UT WOS:000303641300016 PM 21966942 ER PT J AU Merkow, RP Hall, BL Cohen, ME Dimick, JB Wang, E Chow, WB Ko, CY Bilimoria, KY AF Merkow, Ryan P. Hall, Bruce L. Cohen, Mark E. Dimick, Justin B. Wang, Edward Chow, Warren B. Ko, Clifford Y. Bilimoria, Karl Y. TI Relevance of the C-Statistic When Evaluating Risk-Adjustment Models in Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PREDICTION MODELS; FRAMEWORK; MORTALITY; CURVE AB BACKGROUND: The measurement of hospital quality based on outcomes requires risk adjustment. The c-statistic is a popular tool used to judge model performance, but can be limited, particularly when evaluating specific operations in focused populations. Our objectives were to examine the interpretation and relevance of the c-statistic when used in models with increasingly similar case mix and to consider an alternative perspective on model calibration based on a graphical depiction of model fit. STUDY DESIGN: From the American College of Surgeons National Surgical Quality Improvement Program (2008-2009), patients were identified who underwent a general surgery procedure, and procedure groups were increasingly restricted: colorectal-all, colorectal-elective cases only, and colorectal-elective cancer cases only. Mortality and serious morbidity outcomes were evaluated using logistic regression-based risk adjustment, and model c-statistics and calibration curves were used to compare model performance. RESULTS: During the study period, 323,427 general, 47,605 colorectal-all, 39,860 colorectal-elective, and 21,680 colorectal cancer patients were studied. Mortality ranged from 1.0% in general surgery to 4.1% in the colorectal-all group, and serious morbidity ranged from 3.9% in general surgery to 12.4% in the colorectal-all procedural group. As case mix was restricted, c-statistics progressively declined from the general to the colorectal cancer surgery cohorts for both mortality and serious morbidity (mortality: 0.949 to 0.866; serious morbidity: 0.861 to 0.668). Calibration was evaluated graphically by examining predicted vs observed number of events over risk deciles. For both mortality and serious morbidity, there was no qualitative difference in calibration identified between the procedure groups. CONCLUSIONS: In the present study, we demonstrate how the c-statistic can become less informative and, in certain circumstances, can lead to incorrect model-based conclusions, as case mix is restricted and patients become more homogenous. Although it remains an important tool, caution is advised when the c-statistic is advanced as the sole measure of a model performance. (J Am Coll Surg 2012; 214: 822-830. (C) 2012 by the American College of Surgeons) C1 [Merkow, Ryan P.; Hall, Bruce L.; Cohen, Mark E.; Chow, Warren B.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Wang, Edward; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. [Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] John Cochran St Louis VA Med Ctr, Dept Surg, St Louis, MO USA. [Dimick, Justin B.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Chow, Warren B.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Chow, Warren B.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM RMerkow@facs.org FU American College of Surgeons, Chicago, IL FX Drs Merkow and Chow are supported by the American College of Surgeons Clinical Scholars in Residence Program, Chicago, IL. Drs Hall and Bilimoria are consultants to the Division of Research and Optimal Patient Care, American College of Surgeons. NR 14 TC 36 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2012 VL 214 IS 5 BP 822 EP 830 DI 10.1016/j.jamcollsurg.2011.12.041 PG 9 WC Surgery SC Surgery GA 938HI UT WOS:000303724200013 PM 22440055 ER PT J AU Boyce, RD Hanlon, JT Karp, JF Kloke, J Saleh, A Handler, SM AF Boyce, Richard D. Hanlon, Joseph T. Karp, Jordan F. Kloke, John Saleh, Ahlam Handler, Steven M. TI A Review of the Effectiveness of Antidepressant Medications for Depressed Nursing Home Residents SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE Antidepressants; nursing homes; depression; effectiveness ID LONG-TERM-CARE; GERIATRIC DEPRESSION; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; ELDERLY-PATIENTS; CLINICAL-TRIAL; CORNELL SCALE; HEALTH-CARE; LATE-LIFE; SERTRALINE AB Background: Antidepressant medications are the most common psychopharmacologic therapy used to treat depressed nursing home(NH) residents. Despite a significant increase in the rate of antidepressant prescribing over the past several decades, little is known about the effectiveness of these agents in the NH population. Objective: To conduct a systematic review of the literature to examine and compare the effectiveness of antidepressant medications for treating major depressive symptoms in elderly NH residents. Methods: The following databases were searched with searches completed prior to January 2011 and no language restriction: MEDLINE, Embase, PsycINFO, CINHAL, CENTRAL, LILACS, ClinicalTrials. gov, International Standard Randomized Controlled Trial Number Register, and the WHO International Clinical Trial Registry Platform. Additional studies were identified from citations in evidence-based guidelines and reviews as well as book chapters on geriatric depression and pharmacotherapy from several clinical references. Studies were included if they described a clinical trial that assessed the effectiveness of any currently-marketed antidepressant for adults aged 65 years or older, who resided in the NH, and were diagnosed by DSM criteria and/or standardized validated screening instruments with Major Depressive Disorder, minor depression, dysthymic disorder, or Depression in Alzheimer's disease. Results: A total of eleven studies, including four randomized and seven non-randomized open-label trials, met all inclusion and exclusion criteria. It was not feasible to conduct a meta-analysis because the studies were heterogeneous in terms of study design, operational definitions of depression, participant characteristics, pharmacologic interventions, and outcome measures. Of the four randomized trials, two had a control group and did not demonstrate a statistically-significant benefit for antidepressant pharmacotherapy over placebo. While six of the seven non-randomized studies identified a response to an antidepressant, their results must be interpreted with caution as they lacked a comparison group. Conclusions: The limited amount of evidence from randomized and non-randomized open-label trials suggests that depressed NH residents have a modest response to antidepressant medications. Further research using rigorous study designs are needed to examine the effectiveness and safety of antidepressants in depressed NH residents, and to determine the various facility, provider, andpatient factors associated with response totreatment. Copyright (C) 2012 - American Medical Directors Association, Inc. C1 [Boyce, Richard D.; Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA. [Boyce, Richard D.; Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Geriatr Pharmaceut Outcomes & Geroinformat Res &, Pittsburgh, PA USA. [Hanlon, Joseph T.; Handler, Steven M.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.; Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.; Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr GRECC, Pittsburgh, PA USA. [Hanlon, Joseph T.; Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Karp, Jordan F.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Karp, Jordan F.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Kloke, John] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Saleh, Ahlam] Univ Pittsburgh, Hlth Sci Lib Syst, Pittsburgh, PA USA. RP Boyce, RD (reprint author), Parkvale Bldg,Suite M-183,200 Meyran Ave, Pittsburgh, PA 15260 USA. EM rdb20@pitt.edu RI Saleh, Ahlam/G-3766-2013; OI Saleh, Ahlam/0000-0002-3492-3140; Handler, Steven/0000-0002-3940-3224 FU Agency for Healthcare Research and Quality [K12HS019461, R01HS017695, 1R01HS018721-01]; National Institute on Aging [K07AG033174, P30AG024827, T32 AG021885, R01AG034056, R56AG027017, 3U01 AG012553, AG033575]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; National Center for Research resources [KL2 RR024154, 3 UL1 R024153-04S4]; VA Health Services Research [IIR-06-062] FX The corresponding author (R.D.B.) was funded by grant K12HS019461 from the Agency for Healthcare Research and Quality. Additional grant support for the coauthors was provided by an Agency for Healthcare Research and Quality grant (R01HS017695 and 1R01HS018721-01), National Institute on Aging grants (K07AG033174, P30AG024827, T32 AG021885, R01AG034056, R56AG027017, 3U01 AG012553, and AG033575), a National Institute of Mental Health grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), National Center for Research resources grants (KL2 RR024154, 3 UL1 R024153-04S4), and a VA Health Services Research grant (IIR-06-062). The content is solely the responsibility of the authors and does not represent the official views of the Agency for Healthcare Research and Quality or any of the other funding sources. NR 52 TC 18 Z9 18 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2012 VL 13 IS 4 BP 326 EP 331 DI 10.1016/j.jamda.2011.08.009 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 935OA UT WOS:000303527300005 PM 22019084 ER PT J AU Kang, J D'Andrea, AD Kozono, D AF Kang, Josephine D'Andrea, Alan D. Kozono, David TI A DNA Repair Pathway-Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENE-EXPRESSION PROFILES; SENSITIVITY PROTEIN MUS308; HOMOLOGOUS RECOMBINATION; GENOME STABILITY; RECQ HELICASES; CLEAR-CELL; INHIBITION; SURVIVAL; ROLES; MICROARRAY AB Background New tools are needed to predict outcomes of ovarian cancer patients treated with platinum-based chemotherapy. We hypothesized that a molecular score based on expression of genes that are involved in platinum-induced DNA damage repair could provide such prognostic information. Methods Gene expression data was extracted from The Cancer Genome Atlas (TCGA) database for 151 DNA repair genes from tumors of serous ovarian cystadenocarcinoma patients (n = 511). A molecular score was generated based on the expression of 23 genes involved in platinum-induced DNA damage repair pathways. Patients were divided into low (scores 0-10) and high (scores 11-20) score groups, and overall survival (OS) was analyzed by Kaplan-Meier method. Results were validated in two gene expression microarray datasets. Association of the score with OS was compared with known clinical factors (age, stage, grade, and extent of surgical debulking) using univariate and multivariable Cox proportional hazards models. Score performance was evaluated by receiver operating characteristic (ROC) curve analysis. Correlations between the score and likelihood of complete response, recurrence-free survival, and progression-free survival were assessed. Statistical tests were two-sided. Results Improved survival was associated with being in the high-scoring group (high vs low scores: 5-year OS, 40% vs 17%, P < .001), and results were reproduced in the validation datasets (P < .05). The score was the only pretreatment factor that showed a statistically significant association with OS (high vs low scores, hazard ratio of death = 0.40, 95% confidence interval = 0.32 to 0.66, P < .001). ROC curves indicated that the score outperformed the known clinical factors (score in a validation dataset vs clinical factors, area under the curve = 0.65 vs 0.52). The score positively correlated with complete response rate, recurrence-free survival, and progression-free survival (Pearson correlation coefficient [r(2)] = 0.60, 0.84, and 0.80, respectively; P < .001 for all). Conclusion The DNA repair pathway-focused score can be used to predict outcomes and response to platinum therapy in ovarian cancer patients. C1 [D'Andrea, Alan D.; Kozono, David] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Kang, Josephine] Harvard Radiat Oncol Program, Boston, MA USA. RP Kozono, D (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dkozono@lroc.harvard.edu FU Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA FX This work was supported by the Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (internal funds). NR 56 TC 62 Z9 63 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY PY 2012 VL 104 IS 9 BP 670 EP 681 DI 10.1093/jnci/djs177 PG 12 WC Oncology SC Oncology GA 936PM UT WOS:000303602500008 PM 22505474 ER PT J AU Warner, J Hochberg, E AF Warner, Jeremy Hochberg, Ephraim TI Where is the EHR in Oncology? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID ELECTRONIC HEALTH RECORDS; CARE AB Electronic health records (EHRs) have the potential to increase the quality and decrease the cost of cancer care. These twin goals can only be met by a fully functional oncology EHR, which includes at a minimum: searchable data repositories, clinical decision support (CDS), the ability to electronically order chemotherapeutic medications, and the ability to interface with patients via a patient portal. Such fully functional EHRs not only offer patients the best potential for high-quality care, they enable retrospective analysis to answer a wide variety of comparative effectiveness and quality improvement questions. The significant barriers of cost, time pressures, aversion to CDS, and interoperability will need to be overcome if EHRs are to be meaningfully used by the majority of oncologists. (JNCCN 2012;10:584-588) C1 [Hochberg, Ephraim] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Warner, Jeremy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Hochberg, E (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9,9852, Boston, MA 02114 USA. EM ehochberg@partners.org NR 12 TC 3 Z9 3 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2012 VL 10 IS 5 BP 584 EP 588 PG 5 WC Oncology SC Oncology GA 935YI UT WOS:000303557700004 PM 22570289 ER PT J AU Hoppe, RT Advani, RH Ai, WYZ Ambinder, RF Aoun, P Bello, CM Bierman, PJ Blum, KA Chen, R Dabaja, B Duron, Y Forero, A Gordon, LI Hernandez-Ilizaliturri, FJ Hochberg, EP Maloney, DG Mansur, D Mauch, PM Metzger, M Moore, JO Morgan, D Moskowitz, CH Poppe, M Pro, B Winter, JN Yahalom, J Sundar, H AF Hoppe, Richard T. Advani, Ranjana H. Ai, Weiyun Z. Ambinder, Richard F. Aoun, Patricia Bello, Celeste M. Bierman, Philip J. Blum, Kristie A. Chen, Robert Dabaja, Bouthaina Duron, Ysabel Forero, Andres Gordon, Leo I. Hernandez-Ilizaliturri, Francisco J. Hochberg, Ephraim P. Maloney, David G. Mansur, David Mauch, Peter M. Metzger, Monika Moore, Joseph O. Morgan, David Moskowitz, Craig H. Poppe, Matthew Pro, Barbara Winter, Jane N. Yahalom, Joachim Sundar, Hema TI Hodgkin Lymphoma, Version 2.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; STEM-CELL TRANSPLANTATION; INVOLVED-FIELD RADIOTHERAPY; HIGH-DOSE CHEMORADIOTHERAPY; RANDOMIZED-TRIAL; PHASE-2 TRIAL; FREE SURVIVAL; 2 CYCLES; FDG-PET; DISEASE AB The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue. (JNCCN 2012;10:589-597) C1 [Hoppe, Richard T.; Advani, Ranjana H.] Stanford Canc Inst, Stanford, CA USA. [Ai, Weiyun Z.] UCSF Hellen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Ambinder, Richard F.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Aoun, Patricia; Bierman, Philip J.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Bello, Celeste M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Blum, Kristie A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Chen, Robert] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Dabaja, Bouthaina] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Forero, Andres] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Gordon, Leo I.; Winter, Jane N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Mansur, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Mansur, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Mauch, Peter M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Metzger, Monika] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Moore, Joseph O.] Duke Canc Inst, Durham, NC USA. [Morgan, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moskowitz, Craig H.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Poppe, Matthew] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA USA. RP Hoppe, RT (reprint author), Stanford Canc Inst, Stanford, CA USA. RI Blum, Kristie/E-2768-2011; OI Gordon, Leo/0000-0003-1666-7064 NR 34 TC 44 Z9 47 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2012 VL 10 IS 5 BP 589 EP 597 PG 9 WC Oncology SC Oncology GA 935YI UT WOS:000303557700005 PM 22570290 ER PT J AU Martins, RG D'Amico, TA Loo, BW Pinder-Schenck, M Borghaei, H Chaft, JE Ganti, AKP Kong, FM Kris, MG Lennes, IT Wood, DE AF Martins, Renato G. D'Amico, Thomas A. Loo, Billy W., Jr. Pinder-Schenck, Mary Borghaei, Hossein Chaft, Jamie E. Ganti, Apar Kishor P. Kong, Feng-Ming (Spring) Kris, Mark G. Lennes, Inga T. Wood, Douglas E. TI The Management of Patients With Stage IIIA Non-Small Cell Lung Cancer With N2 Mediastinal Node Involvement SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SLOAN-KETTERING EXPERIENCE; PHASE-II; INDUCTION CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; EMISSION-TOMOGRAPHY; NEOADJUVANT THERAPY; ENDOBRONCHIAL ULTRASOUND; RADIATION-THERAPY; CONCURRENT CHEMOTHERAPY AB Patients with stage IIIA non small cell lung cancer, determined based on involvement of ipsilateral mediastinal lymph nodes, represent the most challenging management problem in this disease. Patients with this stage disease may have very different degrees of lymph node involvement. The pathologic confirmation of this involvement is a key step in the therapeutic decision. The difference in the degree of lymph node compromise has prognostic and treatment implications. Based on multiple considerations, patients can be treated with induction chemotherapy, chemoradiotherapy followed by surgery, or definitive chemoradiotherapy without surgery. Data derived from clinical trials have provided incomplete guidance for physicians and their patients. The best therapeutic plan is achieved through the multidisciplinary cooperation of a team specialized in lung cancer. (JNCCN 2012;10:599-613) C1 [Martins, Renato G.; Wood, Douglas E.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [D'Amico, Thomas A.] Duke Canc Inst, Durham, NC USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Pinder-Schenck, Mary] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chaft, Jamie E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ganti, Apar Kishor P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, VA Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. [Kong, Feng-Ming (Spring)] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Martins, RG (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, 825 Eastlake Ave E, Seattle, WA 98109 USA. EM rgmart@u.washington.edu OI Ganti, Apar Kishor/0000-0003-3724-2671 NR 69 TC 20 Z9 20 U1 1 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2012 VL 10 IS 5 BP 599 EP 613 PG 15 WC Oncology SC Oncology GA 935YI UT WOS:000303557700006 PM 22570291 ER PT J AU Rodgers, GM Becker, PS Blinder, M Cella, D Chanan-Khan, A Cleeland, C Coccia, PF Djulbegovic, B Gilreath, JA Kraut, EH Matulonis, UA Millenson, MM Reinke, D Rosenthal, J Schwartz, RN Soff, G Stein, RS Vlahovic, G Weir, AB AF Rodgers, George M., III Becker, Pamela Sue Blinder, Morey Cella, David Chanan-Khan, Asher Cleeland, Charles Coccia, Peter F. Djulbegovic, Benjamin Gilreath, Jeffrey A. Kraut, Eric H. Matulonis, Ursula A. Millenson, Michael M. Reinke, Denise Rosenthal, Joseph Schwartz, Rowena N. Soff, Gerald Stein, Richard S. Vlahovic, Gordana Weir, Alva B., III TI Cancer- and Chemotherapy-Induced Anemia SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID ERYTHROPOIESIS-STIMULATING AGENTS; PLACEBO-CONTROLLED TRIAL; RED-CELL APLASIA; PHASE-III TRIAL; NONHEMOLYTIC TRANSFUSION REACTIONS; CHRONIC KIDNEY-DISEASE; BLOOD-PRODUCT SUPPORT; ADVERSE DRUG EVENTS; PATIENT-LEVEL DATA; QUALITY-OF-LIFE AB Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition. (JNCCN 2012;10:628-653) C1 [Rodgers, George M., III; Gilreath, Jeffrey A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Becker, Pamela Sue] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Blinder, Morey] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Blinder, Morey] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Cella, David] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Chanan-Khan, Asher] Roswell Pk Canc Inst, Buffalo, NY USA. [Cleeland, Charles] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Coccia, Peter F.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Kraut, Eric H.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Kraut, Eric H.] Solove Res Inst, Columbus, OH USA. [Matulonis, Ursula A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Reinke, Denise] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Rosenthal, Joseph] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Schwartz, Rowena N.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Soff, Gerald] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Stein, Richard S.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Weir, Alva B., III] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. RP Rodgers, GM (reprint author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 87 TC 45 Z9 47 U1 0 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2012 VL 10 IS 5 BP 628 EP + PG 13 WC Oncology SC Oncology GA 935YI UT WOS:000303557700008 PM 22570293 ER PT J AU Oklu, R Albadawi, H Watkins, MT Monestier, M Sillesen, M Wicky, S AF Oklu, Rahmi Albadawi, Hassan Watkins, Michael T. Monestier, Marc Sillesen, Martin Wicky, Stephan TI Detection of Extracellular Genomic DNA Scaffold in Human Thrombus: Implications for the Use of Deoxyribonuclease Enzymes in Thrombolysis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CYSTIC-FIBROSIS; ISCHEMIA-REPERFUSION; VENOUS THROMBOSIS; TRAPS; MOUSE; AGE AB Purpose: Mechanisms underlying transition of a thrombus susceptible to tissue plasminogen activator (TPA) fibrinolysis to one that is resistant is unclear. Demonstration of a new possible thrombus scaffold may open new avenues of research in thrombolysis and may provide mechanistic insight into thrombus remodeling. Materials and Methods: Ten human thrombus samples were collected during cases of thrombectomy and open surgical repair of abdominal aortic aneurysms (five samples < 3 d old and five samples > 1 y old). Additionally, an acute murine hindlimb ischemia model was created to evaluate thrombus samples in mice. Human sections were immunostained for the H2A/H2B/DNA complex, myeloperoxidase, fibrinogen, and von Willebrand factor. Mouse sections were immunostained with the H2A antibody. All samples were further evaluated after hematoxylin and eosin and Masson trichrome staining. Results: An extensive network of extracellular histone/DNA complex was demonstrated in the matrix of human ex vivo thrombus. This network is present throughout the highly cellular acute thrombus. However, in chronic thrombi, detection of the histone/DNA network was predominantly in regions of low collagen content and high cell density, which were mostly near the lumen. These regions of high cell density contained neutrophils and monocytes. Similarly, sections from the acute murine hindlimb ischemia model also exhibited extensive immunoreactivity to the histone antibody in the extracellular space within murine thrombi. Conclusions: Extensive detection of genomic DNA associated with histones in the extracellular matrix of human and mouse thrombi suggest the presence of a new thrombus-associated scaffold. C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Albadawi, Hassan; Watkins, Michael T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. [Sillesen, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Monestier, Marc] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19122 USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. EM roklu@partners.org FU American College of Phlebology; National Institutes of Health [R01 AR055843] FX R.O. is the recipient of the American College of Phlebology Investigator Award. M.T.W. is the Isenberg Scholar in Academic Surgery at the Massachusetts General Hospital and the recipient of National Institutes of Health Grant R01 AR055843. NR 27 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2012 VL 23 IS 5 BP 712 EP 718 DI 10.1016/j.jvir.2012.01.072 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 935YB UT WOS:000303557000021 PM 22525027 ER PT J AU Lichterfeld, M Cung, T Seiss, K Rosenberg, ES Pereyra, F Yu, XG AF Lichterfeld, Mathias Thai Cung Seiss, Katherine Rosenberg, Eric S. Pereyra, Florencia Yu, Xu G. TI Shelterin Dysfunction and p16(INK4a)-Mediated Growth Inhibition in HIV-1-Specific CD8 T Cells SO JOURNAL OF VIROLOGY LA English DT Article ID TELOMERE DAMAGE RESPONSE; HIV-1 INFECTION; REPLICATIVE SENESCENCE; DISEASE PROGRESSION; IMMUNE ACTIVATION; EXPRESSION; TRF2; NONPROGRESSORS; PROLIFERATION; MECHANISMS AB HIV-1-specific cytotoxic T cell responses are expanded during advanced HIV-1 infection but seem unable to effectively protect the host against disease progression. These cells are able to produce gamma interferon and remain metabolically active but have defective proliferative activities, shortened telomeric DNA, and other signs of accelerated aging. To investigate the molecular mechanisms underlying the premature senescence of HIV-1-specific T cells, we focused here on the expression and function of a group of six nucleoproteins that are responsible for protecting and maintaining the structural integrity of telomeric DNA and are commonly referred to as "shelterin." We show that in progressive HIV-1 infection, the two major shelterin components TRF2 and TPP1 are selectively reduced in HIV-1-specific CD8 T cells, but not in T cells recognizing alternative viral species. This coincided with increased recruitment of 53BP1, a prominent DNA damage response factor, to telomeric DNA sites and was associated with elevated expression of the tumor suppressor p16(INK4a), which causes cellular growth inhibition in response to structural DNA damage. Notably, defective shelterin function and upregulation of p16(INK4a) remained unaffected by experimental blockade of PD-1, indicating a possibly irreversible structural defect in HIV-1-specific CD8 T cells in progressors that cannot be overcome by manipulation of inhibitory cell-signaling pathways. These data suggest that shelterin dysfunction and ensuing upregulation of the tumor suppressor p16(INK4a) promote accelerated aging of HIV-1-specific T cells during progressive HIV-1 infection. C1 [Thai Cung; Seiss, Katherine; Pereyra, Florencia; Yu, Xu G.] MIT & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Lichterfeld, Mathias; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Yu, XG (reprint author), MIT & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. EM Xyu@partners.org FU U.S. National Institutes of Health [AI078799, AI074415, AI093203]; Doris Duke Charitable Foundation [2009034] FX This study was supported by the U.S. National Institutes of Health (grants AI078799 and AI074415 to X.G.Y. and AI093203 to M.L.). X.G.Y. and M.L. are recipients of the Clinical Scientist Development Award from the Doris Duke Charitable Foundation (grant number 2009034). Recruitment of HIV-1 controllers was supported by the Bill and Melinda Gates Foundation, the Mark and Lisa Schwartz Foundation, and the International HIV Controller Study. NR 42 TC 3 Z9 3 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2012 VL 86 IS 10 BP 5533 EP 5540 DI 10.1128/JVI.00196-12 PG 8 WC Virology SC Virology GA 939DJ UT WOS:000303787100011 PM 22398292 ER PT J AU Valle-Casuso, JC Di Nunzio, F Yang, Y Reszka, N Lienlaf, M Arhel, N Perez, P Brass, AL Diaz-Griffero, F AF Valle-Casuso, Jose Carlos Di Nunzio, Francesca Yang, Yang Reszka, Natalia Lienlaf, Maritza Arhel, Nathalie Perez, Patricio Brass, Abraham L. Diaz-Griffero, Felipe TI TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core SO JOURNAL OF VIROLOGY LA English DT Article ID DNA INTEGRATION; TRANSPORTIN-SR2; DOMAIN; VIRUS; PROTEINS AB TNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to integration. To investigate the mechanistic requirement of TNPO3 in HIV-1 infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3 binds to the HIV-1 core. Overall, this work suggests that TNPO3 interacts with the incoming HIV-1 core in the cytoplasm to assist a process that is important for HIV-1 infection after nuclear import. C1 [Valle-Casuso, Jose Carlos; Di Nunzio, Francesca; Yang, Yang; Reszka, Natalia; Lienlaf, Maritza; Perez, Patricio; Diaz-Griffero, Felipe] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Arhel, Nathalie] Inst Pasteur, Lab Virol Mol & Vaccinol, Paris, France. [Brass, Abraham L.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard U, Boston, MA USA. [Brass, Abraham L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Diaz-Griffero, F (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM Felipe.Diaz-Griffero@einstein.yu.edu RI Di Nunzio, Francesca/A-6153-2014; OI Di Nunzio, Francesca/0000-0003-2879-3164; Arhel, Nathalie/0000-0001-5309-1725 FU Harvard Center for AIDS Research (CFAR); Phillip T. and Susan M. Ragon Institute Foundation; Bill and Melinda Gates Foundation; National Institutes of Health [R01 AI087390, K99/R00, 4R00MH086162-02]; Fondation pour la Recherche Medicale (FRM); Centre National de la Recherche Scientifique (CNRS) FX Funding to A.L.B. for this effort was provided by the Harvard Center for AIDS Research (CFAR), the Phillip T. and Susan M. Ragon Institute Foundation, and the Bill and Melinda Gates Foundation's Global Health Program. This work was funded by NIH grant R01 AI087390 to F.D.-G. and a K99/R00 Pathway to Independence Award to F.D.-G. from the National Institutes of Health, grant 4R00MH086162-02. F.D.N. and N.A. were supported by the Fondation pour la Recherche Medicale (FRM) and the Centre National de la Recherche Scientifique (CNRS). NR 22 TC 36 Z9 36 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2012 VL 86 IS 10 BP 5931 EP 5936 DI 10.1128/JVI.00451-12 PG 6 WC Virology SC Virology GA 939DJ UT WOS:000303787100050 PM 22398280 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Intensifying tumour immunity through combination therapy SO LANCET ONCOLOGY LA English DT Editorial Material ID RESISTANT PROSTATE-CANCER; IMMUNOTHERAPY C1 [Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Canc Vaccine Ctr, Boston, MA 02215 USA. [Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Dranoff, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. EM glenn_dranoff@dfci.harvard.edu FU NCI NIH HHS [P01 CA078378, R01 CA143083] NR 13 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 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2012 VL 13 IS 5 BP 440 EP 442 DI 10.1016/S1470-2045(12)70051-7 PG 4 WC Oncology SC Oncology GA 935HC UT WOS:000303508700025 PM 22326921 ER PT J AU Margolin, K Ernstoff, MS Hamid, O Lawrence, D McDermott, D Puzanov, I Wolchok, JD Clark, JI Sznol, M Logan, TF Richards, J Michener, T Balogh, A Heller, KN Hodi, FS AF Margolin, Kim Ernstoff, Marc S. Hamid, Omid Lawrence, Donald McDermott, David Puzanov, Igor Wolchok, Jedd D. Clark, Joseph I. Sznol, Mario Logan, Theodore F. Richards, Jon Michener, Tracy Balogh, Agnes Heller, Kevin N. Hodi, F. Stephen TI Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID PROGNOSTIC-FACTORS; STEREOTACTIC RADIOSURGERY; CEREBRAL METASTASES; SOLID TUMORS; SURVIVAL; THERAPY; TEMOZOLOMIDE; CONFIDENCE; GUIDELINES; BLOCKADE AB Background Brain metastases commonly develop in patients with melanoma and are a frequent cause of death of patients with this disease. Ipilimumab improves survival in patients with advanced melanoma. We aimed to investigate the safety and activity of this drug specifically in patients with brain metastases. Methods Between July 31, 2008, and June 3, 2009, we enrolled patients with melanoma and brain metastases from ten US centres who were older than 16 years into two parallel cohorts. Patients in cohort A were neurologically asymptomatic and were not receiving corticosteroid treatment at study entry; those in cohort B were symptomatic and on a stable dose of corticosteroids. Patients were to receive four doses of 10 mg/kg intravenous ipilimumab, one every 3 weeks. Individuals who were clinically stable at week 24 were eligible to receive 10 mg/kg intravenous ipilimumab every 12 weeks. The primary endpoint was the proportion of patients with disease control, defined as complete response, partial response, or stable disease after 12 weeks, assessed with modified WHO criteria. Analyses of safety and efficacy included all treated patients. This trial is registered with ClinicalTrials.gov, number NCT00623766. Findings We enrolled 72 patients: 51 into cohort A and 21 into cohort B. After 12 weeks, nine patients in cohort A exhibited disease control (18%, 95% CI 8-31), as did one patient in cohort B (5%, 0.1-24). When the brain alone was assessed, 12 patients in cohort A (24%, 13-38) and two in cohort B (10%, 1-30) achieved disease control. We noted disease control outside of the brain in 14 patients (27%, 16-42) in cohort A and in one individual (5%, 0.1-24) in cohort B. The most common grade 3 adverse events in cohort A were diarrhoea (six patients [12%]) and fatigue (six [12%]); in cohort B, they were dehydration (two individuals [10%]), hyperglycaemia (two [10%]), and increased concentrations of serum aspartate aminotransferase (two [10%]). One patient in each cohort had grade 4 confusion. The most common grade 3 immune-related adverse events were diarrhoea (six patients [12%]) and rash (one [2%]) in cohort A, and rash (one individual [5%]) and increased concentrations of serum aspartate aminotransferase (two [10%]) in cohort B. One patient in cohort A died of drug-related complications of immune-related colitis. Interpretation Ipilimumab has activity in some patients with advanced melanoma and brain metastases, particularly when metastases are small and asymptomatic. The drug has no unexpected toxic effects in this population. C1 [Margolin, Kim] Univ Washington, Seattle, WA 98195 USA. [Ernstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Hamid, Omid] Angeles Clin & Res Inst, Santa Monica, CA USA. [Lawrence, Donald] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Clark, Joseph I.] Loyola Univ, Chicago, IL 60611 USA. [Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. [Logan, Theodore F.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Richards, Jon] Oncol Specialists SC, Park Ridge, IL USA. [Michener, Tracy] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Balogh, Agnes] Bristol Myers Squibb Co, Braine Lalleud, Belgium. [Heller, Kevin N.] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margolin, K (reprint author), Seattle Canc Care Alliance, Seattle, WA 98109 USA. EM kmargoli@seattlecca.org FU Bristol-Myers Squibb FX Bristol-Myers Squibb. NR 32 TC 296 Z9 296 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2012 VL 13 IS 5 BP 459 EP 465 DI 10.1016/S1470-2045(12)70090-6 PG 7 WC Oncology SC Oncology GA 935HC UT WOS:000303508700037 PM 22456429 ER PT J AU Yang, JCH Shih, JY Su, WC Hsia, TC Tsai, CM Ou, SHI Yu, CJ Chang, GC Ho, CL Sequist, LV Dudek, AZ Shahidi, M Cong, XJ Lorence, RM Yang, PC Miller, VA AF Yang, James Chih-Hsin Shih, Jin-Yuan Su, Wu-Chou Hsia, Te-Chun Tsai, Chun-Ming Ou, Sai-Hong Ignatius Yu, Chung-Jen Chang, Gee-Chen Ho, Ching-Liang Sequist, Lecia V. Dudek, Arkadiusz Z. Shahidi, Mehdi Cong, Xiuyu Julie Lorence, Robert M. Yang, Pan-Chyr Miller, Vincent A. TI Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID ADVANCED SOLID TUMORS; TYROSINE KINASE; EGFR MUTATIONS; 1ST-LINE GEFITINIB; OPEN-LABEL; CANCER; INHIBITOR; CHEMOTHERAPY; ERLOTINIB; SURVIVAL AB Background Afatinib is an irreversible ErbB-family blocker with preclinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. We aimed to assess the efficacy of afatinib in patients with lung adenocarcinoma and EGFR mutations. Methods In this phase 2 study, we enrolled patients from 30 centres in Taiwan and the USA with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) with EGFR mutations, who had no more than one previous chemotherapy regimen for advanced disease, an Eastern Cooperative Oncology Group performance status of 0-2, and no previous treatment with EGFR tyrosine-kinase inhibitors. We tested two afatinib starting doses: 50 mg daily and subsequently 40 mg daily, introduced to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). This study is registered with ClinicalTrials.gov, number NCT00525148. Findings 129 patients were treated with afatinib, 99 with a starting dose of 50 mg and 30 with a starting dose of 40 mg. 79 (61%) of 129 patients had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 patients with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 patients with less common mutations. Similar proportions of patients had an objective response when analysed by starting dose (18 [60%] of 30 patients at 40 mg vs 61 [62%] of 99 patients at 50 mg). Of the two most common adverse events (diarrhoea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 [22%] of 99 patients for diarrhoea and 28 [28%] of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two [7%] of 30 patients for both diarrhoea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). We recorded one possibly drug-related death (interstitial lung disease). Interpretation Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations. The efficacy of afatinib 40 mg should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC. C1 [Yang, James Chih-Hsin] Natl Taiwan Univ, Coll Med, Grad Inst Oncol, Taipei 10764, Taiwan. [Yang, James Chih-Hsin] Natl Taiwan Univ, Coll Med, Canc Res Ctr, Taipei 10764, Taiwan. [Shih, Jin-Yuan; Yu, Chung-Jen; Yang, Pan-Chyr] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Su, Wu-Chou] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70428, Taiwan. [Hsia, Te-Chun] China Med Univ, Grad Inst Integrated Med, Taichung, Taiwan. [Hsia, Te-Chun] China Med Univ Hosp, Dept Internal Med, Taichung, Taiwan. [Tsai, Chun-Ming] Taipei Vet Gen Hosp, Chest Dept, Taipei, Taiwan. [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Chang, Gee-Chen] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei 112, Taiwan. [Chang, Gee-Chen] Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan. [Ho, Ching-Liang] Triserv Gen Hosp, Div Hematol Oncol, Taipei, Taiwan. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Dudek, Arkadiusz Z.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Shahidi, Mehdi] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Cong, Xiuyu Julie; Lorence, Robert M.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Miller, Vincent A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Miller, VA (reprint author), Fdn Med, 1 Kendall Sq,B3501, Cambridge, MA 02139 USA. EM vmiller@foundationmedicine.com RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Yang, James Chih-Hsin/0000-0002-5586-5138; YANG, PAN-CHYR/0000-0001-6330-6048; SHIH, JIN-YUAN/0000-0002-2854-5067 FU Boehringer Ingelheim Inc.; Boehringer Ingelheim FX Boehringer Ingelheim Inc.; JC-HY is an advisory board member for Boehringer Ingelheim and has received honoraria from Boehringer Ingelheim (he had received an honorarium from Boehringer Ingelheim before February, 2009, but did not receive any honorarium from Boehringer Ingelheim since then). T-CH received investigator fees from Boehringer Ingelheim. LVS has provided advisory services for Clovis Oncology, GlaxoSmithKline, and Celgene, and has provided uncompensated advisory services for Boehringer Ingelheim, Daiichi-Sankyo, and Merrimack Pharmaceuticals. MS, XJC, and RML are employees of Boehringer Ingelheim. VAM has received honoraria from Boehringer Ingelheim, Clovis Oncology, Astellas, and Genentech, and has a patent application for T790M EGFR diagnosis. VAM was working at Memorial Sloan-Kettering Cancer Center during the design, conduct, and analysis of the trial, but is now an employee of Foundation Medicine-a private company that does not receive any financial backing from Boehringer Ingelheim. All other authors declare that they have no conflicts of interest. NR 33 TC 194 Z9 201 U1 3 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2012 VL 13 IS 5 BP 539 EP 548 DI 10.1016/S1470-2045(12)70086-4 PG 10 WC Oncology SC Oncology GA 935HC UT WOS:000303508700045 PM 22452895 ER PT J AU Galanis, E Wu, WT Cloughesy, T Lamborn, K Mann, B Wen, PY Reardon, DA Wick, W Macdonald, D Armstrong, TS Weller, M Vogelbaum, M Colman, H Sargent, DJ van den Bent, MJ Gilbert, M Chang, S AF Galanis, Evanthia Wu, Wenting Cloughesy, Timothy Lamborn, Kathleen Mann, Bhupinder Wen, Patrick Y. Reardon, David A. Wick, Wolfgang Macdonald, David Armstrong, Terri S. Weller, Michael Vogelbaum, Michael Colman, Howard Sargent, Daniel J. van den Bent, Martin J. Gilbert, Mark Chang, Susan TI Phase 2 trial design in neuro-oncology revisited: a report from the RANO group SO LANCET ONCOLOGY LA English DT Review ID II CLINICAL-TRIALS; NEWLY-DIAGNOSED GLIOBLASTOMA; RANDOMIZED DISCONTINUATION DESIGN; GLIOMAS RESPONSE ASSESSMENT; RECURRENT GLIOBLASTOMA; ADJUVANT TEMOZOLOMIDE; PROGNOSTIC-FACTORS; PLUS TEMOZOLOMIDE; RADIATION-THERAPY; MALIGNANT GLIOMA AB Advances in the management of gliomas, including the approval of agents such as temozolomide and bevacizumab, have created an evolving therapeutic landscape in glioma treatment, thus affecting our ability to reliably use historical controls to comparatively assess the activity of new therapies. Furthermore, the increasing availability of novel, targeted agents-which are competing for a small patient population, in view of the low incidence of primary brain tumours-draws attention to the need to improve the efficiency of phase 2 clinical testing in neuro-oncology to expeditiously transition the most promising of these drugs or combinations to potentially practice-changing phase 3 trials. In this report from the Response Assessment in Neurooncology (RANO) group, we review phase 2 trial designs that can address these challenges and capitalise on scientific and clinical advances in brain tumour treatment in neuro-oncology to accelerate and optimise the selection of drugs deserving further testing in phase 3 trials. Although there is still a small role for single-arm and non-comparative phase 2 designs, emphasis is placed on the potential role that comparative randomised phase 2 designs-such as screening designs, selection designs, discontinuation designs, and adaptive designs, including seamless phase 2/3 designs-can have. The rational incorporation of these designs, as determined by the specific clinical setting and the trial's endpoints or goals, has the potential to substantially advance new drug development in neuro-oncology. C1 [Galanis, Evanthia] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Wu, Wenting; Sargent, Daniel J.] Mayo Clin, Dept Stat, Rochester, MN 55905 USA. [Cloughesy, Timothy] Ronald Reagan UCLA Med Ctr, Neurooncol Program, Los Angeles, CA USA. [Lamborn, Kathleen; Chang, Susan] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Mann, Bhupinder] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Wen, Patrick Y.; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wick, Wolfgang] Univ Heidelberg, Dept Neurooncol, Heidelberg, Germany. [Wick, Wolfgang] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Macdonald, David] London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. [Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Sch Nursing, Dept Integrated Care, Houston, TX USA. [Armstrong, Terri S.; Gilbert, Mark] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Weller, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Vogelbaum, Michael] Cleveland Clin, Dept Neurol Surg, Cleveland, OH 44106 USA. [Colman, Howard] Univ Utah, Dept Neurosurg, Salt Lake City, UT USA. [van den Bent, Martin J.] Erasmus Univ, Med Ctr, Dept Neurooncol, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. RP Galanis, E (reprint author), Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. EM galanis.evanthia@mayo.edu FU Roche; Novartis; Amgen; AstraZeneca; Sanofi-Aventis; Genentech; Vascular Biogenics; Esai; Exelixis; MSD; Boehinger-Ingelheim; Merck; Merck Serono; Bayer Onyx; Myrexis; Schering FX MJvdB has a consultant role with Roche, MSD, Siena Biotech, Antisense Pharma, and Merck Ag; and has received honoraria from MSD and research funding from Roche. MV has a consultant role with Merck, Bristol-Myers Squibb, and Pharmaco-kinesis. TC has a consultant role with Genentech/Roche, Lilly, Novartis, and Agio; and has received honoraria from Merck. PYW has a consultant role with Novartis, Merck, and Stemline Therapeutics; and has received honoraria from Merck and research support from Novartis, Amgen, AstraZeneca, Sanofi-Aventis, Genentech, Vascular Biogenics, Esai, and Exelixis. DAR has a consultant role with Genentech/Roche, EMD Serono, and Merck/Schering; and has received honoraria from Genentech/Roche, EMD Serono, and Merck/Schering. WWi has a consultant role with Roche, Magforce, and MSD; and has received honoraria from MSD and research funding from MSD and Boehinger-Ingelheim. TSA has received honoraria from Merck and research funding from Merck and Genentech. MW has a consultant role with Roche, Merck, and SMD; and has received research funding from Roche and Merck Serono. HC has a consultant role with Castle Biosciences and has received research funding from Bayer Onyx and Myrexis. MG has a consultant role with Genentech, Merck, and Abbott; and has received honoraria and research funding from Merck and Genentech. SC has received research funding from Novartis and Schering. DM has received honoraria from Merck and Roche. EG, WWu, DJS, KL, and BM declare that they have no conflicts of interest in relation to this manuscript. NR 47 TC 23 Z9 23 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2012 VL 13 IS 5 BP E196 EP E204 PG 9 WC Oncology SC Oncology GA 935HC UT WOS:000303508700016 PM 22554547 ER PT J AU Cooley, ME Wang, Q Johnson, BE Catalano, P Haddad, RI Bueno, R Emmons, KM AF Cooley, Mary E. Wang, Qian Johnson, Bruce E. Catalano, Paul Haddad, Robert I. Bueno, Raphael Emmons, Karen M. TI Factors associated with smoking abstinence among smokers and recent-quitters with lung and head and neck cancer SO LUNG CANCER LA English DT Article DE Smoking cessation; Tobacco dependence; Lung cancer; Head and neck cancer; Smoking cessation interventions; Symptom management; Craving ID CONTINUED TOBACCO USE; DEPRESSION SCALE; HOSPITAL ANXIETY; CLINICAL-TRIALS; 1ST YEAR; CESSATION; DIAGNOSIS; PREDICTORS; WITHDRAWAL; BEHAVIOR AB Introduction: Smoking cessation among cancer patients is critical for improving outcomes. Understanding factors associated with smoking abstinence after the diagnosis of cancer can provide direction to develop and test interventions to enhance cessation rates. The purpose of this study was to identify determinants of smoking outcomes among cancer patients. Methods: Standardized questionnaires were used to collect data from 163 smokers or recent-quitters (quit <= 6 months) at study entry of which 132 and 121 had data collected at 3 and 6 months. Biochemical verification was conducted with urinary cotinine and carbon monoxide. Descriptive statistics, Cronbach alpha coefficients, Pearson correlations, Fisher's exact test, and multivariable logistic regression were used for analyses. Results: Seven-day-point-prevalence-abstinence (PPA) rates were 90/132(68%) at 3 months; 46/71 (65%) among lung and 44/61 (72%) among head and neck cancer patients, whereas 7-day-PPA rates were 74/121 (61%) at 6 months; 31/58(53%) among lung and 43/63 (68%) among head and neck cancer patients. Continuous abstinence rates were 63/89(71%) at 3 months; 32/45(71%) among lung and 31/44(70%) among head and neck cancer patients, whereas continuous abstinence rates were 46/89 (52%) at 6 months; 18/45 (40%) among lung and 28/44(64%) among head and neck cancer patients. Lower cancer-related, psychological and nicotine withdrawal symptoms were associated with increased 7-D-PPA abstinence rates at 3 and 6 months in univariate models. In multivariable models, however, decreased craving was significantly related with 7-day-PPA at 3 months and decreased craving and increased self-efficacy were associated with 7-D-PPA at 6 months. Decreased craving was the only factor associated with continuous abstinence at 6 months. Conclusions: Smoking outcomes among lung and head and neck cancer patients appear to have remained the same over the last two decades despite the availability of an increased number of pharmacotherapy options to treat tobacco dependence. Decreased craving and increased self-efficacy were the most consistent factors associated with improved smoking outcomes but symptom control may also play a role in optimal management. Use of combined, and/or higher doses of pharmacotherapy along with behavioral interventions that increase self-efficacy and manage symptoms may promote enhanced cessation rates. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Cooley, Mary E.; Wang, Qian; Johnson, Bruce E.; Catalano, Paul; Haddad, Robert I.; Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bueno, Raphael] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW-521, Boston, MA 02115 USA. EM mary_cooley@dfci.harvard.edu FU National Cancer Institute [1 K07 CA92696-02]; Dana-Farber Cancer Institute FX Source of support: National Cancer Institute 1 K07 CA92696-02 and James B. Gillen Thoracic Oncology Research Fund, Dana-Farber Cancer Institute (Mary E. Cooley). NR 49 TC 17 Z9 17 U1 2 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD MAY PY 2012 VL 76 IS 2 BP 144 EP 149 DI 10.1016/j.lungcan.2011.10.005 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 936WF UT WOS:000303620000003 PM 22093155 ER PT J AU Bowen, SL Ferrero, A Badawi, RD AF Bowen, Spencer L. Ferrero, Andrea Badawi, Ramsey D. TI Quantification with a dedicated breast PET/CT scanner SO MEDICAL PHYSICS LA English DT Article DE PET/CT; positron emission mammography; dedicated; breast cancer ID POSITRON EMISSION MAMMOGRAPHY; COMPONENT-BASED NORMALIZATION; 3D PET; ATTENUATION CORRECTION; IMAGING-SYSTEM; COMPUTED-TOMOGRAPHY; DETECTOR EFFICIENCY; SCATTER CORRECTION; COMPTON SCATTER; CANCER AB Purpose: Dedicated breast PET/CT is expected to have utility in local staging, surgical planning, monitoring of therapy response, and detection of residual disease for breast cancer. Quantitative metrics will be integral to several such applications. The authors present a validation of fully 3D data correction schemes for a custom built dedicated breast PET/CT (DbPET/CT) scanner via F-18-FDG phantom scans. Methods: A component-based normalization was implemented, live-time was estimated with a multicomponent model, and a variance reduced randoms estimate was computed from delayed coincidences. Attenuation factors were calculated by using a CT based segmentation scheme while scatter was computed using a Monte Carlo (MC) simulation method. As no performance standard currently exists for breast PET systems, custom performance tests were created based on prior patient imaging results. Count-rate linearity for live-time and randoms corrections was measured with a decay experiment for a solid polyethylene cylinder phantom with an offset line source. A MC simulation was used to validate attenuation correction, a multicompartment phantom with asymmetric activity distribution provided an assessment of scatter correction, and image uniformity after geometric and detector normalization was measured from a high count scan of a uniform cylinder phantom. Raw data were reconstructed with filtered back projection (FBP) after Fourier rebinning. To quantify performance absolute activity concentrations, contrast recovery coefficients and image uniformity were calculated through region of interest analysis. Results: The most significant source of error was attributed to mispositioning of events due to pileup, presenting in count-related axial and transaxial nonuniformities that were not corrected for with the normalization method used here. Within the range of singles counts observed during clinical trials residual error after applying all corrections was comparable to that of a commercial whole body PET/CT system. Conclusions: The results suggest that DbPET/CT is capable of producing quantitative images under the operating conditions expected during patient imaging. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.3703593] C1 [Bowen, Spencer L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ferrero, Andrea] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Badawi, Ramsey D.] Univ Calif Davis, Med Ctr, Dept Radiol, Sacramento, CA 95817 USA. RP Bowen, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM slbowen@nmr.mgh.harvard.edu FU Susan G. Komen for the Cure foundation [BCT40707455]; National Institutes of Health [NIH-NCI R01 CA129561]; National Institute of Biomedical Imaging and Bioengineering [R01-EB002138]; California Breast Cancer Research Program [11IB-0114] FX The authors thank Dr. Kai Yang and Dr. Michel Tohme for useful discussions, Felipe Godinez for technical assistance, Dr. Abhijit Chaudhari for useful discussion and manuscript preparation, and Dr. John Boone for use of equipment and facilities. Funding was provided in part by the Susan G. Komen for the Cure foundation (Grant No. BCT40707455), the National Institutes of Health (Grant No. NIH-NCI R01 CA129561), the National Institute of Biomedical Imaging and Bioengineering (Grant No. R01-EB002138), and the California Breast Cancer Research Program (Grant No. 11IB-0114). NR 51 TC 3 Z9 3 U1 1 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2012 VL 39 IS 5 BP 2694 EP 2707 DI 10.1118/1.3703593 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 936QE UT WOS:000303604300040 PM 22559640 ER PT J AU Correger, E Murias, G Chacon, E Estruga, A Sales, B Lopez-Aguilar, J Montanya, J Lucangelo, U Garcia-Esquirol, O Villagra, A Villar, J Kacmarek, RM Burgueno, MJ Blanch, L AF Correger, E. Murias, G. Chacon, E. Estruga, A. Sales, B. Lopez-Aguilar, J. Montanya, J. Lucangelo, U. Garcia-Esquirol, O. Villagra, A. Villar, J. Kacmarek, R. M. Burgueno, M. J. Blanch, L. TI Interpretation of ventilator curves in patients with acute respiratory failure SO MEDICINA INTENSIVA LA Spanish DT Review DE Mechanical ventilation; Auto-PEEP; Pressure-volume curve; Stress index; Resistance; Elastance; Ineffective inspiratory effort; Dyssynchrony; Double trigger; Patient-ventilator interaction; Acute respiratory failure ID END-EXPIRATORY PRESSURE; OBSTRUCTIVE PULMONARY-DISEASE; POSITIVE AIRWAY PRESSURE; INDUCED LUNG INJURY; MECHANICAL VENTILATION; VOLUME CURVES; DISTRESS-SYNDROME; FLOW LIMITATION; RELEASE VENTILATION; SUPPORT VENTILATION AB Mechanical ventilation is a therapeutic intervention involving the temporary replacement of ventilatory function with the purpose of improving symptoms in patients with acute respiratory failure. Technological advances have facilitated the development of sophisticated ventilators for viewing and recording the respiratory waveforms, which are a valuable source of information for the clinician. The correct interpretation of these curves is crucial for the correct diagnosis and early detection of anomalies, and for understanding physiological aspects related to mechanical ventilation and patient-ventilator interaction. The present study offers a guide for the interpretation of the airway pressure and flow and volume curves of the ventilator, through the analysis of different clinical scenarios. (C) 2011 Elsevier Espana, S.L. and SEMICYUC. All rights reserved. C1 [Chacon, E.; Estruga, A.; Lopez-Aguilar, J.; Villagra, A.; Burgueno, M. J.; Blanch, L.] Corp Sanitaria, Crit Care Ctr, Hosp Sabadell, Sabadell, Spain. [Correger, E.] Hosp El Cruce, Grp Trabajo Fisiopatol Pulm Expt, Catedra Fisiol, FCM,UNLP, Buenos Aires, DF, Argentina. [Correger, E.] Fdn Favaloro, Buenos Aires, DF, Argentina. [Murias, G.] Clin Bazterrica, Buenos Aires, DF, Argentina. [Murias, G.] Clin Santa Isabel, Buenos Aires, DF, Argentina. [Sales, B.; Lopez-Aguilar, J.; Villagra, A.; Villar, J.; Blanch, L.] ISCiii, CIBER Enfermedades Resp, Madrid, Spain. [Sales, B.; Montanya, J.; Garcia-Esquirol, O.; Blanch, L.] Univ Autonoma Barcelona, Fundacio Parc Tauli, Corp Sanitaria, Univ Parc Tauli, Sabadell, Spain. [Lucangelo, U.] Univ Trieste, Dipartimento Med Perioperatoria, Osped Cattinara, I-34127 Trieste, Italy. [Villar, J.] Hosp Univ Dr Negrin, MODERN, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, R. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kacmarek, R. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Blanch, L (reprint author), Corp Sanitaria, Crit Care Ctr, Hosp Sabadell, Sabadell, Spain. EM lblanch@tauli.cat NR 45 TC 10 Z9 11 U1 0 U2 9 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0210-5691 J9 MED INTENSIVA JI Med. Intensiv. PD MAY PY 2012 VL 36 IS 4 BP 294 EP 306 DI 10.1016/j.medin.2011.08.005 PG 13 WC Critical Care Medicine SC General & Internal Medicine GA 939WH UT WOS:000303849600009 PM 22014424 ER PT J AU El-Shewy, HM Sohn, M Wilson, P Lee, MH Hammad, SM Luttrell, LM Jaffa, AA AF El-Shewy, Hesham M. Sohn, Mimi Wilson, Parker Lee, Mi Hye Hammad, Samar M. Luttrell, Louis M. Jaffa, Ayad A. TI Low-Density Lipoprotein Induced Expression of Connective Tissue Growth Factor via Transactivation of Sphingosine 1-Phosphate Receptors in Mesangial Cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GLYCOSYLATION END-PRODUCTS; PROTEIN-RELATED PROTEIN-2; SMAD SIGNALING CASCADE; P38 MAP KINASE; ENDOTHELIAL-CELLS; DIABETIC-NEPHROPATHY; SPHINGOSINE-1-PHOSPHATE RECEPTORS; ATHEROSCLEROTIC LESIONS; LYSOPHOSPHATIDIC ACID; RENAL-DISEASE AB The pro-fibrotic connective tissue growth factor (CTGF) has been linked to the development and progression of diabetic vascular and renal disease. We recently reported that low-density lipoproteins (LDL) induced expression of CTGF in aortic endothelial cells. However, the molecular mechanisms are not fully defined. Here, we have studied the mechanism by which LDL regulates CTGF expression in renal mesangial cells. In these cells, treatment with pertussis toxin abolished LDL-stimulated activation of ERK1/2 and c-Jun N-terminal kinase (JNK), indicating the involvement of heterotrimeric G proteins in LDL signaling. Treatment with LDL promoted activation and translocation of endogenous sphingosine kinase 1 (SK1) from the cytosol to the plasma membrane concomitant with production of sphingosine-1-phosphate (S1P). Pretreating cells with SK inhibitor, dimethylsphinogsine or down-regulation of SK1 and SK2 revealed that LDL-dependent activation of ERK1/2 and JNK is mediated by SK1. Using a green fluorescent protein-tagged S1P(1) receptor as a biological sensor for the generation of physiologically relevant S1P levels, we found that LDL induced S1P receptor activation. Pretreating cells with S1P(1)/S1P(3) receptor antagonist VPC23019 significantly inhibited activation of ERK1/2 and JNK by LDL, suggesting that LDL elicits G protein-dependent activation of ERK1/2 and JNK by stimulating SK1-dependent transactivation of S1P receptors. Furthermore, S1P stimulation induced expression of CTGF in a dose-dependent manner that was markedly inhibited by blocking the ERK1/2 and JNK signaling pathways. LDL-induced CTGF expression was pertussis toxin sensitive and inhibited by dimethylsphinogsine down-regulation of SK1 and VPC23019 treatment. Our data suggest that SK1-dependent S1P receptor transactivation is upstream of ERK1/2 and JNK and that all three steps are required for LDL-regulated expression of CTGF in mesangial cells. (Molecular Endocrinology 26: 833-845, 2012) C1 [Jaffa, Ayad A.] Amer Univ Beirut, Fac Med, Dept Biochem & Mol Genet, Beirut, Lebanon. [El-Shewy, Hesham M.; Sohn, Mimi; Wilson, Parker; Lee, Mi Hye; Luttrell, Louis M.; Jaffa, Ayad A.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Hammad, Samar M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Jaffa, AA (reprint author), Amer Univ Beirut, Fac Med, Dept Biochem & Mol Genet, Riad El Solh St, Beirut, Lebanon. EM aj24@aub.edu.lb FU NIH [HL077192, HL087986, DK55524]; South Carolina COBRE in Lipidomics and Pathobiology [P2 RR17677]; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center FX This work was supported by NIH Grants HL077192, HL087986 (to A.A.J.), DK55524 (to L.M.L.), the South Carolina COBRE in Lipidomics and Pathobiology (P2 RR17677) (to H.M.E.), and Research Service of the Ralph H. Johnson Veterans Affairs Medical Center (to L.M.L.). NR 62 TC 13 Z9 13 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2012 VL 26 IS 5 BP 833 EP 845 DI 10.1210/me.2011-1261 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940BL UT WOS:000303864900012 PM 22422617 ER PT J AU Carter, SL Cibulskis, K Helman, E McKenna, A Shen, H Zack, T Laird, PW Onofrio, RC Winckler, W Weir, BA Beroukhim, R Pellman, D Levine, DA Lander, ES Meyerson, M Getz, G AF Carter, Scott L. Cibulskis, Kristian Helman, Elena McKenna, Aaron Shen, Hui Zack, Travis Laird, Peter W. Onofrio, Robert C. Winckler, Wendy Weir, Barbara A. Beroukhim, Rameen Pellman, David Levine, Douglas A. Lander, Eric S. Meyerson, Matthew Getz, Gad TI Absolute quantification of somatic DNA alterations in human cancer SO NATURE BIOTECHNOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; COPY-NUMBER ALTERATION; NUCLEOTIDE POLYMORPHISM ARRAYS; HIGH-RESOLUTION ANALYSIS; ACUTE MYELOID-LEUKEMIA; CHROMOSOMAL INSTABILITY; GENETIC EVOLUTION; PROSTATE-CANCER; TUMOR SAMPLES; SOLID TUMORS AB We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity. C1 [Carter, Scott L.; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Onofrio, Robert C.; Winckler, Wendy; Weir, Barbara A.; Beroukhim, Rameen; Lander, Eric S.; Meyerson, Matthew; Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Carter, Scott L.; Helman, Elena] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Shen, Hui; Laird, Peter W.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA. [Zack, Travis] Harvard Univ, Biophys Program, Cambridge, MA 02138 USA. [Zack, Travis; Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Zack, Travis; Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. [Zack, Travis; Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Pellman, David] Harvard Univ, Childrens Hosp, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Dept Pediat Oncol,Sch Med, Boston, MA 02115 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA USA. RP Getz, G (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM gadgetz@broadinstitute.org RI Meyerson, Matthew/E-7123-2012; Laird, Peter/G-8683-2012 FU National Cancer Institute [U24CA126546, U24CA143867, U24CA143845]; National Human Genome Research Institute [T32 HG002295]; US National Institutes of Health (NIH) [5R01 GM083299-14]; Department of Defense [W81XWH-10-1-0222]; NIH/National Institute of General Medical Sciences [5 T32 GM008313]; NIH [K08CA122833, U54CA14379]; National Research Service Award [F32CA113126] FX This work was supported by grants from the National Cancer Institute as part of The Cancer Genome Atlas project: U24CA126546 (M.M.), U24CA143867 (M.M.), and U24CA143845 (G.G.). S.L.C. and E.H. were supported by training grant T32 HG002295 from the National Human Genome Research Institute. In addition, D.P. was supported by the US National Institutes of Health (NIH) - 5R01 GM083299-14; D.A.L. by Department of Defense W81XWH-10-1-0222; T.Z. by NIH/National Institute of General Medical Sciences 5 T32 GM008313; R.B. by NIH K08CA122833 and U54CA143798. B.A.W. was supported by National Research Service Award grant F32CA113126. NR 60 TC 332 Z9 333 U1 5 U2 51 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2012 VL 30 IS 5 BP 413 EP + DI 10.1038/nbt.2203 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 939IP UT WOS:000303803200021 PM 22544022 ER PT J AU Reyon, D Tsai, SQ Khayter, C Foden, JA Sander, JD Joung, JK AF Reyon, Deepak Tsai, Shengdar Q. Khayter, Cyd Foden, Jennifer A. Sander, Jeffry D. Joung, J. Keith TI FLASH assembly of TALENs for high-throughput genome editing SO NATURE BIOTECHNOLOGY LA English DT Article ID ZINC-FINGER NUCLEASES; DNA-BINDING SPECIFICITY; DOUBLE-STRAND BREAKS; EFFECTOR NUCLEASES; GENE MODIFICATION; CELLS; TRANSCRIPTION; PROTEINS; KNOCKOUT AB Engineered transcription activator-like effector nucleases (TALENs) have shown promise as facile and broadly applicable genome editing tools. However, no publicly available high-throughput method for constructing TALENs has been published, and large-scale assessments of the success rate and targeting range of the technology remain lacking. Here we describe the fast ligation-based automatable solid-phase high-throughput (FLASH) system, a rapid and cost-effective method for large-scale assembly of TALENs. We tested 48 FLASH-assembled TALEN pairs in a human cell-based EGFP reporter system and found that all 48 possessed efficient gene-modification activities. We also used FLASH to assemble TALENs for 96 endogenous human genes implicated in cancer and/or epigenetic regulation and found that 84 pairs were able to efficiently introduce targeted alterations. Our results establish the robustness of TALEN technology and demonstrate that FLASH facilitates high-throughput genome editing at a scale not currently possible with other genome modification technologies. C1 [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Foden, Jennifer A.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Foden, Jennifer A.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Reyon, Deepak] Iowa State Univ, Dept Genet Dev & Cell Biol, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA USA. [Reyon, Deepak; Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. EM jsander@partners.org; jjoung@partners.org RI Tsai, Shengdar/G-4600-2012 FU US National Institutes of Health (NIH) [DP1 OD006862]; NIH [P50HG005550, T32 CA009216]; Jim and Ann Orr MGH Research Scholar Award; National Science Foundation [DBI-0923827] FX We thank T. Cathomen for providing polyclonal U2OS-EGFP reporter cells and a T7EI protocol, Y. Fu for deriving the clonal U2OS-EGFP cell line, D. Dobbs for support and encouragement, and M. Maeder, J. Angstman and C. Ramirez for helpful comments. This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award DP1 OD006862 (J.K.J.), NIH P50HG005550 (J.K.J.), the Jim and Ann Orr MGH Research Scholar Award (J.K.J.), NIH T32 CA009216 (J.D.S.) and National Science Foundation DBI-0923827 (D.R.). NR 32 TC 400 Z9 433 U1 12 U2 162 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2012 VL 30 IS 5 BP 460 EP + DI 10.1038/nbt.2170 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 939IP UT WOS:000303803200027 PM 22484455 ER PT J AU Cummings, DE AF Cummings, David E. TI Metabolic surgery for type 2 diabetes SO NATURE MEDICINE LA English DT Editorial Material ID BARIATRIC SURGERY; GASTROINTESTINAL SURGERY; LIFE-STYLE; MECHANISMS; MORTALITY; RISK AB Clinicians note that bariatric operations can dramatically resolve type 2 diabetes, often before and out of proportion to postoperative weight loss. Now two randomized controlled trials formally show superior results from surgical compared with medical diabetes care, including among only mildly obese patients. The concept of 'metabolic surgery' to treat diabetes has taken a big step forward. C1 [Cummings, David E.] Univ Washington, Seattle, WA 98195 USA. [Cummings, David E.] VA Puget Sound Hlth Care Syst, Diabet & Obes Ctr Excellence, Seattle, WA USA. RP Cummings, DE (reprint author), Univ Washington, Seattle, WA 98195 USA. EM davidec@u.washington.edu NR 16 TC 20 Z9 21 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2012 VL 18 IS 5 BP 656 EP 658 DI 10.1038/nm.2773 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 938WE UT WOS:000303763500026 PM 22561818 ER PT J AU Islam, SA Luster, AD AF Islam, Sabina A. Luster, Andrew D. TI T cell homing to epithelial barriers in allergic disease SO NATURE MEDICINE LA English DT Review ID CUTANEOUS LYMPHOCYTE ANTIGEN; CHEMOKINE RECEPTORS CCR4; ACTIVATION-REGULATED CHEMOKINE; SMOOTH-MUSCLE-CELLS; ATOPIC-DERMATITIS; DENDRITIC CELLS; RETINOIC-ACID; T(H)2 CELLS; MOUSE MODEL; TH2 CELLS AB Allergic inflammation develops in tissues that have large epithelial surface areas that are exposed to the environment, such as the lung, skin and gut. In the steady state, antigen-experienced memory T cells patrol these peripheral tissues to facilitate swift immune responses against invading pathogens. In at least two allergy-prone organs, the skin and the gut, memory T cells are programmed during the initial antigen priming to express trafficking receptors that enable them to preferentially home to these organs. In this review we propose that tissue-specific memory and inflammation-specific T cell trafficking facilitates the development of allergic disease in these organs. We thus review recent advances in our understanding of tissue-specific T cell trafficking and how regulation of T cell trafficking by the chemokine system contributes to allergic inflammation in mouse models and in human allergic diseases of the skin, lung and gut. Inflammation-and tissue-specific T lymphocyte trafficking pathways are currently being targeted as new treatments for non-allergic inflammatory diseases and may yield effective new therapeutics for allergic diseases. C1 [Islam, Sabina A.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA. EM aluster@mgh.harvard.edu FU US National Institutes of Health [R37AI040618, U19AI095261] FX The authors were supported by US National Institutes of Health grants R37AI040618 and U19AI095261 to A.D.L. NR 167 TC 87 Z9 90 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2012 VL 18 IS 5 BP 705 EP 715 DI 10.1038/nm.2760 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 938WE UT WOS:000303763500038 PM 22561834 ER PT J AU Guo, W Schafer, S Greaser, ML Radke, MH Liss, M Govindarajan, T Maatz, H Schulz, H Li, SJ Parrish, AM Dauksaite, V Vakeel, P Klaassen, S Gerull, B Thierfelder, L Regitz-Zagrosek, V Hacker, TA Saupe, KW Dec, GW Ellinor, PT MacRae, CA Spallek, B Fischer, R Perrot, A Ozcelik, C Saar, K Hubner, N Gotthardt, M AF Guo, Wei Schafer, Sebastian Greaser, Marion L. Radke, Michael H. Liss, Martin Govindarajan, Thirupugal Maatz, Henrike Schulz, Herbert Li, Shijun Parrish, Amanda M. Dauksaite, Vita Vakeel, Padmanabhan Klaassen, Sabine Gerull, Brenda Thierfelder, Ludwig Regitz-Zagrosek, Vera Hacker, Timothy A. Saupe, Kurt W. Dec, G. William Ellinor, Patrick T. MacRae, Calum A. Spallek, Bastian Fischer, Robert Perrot, Andreas Oezcelik, Cemil Saar, Kathrin Hubner, Norbert Gotthardt, Michael TI RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing SO NATURE MEDICINE LA English DT Article ID FAMILIAL DILATED CARDIOMYOPATHY; RNA-BINDING PROTEINS; ISOFORM EXPRESSION; PASSIVE STIFFNESS; HEART-FAILURE; SR PROTEINS; DISEASE; MUTATIONS; RAT; MYOCARDIUM AB Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. By positional cloning using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the underlying cause of pathological titin isoform expression. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing. In addition to titin (TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats. This network is enriched for genes that have previously been linked to cardiomyopathy, ion homeostasis and sarcomere biology. Our studies emphasize the key role of post-transcriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure. C1 [Schafer, Sebastian; Radke, Michael H.; Liss, Martin; Govindarajan, Thirupugal; Maatz, Henrike; Schulz, Herbert; Dauksaite, Vita; Vakeel, Padmanabhan; Klaassen, Sabine; Gerull, Brenda; Thierfelder, Ludwig; Saar, Kathrin; Hubner, Norbert; Gotthardt, Michael] Max Delbruck Ctr Mol Med, Berlin, Germany. [Guo, Wei; Greaser, Marion L.; Li, Shijun; Parrish, Amanda M.] Univ Wisconsin, Muscle Biol Lab, Madison, WI 53706 USA. [Regitz-Zagrosek, Vera] Univ Med Berlin, Charite, Cardiovasc Res Ctr, Berlin, Germany. [Regitz-Zagrosek, Vera] Univ Med Berlin, Charite, Inst Gender Med, Berlin, Germany. [Hacker, Timothy A.; Saupe, Kurt W.] Univ Wisconsin, Dept Med, Madison, WI USA. [Dec, G. William; Ellinor, Patrick T.; MacRae, Calum A.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. [Spallek, Bastian; Fischer, Robert] Univ Med Berlin, Charite, Univ Kilikum Benjamin Franklin, Berlin, Germany. [Perrot, Andreas; Oezcelik, Cemil] Charite, Campus Virchow Klinikum, Dept Cardiol, D-13353 Berlin, Germany. RP Gotthardt, M (reprint author), Max Delbruck Ctr Mol Med, Berlin, Germany. EM gotthardt@mdc-berlin.de RI Greaser, Marion/C-6147-2012; Govindarajan, Thirupugal/A-8758-2015; OI Greaser, Marion/0000-0002-6583-9566; Radke, Michael/0000-0003-0112-9917; Govindarajan, Thirupugal/0000-0003-1714-1267; Govindarajan, Thirupugal/0000-0003-2660-9730; Schafer, Sebastian/0000-0002-6909-8275; Liss, Martin/0000-0002-0585-7850; Gotthardt, Michael/0000-0003-1788-3172 FU US National Institutes of Health [HL77196, HL075431]; Deutsche Forschungsgemeinschaft, Bonn, Germany; European Research Council [StG282078]; German Ministry of Science and Education (Nationales Genomforschungsnetz, NGFN-Plus Heart Failure Network) and EURATRANS [HEALTH-F4-2010-241504]; American Heart Association FX We are grateful to B. Goldbrich, O. Hummel, S. Lubitz, S. Makino, G. Patone, S. Blachut, R. Plehm, S. Probst, S. Schmidt and M. Wehle for expert technical assistance. R. Hetzer (Deutsches Herzzentrum Berlin) generously provided human cardiac tissue. Mammalian expression vectors for PTBP1 and HuD were gifts from R. Darnell, The Rockefeller University. This work was supported by the US National Institutes of Health grants HL77196 (M.L.G.) and HL075431 (C.A.M.), the Deutsche Forschungsgemeinschaft, Bonn, Germany and the European Research Council grant StG282078 (M.G.), the German Ministry of Science and Education (Nationales Genomforschungsnetz, NGFN-Plus Heart Failure Network) and EURATRANS (HEALTH-F4-2010-241504) (N.H.) and the American Heart Association (P.T.E.). NR 51 TC 106 Z9 111 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2012 VL 18 IS 5 BP 766 EP U162 DI 10.1038/nm.2693 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 938WE UT WOS:000303763500044 PM 22466703 ER PT J AU Mungamuri, SK Benson, EK Wang, SM Gu, W Lee, SW Aaronson, SA AF Mungamuri, Sathish Kumar Benson, Erica Kay Wang, Shaomeng Gu, Wei Lee, Sam W. Aaronson, Stuart A. TI p53-mediated heterochromatin reorganization regulates its cell fate decisions SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID WILD-TYPE P53; COVALENT HISTONE MODIFICATIONS; LACKING FUNCTIONAL P53; DNA-DAMAGE; NEGATIVE REGULATION; SWI/SNF COMPLEX; GENE-EXPRESSION; IN-VIVO; CHROMATIN; CANCER AB p53 is a major sensor of cellular stresses, and its activation influences cell fate decisions. We identified SUV39H1, a histone code 'writer' responsible for the histone H3 Lys9 trimethylation (H3K9me3) mark for 'closed' chromatin conformation, as a target of p53 repression. SUV39H1 downregulation was mediated transcriptionally by p21 and post-translationally by MDM2. The H3K9me3 repression mark was found to be associated with promoters of representative p53 target genes and was decreased upon p53 activation. Overexpression of SUV39H1 maintained higher levels of the H3K9me3 mark on these promoters and was associated with decreased p53 promoter occupancy and decreased transcriptional induction in response to p53. Conversely, SUV39H1 pre-silencing decreased H3K9me3 levels on these promoters and enhanced the p53 apoptotic response. These findings uncover a new layer of p53-mediated chromatin regulation through modulation of histone methylation at p53 target promoters. C1 [Mungamuri, Sathish Kumar; Benson, Erica Kay; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Gu, Wei] Columbia Univ, Coll Phys & Surg, Inst Canc Genet, Dept Pathol & Cell Biol, New York, NY USA. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. EM Stuart.Aaronson@mssm.edu FU National Cancer Institute [P01CA080058] FX The authors would like to thank E. Bernstein and her lab members as well as C. Munoz-Fontela, M. Kracikova and W. Murk for helpful discussions. The project was supported by grant P01CA080058 from the National Cancer Institute (to S.A.A. and S.W.L.). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the US National Institutes of Health. NR 60 TC 22 Z9 23 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2012 VL 19 IS 5 BP 478 EP U32 DI 10.1038/nsmb.2271 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 936SV UT WOS:000303611200004 PM 22466965 ER PT J AU Jia, HQ Pallos, J Jacques, V Lau, A Tang, B Cooper, A Syed, A Purcell, J Chen, Y Sharma, S Sangrey, GR Darnell, SB Plasterer, H Sadri-Vakili, G Gottesfeld, JM Thompson, LM Rusche, JR Marsh, JL Thomas, EA AF Jia, Haiqun Pallos, Judit Jacques, Vincent Lau, Alice Tang, Bin Cooper, Andrew Syed, Adeela Purcell, Judith Chen, Yi Sharma, Shefali Sangrey, Gavin R. Darnell, Shayna B. Plasterer, Heather Sadri-Vakili, Ghazaleh Gottesfeld, Joel M. Thompson, Leslie M. Rusche, James R. Marsh, J. Lawrence Thomas, Elizabeth A. TI Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Neurodegenerative; Striatum; Disease; Epigenetic; Therapeutic; Chromatin; Gene expression ID MOUSE MODEL; TRANSCRIPTIONAL ABNORMALITIES; GENE-EXPRESSION; TRANSGENIC MICE; NERVOUS-SYSTEM; NEURODEGENERATION; TOXICITY; CHEMOTHERAPY; NUCLEOSOME; REPRESSION AB We have previously demonstrated amelioration of Huntington's disease (HD)-related phenotypes in R6/2 transgenic mice in response to treatment with the novel histone deacetylase (HDAC) inhibitor 4b. Here we have measured the selectivity profiles of 4b and related compounds against class I and class II HDACs and have tested their ability to restore altered expression of genes related to HD pathology in mice and to rescue disease effects in cell culture and Drosophila models of HD. R6/2 transgenic and wild-type (wt) mice received daily injections of HDAC inhibitors for 3 days followed by real-time PCR analysis to detect expression differences for 13 HD-related genes. We find that HDACi 4b and 136, two compounds showing high potency for inhibiting HDAC3 were most effective in reversing the expression of genes relevant to HD, including Ppp1r1b, which encodes DARPP-32, a marker for medium spiny striatal neurons. In contrast, compounds targeting HDAC1 were less effective at correcting gene expression abnormalities in R6/2 transgenic mice, but did cause significant increases in the expression of selected genes. An additional panel of 4b-related compounds was tested in a Drosophila model of HD and in STHdh(Q111) striatal cells to further distinguish HDAC selectivity. Significant improvement in huntingtin-elicited Drosophila eye neurodegeneration in the fly was observed in response to treatment with compounds targeting human HDAC1 and/or HDAC3. In STHdh(Q111) striatal cells, the ability of HDAC inhibitors to improve huntingtin-elicited metabolic deficits correlated with the potency at inhibiting HDAC1 and HDAC3, although the IC50 values for HDAC1 inhibition were typically 10-fold higher than for inhibition of HDAC3. Assessment of HDAC protein localization in brain tissue by Western blot analysis revealed accumulation of HDAC1 and HDAC3 in the nucleus of HD transgenic mice compared to wt mice, with a concurrent decrease in cytoplasmic localization, suggesting that these HDACs contribute to a repressive chromatin environment in HD. No differences were detected in the localization of HDAC2, HDAC4 or HDAC7. These results suggest that inhibition of HDACs 1 and 3 can relieve HD-like phenotypes in model systems and that HDAC inhibitors targeting these isotypes might show therapeutic benefit in human HD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Jia, Haiqun; Tang, Bin; Gottesfeld, Joel M.; Thomas, Elizabeth A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Pallos, Judit; Syed, Adeela; Purcell, Judith; Marsh, J. Lawrence] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Jacques, Vincent; Cooper, Andrew; Chen, Yi; Sharma, Shefali; Plasterer, Heather; Rusche, James R.] Repligen Corp, Res & Dev, Waltham, MA USA. [Lau, Alice; Thompson, Leslie M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Sangrey, Gavin R.; Darnell, Shayna B.; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, NeuroEpigenet Lab, MassGeneral Inst Neurodegenerat Dis, Charlestown, MA USA. [Thompson, Leslie M.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. RP Thomas, EA (reprint author), Scripps Res Inst, Dept Mol Biol, SP-2030,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM bthomas@scripps.edu RI Jia, Haiqun/B-1305-2012; OI Jia, Haiqun/0000-0003-1606-4861; Gottesfeld, Joel/0000-0002-4643-5777 FU NIH [R01NS44169, HDSA35326, R01NS045283, R01NS055158, U01NS063953, R01NS62856] FX The authors gratefully acknowledge the support of: NIH R01NS44169 to EAT.; HDSA35326 and NIH R01NS045283 to J.LM.; NIH R01NS055158, U01NS063953 and R01NS62856 to J.M.G.; and to Repligen Corporation. NR 42 TC 54 Z9 54 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2012 VL 46 IS 2 BP 351 EP 361 DI 10.1016/j.nbd.2012.01.016 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 937BC UT WOS:000303633000012 PM 22590724 ER PT J AU Walcott, BP Edlow, BL Xia, ZQ Kahle, KT Nahed, BV Schmahmann, JD AF Walcott, Brian P. Edlow, Brian L. Xia, Zongqi Kahle, Kristopher T. Nahed, Brian V. Schmahmann, Jeremy D. TI Steroid Responsive A3243G Mutation MELAS Clinical and Radiographic Evidence for Regional Hyperperfusion Leading to Neuronal Loss SO NEUROLOGIST LA English DT Article DE mitochondrial encephalopathy; stroke; apoptosis; hyperperfusion; diffusion-tensor imaging; arterial spin labeling ID STROKE-LIKE EPISODES; MITOCHONDRIAL MYOPATHY; LACTIC-ACIDOSIS; HUMAN CEREBELLUM; ONSET MELAS; L-ARGININE; ENCEPHALOPATHY; ENCEPHALOMYOPATHIES; PATIENT; BRAIN AB Introduction Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a multisystem disorder caused by systemic cellular metabolic derangement that is characterized predominantly by rapidly progressive deterioration of the central nervous system. Case Report: We describe a patient with an abrupt onset of rapidly recurring episodes of aphasia, hemianopsia, and parietal pseudocerebellar ataxia, leading to the diagnosis of A3243G mutation MELAS. These stroke-like episodes appeared to be initiated by metabolic derangement, as evidenced by lactic-acid elevation in the cerebral spinal fluid and lactate peaks observed on magnetic resonance spectroscopy. Magnetic resonance imaging further revealed that neuronal loss during the acute episodes occurred in regions of paradoxically increased cerebral blood flow. Diffusion-tensor and arterial-spin-labeled perfusion imaging showed that the volume of tissue loss after the stroke-like episodes greatly exceeded the limits of the cortical areas affected by the initial metabolic insult. The patient was consented to a trial of compassionate use, high-dose intravenous corticosteroids, resulting in marked and sustained clinical improvement. Conclusions: The majority of neurons lost in an acute episode are injured not by a primary failure to meet metabolic demand, but by a poorly regulated compensatory hyperperfusion response. Regional hyperperfusion leads to apoptotic cell death through a progression from vasogenic to cytotoxic edema. The efficacy of corticosteroids in our study patient demonstrates that inflammatory mediators and blood-brain barrier dysfunction may play a role in the pathophysiological cascade that leads to the regional hyperperfusion in MELAS. C1 [Walcott, Brian P.; Kahle, Kristopher T.; Nahed, Brian V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Edlow, Brian L.; Xia, Zongqi; Schmahmann, Jeremy D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Neuroanat & Cerebellar Neurobiol, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, White Bldg Room 502,55 Fruit St, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 45 TC 5 Z9 5 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD MAY PY 2012 VL 18 IS 3 BP 159 EP 170 DI 10.1097/NRL.0b013e318247bcd8 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 937IT UT WOS:000303652900013 PM 22549360 ER PT J AU Barral, S Bird, T Goate, A Farlow, MR Diaz-Arrastia, R Bennett, DA Graff-Radford, N Boeve, BF Sweet, RA Stern, Y Wilson, RS Foroud, T Ott, J Mayeux, R AF Barral, S. Bird, T. Goate, A. Farlow, M. R. Diaz-Arrastia, R. Bennett, D. A. Graff-Radford, N. Boeve, B. F. Sweet, R. A. Stern, Y. Wilson, R. S. Foroud, T. Ott, J. Mayeux, R. CA Natl Inst Aging Late-Onset Alzheim TI Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory SO NEUROLOGY LA English DT Article ID ONSET ALZHEIMERS-DISEASE; GENOME-WIDE ASSOCIATION; COGNITIVE DECLINE; APOLIPOPROTEIN-E; IDENTIFIES VARIANTS; EPSILON-4 ALLELE; AGE; FAMILY; METABOLISM; HEALTH AB Objective: Several genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks. An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes. Methods: Using data from 1,365 subjects in the National Institute on Aging Late-Onset Alzheimer's Disease Family Study, we conducted a family-based association study in which we tabulated MLGPs for SNPs at CR1, BIN1, CLU, PICALM, and APOE. We used generalized estimating equations to model episodic memory as the dependent endophenotype of LOAD and the MLGPs as predictors while adjusting for sex, age, and education. Results: Several genotype patterns influenced episodic memory performance. A pattern that included PICALM and CLU was the strongest genotypic profile for lower memory performance (beta = -0.32, SE = 0.19, p = 0.021). The effect was stronger after addition of APOE (p = 0.016). Two additional patterns involving PICALM, CR1, and APOE and another pattern involving PICALM, BIN1, and APOE were also associated with significantly poorer memory performance (beta = -0.44, SE = 0.09, p = 0.009 and beta = -0.29, SE = 0.07, p = 0.012) even after exclusion of patients with LOAD. We also identified genotype pattern involving variants in PICALM, CLU, and APOE as a predictor of better memory performance (beta = 0.26, SE = 0.10, p = 0.010). Conclusions: MLGPs provide an alternative analytical approach to predict an individual's genetic risk for episodic memory performance, a surrogate indicator of LOAD. Identifying genotypic patterns contributing to the decline of an individual's cognitive performance may be a critical step along the road to preclinical detection of Alzheimer disease. Neurology (R) 2012;78:1464-1471 C1 [Barral, S.; Stern, Y.; Mayeux, R.] Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Barral, S.; Stern, Y.; Mayeux, R.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Bird, T.] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. [Bird, T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Goate, A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Farlow, M. R.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Foroud, T.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. [Diaz-Arrastia, R.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Bennett, D. A.; Wilson, R. S.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Graff-Radford, N.] Mayo Clin, Dept Neurol, Coll Med, Jacksonville, FL 32224 USA. [Boeve, B. F.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Sweet, R. A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Ott, J.] Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China. RP Mayeux, R (reprint author), Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, 630 W 168th St, New York, NY 10032 USA. EM rpm2@columbia.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIH [HHSN268200782096C]; NIA [U24AG26396, U24AG021886, R01AG17917, P50AG8702, P30AG10161, P30AG013846, P30AG028377, P30AG010133, P50AG05134, P50AG016574]; NSFC from the Chinese Government [30730057]; Alzheimer Disease Genetic Consortium; Athena Diagnostics, Inc.; AstraZeneca; Genetech; Pfizer; Danone Research; Elan Pharma; Eli Lilly; Novartis; OctaPharma; sanofi-aventis; Sonexa Therapeutics; Eisai; Medivation; Janssen; Allon; Forest; Cephalon Inc.; Allon Pharmaceuticals; Mangurian Foundation; Alzheimer Association; Behavioral Neurology of Dementia; Rush University Medical Center; Natural Science Foundation of China; N I A [P50AG05138, P30AG013854, P30AG08017, P50AG016582, P50AG016570, P30AG028383, P30AG010124, P50AG005133, R01AG027224, P50AG05142, P30AG012300, P50AG05136, P50AG05681] FX Supported by NIH and NIA grants U24AG26396, U24AG021886, R01AG17917, P50AG8702, P30AG10161, P30AG013846, P30AG028377, P30AG010133, P50AG05134, P50AG016574, P50AG05138, P30AG013854, P30AG08017, P50AG016582, P50AG016570, P30AG028383, P30AG010124, P50AG005133, R01AG027224, P50AG05142, P30AG012300, P50AG05136, and P50AG05681 and NSFC grant 30730057 from the Chinese Government to J. Ott. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University (contract HHSN268200782096C). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, but did review the manuscript before submission.; Dr. Barral receives research support from Alzheimer Disease Genetic Consortium. Dr. Bird receives research support from Athena Diagnostics, Inc. Dr. Goate serves as consultant for AstraZeneca; serves as an expert testimony for Howrey & Associates; receives research support from AstraZeneca, Genetech, Pfizer, and NIA; and holds patent royalties from Taconic (Tau mutation patent). Dr. Farlow serves as a board member for Medivation, Merck, and INC Res/Toyama; serves as a consultant for Accera, Astellas, Baxter, Bristol Meyers Squibb, GE Healthcare, Novartis, Pfizer, Prana, and sanofi-aventis; serves as an expert testimony for Pfizer; receives research support from Danone Research, Elan Pharma, Eli Lilly, Novartis, Genetech, OctaPharma, Pfizer, sanofi-aventis, Sonexa Therapeutics, Eisai, and NIA; holds a patent from Elan and patent royalties from UpTo-Date; and holds stock options from QR Pharm and MedAvante. Dr. Diaz-Arrastia receives research support from NIH. Dr. Bennett receives research support from NIH. Dr. Graff-Radford serves as board member of The Neurologist; serves as a consultant for Codman; and receives research support from Medivation, Janssen, Allon, Forest, and NIA. Dr. Boeve receives research support from Cephalon Inc., Allon Pharmaceuticals, Mangurian Foundation, Alzheimer Association, and NIH; receives royalties as a co-editor of Behavioral Neurology of Dementia; and receives support for development of educational presentations from the American Academy of Neurology. Dr. Sweet receives research support from NIH. Dr. Stern serves as consultant for Allergan Inc., Cephalon Inc., Elan Corporation, Eisai Inc., Pfizer, Ortho-McNeil Neurologics, Merck Serono, GlaxoSmithKline, Eli Lilly, Janssen, and NIH. Dr. Wilson receives research support from a grant from Rush University Medical Center. Dr. Foroud receives research support from NIH. Dr. Ott receives research support from Natural Science Foundation of China. Dr. Mayeux receives research support from NIH. Go to Neurology. org for full disclosures. NR 37 TC 38 Z9 38 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 2012 VL 78 IS 19 BP 1464 EP 1471 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 939AW UT WOS:000303776900007 PM 22539578 ER PT J AU Korn, D AF Korn, David TI A perspective on personalized medicine: Dr David Korn SO PERSONALIZED MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Korn, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM david_korn@harvard.edu NR 1 TC 1 Z9 1 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAY PY 2012 VL 9 IS 3 BP 259 EP 263 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 937ZJ UT WOS:000303702400006 ER PT J AU Yigit, MV Moore, A Medarova, Z AF Yigit, Mehmet V. Moore, Anna Medarova, Zdravka TI Magnetic Nanoparticles for Cancer Diagnosis and Therapy SO PHARMACEUTICAL RESEARCH LA English DT Review DE cancer; diagnosis; drug delivery; gene delivery; iron oxide nanoparticle; magnetic nanoparticle; molecular imaging; MRI; nanomedicine; siRNA; therapy ID IRON-OXIDE NANOPARTICLES; MRI CONTRAST AGENTS; IN-VIVO; SUPERPARAMAGNETIC NANOPARTICLES; MAGNETOFLUORESCENT NANOPARTICLES; PHYSICOCHEMICAL CHARACTERISTICS; BIOMEDICAL APPLICATIONS; CLINICAL-APPLICATIONS; SURFACE MODIFICATION; ANTICANCER ACTIVITY AB Nanotechnology is evolving as a new field that has a potentially high research and clinical impact. Medicine, in particular, could benefit from nanotechnology, due to emerging applications for noninvasive imaging and therapy. One important nanotechnological platform that has shown promise includes the so-called iron oxide nanoparticles. With specific relevance to cancer therapy, iron oxide nanoparticle-based therapy represents an important alternative to conventional chemotherapy, radiation, or surgery. Iron oxide nanoparticles are usually composed of three main components: an iron core, a polymer coating, and functional moieties. The biodegradable iron core can be designed to be superparamagnetic. This is particularly important, if the nanoparticles are to be used as a contrast agent for noninvasive magnetic resonance imaging (MRI). Surrounding the iron core is generally a polymer coating, which not only serves as a protective layer but also is a very important component for transforming nanoparticles into biomedical nanotools for in vivo applications. Finally, different moieties attached to the coating serve as targeting macromolecules, therapeutics payloads, or additional imaging tags. Despite the development of several nanoparticles for biomedical applications, we believe that iron oxide nanoparticles are still the most promising platform that can transform nanotechnology into a conventional medical discipline. C1 [Yigit, Mehmet V.; Moore, Anna; Medarova, Zdravka] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Medarova, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Bldg 75,13th St, Charlestown, MA 02129 USA. EM zmedarova@partners.org FU NCI NIH HHS [R01 CA163461] NR 64 TC 76 Z9 76 U1 8 U2 150 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD MAY PY 2012 VL 29 IS 5 BP 1180 EP 1188 DI 10.1007/s11095-012-0679-7 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 934RJ UT WOS:000303463300003 PM 22274558 ER PT J AU Holowka, DW Marx, BP Kaloupek, DG Keane, TM AF Holowka, Darren W. Marx, Brian P. Kaloupek, Danny G. Keane, Terence M. TI PTSD Symptoms Among Male Vietnam Veterans: Prevalence and Associations With Diagnostic Status SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; symptoms; comorbidity; veteran ID POSTTRAUMATIC-STRESS-DISORDER; COMMON MENTAL-DISORDERS; LONGITUDINAL COURSE; WAR AB The present study examined reported rates of specific posttraumatic stress disorder (PTSD) symptoms in a veteran sample and the extent to which specific symptoms predicted PTSD diagnostic status. A sample of 1325 unmedicated male Vietnam veterans were interviewed using the Structured Clinical Interview for the Diagnostic and Statistical Manual, 3rd edition revised (DSM-III-R) by doctoral-level clinicians. Of the total sample, 798 met diagnostic criteria for current PTSD, 189 met criteria for a lifetime diagnosis of PTSD, and 338 did not meet criteria for either current or lifetime PTSD. Overall, participants endorsed a median of 9, and a mean of 8.4 (SD = 5.4) out of 17 possible PTSD symptoms. The most frequently endorsed symptoms among participants meeting criteria for current PTSD were hypervigilance and detachment from others, followed by intrusive recollections and sleep difficulties. The symptoms with the greatest diagnostic sensitivity in this sample were hypervigilance and detachment from others and those with the greatest diagnostic specificity were flashbacks and nightmares. Intrusive recollections and interpersonal detachment were the overall best predictors of current PTSD diagnostic status. Psychiatric comorbidity was associated with increased overall symptom endorsement rather than the presence of a different pattern of symptom distribution. The finding that hyperarousal and detachment symptoms are more strongly associated with PTSD diagnosis is consistent with reports from other studies conducted with veterans and other trauma-exposed samples. However, certain symptoms were found to occur at higher rates than have been reported in different populations with PTSD. C1 [Holowka, Darren W.; Marx, Brian P.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Holowka, Darren W.; Marx, Brian P.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B4, 150 S Huntington Ave, Boston, MA 02130 USA. EM Brian.marx@va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 22 TC 5 Z9 5 U1 0 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAY PY 2012 VL 4 IS 3 BP 285 EP 292 DI 10.1037/a0023267 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 941JI UT WOS:000303959100006 ER PT J AU Dutra, L de Blank, G Scheiderer, E Taft, C AF Dutra, Lissa de Blank, Gabriel Scheiderer, Emily Taft, Casey TI Correlates of Female Veterans' Perpetration of Relationship Aggression SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE intimate partner violence; aggression; domestic violence; veterans ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; VIETNAM VETERANS; PTSD SYMPTOMATOLOGY; MILITARY VETERANS; COMBAT VETERANS; MEN; ADJUSTMENT; ASSOCIATIONS; RELIABILITY AB Little research to dale has examined intimate partner aggression perpetration among female veterans, despite the increasing number of women veterans and a greater focus on women's aggression in civilian sample investigations. The present study examined rates and correlates of physical and psychological intimate partner aggression in a sample of 89 female Vietnam veterans. Variables examined included aggression perpetrated by both partners, combat exposure, psychiatric symptoms (posttraumatic stress disorder, depressive episodes, substance abuse disorders, and antisocial personality disorder), negative childhood experiences (childhood physical abuse and witness of parental aggression), and marital adjustment. Findings demonstrated that although women veterans were significantly more likely to perpetrate physical intimate partner aggression than were their male partners, there were no gender differences with respect to psychological aggression perpetration. Multiple regression analyses revealed male-perpetrated physical aggression to be the only unique significant predictor of female-perpetrated physical aggression, whereas male-perpetrated psychological aggression and depressive symptoms were significant predictors of female-perpetrated psychological aggression. Potential clinical implications of these findings and directions for future research are discussed. C1 [Dutra, Lissa; Scheiderer, Emily] Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Jamaica Plain, MA USA. [Dutra, Lissa; Scheiderer, Emily; Taft, Casey] VA Boston Healthcare Syst, Boston, MA USA. [de Blank, Gabriel] Univ Virginia, Curry Sch Educ, Charlottesville, VA 22903 USA. [Taft, Casey] Natl Ctr Posttraumat Stress Disorder, Behav Sci Div, Washington, DC USA. [Taft, Casey] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Dutra, L (reprint author), Natl Ctr Posttraumat Stress Disorder 116B5, Womens Hlth Sci Div, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM lissamdutra@gmail.com NR 43 TC 4 Z9 4 U1 1 U2 8 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAY PY 2012 VL 4 IS 3 BP 323 EP 329 DI 10.1037/a0026849 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 941JI UT WOS:000303959100010 ER PT J AU Palacios, IF Arzamendi, D AF Palacios, Igor F. Arzamendi, Dabit TI Structural Heart Intervention. Beyond Transcatheter Valve Therapy SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Editorial Material ID PATENT FORAMEN OVALE; PERCUTANEOUS CLOSURE; ATRIAL-FIBRILLATION; SEPTAL-DEFECT; FOLLOW-UP; MANAGEMENT; WARFARIN; OUTCOMES; STENOSIS; STROKE C1 [Arzamendi, Dabit] Hosp Santa Creu & Sant Pau, Serv Cardiol, Barcelona 08025, Spain. [Palacios, Igor F.] Massachusetts Gen Hosp, Intervent Cardiol Dept, Boston, MA 02114 USA. RP Arzamendi, D (reprint author), Hosp Santa Creu & Sant Pau, Serv Cardiol, St Antoni Maria Claret 167, Barcelona 08025, Spain. EM darzamendi@santpau.cat NR 21 TC 7 Z9 8 U1 0 U2 1 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD MAY PY 2012 VL 65 IS 5 BP 405 EP 413 DI 10.1016/j.recesp.2011.12.022 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 940EE UT WOS:000303872000003 PM 22436657 ER PT J AU Perkins, HS Cortez, JD Hazuda, HP AF Perkins, Henry S. Cortez, Josie D. Hazuda, Helen P. TI Diversity of Patients' Beliefs about the Soul after Death and Their Importance in End-of-Life Care SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE attitude toward death; cross-cultural comparison; end of life; palliative care; terminal care ID SPIRITUAL CARE; DYING PATIENTS; DECISION-MAKING; CANCER-PATIENTS; TREATMENT PREFERENCES; AFRICAN-AMERICANS; MEDICAL-PRACTICE; CULTURAL ISSUES; PALLIATIVE CARE; FAMILY-MEMBERS AB Background: Because beliefs about the soul after death affect the dying experience, patients and survivors may want to discuss those beliefs with their healthcare provider; however, almost no medical research describes such beliefs, leaving healthcare professionals ill prepared to respond. This exploratory study begins the descriptive process. Methods: Assuming that culture is key, we asked older adult Mexican American (MA), European American (EA), and African American (AA) inpatients their beliefs about whether the soul lives on after physical death; if so, where; and what the "afterlife" is like. Results: Some beliefs varied little across the sample. For example, most participants said that the soul lives on after physical death, leaves the body immediately at death, and eventually reaches heaven. Many participants also said death ends physical suffering; however, other beliefs varied distinctly by ethnic group or sex. More AAs than MAs or EAs said that they believed that the soul after physical death exists in the world (57% vs 35% and 33%) or interacts with the living (43% vs 31% and 28%). Furthermore, in every ethnic group more women than men said they believed that the soul exists in the world (42% vs 29% for MAs, 45% vs 14% for EAs, and 71% vs 43% for AAs). Conclusions: As death nears, patients or survivors may want to discuss beliefs about the soul after death with their healthcare provider. This preliminary study characterizes some of those beliefs. By suggesting questions to ask and responses to give, the study provides healthcare professionals a supportive, knowledgeable way to participate in such discussions. C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. Intercultural Dev Res Assoc, San Antonio, TX USA. Audie L Murphy Med Ctr, Dept Vet Affairs, San Antonio, TX USA. RP Perkins, HS (reprint author), POB 1696, Dearborn, MI 48121 USA. EM perkins@uthscsa.edu FU John A. Hartford Foundation; American Federation on Aging Research; US Department of Veterans Affairs; Medical Dean's Office at the University of Texas Health Science Center at San Antonio FX Support for the research was provided by the John A. Hartford Foundation, the American Federation on Aging Research, the US Department of Veterans Affairs, and the Medical Dean's Office at the University of Texas Health Science Center at San Antonio. NR 67 TC 2 Z9 2 U1 1 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0038-4348 EI 1541-8243 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2012 VL 105 IS 5 BP 266 EP 272 DI 10.1097/SMJ.0b013e3182549eda PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 937SM UT WOS:000303678900006 PM 22561539 ER PT J AU Boninger, ML Brienza, D Charlifue, S Chen, YY Curley, KC Graves, DE Groah, S Heinemann, AW Hudson, LM Jackson, AB Johnson, KL Kalpakjian, CZ Kusiak, A Larson, KE Agustin, TS Sherwood, AM Shinowara, N Stripling, T Tate, D AF Boninger, M. L. Brienza, D. Charlifue, S. Chen, Y-Y Curley, K. C. Graves, D. E. Groah, S. Heinemann, A. W. Hudson, L. M. Jackson, A. B. Johnson, K. L. Kalpakjian, C. Z. Kusiak, A. Larson, K. E. Agustin, T. S. Sherwood, A. M. Shinowara, N. Stripling, T. Tate, D. TI State of the Science Conference in Spinal Cord Injury Rehabilitation 2011: introduction SO SPINAL CORD LA English DT Editorial Material DE spinal cord injury; rehabilitation; research funding ID MODEL SYSTEMS C1 [Heinemann, A. W.] Northwestern Univ, Dept Phys Med & Rehabil, Ctr Rehabil Outcomes Res, Feinberg Sch Med,Rehabil Inst Chicago, Chicago, IL 60611 USA. [Boninger, M. L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, M. L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Brienza, D.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Rehabil Engn Res Ctr Spinal Cord Injury, Pittsburgh, PA USA. [Charlifue, S.] Craig Hosp, SCI Model Syst, Englewood, CO USA. [Chen, Y-Y] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Curley, K. C.] USA, Telemed & Adv Technol Res Ctr, Med Res & Mat Command, ATTN MCMR RTC, Ft Detrick, MD USA. [Curley, K. C.] Ctr Disaster & Humanitarian Assistance Med, Dept Sci & Med, Bethesda, MD USA. [Curley, K. C.] Uniformed Serv Univ Hlth Sci, Dept Biomed Informat, Bethesda, MD 20814 USA. [Curley, K. C.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. [Graves, D. E.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Groah, S.] Natl Rehabil Hosp, Washington, DC USA. [Hudson, L. M.] Shepherd Ctr, SE Reg SCI Model Syst, Atlanta, GA USA. [Jackson, A. B.] Univ Alabama Birmingham, Sch Med, Dept PM&R, Birmingham, AL USA. [Johnson, K. L.] Univ Washington, Sch Med, Dept Rehabil Med, Div Rehabil Counseling, Seattle, WA 98195 USA. [Kalpakjian, C. Z.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Kusiak, A.] US EPA, Off Res & Dev, Dept Vet Affairs, Washington, DC 20460 USA. [Larson, K. E.] NSCIA, Elmhurst, NY USA. [Agustin, T. S.] Natl Inst Disabil & Rehabil Res, OSERS US Dept Educ, Washington, DC USA. [Sherwood, A. M.] Baylor Coll Med, Washington, DC USA. [Shinowara, N.] NICHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD USA. [Stripling, T.] Larkview Court, Fairfax Stn, VA USA. [Tate, D.] Univ Michigan, Michigan Burlington Off Ctr, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. RP Heinemann, AW (reprint author), Northwestern Univ, Dept Phys Med & Rehabil, Ctr Rehabil Outcomes Res, Feinberg Sch Med,Rehabil Inst Chicago, 345 E Super St, Chicago, IL 60611 USA. EM a-heinemann@northwestern.edu RI Heinemann, Allen /K-6283-2012; OI Heinemann, Allen /0000-0003-2782-7326; Sherwood, Arthur/0000-0002-0110-4317; Boninger, Michael/0000-0001-6966-919X FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153] NR 2 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAY PY 2012 VL 50 IS 5 SI SI BP 342 EP 343 DI 10.1038/sc.2012.13 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 938ZF UT WOS:000303771700002 PM 22450887 ER PT J AU Boninger, M French, J Abbas, J Nagy, L Ferguson-Pell, M Taylor, SJ Rodgers, M Saunders, N Peckham, H Marshall, R Sherwood, A AF Boninger, M. French, J. Abbas, J. Nagy, L. Ferguson-Pell, M. Taylor, S. J. Rodgers, M. Saunders, N. Peckham, H. Marshall, R. Sherwood, A. TI Technology for mobility in SCI 10 years from now SO SPINAL CORD LA English DT Article DE spinal cord injury; mobility; assistive technology; International Classification of Function ID SPINAL-CORD-INJURY; VIRTUAL-REALITY; REHABILITATION; WALKING; DESIGN; EXOSKELETONS; MULTICENTER; INTERFACE; MEDICINE; THERAPY AB Objectives: To identify technological advances and that are likely to have a great impact on the quality of life and participation in individuals with spinal cord injury (SCI). Methods: In this paper we use the International Classification of Function to frame a discussion on how technology is likely to impact SCI in 10 years. In addition, we discuss the implication of technological advances on future research. Results/Conclusion: Although technology advances are exciting, a large challenge for the research community will be how to effectively apply and deploy this technology. Advances occurring in the next 10 years that reduce cost of technology may be more important to the population with SCI than brand new technologies. Social context is everything. As a research community we must advocate for better systems of care. Advocating now for better care will lead to a world in 2020 that is ready to adopt new technologies that are truly transformative. Spinal Cord (2012) 50, 358-363; doi:10.1038/sc.2011.165; published online 17 January 2012 C1 [Boninger, M.] UPMC Rehabil Inst, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Boninger, M.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [French, J.] Neurotech Network, Tampa, FL USA. [Abbas, J.] Arizona State Univ, Sch Biol & Hlth Syst Engn, Ctr Adapt Neural Syst, Tempe, AZ USA. [Nagy, L.] MetroHlth Rehabil Inst Ohio, Community Advisory Board, Cleveland, OH USA. [Ferguson-Pell, M.] Univ Alberta, Fac Rehabil Med, Edmonton, AB, Canada. [Taylor, S. J.] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Rodgers, M.] Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. [Rodgers, M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Saunders, N.] Univ Melbourne, Dept Pharmacol, Parkville, Vic 3052, Australia. [Peckham, H.] Case Western Reserve Univ, Dept Biomed Engn, Sch Med, Cleveland, OH 44106 USA. [Peckham, H.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Marshall, R.] Univ Adelaide, Fac Hlth Sci, Sch Med, Adelaide, SA, Australia. [Sherwood, A.] Natl Inst Disabil & Rehabil Res, US Dept Educ, Washington, DC USA. RP Boninger, M (reprint author), UPMC Rehabil Inst, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA. EM boninger@pitt.edu OI Sherwood, Arthur/0000-0002-0110-4317; Saunders, Norman/0000-0001-6660-7639; Boninger, Michael/0000-0001-6966-919X; Abbas, James/0000-0002-3647-7041 NR 36 TC 3 Z9 3 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAY PY 2012 VL 50 IS 5 SI SI BP 358 EP 363 DI 10.1038/sc.2011.165 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 938ZF UT WOS:000303771700005 PM 22249329 ER PT J AU Heinemann, AW Steeves, JD Boninger, M Groah, S Sherwood, AM AF Heinemann, A. W. Steeves, J. D. Boninger, M. Groah, S. Sherwood, A. M. TI State of the science in spinal cord injury rehabilitation 2011: informing a new research agenda SO SPINAL CORD LA English DT Article DE spinal cord injury; rehabilitation; research funding AB Study design: This manuscript summarizes recommendations from the State of the Science Conference in Spinal Cord Injury Rehabilitation 2011. Objectives: To develop an agenda for spinal cord injury (SCI) rehabilitation research in the next decade. Setting: Participants scheduled planning meetings and then gathered at the 2011 joint meeting of the American Spinal Injury Association and International Spinal Cord Society in Washington DC. Methods: Recommendations were made by an international, multidisciplinary team that met in large plenary sessions and breakout groups during the meeting. Results: Recommendations are organized by conference track, including neurological and functional recovery; technology issues; aging with spinal cord injury; and employment, psychosocial and quality of life issues. Conclusion: A number of themes emerged across the conference tracks, including the need for improved measures of process and outcome constructs, application of qualitative and quantitative research designs, and use of contemporary statistical analytic approaches. Participants emphasized the value of collaborative research that uses the latest methods, techniques and information. Spinal Cord (2012) 50, 390-397; doi:10.1038/sc.2012.12; published online 20 March 2012 C1 [Heinemann, A. W.] Northwestern Univ, Ctr Rehabil Outcomes Res, Feinberg Sch Med, Rehabil Inst Chicago, Chicago, IL 60611 USA. [Heinemann, A. W.] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. [Steeves, J. D.] Blusson Spinal Cord Ctr, ICORD, UBC, Vancouver, BC, Canada. [Boninger, M.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, M.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Groah, S.] Georgetown Univ, Washington, DC USA. [Groah, S.] Natl Rehabil Hosp, SCI Res, Washington, DC USA. [Sherwood, A. M.] Natl Inst Disabil & Rehabil Res, US Dept Educ, Washington, DC USA. RP Heinemann, AW (reprint author), Northwestern Univ, Ctr Rehabil Outcomes Res, Feinberg Sch Med, Rehabil Inst Chicago, 345 E Super St, Chicago, IL 60611 USA. EM a-heinemann@northwestern.edu RI Heinemann, Allen /K-6283-2012; OI Heinemann, Allen /0000-0003-2782-7326; Sherwood, Arthur/0000-0002-0110-4317; Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability and Rehabilitation Research (NIDRR); US Army Medical Research and Materiel Command; University of Pittsburgh Rehabilitation Engineering Research Center on SCI; Craig H Neilsen Foundation; Christopher and Dana Reeve Foundation; Ontario Neurotrauma Foundation; Miami Project to Cure Paralysis; International Spinal Cord Society; National Institute of Biomedical Imaging and Bioengineering; US Department of Veterans Affairs FX The authors acknowledge the contributions of individuals who served as scribe and facilitators of the break-out sessions, including Charles Bombardier, Barbara Bregman, David Brennan, David Brienza, Pat Brown, Tom Bryce, Dave Chen, Jennifer Collinger, Marcel Dijkers, Bill Donovan, Martin Forchheimer, Jeanne Hoffman, Sarah Huey, Amie Jackson, Susan Knoblach, John 'Kip' Kramer, Audrey Kusiak, Dan Lammertse, Eric Larson, Alex Libin, Inger Ljungberg, Ralph Marino, Greg Nemunaitis, Michelle Oyster, Miriam I Philmon, Jason Plemel, Scott Richards, Jennifer Stevenson, Thomas Stripling, Nancy Shinowara, Norman Saunders, Denise Tate, and Gale Whiteneck. Their contributions were critical to the success of the conference. The authors also acknowledge the support of the National Institute on Disability and Rehabilitation Research (NIDRR), the NIDRR Spinal Cord Injury Model System Program, the US Army Medical Research and Materiel Command, the University of Pittsburgh Rehabilitation Engineering Research Center on SCI, the Craig H Neilsen Foundation, the Christopher and Dana Reeve Foundation, the Ontario Neurotrauma Foundation, The Miami Project to Cure Paralysis, the International Spinal Cord Society, the National Institute of Biomedical Imaging and Bioengineering, and the US Department of Veterans Affairs. Finally, the authors acknowledge the efforts of the Steering Committee, and the input of the meeting participants. NR 12 TC 7 Z9 8 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD MAY PY 2012 VL 50 IS 5 SI SI BP 390 EP 397 DI 10.1038/sc.2012.12 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 938ZF UT WOS:000303771700011 PM 22430512 ER PT J AU Kelly, AG Hellkamp, AS Olson, D Smith, EE Schwamm, LH AF Kelly, Adam G. Hellkamp, Anne S. Olson, DaiWai Smith, Eric E. Schwamm, Lee H. TI Predictors of Rapid Brain Imaging in Acute Stroke Analysis of the Get With The Guidelines-Stroke Program SO STROKE LA English DT Article DE imaging; quality improvement; stroke ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; TIME; THROMBOLYSIS; EMERGENCY; KNOWLEDGE; REGISTRY; ARRIVAL; ATTACK; DELAYS AB Background and Purpose-National guidelines recommend patients with acute stroke undergo brain imaging within 25 minutes of emergency department arrival. Delayed brain imaging may reduce the effectiveness of thrombolysis or render patients ineligible. Methods-Data from the Get With The Guidelines-Stroke program from 2003 to 2009 were analyzed to determine overall imaging rates, temporal trends, and predictive variables associated with door-to-imaging times in patients who presented to an emergency department within 2 hours of stroke symptom onset and did not have clear reasons for withholding thrombolysis. Multivariable logistic regression adjusting for within-hospital clustering was performed to identify independent predictors of brain imaging within 25 minutes of emergency department arrival. Results-Brain imaging was performed within 25 minutes in 41.7% of patients. Rates of imaging within 25 minutes increased from 2003 to 2009 (33.3%-44.5%). In the multivariable model, the following variables were associated with less likelihood of imaging being completed within 25 minutes: age > 70 years; female gender; nonwhite race; history of diabetes, peripheral vascular disease, or prosthetic heart valve; transportation other than ambulance; arrival > 60 minutes after symptom onset; and hospital location in the Northeast. Patients with National Institutes of Health Stroke Scale scores of 16 to 25 (compared with other strata) were most likely to have imaging completed within 25 minutes. Conclusions-Most patients with acute stroke symptoms do not have brain imaging performed within the recommended 25 minutes. Future quality improvement initiatives should focus on reducing door-to-imaging times with a specific emphasis on the predictive variables identified in this analysis. (Stroke. 2012;43:1279-1284.) C1 [Kelly, Adam G.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada. [Hellkamp, Anne S.; Olson, DaiWai] Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kelly, AG (reprint author), Univ Rochester, Med Ctr, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. EM Adam_Kelly@urmc.rochester.edu OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Get With The Guidelines Young Investigator Award; Ortho-McNeil; Boehringer-Ingelheim; Merck; Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable FX Supported in part by a Get With The Guidelines Young Investigator Award. The GWTG-Stroke program is provided by the American Heart Association and is currently supported in part by a charitable contribution from Ortho-McNeil. Get With The Guidelines-Stroke has been funded in the past through support from Boehringer-Ingelheim, Merck, Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership, and the American Heart Association Pharmaceutical Roundtable. NR 21 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2012 VL 43 IS 5 BP 1279 EP + DI 10.1161/STROKEAHA.111.626374 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 936PO UT WOS:000303602700026 PM 22442169 ER PT J AU Yoo, AJ Chaudhry, ZA Nogueira, RG Lev, MH Schaefer, PW Schwamm, LH Hirsch, JA Gonzalez, RG AF Yoo, Albert J. Chaudhry, Zeshan A. Nogueira, Raul G. Lev, Michael H. Schaefer, Pamela W. Schwamm, Lee H. Hirsch, Joshua A. Gonzalez, R. Gilberto TI Infarct Volume Is a Pivotal Biomarker After Intra-Arterial Stroke Therapy SO STROKE LA English DT Article DE acute stroke; imaging; infarct volume; intra-arterial therapy ID ACUTE ISCHEMIC-STROKE; TABLE STAIR RECOMMENDATIONS; EARLY RECANALIZATION; LESION VOLUME; BRAIN-TISSUE; DIFFUSION; TRIAL; TIME; MRI; CT AB Background and Purpose-Pretreatment infarct volume appears to predict clinical outcome after intra-arterial therapy. To confirm the importance of infarct size in patients undergoing intra-arterial therapy, we sought to characterize the relationship between final infarct volume (FIV) and long-term functional outcome in a prospective cohort of endovascularly treated patients. Methods-From our prospective intra-arterial therapy database, we identified 107 patients with acute ischemic stroke with anterior circulation proximal artery occlusions who underwent final infarct imaging and had 3-month modified Rankin Scale scores. Clinical, imaging, treatment, and outcome data were analyzed. Results-Mean age was 66.6 years. Median admission National Institutes of Health Stroke Scale score was 17. Reperfusion (Thrombolysis In Cerebral Infarction 2A-3) was achieved in 78 (72.9%) patients. Twenty-seven (25.2%) patients achieved a 3-month good outcome (modified Rankin Scale 0-2), and 30 (28.0%) died. Median FIV was 71.4 cm(3). FIV independently correlated with functional outcome across the entire modified Rankin Scale. In receiver operating characteristic analysis, it was the best discriminator of both good outcome (area under the curve=0.857) and mortality (area under the curve=0.772). A FIV of approximately 50 cm(3) demonstrated the greatest accuracy for distinguishing good versus poor outcome, and a FIV of approximately 90 cm(3) was highly specific for a poor outcome. The interaction term between FIV and age was the only independent predictor of good outcome (P < 0.0001). The impact of FIV was accentuated in patients < 80 years. Conclusions-Among patients with anterior circulation acute ischemic stroke who undergo intra-arterial therapy, final infarct volume is a critical determinant of 3-month functional outcome and appears suitable as a surrogate biomarker in proof-of-concept intra-arterial therapy trials. (Stroke. 2012;43:1323-1330.) C1 [Yoo, Albert J.; Chaudhry, Zeshan A.; Lev, Michael H.; Schaefer, Pamela W.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. [Yoo, Albert J.; Chaudhry, Zeshan A.; Nogueira, Raul G.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. [Nogueira, Raul G.; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Yoo, AJ (reprint author), 55 Fruit St,GRB241, Boston, MA 02114 USA. EM ajyoo@partners.org OI Schwamm, Lee/0000-0003-0592-9145 FU Penumbra, Inc; GE Healthcare FX Drs Yoo and Gonzalez receive research support from Penumbra, Inc. Dr Lev receives research support from GE Healthcare and is consultant to Co-Axia, GE Healthcare, and Millennium Pharmaceuticals. NR 43 TC 74 Z9 75 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2012 VL 43 IS 5 BP 1323 EP 1330 DI 10.1161/STROKEAHA.111.639401 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 936PO UT WOS:000303602700033 PM 22426317 ER PT J AU Zhang, F Wang, SP Zhang, MJ Weng, ZF Li, PY Gan, Y Zhang, LL Cao, GD Gao, YQ Leak, RK Sporn, MB Chen, J AF Zhang, Feng Wang, Suping Zhang, Meijuan Weng, Zhongfang Li, Peiying Gan, Yu Zhang, Lili Cao, Guodong Gao, Yanqin Leak, Rehana K. Sporn, Michael B. Chen, Jun TI Pharmacological Induction of Heme Oxygenase-1 by a Triterpenoid Protects Neurons Against Ischemic Injury SO STROKE LA English DT Article DE CDDO; cytoprotective; Nrf2; stroke ID CEREBRAL-ARTERY OCCLUSION; NITRIC-OXIDE PRODUCTION; SYNTHETIC TRITERPENOIDS; CDDO-IMIDAZOLIDE; POTENT INDUCERS; MOUSE MODEL; IN-VIVO; NRF2; PATHWAY; INHIBITION AB Background and Purpose-Heme oxygenase-1 (HO-1) is an inducible Phase 2 enzyme that degrades toxic heme; its role in cerebral ischemia is not fully understood. We hypothesize that chemically induced HO-1 upregulation with the novel triterpenoid CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a robust inducer of Phase 2 genes, protects neurons against ischemic injury. Methods-Using 3 different models of ischemia, including oxygen-glucose deprivation in neuronal cultures, global ischemia in rats, and focal ischemia in mice, we determined (1) whether CDDO-Im induces HO-1 expression and protects against ischemic injury; and (2) whether HO-1 inhibition disrupts the neuroprotective effect of CDDO-Im. Results-CDDO-Im treatment (50-300 nmol/L) resulted in 8-fold HO-1 upregulation in cultured neurons and protected against oxygen-glucose deprivation. The protection was abolished when the cultures were transfected with nuclear factor (erythroid-derived 2) like-2-shRNA or coincubated with tin protoporphyrin IX, a specific HO-1 inhibitor. In the rat model of global ischemia, intracerebroventricular infusion of CDDO-Im (0.5-1.5 mu g) augmented HO-1 expression in hippocampal neurons and resulted in significant increases in CA1 neuronal survival after global ischemia. To further strengthen the clinical relevance of the CDDO-Im treatment, we tested its effects in the mouse model of temporary focal ischemia (60 minutes). Postischemic intraperitoneal injection of CDDO-Im (10-100 mu g) enhanced HO-1 expression and significantly reduced neurological dysfunction and infarct volume. Intracerebroventricular infusion of tin protoporphyrin IX reduced the neuroprotective effect of CDDO-Im against global and focal ischemia. Conclusions-CDDO-Im confers neuroprotection against ischemic injury by upregulating HO-1, suggesting that enhance of HO-1 expression may be a legitimate strategy for therapeutic intervention of stroke. (Stroke. 2012;43:1390-1397.) C1 [Zhang, Feng; Wang, Suping; Zhang, Meijuan; Weng, Zhongfang; Li, Peiying; Gan, Yu; Zhang, Lili; Cao, Guodong; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Cerebrovasc Dis, Pittsburgh, PA 15213 USA. [Zhang, Feng; Wang, Suping; Weng, Zhongfang; Li, Peiying; Gan, Yu; Zhang, Lili; Cao, Guodong; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Mylan Sch Pharm, Pittsburgh, PA 15219 USA. [Sporn, Michael B.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03756 USA. [Sporn, Michael B.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Zhang, Feng; Wang, Suping; Weng, Zhongfang; Zhang, Lili; Cao, Guodong; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. EM zhanfx2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Zhang, Meijuan/0000-0002-5375-5349; Zhang, Feng/0000-0001-7275-9989 FU National Institutes of Health [NS36736, NS43802, NS45048]; VA Merit Review Grant; American Heart Association [10SDG2560122] FX This work was supported by funds from the National Institutes of Health (NS36736, NS43802, and NS45048 to J.C.), the VA Merit Review Grant to J.C., and the American Heart Association (10SDG2560122 to F.Z.). NR 36 TC 38 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2012 VL 43 IS 5 BP 1390 EP + DI 10.1161/STROKEAHA.111.647420 PG 13 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 936PO UT WOS:000303602700043 PM 22461332 ER PT J AU Ellis, C Simpson, AN Bonilha, H Mauldin, PD Simpson, KN AF Ellis, Charles Simpson, Annie N. Bonilha, Heather Mauldin, Patrick D. Simpson, Kit N. TI The One-Year Attributable Cost of Poststroke Aphasia SO STROKE LA English DT Article DE aphasia; costs ID ISCHEMIC-STROKE; REHABILITATION; EPIDEMIOLOGY; CARE AB Background and Purpose-Little is known about the contribution of aphasia to the cost of care for patients who experience stroke. Methods-We retrospectively examined a cohort of South Carolina Medicare beneficiaries who experienced ischemic stroke in 2004 to determine the attributable cost of aphasia. Univariate analyses were used to compare demographic, comorbidity, and severity differences between individuals with poststroke aphasia and those without aphasia. Differences in payments by Medicare because of stroke were examined using a gamma-distributed generalized linear multivariate model. Results-Three thousand, two hundred Medicare beneficiaries experienced ischemic stroke in South Carolina in 2004, and 398 beneficiaries had poststroke aphasia. Patients with aphasia experienced longer length of stays, greater morbidity, and greater mortality than did those without aphasia. In adjusted models that controlled for relevant covariates, the attributable 1-year cost of aphasia was estimated at $1703. Conclusions-Aphasia adds to the cost of stroke-related care, above the cost of stroke alone. (Stroke. 2012;43:1429-1431.) C1 [Ellis, Charles; Simpson, Annie N.; Bonilha, Heather; Simpson, Kit N.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Ellis, Charles] Ralph H Johnson VA Med Ctr, VA Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA. [Simpson, Annie N.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Med Univ S Carolina, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. [Simpson, Kit N.] Med Univ S Carolina, Dept Hlth Adm & Policy, Charleston, SC 29425 USA. RP Ellis, C (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM ellisc@musc.edu FU Veterans Health Administration Health Services [07-012-3]; NIH/NCRR [UL1 RR029880] FX C.E. is supported by a career development award (CDA# 07-012-3) from the Veterans Health Administration Health Services Research and Development program.; H. B. is supported by NIH/NCRR grant #UL1 RR029880. NR 15 TC 33 Z9 34 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2012 VL 43 IS 5 BP 1429 EP + DI 10.1161/STROKEAHA.111.647339 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 936PO UT WOS:000303602700053 PM 22343643 ER PT J AU Dzik, W AF Dzik, Walter Sunny TI Reversal of drug-induced anticoagulation: old solutions and new problems SO TRANSFUSION LA English DT Article ID PROTHROMBIN COMPLEX CONCENTRATE; RECOMBINANT FACTOR VIIA; FRESH-FROZEN PLASMA; WARFARIN-ASSOCIATED COAGULOPATHY; INTERNATIONAL NORMALIZED RATIO; INTRACEREBRAL HEMORRHAGE; VITAMIN-K; INTRACRANIAL HEMORRHAGE; ATRIAL-FIBRILLATION; EMERGENCY REVERSAL AB Anticoagulant drugs are taken by millions of patients throughout the world. Warfarin has been the most widely prescribed anticoagulant for decades. In recent years, new oral anticoagulants have been approved for use, are being positioned as alternatives to warfarin, and represent an enormous market opportunity for pharmaceutical companies. Requests for urgent reversal of anticoagulants are not uncommon especially in the setting of critical bleeding. This review summarizes information on reversal of warfarin by vitamin K, plasma, prothrombin complex concentrates, and recombinant VIIa. In addition, we emphasize the lack of current evidence supporting reversibility of the new oral direct thrombin inhibitors and Factor Xa inhibitors. This review is presented to assist transfusion medicine specialists, hematologists, and other clinicians who prescribe blood components for reversal of drug-induced anticoagulation. C1 J224 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, W (reprint author), J224 Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 42 TC 29 Z9 30 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAY PY 2012 VL 52 SU 1 SI SI BP 45S EP 55S DI 10.1111/j.1537-2995.2012.03690.x PG 11 WC Hematology SC Hematology GA 940VB UT WOS:000303920100008 PM 22578371 ER PT J AU Lui, FE Yu, BL Baron, DM Lei, C Zapol, WM Kluger, R AF Lui, Francine E. Yu, Binglan Baron, David M. Lei, Chong Zapol, Warren M. Kluger, Ronald TI Hemodynamic responses to a hemoglobin bis-tetramer and its polyethylene glycol conjugate SO TRANSFUSION LA English DT Article ID CROSS-LINKED HEMOGLOBIN; NITRITE REDUCTASE-ACTIVITY; CELL-FREE HEMOGLOBIN; ENDOTHELIAL DYSFUNCTION; OXYGEN CARRIERS; OXIDE; BLOOD; COOPERATIVITY; SUBSTITUTES; GENERATION AB BACKGROUND: The design of hemoglobin-based oxygen carriers (HBOCs) poses a significant challenge as clinical trials of many materials have reported adverse side effects that may come from the scavenging of the vasodilator nitric oxide (NO). A compensating reaction, reduction of endogenous nitrite by hemoglobin (Hb) and its derivatives, generates NO. Polyethylene glycol (PEG) conjugation of Hb enhances the rate of the reaction. STUDY DESIGN AND METHODS: Hemoglobin bis-tetramers (BT) and their PEGylated derivative (BT-PEG) bind oxygen with a degree of cooperativity and also have significantly enhanced nitrite reductase activity compared to the native protein. Circulatory evaluation will test if the properties of BT and BT-PEG are reflected in their effects in vivo. BT and BT-PEG were evaluated as infusions into healthy wild-type (WT) and diabetic (db/db) mouse models. The effects were compared to infusions of murine Hb. RESULTS: The materials were found not to cause significant increases in systemic blood pressure in either WT mice or db/db mice. The latter are highly sensitive to NO scavenging. Further hemodynamic measurements in WT mice indicate that while a slight increase in systemic vascular resistance (SVR) was observed after infusion of BT, the extent is not significant. No change in SVR from baseline was observed after infusion of BT-PEG. CONCLUSION: The enlarged Hb derivatives do not evoke unfavorable circulatory responses that have been noted to result from infusion of Hb derivatives. These results suggest that a compromise between the P50, n50, and nitrite reductase activity of a Hb derivative can serve as the basis for producing HBOCs that can be tested for vasoactivity. C1 [Kluger, Ronald] Univ Toronto, Dept Chem, Davenport Chem Res Labs, Toronto, ON M3B 1J7, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesia Ctr Crit Care Res,Dept Anesthesia & Cr, Boston, MA USA. RP Kluger, R (reprint author), Univ Toronto, Dept Chem, Davenport Chem Res Labs, Toronto, ON M3B 1J7, Canada. EM rkluger@chem.utoronto.ca FU Canadian Blood Services, Inc., through the Canadian Institutes of Health Research FX Supported by the Canadian Blood Services, Inc., through the Canadian Institutes of Health Research. NR 32 TC 5 Z9 5 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2012 VL 52 IS 5 BP 974 EP 982 DI 10.1111/j.1537-2995.2011.03421.x PG 9 WC Hematology SC Hematology GA 940GB UT WOS:000303876900009 PM 22070638 ER PT J AU Chalancon, G Ravarani, CNJ Balaji, S Martinez-Arias, A Aravind, L Jothi, R Babu, MM AF Chalancon, Guilhem Ravarani, Charles N. J. Balaji, S. Martinez-Arias, Alfonso Aravind, L. Jothi, Raja Babu, M. Madan TI Interplay between gene expression noise and regulatory network architecture SO TRENDS IN GENETICS LA English DT Review DE expression noise; gene regulatory network; persistence; phenotypic variation; single-cell analysis; differentiation; development ID DETERMINES CELL FATE; ESCHERICHIA-COLI; SINGLE-CELL; GENOMIC ANALYSIS; DYNAMICS; VARIABILITY; TRANSCRIPTION; EVOLUTION; SELECTION; YEAST AB Complex regulatory networks orchestrate most cellular processes in biological systems. Genes in such networks are subject to expression noise, resulting in isogenic cell populations exhibiting cell-to-cell variation in protein levels. Increasing evidence suggests that cells have evolved regulatory strategies to limit, tolerate or amplify expression noise. In this context, fundamental questions arise: how can the architecture of gene regulatory networks generate, make use of or be constrained by expression noise? Here, we discuss the interplay between expression noise and gene regulatory network at different levels of organization, ranging from a single regulatory interaction to entire regulatory networks. We then consider how this interplay impacts a variety of phenomena, such as pathogenicity, disease, adaptation to changing environments, differential cell-fate outcome and incomplete or partial penetrance effects. Finally, we highlight recent technological developments that permit measurements at the single-cell level, and discuss directions for future research. C1 [Chalancon, Guilhem; Ravarani, Charles N. J.; Babu, M. Madan] MRC, Mol Biol Lab, Cambridge CB2 0QH, England. [Balaji, S.] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Balaji, S.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Balaji, S.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Martinez-Arias, Alfonso] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Chalancon, G (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England. EM guilhem@mrc-lmb.cam.ac.uk; madanm@mrc-lmb.cam.ac.uk RI Martinez Arias, Alfonso/F-1966-2010; Jothi, Raja/G-3780-2015 FU Gates Cambridge Scholarship; Knox Trinity studentship; AFR; Medical Research Council; EMBO; HFSP [RGY0073/2010]; European Research Council; NIH, National Institute of Environmental Health Sciences [1ZIAES102625-03]; NLM, NCBI FX We thank Mania Buljan, Kai Kruse, Elizabeth Ing-Simmons and Andrew Deonarine for helpful remarks. This work was supported by the Gates Cambridge Scholarship and the Knox Trinity studentship (G.C.), the AFR Grant Scheme (C.N.J.R.), the Medical Research Council (G.C., C.N.J.R. and M.M.B.), EMBO young investigator program, HFSP (RGY0073/2010; M.M.B.), European Research Council (AM.-A.) and the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (RJ: 1ZIAES102625-03) and NLM, NCBI (L.A.). NR 125 TC 74 Z9 75 U1 5 U2 70 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 2012 VL 28 IS 5 BP 221 EP 232 DI 10.1016/j.tig.2012.01.006 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 937BU UT WOS:000303634800004 PM 22365642 ER PT J AU Verma, AA Bohnen, JD AF Verma, Amol A. Bohnen, Jordan D. TI Bridging the Leadership Development Gap: Recommendations for Medical Education SO ACADEMIC MEDICINE LA English DT Letter C1 [Verma, Amol A.] Univ Toronto, Fac Med, Toronto, ON, Canada. [Bohnen, Jordan D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Verma, AA (reprint author), Univ Toronto, Fac Med, Toronto, ON, Canada. EM amol.verma@utoronto.ca OI Verma, Amol/0000-0001-6857-931X NR 6 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2012 VL 87 IS 5 BP 549 EP 550 DI 10.1097/ACM.0b013e31824d550e PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 933TD UT WOS:000303384700004 PM 22531581 ER PT J AU Hirsh, D Gaufberg, E Ogur, B Cohen, P Krupat, E Cox, M Pelletier, S Bor, D AF Hirsh, David Gaufberg, Elizabeth Ogur, Barbara Cohen, Pieter Krupat, Edward Cox, Malcolm Pelletier, Stephen Bor, David TI Educational Outcomes of the Harvard Medical School-Cambridge Integrated Clerkship: A Way Forward for Medical Education SO ACADEMIC MEDICINE LA English DT Article ID CLINICAL EDUCATION; HIDDEN CURRICULUM; PATIENT-CENTEREDNESS; STUDENTS; CONTINUITY; COMMUNITY; PROGRAM; REFORM; MODEL; CARE AB Purpose The authors report data from the Harvard Medical School-Cambridge Integrated Clerkship (CIC), a model of medical education in which students' entire third year consists of a longitudinal, integrated curriculum. The authors compare the knowledge, skills, and attitudes of students completing the CIC with those of students completing traditional third-year clerkships. Method The authors compared 27 students completing the first three years of the CIC (2004-2007) with 45 students completing clerkships at other Harvard teaching hospitals during the same period. At baseline, no significant between-group differences existed (Medical College Admission Test and Step 1 scores, second-year objective structured clinical examination [OSCE] performance, attitudes toward patient-centered care, and plans for future practice) in any year. The authors compared students' National Board of Medical Examiners Subject and Step 2 Clinical Knowledge scores, OSCE performance, perceptions of the learning environment, and attitudes toward patient-centeredness. Results CIC students performed as well as or better than their traditionally trained peers on measures of content knowledge and clinical skills. CIC students expressed higher satisfaction with the learning environment, more confidence in dealing with numerous domains of patient care, and a stronger sense of patient-centeredness. Conclusions CIC students are at least as well as and in several ways better prepared than their peers. CIC students also demonstrate richer perspectives on the course of illness, more insight into social determinants of illness and recovery, and increased commitment to patients. These data suggest that longitudinal integrated clerkships offer students important intellectual, professional, and personal benefits. C1 [Hirsh, David; Gaufberg, Elizabeth; Ogur, Barbara; Cohen, Pieter; Bor, David] Cambridge Hlth Alliance, Cambridge, MA 02139 USA. [Hirsh, David; Gaufberg, Elizabeth; Ogur, Barbara; Cohen, Pieter; Bor, David] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Gaufberg, Elizabeth] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Krupat, Edward] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Krupat, Edward; Pelletier, Stephen] Harvard Univ, Sch Med, Ctr Evaluat, Boston, MA USA. [Cox, Malcolm] Univ Penn, Dept Med, Sch Med, Washington, DC USA. [Cox, Malcolm] US Dept Vet Affairs, Washington, DC USA. RP Hirsh, D (reprint author), Cambridge Hlth Alliance, 1493 Cambridge St, Cambridge, MA 02139 USA. EM david_hirsh@hms.harvard.edu FU Cambridge Health Alliance; Harvard Medical School Academy of Educators; Association of American Medical Colleges, New York Academy of Medicine, Macy Foundation [281918] FX The authors wish to thank the following individuals for their wise teaching and advice, their outstanding work in creating and advancing the CIC, and for inspiration that led to this report: Ronald Arky, MD, Elizabeth Armstrong, PhD, Kirsten Austad, Jeremiah Barondess, MD, Maren Batalden, MD, MPH, Carolyn Bernstein, MD, Jack Burke, Jr, MD, MPH, Jeanette Callahan, MD, Steve Carter, MBA, Allison Cook, EdM, MA, Molly Cooke, MD, Jules Dienstag, MD, Jeffrey Flier, MD, Martha Garcia, MD, Arundhati Ghosh, MD, James Gordon, MD, Wendy Gutterson, MS, Frederic Hafferty, PhD, Kathleen Harney, MD, Carol Hulka, MD, David Irby, PhD, Dennis Keefe, MBA, Robert Kegan, PhD, Judy Klickstein, MS, Kathy Kosinski, MD, David Link, MD, Bridget O'Brien, PhD, Joseph Martin, MD, PhD, Robert Meyer, MD, Stephen Schwaitzberg, MD, Gary Setnick, MD, Kitt Shaffer, MD, PhD, Derri Shtasel, MD, MPH, William Silen, MD, Art Spector, MD, George Thibault, MD, Todd Thompson, MD, Joseph Velletri, Ronald Weintraub, MD, and Michael Whitcomb, MD. Indeed, the authors thank all the students, faculty, and administrators of the CIC. The authors also thank the Cambridge Health Alliance and the Harvard Medical School Academy of Educators for their financial support.; Association of American Medical Colleges, New York Academy of Medicine, Macy Foundation Grant (#281918) from 2004 to 2006. NR 57 TC 62 Z9 64 U1 4 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2012 VL 87 IS 5 BP 643 EP 650 DI 10.1097/ACM.0b013e31824d9821 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 933TD UT WOS:000303384700027 PM 22450189 ER PT J AU Berman, R Powe, C Carnevale, J Chao, A Knudsen, J Nguyen, A Edgman-Levitan, S AF Berman, Rebecca Powe, Camille Carnevale, Julia Chao, Andrew Knudsen, Janine Anthony Nguyen Edgman-Levitan, Susan TI The Crimson Care Collaborative: A Student-Faculty Initiative to Increase Medical Students' Early Exposure to Primary Care SO ACADEMIC MEDICINE LA English DT Article ID SPECIALTIES; EDUCATION; CHOICES AB The current shortage of primary care physicians (PCPs), particularly as more individuals obtain health insurance and seek primary care services, is a growing national concern. The Crimson Care Collaborative (CCC) is a joint student-faculty initiative in post-healthcare-reform Massachusetts that was started with the explicit goal of attracting medical students to primary care careers. It fills a niche for student-run clinics, providing evening access to primary care services for patients without a PCP and urgent care services for patients of a Massachusetts General Hospital-affiliated internal medicine clinic, with the aim of decreasing emergency department use in both groups. Unlike other student-run clinics, CCC is integrated into the mainstream health care structure of an existing primary care clinic and, because of universal health insurance coverage in Massachusetts, can bill for its services. In addition to the clinical services offered, the student-run research team evaluates the quality of care and the patients' experiences at the clinic. This article describes the creation and development of CCC, including a brief overview of clinic operations, social services, research, laboratory services, student and patient education programs, and finance. In the wake of the Patient Protection and Affordable Care Act of 2010, CCC is an example of how students can aid the transition to universal health care in the United States and how medical schools can expose students early in their training to primary care and clinic operations. C1 [Berman, Rebecca] John D Stoeckle Ctr Primary Care Innovat, Div Gen Med, Boston, MA 02114 USA. [Berman, Rebecca; Edgman-Levitan, Susan] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. [Berman, Rebecca; Knudsen, Janine; Anthony Nguyen] Harvard Univ, Sch Med, Boston, MA USA. [Berman, Rebecca; Powe, Camille; Carnevale, Julia; Chao, Andrew; Knudsen, Janine] Crimson Care Collaborat, Boston, MA USA. RP Berman, R (reprint author), John D Stoeckle Ctr Primary Care Innovat, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM raberman@partners.org FU Yawkey Foundation; Stoeckle Center for Primary Care Innovation; Massachusetts General Hospital; Arnold P. Gold Foundation FX CCC is supported by the Yawkey Foundation, the Stoeckle Center for Primary Care Innovation, the Massachusetts General Hospital and the Arnold P. Gold Foundation. NR 16 TC 13 Z9 13 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2012 VL 87 IS 5 BP 651 EP 655 DI 10.1097/ACM.0b013e31824d5269 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 933TD UT WOS:000303384700028 PM 22450186 ER PT J AU Yang, SZ Mulvey, EP AF Yang, Suzanne Mulvey, Edward P. TI Violence risk: Re-defining variables from the first-person perspective SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE Mentally ill offenders; Prevention; Structured clinical judgment; Subjective experience; Violence risk assessment ID MENTALIZATION-BASED TREATMENT; SELF-APPRAISAL QUESTIONNAIRE; INTIMATE PARTNER VIOLENCE; SHORT-TERM ASSESSMENT; ATTRIBUTIONAL STYLE; PSYCHIATRIC-PATIENTS; AGGRESSIVE-BEHAVIOR; BORDERLINE PERSONALITY; PREDICTIVE-VALIDITY; PREMEDITATED AGGRESSION AB Over the past 25 years, there have been notable advances in violence risk assessment of mentally ill individuals using actuarial methods to define high versus low risk groups. A focus on readily observable risk factors, however, has led to a relative neglect of how the offender's subjective states may be valuable to consider in research on the ongoing assessment and prevention of violence. We argue for the relevance of considering idiographic features of subjective experience in the development of structured assessment methods. We then identify three heuristic groups of existing constructs related to aggressive and illegal behavior that may capture modifiable, time-varying aspects of mental functioning leading up to involvement in an act of violence. These hypothesized domains are: (i) construal of intent and cause; (ii) normative reference points; and (iii) emotion recognition and regulation. We suggest that risk state for violence can be studied in a parsimonious and direct manner through systematic research on coded speech samples. The coding method for such an assessment procedure would be almost identical to existing structured clinical judgment instruments with the difference that variables be defined from a first-person point of view. Some implications of this approach for the tertiary prevention of violence in high-risk individuals are described. Published by Elsevier Ltd. C1 [Yang, Suzanne] Vet Affairs Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA USA. [Yang, Suzanne; Mulvey, Edward P.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Yang, SZ (reprint author), VISN4 VA Pittsburgh Healthcare Syst, MIRECC, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM yangs@upmc.edu FU NIMH NIH HHS [T32 MH016804-30, T32 MH016804] NR 153 TC 4 Z9 5 U1 4 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 EI 1873-6335 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD MAY-JUN PY 2012 VL 17 IS 3 BP 198 EP 207 DI 10.1016/j.avb.2012.02.001 PG 10 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 934ZU UT WOS:000303487400004 PM 23878518 ER PT J AU Bottonari, KA Tripathi, SP Fortney, JC Curran, G Rimland, D Rodriguez-Barradas, M Gifford, AL Pyne, JM AF Bottonari, Kathryn A. Tripathi, Shanti P. Fortney, John C. Curran, Geoff Rimland, David Rodriguez-Barradas, Maria Gifford, Allen L. Pyne, Jeffrey M. TI Correlates of Antiretroviral and Antidepressant Adherence Among Depressed HIV-Infected Patients SO AIDS PATIENT CARE AND STDS LA English DT Article ID NEUROPSYCHIATRIC INTERVIEW MINI; SELF-REPORTED ADHERENCE; MEDICATION ADHERENCE; COLLABORATIVE CARE; INHIBITOR THERAPY; VALIDITY; RECOMMENDATIONS; NONADHERENCE; RELIABILITY; SUPPRESSION AB Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n = 146), an antiretroviral (n = 192), or both (n = 113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence'' or "90% or greater adherence.'' After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n = 146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n = 112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n = 113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (beta = 1.62, p = 0.17), however, antidepressant adherence did predict antiretroviral adherence (beta = 2.30, p < 0.05). C1 [Bottonari, Kathryn A.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Tripathi, Shanti P.; Fortney, John C.; Curran, Geoff; Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, N Little Rock, AR USA. [Tripathi, Shanti P.; Fortney, John C.; Curran, Geoff; Pyne, Jeffrey M.] Univ Arkansas Med Sci, Coll Med, UAMS Psychiat Res Inst, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria] VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Gifford, Allen L.] Edith Nourse VA Med Ctr, HSRD Ctr Excellence, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gifford, Allen L.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Bottonari, KA (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM Kathryn.Bottonari@va.gov NR 45 TC 14 Z9 14 U1 4 U2 6 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 2012 VL 26 IS 5 BP 265 EP 273 DI 10.1089/apc.2011.0218 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 934HU UT WOS:000303435800004 PM 22536930 ER PT J AU Capron, DW Gonzalez, A Parent, J Zvolensky, MJ Schmidt, NB AF Capron, Daniel W. Gonzalez, Adam Parent, Justin Zvolensky, Michael J. Schmidt, Norman B. TI Suicidality and Anxiety Sensitivity in Adults with HIV SO AIDS PATIENT CARE AND STDS LA English DT Article ID ANTIRETROVIRAL THERAPY; POSITIVE PERSONS; INFECTED INDIVIDUALS; DEPRESSIVE SYMPTOMS; GENERAL-POPULATION; DRUG-USE; VALIDATION; ASSOCIATION; PREDICTION; DISORDERS AB Suicide rates among HIV-positive individuals are more than three times higher than in the general population. Anxiety sensitivity (AS) may be clinically relevant to increasing our understanding of suicide among individuals with HIV. Specifically, relations between AS cognitive concerns and suicide related outcomes have been observed across a range of populations. The current investigation sought to examine the effect of AS and individual AS subfactors (i.e., cognitive, physical, and social concerns) in relation to suicidality in a sample of adults with HIV. Participants were 164 adults with HIV (17.1% women; mean age = 48.40) recruited from AIDS service organizations in Vermont/New Hampshire and New York City. Findings from the current study indicate that AS cognitive concerns (beta = 0.46, p = 0.001), but not the global AS factor, are positively associated with elevated rates of suicidality among persons with HIV above and beyond demographics, HIV relevant factors, and negative affectivity. There was also a negative trend for AS physical concerns in terms of suicidality (beta = -0.25, p = 0.07). Clinicians may benefit from implementing AS reduction strategies with HIV-positive persons who endorse elevated suicide risk as well as elevated AS cognitive concerns. The current study is limited by a cross-sectional design and lack of suicide attempt history. Future work would benefit from longitudinal examination of the observed relations, further inquiry regarding the relation between AS physical concerns and suicidality and a more comprehensive assessment of suicidality. C1 [Capron, Daniel W.; Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Gonzalez, Adam] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Parent, Justin] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX USA. RP Gonzalez, A (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM agonzalez14@partners.org FU McNeil Prevention and Community Psychology grant; University of Vermont FX This project was funded by a McNeil Prevention and Community Psychology grant awarded to Dr. Gonzalez and a University of Vermont Undergraduate Research Endeavors Competitive Award granted to Mr. Parent. We also acknowledge recruitment efforts by AIDS Service Organizations in Vermont and New Hampshire and by Michael Hickey, LMSW at Village Care in New York City. NR 45 TC 28 Z9 29 U1 5 U2 14 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 2012 VL 26 IS 5 BP 298 EP 303 DI 10.1089/apc.2011.0429 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 934HU UT WOS:000303435800008 PM 22401761 ER PT J AU Hahn, JA Dobkin, LM Mayanja, B Emenyonu, NI Kigozi, IM Shiboski, S Bangsberg, DR Gnann, H Weinmann, W Wurst, FM AF Hahn, Judith A. Dobkin, Loren M. Mayanja, Bernard Emenyonu, Nneka I. Kigozi, Isaac M. Shiboski, Stephen Bangsberg, David R. Gnann, Heike Weinmann, Wolfgang Wurst, Friedrich M. TI Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Positive Patients in Sub-Saharan Africa SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Biomarker; Phosphatidylethanol; HIV; Africa ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; ETHYL GLUCURONIDE; SOUTH-AFRICA; SELF-REPORTS; BLOOD; MARKER; ETHANOL; ABUSE; PERFORMANCE; DRINKING AB Background: Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions: The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable. C1 [Hahn, Judith A.; Emenyonu, Nneka I.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dobkin, Loren M.] Univ Calif San Francisco, Bixby Ctr Reprod Hlth, San Francisco, CA 94143 USA. [Mayanja, Bernard; Kigozi, Isaac M.; Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Shiboski, Stephen] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Gnann, Heike; Weinmann, Wolfgang] Univ Freiburg, Univ Med Ctr, Inst Legal Med, D-79106 Freiburg, Germany. [Weinmann, Wolfgang] Univ Bern, Fac Med, Inst Forens Med, CH-3012 Bern, Switzerland. [Wurst, Friedrich M.] Paracelsus Med Univ, Christian Doppler Clin, Dept Psychiat & Psychotherapy 2, Salzburg, Austria. RP Hahn, JA (reprint author), Univ Calif San Francisco, Dept Med, Box 0886, San Francisco, CA 94143 USA. EM judy.hahn@ucsf.edu FU NIH/NIAAA [R21 AA015897] FX JAH, DRB, NIE, BM, and FMW were responsible for the study concept and design. JAH, BM, NIE, IMK, and LMD implemented the study and collected the data. HG and WW performed the phosphatidylethanol testing. JH and FMW performed the data analysis and SS assisted with data analysis and interpretation of findings. JH and FMW drafted the manuscript and all authors provided critical revision of the manuscript for important intellectual content and approved the final version for publication. This study was funded by NIH/NIAAA R21 AA015897. NR 60 TC 29 Z9 30 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2012 VL 36 IS 5 BP 854 EP 862 DI 10.1111/j.1530-0277.2011.01669.x PG 9 WC Substance Abuse SC Substance Abuse GA 933UJ UT WOS:000303388500013 PM 22150449 ER PT J AU Verplaetse, TL Rasmussen, DD Froehlich, JC Czachowski, CL AF Verplaetse, Terril L. Rasmussen, Dennis D. Froehlich, Janice C. Czachowski, Cristine L. TI Effects of Prazosin, an alpha(1)-Adrenergic Receptor Antagonist, on the Seeking and Intake of Alcohol and Sucrose in Alcohol-Preferring (P) Rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Prazosin; Alcohol; P Rats; Sipper Tube; Noradrenergic ID CHRONIC DAILY ETHANOL; WITHDRAWAL; DEPENDENCE; ACAMPROSATE; ABSTINENCE; DISORDERS; DRINKING; BRAIN; LINES AB Background: Previous studies show that prazosin, an alpha 1-adrenergic receptor antagonist, decreases alcohol drinking in animal models of alcohol use and dependence [Rasmussen et similar to al. (2009) Alcohol Clin Exp Res 3:264272; Walker et similar to al. (2008) Alcohol 42:9197] and in alcohol-dependent men [Simpson et similar to al. (2009) Alcohol Clin Exp Res 33:255263]. This study extended these findings by using a paradigm that allows for separate assessment of prazosin on motivation to seek versus consume alcohol or sucrose in selectively bred rats. Methods: Alcohol-preferring (P) rats were trained to complete an operant response that resulted in access to either 2% sucrose or 10% alcohol. A 4-week Seeking Test Phase examined responding in single, weekly extinction sessions when no reinforcer could be obtained. A 4-week Drinking Test Phase consisted of rats lever-pressing to pay a specified amount up front to gain access to unlimited alcohol (or sucrose) for a 20-minute period. On Seeking and Drinking test days, prazosin (0.0, 0.5, 1.0, and 1.5 mg/kg) was administered intraperitoneally 30 minutes prior to behavioral sessions. Results: Rats were self-administering an average of 0.9 (+/-0.09) g/kg alcohol on vehicle test day and had pharmacologically relevant blood ethanol concentrations. Prazosin significantly decreased alcohol seeking at all doses tested. The highest dose of prazosin also increased the latency to first response for alcohol and decreased alcohol intake. While sucrose-seeking and intake were similarly affected by prazosin, the high dose of prazosin did not increase response latency. Conclusions: These findings are consistent with and extend previous research and suggest that prazosin decreases motivation to initiate and engage in alcohol consumption. The specificity of prazosin in attenuating the initiation of alcohol- but not sucrose-seeking suggests that this effect is not because of prazosin-induced motor-impairment or malaise. Together with previous findings, these data suggest that prazosin may be an effective pharmacotherapy, with specific application in people that drink excessively or have a genetic predisposition to alcohol abuse. C1 [Rasmussen, Dennis D.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. [Rasmussen, Dennis D.] Univ Washington, Seattle, WA 98195 USA. [Froehlich, Janice C.] Indiana Univ, Dept Med, Indianapolis, IN USA. [Czachowski, Cristine L.] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA. [Verplaetse, Terril L.; Czachowski, Cristine L.] Indiana Univ, Dept Psychol, Indianapolis, IN 46204 USA. RP Czachowski, CL (reprint author), Indiana Univ Sch Med, Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA. EM cczachow@iupui.edu FU National Institute on Alcohol Abuse and Alcoholism [R01AA018604, P60AA007611, R01AA016101]; Department of Veterans Affairs [P20AA017839] FX This work was supported by grants from the National Institute on Alcohol Abuse and Alcoholism R01AA018604 (JCF and DDR); P60AA007611 (JCF and CLC); R01AA016101 (CLC); Department of Veterans Affairs and P20AA017839 (DDR). NR 24 TC 18 Z9 18 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2012 VL 36 IS 5 BP 881 EP 886 DI 10.1111/j.1530-0277.2011.01653.x PG 6 WC Substance Abuse SC Substance Abuse GA 933UJ UT WOS:000303388500016 PM 21981346 ER PT J AU Bauer, LK Caro, MA Beach, SR Mastromauro, CA Lenihan, E Januzzi, JL Huffman, JC AF Bauer, Leah K. Caro, Mario A. Beach, Scott R. Mastromauro, Carol A. Lenihan, Emma Januzzi, James L. Huffman, Jeff C. TI Effects of Depression and Anxiety Improvement on Adherence to Medication and Health Behaviors in Recently Hospitalized Cardiac Patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; HEART-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; RISK-FACTOR; OUTCOMES; SYMPTOMS; VALIDITY; RECOMMENDATIONS; INTERVENTION AB Impaired adherence to medications and health behaviors may mediate the connection between psychiatric symptoms and mortality in cardiac patients. This study assessed the association between improvements in depression/anxiety and self-reported adherence to health behaviors in depressed cardiac patients in the 6 months after cardiac hospitalization. Data were analyzed from depressed patients on inpatient cardiac units who were hospitalized for acute coronary syndrome, heart failure, or arrhythmia and enrolled in a randomized trial of collaborative care depression management (n = 134 in primary analysis). Measurements of depression (Patient Health Questionnaire-9), anxiety (Hospital Anxiety and Depression Scale, Anxiety subscale), and adherence to secondary prevention behaviors (Medical Outcomes Study-Specific Adherence Scale items) were obtained at baseline, 6 weeks 12 weeks, and 6 months. The association between improvement in depression/anxiety and adherence was assessed by linear regression after accounting for the effects of multiple relevant covariates. At all time points improvement in the Patient Health Questionnaire-9 was significantly and independently associated with self-reported adherence to medications and secondary prevention behaviors. In contrast, improvement in the Hospital Anxiety and Depression Scale, Anxiety subscale was associated with improved adherence only at 6 weeks. In conclusion, in a cohort of depressed cardiac patients, improvement in depression was consistently and independently associated with superior self-reported adherence to medications and secondary prevention behaviors across a 6-month span, whereas improvement in anxiety was not. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:1266-1271) C1 [Bauer, Leah K.; Beach, Scott R.; Januzzi, James L.; Huffman, Jeff C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bauer, Leah K.; Caro, Mario A.; Mastromauro, Carol A.; Lenihan, Emma] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jhuffman@partners.org NR 30 TC 40 Z9 42 U1 0 U2 15 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 2012 VL 109 IS 9 BP 1266 EP 1271 DI 10.1016/j.amjcard.2011.12.017 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 937EZ UT WOS:000303643100005 PM 22325974 ER PT J AU Hudson, DW Holzmueller, CG Pronovost, PJ Gianci, SJ Pate, ZT Wahr, J Heitmiller, ES Thompson, DA Martinez, EA Marsteller, JA Gurses, AP Lubomski, LH Goeschel, CA Pham, JC AF Hudson, Daniel W. Holzmueller, Christine G. Pronovost, Peter J. Gianci, Sebastiana J. Pate, Zack T. Wahr, Joyce Heitmiller, Eugenie S. Thompson, David A. Martinez, Elizabeth A. Marsteller, Jill A. Gurses, Ayse P. Lubomski, Lisa H. Goeschel, Christine A. Julius Cuong Pham TI Toward Improving Patient Safety Through Voluntary Peer-to-Peer Assessment SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE patient safety; nuclear safety; peer assessment; peer-assisted learning ID HEALTH-CARE; MANAGEMENT; HAZARDS AB Health care has primarily used retrospective review approaches to identify and mitigate hazards, with little evidence of measurable and sustained improvements in patient safety. Conversely, the nuclear power industry has used a prospective peer-to-peer (P2P) assessment process grounded in open information exchange and cooperative organizational learning to realize substantial and sustainable improvements in safety. In comparing approaches, it is evident that health care's sluggish progress stems from weaknesses in hazard identification and mitigation and in organizational learning. This article proposes creating and implementing a structured prospective P2P assessment model in health care, similar to that used in the nuclear power industry, to accelerate improvements in patient safety. C1 [Hudson, Daniel W.; Holzmueller, Christine G.; Pronovost, Peter J.; Gianci, Sebastiana J.; Heitmiller, Eugenie S.; Thompson, David A.; Marsteller, Jill A.; Gurses, Ayse P.; Lubomski, Lisa H.; Goeschel, Christine A.; Julius Cuong Pham] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Hudson, Daniel W.] US Nucl Regulatory Commiss, Rockville, MD USA. [Pate, Zack T.] Inst Nucl Power Operat, Atlanta, GA USA. [Wahr, Joyce] Univ Michigan, Ann Arbor, MI 48109 USA. [Martinez, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pham, JC (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. EM jpham3@jhmi.edu FU Agency for Healthcare Research and Quality [K01HS018762, HHSA290200600022I, 1R18HS019934-01, K08HS013904]; National Institutes of Health; Robert Wood Johnson Foundation; Commonwealth Fund for research related to measuring and improving patient safety; National Patient Safety Foundation; Society for Cardiovascular Anesthesia Foundation (SCAF); England National Patient Safety Agency (NPSA); National Health Services; National Patient Safety Agency; Society of Cardiovascular Anesthesiologists Foundation FX The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dr Pronovost reports receiving grant or contract support from the Agency for Healthcare Research and Quality, the National Institutes of Health, the Robert Wood Johnson Foundation, and The Commonwealth Fund for research related to measuring and improving patient safety; honoraria from various hospitals and health care systems and the Leigh Bureau to speak on quality and safety; consultancy with the Association for Professionals in Infection Control and Epidemiology, Inc; and book royalties for authoring Safe Patients, Smart Hospitals: How One Doctor's Checklist Can Help Us Change Health Care From the Inside Out. Dr Wahr reports receiving consulting fees to advise on clinical trial design and data analysis for medical device research for Nonin Medical (Plymouth, MN), Uroplasty (Edina, MN), and Emerson Consulting (Minnetonka, MN). Dr Gurses reports receiving grant support from the Agency for Healthcare Research and Quality (K01HS018762), the National Patient Safety Foundation, and the Robert Wood Johnson Foundation. Dr Goeschel reports receiving honoraria from hospitals, health care affiliates, professional societies, and government agencies for speaking on topics related to quality, patient safety, health care policy, and health care leadership. She has received contractual support from the Society for Cardiovascular Anesthesia Foundation (SCAF) and from the England National Patient Safety Agency (NPSA). She is a senior advisor to the World Health Organization Patient Safety Programme and currently receives contractual support for efforts to reduce central line-associated bloodstream infections in hospitals across the United States (AHRQ grant #HHSA290200600022I, TO #7, Modification #1) and catheter-associated urinary tract infections (AHRQ grant # HHSA290200600022I, Task Order # 8). She also receives support on an AHRQ grant to improve care for cardiac surgical patients (1R18HS019934-01). Dr Martinez reports receiving contractual support from the National Health Services, National Patient Safety Agency, and grant support from the Agency for Healthcare Research and Quality (K08HS013904). Dr Marsteller reports receiving contractual support from the Society of Cardiovascular Anesthesiologists Foundation. Dr Pham reports receiving contractual support from the National Health Services, National Patient Safety Agency. This journal article was prepared, in part, by an employee of the United States Nuclear Regulatory Commission (NRC) on his own time apart from his regular duties. NRC has neither approved nor disapproved its technical content. NR 28 TC 9 Z9 9 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAY-JUN PY 2012 VL 27 IS 3 BP 201 EP 209 DI 10.1177/1062860611421981 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 936QJ UT WOS:000303604800004 PM 22202557 ER PT J AU Thanos, A Morizane, Y Murakami, Y Giani, A Mantopoulos, D Kayama, M Roh, MI Michaud, N Pawlyk, B Sandberg, M Young, LH Miller, JW Vavvas, DG AF Thanos, Aristomenis Morizane, Yuki Murakami, Yusuke Giani, Andrea Mantopoulos, Dimosthenis Kayama, Maki Roh, Mi In Michaud, Norman Pawlyk, Basil Sandberg, Michael Young, Lucy H. Miller, Joan W. Vavvas, Demetrios G. TI Evidence for Baseline Retinal Pigment Epithelium Pathology in the Trp1-Cre Mouse SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; CRE RECOMBINASE; TRANSGENIC MICE; VISUAL FUNCTION; YEAST GENOME; LOX SITES; IN-VIVO; EXPRESSION; CELLS; GENE AB The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies. (Am J Pathol 2012, 180:1917-1927; DOI: 10.1016/j.ajpath.2012.01.017) C1 [Thanos, Aristomenis; Morizane, Yuki; Murakami, Yusuke; Giani, Andrea; Mantopoulos, Dimosthenis; Kayama, Maki; Roh, Mi In; Michaud, Norman; Young, Lucy H.; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA. [Pawlyk, Basil; Sandberg, Michael] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat,Dept Opht, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU Bacardi Fund; Research to Prevent Blindness Foundation; Lions Eye Research Fund; Foundation Fighting Blindness; Onassis Foundation; Bausch & Lomb Vitreoretinal Fellowship; National Eye Institute (MEEI) [EY014104] FX Supported by Bacardi Fund (D.G.V.), Research to Prevent Blindness Foundation (D.G.V.), Lions Eye Research Fund (D.G.V.), Foundation Fighting Blindness (B.P. and M.S.), Onassis Foundation (D.G.V.), a Bausch & Lomb Vitreoretinal Fellowship (Y.Mo., M.K.), and a grant from the National Eye Institute (MEEI Core Grant EY014104). NR 44 TC 18 Z9 18 U1 0 U2 3 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 2012 VL 180 IS 5 BP 1917 EP 1927 DI 10.1016/j.ajpath.2012.01.017 PG 11 WC Pathology SC Pathology GA 937EE UT WOS:000303641000017 PM 22429967 ER PT J AU Vagin, O Dada, LA Tokhtaeva, E Sachs, G AF Vagin, Olga Dada, Laura A. Tokhtaeva, Elmira Sachs, George TI The Na-K-ATPase alpha(1)beta(1) heterodimer as a cell adhesion molecule in epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE Na-K-ATPase beta(1) subunit; epithelial junctions; trans-dimerization ID NA,K-ATPASE BETA-SUBUNIT; NECTIN-LIKE MOLECULES; TIGHT-JUNCTION; E-CADHERIN; GLYCOSYLATION AFFECTS; ADHERENS JUNCTIONS; CANCER PROGRESSION; FUNCTIONAL ROLES; ANKYRIN-BINDING; TRANSPORT AB Vagin O, Dada LA, Tokhtaeva E, Sachs G. The Na-K-ATPase alpha(1)beta(1) heterodimer as a cell adhesion molecule in epithelia. Am J Physiol Cell Physiol 302: C1271-C1281, 2012. First published January 25, 2012; doi:10.1152/ajpcell.00456.2011.-The ion gradients generated by the Na-K-ATPase play a critical role in epithelia by driving transepithelial transport of various solutes. The efficiency of this Na-K-ATPase-driven vectorial transport depends on the integrity of epithelial junctions that maintain polar distribution of membrane transporters, including the basolateral sodium pump, and restrict paracellular diffusion of solutes. The review summarizes the data showing that, in addition to pumping ions, the Na-K-ATPase located at the sites of cell-cell junction acts as a cell adhesion molecule by interacting with the Na-K-ATPase of the adjacent cell in the intercellular space accompanied by anchoring to the cytoskeleton in the cytoplasm. The review also discusses the experimental evidence on the importance of a specific amino acid region in the extracellular domain of the Na-K-ATPase beta(1) subunit for the Na-K-ATPase trans-dimerization and intercellular adhesion. Furthermore, a possible role of N-glycans linked to the Na-K-ATPase beta(1) subunit in regulation of epithelial junctions by modulating beta(1)-beta(1) interactions is discussed. C1 [Vagin, Olga; Tokhtaeva, Elmira; Sachs, George] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. [Vagin, Olga; Tokhtaeva, Elmira; Sachs, George] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Dada, Laura A.] Northwestern Univ, Div Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Vagin, O (reprint author), VAGLAHS W LA, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institutes of Health [DK-077149, R37-HL-48129] FX The work was supported by National Institutes of Health Grants DK-077149 and R37-HL-48129. NR 91 TC 28 Z9 29 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 2012 VL 302 IS 9 BP C1271 EP C1281 DI 10.1152/ajpcell.00456.2011 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 937MV UT WOS:000303663500002 PM 22277755 ER PT J AU Degeling, MH Maguire, CA Bovenberg, MSS Tannous, BA AF Degeling, M. Hannah Maguire, Casey A. Bovenberg, M. Sarah S. Tannous, Bakhos A. TI Sensitive Assay for Mycoplasma Detection in Mammalian Cell Culture SO ANALYTICAL CHEMISTRY LA English DT Article ID IN-VIVO; LUCIFERASE; INFECTION; TRANSFORMATION AB Mycoplasma contamination in mammalian cell cultures is often overlooked yet is a serious issue which can induce a myriad of cellular changes leading to false interpretation of experimental results. Here, we present a simple and sensitive assay to monitor mycoplasma contamination (mycosensor) based on degradation of the Gaussia luciferase reporter in the conditioned medium of cells. This assay proved to be more sensitive as compared to a commercially available bioluminescent assay in detecting mycoplasma contamination in seven different cell lines. The Gaussia luciferase mycosensor assay provides an easy tool to monitor mammalian cell contaminants in a high-throughput fashion. C1 [Degeling, M. Hannah; Maguire, Casey A.; Bovenberg, M. Sarah S.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Dept Neurol, Expt Therapeut & Mol Imaging Lab,Neurosci Ctr, Boston, MA 02114 USA. [Degeling, M. Hannah; Maguire, Casey A.; Bovenberg, M. Sarah S.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Degeling, M. Hannah; Bovenberg, M. Sarah S.] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU NIH/NCI [4R00CA126839]; NIH/NINDS [P30NS045776, 1R0INS064983]; American Brain Tumor Association; Fulbright scholarship; Saal van Zwanenberg Foundation, VSB fonds, Dr. Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Jo Keur (Leiden hospital); Huygens Scholarship Program, VSB fonds; Saal van Zwanenberg Foundation FX M.H.D. and C.A.M, contributed equally to this work. This work was supported by grant from NIH/NCI 4R00CA126839 and NIH/NINDS P30NS045776 and 1R0INS064983 (B.A.T.). C.A.M. is supported by a Fellowship from the American Brain Tumor Association. M.H.D. is supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSB fonds, Dr. Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), and the Hersenstichting brain fund as well as the Jo Keur (Leiden hospital). M.S.S.B. was supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB fonds, and the Saal van Zwanenberg Foundation. We thank Kristan van der Vos for assistance with cell culture. NR 15 TC 3 Z9 3 U1 2 U2 19 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 2012 VL 84 IS 9 BP 4227 EP 4232 DI 10.1021/ac2033112 PG 6 WC Chemistry, Analytical SC Chemistry GA 933GS UT WOS:000303349200052 PM 22506739 ER PT J AU Ignatiadis, M Singhal, SK Desmedt, C Haibe-Kains, B Criscitiello, C Andre, F Loi, S Piccart, M Michiels, S Sotiriou, C AF Ignatiadis, M. Singhal, S. K. Desmedt, C. Haibe-Kains, B. Criscitiello, C. Andre, F. Loi, S. Piccart, M. Michiels, S. Sotiriou, C. TI GENE MODULES AND PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN BREAST CANCER. A POOLED ANALYSIS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th IMPAKT Breast Cancer Conference CY MAY 03-05, 2012 CL Brussels, BELGIUM C1 [Ignatiadis, M.] Inst Jules Bordet, Breast Canc Translat Res Lab, Dept Med Oncol, B-1000 Brussels, Belgium. [Haibe-Kains, B.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Andre, F.] Univ Paris 11, Dept Med Oncol, Paris, France. [Andre, F.] Univ Paris 11, INSERM, U981, Paris, France. RI Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013; Loi, Sherene/H-1979-2016 OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels, Stefan/0000-0002-6963-2968; NR 0 TC 1 Z9 1 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 2012 VL 23 SU 2 MA 9O_PR BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 937IW UT WOS:000303653200010 ER PT J AU Azim, HA Michiels, S Bedard, PL Singhal, SK Criscitiello, C Ignatiadis, M Haibe-Kains, B Piccart, M Sotiriou, C Loi, S AF Azim, H. A., Jr. Michiels, S. Bedard, P. L. Singhal, S. K. Criscitiello, C. Ignatiadis, M. Haibe-Kains, B. Piccart, M. Sotiriou, C. Loi, S. TI BIOLOGY OF BREAST CANCER DIAGNOSED IN YOUNG WOMEN: POOLED GENE EXPRESSION ANALYSIS FROM 3522 PATIENTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th IMPAKT Breast Cancer Conference CY MAY 03-05, 2012 CL Brussels, BELGIUM C1 [Azim, H. A., Jr.; Michiels, S.; Singhal, S. K.; Criscitiello, C.; Ignatiadis, M.; Piccart, M.; Sotiriou, C.; Loi, S.] Inst Jules Bordet, Breast Canc Translat Res Lab, B-1000 Brussels, Belgium. [Bedard, P. L.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Singhal, S. K.; Criscitiello, C.; Ignatiadis, M.; Piccart, M.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Haibe-Kains, B.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RI Haibe-Kains, Benjamin/D-3702-2011; Michiels, Stefan/L-1516-2013; Loi, Sherene/H-1979-2016 OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Michiels, Stefan/0000-0002-6963-2968; NR 0 TC 1 Z9 1 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 2012 VL 23 SU 2 MA 14O_PR BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 937IW UT WOS:000303653200015 ER PT J AU Dowsett, M Procter, M de Azambuja, E Scullion, MJ Gelber, RD Leyland-Jones, B AF Dowsett, M. Procter, M. de Azambuja, E. Scullion, M. J. Gelber, R. D. Leyland-Jones, B. TI HER2 EXTRACELLULAR DOMAIN LEVELS IN PATIENTS WITH HER2-POSITIVE EARLY BREAST CANCER EXPERIENCING DISEASE PROGRESSION: CASE-CONTROL COMPARISON OF SAMPLES FROM THE HERA STUDY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th IMPAKT Breast Cancer Conference CY MAY 03-05, 2012 CL Brussels, BELGIUM C1 [Dowsett, M.] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England. [Procter, M.] Frontier Sci Ltd, Stat, Kingussie, Scotland. [de Azambuja, E.] Inst Jules Bordet, Br EAST Data Ctr, B-1000 Brussels, Belgium. [Scullion, M. J.] Roche Prod Ltd, Roche Prod Dev Clin Oncol, Welwyn Garden City AL7 3AY, Herts, England. [Gelber, R. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leyland-Jones, B.] Emory Winship Canc Inst, Atlanta, GA USA. NR 0 TC 1 Z9 1 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 2012 VL 23 SU 2 MA 19P BP 20 EP 20 PG 1 WC Oncology SC Oncology GA 937IW UT WOS:000303653200020 ER PT J AU Rugo, H Piccart, M Hortobagyi, G Noguchi, S Gnant, M Campone, M Bauly, H Mukhopadhyay, P Sahmoud, T Baselga, J AF Rugo, H. Piccart, M. Hortobagyi, G. Noguchi, S. Gnant, M. Campone, M. Bauly, H. Mukhopadhyay, P. Sahmoud, T. Baselga, J. TI UPDATED RESULTS OF THE BOLERO-2 PHASE III TRIAL EVALUATING EVEROLIMUS (EVE) FOR POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST CANCER (ABC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th IMPAKT Breast Cancer Conference CY MAY 03-05, 2012 CL Brussels, BELGIUM C1 [Rugo, H.] Univ Calif San Francisco, Dept Med, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA USA. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Hortobagyi, G.] Univ Texas MD Anderson Canc Ctr, Dept Breast Canc & Gynecol, Houston, TX 77030 USA. [Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Campone, M.] Ctr Rene Gauducheau, St Herblain, France. [Bauly, H.] Novartis Pharma AG, Clin Dev, Basel, Switzerland. [Mukhopadhyay, P.] Novartis Pharmaceut, Clin Dev, E Hanover, NJ USA. [Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dev, E Hanover, NJ USA. [Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol Serv, Boston, MA USA. [Baselga, J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 4 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 2012 VL 23 SU 2 MA 109P BP 46 EP 46 PG 1 WC Oncology SC Oncology GA 937IW UT WOS:000303653200108 ER PT J AU Cortes, J Calvo, V Ramirez-Merino, N O'Shaughnessy, J Brufsky, A Robert, N Vidal, M Munoz, E Perez, J Dawood, S Saura, C Di Cosimo, S Gonzalez-Martin, A Bellet, M Silva, OE Miles, D Llombart, A Baselga, J AF Cortes, J. Calvo, V. Ramirez-Merino, N. O'Shaughnessy, J. Brufsky, A. Robert, N. Vidal, M. Munoz, E. Perez, J. Dawood, S. Saura, C. Di Cosimo, S. Gonzalez-Martin, A. Bellet, M. Silva, O. E. Miles, D. Llombart, A. Baselga, J. TI Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis SO ANNALS OF ONCOLOGY LA English DT Article DE adverse events; bevacizumab; breast cancer; meta-analysis; safety; toxicity ID RANDOMIZED CONTROLLED-TRIALS; GASTROINTESTINAL PERFORATION; GROWTH-FACTOR; PHASE-III; ANGIOGENESIS; BIAS AB Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade >= 3 arterial or venous thromboembolic events, GI perforation, or fatal events. C1 [Cortes, J.; Vidal, M.; Munoz, E.; Perez, J.; Saura, C.; Di Cosimo, S.; Bellet, M.] Vall Hebron Univ Hosp, Dept Med Oncol, Barcelona 08035, Spain. [Calvo, V.] Hosp Ramon & Cajal, Dept Med Oncol, E-28034 Madrid, Spain. [Ramirez-Merino, N.] Hosp Univ Guadalajara, Dept Med Oncol, Guadalajara, Spain. [O'Shaughnessy, J.] Baylor Charles Sammons Canc Ctr, Dept Med Oncol, Dallas, TX USA. [O'Shaughnessy, J.] US Oncol, Dallas, TX USA. [Brufsky, A.] Univ Pittsburgh, Med Ctr, Dept Med Oncol, Pittsburgh, PA USA. [Robert, N.] Virginia Canc Specialists, US Oncol, Dept Med Oncol, Fairfax, VA USA. [Dawood, S.] Dubai Hosp, Dubai Hlth Author, Dept Med Oncol, Dubai, U Arab Emirates. [Gonzalez-Martin, A.] MD Anderson Canc Ctr, Dept Med Oncol, Madrid, Spain. [Silva, O. E.] Univ Miami, Leonard M Miller Sch Med, Dept Med Oncol, Miami, FL USA. [Miles, D.] Mt Vernon Canc Ctr, Dept Med Oncol, Northwood, Middx, England. [Llombart, A.] Arnau de Vilanova Hosp, Dept Med Oncol, Lerida, Spain. [Baselga, J.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Cortes, J (reprint author), Vall Hebron Univ Hosp, Dept Oncol, P Vall Hebron 129-139, Barcelona 08035, Spain. EM jacortes@vhio.net RI Llombart-Cussac, Antonio/A-6706-2010; Serena, Di Cosimo/E-9418-2017; OI Serena, Di Cosimo/0000-0002-4666-8052; Cortes, Javier/0000-0001-7623-1583; Saura, Cristina/0000-0001-8296-5065 NR 27 TC 33 Z9 34 U1 0 U2 9 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 2012 VL 23 IS 5 BP 1130 EP 1137 DI 10.1093/annonc/mdr432 PG 8 WC Oncology SC Oncology GA 933CH UT WOS:000303336400007 PM 21976387 ER PT J AU Ejlertsen, B Aldridge, J Nielsen, KV Regan, MM Henriksen, KL Lykkesfeldt, AE Muller, S Gelber, RD Price, KN Rasmussen, BB Viale, G Mouridsen, H AF Ejlertsen, B. Aldridge, J. Nielsen, K. V. Regan, M. M. Henriksen, K. L. Lykkesfeldt, A. E. Muller, S. Gelber, R. D. Price, K. N. Rasmussen, B. B. Viale, G. Mouridsen, H. CA Danish Breast Cancer Cooperative G BIG 1-98 Collaborative Grp Int Breast Cancer Study Grp TI Prognostic and predictive role of ESR1 status for postmenopausal patients with endocrine-responsive early breast cancer in the Danish cohort of the BIG 1-98 trial SO ANNALS OF ONCOLOGY LA English DT Article DE aromatase inhibitor; breast cancer; ERBB2; ESR1; HER2; tamoxifen ID GENE AMPLIFICATION; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIAL; LETROZOLE; THERAPY; EXPRESSION; ESTROGEN; WOMEN; INDEX; RECURRENCE AB Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis. ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER >= 1% after central review. By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio >= 2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio < 0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02). ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer. C1 [Ejlertsen, B.; Mouridsen, H.] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Danish Breast Canc Cooperat Grp,Stat Ctr, Copenhagen, Denmark. [Aldridge, J.; Regan, M. M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Stat, Int Breast Canc Study Grp, Boston, MA 02115 USA. [Nielsen, K. V.; Muller, S.] Dako AS, Glostrup, Denmark. [Regan, M. M.; Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Regan, M. M.; Gelber, R. D.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Henriksen, K. L.; Lykkesfeldt, A. E.] Danish Canc Soc, Inst Canc Biol, Dept Breast Canc Res, Copenhagen, Denmark. [Gelber, R. D.; Price, K. N.] Frontier Sci & Technol Res Fdn Inc, Ctr Stat, Int Breast Canc Study Grp, Boston, MA USA. [Rasmussen, B. B.] Copenhagen Univ Hosp, Herlev Hosp, Dept Pathol, Herlev, Denmark. [Viale, G.] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Int Breast Canc Study Grp,Pathol Review Off, Milan, Italy. RP Ejlertsen, B (reprint author), Rigshosp, DBCG, Bldg 2501,9 Blegdamsvej, DK-2100 Copenhagen, Denmark. EM ejlertsen@rh.dk FU Danish Ministry of Health [2006-12103-272]; Danish Council for Strategic Research, 'Fonden til fremme af klinisk eksperimentel cancerforskning specielt vedrorende cancer mammae' [2101-07-0022]; United States National Institutes of Health [CA-75362] FX Danish Ministry of Health (2006-12103-272); The Danish Council for Strategic Research (2101-07-0022), 'Fonden til fremme af klinisk eksperimentel cancerforskning specielt vedrorende cancer mammae'; United States National Institutes of Health (CA-75362). NR 28 TC 7 Z9 7 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 2012 VL 23 IS 5 BP 1138 EP 1144 DI 10.1093/annonc/mdr438 PG 7 WC Oncology SC Oncology GA 933CH UT WOS:000303336400008 PM 21986093 ER PT J AU Michaelson, MD Bellmunt, J Hudes, GR Goel, S Lee, RJ Kantoff, PW Stein, CA Lardelli, P Pardos, I Kahatt, C Nieto, A Cullell-Young, M Lewis, NL Smith, MR AF Michaelson, M. D. Bellmunt, J. Hudes, G. R. Goel, S. Lee, R. J. Kantoff, P. W. Stein, C. A. Lardelli, P. Pardos, I. Kahatt, C. Nieto, A. Cullell-Young, M. Lewis, N. L. Smith, M. R. TI Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; docetaxel; prostate cancer; second-line; trabectedin ID CLINICAL-TRIALS; ABIRATERONE ACETATE; WORKING GROUP; DOCETAXEL; RECOMMENDATIONS; ET-743 AB This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC). Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m(2) for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m(2) (Cohort B1, n = 5) and 1.2 mg/m(2) (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP). Trabectedin resulted in PSA declines >= 50% in 12.5% (Cohort A) and 10.5% (Cohort B2) of patients. Among men pretreated with taxane-based chemotherapy, PSA response was 13.6% (Cohort A) and 15.4% (Cohort B2). PSA responses lasted 4.1-8.6 months, and median TTP was 1.5 months (Cohort A) and 1.9 months (Cohort B2). The dose of 1.5 mg/m(2) (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m(2) q3wk and 0.58 mg/m(2) weekly, the most common adverse events were nausea, fatigue and transient neutropenia and transaminase increase. Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer. C1 [Michaelson, M. D.; Lee, R. J.; Smith, M. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bellmunt, J.] Hosp del Mar, Med Oncol Serv, Barcelona, Spain. [Hudes, G. R.; Lewis, N. L.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Goel, S.; Stein, C. A.] Montefiore Einstein Canc Ctr, Dept Oncol, Bronx, NY USA. [Kantoff, P. W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lardelli, P.; Pardos, I.; Kahatt, C.; Nieto, A.; Cullell-Young, M.] PharmaMar, Clin R&D, Madrid, Spain. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org OI Michaelson, Dror/0000-0001-9249-6338 FU PharmaMar; JJ FX M. D. Michaelson's institution received research funding from PharmaMar and J & J; SG received research funding from PharmaMar; JB received honoraria for a PharmaMar advisory board; RJL served on an advisory board for Amgen (with compensation). NR 21 TC 7 Z9 7 U1 0 U2 3 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 2012 VL 23 IS 5 BP 1234 EP 1240 DI 10.1093/annonc/mdr399 PG 7 WC Oncology SC Oncology GA 933CH UT WOS:000303336400022 PM 21930687 ER PT J AU Kaufmann, M von Minckwitz, G Mamounas, EP Cameron, D Carey, LA Cristofanilli, M Denkert, C Eiermann, W Gnant, M Harris, JR Karn, T Liedtke, C Mauri, D Rouzier, R Ruckhaeberle, E Semiglazov, V Symmans, WF Tutt, A Pusztai, L AF Kaufmann, Manfred von Minckwitz, Gunter Mamounas, Elefhterios P. Cameron, David Carey, Lisa A. Cristofanilli, Massimo Denkert, Carsten Eiermann, Wolfgang Gnant, Michael Harris, Jay R. Karn, Thomas Liedtke, Cornelia Mauri, Davide Rouzier, Roman Ruckhaeberle, Eugen Semiglazov, Vladimir Symmans, W. Fraser Tutt, Andrew Pusztai, Lajos TI Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID PATHOLOGICAL COMPLETE RESPONSE; SURGICAL ADJUVANT BREAST; PHASE-III TRIAL; RANDOMIZED-TRIAL; EXPERT PANEL; PREOPERATIVE CHEMOTHERAPY; ENDOCRINE THERAPY; CYCLOPHOSPHAMIDE CHEMOTHERAPY; GUIDELINE RECOMMENDATIONS; CLINICAL-ONCOLOGY/COLLEGE AB The use of neoadjuvant systemic therapy (NST) for the treatment of primary breast cancer has constantly increased, especially in trials of new therapeutic regimens. In the 1980 s, NST was shown to substantially improve breast-conserving surgery rates and was first typically used for patients with inoperable locally advanced or inflammatory breast cancer. Investigators have since also used NST as an in vivo test for chemosensitivity by assessing pathologic complete response. Today, by using pathologic response and other biomarkers as intermediate end points, results from trials of new regimens and therapies that use NST are aimed to precede and anticipate the results from larger adjuvant trials. In 2003, a panel of representatives from various breast cancer clinical research groups was first convened in Biedenkopf to formulate recommendations on the use of NST. The obtained consensus was updated in two subsequent meetings in 2004 and 2006. The most recent conference on recommendations on the use of NST took place in 2010 and forms the basis of this report. C1 [Kaufmann, Manfred; Karn, Thomas; Ruckhaeberle, Eugen] Goethe Univ Frankfurt, Dept Gynecol & Obstet, Frankfurt, Germany. [Kaufmann, Manfred; Karn, Thomas; Ruckhaeberle, Eugen] Goethe Univ Frankfurt, Breast Unit, Frankfurt, Germany. [von Minckwitz, Gunter] German Breast Grp, Neu Isenburg, Germany. [Mamounas, Elefhterios P.] Aultman Canc Ctr, Canton, OH USA. [Cameron, David] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Carey, Lisa A.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Cristofanilli, Massimo] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Denkert, Carsten] Univ Hosp Charite, Inst Pathol, Berlin, Germany. [Eiermann, Wolfgang] Womens Hosp Med Ctr, Red Cross Clin, Munich, Germany. [Gnant, Michael] Med Univ Vienna, Dept Surg, Vienna, Austria. [Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Liedtke, Cornelia] Univ Hosp Muenster, Dept Gynecol & Obstet, Munster, Germany. [Mauri, Davide] Gen Hosp Lamia, Dept Med Oncol, Lamia, Greece. [Rouzier, Roman] Hop Tenon, Dept Obstet & Gynecol, F-75970 Paris, France. [Semiglazov, Vladimir] NN Petrov Oncol Res Inst, St Petersburg, Russia. [Symmans, W. Fraser] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Tutt, Andrew] Kings Coll London, Sch Med, Breakthrough Breast Canc Res Unit, London WC2R 2LS, England. [Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. RP Kaufmann, M (reprint author), Goethe Univ Frankfurt, Dept Gynecol & Obstet, Frankfurt, Germany. EM M.Kaufmann@em.uni-frankfurt.de RI karn, t/C-7452-2013; OI karn, t/0000-0002-3264-6573; Denkert, Carsten/0000-0002-2249-0982; Gnant, Michael/0000-0003-1002-2118; Semiglazov, Vladimir/0000-0003-0077-9619 FU BANSS Foundation, Biedenkopf, Germany; BANSS Foundation in Biedenkopf an der Lahn, Germany FX We thank the independent BANSS Foundation, Biedenkopf, Germany, for financial support, and the GBG GmbH, Neu Isenburg, Germany for logistical support of the meeting. All members of the panel had input in the discussion and formulation of the article. This consensus symposium received financial support from the BANSS Foundation, a nonprofit body based in Biedenkopf an der Lahn, Germany. Both the symposium and the preparation of this article was conducted independent of the pharmaceutical industry. The report was drafted in its entirety by the meeting participants without any paid assistance. NR 70 TC 130 Z9 136 U1 0 U2 14 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 2012 VL 19 IS 5 BP 1508 EP 1516 DI 10.1245/s10434-011-2108-2 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 933PV UT WOS:000303375400022 PM 22193884 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI It Is the Journey, Not the Destination SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 11 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2012 VL 93 IS 5 BP 1404 EP 1415 DI 10.1016/j.athoracsur.2011.11.078 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 935RZ UT WOS:000303539200011 PM 22541173 ER PT J AU Mullen, TD Obeid, LM AF Mullen, Thomas D. Obeid, Lina M. TI Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE Apoptosis; Ceramide; Ceramide synthase; De novo sphingolipid synthesis; Programmed cell death; Salvage pathway; Serine palmitoyl transferase; Sphingomyelinase ID PROTEIN-KINASE-C; RADIATION-INDUCED APOPTOSIS; PROSTATE-CANCER CELLS; NECROSIS-FACTOR-ALPHA; HUMAN GLIOMA-CELLS; MAMMALIAN SERINE-PALMITOYLTRANSFERASE; CANNABINOID-INDUCED APOPTOSIS; INOSTAMYCIN-INDUCED APOPTOSIS; PERMEABILITY TRANSITION PORE; LONGEVITY ASSURANCE GENE-1 AB Programmed cell death, or apoptosis, is a complex process whereby eukaryotic cells react to physiologic or pathophysiologic stimuli by undergoing genetically programmed suicide. Programmed cell death involves many well-characterized signaling pathways including permeabilization of the mitochondrial outer membrane and activation of caspases. Other pathways, such as pro-apoptotic lipid signaling, are less understood despite many years of study. The sphingolipid ceramide has received considerable attention as a key regulator of programmed cell death, yet the mechanisms of its up-regulation and ability to control cell fate remain ill-defined. In this review, we will examine the connections between sphingolipid metabolism and programmed cell death with a focus on the role of de novo sphingolipid synthesis and sphingosine salvage in producing pro-apoptotic ceramide. We will also highlight the evidence supporting an increasingly complex role for ceramide in regulating apoptosis and provide a framework in which to ask new questions about the functions of this enigmatic lipid. C1 [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Mullen, Thomas D.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), 114 Doughty St,Room 603 STRB,MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU MUSC (NIH/NIEHS) [5T32ES012878]; NIH/NIEHS [1 F30 ES016975-01]; Office of Research and Development, Dept. of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC; NIH/NIGMS [R01 GM062887]; NIH/NIA [R01 AG016583]; NIH/NCCR [P20 RR17677] FX Support for this work was provided by MUSC Department of Pharmaceutical Sciences Training Program in Environmental Stress Signaling (NIH/NIEHS 5T32ES012878) and Ruth L. Kirschstein National Research Service Award (NIH/NIEHS 1 F30 ES016975-01) for T.D.M. Work was supported in part by a MERIT Award (to L.M.O.) by the Office of Research and Development, Dept. of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC. NIH/NIGMS R01 GM062887, NIH/NIA R01 AG016583, and NIH/NCCR P20 RR17677 (to L.M.O.). We also would like to thank Jillian Michaud-King for her assistance in editing this manuscript. NR 269 TC 51 Z9 52 U1 7 U2 28 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAY PY 2012 VL 12 IS 4 BP 340 EP 363 PG 24 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 936UA UT WOS:000303614300006 PM 21707511 ER PT J AU Marrari, A Wagner, AJ Hornick, JL AF Marrari, Andrea Wagner, Andrew J. Hornick, Jason L. TI Predictors of Response to Targeted Therapies for Gastrointestinal Stromal Tumors SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID IMATINIB MESYLATE; TYROSINE KINASE; SUCCINATE-DEHYDROGENASE; PROGNOSTIC-FACTORS; GERMLINE MUTATION; CARNEY-STRATAKIS; PDGFRA MUTATIONS; DOSE IMATINIB; KIT; DIAGNOSIS AB Context.-The inhibition of oncogenic kinase signaling is a successful strategy to treat both hematologic and solid malignancies. Patients with chronic myelogenous leukemia, lung adenocarcinoma, renal cell carcinoma, and gastrointestinal stromal tumors are experiencing tremendous clinical benefits from targeted therapies in the form of kinase inhibitors. These drugs marked a revolution in cancer treatment, not only for their safety and efficacy, but also because they continue to expand our knowledge of the pathophysiology of cancer. Objective.-To provide a summary of the biologic predictors of gastrointestinal stromal tumor behavior and response to targeted therapies that currently help guide clinical decision making. Data Sources.-Published articles pertaining to the diagnosis, molecular genetics, prognostication, clinical behavior, and treatment of gastrointestinal stromal tumors, as well as experiences in a multidisciplinary sarcoma clinic. Conclusions.-In gastrointestinal stromal tumors, the strongest predictor of response to targeted therapies is the mutational status of KIT or PDGFRA. Patients whose tumors harbor a KIT exon 11 mutation benefit the most from imatinib mesylate therapy, in terms of response rate, progression-free survival, and overall survival. Conversely, tumors without detectable mutations in either gene ("wild-type" gastrointestinal stromal tumors) are generally not responsive to imatinibmesylate. (Arch Pathol Lab Med. 2012; 136:483-489; doi: 10.5858/arpa.2011-0082-RA) C1 [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Marrari, Andrea; Wagner, Andrew J.; Hornick, Jason L.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Wagner, Andrew J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wagner, Andrew J.; Hornick, Jason L.] Harvard Univ, Sch Med, Boston, MA USA. RP Hornick, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org NR 64 TC 15 Z9 16 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2012 VL 136 IS 5 BP 483 EP 489 DI 10.5858/arpa.2011-0082-RA PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 936OU UT WOS:000303600700007 PM 22229850 ER PT J AU Strle, K Shin, JJ Glickstein, LJ Steere, AC AF Strle, Klemen Shin, Junghee J. Glickstein, Lisa J. Steere, Allen C. TI Association of a toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BORRELIA-BURGDORFERI; DISEASE SPIROCHETE; ERYTHEMA MIGRANS; IMMUNE-RESPONSE; HIGH-FREQUENCY; UNITED-STATES; SUSCEPTIBILITY; TLR1; SKIN; ACRODERMATITIS AB Objective Single-nucleotide polymorphisms (SNPs) that alter immune function, inflammatory responses, and disease susceptibility have been identified in several genes encoding Toll-like receptors (TLRs). The TLR SNPs with the best evidence of an effect on immune function are those in TLR1 (1805GG), TLR2 (2258GA), and TLR5 (1174CT). This study was undertaken to assess the frequency and functional outcomes of these polymorphisms in patients with Lyme disease. Methods SNP frequencies and functional outcomes were assessed in 248 patients with Lyme disease. Cytokine and chemokine levels were determined using multiplex assays in the serum of patients with erythema migrans (EM), joint fluid of patients with Lyme arthritis, and supernatants of Borrelia burgdorferistimulated peripheral blood mononuclear cells (PBMCs) from patients with Lyme arthritis. Results The frequency of the TLR1-1805GG polymorphism was greater in patients with antibiotic-refractory arthritis compared with patients with EM or those with antibiotic-responsive arthritis. Early in the illness, patients with EM carrying 1805GG, primarily those infected with B burgdorferi 16S23S ribosomal spacer RNA intergenic type 1 (RST1) strains, had higher serum levels of interferon-? (IFN?), CXCL9, and CXCL10 and had more severe infection than EM patients carrying the 1805TG/TT polymorphism. These inflammatory responses were amplified in patients with Lyme arthritis, and the highest responses were observed in patients with 1805GG in the antibiotic-refractory group who had been infected with RST1 strains. When PBMCs from patients with Lyme arthritis were stimulated with a B burgdorferi RST1 strain, the 1805GG group had a significantly larger fold increase in the levels of IFN?, CCL2, CXCL9, and CXCL10 compared to the 1805TG/TT group. In contrast, the TLR2 and TLR5 polymorphisms did not vary in frequency or function among the groups. Conclusion The TLR1-1805GG polymorphism in B burgdorferi RST1infected patients was associated with stronger Th1-like inflammatory responses, an environment that may set the stage for antibiotic-refractory arthritis. C1 [Strle, Klemen] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Strle, Klemen; Shin, Junghee J.; Glickstein, Lisa J.; Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA. RP Strle, K (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 55 Fruit St,CNY149-8301, Boston, MA 02114 USA. EM kstrle@partners.org FU NIH [AR-020358, AR-007258]; English, Bonter, Mitchell Foundation; Massachusetts General Hospital; Eshe Fund; Walter J. and Lille A. Berbecker Foundation; Arthritis Foundation FX Supported in part by the NIH (grant AR-020358), the English, Bonter, Mitchell Foundation, the Lyme/Arthritis Research Fund at Massachusetts General Hospital, and the Eshe Fund. Dr. Strle's work was supported by a scholarship from the Walter J. and Lille A. Berbecker Foundation and by a postdoctoral fellowship from the Arthritis Foundation. Dr. Shin's work was supported by an NIH training grant (AR-007258) and by a scholarship from the Walter J. and Lille A. Berbecker Foundation. NR 50 TC 42 Z9 43 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2012 VL 64 IS 5 BP 1497 EP 1507 DI 10.1002/art.34383 PG 11 WC Rheumatology SC Rheumatology GA 931SG UT WOS:000303239000026 PM 22246581 ER PT J AU Gaffo, AL Schumacher, HR Saag, KG Taylor, WJ Dinnella, J Outman, R Chen, L Dalbeth, N Sivera, F Vazquez-Mellado, J Chou, CT Zeng, XJ Perez-Ruiz, F Kowalski, SC Goldenstein-Schainberg, C Chen, L Bardin, T Singh, JA AF Gaffo, Angelo L. Schumacher, H. Ralph Saag, Kenneth G. Taylor, William J. Dinnella, Janet Outman, Ryan Chen, Lang Dalbeth, Nicola Sivera, Francisca Vazquez-Mellado, Janitzia Chou, Chung-Tei Zeng, Xuejun Perez-Ruiz, Fernando Kowalski, Sergio C. Goldenstein-Schainberg, Claudia Chen, Lan Bardin, Thomas Singh, Jasvinder A. TI Developing a provisional definition of flare in patients with established gout SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOLOGY 1990 CRITERIA; HEALTH-ASSESSMENT QUESTIONNAIRE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HENOCH-SCHONLEIN PURPURA; WEGENER GRANULOMATOSIS; PROSPECTIVE VALIDATION; POLYARTERITIS-NODOSA; PSORIATIC-ARTHRITIS; TAKAYASU ARTERITIS; DISEASE-ACTIVITY AB Objective Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. Methods Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. Results The mean +/- SD age of the study participants was 56.2 +/- 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (010 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). Conclusion We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials. C1 [Gaffo, Angelo L.; Saag, Kenneth G.; Outman, Ryan; Chen, Lang; Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Schumacher, H. Ralph] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Schumacher, H. Ralph; Dinnella, Janet] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Taylor, William J.] Univ Otago, Wellington, New Zealand. [Dalbeth, Nicola] Univ Auckland, Sch Med, Auckland, New Zealand. [Sivera, Francisca] Gen Hosp Univ Alicante, E-03080 Alicante, Spain. [Sivera, Francisca] Univ Miguel Hernandez, Alicante, Spain. [Vazquez-Mellado, Janitzia] Hosp Gen Mexico City, Mexico City, DF, Mexico. [Vazquez-Mellado, Janitzia] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Chou, Chung-Tei] Vet Gen Hosp, Taipei, Taiwan. [Zeng, Xuejun] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Zeng, Xuejun] Chinese Acad Med Sci, Beijing, Peoples R China. [Perez-Ruiz, Fernando] Hosp Cruces, Baracaldo, Pais Vasco, Spain. [Kowalski, Sergio C.; Goldenstein-Schainberg, Claudia] Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil. [Chen, Lan] Penn Presbyterian Med Ctr, Philadelphia, PA USA. [Bardin, Thomas] Hop Lariboisiere, AP HP, F-75475 Paris, France. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com RI PEREZ-RUIZ, FERNANDO/E-4844-2012; , Ivan/D-6804-2012; OI , Ivan/0000-0002-3108-058X; singh, jasvinder/0000-0003-3485-0006; Perez-Ruiz, Fernando/0000-0002-5268-1894 FU American College of Rheumatology; European League Against Rheumatism; Novartis; Ardea Biosciences; Savient; Takeda; Menarini; Ipsen; Roche FX Supported in part by a grant from the American College of Rheumatology and the European League Against Rheumatism.; Dr. Saag has received consulting fees from Novartis, Ardea Biosciences, and Savient (less than $10,000 each) and has received research funding from Takeda. Dr. Perez-Ruiz has received consulting fees and/or speaking fees from Novartis, Ardea Biosciences, Menarini, and Savient (less than $10,000 each). Dr. Bardin has received consulting fees and/or speaking fees from Ipsen, Menarini, Novartis, Roche, and Ardea Biosciences (less than $10,000 each). NR 34 TC 19 Z9 20 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2012 VL 64 IS 5 BP 1508 EP 1517 DI 10.1002/art.33483 PG 10 WC Rheumatology SC Rheumatology GA 931SG UT WOS:000303239000027 PM 22083456 ER PT J AU Lagares, D Busnadiego, O Garcia-Fernandez, RA Kapoor, M Liu, SX Carter, DE Abraham, D Shi-Wen, X Carreira, P Fontaine, BA Shea, BS Tager, AM Leask, A Lamas, S Rodriguez-Pascual, F AF Lagares, David Busnadiego, Oscar Garcia-Fernandez, Rosa Ana Kapoor, Mohit Liu, Shangxi Carter, David E. Abraham, David Shi-Wen, Xu Carreira, Patricia Fontaine, Benjamin A. Shea, Barry S. Tager, Andrew M. Leask, Andrew Lamas, Santiago Rodriguez-Pascual, Fernando TI Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR; ENDOTHELIAL-CELLS; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; SYSTEMIC-SCLEROSIS; IN-VIVO; INTEGRIN; FAK; FIBROBLASTS AB Objective Enhanced adhesive signaling, including activation of focal adhesion kinase (FAK), is a hallmark of fibroblasts from lung fibrosis patients, and FAK has therefore been hypothesized to be a key mediator of this disease. This study was undertaken to characterize the contribution of FAK to the development of pulmonary fibrosis both in vivo and in vitro. Methods FAK expression and activity were analyzed in lung tissue samples from lung fibrosis patients by immunohistochemistry. Mice orally treated with the FAK inhibitor PF-562,271, or with small interfering RNA (siRNA)mediated silencing of FAK were exposed to intratracheally instilled bleomycin to induce lung fibrosis, and lungs were harvested for histologic and biochemical analysis. Using endothelin 1 (ET-1) as a stimulus, cell adhesion and contraction, as well as profibrotic gene expression, were studied in fibroblasts isolated from wild-type and FAK-deficient mouse embryos. ET1mediated FAK activation and gene expression were studied in primary mouse lung fibroblasts, as well as in wild-type and beta 1 integrindeficient mouse fibroblasts. Results FAK expression and activity were up-regulated in fibroblast foci and remodeled vessels from lung fibrosis patients. Pharmacologic or siRNA-mediated targeting of FAK resulted in marked abrogation of bleomycin-induced lung fibrosis in mice. Loss of FAK impaired the acquisition of a profibrotic phenotype in response to ET-1. Profibrotic gene expression leading to myofibroblast differentiation required cell adhesion, and was driven by JNK activation through beta 1 integrin/FAK signaling. Conclusion These results implicate FAK as a central mediator of fibrogenesis, and highlight this kinase as a potential therapeutic target in fibrotic diseases. C1 [Lagares, David; Busnadiego, Oscar; Lamas, Santiago; Rodriguez-Pascual, Fernando] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. [Lagares, David; Busnadiego, Oscar; Lamas, Santiago; Rodriguez-Pascual, Fernando] Fdn Renal Inigo Alvarez de Toledo, Madrid, Spain. [Busnadiego, Oscar; Rodriguez-Pascual, Fernando] CSIC, Ctr Invest Cardiovasc, Barcelona, Spain. [Busnadiego, Oscar; Rodriguez-Pascual, Fernando] Inst Catala Ciencies Cardiovasc, Barcelona, Spain. [Garcia-Fernandez, Rosa Ana] Univ Complutense Madrid, Madrid, Spain. [Kapoor, Mohit] Univ Montreal, Hosp Res Ctr, Montreal, PQ, Canada. [Liu, Shangxi] Univ Western Ontario, London, ON, Canada. [Carter, David E.] London Reg Genom Ctr, London, ON, Canada. [Abraham, David; Shi-Wen, Xu] UCL, London, England. [Carreira, Patricia] Hosp Univ 12 Octubre, Madrid, Spain. [Fontaine, Benjamin A.; Shea, Barry S.; Tager, Andrew M.] Massachusetts Gen Hosp, Charlestown, MA USA. RP Rodriguez-Pascual, F (reprint author), Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Nicolas Cabrera 1, E-28049 Madrid, Spain. EM frodriguez@cbm.uam.es RI Leask, Andrew/G-5217-2015; Lamas, Santiago /G-7308-2015 OI Lamas, Santiago /0000-0001-5166-4155 FU Ministerio de Ciencia e Innovacion [SAF2006-02410, SAF2009-09085, SAF2009-07520, Consolider CSD-2007-0020: ROSASNET]; Comunidad Autonoma de Madrid (CARDIOVREP Consortium); Sociedad Espanola de Nefrologia; Fundacion Medica Mutua Madrilena (Fundacion MM); Fundacion Genoma Espana; Canadian Institutes of Health Research; Canadian Foundation for Innovation; Ontario Thoracic Society; NIH [R01-HL-095732, K08-HL-105656] FX Supported by the Ministerio de Ciencia e Innovacion, Plan Nacional de I+D+I (grants SAF2006-02410, SAF2009-09085, SAF2009-07520, and Consolider CSD-2007-0020: ROSASNET), the Comunidad Autonoma de Madrid (CARDIOVREP Consortium), the Sociedad Espanola de Nefrologia (Senefro grant), the Fundacion Medica Mutua Madrilena (Fundacion MM grant), the Fundacion Genoma Espana (Meica project), the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Ontario Thoracic Society, and the NIH (grants R01-HL-095732 and K08-HL-105656). NR 56 TC 38 Z9 41 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAY PY 2012 VL 64 IS 5 BP 1653 EP 1664 DI 10.1002/art.33482 PG 12 WC Rheumatology SC Rheumatology GA 931SG UT WOS:000303239000040 PM 22492165 ER PT J AU Mohtadi, NGH Griffin, DR Pedersen, ME Chan, D Safran, MR Parsons, N Sekiya, JK Kelly, BT Werle, JR Leunig, M McCarthy, JC Martin, HD Byrd, JWT Philippon, MJ Martin, RL Guanche, CA Clohisy, JC Sampson, TG Kocher, MS Larson, CM AF Mohtadi, Nicholas G. H. Griffin, Damian R. Pedersen, M. Elizabeth Chan, Denise Safran, Marc R. Parsons, Nicholas Sekiya, Jon K. Kelly, Bryan T. Werle, Jason R. Leunig, Michael McCarthy, Joseph C. Martin, Hal D. Byrd, J. W. Thomas Philippon, Marc J. Martin, RobRoy L. Guanche, Carlos A. Clohisy, John C. Sampson, Thomas G. Kocher, Mininder S. Larson, Christopher M. CA MAHORN TI The Development and Validation of a Self-Administered Quality-of-Life Outcome Measure for Young, Active Patients With Symptomatic Hip Disease: The International Hip Outcome Tool (iHOT-33) SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID WESTERN ONTARIO; CLINICAL IMPORTANCE; COSMIN CHECKLIST; RATING SYSTEMS; ROTATOR CUFF; SCORE; OSTEOARTHRITIS; RESPONSIVENESS; REPLACEMENT; QUESTIONNAIRE AB Purpose: The purpose of this study was to develop a self-administered evaluative tool to measure health-related quality of life in young, active patients with hip disorders. Methods: This outcome measure was developed for active patients (aged 18 to 60 years, Tegner activity level >= 4) presenting with a variety of symptomatic hip conditions. This multicenter study recruited patients from international hip arthroscopy and arthroplasty surgeon practices. The outcome was created using a process of item generation (51 patients), item reduction (150 patients), and pretesting (31 patients). The questionnaire was tested for test-retest reliability (123 patients); face, content, and construct validity (51 patients); and responsiveness over a 6-month period in post-arthroscopy patients (27 patients). Results: Initially, 146 items were identified. This number was reduced to 60 through item reduction, and the items were categorized into 4 domains: (1) symptoms and functional limitations; (2) sports and recreational physical activities; (3) job-related concerns; and (4) social, emotional, and lifestyle concerns. The items were then formatted using a visual analog scale. Test-retest reliability showed Pearson correlations greater than 0.80 for 33 of the 60 questions. The intraclass correlation statistic was 0.78, and the Cronbach alpha was.99. Face validity and content validity were ensured during development, and construct validity was shown with a correlation of 0.81 to the Non-Arthritic Hip Score. Responsiveness was shown with a paired t test (P <= .01), effect size of 2.0, standardized response mean of 1.7, responsiveness ratio of 6.7, and minimal clinically important difference of 6 points. Conclusions: We have developed a new quality-of-life patient-reported outcome measure, the 33-item International Hip Outcome Tool (iHOT-33). This questionnaire uses a visual analog scale response format designed for computer self-administration by young, active patients with hip pathology. Its development has followed the most rigorous methodology involving a very large number of patients. The iHOT-33 has been shown to be reliable; shows face, content, and construct validity; and is highly responsive to clinical change. In our opinion the iHOT-33 can be used as a primary outcome measure for prospective patient evaluation and randomized clinical trials. C1 [Mohtadi, Nicholas G. H.; Chan, Denise] Univ Calgary, Sport Med Ctr, Calgary, AB T2N 1N4, Canada. [Griffin, Damian R.; Parsons, Nicholas] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Pedersen, M. Elizabeth] Univ Alberta, Edmonton, AB, Canada. [Safran, Marc R.] Stanford Univ, Redwood City, CA USA. [Sekiya, Jon K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kelly, Bryan T.] Weill Cornell Med Coll, New York, NY USA. [Leunig, Michael] Schulthess Clin, Zurich, Switzerland. [McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Martin, Hal D.] Oklahoma Sports Sci & Orthopaed, Hip Clin, Oklahoma City, OK USA. [Byrd, J. W. Thomas] Nashville Sports Med & Orthopaed Ctr, Nashville, TN USA. [Philippon, Marc J.] Steadman Philippon Res Inst, Vail, CO USA. [Martin, RobRoy L.] Duquesne Univ, Pittsburgh, PA 15219 USA. [Guanche, Carlos A.] So Calif Orthoped Inst, Van Nuys, CA USA. [Clohisy, John C.] Washington Univ, Sch Med, St Louis, MO USA. [Sampson, Thomas G.] Post St Orthopaed & Sports Med, San Francisco, CA USA. [Kocher, Mininder S.] Harvard Univ, Sch Med, Boston, MA USA. [Kocher, Mininder S.] Childrens Hosp Boston, Boston, MA USA. [Larson, Christopher M.] Twin Cities Orthoped, Minnesota Orthoped Sports Med Inst, Edina, MN USA. RP Mohtadi, NGH (reprint author), Univ Calgary, Sport Med Ctr, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada. EM mohtadi@ucalgary.ca RI Leunig, Michael/E-7951-2017; OI Leunig, Michael/0000-0002-2036-5416; Parsons, Nick/0000-0001-9975-888X; Guanche, Carlos/0000-0002-4897-5443 FU Canadian Orthopaedic Foundation; Calgary Orthopaedic Research and Development Fund; Calgary Surgical Research Development Fund; Alberta Bone and Joint Institute; McCaig Professorship; Smith Nephew; ConMed Linvatec; Ossur; Zimmer; Wright Medical; Institutional-Zimmer; Biomet; Arthrex; Siemens FX The authors report the following potential conflict of interest or source of funding in relation to this article: Canadian Orthopaedic Foundation, Calgary Orthopaedic Research and Development Fund, Calgary Surgical Research Development Fund, Alberta Bone and Joint Institute, and McCaig Professorship. All funding agencies represent noncommercial third-party granting agencies or charitable foundations.; Research or institutional support from companies or suppliers: M. R. S. (fellowship support from Smith & Nephew, ConMed Linvatec, Ossur, and Zimmer); D. R. G. (Wright Medical); J.C.M. (Institutional-Zimmer, Biomet, and Smith & Nephew); J.W.T.B. (Smith & Nephew); C. M. L. (Smith & Nephew and Arthrex); J.C.C. (Zimmer); and M.J.P. (Smith & Nephew, Siemens, Ossur, and Arthrex). NR 67 TC 81 Z9 83 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD MAY PY 2012 VL 28 IS 5 BP 595 EP U214 DI 10.1016/j.arthro.2012.03.013 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 934PI UT WOS:000303456000004 PM 22542433 ER PT J AU Jarrett, RB Minhajuddin, A Borman, PD Dunlap, L Segal, ZV Kidner, CL Friedman, ES Thase, ME AF Jarrett, Robin B. Minhajuddin, Abu Borman, Patricia D. Dunlap, Lauren Segal, Zindel V. Kidner, Cindy L. Friedman, Edward S. Thase, Michael E. TI Cognitive reactivity, dysfunctional attitudes, and depressive relapse and recurrence in cognitive therapy responders SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Depression; Cognitive therapy; Cognitive reactivity; Mood induction; Dysfunctional attitudes ID FOLLOW-UP; EMOTIONAL REACTIVITY; UNIPOLAR DEPRESSION; RATING-SCALE; SAD MOOD; DISORDERS; VALIDITY; VULNERABILITY; SYMPTOMS; ANXIETY AB Dysfunctional attitudes can foreshadow depressive relapse/recurrence. Priming mood, through induction paradigms, is hypothesized to activate dysfunctional attitudes. Cognitive reactivity (CR) refers to mood-linked increases in dysfunctional attitudes after priming. Here we explored the extent to which CR as well as residual, unprimed, dysfunctional attitudes predicted depressive relapse/recurrence among depressed patients who responded to acute phase cognitive therapy (CT). Consenting adults, aged 18-70, with recurrent major depressive disorder (n = 523) participated in a two-site randomized controlled trial examining the durability of continuation phase treatments. Patients received 16-20 sessions of CT. Among the 245 incompletely remitted responders, 213 agreed to undergo a mood induction paradigm. After 8 months of continuation phase treatments, participants were followed an additional 24 months. Although the mood induction significantly lowered mood in 80% of responders, the expected CR was not evident. By contrast, higher unprimed dysfunctional attitudes following CT did predict relapse/recurrence over 20 and 32 months post-randomization. The findings of this large longitudinal study of incompletely remitted CT responders challenge the notion that it is necessary to prime mood in order to maximize dysfunctional attitudes' prediction of relapse and/or recurrence. While findings cannot be generalized beyond CT responders, they emphasize the clinical importance of reducing dysfunctional attitudes in preventing depression. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Jarrett, Robin B.; Borman, Patricia D.; Dunlap, Lauren; Kidner, Cindy L.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Minhajuddin, Abu] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Segal, Zindel V.] Univ Toronto, Dept Psychiat, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Friedman, Edward S.; Thase, Michael E.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19102 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Jarrett, RB (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Robin.Jarrett@UTSouthwestern.edu; Abu.Minhajuddin@UTSouthwestern.edu; TrishBormanPhD@gmail.com; Lauren.Dunlap@UTSouthwestern.edu; Zindel_Segal@camh.net; Cindy.Kidner@alumni.UTSouthwestern.edu; Friedmane@upmc.edu; Thase@mail.med.upenn.edu RI Segal, Zindel/F-8008-2014 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [UL1 RR024153]; NIMH NIH HHS [R01 MH069618-04, R01 MH058356-11, R01 MH069619, R01 MH058356, K24 MH001571, R01 MH069619-05, R01 MH058397-11, K24 MH001571-10, R01 MH058397, R01 MH069618] NR 53 TC 20 Z9 20 U1 6 U2 35 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD MAY PY 2012 VL 50 IS 5 BP 280 EP 286 DI 10.1016/j.brat.2012.01.008 PG 7 WC Psychology, Clinical SC Psychology GA 937CS UT WOS:000303637200002 PM 22445946 ER PT J AU Keever-Taylor, CA Devine, SM Soiffer, RJ Mendizabal, A Carter, S Pasquini, MC Hari, PN Stein, A Lazarus, HM Linker, C Goldstein, SC Stadtmauer, EA O'Reilly, RJ AF Keever-Taylor, Carolyn A. Devine, Steven M. Soiffer, Robert J. Mendizabal, Adam Carter, Shelly Pasquini, Marcelo C. Hari, Parameswaran N. Stein, Anthony Lazarus, Hillard M. Linker, Charles Goldstein, Steven C. Stadtmauer, Edward A. O'Reilly, Richard J. TI Characteristics of CliniMACS (R) System CD34-Enriched T Cell-Depleted Grafts in a Multicenter Trial for Acute Myeloid Leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0303 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic stem cell transplantation; T cell depletion; Clinical trial; Graft processing; Blood and Marrow Transplant Clinical Trials Network ID VERSUS-HOST-DISEASE; ACUTE MYELOGENOUS LEUKEMIA; HIGH-RISK; PHASE-II; RELAPSE; DEVICE; REMISSION; SELECTION; CHILDREN AB Eight centers participated in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303 to determine the effect of extensive T cell depletion (TCD) on the outcome of HLA matched sibling donor transplantation for acute myeloid leukemia. One goal of the study was to determine if TCD could be performed uniformly among study sites. TCD was achieved using the CliniMACS (R) CD34 Reagent System for CD34 enrichment. Processed grafts needed to contain >= 2.0 x 10(6) CD34(+) cells/kg with a target of 5.0 x 10(6) CD34(+) cells/kg and <10(5) CD3(+) T cells/kg. Up to 3 collections were allowed to achieve the minimum CD34(+) cell dose. In total, 86 products were processed for 44 patients. Differences in the starting cell products between centers were seen in regard to total nucleated cells, CD34(+) cells, and CD3(+) T cells, which could in part be ascribed to a higher dose of granulocyte-colony stimulating factor used for mobilization early in the trial. Differences between centers in processing outcomes were minimal and could be ascribed to starting cell parameters or to differences in graft analysis methods. Multivariate analysis showed that CD34(+) cell recovery (66.1% +/- 20.3%) was inversely associated with the starting number of CD34(+) cells (P = .02). Median purity of the CD34 enriched fraction was 96.7% (61.5%-99.8%) with monocytes and B cells the most common impurity. All patients received the minimum CD34(+) cell dose, and 39 patients (89%) came within 10% or exceeded the target CD34(+) cell dose without exceeding the maximum T cell dose. All patients proceeded to transplantation and all achieved initial engraftment. Products processed at multiple centers using the CliniMACS System for CD34 enrichment were comparably and uniformly highly enriched for CD34(+) cells, with good CD34(+) cell recovery and very low CD3(+) T cell content. Biol Blood Marrow Transplant 18: 690-697 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Keever-Taylor, Carolyn A.; Pasquini, Marcelo C.; Hari, Parameswaran N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Devine, Steven M.] Ohio State Univ, Columbus, OH 43210 USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mendizabal, Adam; Carter, Shelly] EMMES Corp, Rockville, MD USA. [Stein, Anthony] City Hope Natl Med Ctr, Duarte, CA USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Linker, Charles] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldstein, Steven C.; Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Keever-Taylor, CA (reprint author), Med Coll Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM ckeever@mcw.edu FU National Heart, Lung, and Blood Institute [U01HL069294]; National Cancer Institute FX The Blood and Marrow Transplant Clinical Trials Network is supported in part by grant #U01HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute. We thank Miltenyi Biotec for support of this trial. In addition to the first author, this study could not have been performed without the contributions of the other key laboratory personnel at the clinical sites including: Grace Kao, MD, Dana Farber Cancer Institute; Lynn O'Donnell, PhD, The Ohio State University; Nancy Collins, PhD, Memorial Sloan-Kettering Cancer Center; Dave DiGiusto, PhD, City of Hope; Robert M. Fox, RN, ND, University Hospitals Case Medical Center; Joy Cruz, MT(ASCP)SBB, University of California-San Francisco; Una O'Doherty, MD, PhD, Abramson Cancer Center of the University of Pennsylvania. NR 17 TC 17 Z9 17 U1 0 U2 2 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 2012 VL 18 IS 5 BP 690 EP 697 DI 10.1016/j.bbmt.2011.08.017 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 935YQ UT WOS:000303558500006 PM 21875505 ER PT J AU Abou-Nassar, KE Kim, HT Blossom, J Ho, VT Soiffer, RJ Cutler, CS Alyea, EP Koreth, J Antin, JH Armand, P AF Abou-Nassar, Karim E. Kim, Haesook T. Blossom, Jeff Ho, Vincent T. Soiffer, Robert J. Cutler, Corey S. Alyea, Edwin P. Koreth, John Antin, Joseph H. Armand, Philippe TI The Impact of Geographic Proximity to Transplant Center on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic stem cell transplantation; Geography; Geographic proximity; Distance; Overall survival ID HEALTH-CARE; MARROW TRANSPLANTATION; SURVIVAL; CANCER; ACCESS; ENGLAND; ACCESSIBILITY; MANAGEMENT; BLOOD AB Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) need access to specialized care. We hypothesized that access to the transplant center after HSCT may be challenging for patients living in geographically distant areas, and that this would have an adverse effect on their outcome. We analyzed 1912 adult patients who underwent allogeneic HSCT at the Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) between 1996 and 2009 and who resided within 6 hours driving time of the institution. Driving time from primary residence to DF/BWCC based on zipcode was determined using geographic information systems. The median driving time (range) to DF/BWCC was 72 (2-358) minutes. When patients were stratified by driving time quartile, overall survival (OS) after HSCT was similar in the first year but worse after I year in patients in the top quartile (>= 160 minutes driving time). In a landmark analysis of the 909 patients alive and free of disease at I year, 5-year OS was 76% and 65% for patients in the first (<= 40 minutes) and fourth (>= 160 minutes) quartiles, respectively (P = .027). This was confirmed in a multivariable analysis. The difference appeared to be mostly because of an increase in nonrelapse mortality. The number of visits to the transplant center between day 100 and 365 after HSCT declined significantly with increasing driving time to the transplant center, which was independently associated with worse survival. Long driving time to the transplant center is associated with worse OS in patients alive and disease-free 1 year after HSCT, independently of other patient-, disease-, and HSCT-related variables. This may be in part related to the lower frequency of post-HSCT visits in patients living farther away. Biol Blood Marrow Transplant 18: 708-715 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Armand, Philippe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Abou-Nassar, Karim E.] Univ Ottawa, Dept Med, Div Hematol, Ottawa Hosp, Ottawa, ON, Canada. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Blossom, Jeff] Harvard Univ, Ctr Geog Anal, Cambridge, MA 02138 USA. RP Armand, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Philippe_armand@dfci.harvard.edu FU NIH [CA142106]; Jock and Bunny Adams Research, and Education Endowment, CA FX This work was supported in part by NIH Grant CA142106, Jock and Bunny Adams Research, and Education Endowment, CA. NR 19 TC 16 Z9 16 U1 1 U2 2 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 2012 VL 18 IS 5 BP 708 EP 715 DI 10.1016/j.bbmt.2011.08.022 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 935YQ UT WOS:000303558500008 PM 21906576 ER PT J AU Chen, YB Aldridge, J Kim, HT Ballen, KK Cutler, C Kao, G Liney, D Bourdeau, G Alyea, EP Armand, P Koreth, J Ritz, J Spitzer, TR Soiffer, RJ Antin, JH Ho, VT AF Chen, Yi-Bin Aldridge, Julie Kim, Haesook T. Ballen, Karen K. Cutler, Corey Kao, Grace Liney, Deborah Bourdeau, Greg Alyea, Edwin P. Armand, Philippe Koreth, John Ritz, Jerome Spitzer, Thomas R. Soiffer, Robert J. Antin, Joseph H. Ho, Vincent T. TI Reduced-Intensity Conditioning Stem Cell Transplantation: Comparison of Double Umbilical Cord Blood and Unrelated Donor Grafts SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE RIC; Umbilical cord blood transplantation ID ADULT RECIPIENTS; COMPETING RISK; SURVIVAL; DISEASE; CHIMERISM AB There are little data comparing umbilical cord blood (UBC) and conventional stem cell sources for reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of RIC HCST using double UCB (dUCB) grafts and RIC HSCT using unrelated donor (URD) grafts. The study included 64 dUCB transplantations and 221 URD transplantations performed at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2004 and 2008. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 14.1% for dUCB and 20.3% for URD (P = .32). The 2-year cumulative incidence of chronic GVHD was significantly lower in dUCB compared with URD (21.9% versus 53.9%; P < .0001). The 2-year cumulative incidence of nonrelapse mortality was significantly higher in dUCB (26.9% versus 10.4%; P = .0009). In our analysis, dUCB HSCT and URD HSCT had comparable 3-year overall survival (46% in dUCB and 50% in URD; P = .49) and progression-free survival (30% in dUCB and 40% in URD; P = .47). dUCBT was associated with greater nonrelapse mortality despite less chronic GVHD. Our findings suggest that the use of 2 partially matched UCB units appears to be a suitable alternative for patients undergoing RIC HSCT without an HLA-matched donor. Biol Blood Marrow Transplant 18: 805-812 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Aldridge, Julie; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cutler, Corey; Kao, Grace; Liney, Deborah; Bourdeau, Greg; Alyea, Edwin P.; Armand, Philippe; Koreth, John; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Chen, YB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit, 55 Fruit St, Boston, MA 02114 USA. EM ychen6@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU Jock and Bunny Adams Research and Education Endowment; Leukemia & Lymphoma Society FX This work was supported in part by the Jock and Bunny Adams Research and Education Endowment. Yi-Bin Chen is a recipient of a career development award in clinical research from the Leukemia & Lymphoma Society. The authors have no conflicts of interest to disclose. NR 26 TC 47 Z9 47 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 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2012 VL 18 IS 5 BP 805 EP 812 DI 10.1016/j.bbmt.2011.10.016 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 935YQ UT WOS:000303558500020 PM 22015993 ER PT J AU Lightdale, JR Randolph, AG Tran, CM Jiang, HY Colon, A Houlahan, K Billet, A Sloan, S Lehmann, LE AF Lightdale, Jenifer R. Randolph, Adrienne G. Tran, Chau M. Jiang, Hongyu Colon, Andrea Houlahan, Kathleen Billet, Amy Sloan, Steven Lehmann, Leslie E. TI Impact of a Conservative Red Blood Cell Transfusion Strategy in Children Undergoing Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Marrow and stem cell transplantation; Transfusion medicine; Red blood cells; Hematopoietic stem cell transplantation; Pediatric; Transfusion strategies ID INTENSIVE-CARE; MARROW-TRANSPLANTATION; TRIAL AB A 2008 randomized trial of critically ill, but stable, children reported the safety of transfusing red blood cells at a hemoglobin threshold of 7 g/dL. In 2009, we adopted the same transfusion criteria in our hematopoietic stem cell transplantation patients. Regression modeling was used to compare data obtained during primary admission for hematopoietic stem cell transplantation in calendar years before and after our practice change. Sixty-six patients admitted in the preintervention year were compared with 75 postintervention. Pre- and postpatients were similar in diagnoses and type of transplantations. Postintervention, median hemoglobin pretransfusion significantly decreased from 8.8 g/dL to 6.8 g/dL (P < .0001). In addition, transfused red blood cell units received by patients dropped from 4 (interquartile range [IQR] 3, 8) to 3 (IQR, 2, 5), (P = .002), and number of transfusion days per patients decreased from 4 (IQR, 2,5) to 3 (IQR, 2, 5), (P = .01). There were no differences in length of stay, time to engraftment, or 100-day mortality. Median blood product charges per patient significantly decreased ($3,624 [IQR, $2,265, $6,040] to $2,185 [IQR, $1,812, $3,997], P = .004). Our initial experience suggests that implementation of a conservative transfusion strategy in otherwise stable children undergoing hematopoietic stem cell transplantation appears safe and lowers transfusion exposures. Biol Blood Marrow Transplant 18: 813-817 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Lightdale, Jenifer R.; Billet, Amy; Lehmann, Leslie E.] Childrens Hosp Boston, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Lightdale, Jenifer R.; Randolph, Adrienne G.; Jiang, Hongyu; Billet, Amy; Sloan, Steven; Lehmann, Leslie E.] Harvard Univ, Sch Med, Boston, MA USA. [Randolph, Adrienne G.] Childrens Hosp Boston, Dept Anesthesia, Crit Care Div, Boston, MA 02115 USA. [Tran, Chau M.; Jiang, Hongyu] Childrens Hosp Boston, Clin Res Ctr, Boston, MA 02115 USA. [Colon, Andrea] Childrens Hosp Boston, Program Patient Safety & Qual, Boston, MA 02115 USA. [Houlahan, Kathleen] Childrens Hosp Boston, Patient Serv Pediat Oncol Hematol & Stem Cell Tra, Dept Nursing, Boston, MA 02115 USA. [Houlahan, Kathleen; Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Billet, Amy; Sloan, Steven] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. RP Lightdale, JR (reprint author), Childrens Hosp Boston, Dept Med, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM jenifer.lightdale@childrens.harvard.edu OI Randolph, Adrienne/0000-0002-3084-3071 FU Physician's Organization; Transfusion Committee, the Department of Laboratory Medicine; Information Systems Databases (ISD) team; Program for Patient Safety and Quality (PPSQ); Clinical Research Program; Physician's Organization at Children's Hospital Boston FX The authors acknowledge support for this project from the following organizations at Children's Hospital Boston: the Physician's Organization; the Transfusion Committee, the Department of Laboratory Medicine; the Information Systems Databases (ISD) team; the Program for Patient Safety and Quality (PPSQ) and the Clinical Research Program. We also thank the following individuals for their assistance: Maureen A. Beaton, MT(ASCP)BB, CQA(ASQ); Patricia A. Branowicki, MS, RN, NEA-BC; Lisa Morrissey, RN; and Erica P. Louras. Our project was funded through the Physician's Organization at Children's Hospital Boston. NR 11 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2012 VL 18 IS 5 BP 813 EP 817 DI 10.1016/j.bbmt.2011.10.043 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 935YQ UT WOS:000303558500021 PM 22080050 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Altshuler, LL Glahn, DC Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Altshuler, Lori L. Glahn, David C. Green, Michael F. TI Cross-diagnostic comparison of duration mismatch negativity and P3a in bipolar disorder and schizophrenia SO BIPOLAR DISORDERS LA English DT Article DE auditory processing; bipolar disorder; mismatch negativity; P3a; schizophrenia ID EVENT-RELATED POTENTIALS; AUDITORY SENSORY MEMORY; ELECTROPHYSIOLOGICAL INDEXES; SPECTRUM DISORDERS; DEVIANCE DETECTION; NMDA ANTAGONIST; MESSENGER-RNA; TEMPORAL-LOBE; RATING-SCALE; DEFICITS AB Jahshan C, Wynn JK, Mathis KI, Altshuler LL, Glahn DC, Green MF. Cross-diagnostic comparison of duration mismatch negativity and P3a in bipolar disorder and schizophrenia. ?Bipolar Disord 2012: 14: 239248. (C) 2012 The Authors. Journal compilation (C) 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder and schizophrenia share common pathophysiological processes and may have similar perceptual abnormalities. Mismatch negativity (MMN) and P3a event-related potentials associated with auditory preattentional processing have been extensively studied in schizophrenia, but rarely in bipolar disorder. Furthermore, MMN and P3a have not been examined between diagnostic subgroups of patients with bipolar disorder. We evaluated MMN and P3a in patients with bipolar disorder compared to patients with schizophrenia and healthy controls. Methods: MMN and P3a were assessed in 52 bipolar disorder patients, 30 schizophrenia patients, and 27 healthy control subjects during a duration-deviant auditory oddball paradigm. Results: Significant MMN and P3a amplitude reductions were present in patients with bipolar disorder and schizophrenia relative to controls. The MMN reduction was more prominent in patients with schizophrenia than bipolar disorder, at a trend level. P3a did not differ significantly between patient groups. There were no MMN or P3a differences between patients with bipolar I (n = 34) and bipolar II (n = 18) disorder. Patients with bipolar I disorder failed to show lateralized MMN, in contrast to the other groups. No MMN or P3a differences were found between patients with bipolar disorder taking (n = 12) and not taking (n = 40) lithium, as well as between those taking (n = 30) and not taking (n = 22) antipsychotic medications. Conclusions: Patients with bipolar disorder showed deficits in preattentive auditory processing, including MMN deficits that are less severe and P3a deficits that are slightly more pronounced, than those seen in schizophrenia. C1 [Jahshan, Carol; Wynn, Jonathan K.; Mathis, Kristopher I.; Altshuler, Lori L.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Altshuler, Lori L.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Glahn, David C.] Yale Univ, Sch Med, Olin Neuropsychiat Res Ctr, Inst Living, New Haven, CT USA. [Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC, Bldg 210,Room 106,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM caroljahshan@hotmail.com RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH089634] FX This work was supported by a grant from the National Institute of Mental Health (MH089634 to MFG). The authors wish to thank Crystal Gibson, Cory Tripp, Katie Weiner, Mark McGee, Christen Waldon, and Amanda Bender for their assistance with recruitment and testing. NR 67 TC 27 Z9 27 U1 0 U2 10 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 2012 VL 14 IS 3 BP 239 EP 248 DI 10.1111/j.1399-5618.2012.01008.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 934IO UT WOS:000303438000003 PM 22548897 ER PT J AU Girish, S Gupta, M Wang, B Lu, D Krop, IE Vogel, CL Burris, HA LoRusso, PM Yi, JH Saad, O Tong, B Chu, YW Holden, S Joshi, A AF Girish, Sandhya Gupta, Manish Wang, Bei Lu, Dan Krop, Ian E. Vogel, Charles L. Burris, Howard A., III LoRusso, Patricia M. Yi, Joo-Hee Saad, Ola Tong, Barbara Chu, Yu-Waye Holden, Scott Joshi, Amita TI Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody-drug conjugate in development for the treatment of HER2-positive cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Trastuzumab emtansine; T-DM1; Breast cancer; HER2; Antibody-drug conjugate ID BREAST-CANCER; MONOCLONAL-ANTIBODIES; CHEMOTHERAPY; MAYTANSINE; MBC AB Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate comprising trastuzumab and DM1, a microtubule polymerization inhibitor, covalently bound via a stable thioether linker. To characterize the pharmacokinetics (PK) of T-DM1 in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, data from four studies (TDM3569g, TDM4258g, TDM4374g, and TDM4688g) of single-agent T-DM1 administered at 3.6 mg/kg every 3 weeks (q3w) were assessed in aggregate. Multiple analytes-T-DM1, total trastuzumab (TT), DM1, and key metabolites-were quantified using enzyme-linked immunosorbent assays or liquid chromatography tandem mass spectrometry. PK parameters of T-DM1, TT, and DM1 exposure were calculated using standard noncompartmental approaches and correlated to efficacy (objective response rate) and safety (platelet counts, hepatic transaminase concentrations). Immunogenicity was evaluated by measuring anti-therapeutic antibodies (ATA) to T-DM1 after repeated dosing using validated bridging antibody electrochemiluminescence or enzyme-linked immunosorbent assays. PK parameters for T-DM1, TT, and DM1 were consistent across studies at cycle 1 and steady state. T-DM1 PK was not affected by residual trastuzumab from prior therapy or circulating extracellular domain of HER2. No significant correlations were observed between T-DM1 exposure and efficacy, thrombocytopenia, or increased concentrations of transaminases. Across the studies, ATA formation was detected in 4.5% (13/286) of evaluable patients receiving T-DM1 q3w. The PK profile of single-agent T-DM1 (3.6 mg/kg q3w) is predictable, well characterized, and unaffected by circulating levels of HER2 extracellular domain or residual trastuzumab. T-DM1 exposure does not correlate with clinical responses or key adverse events. C1 [Girish, Sandhya; Gupta, Manish; Wang, Bei; Lu, Dan; Yi, Joo-Hee; Saad, Ola; Tong, Barbara; Chu, Yu-Waye; Holden, Scott; Joshi, Amita] Genentech Inc, San Francisco, CA 94080 USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vogel, Charles L.] Sylvester Comprehens Canc Ctr, Deerfield Beach, IL USA. [Burris, Howard A., III] Sarah Cannon Res Inst, Nashville, TN USA. [LoRusso, Patricia M.] Karmanos Canc Ctr, Detroit, MI USA. RP Girish, S (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA. EM girish.sandhya@gene.com FU Genentech, Inc. FX S.G., M.G., B.W., D.L., J-H Y., O.S., B.T., Y.-W.C., S.H., and A.J. are employees of Genentech, Inc. I.K. has received research funding from Genentech, Inc. C.L.V. has served on advisory boards for Genentech, Inc. and has been an expert witness for F. HoVman-La Roche Ltd. The Sylvester Comprehensive Cancer Center (C.L.V.'s institution) has received research funding from Genentech, Inc. P.M.L. has received honoraria from Genentech, Inc. NR 29 TC 91 Z9 98 U1 7 U2 40 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 2012 VL 69 IS 5 BP 1229 EP 1240 DI 10.1007/s00280-011-1817-3 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 934CK UT WOS:000303418500014 PM 22271209 ER PT J AU Zhou, J Yuen, NK Zhan, Q Velazquez, EF Murphy, GF Giobbie-Hurder, A Hodi, FS AF Zhou, Jun Yuen, Noah K. Zhan, Qian Velazquez, Elsa F. Murphy, George F. Giobbie-Hurder, Anita Hodi, F. Stephen TI Immunity to the melanoma inhibitor of apoptosis protein (ML-IAP; livin) in patients with malignant melanoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Melanoma; ML-IAP; Livin; Immune responses ID T-CELL RESPONSES; TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN-LOSS VARIANTS; CANCER-PATIENTS; LUNG-CANCER; SURVIVIN; GENE; EXPRESSION; TARGET; NY-ESO-1 AB Therapeutic targeting of melanoma antigens frequently focuses on the melanocyte differentiation or cancer-testis families. Antigen-loss variants can often result, as these antigens are not critical for tumor cell survival. Exploration of functionally relevant targets has been limited. The melanoma inhibitor of apoptosis protein (ML-IAP; livin) is overexpressed in melanoma, contributing to disease progression and treatment resistance. Improved understanding of the significance of ML-IAP immune responses in patients has possible therapeutic applications. We found ML-IAP frequently expressed in melanoma metastases by immunohistochemistry. To assess spontaneous immunity to ML-IAP, an overlapping peptide library representing full-length protein was utilized to screen cellular responses in stage I-IV patients and healthy controls by ELISPOT. A broad array of CD4(+) and CD8(+) cellular responses against ML-IAP was observed with novel class I and class II epitopes identified. Specific HLA-A*0201 epitopes were analyzed further for frequency of reactivity. The generation of specific CD4(+) and cytotoxic T cells revealed potent functional capability including cytokine responsiveness to melanoma cell lines and tumor cell killing. In addition, recombinant ML-IAP protein used in an ELISA demonstrated high titer antibody responses in a subset of patients. Several melanoma patients who received CTLA-4 blockade with ipilimumab developed augmented humoral immune responses to ML-IAP as a function of treatment which was associated with beneficial clinical outcomes. High frequency immune responses in melanoma patients, associations with favorable treatment outcomes, and its essential role in melanoma pathogenesis support the development of ML-IAP as a disease marker and therapeutic target. C1 [Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhou, Jun; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Zhou, Jun; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Dis Ctr, Boston, MA USA. [Yuen, Noah K.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96813 USA. [Zhan, Qian; Velazquez, Elsa F.; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu OI Murphy, George/0000-0003-3464-793X FU Ron Gelb Melanoma Research Fund; Dana-Farber Cancer Institute FX This work was supported in part by The Ron Gelb Melanoma Research Fund and Malcolm and Emily Mac Naught Fund for Melanoma Research at Dana-Farber Cancer Institute. The authors do not have additional financial relationships with the organizations that sponsored the research. NR 45 TC 10 Z9 13 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 2012 VL 61 IS 5 BP 655 EP 665 DI 10.1007/s00262-011-1124-1 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 935HL UT WOS:000303509600005 PM 22033581 ER PT J AU Koo, S Baden, LR Marty, FM AF Koo, S. Baden, L. R. Marty, F. M. TI Post-diagnostic kinetics of the (1 -> 3)-beta-D-glucan assay in invasive aspergillosis, invasive candidiasis and Pneumocystis jirovecii pneumonia SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE ss-glucan; candidiasis; galactomannan; invasive aspergillosis; invasive fungal disease; kinetics; Pneumocystis jirovecii ID BETA-D-GLUCAN; MYCOSES STUDY-GROUP; FUNGAL-INFECTIONS; EUROPEAN-ORGANIZATION; CLINICAL-TRIALS; GALACTOMANNAN; SERUM; ANTIGENEMIA; SURROGATE; LEUKEMIA AB The kinetics of serum (1 ? 3)-beta-d-glucan (BG) following the diagnosis of invasive fungal disease and administration of antifungal therapy are poorly characterized. It is unknown whether early BG changes have prognostic implications. We assessed the post-diagnostic kinetics of BG in patients with an initial serum BG =80 pg/mL and at least one additional post-diagnostic BG value in the setting of invasive aspergillosis (IA, n = 69), invasive candidiasis (IC, n = 40), or Pneumocystis jirovecii pneumonia (PCP, n = 18), treated with antifungal therapy. Clinical failure of antifungal therapy and mortality were assessed at 6 and 12 weeks, and Cox modelling was used to assess the hazard of initial BG and change in BG at 1 or 2 weeks for these outcomes. In patients with at least two BG values, median initial BG was >500 pg/mL (interquartile range (IQR) 168 to >500; range 80 to >500) in IA, 136 pg/mL (IQR 88 to >500; range 31 to >500) in IC and >500 pg/mL (IQR 235 to >500; range 86 to >500) in PCP. In patients with at least two BG values through to 1 week after diagnosis, overall 1-week decline in BG was 0 pg/mL (IQR 053) in IA, 0 (IQR - 65 to 12) in IC and 17 (IQR 082) in PCP. Most patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL. Initial BG and the early trajectory of BG were not predictive of 6-week or 12-week clinical failure or mortality. Whereas BG eventually declines in patients with IA, IC and PCP, it lacks prognostic value within a clinically meaningful time frame. C1 [Koo, S.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, S.; Baden, L. R.; Marty, F. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koo, S.; Baden, L. R.; Marty, F. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 FU Harvard Catalyst | The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This work was supported in part by Harvard Catalyst | The Harvard Clinical and Translational Science Center (NIH Award # UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers). All authors report no relevant conflicts of interest. NR 23 TC 21 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD MAY PY 2012 VL 18 IS 5 BP E122 EP E127 DI 10.1111/j.1469-0691.2012.03777.x PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 927JQ UT WOS:000302903900003 PM 22404638 ER PT J AU Blais, MA Sinclair, SJ Baity, MR Worth, J Weiss, AP Ball, LA Herman, J AF Blais, Mark A. Sinclair, Samuel J. Baity, Matthew R. Worth, Jonathan Weiss, Anthony P. Ball, Laurie Ansorge Herman, John TI Measuring Outcomes in Adult Outpatient Psychiatry SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Outcomes Measurement; Treatment as Usual; Adult Psychiatry ID MENTAL-HEALTH TREATMENT; CLINICAL-SIGNIFICANCE; ANXIETY DISORDERS; PSYCHOTHERAPY; METAANALYSIS; DEPRESSION; CARE; MODEL; MANAGEMENT; EFFICACY AB Despite growing pressure for accountability, mental health professionals continue to debate the value of routinely measuring treatment outcomes. This paper sought to move the outcomes measurement debate forward by reviewing some of the current limitations in outcomes methodology and by providing initial strategies to address them. Using these strategies, we evaluated outcomes for a large diagnostically diverse group of adult outpatients receiving treatment as usual (TAU) within an academic medical centre. Initial self-report and clinician-rated assessments were obtained from 5546 patients, and follow-up data were obtained from 1572 (28%) patients. Using the subset of patients with the follow-up data, we determined treatment effect sizes, rates of reliable improvement (and deterioration) and rates of clinically significant improvement for all patients and for specific diagnostic groups (depression, anxiety, substance abuse, mood disorders not otherwise specified, bipolar and psychotic conditions). TAU outcomes for depression and anxiety were also compared with benchmarks derived from the randomized controlled trial literature. Lastly, the impact of patient or sample characteristics on outcome was explored. Overall, these findings generally support the benefit of TAU over no treatment while also highlighting both the utility and limitations inherent in the current approaches to evaluating treatment outcomes. Suggestions for improving outcomes measurement are provided. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Blais, Mark A.; Sinclair, Samuel J.; Worth, Jonathan; Weiss, Anthony P.; Ball, Laurie Ansorge; Herman, John] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA. [Blais, Mark A.; Sinclair, Samuel J.; Worth, Jonathan; Weiss, Anthony P.; Herman, John] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Baity, Matthew R.] Alliant Int Univ, Calif Sch Profess Psychol, Sacramento, CA USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, 1 Bowdoin Sq,702, Boston, MA 02114 USA. EM Mblais@partners.org NR 43 TC 10 Z9 10 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD MAY-JUN PY 2012 VL 19 IS 3 BP 203 EP 213 DI 10.1002/cpp.749 PG 11 WC Psychology, Clinical SC Psychology GA 934JT UT WOS:000303441100002 PM 21416558 ER PT J AU Dunn, EC Gilman, SE Willett, JB Slopen, NB Molnar, BE AF Dunn, Erin C. Gilman, Stephen E. Willett, John B. Slopen, Natalie B. Molnar, Beth E. TI THE IMPACT OF EXPOSURE TO INTERPERSONAL VIOLENCE ON GENDER DIFFERENCES IN ADOLESCENT-ONSET MAJOR DEPRESSION: RESULTS FROM THE NATIONAL COMORBIDITY SURVEY REPLICATION (NCS-R) SO DEPRESSION AND ANXIETY LA English DT Article DE depression; violence; mediation; stress exposure; stress reactivity ID STRESSFUL LIFE EVENTS; CHILD SEXUAL-ABUSE; DSM-IV DISORDERS; COMMUNITY SAMPLE; MENTAL-HEALTH; RISK-FACTORS; PREVALENCE; PSYCHOPATHOLOGY; VICTIMIZATION; EPIDEMIOLOGY AB Background Beginning in adolescence, females are at significantly higher risk for depression than males. Despite substantial efforts, gaps remain in our understanding of this disparity. This study tested whether gender differences in adolescent-onset depression arise because of female's greater exposure or sensitivity to violence. Methods Data came from 5,692 participants in the National Comorbidity Survey Replication. Trained interviewers collected data about major depression and participants exposure to four types of interpersonal violence (physical abuse, sexual assault, rape, and witnessing violence) using a modified version of the Composite International Diagnostic Interview. We used discrete time survival analysis to investigate gender differences in the risk of adolescent onset depression. Results Of the entire sample, 5.7% met DSM-IV criteria for depression by age 18; 5.8% of the sample reported being physically abused, 11.7% sexually assaulted, 8.5% raped, and 13.2% witnessed violence by age 18. Females had 1.51 times higher odds of depression by age 18 than males. Exposure to all types of violence was associated with an increased odds of depression in both the past year and the years following exposure. Adjusting for exposure to violence partially attenuated the association between gender and depression, especially for sexual assault (odds ratio [OR] attenuated = 1.28; 15.23%) and rape (OR attenuated = 1.32; 12.59%). There was no evidence that females were more vulnerable to the effects of violence than males. Discussion Gender differences in depression are partly explained by females higher likelihood of experiencing interpersonal violence. Reducing exposure to sexual assault and rape could therefore mitigate gender differences in depression. C1 [Dunn, Erin C.; Gilman, Stephen E.; Molnar, Beth E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, John B.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Slopen, Natalie B.] Harvard Univ, Ctr Dev Child, Cambridge, MA 02138 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02144 USA. EM erindunn@pngu.mgh.harvard.edu RI Gilman, Stephen/E-7632-2010; OI Gilman, Stephen/0000-0002-8331-6419; Willett, John/0000-0001-7183-350X FU National Institute of Mental Health [MH088074]; Maternal and Child Health Bureau [T76MC00001, T03MC07648] FX Dr. Dunn was supported by predoctoral training grants from the National Institute of Mental Health (MH088074) and the Maternal and Child Health Bureau (T76MC00001 and T03MC07648). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. We thank Amy P. Cohen for her assistance in data analysis. NR 56 TC 19 Z9 21 U1 3 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2012 VL 29 IS 5 BP 392 EP 399 DI 10.1002/da.21916 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 934JP UT WOS:000303440700004 PM 22447513 ER PT J AU Zisook, S Corruble, E Duan, NH Iglewicz, A Karam, EG Lanuoette, N Lebowitz, B Pies, R Reynolds, C Seay, K Shear, MK Simon, N Young, IT AF Zisook, Sidney Corruble, Emmanuelle Duan, Naihua Iglewicz, Alana Karam, Elie G. Lanuoette, Nicole Lebowitz, Barry Pies, Ronald Reynolds, Charles Seay, Kathryn Shear, M. Katherine Simon, Naomi Young, Ilanit Tal TI THE BEREAVEMENT EXCLUSION AND DSM-5 SO DEPRESSION AND ANXIETY LA English DT Review DE bereavement; grief; major depressive disorder; psychiatric diagnosis; nosology; DSM-5 ID ELIMINATION VS. EXPANSION; MAJOR DEPRESSIVE DISORDER; MAIN EFFECT EVEN; COMPLICATED GRIEF; DIAGNOSTIC-CRITERIA; WIDOWHOOD; VALIDITY; COMORBIDITY; PREVALENCE; EPISODE AB Background Pre-DSM-III (where DSM is Diagnostic and Statistical Manual), a series of studies demonstrated that major depressive syndromes were common after bereavement and that these syndromes often were transient, not requiring treatment. Largely on the basis of these studies, a decision was made to exclude the diagnosis of a major depressive episode (MDE) if symptoms could be better accounted for by bereavement than by MDE unless symptoms were severe and very impairing. Thus, since the publication of DSM-III in 1980, the official position of American Psychiatry has been that recent bereavement may be an exclusion criterion for the diagnosis of an MDE. This review article attempts to answer the question, Does the best available research favor continuing the bereavement exclusion (BE) in DSM-5? We have previously discussed the proposal by the DSM-5 Mood Disorders Work Group to remove the BE from DSM-5. Methods Prior reviews have evaluated the validity of the BE based on studies published through 2006. The current review adds research studies published since 2006 and critically examines arguments for and against retaining the BE in DSM-5. Results The preponderance of data suggests that bereavement-related depression is not different from MDE that presents in any other context; it is equally genetically influenced, most likely to occur in individuals with past personal and family histories of MDE, has similar personality characteristics and patterns of comorbidity, is as likely to be chronic and/or recurrent, and responds to antidepressant medications. Conclusions We conclude that the BE should not be retained in DSM-5. C1 [Zisook, Sidney; Iglewicz, Alana; Lanuoette, Nicole; Lebowitz, Barry; Young, Ilanit Tal] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA. [Zisook, Sidney; Iglewicz, Alana; Lanuoette, Nicole; Young, Ilanit Tal] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Zisook, Sidney; Iglewicz, Alana; Lanuoette, Nicole; Young, Ilanit Tal] Vet Med & Res Fdn, La Jolla, CA USA. [Corruble, Emmanuelle] Bicetre Univ Hosp, AP HP, INSERM, U669,Dept Psychiat, Paris, France. [Duan, Naihua; Lebowitz, Barry] Columbia Univ, Dept Biostat, New York, NY USA. [Duan, Naihua; Lebowitz, Barry] Columbia Univ, Dept Psychiat, New York, NY USA. [Duan, Naihua] New York State Psychiat Inst & Hosp, Div Biostat & Data Coordinat, New York, NY 10032 USA. [Karam, Elie G.] Balamand Univ, Dept Psychiat & Clin Psychol, St George Hosp, Univ Med Ctr, Beirut, Lebanon. [Karam, Elie G.] MIND, Fac Med, Beirut, Lebanon. [Karam, Elie G.] IDRAAC, Beirut, Lebanon. [Pies, Ronald] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Pies, Ronald] Tufts Univ, Sch Med, Dept Psychiat, Boston, MA 02111 USA. [Reynolds, Charles] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Reynolds, Charles] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Community & Behav Hlth Sci, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Seay, Kathryn] Univ Calif San Diego, La Jolla, CA 92093 USA. [Seay, Kathryn] San Diego State Joint Doctoral Program Clin Psych, La Jolla, CA USA. [Reynolds, Charles] Vet Med Educ & Res Fdn, La Jolla, CA USA. [Shear, M. Katherine] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Shear, M. Katherine] Columbia Univ, Sch Social Work, Complicated Grief Treatment Res Program, New York, NY USA. [Simon, Naomi] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi] Massachusetts Gen Hosp, Complicated Grief Program, Boston, MA 02114 USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,9116A, San Diego, CA 92093 USA. EM szisook@ucsd.edu FU National Institute of Mental Health [R01MH085297]; American Foundation of Suicide Prevention FX This work was supported by National Institute of Mental Health grant R01MH085297 and a grant from the American Foundation of Suicide Prevention. NR 52 TC 33 Z9 35 U1 4 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2012 VL 29 IS 5 BP 425 EP 443 DI 10.1002/da.21927 PG 19 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 934JP UT WOS:000303440700008 PM 22495967 ER PT J AU Papakostas, GH Fan, H Tedeschini, E AF Papakostas, George H. Fan, Hua Tedeschini, Enrico TI Severe and anxious depression: Combining definitions of clinical sub-types to identify patients differentially responsive to selective serotonin reuptake inhibitors SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Subtype; Depression; Anxiety; Severity; Moderator ID STAR-ASTERISK-D; POOLED ANALYSIS; MAJOR DEPRESSION; PREDICT RESPONSE; ESCITALOPRAM; DISORDER; PLACEBO; EFFICACY; METAANALYSIS; OUTPATIENTS AB Patients with severe major depressive disorder are more likely than those with mild/moderate depression to experience the relative benefits of antidepressant therapy versus placebo. Several studies have, unexpectedly, failed to show a similar antidepressant placebo discrepancy between patients with versus without anxious depression, although patients with anxious depression are more likely to meet criteria for severe depression than those without. The aim of this study was to confirm the absence of treatment moderating effects for anxious depression in a general clinical trial population, and to examine for the presence of treatment moderating effects in severe depression. Patient-level outcome data from all randomized, double-blind, placebo-controlled trials involving the use of the selective serotonin reuptake inhibitor escitalopram for adults with major depressive disorder sponsored by H. Lundbeck A/S or Forest Laboratories were pooled. Studies focusing on patients with a specific axis-I or -III co-morbidity were excluded. Data from five trials were pooled. Anxious depression was not found to serve as a treatment moderator for selective serotonin reuptake inhibitor therapy versus placebo. However, when patients with severe depression were analyzed separately, anxious depression significantly influenced the relative degree of symptom reduction with selective serotonin reuptake inhibitors versus placebo (p = 0.0094). In fact, the numbers needed to treat for remission for these two sub-types were the largest and smallest reported to date from analyses of large datasets of antidepressants (22 for severe anxious versus 4 for severe non-anxious depression). Subdividing patients with severe major depressive disorder into those with versus without anxious depression results in the characterization of sub-types that are particularly "responsive" (severe non-anxious) and "unresponsive" (severe anxious) to selective serotonin reuptake inhibitor therapy (relative to placebo). These findings are preliminary, of yet undetermined clinical relevance, and warrant replication and further exploration. (C) 2011 Elsevier B.V. and ECNP. All rights reserved. C1 [Papakostas, George H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Papakostas, George H.; Tedeschini, Enrico] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fan, Hua] H Lundbeck & Co AS, Copenhagen, Denmark. [Tedeschini, Enrico] Univ Modena & Reggio Emilia, Modena, Italy. RP Papakostas, GH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Astra Zeneca PLC; Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics FX Dr. George Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca PLC, Bristol-Myers Squibb Company, Dey Pharma Inc., Eli Lilly Co., GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Shire Pharmaceuticals, and Wyeth, Inc. Dr. Papakostas has received honoraria from Abbott Laboratories, Astra Zeneca PLC, Bristol-Myers Squibb Company, Dey Pharma, Inc., Eli Lilly Co., Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, H. Lundbeck A/s, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth Inc. Dr. Papakostas has received research support from Astra Zeneca PLC, Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). Dr. Papakostas has, in the past but not presently, served on the speaker's bureau for Bristol-Myers Squibb Co. and Pfizer, Inc. NR 32 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAY PY 2012 VL 22 IS 5 BP 347 EP 355 DI 10.1016/j.euroneuro.2011.09.009 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 935WJ UT WOS:000303552600004 PM 22099607 ER PT J AU Blanch, L Sales, B Montanya, J Lucangelo, U Garcia-Esquirol, O Villagra, A Chacon, E Estruga, A Borelli, M Burgueno, MJ Oliva, JC Fernandez, R Villar, J Kacmarek, R Murias, G AF Blanch, Lluis Sales, Bernat Montanya, Jaume Lucangelo, Umberto Garcia-Esquirol, Oscar Villagra, Ana Chacon, Encarna Estruga, Anna Borelli, Massimo Jose Burgueno, Ma Oliva, Joan C. Fernandez, Rafael Villar, Jesus Kacmarek, Robert Murias, Gaston TI Validation of the Better Care(A (R)) system to detect ineffective efforts during expiration in mechanically ventilated patients: a pilot study SO INTENSIVE CARE MEDICINE LA English DT Article DE Mechanical ventilation; Patient-ventilator dyssynchronies; Ineffective inspiratory efforts during expiration; Expiratory flow pattern; Expert clinicians analysis; Automatic algorithms ID RESPIRATORY-FAILURE; FLOW; ASYNCHRONIES AB Ineffective respiratory efforts during expiration (IEE) are a problem during mechanical ventilation (MV). The goal of this study is to validate mathematical algorithms that automatically detect IEE in a computerized (Better Care(A (R))) system that obtains and processes data from intensive care unit (ICU) ventilators in real time. The Better Care(A (R)) system, integrated with ICU health information systems, synchronizes and processes data from bedside technology. Algorithms were developed to analyze airflow waveforms during expiration to determine IEE. Data from 2,608,800 breaths from eight patients were recorded. From these breaths 1,024 were randomly selected. Five experts independently analyzed the selected breaths and classified them as IEE or not IEE. Better Care(A (R)) evaluated the same 1,024 breaths and assigned a score to each one. The IEE score cutoff point was determined based on the experts' analysis. The IEE algorithm was subsequently validated using the electrical activity of the diaphragm (EAdi) signal to analyze 9,600 breaths in eight additional patients. Optimal sensitivity and specificity were achieved by setting the cutoff point for IEE by Better Care(A (R)) at 42%. A score > 42% was classified as an IEE with 91.5% sensitivity, 91.7% specificity, 80.3% positive predictive value (PPV), 96.7% negative predictive value (NPV), and 79.7% Kappa index [confidence interval (CI) (95%) = (75.6%; 83.8%)]. Compared with the EAdi, the IEE algorithm had 65.2% sensitivity, 99.3% specificity, 90.8% PPV, 96.5% NPV, and 73.9% Kappa index [CI (95%) = (71.3%; 76.3%)]. In this pilot, Better Care(A (R)) classified breaths as IEE in close agreement with experts and the EAdi signal. C1 [Blanch, Lluis; Garcia-Esquirol, Oscar; Villagra, Ana; Chacon, Encarna; Estruga, Anna; Jose Burgueno, Ma] Univ Autonoma Barcelona, Crit Care Ctr, Hosp Sabadell, Sabadell 08208, Spain. [Blanch, Lluis; Sales, Bernat; Villagra, Ana; Fernandez, Rafael; Villar, Jesus] ISCiii, CIBER Enfermedades Respiratorias, Madrid, Spain. [Blanch, Lluis; Sales, Bernat; Montanya, Jaume; Garcia-Esquirol, Oscar; Oliva, Joan C.] Univ Autonoma Barcelona, Fundacio Parc Tauli, Sabadell 08208, Spain. [Lucangelo, Umberto; Borelli, Massimo] Univ Trieste, Dept Perioperat Med Intens Care & Emergency, Cattinara Hosp, Trieste, Italy. [Fernandez, Rafael] Manresa & Univ Internac Catalunya, Servei Med Intens, Fundacio Althaia, Barcelona, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, MODERN, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kacmarek, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Murias, Gaston] Clin Bazterr & Clin Santa Isabel, Buenos Aires, DF, Argentina. RP Blanch, L (reprint author), Univ Autonoma Barcelona, Crit Care Ctr, Hosp Sabadell, Corporacio Sanitaria Univ Parc Tauli 1, Sabadell 08208, Spain. EM lblanch@tauli.cat RI Fernandez, Rafael/A-9586-2010 OI Fernandez, Rafael/0000-0001-5711-5317 FU Fundacio Parc Tauli; Caixa Sabadell; ISCIII [PI09/91074]; CIBERes; Plan Avanza [TSI-020302-2008-38]; MCYIN; MITYC (Spain) FX This work is partially funded by: Fundacio Parc Tauli, Caixa Sabadell, ISCIII PI09/91074, CIBERes, Plan Avanza TSI-020302-2008-38, MCYIN, and MITYC (Spain). NR 23 TC 20 Z9 21 U1 0 U2 2 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 2012 VL 38 IS 5 BP 772 EP 780 DI 10.1007/s00134-012-2493-4 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 934OH UT WOS:000303453200005 PM 22297667 ER PT J AU de la Oliva, P Schuffelmann, C Gomez-Zamora, A Villar, J Kacmarek, RM AF de la Oliva, Pedro Schueffelmann, Cristina Gomez-Zamora, Ana Villar, Jesus Kacmarek, Robert M. TI Asynchrony, neural drive, ventilatory variability and COMFORT: NAVA versus pressure support in pediatric patients. A non-randomized cross-over trial SO INTENSIVE CARE MEDICINE LA English DT Article DE Pediatrics; Neurally adjusted ventilatory assist; Pressure support; Mechanical ventilation; Patient-ventilator interaction; Comfort ID ACUTE RESPIRATORY-FAILURE; MECHANICAL VENTILATION; VARIATIONAL ACTIVITY; PROPORTIONAL ASSIST; INFANTS; DISEASE; INTERCOSTAL; DIAPHRAGM; CHILDREN; DYSPNEA AB To determine if neurally adjusted ventilatory assist (NAVA) improves asynchrony, ventilatory drive, breath-to-breath variability and COMFORT score when compared to pressure support (PS). This is a non-randomized short-term cross-over trial in which 12 pediatric patients with asynchrony (auto-triggering, double triggering or non-triggered breaths) were enrolled. Four sequential 10-min periods of data were recorded after 20 min of ventilatory stabilization (wash-out) at each of the following settings: baseline PS with the ventilator settings determined by the attending physician (1-PSb); PS after optimization (2-PSopt); NAVA level set so that maximum inspiratory pressure (P (max)) equaled P (max) in PS (3-NAVA); same settings as in 2-PSopt (4-PSopt). The median asynchrony index was significantly lower during NAVA (2.0 %) than during 2-PSopt (8.5 %, p = 0.017) and 4-PSopt (7.5 %, p = 0.008). In NAVA mode, the NAVA trigger accounted on average for 66 % of triggered breaths. The median trigger delay with respect to neural inspiratory time was significantly lower during NAVA (8.6 %) than during 2-PSopt (25.2 %, p = 0.003) and 4-PSopt (28.2 %, p = 0.0005). The median electrical activity of the diaphragm (EAdi) change during trigger delay normalized to maximum inspiratory EAdi difference was significantly lower during NAVA (5.3 %) than during 2-PSopt (21.7 %, p = 0.0005) and 4-PSopt (24.6 %, p = 0.001). The coefficient of variation of tidal volume was significantly higher during NAVA (44.2 %) than during 2-PSopt (19.8 %, p = 0.0002) and 4-PSopt (23.0 %, p = 0.0005). The median COMFORT score during NAVA (15.0) was lower than that during 2-PSopt (18.0, p = 0.0125) and 4-PSopt (17.5, p = 0.039). No significant changes for any variable were observed between 1-PSb and 2-PSopt. Neurally adjusted ventilatory assist as compared to optimized PS results in improved synchrony, reduced ventilatory drive, increased breath-to-breath mechanical variability and improved patient comfort. C1 [de la Oliva, Pedro; Schueffelmann, Cristina; Gomez-Zamora, Ana] Hosp Univ Materno Infantil, Pediat Intens Care Unit UCIP, Madrid 28046, Spain. [de la Oliva, Pedro] Univ Autonoma Madrid, Dept Paediat, Madrid, Spain. [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP de la Oliva, P (reprint author), Hosp Univ Materno Infantil, Pediat Intens Care Unit UCIP, Paseo de la Castellana 261, Madrid 28046, Spain. EM poliva.hulp@salud.madrid.org FU Maquet Critical Care AB (Solna, Sweden); Hospital Universitario La Paz (Madrid, Spain) FX This study was performed at the Pediatric ICU of the Hospital Universitario Materno-Infantil La Paz. Madrid. Spain. The study was supported, in part, by Maquet Critical Care AB (Solna, Sweden) and by the Hospital Universitario La Paz (Madrid, Spain). NR 31 TC 36 Z9 36 U1 0 U2 11 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 2012 VL 38 IS 5 BP 838 EP 846 DI 10.1007/s00134-012-2535-y PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 934OH UT WOS:000303453200013 PM 22481227 ER PT J AU Shaw, JA Herzog, DB Clark, VL Berner, LA Eddy, KT Franko, DL Lowe, MR AF Shaw, Jena A. Herzog, David B. Clark, Vicki L. Berner, Laura A. Eddy, Kamryn T. Franko, Debra L. Lowe, Michael R. TI Elevated pre-morbid weights in bulimic individuals are usually surpassed post-morbidly: Implications for perpetuation of the disorder SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE bulimia nervosa; weight gain; weight suppression ID EATING ATTITUDES TEST; ANOREXIA-NERVOSA; FOLLOW-UP; DIETARY RESTRAINT; BODY-IMAGE; SUPPRESSION; VALIDITY; GAIN; VALIDATION; SCHEDULE AB Objective: To determine how often patients diagnosed with bulimia nervosa (BN) surpass their highest pre-morbid weight during the course of their disorder. Method: The weight histories of individuals with BN were determined using retrospective weight data (Study 1) and combined retrospective/prospective data (Study 2). Results: Retrospective analyses indicated that 59.0% (n = 46) and 61.8% (n 5 110), respectively, reported that their highest weight was reached after developing BN. In Study 2, 35.3% of participants superseded their highest pre-enrollment weights during 8 years of follow-up, and 71.6% reached a post-morbid highest weight before remission. Across studies, the primary difference between patients who did and did not reach their highest weight post-morbidly was that those who did had an earlier age of onset and longer duration of BN. Discussion: Findings are discussed in terms of possible links between BN and weight-gain proneness, weight fluctuation across the course of BN, and implications for treating BN. (C) 2012 by Wiley Periodicals, Inc. C1 [Shaw, Jena A.; Clark, Vicki L.; Berner, Laura A.; Lowe, Michael R.] Drexel Univ, Dept Psychol, Philadelphia, PA 19102 USA. [Herzog, David B.; Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Franko, Debra L.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. RP Lowe, MR (reprint author), Drexel Univ, Dept Psychol, MS 626,245 N 15th St, Philadelphia, PA 19102 USA. EM lowe@drexel.edu OI Shaw, Jena/0000-0003-3587-4130 FU National Institute of Mental Health [R34 MH 071691, 5R01 MH 38333 05] FX Supported by grants R34 MH 071691 (M.R.L.) and 5R01 MH 38333 05 (D.B.H.) from National Institute of Mental Health. NR 42 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2012 VL 45 IS 4 BP 512 EP 523 DI 10.1002/eat.20985 PG 12 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 922KT UT WOS:000302546500005 PM 22271593 ER PT J AU Tsai, CL Lee, WY Hanania, NA Camargo, CA AF Tsai, Chu-Lin Lee, Wen-Ya Hanania, Nicola A. Camargo, Carlos A., Jr. TI Age-related differences in clinical outcomes for acute asthma in the United States, 2006-2008 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Acute asthma; age; emergency department; outcomes ID OLDER-ADULTS; EMERGENCY-DEPARTMENT; PROSPECTIVE MULTICENTER; HOSPITAL ADMISSION; SEX-DIFFERENCES; EXACERBATIONS; EPIDEMIOLOGY; MEDICATIONS; POPULATION; GUIDELINES AB Background: Little is known about the effect of age on acute asthma outcomes. Objective: We sought to investigate age-related differences in the emergency department (ED) presentation and clinical outcomes for patients with acute asthma. Methods: We analyzed the 2006-2008 Nationwide Emergency Department Sample, the largest, all-payer, US ED and inpatient database. ED visits for acute asthma were identified with a principal diagnosis of International Classification of Disease, ninth revision, Clinical Modification code 493.xx. Patients were divided into 3 age groups: children (<18 years), younger adults (18-54 years), and older adults (>= 55 years). The outcome measures were in-hospital all-cause mortality, near-fatal asthma-related events (noninvasive or mechanical ventilation), hospital charges, admission rates, and hospital length of stay. Results: There were an estimated 1,813,000 visits annually for acute asthma from approximately 4,700 EDs. The estimated overall annual number of in-hospital asthma-related deaths was 1,144 (0.06%); 101 died in the ED, and 1,043 died as inpatients. By age group, there were 37 asthma-related deaths per year in children, 204 in younger adults, and 903 in older adults. Compared with younger adults, older adults had higher mortality, had higher rates of near-fatal asthma-related events, had higher hospital charges, were more likely to be hospitalized, and had a longer hospital length of stay (P < .001 for all). After adjusting for comorbidities, older asthmatic patients had a 5-fold increased risk of overall mortality (adjusted odds ratio, 5.2; 95% CI, 4.0-6.9), compared with younger adults. Conclusions: Older adults with acute asthma have a substantial burden of morbidity and mortality. With the US population aging, there is an urgent need for targeted interventions for this high-risk population. (J Allergy Clin Immunol 2012;129:1252-8.) C1 [Tsai, Chu-Lin; Lee, Wen-Ya] Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Hanania, Nicola A.] Baylor Coll Med, Dept Med, Sect Pulm & Crit Care Med, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Tsai, CL (reprint author), Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, 1200 Herman Pressler,Suite W610, Houston, TX 77030 USA. EM cltsai@post.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality [R03HS020722]; GlaxoSmithKline; Sanofi-Aventis FX Supported by grant no. R03HS020722 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.; Disclosure of potential conflict of interest: C. A. Camargo, Jr, is a consultant for Dey, Genentech, Merck, Novartis, and Pfizer and has received research support from GlaxoSmithKline and Sanofi-Aventis. The rest of the authors declare that they have no relevant conflicts of interest. NR 51 TC 45 Z9 45 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2012 VL 129 IS 5 BP 1252 EP U363 DI 10.1016/j.jaci.2012.01.061 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 934CG UT WOS:000303418000011 PM 22385630 ER PT J AU Yagil, Z Erlich, TH Ofir-Birin, Y Tshori, S Kay, G Yekhtin, Z Fisher, DE Cheng, C Wong, WSF Hartmann, K Razin, E Nechushtan, H AF Yagil, Zohar Erlich, Tal Hadad Ofir-Birin, Yifat Tshori, Sagi Kay, Gillian Yekhtin, Zanna Fisher, David E. Cheng, Chang Wong, W. S. Fred Hartmann, Karin Razin, Ehud Nechushtan, Hovav TI Transcription factor E3, a major regulator of mast cell-mediated allergic response SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; mast cells; degranulation; histamine; cytokine secretion; transcription factor E3 knockout mice ID MOUSE MICROPHTHALMIA LOCUS; MUTANT MICE; OSTEOCLAST DEVELOPMENT; FACTOR FAMILY; KIT-LIGAND; TFE3; MITF; EXPRESSION; ACTIVATOR; PROTEIN AB Background: Microphthalmia transcription factor, an MiT transcription family member closely related to transcription factor E3 (TFE3), is essential for mast cell development and survival. TFE3 was previously reported to play a role in the functions of B and T cells; however, its role in mast cells has not yet been explored. Objective: We sought to explore the role played by TFE3 in mast cell function. Methods: Mast cell numbers were evaluated by using toluidine blue staining. FACS analysis was used to determine percentages of Kit and Fc epsilon RI double-positive cells in the peritoneum of wildtype (WT) and TFE3 knockout (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In vivo plasma histamine levels were measured after immunologic triggering of these mice. Results: No significant differences in mast cell numbers between WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However, TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and Fc epsilon RI+ peritoneal and cultured mast cells. Surface expression levels of FceRI in TFE3(-/-) peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3-/- mice showed a marked decrease in degranulation and mediator secretion. In vivo experiments showed that the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was substantially less than that seen in WT mice. Conclusion: TFE3 is a novel regulator of mast cell functions and as such could emerge as a new target for the manipulation of allergic diseases. (J Allergy Clin Immunol 2012;129:1357-66.) C1 [Yagil, Zohar; Erlich, Tal Hadad; Ofir-Birin, Yifat; Kay, Gillian; Razin, Ehud] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem & Mol Biol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel. [Tshori, Sagi] Hadassah Hebrew Univ, Dept Nucl Med, Med Ctr, Jerusalem, Israel. [Yekhtin, Zanna] Hadassah Hebrew Univ, Dept Bone Marrow Transplantat & Canc Immunotherap, Med Ctr, Jerusalem, Israel. [Nechushtan, Hovav] Hadassah Hebrew Univ, Dept Oncol, Med Ctr, Jerusalem, Israel. [Fisher, David E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheng, Chang; Wong, W. S. Fred] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Natl Univ Hlth Syst, Singapore 117595, Singapore. [Wong, W. S. Fred] Natl Univ Singapore, Program Immunol, Inst Life Sci, Singapore 117548, Singapore. [Hartmann, Karin] Univ Cologne, Dept Dermatol, Cologne, Germany. RP Razin, E (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem & Mol Biol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel. EM ehudr@ekmd.huji.ac.il RI Wong, W.S. Fred/D-8205-2013; Hartmann, Karin/N-4865-2015; Kay, Gillian/F-3474-2014; OI Hartmann, Karin/0000-0002-4595-8226; Kay, Gillian/0000-0003-0966-2388; Erlich, Tal/0000-0003-0601-2574 FU United States Binational Science Foundation; Israeli Academy of Science; Deutsches Krebsforschungszentrum (DKFZ); Israel's Ministry of Science and Technology (MOST); German-Israeli Foundation for Scientific Research and Development; National Research Foundation of Singapore (HUJ-CREATE); Morasha Foundation; Canadian Friends of Hebrew University; Binational Science Foundation; Israel Science Foundation FX Supported by the United States Binational Science Foundation (E.R. and D.E.F.), the Israeli Academy of Science (E.R.), the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Science and Technology (MOST) (E.R.), the German-Israeli Foundation for Scientific Research and Development (K.H. and E.R.), the National Research Foundation of Singapore (HUJ-CREATE; E.R.), and the Morasha Foundation Fund (H.N.). Z.Y. was supported by the Canadian Friends of Hebrew University.; Z. Yagil, T. Hadad Erlich, Y. Ofir-Birin, and E. Razin receive research support from the Binational Science Foundation, the German-Israeli Foundation for Scientific Research and Development, and the Israel Science Foundation. K. Hartmann has consultant arrangements with Novartis Pharma, ALK-Abello, and Shire and receives research support from the German-Israeli Foundation for Scientific Research and Development. H. Nechushtan receives research support from the Israel Science Foundation. The rest of the authors declare that they have no relevant conflicts of interest. NR 35 TC 10 Z9 10 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2012 VL 129 IS 5 BP 1357 EP U249 DI 10.1016/j.jaci.2011.11.051 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA 934CG UT WOS:000303418000027 PM 22360977 ER PT J AU Winkler, T Venegas, JG AF Winkler, Tilo Venegas, Jose G. TI Are all airways equal? SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID HYPERPOLARIZED HE-3 MRI; VENTILATION; ASTHMA; PERFUSION; CT C1 [Winkler, Tilo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM twinkler@vqpet.mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [R01 HL087281] NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 2012 VL 112 IS 9 BP 1431 EP 1432 DI 10.1152/japplphysiol.00253.2012 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 937MY UT WOS:000303663800003 PM 22383504 ER PT J AU Kelly, VJ Brown, NJ Sands, SA Borg, BM King, GG Thompson, BR AF Kelly, Vanessa J. Brown, Nathan J. Sands, Scott A. Borg, Brigitte M. King, Gregory G. Thompson, Bruce R. TI Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE conductance; reactance; airway closure; airway heterogeneity; airway remodeling ID ALVEOLAR SURFACE-TENSION; HYPERPOLARIZED HE-3 MRI; LUNG-TISSUE MECHANICS; DEEP INSPIRATIONS; ASYMPTOMATIC ASTHMA; RESPIRATORY SYSTEM; HEALTHY-SUBJECTS; TIDAL STRETCHES; IN-VITRO; RESISTANCE AB Kelly VJ, Brown NJ, Sands SA, Borg BM, King GG, Thompson BR. Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma. J Appl Physiol 112: 1494-1503, 2012. First published February 23, 2012; doi:10.1152/japplphysiol.01259.2011.-Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity. C1 [Kelly, Vanessa J.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kelly, Vanessa J.; Sands, Scott A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kelly, Vanessa J.; Thompson, Bruce R.] Monash Univ, Dept Med Nursing & Hlth Sci, Clayton, Vic, Australia. [Kelly, Vanessa J.; Brown, Nathan J.; King, Gregory G.; Thompson, Bruce R.] Cooperat Res Ctr Asthma & Airways, Glebe, NSW, Australia. [Kelly, Vanessa J.; Brown, Nathan J.; King, Gregory G.; Thompson, Bruce R.] Woolcock Inst Med Res, Glebe, NSW, Australia. [Kelly, Vanessa J.; Borg, Brigitte M.; Thompson, Bruce R.] Alfred Hosp, Dept Allergy Immunol & Resp Med, Prahran, Vic 3181, Australia. [Sands, Scott A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. RP Kelly, VJ (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St,Thier 4-429, Boston, MA 02114 USA. EM vjkelly@partners.org RI Brown, Nathan/H-4317-2011; OI Brown, Nathan/0000-0001-7149-8895; Thompson, Bruce/0000-0002-5885-0652 FU National Health and Medical Research Council of Australia [521808, 486101, 491103]; Cooperative Research Centre for Asthma and Airways; American Australian Association; Boehringer Ingelheim; Pfizer; AstraZeneca; GlaxoSmithKline FX V. J. Kelly was supported by National Health and Medical Research Council of Australia Grant 521808 and research grants from the Cooperative Research Centre for Asthma and Airways and the American Australian Association. B. R. Thompson also received financial support through National Health and Medical Research Council of Australia Grants 486101 and 491103.; V. J. Kelly, N. J. Brown, S. A. Sands, B. M. Borg, and B. R. Thompson have no conflicts of interest to disclose. G. G. King has received various travel sponsorships from Boehringer Ingelheim, Pfizer, AstraZeneca, and GlaxoSmithKline. The authors' affiliation, the Woolcock Institute of Medical Research, receives unrestricted grants from Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline and has current and past consultancy agreements with Pfizer, Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. NR 50 TC 18 Z9 19 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 2012 VL 112 IS 9 BP 1494 EP 1503 DI 10.1152/japplphysiol.01259.2011 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 937MY UT WOS:000303663800012 PM 22362406 ER PT J AU Ritt, LE Oliveira, RB Myers, J Arena, R Peberdy, MA Bensimhon, D Chase, P Forman, D Guazzi, M AF Ritt, Luiz Eduardo Oliveira, Ricardo Brandao Myers, Jonathan Arena, Ross Peberdy, Mary Ann Bensimhon, Daniel Chase, Paul Forman, Daniel Guazzi, Marco TI Patients With Heart Failure in the "Intermediate Range" of Peak Oxygen Uptake SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Article DE cardiopulmonary exercise test; heart failure; mortality ID RATE RECOVERY; VENTILATORY RESPONSE; AMBULATORY PATIENTS; EXERCISE; PROGNOSIS; MORTALITY; TRANSPLANTATION; RECOMMENDATIONS; VALIDATION; EFFICIENCY AB PURPOSE: While patients with heart failure who achieve a peak oxygen uptake (peak (V) over dotO(2)) of 10 mL.kg(-1).min(-1) or less are often considered for intensive surveillance or intervention, those achieving 14 mL.kg(-1).min(-1) or more are generally considered to be at lower risk. Among patients in the "intermediate" range of 10.1 to 13.9 mL.kg(-1).min(-1), optimally stratifying risk remains a challenge. METHODS: Patients with heart failure (N = 1167) referred for cardiopulmonary exercise testing were observed for 21 +/- 13 months. Patients were classified into 3 groups of peak (V) over dotO(2) (<= 10, 10.1-13.9, and >= 14 mL.kg(-1).min(-1)). The ability of heart rate recovery at 1 minute (HRR1) and the minute ventilation/carbon dioxide output ((V) over dotE/(V) over dotCO(2)) slope to complement peak (V) over dotO(2) in predicting cardiovascular mortality were determined. RESULTS: Peak (V) over dotO(2), HRR1 (<16 beats per minute), and the (V) over dotE/(V) over dotCO(2) slope (> 34) were independent predictors of mortality (hazard ratio 1.6, 95% CI: 1.2-2.29, P = .006; hazard ratio 1.7, 95% CI: 1.1-2.5, P = .008; and hazard ratio 2.4, 95% CI: 1.6-3.4, P < .001, respectively). Compared with those achieving a peak (V) over dotO(2) >= 14 mL.kg(-1).min(-1), patients within the intermediate range with either an abnormal (V) over dotE/(V) over dotCO(2) slope or HRR1 had a nearly 2-fold higher risk of cardiac mortality. Those with both an abnormal HRR1 and (V) over dotE/(V) over dotCO(2) slope had a higher mortality risk than those with a peak (V) over dotO(2) <= 10 mL.kg(-1).min(-1). Survival was not different between those with a peak (V) over dotO(2) <= 10 mL.kg(-1).min(-1) and those in the intermediate range with either an abnormal HRR1 or (V) over dotE/(V) over dotCO(2) slope. CONCLUSIONS: HRR1 and the (V) over dotE/(V) over dotO(2) slope effectively stratify patients with peak (V) over dotO(2) within the intermediate range into distinct groups at high and low risk. C1 [Ritt, Luiz Eduardo] Hosp Santa Izabel, Salvador, BA, Brazil. [Ritt, Luiz Eduardo] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Oliveira, Ricardo Brandao] Univ Estado Rio De Janeiro, Rio De Janeiro, Brazil. [Myers, Jonathan] Stanford Univ, VA Palo Alto Hlth Care Syst, Div Cardiol, Palo Alto, CA 94304 USA. [Arena, Ross] Univ New Mexico, Div Cardiol, Dept Internal Med, Albuquerque, NM 87131 USA. [Arena, Ross] Univ New Mexico, Phys Therapy Program, Dept Orthopaed, Albuquerque, NM 87131 USA. [Peberdy, Mary Ann] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. [Bensimhon, Daniel; Chase, Paul] LeBauer Cardiovasc Res Fdn, Greensboro, NC USA. [Forman, Daniel] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Forman, Daniel] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Guazzi, Marco] Univ Milan, San Paolo Hosp, Div Cardiol, Milan, Italy. RP Myers, J (reprint author), VA Palo Alto Hlth Care Syst, Cardiol Div 111C, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM drj993@aol.com RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 33 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-7501 J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD MAY-JUN PY 2012 VL 32 IS 3 BP 141 EP 146 DI 10.1097/HCR.0b013e31824f9ddf PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 937OR UT WOS:000303668300004 PM 22487616 ER PT J AU Simao, F Pagnussat, AS Seo, JH Nayaratna, D Leung, W Lok, J Guo, SZ Waeber, C Salbego, CG Lo, EH AF Simao, Fabricio Pagnussat, Aline S. Seo, Ji Hae Nayaratna, Deepti Leung, Wendy Lok, Josephine Guo, Shuzhen Waeber, Christian Salbego, Christianne G. Lo, Eng H. TI Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE angiogenesis; endothelium; eNOS; MMPs; resveratrol; VEGF ID RAT-BRAIN; STROKE; BLOOD; NEUROGENESIS; SYNTHASE; EXPRESSION; POLYPHENOLS; MIGRATION; RECOVERY; PATHWAY AB Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of beta-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 884-895; doi:10.1038/jcbfm.2012.2; published online 8 February 2012 C1 [Simao, Fabricio; Seo, Ji Hae; Nayaratna, Deepti; Leung, Wendy; Lok, Josephine; Guo, Shuzhen; Salbego, Christianne G.; Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Simao, Fabricio; Seo, Ji Hae; Nayaratna, Deepti; Leung, Wendy; Lok, Josephine; Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Simao, Fabricio; Salbego, Christianne G.] Univ Fed Rio Grande do Sul, Dept Bioquim, Inst Ciencias Basicas Saude, Porto Alegre, RS, Brazil. [Pagnussat, Aline S.] Univ Fed Pampa UNIPAMPA, Dept Fisioterapia, Uruguaiana, RS, Brazil. [Lok, Josephine] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Charlestown, MA 02115 USA. [Waeber, Christian] Harvard Univ, Sch Med, Dept Neurol, Stroke & Neurovasc Regulat Lab,Massachusetts Gen, Charlestown, MA 02115 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu RI simao, fabricio/A-4621-2013; Salbego, Christianne/C-5247-2013; Waeber, Christian/A-8333-2009; Pagnussat, Aline/N-9335-2015 OI simao, fabricio/0000-0002-6229-7618; Waeber, Christian/0000-0001-6078-0027; Pagnussat, Aline/0000-0001-7837-5855 FU National Institutes of Health; Conselho Nacional de Desenvolvimento e Pesquisa (CNPq) FX This work was supported in part by Grants from the National Institutes of Health and a fellowship from Conselho Nacional de Desenvolvimento e Pesquisa (CNPq). NR 35 TC 32 Z9 35 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2012 VL 32 IS 5 BP 884 EP 895 DI 10.1038/jcbfm.2012.2 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 936YM UT WOS:000303625900013 PM 22314268 ER PT J AU Shetty, RD Velu, V Titanji, K Bosinger, SE Freeman, GJ Silvestri, G Amara, RR AF Shetty, Ravi Dyavar Velu, Vijayakumar Titanji, Kehmia Bosinger, Steven E. Freeman, Gordon J. Silvestri, Guido Amara, Rama Rao TI PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CD8 T-CELLS; IMMUNE ACTIVATION; TIGHT JUNCTIONS; HIV-INFECTION; EXPRESSION; VACCINATION; CLAUDIN-5; DISEASE AB Hyperimmune activation is a strong predictor of disease progression during pathogenic immunodeficiency virus infections and is mediated in part by sustained type I IFN signaling in response to adventitious microbial infection. The immune inhibitory receptor programmed death-1 (PD-1) regulates functional exhaustion of virus-specific CD8(+) T cells during chronic infections, and in vivo PD-1 blockade has been shown to improve viral control of SIV. Here, we show that PD-1 blockade during chronic SW infection markedly reduced the expression of transcripts associated with type I IFN signaling in the blood and colorectal tissue of rhesus macaques (RMs). The effect of PD-1 blockade on type I IFN signaling was durable and persisted even under conditions of high viremia. Reduced type I IFN signaling was associated with enhanced expression of some of the junction-associated genes in colorectal tissue and with a profound decrease in plasma LPS levels, suggesting a possible repair of gut-associated junctions and decreased microbial translocation into the blood. PD-1 blockade enhanced immunity to gut-resident pathogenic bacteria, control of gut-associated opportunistic infections, and survival of SIV-infected RMs. Our results suggest PD-1 blockade as a potential novel therapeutic approach to enhance combination antiretroviral therapy by suppressing hyperimmune activation in HIV-infected individuals. C1 [Shetty, Ravi Dyavar; Velu, Vijayakumar; Titanji, Kehmia; Bosinger, Steven E.; Silvestri, Guido; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Silvestri, Guido] Emory Univ, Dept Pathol, Atlanta, GA 30329 USA. [Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30329 USA. RP Amara, RR (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM ramara@emory.edu RI DYAVAR, SHETTY RAVI/I-4541-2013; OI DYAVAR, SHETTY RAVI/0000-0002-3611-8057; Velu, Vijayakumar/0000-0003-4238-1924 NR 22 TC 47 Z9 47 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 2012 VL 122 IS 5 BP 1712 EP 1716 DI 10.1172/JCI60612 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 935BG UT WOS:000303491400020 ER PT J AU Conkrite, K Sundby, M Mu, D Mukai, S MacPherson, D AF Conkrite, Karina Sundby, Maggie Mu, David Mukai, Shizuo MacPherson, David TI Cooperation between Rb and Art in suppressing mouse retinoblastoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR SUPPRESSION; P53 PATHWAY; IN-VIVO; GENE; MUTATIONS; PROGRESSION; EXPRESSION; MODELS; CANCER; CELLS AB Retinoblastoma is a pediatric cancer that has served as a paradigm for tumor suppressor gene function. Retinoblastoma is initiated by RB gene mutations, but the subsequent cooperating mutational events leading to tumorigenesis are poorly characterized. We investigated what these additional genomic alterations might be using human retinoblastoma samples and mouse models. Array-based comparative genomic hybridization studies revealed deletions in the CDKN2A locus that include ARF and P16INK4A, both of which encode tumor suppressor proteins, in both human and mouse retinoblastoma. Through mouse genetic analyses, we found that Arfwas the critical tumor suppressor gene in the deleted region. In mice, inactivation of one allele of Arf cooperated with Rh and p107 loss to rapidly accelerate retinoblastoma, with frequent loss of heterozygosity (LOH) at the Arf locus. Arf has been reported to exhibit p53-independent tumor suppressor roles in other systems; however, our results showed no additive effect of p53 and Arf coinactivation in promoting retinoblastoma. Moreover, p53 inactivation completely eliminated any selection for ArfLOH. Thus, our data reveal important insights into the p53 pathway in retinoblastoma and show that Arf is a key collaborator with Rb in retinoblastoma suppression. C1 [Conkrite, Karina; Sundby, Maggie; MacPherson, David] Carnegie Inst, Dept Embryol, Baltimore, MD 21218 USA. [Mu, David] Penn State Univ, Coll Med, Dept Pathol, Hershey, PA USA. [Mu, David] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA USA. [Mukai, Shizuo] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP MacPherson, D (reprint author), Carnegie Inst, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA. EM macpherson@ciwemb.edu RI Mu, David/E-8933-2011 OI Mu, David/0000-0002-7762-0182 FU NCI/NIH [R015R01CA148867]; Mukai Fund FX The authors thank Tyler Jacks, Charles Sherr, Anton Berns, Ron Depinho, and Peter Gruss for providing valuable mouse strains used in these studies. The laboratory of D. MacPherson is supported by grant R015R01CA148867 from the NCI/NIH. S. Mukai received support from the Mukai Fund. NR 34 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2012 VL 122 IS 5 BP 1726 EP 1733 DI 10.1172/JCI61403 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 935BG UT WOS:000303491400022 PM 22484813 ER PT J AU Greenstein, RJ Cameron, DW Brown, ST AF Greenstein, Robert J. Cameron, D. William Brown, Sheldon T. TI On the zoonosis of M. avium subspecies paratuberculosis (MAP) SO JOURNAL OF CROHNS & COLITIS LA English DT Letter ID CROHNS-DISEASE C1 [Greenstein, Robert J.] James J Peters VAMC, Dept Surg, Bronx, NY USA. [Cameron, D. William] Ottawa Hosp, Res Inst, Univ Ottawa, Div Infect Dis, Ottawa, ON, Canada. RP Greenstein, RJ (reprint author), James J Peters VAMC, Dept Surg, Bronx, NY USA. EM BGAxis@aol.com OI Cameron, Bill/0000-0002-0090-3539 NR 6 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 J9 J CROHNS COLITIS JI J. Crohns Colitis PD MAY PY 2012 VL 6 IS 4 BP 504 EP 504 DI 10.1016/j.crohns.2012.01.006 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 937DM UT WOS:000303639200016 PM 22398086 ER PT J AU Raitt, MH Kusumoto, W AF Raitt, Merritt H. Kusumoto, Walter TI Correlations among the frequencies of atrial activity on the surface electrocardiogram, intracardiac atrial electrograms, and the atrial effective refractory period in patients with atrial fibrillation SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article ID CYCLE LENGTH; PROCAINAMIDE; TERMINATION; IBUTILIDE AB Background: The frequency of surface atrial electrocardiogram (ECG) depolarization has been postulated to reflect the atrial effective refractory period (AERP). Methods: Frequency analysis of surface ECGs after QRST subtraction and of electrograms from 4 right atrium and 4 coronary sinus electrode pairs was performed in 38 patients in atrial fibrillation. The AERP was measured in the right atrium and coronary sinus 10 minutes after cardioversion. Results: The correlation between the dominant frequencies of intracardiac electrograms and atrial activity in leads I, II, and V-1 were 0.89, 0.85, and 0.88, respectively (all P < .001). The correlation between the average AERP and the frequency of atrial activity in the surface leads was 0.50, 0.45, and 0.47 (all P < .005). Conclusion: In atrial fibrillation, the frequency of atrial depolarization measured from the surface ECG is highly correlated with intracardiac atrial frequency. However, the correlation between the frequency of surface atrial activity and atrial refractoriness, although significant, is not strong. Published by Elsevier Inc. C1 [Raitt, Merritt H.] Portland VA Med Ctr, Portland, OR 97239 USA. [Raitt, Merritt H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kusumoto, Walter] Arrhythmia Ctr No Calif, Chico, CA USA. RP Raitt, MH (reprint author), Portland VA Med Ctr, P-3 CARD, Portland, OR 97239 USA. EM merritt.raitt@va.gov FU Department of Veterans Affairs FX Supported by the Department of Veterans Affairs Merit Review Entry Program. NR 16 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2012 VL 45 IS 3 BP 296 EP 303 DI 10.1016/j.jlectrocard.2011.12.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 935VF UT WOS:000303549600025 PM 22280798 ER PT J AU Mason, MF Bar, M AF Mason, Malia F. Bar, Moshe TI The Effect of Mental Progression on Mood SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article DE fluency; mood; affect; goals; attention ID RUMINATIVE RESPONSE STYLE; POSITIVE AFFECT; NEUROTICISM; DURATION; EPISODES AB Mood affects the way people think. But can the way people think affect their mood? In the present investigation, we examined this promising link by testing whether mood is influenced by the presence or absence of associative progression by manipulating the scope of participants' information processing and measuring their subsequent mood. In agreement with our hypothesis, processing that involved associative progression was associated with relatively better moods than processing that was restricted to a single topic (Experiment 1). Experiment 2 ruled out the possibility that conceptual plurality alone accounted for these mood differences; results converge with the view that mood is affected by the degree to which thoughts advance conceptually. C1 [Mason, Malia F.] Columbia Univ, Columbia Business Sch, Management Div, New York, NY 10027 USA. [Bar, Moshe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Charlestown, MA 02129 USA. RP Mason, MF (reprint author), Columbia Univ, Columbia Business Sch, Management Div, 3022 Broadway,Uris Hall,Room 720, New York, NY 10027 USA. EM maliamason@columbia.edu; bar@nmr.mgh.harvard.edu FU NIMH NIH HHS [R01 MH084940-01A2, R01 MH084940, R01MH084940]; NINDS NIH HHS [R01 NS050615, R01 NS050615-01, R01NS50615] NR 29 TC 8 Z9 8 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-3445 J9 J EXP PSYCHOL GEN JI J. Exp. Psychol.-Gen. PD MAY PY 2012 VL 141 IS 2 BP 217 EP 221 DI 10.1037/a0025035 PG 5 WC Psychology, Experimental SC Psychology GA 936YL UT WOS:000303625800004 PM 21823806 ER PT J AU Strehlow, AJ Robertson, MJ Zerger, S Rongey, C Arangua, L Farrell, E O'Sullivan, A Gelberg, L AF Strehlow, Aaron J. Robertson, Marjorie J. Zerger, Suzanne Rongey, Catherine Arangua, Lisa Farrell, Ed O'Sullivan, Adele Gelberg, Lillian TI Hepatitis C among Clients of Health Care for the Homeless Primary Care Clinics SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Homeless; hepatitis C; Health Care for the Homeless; tattoos; injection drug use; prison; risk factors; primary care clinics; blood borne disease; infectious disease; sexual risk ID VIRUS-INFECTION; UNITED-STATES; SAN-FRANCISCO; PREVALENCE; MANAGEMENT; RISK; POPULATION; PRISONS; ADULTS; SEROPREVALENCE AB Objectives. To describe the prevalence, distribution and risk factors for hepatitis C virus (HCV) infection among homeless adults using eight Health Care for the Homeless (HCH) clinics nationally. Methods. Data were collected for 387 participants through blood draws, structured interviews, chart reviews. Results. Overall prevalence of HCV-antibody positivity was 31.0%, including 70.0% among injection drug users and 15.5% among reported non-injectors. Much HCV infection was hidden as the majority (53.3%) of HCV-antibody positive participants was unaware of their status. Independent risk factors for HCV among the total sample included injection drug use, prison, and tattoos; among injectors, risk factors included prison and three or more years of injection drug use; among reported non-injectors, risk factors included tattoos and prison. Conclusion. These HCH clinics serve high concentrations of HCV-infected injectors, making these and similar clinics priority intervention sites for aggressive screening, education, testing, and treatment for HCV and other blood-borne diseases. C1 [Rongey, Catherine] San Francisco VA Med Ctr, San Francisco, CA USA. [Rongey, Catherine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Arangua, Lisa] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Farrell, Ed] Clin Family Hlth Serv, Thornton, CO USA. [O'Sullivan, Adele] Circle City, Phoenix, AZ USA. [Gelberg, Lillian] UCLA David Geffen Sch Med, Los Angeles, CA USA. RP Strehlow, AJ (reprint author), 1228 N La Cienega Blvd 102, W Hollywood, CA 90069 USA. EM astrehlo@ucla.edu FU NIDA NIH HHS [R01 DA014294, R01-DA14294,] NR 45 TC 14 Z9 14 U1 0 U2 6 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2012 VL 23 IS 2 BP 811 EP 833 PG 23 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 934EY UT WOS:000303427600027 PM 22643626 ER PT J AU Jenkins, MK Moon, JJ AF Jenkins, Marc K. Moon, James J. TI The Role of Naive T Cell Precursor Frequency and Recruitment in Dictating Immune Response Magnitude SO JOURNAL OF IMMUNOLOGY LA English DT Review ID EX-VIVO ANALYSIS; MHC CLASS-I; REPERTOIRE DIVERSITY; THYMIC SELECTION; INFLUENZA-VIRUS; ANTIGEN; PEPTIDE; EPITOPE; INFECTION; MICE AB Recent advances in technology have led to the realization that the populations of naive T cells specific for different foreign peptide:MHC (p:MHC) ligands vary in size. This variability is due, in part, to the fact that certain peptides contain amino acids that engage in particularly favorable interactions with TCRs. In addition, deletion of clones with cross-reactivity for self-p:MHC ligands may reduce the size of some naive populations. In many cases, the magnitude of the immune response to individual p:MHC epitopes correlates with the size of the corresponding naive populations. However, this simple relationship may be complicated by variability in the efficiency of T cell recruitment into the immune response. The knowledge that naive population size can predict immune response magnitude may create opportunities for production of more effective subunit vaccines. The Journal of Immunology, 2012, 188: 4135-4140. C1 [Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. RP Jenkins, MK (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, 2101 6th St SE,Campus Code 2641, Minneapolis, MN 55455 USA. EM jenki002@umn.edu RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 FU National Institutes of Health [AI027998, AI039614] FX This work was supported in part by National Institutes of Health Grants AI027998 and AI039614. NR 57 TC 100 Z9 100 U1 1 U2 11 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 2012 VL 188 IS 9 BP 4135 EP 4140 DI 10.4049/jimmunol.1102661 PG 6 WC Immunology SC Immunology GA 932OH UT WOS:000303299900003 PM 22517866 ER PT J AU Oh, SF Dona, M Fredman, G Krishnamoorthy, S Irimia, D Serhan, CN AF Oh, Sungwhan F. Dona, Maria Fredman, Gabrielle Krishnamoorthy, Sriram Irimia, Daniel Serhan, Charles N. TI Resolvin E2 Formation and Impact in Inflammation Resolution SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIINFLAMMATORY ACTIONS; PRORESOLVING MEDIATORS; PROMOTE RESOLUTION; LIPID MEDIATORS; RECEPTOR; E1; IDENTIFICATION; CIRCUITS; SIGNALS; ASPIRIN AB Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1-10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein-coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (K-d 24.7 +/- 10.1 nM) and resolvin E1 activation of recombinant G-protein-coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses. The Journal of Immunology, 2012, 188: 4527-4534. C1 [Oh, Sungwhan F.; Dona, Maria; Fredman, Gabrielle; Krishnamoorthy, Sriram; Serhan, Charles N.] Harvard Univ, Sch Med,Pain Med, Brigham & Womens Hosp,Anesthesiol,Perioperat &, Ctr Expt Therapeut & Reperfus Injury,Dept, Boston, MA 02115 USA. [Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA. RP Serhan, CN (reprint author), Harvard Univ, Sch Med,Pain Med, Brigham & Womens Hosp,Anesthesiol,Perioperat &, Ctr Expt Therapeut & Reperfus Injury,Dept, 77 Ave Louis Pasteur,HIM 829, Boston, MA 02115 USA. EM cnserhan@zeus.bwh.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU National Institutes of Health [R01GM038765, P01GM095467, R01DE019938] FX This work was supported in part by National Institutes of Health Grants R01GM038765, P01GM095467 (to C.N.S.), and R01DE019938 (to C.N.S. and D.I.). NR 51 TC 40 Z9 40 U1 0 U2 12 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 2012 VL 188 IS 9 BP 4527 EP 4534 DI 10.4049/jimmunol.1103652 PG 8 WC Immunology SC Immunology GA 932OH UT WOS:000303299900046 PM 22450811 ER PT J AU Janeway, KA Pappo, A AF Janeway, Katherine A. Pappo, Alberto TI Treatment Guidelines for Gastrointestinal Stromal Tumors in Children and Young Adults SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE gastrointestinal stromal tumor; pediatric; child; succinate dehydrogenase ID OF-THE-LITERATURE; IMATINIB MESYLATE; SUCCINATE-DEHYDROGENASE; PEDIATRIC-PATIENTS; TYROSINE KINASE; KIT ACTIVATION; MUTATIONS; SUNITINIB; DIAGNOSIS; GIST AB Gastrointestinal stromal tumor (GIST) occurring in the pediatric population has a unique biology and natural history when compared to GIST occurring in adults. As a result of these unique features, management of GIST in children may need to differ from management of GIST in adults. GIST is a very rare disease in children. Consequently prospective clinical trials have not been performed. A review of the biology, clinical presentation and natural history of GIST in children is presented. Guidelines for diagnostic evaluation and management of GIST in children are presented. The presented guidelines are based on clinical experience and data from case reports and case series. C1 [Janeway, Katherine A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Pappo, Alberto] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Janeway, KA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM katherine_janeway@dfci.harvard.edu NR 33 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY PY 2012 VL 34 SU 2 BP S69 EP S72 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 939BR UT WOS:000303782300007 PM 22525410 ER PT J AU Schultz, KAP Schneider, DT Pashankar, F Ross, J Frazier, L AF Schultz, Kris Ann P. Schneider, Dominik T. Pashankar, Farzana Ross, Jonathan Frazier, Lindsay TI Management of Ovarian and Testicular Sex Cord-stromal Tumors in Children and Adolescents SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE ovarian neoplasms; testicular neoplasms; DICER1; sex cord stromal tumors; Sertoli-Leydig; juvenile granulosa cell tumor; genetics ID GRANULOSA-CELL TUMOR; BLEOMYCIN COMBINATION CHEMOTHERAPY; DICER1 MUTATIONS; PLEUROPULMONARY BLASTOMA; PARATESTICULAR TUMORS; TESTIS TUMORS; CISPLATIN; REGISTRY; ETOPOSIDE; INFANTS AB Pediatric ovarian and testicular sex cord-stromal tumors are distinct from germ cell neoplasms and may present with palpable mass or signs of hormone production. Both may be associated with specific genetic syndromes. Staging for ovarian sex cord-stromal tumors is based on the International Federation of Gynecology and Obstetrics classification for ovarian carcinoma. Treatment for those with high risk disease includes multiagent chemotherapy. Testicular stromal tumors often, though not always, follow a benign course. Additional research will help to define optimal treatment strategies for children with these rare tumors. C1 [Schultz, Kris Ann P.] Childrens Hosp & Clin Minnesota, Minneapolis, MN 55404 USA. [Schneider, Dominik T.] Klinikum Dortmund, Dortmund, Germany. [Pashankar, Farzana] Yale Univ, New Haven, CT USA. [Ross, Jonathan] Rainbow Babies & Childrens Hosp, Univ Hosp, Cleveland, OH 44106 USA. [Frazier, Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schultz, KAP (reprint author), Childrens Hosp & Clin Minnesota, 2530 Chicago Ave S, Minneapolis, MN 55404 USA. EM krisann.schultz@childrensmn.org FU Children's Oncology Group; MAKEI group; Pine Tree Apple Tennis Classic; Barbara and Hubertus Trettner Fund FX The authors thank Children's Oncology Group, the MAKEI group, and Pine Tree Apple Tennis Classic for their support of clinical research in the field of rare tumors. DTS is supported by the Barbara and Hubertus Trettner Fund. All authors warmly thank the children and families participating in the registries and clinical studies on whom this guideline is based. NR 57 TC 10 Z9 10 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY PY 2012 VL 34 SU 2 BP S55 EP S63 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 939BR UT WOS:000303782300005 PM 22525408 ER PT J AU Seitz, AL Reinold, M Schneider, RA Gill, TJ Thigpen, C AF Seitz, Amee L. Reinold, Michael Schneider, Robert A. Gill, Thomas J. Thigpen, Charles TI No Effect of Scapular Position on 3-Dimensional Scapular Motion in the Throwing Shoulder of Healthy Professional Pitchers SO JOURNAL OF SPORT REHABILITATION LA English DT Article DE kinematics; athletic therapy; motion analysis; sport ID ELECTROMAGNETIC TRACKING DEVICE; GLENOHUMERAL JOINT; IMPINGEMENT SYNDROME; BASEBALL PITCHERS; CLINICAL METHOD; IN-VIVO; PART 1; KINEMATICS; RELIABILITY; DYSKINESIS AB Context: Differences in 3-dimensional (3D) scapular motion have been reported between healthy baseball position players and healthy nonoverhead athletic controls, as well as players diagnosed with shoulder impingement syndrome. These alterations are theorized to be the result of adaptations due to the demands of repetitive throwing. However, comparisons between the throwing and nonthrowing shoulders are commonly used to infer normal motion. Objective: The purpose of this study was to compare 3D scapular kinematics between the throwing and nonthrowing shoulders in asymptomatic professional male baseball pitchers. Design: Cross-sectional study. Setting: Laboratory. Participants: 45 asymptomatic professional baseball pitchers participating without restrictions during preseason training. Interventions: An electromagnetic tracking system was used to assess 3D scapular orientation at rest and during weighted (2.3-kg) shoulder flexion across discrete humeral-flexion angles (rest, 30 degrees, 60 degrees, 90 degrees, 120 degrees, and maximum). Main Outcome Measure: 3D scapular upward/downward rotation (UR/DR), anteroposterior (AP) tilt, and internal/external rotation (IR/ER). Separate mixed-model ANOVAs (Side x Angle) for each scapular motion were used to compare the throwing and the nonthrowing shoulder across all angles. Results: There were significant side-to-side differences with scapular UR/DR (P < .001), AP tilt (P < .001), and IR/ER (P < .001). The throwing scapula displayed greater mean UR (increase = 3.6 degrees, SE = 0.50) and anterior/posterior tilt (increase = 2.1 degrees, SE = 0.60) and less mean IR (decrease = 2.1 degrees, SE = 0.66) than the nonthrowing shoulder averaged across all arm angles. Conclusions: In asymptomatic professional pitchers, the throwing shoulder's scapular position differs across all arm angles from that of the nonthrowing shoulder, but the motion does not differ. Scapular asymmetry that is consistent throughout arm elevation may be indicative not of pathology but, potentially, of a normal adaptation of the pitching shoulder. C1 [Seitz, Amee L.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Reinold, Michael] Boston Red Sox Baseball, Athlet Training Dept, Boston, MA USA. [Schneider, Robert A.] Balanced Phys Therapy, Durham, NC USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Sports Med Dept, Boston, MA 02114 USA. [Thigpen, Charles] Proaxis Therapy, Greenville, SC USA. RP Seitz, AL (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. RI Lempereur, Mathieu/G-5470-2012; Seitz, Amee/J-3258-2012 OI Seitz, Amee/0000-0002-4272-1354 FU Foundation for Physical Therapy; Orthopedic Research Foundation of the Carolinas; University of North Florida Brooks Rehabilitation Foundation FX Funding for this study was provided by the Foundation for Physical Therapy, the Orthopedic Research Foundation of the Carolinas, and the University of North Florida Brooks Rehabilitation Foundation. NR 42 TC 5 Z9 5 U1 0 U2 7 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1056-6716 J9 J SPORT REHABIL JI J. Sport Rehabil. PD MAY PY 2012 VL 21 IS 2 BP 186 EP 193 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 936YU UT WOS:000303627000014 PM 22622383 ER PT J AU Brown, D Wagner, CA AF Brown, Dennis Wagner, Carsten A. TI Molecular Mechanisms of Acid-Base Sensing by the Kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID SOLUBLE ADENYLYL-CYCLASE; RECEPTOR-RELATED RECEPTOR; RENAL PROXIMAL TUBULES; THICK ASCENDING LIMB; A-INTERCALATED CELLS; VACUOLAR H+-ATPASE; METABOLIC-ACIDOSIS; MESSENGER-RNA; V-ATPASE; CO2-INDUCED STIMULATION AB A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO2 status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process. C1 [Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Wagner, Carsten A.] Univ Zurich, Inst Physiol, Zurich, Switzerland. [Wagner, Carsten A.] Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. RP Brown, D (reprint author), Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Simches Res Bldg,185 Cambridge St,CPZN 8020, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU National Institutes of Health [DK42956]; EU; Swiss National Science Foundation FX Work in the laboratories of the authors has been supported by grants from the National Institutes of Health (DK42956) to D.B. and the FP7 EU Framework program and the Swiss National Science Foundation to C.A.W. NR 78 TC 26 Z9 26 U1 2 U2 19 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2012 VL 23 IS 5 BP 774 EP 780 DI 10.1681/ASN.2012010029 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 937DA UT WOS:000303638000005 PM 22362904 ER PT J AU Vasterling, JJ Dikmen, S AF Vasterling, Jennifer J. Dikmen, Sureyya TI Mild Traumatic Brain Injury and Posttraumatic Stress Disorder: Clinical and Conceptual Complexities SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Editorial Material ID OUTCOMES; PTSD C1 [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Dikmen, Sureyya] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, Psychol Serv, 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov; Dikmen@u.washington.edu NR 12 TC 13 Z9 13 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2012 VL 18 IS 3 BP 390 EP 393 DI 10.1017/S1355617712000367 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 937VG UT WOS:000303690500001 PM 22559162 ER PT J AU Meissner, MH Gloviczki, P Comerota, AJ Dalsing, MC Eklof, BG Gillespie, DL Lohr, JM McLafferty, RB Murad, MH Padberg, F Pappas, P Raffetto, JD Wakefield, TW AF Meissner, Mark H. Gloviczki, Peter Comerota, Anthony J. Dalsing, Michael C. Eklof, Bo G. Gillespie, David L. Lohr, Joann M. McLafferty, Robert B. Murad, M. Hassan Padberg, Frank Pappas, Peter Raffetto, Joseph D. Wakefield, Thomas W. TI Early thrombus removal strategies for acute deep venous thrombosis: Clinical Practice Guidelines of the Society for Vascular Surgery and the American Venous Forum SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PHLEGMASIA-CERULEA-DOLENS; CATHETER-DIRECTED THROMBOLYSIS; ILIOFEMORAL VEIN-THROMBOSIS; QUALITY-OF-LIFE; TERM-FOLLOW-UP; PERCUTANEOUS MECHANICAL THROMBECTOMY; HEPARIN-INDUCED THROMBOCYTOPENIA; MAGNETIC-RESONANCE VENOGRAPHY; ELASTIC COMPRESSION STOCKINGS; POSTTHROMBOTIC-SYNDROME AB Background: The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. Objective: A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. Methods: Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). Results: On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of <14 days in duration (Grade 2C) and strongly recommend their use in patients with limb-threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). Conclusions: Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We anticipate revision of these guidelines as additional evidence becomes available. (J Vasc Surg 2012;55:1449-62.) C1 [Meissner, Mark H.] Univ Washington, Sch Med, Dept Surg, Div Vasc Surg, Seattle, WA 98195 USA. [Gloviczki, Peter] Mayo Clin, Div Vasc & Endovasc Surg, Dept Surg, Rochester, MN USA. [Comerota, Anthony J.] Jobst Vasc Ctr, Vasc Surg Sect, Toledo, OH USA. [Dalsing, Michael C.] Indiana Univ Sch Med, Dept Surg, Vasc Surg Sect, Indianapolis, IN USA. [Eklof, Bo G.] Lund Univ, Helsingborg, Germany. [Gillespie, David L.] Univ Rochester, Sch Med & Dent, Dept Surg, Div Vasc Surg, Rochester, NY 14627 USA. [Lohr, Joann M.] Lohr Surg Specialists, Cincinnati, OH USA. [McLafferty, Robert B.] So Illinois Univ, Dept Surg, Div Vasc Surg, Springfield, IL USA. [Murad, M. Hassan] Mayo Clin, Dept Prevent Occupat & Aerosp Med, Rochester, MN USA. [Padberg, Frank] Univ Med & Dent New Jersey, Dept Surg, Div Vasc Surg, Newark, NJ 07103 USA. [Pappas, Peter] Brooklyn Hosp Ctr, Dept Surg, New York, NY USA. [Raffetto, Joseph D.] VA Boston Healthcare Syst, Dept Surg, Div Vasc Surg, W Roxbury, MA USA. [Wakefield, Thomas W.] Univ Michigan, Dept Surg, Vasc Surg Sect, Ann Arbor, MI 48109 USA. RP Meissner, MH (reprint author), Univ Washington, Sch Med, Dept Surg, Div Vasc Surg, Box 356410,1959 NE Pacific St, Seattle, WA 98195 USA. EM meissner@u.washington.edu OI Gillespie, David/0000-0002-4378-9465; Murad, Mohammad Hassan/0000-0001-5502-5975 NR 107 TC 78 Z9 88 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2012 VL 55 IS 5 BP 1449 EP 1462 DI 10.1016/j.jvs.2011.12.081 PG 14 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 934LV UT WOS:000303446700028 PM 22469503 ER PT J AU Cronenwett, JL Kraiss, LW Cambria, RP AF Cronenwett, Jack L. Kraiss, Larry W. Cambria, Richard P. TI The Society for Vascular Surgery Vascular Quality Initiative SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID AORTIC-ANEURYSM REPAIR; PREDICTING 1-YEAR MORTALITY; LOWER-EXTREMITY BYPASS; NORTHERN NEW-ENGLAND; CAROTID-ENDARTERECTOMY; REGISTRY AB The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) is designed to improve the quality, safety, effectiveness, and cost of vascular health care. It uses the structure of a Patient Safety Organization to permit collection of patient-identified information but protect benchmarked comparisons from legal discovery. The SVS VQI is uniquely organized as a distributed network of regional quality groups to facilitate local translation of registry data into practice change while maintaining the power of a national registry. Detailed data specific to each commonly performed open and endovascular procedure are collected, both in-hospital and at >= 1 year of follow-up. Quality measures are reported to physicians and hospitals, which allow anonymous risk-adjusted benchmarking within regions or nationally. All specialties that perform vascular procedures are included, and international participation is encouraged. This review describes the current status of the SVS VQI. (J Vasc Surg 2012;55:1529-37.) C1 [Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03756 USA. [Kraiss, Larry W.] Univ Utah, Div Vasc Surg, Salt Lake City, UT USA. [Cambria, Richard P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA USA. RP Cronenwett, JL (reprint author), Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM j.cronenwett@hitchcock.org NR 39 TC 43 Z9 43 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2012 VL 55 IS 5 BP 1529 EP 1537 DI 10.1016/j.jvs.2012.03.016 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 934LV UT WOS:000303446700044 PM 22542349 ER PT J AU Grebely, J Prins, M Hellard, M Cox, AL Osburn, WO Lauer, G Page, K Lloyd, AR Dore, GJ AF Grebely, Jason Prins, Maria Hellard, Margaret Cox, Andrea L. Osburn, William O. Lauer, Georg Page, Kimberly Lloyd, Andrew R. Dore, Gregory J. CA Int Collaboration Incident HIV TI Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine SO LANCET INFECTIOUS DISEASES LA English DT Review ID SPONTANEOUS VIRAL CLEARANCE; ADAPTIVE IMMUNE-RESPONSES; SPONTANEOUS HCV CLEARANCE; SINGLE-SOURCE OUTBREAK; HIV-INFECTED PATIENTS; NATURAL-HISTORY; NEUTRALIZING ANTIBODIES; RECOVERED CHIMPANZEES; PROTECTIVE IMMUNITY; ACUTE-PHASE AB Hepatitis C virus (HCV) was discovered more than two decades ago, but progress towards a vaccine has been slow. HCV infection will spontaneously clear in about 25% of people. Studies of spontaneous HCV clearance in chimpanzees and human beings have identified host and viral factors that could be important in the control of HCV infection and the design of HCV vaccines. Although data from studies of chimpanzees suggest that protection against reinfection is possible after spontaneous clearance, HCV is a human disease. Results from studies of reinfection risk after spontaneous clearance in injecting drug users are conflicting, but some people seem to have protection against HCV persistence. To guide future vaccine development, we assess data from studies of HCV reinfection after spontaneous clearance, discuss flaws in the methods of previous human studies, and suggest essential components for future investigations of control of HCV infection. C1 [Grebely, Jason; Dore, Gregory J.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia. [Lloyd, Andrew R.] Univ New S Wales, Sch Med Sci, Inflammat & Infect Res Ctr, Sydney, NSW, Australia. [Prins, Maria] Publ Hlth Serv, Amsterdam, Netherlands. [Prins, Maria] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Ctr Infect & Immun Amsterdam, NL-1105 AZ Amsterdam, Netherlands. [Hellard, Margaret] Burnet Inst, Ctr Populat Hlth, Melbourne, Vic, Australia. [Cox, Andrea L.; Osburn, William O.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Lauer, Georg] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lauer, Georg] Harvard Univ, Sch Med, Boston, MA USA. [Page, Kimberly] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Grebely, J (reprint author), Univ New S Wales, Kirby Inst Infect & Immun Soc, Viral Hepatitis Clin Res Program, Sch Med Sci, Darlinghurst, NSW 2010, Australia. EM jgrebely@kirby.unsw.edu.au OI Page, Kimberly/0000-0002-7120-1673 FU Australian Government Department of Health and Ageing; National Health and Medical Research Council Career Development; Public Health Service of Amsterdam; National Health and Medical Research Council Senior Researcher; US National Institutes of Health [U19 A1040035, R01 A1077757, U19 A1066345, U19 A1082630, 5R01DA016017, 1R01DA031056-01A1]; Damon Runyon Foundation; Dana Foundation; UCSF [UCSF P30 DK026743]; National Health and Medical Research Council Practitioner Fellowships FX Maria Prins was a Senior Visiting Fellow at the Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia when she drafted parts of the manuscript. We thank Campbell Aitken (Burnet Institute, Australia), Jennifer Evans (University of California San Francisco, USA), Thijs van de Laar (Amsterdam Public Health Service, Netherlands), Bart Grady (Amsterdam Public Health Service, Netherlands), and Charlotte van den Berg (Amsterdam Public Health Service, Netherlands) for assisting with the preparation of data; and Tanya Applegate (Kirby Institute for Infection and Immunity in Society, Australia) for her constructive comments during the preparation of this report. This report was funded by the Australian Government Department of Health and Ageing. The views expressed in this report do not necessarily represent the position of the Australian Government. JG is supported by a National Health and Medical Research Council Career Development Fellowship. MP was supported by the Public Health Service of Amsterdam. MH was supported by a National Health and Medical Research Council Senior Researcher Fellowship. ALC and WOO were supported by the US National Institutes of Health (U19 A1040035 and R01 A1077757), the Damon Runyon Foundation, and the Dana Foundation. GL is supported by the US National Institutes of Health (U19 A1066345 and U19 A1082630). KP was supported by US National Institutes of Health (5R01DA016017 and 1R01DA031056-01A1) and the UCSF Liver Center (UCSF P30 DK026743). ARL and GJD were supported by National Health and Medical Research Council Practitioner Fellowships. NR 81 TC 71 Z9 73 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD MAY PY 2012 VL 12 IS 5 BP 408 EP 414 PG 7 WC Infectious Diseases SC Infectious Diseases GA 934DF UT WOS:000303422700021 PM 22541630 ER PT J AU Dagher, J Du, YPP AF Dagher, Joseph Du, Yiping P. TI Efficient and robust estimation of blood oxygenation levels in single cerebral veins SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Blood oxygenation; Single vessel; BOLD; Numerical modeling; Estimation; Venous blood; Quantitative fMRI ID EXTRACTION FRACTION; SIGNAL BEHAVIOR; VOLUME; MRI AB Blood oxygenation level is an important measure that can be used alongside functional magnetic resonance imaging data in order to obtain closer correlates of neuronal activation. A robust estimate of this measure has thus far not been demonstrated. This is mainly due to the lack of knowledge of the underlying parameters which influence the numerical estimates of blood oxygenation. In this paper, we present a systematic analysis of the estimation performance of venous hemoglobin oxygen saturation (Y-v) as a function of noise, physiologic and geometric parameters. Furthermore, we present a novel algorithm for estimating Y-v from the temporal decay of an MR signal. The proposed algorithm incorporates prior information about the functional dependence between Y-v and relaxation rates. We compare our algorithm to an existing method in the literature and analyze the estimation performance. We show that our proposed algorithm is more efficient, achieving gains in performance as high as 92 %. We also show how our estimation algorithm takes advantage of signal features that are specific to the underlying physiology and geometry. We argue that optimal acquisition sequences, and corresponding estimation methods, should take into account such features in order to obtain robust estimates of blood oxygenation. C1 [Dagher, Joseph; Du, Yiping P.] Univ Colorado, Sch Med, Dept Psychiat, Brain Imaging Ctr, Denver, CO 80045 USA. RP Dagher, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM dagher@nmr.mgh.harvard.edu FU NIH [T32MH015442]; University of Colorado, Denver FX This work has been supported by NIH grant T32MH015442, and in part by the Developmental Psychobiology Research Fund at the University of Colorado, Denver. The views expressed in this paper do not reflect the official views of NIH. The authors would like to thank Prof. Robert Freedman for his contributions and helpful discussion. NR 20 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD MAY PY 2012 VL 50 IS 5 BP 473 EP 482 DI 10.1007/s11517-012-0886-8 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 933IS UT WOS:000303354700005 PM 22415740 ER PT J AU Viola, GM Awan, LL Ostrosky-Zeichner, L Chan, WY Darouiche, RO AF Viola, George M. Awan, Leah L. Ostrosky-Zeichner, Luis Chan, Wenyaw Darouiche, Rabih O. TI Infections of Cardiac Implantable Electronic Devices A Retrospective Multicenter Observational Study SO MEDICINE LA English DT Article ID CARDIOVERTER-DEFIBRILLATORS; RISK-FACTORS; PERMANENT PACEMAKER; CONSECUTIVE PATIENTS; UNITED-STATES; MANAGEMENT; ENDOCARDITIS; DIAGNOSIS; RATES; BACTEREMIA AB Infections of cardiac implantable electronic devices (CIED) can cause significant morbidity, mortality, and financial burden. Although staphylococcal organisms account for most infections of these cardiac devices, approximately 20% of all CIED-related infections are caused by non-Staphylococcus species. Herein we describe and compare the demographics, clinical presentation, and outcomes of Staphylococcus aureus and non-staphylococcal infections of CIED. We performed a retrospective, multicenter, observational study of patients from 4 academic hospitals in Houston between 2002 and 2009. All 80 identified non-staphylococcal CIED-related infections were matched, at a 1:1 ratio, to S. aureus infections. Although the demographics and general comorbidities in the 2 study groups were relatively similar, the S. aureus group had a higher proportion of patients with coronary artery disease, diabetes mellitus, and end-stage renal disease. Additionally, 81% of S. aureus compared with only 48.5% of the non-staphylococcal CIED-related infections were health care-associated (p < 0.001). Furthermore, when compared to non-staphylococcal infections, the S. aureus group had more indwelling intravascular foreign material (p < 0.001), more rapid clinical progression (p < 0.001), and overall worse clinical presentation (p < 0.001). However, after stratifying by clinical presentation, the mortality rates in the 2 groups were similar (p = 0.45). Since approximately one-fifth of all CIED-related infections are caused by non-staphylococcal organisms, and untimely antibiotic treatment can result in serious complications, it may be prudent to broaden empiric antimicrobial therapy to cover both Gram-positive and -negative bacteria, until the causative organism is identified. C1 [Viola, George M.] Univ Texas MD Anderson Canc Ctr, Dept Internal Med, Div Infect Dis, Houston, TX 77030 USA. [Viola, George M.; Awan, Leah L.; Darouiche, Rabih O.] Univ Texas MD Anderson Canc Ctr, Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Ostrosky-Zeichner, Luis] Univ Texas Houston, Sch Med, Houston, TX USA. [Darouiche, Rabih O.] Univ Texas Hlth Sci Ctr, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Chan, Wenyaw] Univ Texas Hlth Ctr, Div Biostat, Houston, TX USA. RP Viola, GM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Internal Med, Div Infect Dis, 1515 Holcombe Blvd,Unit 1460, Houston, TX 77030 USA. EM GMViola@mdanderson.org FU Michael E. DeBakey Veterans Affairs Medical Center; Methodist Hospital; Memorial Hermann Hospital, at Houston, Texas; St. Luke's Episcopal Hospital FX We are thankful for the support provided by the Michael E. DeBakey Veterans Affairs Medical Center, St. Luke's Episcopal Hospital, the Methodist Hospital, and the Memorial Hermann Hospital, at Houston, Texas. NR 32 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2012 VL 91 IS 3 BP 123 EP 130 DI 10.1097/MD.0b013e31825592a7 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 936QK UT WOS:000303604900001 PM 22543626 ER PT J AU Vesco, KK Marshall, LM Nelson, HD Humphrey, L Rizzo, J Pedula, KL Cauley, JA Ensrud, KE Hochberg, MC Antoniucci, D Hillier, TA AF Vesco, Kimberly K. Marshall, Lynn M. Nelson, Heidi D. Humphrey, Linda Rizzo, Joanne Pedula, Kathryn L. Cauley, Jane A. Ensrud, Kristine E. Hochberg, Marc C. Antoniucci, Diana Hillier, Teresa A. CA Study Osteoporotic Fractures TI Surgical menopause and nonvertebral fracture risk among older US women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Database search terms; Menopause; Fracture; Oophorectomy ID BONE-MINERAL DENSITY; SERVICES TASK-FORCE; RECOMMENDATION STATEMENT; BILATERAL OOPHORECTOMY; OSTEOPOROTIC FRACTURES; PREMATURE MENOPAUSE; HORMONE-THERAPY; UNITED-STATES; HIP FRACTURE; HYSTERECTOMY AB Objective: The aim of this study was to determine whether older postmenopausal women with a history of bilateral oophorectomy before natural menopause (surgical menopause) have a higher risk of nonvertebral postmenopausal fracture than women with natural menopause. Methods: We used 21 years of prospectively collected incident fracture data from the ongoing Study of Osteoporotic Fractures, a cohort study of community-dwelling women without previous bilateral hip fracture who were 65 years or older at enrollment, to determine the risk of hip, wrist, and any nonvertebral fracture. X-2 and t tests were used to compare the two groups on important characteristics. Multivariable Cox proportional hazards regression models stratified by baseline oral estrogen use status were used to estimate the risk of fracture. Results: Baseline characteristics differed significantly among the 6,616 women within the Study of Osteoporotic Fractures who underwent either surgical (1,157) or natural (5,459) menopause, including mean age at menopause (44.3 +/- 7.4 vs 48.9 +/- 4.9 y, P < 0.001) and current use of oral estrogen (30.2% vs 6.5%, P < 0.001). Fracture rates were not significantly increased for surgical versus natural menopause, even among women who had never used oral estrogen (hip fracture: hazard ratio [HR], 0.87; 95% CI, 0.63-1.21; wrist fracture: HR, 1.10; 95% CI, 0.78-1.57; any nonvertebral fracture: HR, 1.11; 95% CI, 0.93-1.32). Conclusions: These data provide some reassurance that the long-term risk of nonvertebral fracture is not substantially increased for postmenopausal women who experienced premenopausal bilateral oophorectomy, compared with postmenopausal women with intact ovaries, even in the absence of postmenopausal estrogen therapy. C1 [Vesco, Kimberly K.] Kaiser Permanente NW, Ctr Hlth Res, Sci Programs Dept, Portland, OR 97227 USA. [Vesco, Kimberly K.; Humphrey, Linda] Portland VA Med Ctr, Portland, OR USA. [Marshall, Lynn M.; Humphrey, Linda] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Nelson, Heidi D.; Humphrey, Linda] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Nelson, Heidi D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Nelson, Heidi D.] Providence Hlth & Serv, Women & Childrens Hlth Res Ctr, Portland, OR USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ensrud, Kristine E.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Hochberg, Marc C.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Hochberg, Marc C.] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Antoniucci, Diana] Univ Calif San Francisco, Dept Med, Endocrine Res Unit, San Francisco Dept Vet Affairs Med Ctr, San Francisco, CA USA. RP Vesco, KK (reprint author), Kaiser Permanente NW, Ctr Hlth Res, Sci Programs Dept, 3800 N Interstate Ave, Portland, OR 97227 USA. EM Kimberly.k.vesco@kpchr.org OI Cauley, Jane A/0000-0003-0752-4408 FU NIA NIH HHS [2 R01 AG005394-22A1, 2 R01 AG027574-22A1, R01 AG005394, R01 AG005407, R01 AG027574, R01 AG027574-27, R01 AG027576, R01 AG027576-22]; NIAMS NIH HHS [AR35582, AR35583, AR35584, R01 AR035582, R01 AR035583, R01 AR035584] NR 32 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY PY 2012 VL 19 IS 5 BP 510 EP 516 DI 10.1097/gme.0b013e318239caeb PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 934AN UT WOS:000303411200007 PM 22547252 ER PT J AU Gleason, CE Dowling, NM Friedman, E Wharton, W Asthana, S AF Gleason, Carey E. Dowling, N. Maritza Friedman, Elliot Wharton, Whitney Asthana, Sanjay TI Using predictors of hormone therapy use to model the healthy user bias: how does healthy user status influence cognitive effects of hormone therapy? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Hormone therapy; Healthy user; Cognition; Menopause; Selection bias; Executive functioning ID ESTROGEN REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; INITIATIVE MEMORY; PLUS PROGESTIN; ALZHEIMER-DISEASE; DETERMINANTS; RISK AB Objective: This study investigated the phenomenon known as the healthy user bias by equating hormone therapy (HT) use (past or current) with healthy user status. Methods: Data from the Survey of Midlife in the United States were used to identify the predictors of HT use. The unique Survey of Midlife in the United States data include psychological, demographic, health-related, and behavioral variables as well as history of HT use. Predictors of HT use were combined to derive propensity scores, describing the likelihood that a woman was an HT user, based on her psychological, demographic, physical, and behavioral profile (ie, likelihood of being a healthy user) as opposed to her actual use of HT. Finally, cognitive performance on an executive function test was examined in women stratified by propensity score. Results: Using a multiple logistic regression model, nine variables emerged as predictors of HT use. The nine variables were used to estimate the propensity or conditional probability of using HT for each subject; resultant propensity scores were ranked and divided into tertiles. Women in the highest tertile demonstrated shorter median response latencies on a test of executive function than did women who did not use HT. Conclusions: From an array of psychological, medical, and behavioral variables, nine emerged as predictors of HT use. If validated, these features may serve as a means of estimating the phenomenon known as healthy user bias. Moreover, these data suggest that the degree to which a woman fits a model of a healthy user may influence cognitive response to HT. C1 [Gleason, Carey E.; Wharton, Whitney; Asthana, Sanjay] Univ Wisconsin, Dept Med, Div Geriatr & Gerontol, Sch Med & Publ Hlth, Madison, WI USA. [Gleason, Carey E.; Wharton, Whitney; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Gleason, Carey E.; Dowling, N. Maritza; Wharton, Whitney; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Friedman, Elliot] Univ Wisconsin, Inst Aging, Madison, WI USA. RP Gleason, CE (reprint author), Madison VA GRECC D4211, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU National Institutes of Health [K23 AG024302, P50 AG033514] FX This research was supported by funding from the National Institutes of Health (K23 AG024302; P50 AG033514). NR 45 TC 5 Z9 5 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY PY 2012 VL 19 IS 5 BP 524 EP 533 DI 10.1097/gme.0b013e318238ff2c PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 934AN UT WOS:000303411200009 PM 22207317 ER PT J AU Maguire, CA Balaj, L Sivaraman, S Crommentuijn, MHW Ericsson, M Mincheva-Nilsson, L Baranov, V Gianni, D Tannous, BA Sena-Esteves, M Breakefield, XO Skog, J AF Maguire, Casey A. Balaj, Leonora Sivaraman, Sarada Crommentuijn, Matheus H. W. Ericsson, Maria Mincheva-Nilsson, Lucia Baranov, Vladimir Gianni, Davide Tannous, Bakhos A. Sena-Esteves, Miguel Breakefield, Xandra O. Skog, Johan TI Microvesicle-associated AAV Vector as a Novel Gene Delivery System SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRAL VECTORS; CELL-DERIVED EXOSOMES; HEPARAN-SULFATE; MAMMALIAN-CELLS; HEMOPHILIA-B; VIRUS TYPE-1; THERAPY; EXPRESSION; PROTEINS; VESICLES AB Adeno-associated virus (AAV) vectors have shown remarkable efficiency for gene delivery to cultured cells and in animal models of human disease. However, limitations to AAV vectored gene transfer exist after intravenous transfer, including off-target gene delivery (e.g., liver) and low transduction of target tissue. Here, we show that during production, a fraction of AAV vectors are associated with microvesicles/exosomes, termed vexosomes (vector-exosomes). AAV capsids associated with the surface and in the interior of microvesicles were visualized using electron microscopy. In cultured cells, vexosomes outperformed conventionally purified AAV vectors in transduction efficiency. We found that purified vexosomes were more resistant to a neutralizing anti-AAV antibody compared to conventionally purified AAV. Finally, we show that vexosomes bound to magnetic beads can be attracted to a magnetized area in cultured cells. Vexosomes represent a unique entity which offers a promising strategy to improve gene delivery. C1 [Maguire, Casey A.; Balaj, Leonora; Sivaraman, Sarada; Crommentuijn, Matheus H. W.; Tannous, Bakhos A.; Breakefield, Xandra O.; Skog, Johan] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maguire, Casey A.; Balaj, Leonora; Sivaraman, Sarada; Crommentuijn, Matheus H. W.; Tannous, Bakhos A.; Breakefield, Xandra O.; Skog, Johan] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Mincheva-Nilsson, Lucia; Baranov, Vladimir] Umea Univ, Dept Clin Microbiol Clin Immunol, Umea, Sweden. [Gianni, Davide; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Gene Therapy Ctr, Worcester, MA USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Skog, J (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM skog.johan@mgh.harvard.edu OI Crommentuijn, Matheus/0000-0001-8217-5370 FU NCI [P50 CA86355, P01 CA069246, RO1 CA141150]; NIH/NINDS [P30NS045776]; American Brain Tumor Association; NINDS [P30NS4577] FX This work was supported by NCI P50 CA86355 (C.A.M., B.A.T., X.O.B.), NCI P01 CA069246 (X.O.B.), NCI RO1 CA141150 (X.O.B.), NIH/NINDS P30NS045776 (B.A.T.), and American Brain Tumor Association (J.S., C.A.M.). We thank the MGH Nucleic Acid Quantitation Core facility (with assistance from Luba Zagachin) supported by NINDS grant #P30NS4577 for the use of the thermal cyclers for quantitative PCR. We would also like to thank Igor Bagayev of the confocal microscopy core for assistance with fluorescence microscopy. For the electron microscopy data acquisition and analysis, we would like to thank the Harvard Conventional electron microscopy core as well as Howard Mulhern of Children's Hospital Boston Electron Microscope facility. We thank Emily Mills for generating the artwork in Figure 7. We thank Kristan van der Vos for helpful discussions and technical advice. J.S. and C.A.M. are inventors on a patent application involving vexosome technology. J.S. holds equity in, and is an employee of Exosome Diagnostics, Inc. NR 45 TC 55 Z9 55 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 IS 5 BP 960 EP 971 DI 10.1038/mt.2011.303 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YS UT WOS:000303484300012 PM 22314290 ER PT J AU Cramer, F Christensen, CL Badding, M Dean, DA Poulsen, HS AF Cramer, Frederik Christensen, Camilla L. Badding, Melissa Dean, David A. Poulsen, Hans S. TI Implementation of a Nuclear Factor Kappa B DNA Nuclear Targeting Sequence Improves In Vitro Suicide Gene Therapy Efficacy in Both Small- and Non-Small Cell Lung Cancer Cell Lines SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Cramer, Frederik; Poulsen, Hans S.] Univ Copenhagen Hosp, Dept Radiat Biol, DK-2100 Copenhagen, Denmark. [Christensen, Camilla L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Badding, Melissa; Dean, David A.] Univ Rochester, Dept Pediat, Rochester, NY 14627 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 128 BP S52 EP S52 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600129 ER PT J AU Crommentuijn, MHW Maguire, CA Bovenberg, S Badr, CE Tannous, BA AF Crommentuijn, Matheus H. W. Maguire, Casey A. Bovenberg, Sarah Badr, Christian E. Tannous, Bakhos A. TI A Transcriptionally Targeted, Systemically Administered AAV-sTRAIL in Combination with Lanatoside C for Glioblastoma Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Crommentuijn, Matheus H. W.; Maguire, Casey A.; Bovenberg, Sarah; Badr, Christian E.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Charlestown, MA USA. [Crommentuijn, Matheus H. W.] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Crommentuijn, Matheus H. W.; Maguire, Casey A.; Bovenberg, Sarah; Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, Sarah] Leiden Univ, Dept Neurosurg, Med Ctr, Leiden, Netherlands. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 685 BP S264 EP S265 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600682 ER PT J AU Kanai, R Wakimoto, H Tshilenge, KT Martuza, RL Rabkin, SD AF Kanai, Ryuichi Wakimoto, Hiroaki Tshilenge, Kizito-Tshitoko Martuza, Robert L. Rabkin, Samuel D. TI Effect of gamma 34.5 Deletions on Oncolytic Herpes Simplex Virus Activity in Glioblastoma Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Kanai, Ryuichi; Wakimoto, Hiroaki; Tshilenge, Kizito-Tshitoko; Martuza, Robert L.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Boston, MA 02114 USA. [Kanai, Ryuichi] Keio Univ, Tokyo, Japan. [Tshilenge, Kizito-Tshitoko] Ecole Normale Super Lyon, F-69364 Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 200 BP S79 EP S79 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600201 ER PT J AU Lai, CP Maguire, CA Armata, IA Tannous, BA Breakefield, XO AF Lai, Charles P. Maguire, Casey A. Armata, Ioanna A. Tannous, Bakhos A. Breakefield, Xandra O. TI Non-Invasive, Multimodal Imaging of Microvesicles with Metabolically Biotinylated, Membrane-Bound Gaussia Luciferase SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Lai, Charles P.; Maguire, Casey A.; Armata, Ioanna A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Charlestown, MA USA. [Lai, Charles P.; Maguire, Casey A.; Armata, Ioanna A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Neurosci Program, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 627 BP S241 EP S241 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600625 ER PT J AU Maeder, ML Angstman, JF Linder, SJ Reyon, D Joung, JK AF Maeder, Morgan L. Angstman, James F. Linder, Sam J. Reyon, Deepak Joung, J. Keith TI Upregulation of the Pluripotency-Associated miRNA 302-367 Cluster Using Engineered Transcription Activator-Like Effector (TALE) Activators SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Maeder, Morgan L.; Angstman, James F.; Linder, Sam J.; Reyon, Deepak; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Biol & Biomed Sci Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 499 BP S193 EP S193 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600499 ER PT J AU Maguire, CA Crommentuijn, M Skog, J Breakefield, XO Tannous, BA AF Maguire, Casey A. Crommentuijn, Matheus Skog, Johan Breakefield, Xandra O. Tannous, Bakhos A. TI In Vivo Gene Delivery Using Microvesicle-Associated AAV SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Maguire, Casey A.; Crommentuijn, Matheus; Skog, Johan; Breakefield, Xandra O.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 119 BP S49 EP S49 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600120 ER PT J AU Parekkadan, B AF Parekkadan, Biju TI Pharmacokinetic-Guided Delivery of Mesenchymal Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Parekkadan, Biju] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 752 BP S290 EP S290 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600747 ER PT J AU Prabhakar, S Taherian, M Gianni, D Conlon, TJ Rachamimov, AS Esteves, MS Breakefield, XO Brenner, GJ AF Prabhakar, Shilpa Taherian, Mehran Gianni, Davide Conlon, Thomas J. Rachamimov, Anat S. Esteves, Miguel S. Breakefield, Xandra O. Brenner, Gary J. TI Regression of Schwannomas Induced by AAV-Mediated Delivery of Caspase-1 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Prabhakar, Shilpa; Taherian, Mehran; Rachamimov, Anat S.; Breakefield, Xandra O.; Brenner, Gary J.] Massachusetts Gen Hosp, Charlestown, MA USA. MGH, Charlestown, MA USA. UMASS Med Sch, Worcester, MA USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 357 BP S140 EP S140 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600358 ER PT J AU Rahman, S Kuhle, J Maeder, M Riedel, H Cantz, T Joung, K Schambach, A Cathomen, T AF Rahman, Shamim Kuehle, Johannes Maeder, Morgan Riedel, Heimo Cantz, Tobias Joung, Keith Schambach, Axel Cathomen, Toni TI Zinc-Finger Nuclease-Mediated Correction of RS-SCID SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Rahman, Shamim; Kuehle, Johannes; Schambach, Axel; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, D-3000 Hannover, Germany. [Riedel, Heimo] Robert C Byrd Hlth Sci Ctr, Dept Biochem, Morgantown, WV USA. [Cantz, Tobias] REBIRTH Cluster Excellence, JRG Stem Cell Biol, Hannover, Germany. [Maeder, Morgan; Joung, Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 308 BP S122 EP S122 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600309 ER PT J AU Ramirez, CL Certo, MT Mussolino, C Goodwin, M Cradick, TJ McCaffrey, AP Cathomen, T Scharenberg, AM Joung, JK AF Ramirez, Cherie L. Certo, Michael T. Mussolino, Claudio Goodwin, Mathew Cradick, Thomas J. McCaffrey, Anton P. Cathomen, Toni Scharenberg, Andrew M. Joung, J. Keith TI Engineered Zinc Finger Nickases for Stimulating Homology-Directed Repair with Decreased Mutagenic Effects SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Ramirez, Cherie L.; Goodwin, Mathew; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA. [Ramirez, Cherie L.; Goodwin, Mathew; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Biol & Biomed Sci Program, Grad Sch Arts & Sci, Boston, MA 02115 USA. [Certo, Michael T.] Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98195 USA. [Certo, Michael T.; Scharenberg, Andrew M.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Mussolino, Claudio; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, Hannover, Germany. [Cradick, Thomas J.; McCaffrey, Anton P.] Univ Iowa, Dept Internal Med, Sch Med, Iowa City, IA 52242 USA. [Cradick, Thomas J.] Emory Univ, Atlanta, GA 30322 USA. [Cradick, Thomas J.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [McCaffrey, Anton P.] TriLink BioTechnol Inc, Dept Cell Biol, San Diego, CA USA. [Scharenberg, Andrew M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 304 BP S120 EP S120 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600305 ER PT J AU Reyon, D Tsai, SQ Khayter, C Foden, JA Sander, JD Joung, JK AF Reyon, Deepak Tsai, Shengdar Q. Khayter, Cyd Foden, Jennifer A. Sander, Jeffry D. Joung, J. Keith TI High-Throughput Gene Editing in Human Cells Enabled by Fast Ligation-Based Automatable Solid-Phase High-Throughput (FLASH) Assembly of TALENs SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Foden, Jennifer A.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Reyon, Deepak; Tsai, Shengdar Q.; Khayter, Cyd; Foden, Jennifer A.; Sander, Jeffry D.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Reyon, Deepak] Iowa State Univ, Dept Genet Dev & Cell Biol, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA USA. [Tsai, Shengdar Q.; Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 310 BP S122 EP S123 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600311 ER PT J AU Teng, J de Gooijer, MC Tannous, BA AF Teng, Jian de Gooijer, Mark C. Tannous, Bakhos A. TI Lanatoside C Enhances the Therapeutic Efficacy of Secreted TRAIL Expressed by Human Neural Stem Cells in an Orthotopic Invasive Primary Glioblastoma Model SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Teng, Jian; de Gooijer, Mark C.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Teng, Jian; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [de Gooijer, Mark C.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 474 BP S184 EP S184 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600475 ER PT J AU van der Vos, KE Skog, J Breakefield, XO AF van der Vos, Kristan E. Skog, Johan Breakefield, Xandra O. TI Intercellular Transfer of microRNAs Via Tumor Microvesicles SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 16-19, 2012 CL Philadelphia, PA SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [van der Vos, Kristan E.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [van der Vos, Kristan E.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Skog, Johan] Exosome Diagnost Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2012 VL 20 SU 1 MA 686 BP S265 EP S265 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934YU UT WOS:000303484600683 ER PT J AU Farkash, EA Colvin, RB AF Farkash, Evan A. Colvin, Robert B. TI Diagnostic challenges in chronic antibody-mediated rejection SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID CHRONIC ALLOGRAFT-REJECTION; RENAL-ALLOGRAFTS; NK CELLS; C4D; ALLOANTIBODY; BIOPSIES; INJURY AB Measurement of glomerular and peritubular capillaritis in kidney transplant biopsy samples identifies allograft dysfunction associated with alloantibodies. Sis et al. show that this technique has a higher sensitivity but lower specificity than the current diagnostic criteria using peritubular capillary C4d deposition, and that capillaritis is an independent predictor of progression to graft failure. C1 [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu FU NIAID NIH HHS [U19 AI102405] NR 10 TC 20 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD MAY PY 2012 VL 8 IS 5 BP 255 EP 257 DI 10.1038/nrneph.2012.61 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 933OP UT WOS:000303371900001 PM 22450441 ER PT J AU Garvey, AJ Kalman, D Hoskinson, RA Kinnunen, T Wadler, BM Thomson, CC Rosner, B AF Garvey, Arthur J. Kalman, David Hoskinson, Randall A., Jr. Kinnunen, Taru Wadler, Brianna M. Thomson, Carey C. Rosner, Bernard TI Front-Loaded Versus Weekly Counseling for Treatment of Tobacco Addiction SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKING; INTERVENTIONS; ABSTINENCE AB Approximately 60%-70% of cigarette smokers who try to quit relapse by 2 weeks postcessation. We tested the efficacy of a front-loaded (FL) counseling intervention whose goal was to increase the likelihood of successful early abstinence and subsequent long-term abstinence. We randomized 278 adult smokers to an FL or weekly behavioral smoking cessation counseling schedule. The total number of sessions across treatment was the same for both groups. However, those assigned to the FL schedule received 6 counseling sessions in the first 2 weeks postcessation, while those in the weekly condition received 2 sessions. Participants in both groups also received standard nicotine patch treatment. At 1 year postcessation, FL participants were significantly less likely to have relapsed when continuous abstinence was used as the definition of abstinence/relapse (11.7% abstinent vs. 6.3%, hazard ratio [HR] = 0.69, p = .007); and there were nonsignificant trends for FL subjects to have better outcomes when abstinence was defined as never smoking for 7 or more consecutive days nor for 7 or more consecutive episodes (18.4% abstinent vs. 14.8%, HR = 0.83, p = .20) and as point prevalence abstinence (15.6% abstinent vs. 12.9%, p = .11). The relationship between FL counseling treatment and continuous abstinence was partially mediated by higher postcessation levels of social support perceived from counseling and greater use of cessation-related coping strategies. We conclude that FL counseling is a promising treatment model that should be evaluated further, perhaps using modifications of the FL schedule used in this study. C1 [Garvey, Arthur J.] Harvard Univ, Sch Dent Med, Smoking Res Program, Boston, MA 02109 USA. [Kalman, David] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Hoskinson, Randall A., Jr.] Brown Univ, Sch Med, Rhode Isl Hosp, Providence, RI 02912 USA. [Wadler, Brianna M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Thomson, Carey C.] Harvard Univ, Sch Med, Mt Auburn Hosp, Boston, MA USA. [Rosner, Bernard] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Garvey, AJ (reprint author), Harvard Univ, Sch Dent Med, Smoking Res Program, 31 State St, Boston, MA 02109 USA. EM arthur_garvey@hms.harvard.edu FU National Institute on Drug Abuse of the National Institutes of Health [5 R01 DA016739] FX This study was supported by grant 5 R01 DA016739 from the National Institute on Drug Abuse of the National Institutes of Health. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. NR 12 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2012 VL 14 IS 5 BP 578 EP 585 DI 10.1093/ntr/ntr256 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 933BS UT WOS:000303334800009 PM 22058190 ER PT J AU Basu-Roy, U Seo, E Ramanathapuram, L Rapp, TB Perry, JA Orkin, SH Mansukhani, A Basilico, C AF Basu-Roy, U. Seo, E. Ramanathapuram, L. Rapp, T. B. Perry, J. A. Orkin, S. H. Mansukhani, A. Basilico, C. TI Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas SO ONCOGENE LA English DT Article DE osteosarcoma; wnt signaling; cancer stem cell; mesenchymal tumors; differentiation; sarcosphere ID CANCER STEM-CELLS; TRANSCRIPTION FACTOR SOX2; OSTEOBLAST DIFFERENTIATION; PROGENITOR CELLS; BETA-CATENIN; MOUSE MODEL; WNT; GROWTH; SARCOMA; LINEAGE AB Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor-initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma (mOS) cell lines as well as in the tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by short-hairpin RNAs in independent mOS-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these cells maintain a requirement for Sox2 for tumorigenicity. Our data indicate that Sox2 is required for osteosarcoma cell self renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas. Oncogene (2012) 31, 2270-2282; doi:10.1038/onc.2011.405; published online 19 September 2011 C1 [Basu-Roy, U.; Seo, E.; Mansukhani, A.; Basilico, C.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. [Ramanathapuram, L.] NYU, Coll Dent, New York, NY 10016 USA. [Rapp, T. B.] NYU, Sch Med, Dept Orthoped Surg, New York, NY 10016 USA. [Perry, J. A.; Orkin, S. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Perry, J. A.; Orkin, S. H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Perry, J. A.; Orkin, S. H.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, Boston, MA USA. RP Mansukhani, A (reprint author), NYU, Sch Med, Dept Microbiol, 550 1st Ave, New York, NY 10016 USA. EM Alka.Mansukhani@med.nyu.edu; Claudio.Basilico@med.nyu.edu OI , Tim/0000-0002-1444-0803; Mansukhani, Alka/0000-0003-1020-3242 FU PHS from the NIAMS [AR051358]; NIDCR [DE013745]; NCI; Children's Cancer Research Fund; St Baldrick's Foundation FX We thank Dr E De Stanchina (Antitumor Assessment Facility, Memorial Sloan Kettering Cancer Center, New York, NY) for excellent services and advice with the xenograft assays. Thanks to Dr J Durbin, NYU TABS, for help with tissue acquisition. This investigation was supported by PHS Grants AR051358 from the NIAMS and DE013745 from the NIDCR, and by an NCI UO1 award (to SHO). UBR is a recipient of a fellowship from The Children's Cancer Research Fund in memory of Dr A Rausen. AM is a recipient of a research grant from St Baldrick's Foundation. JAP is a postdoctoral fellow of the American Cancer Society. SHO is an Investigator of the Howard Hughes Medical Institute. NR 59 TC 66 Z9 71 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 2012 VL 31 IS 18 BP 2270 EP 2282 DI 10.1038/onc.2011.405 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 936SR UT WOS:000303610800003 PM 21927024 ER PT J AU Rudnisky, CJ Belin, MW Todani, A Al-Arfaj, K Ament, JD Zerbe, BJ Ciolino, JB AF Rudnisky, Christopher J. Belin, Michael W. Todani, Amit Al-Arfaj, Khalid Ament, Jared D. Zerbe, Brian J. Ciolino, Joseph B. CA Boston Type 1 Keratoprosthesis Stu TI Risk Factors for the Development of Retroprosthetic Membranes with Boston Keratoprosthesis Type 1 Multicenter Study Results SO OPHTHALMOLOGY LA English DT Article AB Objective: The purpose of this study was to identify possible risk factors for retroprosthetic membrane (RPM) development in a large, multicenter cohort of patients receiving a Boston type 1 keratoprosthesis. Design: Cohort study. Participants: The final analysis included 265 eyes of 265 patients who underwent implantation of a Boston keratoprosthesis type I device between January 2003 and July 2008 by 1 of 19 surgeons at 18 medical centers. Methods: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site. Main Outcome Measures: The primary outcome was the presence or absence of an RPM during the follow-up period. Results: The average age of patients was 63.3 +/- 19.1 years, 48.5% of the patients were female, and 52.5% of procedures were performed on the right eye. The mean follow-up time was 17.8 +/- 14.9 months. The majority (85.4%; n = 222) had undergone an average of 2.2 +/- 1.2 (range, 1-8) penetrating keratoplasties before keratoprosthesis implantation, and 38 eyes (14.6%) received a primary keratoprosthesis. The overall RPM formation rate was 31.7% (n = 84). The most significant risk factor for RPM development was infectious keratitis (as a surgical indication for keratoprosthesis surgery itself), resulting in a rate of RPM formation of 70.6%. As an independent risk factor, the hazard ratio (HR) of RPM development in these eyes was 3.20 (95% confidence interval, 1.66-6.17). Aniridia was also an independent risk factor for RPM development (HR, 3.13; 95% confidence interval, 1.10-8.89). Conclusions: Formation of RPM is a common complication of keratoprosthesis surgery, occurring in approximately one-third of cases. Eyes at the highest risk of RPM development are those receiving corneal replacement for infectious keratitis and aniridia. C1 [Todani, Amit; Al-Arfaj, Khalid; Ament, Jared D.; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Rudnisky, Christopher J.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada. [Belin, Michael W.] Univ Arizona, Dept Ophthalmol, Tucson, AZ USA. [Todani, Amit; Al-Arfaj, Khalid; Zerbe, Brian J.; Ciolino, Joseph B.] Albany Med Coll, Albany Med Ctr, Dept Ophthalmol, Albany, NY 12208 USA. [Al-Arfaj, Khalid] Dammam Univ, Dept Ophthalmol, Dammam, Saudi Arabia. [Zerbe, Brian J.] Solim Med Ctr, Dushanbe, Tajikistan. RP Ciolino, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI [1K08EY019686-01] FX Funded by NEI 1K08EY019686-01 (JBC), New England Cornea Transplant Research Fund (J.B.C.). NR 13 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2012 VL 119 IS 5 BP 951 EP 955 DI 10.1016/j.ophtha.2011.11.030 PG 5 WC Ophthalmology SC Ophthalmology GA 933XM UT WOS:000303399800010 PM 22361316 ER PT J AU Arita, R Yanagi, Y Honda, N Maeda, S Maeda, K Kuchiba, A Yamaguchi, T Yanagihara, Y Suzuki, H Amano, S AF Arita, Reiko Yanagi, Yasuo Honda, Norihiko Maeda, Shuji Maeda, Koshi Kuchiba, Aya Yamaguchi, Takuhiro Yanagihara, Yoshitsugu Suzuki, Hiroshi Amano, Shiro TI Caffeine Increases Tear Volume Depending on Polymorphisms within the Adenosine A2a Receptor Gene and Cytochrome P450 1A2 SO OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; MENISCUS HEIGHT; DRY EYE; INDUCED ANXIETY; COFFEE INTAKE; RISK; ASSOCIATION; DISEASE; CYP1A2; GENOTYPE AB Purpose: The primary aim of the present study was to examine the effect of caffeine on tear volume. The secondary aim was to investigate the relation between caffeine-induced changes in tear volume and polymorphisms in ADORA2A and CYP1A2. Design: Double-masked, placebo-controlled, crossover study. Participants: Seventy-eight healthy volunteers were recruited for the study. Methods: Subjects participated in 2 sessions in which they received capsules containing either placebo or caffeine. The caffeine capsules were given to the subjects to keep the caffeine volume per body weight within 5 to 7 mg/kg. After caffeine intake, tear meniscus height (TMH) was measured. Subjects provided a blood sample for genotyping. Main Outcome Measures: Tear meniscus height, single nucleotide polymorphism. Results: The tear volume increased after caffeine consumption. The net increase in TMH was 0.08 mm (95% confidence interval, 0.05-0.10) greater when participants were given caffeine than when given placebo (P<0.0001). In ADORA2A, the difference in the net increase in TMH for participants who were heterozygous at rs5751876 and rs2298383 was 0.07 mm (P = 0.001) and who were minor homozygous was 0.08 mm (P = 0.007). In CYP1A2, the net increase in TMH for participants who were minor homozygous at rs2472304 was lower than for those who were major homozygous; the difference was 0.06 mm (P = 0.039). Conclusions: Caffeine intake increases tear volume and polymorphisms within ADORA2A, and CYP1A2 is associated with the tear increase after caffeine intake. Genetic polymorphisms had a significant effect on tear meniscus that was of limited clinical significance. C1 [Arita, Reiko] Itoh Clin, Saitama, Japan. [Arita, Reiko; Yanagi, Yasuo; Honda, Norihiko; Amano, Shiro] Univ Tokyo, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. [Maeda, Shuji; Maeda, Koshi] Maeda Ophthalm Clin, Fukushima, Japan. [Kuchiba, Aya] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kuchiba, Aya] Harvard Univ, Sch Med, Boston, MA USA. [Yamaguchi, Takuhiro] Tohoku Univ, Grad Sch Med, Div Biostat, Sendai, Miyagi 980, Japan. [Yanagihara, Yoshitsugu; Suzuki, Hiroshi] Tokyo Univ Hosp, Dept Pharm, Tokyo 113, Japan. RP Arita, R (reprint author), 626-11 Minaminakano,Minuma Ku, Saitama 3370042, Japan. EM ritoh@za2.so-net.ne.jp NR 41 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2012 VL 119 IS 5 BP 972 EP 978 DI 10.1016/j.ophtha.2011.11.033 PG 7 WC Ophthalmology SC Ophthalmology GA 933XM UT WOS:000303399800013 PM 22336631 ER PT J AU Sharma, A Mendez, E Yueh, B Lohavanichbutr, P Houck, J Doody, DR Futran, ND Upton, MP Schwartz, SM Chen, C AF Sharma, Arun Mendez, Eduardo Yueh, Bevan Lohavanichbutr, Pawadee Houck, John Doody, David R. Futran, Neal D. Upton, Melissa P. Schwartz, Stephen M. Chen, Chu TI Human Papillomavirus-Positive Oral Cavity and Oropharyngeal Cancer Patients Do Not Have Better Quality-of-Life Trajectories SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT AAO-HNSF Annual Meeting and OTO EXPO CY SEP 10-14, 2011 CL San Francisco, CA SP AAO, HNSF DE head and neck cancer; quality of life; epidemiology/outcomes research; head and neck surgery; human papillomavirus; oropharyngeal squamous cell carcinoma ID NECK-CANCER; HEAD; SURVIVAL; TRENDS; RACE AB Objective. To determine the role of human papillomavirus (HPV) status on quality of life (QOL) in patients with oral cavity and oropharyngeal squamous cell carcinoma (OSCC). Since OSCC that are associated with high-risk HPV have an improved response to treatment and survival, we hypothesized that patients with these tumors would have better QOL trajectories. Study Design. Prospective cohort study. Setting. Tertiary care academic medical center and 2 affiliated hospitals. Subjects and Methods. Head and neck-specific QOL was determined using the University of Washington Quality of Life scale version 4 in patients with newly diagnosed invasive OSSC (N = 228). Results. Pretreatment QOL was higher in patients with high-risk HPV-associated tumors compared with patients with HPV-negative or low-risk HPV-associated tumors (P = .015). Patients with high-risk HPV-associated tumors had larger decreases in QOL from pretreatment to immediate post-treatment compared with patients with HPV-negative or low-risk HPV-associated tumors (P = .041). There was no association between HPV status and 1-year posttreatment QOL. Conclusion. Among OSCC patients, high-risk HPV-associated tumors were associated with higher pretreatment QOL and a larger decrease in QOL from pretreatment to immediate posttreatment, suggesting that treatment intensity in this unique population may adversely affect QOL. C1 [Lohavanichbutr, Pawadee; Houck, John; Doody, David R.; Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. [Sharma, Arun; Mendez, Eduardo; Futran, Neal D.; Chen, Chu] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Yueh, Bevan] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA. [Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Chen, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,Mailstop M5-C-800, Seattle, WA 98109 USA. EM cchen@fhcrc.org OI Yueh, Bevan/0000-0003-1380-1053; Schwartz, Stephen/0000-0001-7499-8502 FU NCI NIH HHS [R01 CA095419, R01CA095419]; NCRR NIH HHS [KL2 RR025015, 1K1L2RR025015-01, KL2 RR025015-01] NR 16 TC 23 Z9 23 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2012 VL 146 IS 5 BP 739 EP 745 DI 10.1177/0194599811434707 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 935YY UT WOS:000303559300012 PM 22275190 ER PT J AU Jung, D Gray, ST AF Jung, David Gray, Stacey T. TI Silent Sinus Syndrome after Lateral Fracture of the Inferior Turbinate SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE silent sinus syndrome; turbinate lateral fracture; endoscopic sinus surgery; maxillary sinus atelectasis ID ENOPHTHALMOS; COMPLICATION C1 [Jung, David] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Jung, D (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM david_jung@meei.harvard.edu NR 5 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2012 VL 146 IS 5 BP 863 EP 864 DI 10.1177/0194599811424041 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 935YY UT WOS:000303559300031 PM 21952356 ER PT J AU Heyworth, L Paquin, AM Stewart, M Marcello, T Martin, T Archambeault, C Simon, SR AF Heyworth, Leonie Paquin, Allison M. Stewart, Max Marcello, Thomas Martin, Tracey Archambeault, Cliona Simon, Steven R. TI Secure Messaging for Medication Reconciliation Tool (SMMRT): A "smart" approach to post-discharge medication reviews SO PHARMACOTHERAPY LA English DT Meeting Abstract C1 [Heyworth, Leonie; Paquin, Allison M.; Stewart, Max; Marcello, Thomas; Martin, Tracey; Simon, Steven R.] VA Boston Healthcare Syst, Boston, MA USA. [Archambeault, Cliona] New England Vet Engn Resource Ctr VERC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2012 VL 32 IS 5 BP E121 EP E121 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 934IH UT WOS:000303437200043 ER PT J AU Hamblin, MR AF Hamblin, Michael R. TI Antimicrobial Photodynamic Therapy and Photodynamic Inactivation, or Killing Bugs with Dyes and Light-A Symposium-in-Print SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Editorial Material ID PSEUDOMONAS-AERUGINOSA; CANDIDA-ALBICANS; VITRO; PHOTOINACTIVATION; RESISTANCE; PHOTOSENSITIZERS; DERIVATIVES; INFECTIONS; HYPERICIN; PORPHYRIN C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA137108]; NIAID NIH HHS [R01AI050875] NR 34 TC 2 Z9 2 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2012 VL 88 IS 3 BP 496 EP 498 DI 10.1111/j.1751-1097.2012.01139.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 935EH UT WOS:000303501300002 PM 22497420 ER PT J AU Vera, DMA Haynes, MH Ball, AR Dai, TH Astrakas, C Kelso, MJ Hamblin, MR Tegos, GP AF Adolfo Vera, Domingo Mariano Haynes, Mark H. Ball, Anthony R. Dai, Tianhong Astrakas, Christos Kelso, Michael J. Hamblin, Michael R. Tegos, George P. TI Strategies to Potentiate Antimicrobial Photoinactivation by Overcoming Resistant Phenotypes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID STAPHYLOCOCCUS-EPIDERMIDIS BIOFILMS; GRAM-NEGATIVE BACTERIA; TOLUIDINE-BLUE-O; MEDIATED PHOTODYNAMIC INACTIVATION; PSEUDOMONAS-AERUGINOSA BIOFILMS; MULTIDRUG TRANSPORTER BMR; N-METHYL-PYRIDYL; EFFLUX PUMP; IN-VITRO; CRYSTAL-STRUCTURE AB Conventional antimicrobial strategies have become increasingly ineffective due to the emergence of multidrug resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered the exploration of alternative treatments and unconventional approaches towards controlling microbial infections. Photodynamic therapy (PDT) was originally established as an anticancer modality and is currently used in the treatment of age-related macular degeneration. The concept of photodynamic inactivation requires cell exposure to light energy, typically wavelengths in the visible region that causes the excitation of photosensitizer molecules either exogenous or endogenous, which results in the production of reactive oxygen species (ROS). ROS produce cell inactivation and death through modification of intracellular components. The versatile characteristics of PDT prompted its investigation as an anti-infective discovery platform. Advances in understanding of microbial physiology have shed light on a series of pathways, and phenotypes that serve as putative targets for antimicrobial drug discovery. Investigations of these phenotypic elements in concert with PDT have been reported focused on multidrug efflux systems, biofilms, virulence and pathogenesis determinants. In many instances the results are promising but only preliminary and require further investigation. This review discusses the different antimicrobial PDT strategies and highlights the need for highly informative and comprehensive discovery approaches. C1 [Tegos, George P.] Univ New Mexico, Sch Med, Dept Pathol, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Adolfo Vera, Domingo Mariano] Univ Nacl Mar del Plata, Fac Ciencias Exactas & Nat, Dept Chem, Mar Del Plata, Buenos Aires, Argentina. [Ball, Anthony R.] Toxikon Corp, Bedford, MA USA. [Tegos, George P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Dai, Tianhong; Hamblin, Michael R.; Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Astrakas, Christos] Democritus Univ, Thrace Med Sch, Div Internal Med, Alexandroupolis, Greece. [Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Tegos, GP (reprint author), Univ New Mexico, Sch Med, Dept Pathol, Ctr Mol Discovery, Albuquerque, NM 87131 USA. EM gtegos@salud.unm.edu OI Kelso, Michael/0000-0001-7809-6637; Hamblin, Michael/0000-0001-6431-4605 FU NIH [5U54MH084690-02, RO1 AI050875]; US Air Force MFEL [FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research Foundation [109421] FX George P. Tegos is supported by the NIH (grant 5U54MH084690-02). Research conducted in the Hamblin Laboratory was supported by NIH (RO1 AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079). TD was partially supported by a Bullock-Wellman Fellowship Award and an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). NR 127 TC 34 Z9 38 U1 4 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2012 VL 88 IS 3 BP 499 EP 511 DI 10.1111/j.1751-1097.2012.01087.x PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 935EH UT WOS:000303501300003 PM 22242675 ER PT J AU Hudkins, M O'Neill, J Tobias, MC Bartzokis, G London, ED AF Hudkins, Matthew O'Neill, Joseph Tobias, Marc C. Bartzokis, George London, Edythe D. TI Cigarette smoking and white matter microstructure SO PSYCHOPHARMACOLOGY LA English DT Article DE White matter; Diffusion tensor imaging; Nicotine dependence; Magnetic resonance imaging; Fractional anisotropy; Tobacco ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CEREBRAL-BLOOD-FLOW; HUMAN BRAIN; FRACTIONAL ANISOTROPY; ALZHEIMERS-DISEASE; DIFFUSION; SMOKERS; INTEGRITY; DEPENDENCE; EXPOSURE AB Diffusion tensor imaging has been used before in testing associations between cigarette smoking and white matter integrity, with inconsistent results. Published reports indicate higher fractional anisotropy (FA, a measure of linear water diffusion) in some brain regions and lower FA in others in adult smokers compared to nonsmokers. Adolescent smokers exhibited elevated FA at several brain regions and a positive correlation of FA in the genu corpus callosum with exposure to smoking (pack-years). To help resolve prior discrepancies, we studied adults, sampling multiple brain regions, and testing for relationships to clinical features of nicotine dependence and exposure to smoking. Brain MRI scans (1.5 T) were acquired, and FA and apparent diffusion coefficient (ADC, a measure of random diffusion) were assayed in corpus callosum and prefrontal white matter, corona radiata, internal capsule, cingulum bundle, and hippocampal perforant fibers in 18 smokers (33.7 +/- 7.9 years of age) and 18 age- and gender-matched nonsmokers. ADC showed no group difference, but smokers had higher (4.3-21.1%) FA than nonsmokers. The differences were significant in right prefrontal white matter, cingulum, and genu corpus callosum. FA in several regions was negatively correlated with nicotine dependence or cigarettes/day. Combined with earlier findings, these results suggest a model of changing trajectories whereby FA is higher with tobacco exposure during adolescence and declines with continued smoking in adulthood. This notion is supported by the observation that, at multiple sampling sites, participants who had started smoking earlier in life had higher FA than those who had started later. C1 [Hudkins, Matthew; O'Neill, Joseph] UCLA Semel Inst Neurosci & Biobehav Studies, Div Child & Adolescent Psychiat, Los Angeles, CA 90024 USA. [Tobias, Marc C.; London, Edythe D.] UCLA Semel Inst Neurosci & Biobehav Studies, Lab Mol Neuroimaging, Los Angeles, CA 90024 USA. [Bartzokis, George; London, Edythe D.] UCLA Brain Res Inst, Los Angeles, CA USA. [Bartzokis, George] Univ Calif Los Angeles, Dept Neurol, Div Brain Mapping, Lab Neuroimaging, Los Angeles, CA 90024 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [London, Edythe D.] UCLA Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP O'Neill, J (reprint author), UCLA Semel Inst Neurosci & Biobehav Studies, Div Child & Adolescent Psychiat, 760 Westwood Plaza,58-227A, Los Angeles, CA 90024 USA. EM joneill@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU National Institutes of Health [P20DA022539, R01DA020726, R03DA20512, R21DA023192, MOIRR00865]; Katherine K. and Thomas P. Pike Chair in Addiction Studies; Marjorie Green Family Trust; UCLA [20063287]; Philip Morris USA FX This work was supported by grants from the National Institutes of Health [P20DA022539, R01DA020726-EDL; R03DA20512, R21DA023192 -JON; and MOIRR00865 (UCLA General Clinical Research Center)]. Additional funding was provided by endowments from the Katherine K. and Thomas P. Pike Chair in Addiction Studies and the Marjorie Green Family Trust (EDL). Research support for projects other than the one reported here was supplied to Dr. Edythe London under UCLA contract (number 20063287) with Philip Morris USA. NR 50 TC 29 Z9 30 U1 3 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2012 VL 221 IS 2 BP 285 EP 295 DI 10.1007/s00213-011-2621-9 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 934PT UT WOS:000303457600010 PM 22215225 ER PT J AU Giani, A Peroglio, A Staurenghi, G AF Giani, Andrea Peroglio, Antonio Staurenghi, Giovanni TI REPEATABILITY AND REPRODUCIBILITY OF RETINAL THICKNESS MEASUREMENTS WITH SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY USING DIFFERENT SCAN PARAMETERS SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE repeatability; reproducibility; retinal thickness; SD-OCT ID DIABETIC MACULAR EDEMA; INSTRUMENTS; ANALYZER AB Purpose: To evaluate repeatability (test-retest) and reproducibility of retinal thickness measurements using spectral-domain optical coherence tomography with different densities of A-scans per B-scan and different frames per B-scan for real-time averaging. Methods: Twelve healthy subjects were analyzed by spectral-domain optical coherence tomography. Raster lines analysis with 19 B-scans over the examined area centered on the macula was performed. Images were acquired both in standard-density (768 A-scans/B-scan) and high-density (1,536 A-scans/B-scan) modalities. Moreover, images were acquired using 2 and 20 frames/B-scan for real-time averaging. Each analysis was repeated twice to test for repeatability. Results: Intersession repeatability was good for all studied analysis protocols, with Lin concordance correlation coefficient values ranging between 0.88 and 1.00. Reproducibility assessment showed consistent retinal thickness measurements using variable scan density, with Bland-Altman limits of agreement of -6 mu m to 6 mu m in the central area. Reproducibility assessment showed consistent retinal thickness measurements using different number of frames used in the real-time averaging process, with Bland-Altman limits of agreement of -8 mu m to 4 mu m in the central area. Conclusion: Spectral-domain optical coherence tomography is a very reliable tool for central retinal thickness assessment. Changes in the number of A-scans/B-scan and in frames used for real-time averaging do not affect repeatability and reproducibility. RETINA 32:1007-1012, 2012 C1 [Giani, Andrea; Peroglio, Antonio; Staurenghi, Giovanni] Univ Milan, Sacco Hosp, Dept Clin Sci Luigi Sacco, Eye Clin, I-20100 Milan, Italy. [Giani, Andrea] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. RP Staurenghi, G (reprint author), Univ Milan, Sacco Hosp, Dept Clin Sci Luigi Sacco, Eye Clin, Via GB Grassi 74, I-20100 Milan, Italy. EM giovanni.staurenghi@unimi.it NR 22 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY PY 2012 VL 32 IS 5 BP 1007 EP 1012 DI 10.1097/IAE.0b013e31822f5660 PG 6 WC Ophthalmology SC Ophthalmology GA 935EQ UT WOS:000303502200019 PM 22366899 ER PT J AU Samir, AE Vij, A Seale, MK Desai, G Halpern, E Faquin, WC Parangi, S Hahn, PF Daniels, GH AF Samir, Anthony E. Vij, Abhinav Seale, Melanie K. Desai, Gaurav Halpern, Elkan Faquin, William C. Parangi, Sareh Hahn, Peter F. Daniels, Gilbert H. TI Ultrasound-Guided Percutaneous Thyroid Nodule Core Biopsy: Clinical Utility in Patients with Prior Nondiagnostic Fine-Needle Aspirate SO THYROID LA English DT Article ID SCIENCE CONFERENCE; MANAGEMENT; CANCER; GLAND; US; DIAGNOSIS; SOLITARY; CYTOLOGY; GUIDANCE; STATE AB Background: Five percent to 20% of thyroid nodule fine-needle aspiration (FNA) samples are nondiagnostic. The objective of this study was to determine whether a combination of FNA and core biopsy (CFNACB) would yield a higher proportion of diagnostic readings compared with FNA alone in patients with a history of one or more prior nondiagnostic FNA readings. Methods: We conducted a retrospective study of 90 core biopsies (CBs) performed in 82 subjects (55 women and 27 men) between 2006 and 2008 in an outpatient clinic. Results: CFNACB yielded a diagnostic reading in 87%. The diagnostic reading yield of the CB component of CFNACB was significantly superior to the concurrent FNA component, with CB yielding a diagnosis in 77% of cases and FNA yielding a diagnosis in 47% (p < 0.0001). The combination of CB and FNA had a higher diagnostic reading yield than either alone. In 69 nodules that had only one prior nondiagnostic FNA, CB was diagnostic in 74%, FNA was diagnostic in 52%, CFNACB was diagnostic in 87%, and CB performed significantly better than FNA (p = 0.0135). In 21 nodules with two or more prior nondiagnostic FNAs, CFNACB and CB were diagnostic in 86%, FNA was diagnostic in 29%, and CB was significantly better than FNA (p = 0.0005). Clinical, ultrasound, or histopathologic follow-up was available for 81% (73/90) of the CFNACB procedures. No subject with a benign CFNACB reading was diagnosed with thyroid malignancy in the follow-up period (range 4-37 months, mean 18 months), although one subject had minimal increase in nodule size and was awaiting repeat sonog-raphy at study conclusion. Conclusion: Thyroid nodule CFNACB is safe and clinically useful in selected patients when a prior FNA reading is nondiagnostic. CFNACB is superior to either CB or FNA alone. CFNACB should be strongly considered as an alternative to surgery in individuals with two prior nondiagnostic FNAs. C1 [Samir, Anthony E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Halpern, Elkan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA 02114 USA. RP Samir, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM asamir@partners.org OI Samir, Anthony/0000-0002-7801-8724 FU NCI NIH HHS [R01 CA149738] NR 34 TC 52 Z9 57 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD MAY PY 2012 VL 22 IS 5 BP 461 EP 467 DI 10.1089/thy.2011.0061 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935UI UT WOS:000303546500003 PM 22304390 ER PT J AU Passon, N Puppin, C Lavarone, E Bregant, E Franzoni, A Hershman, JM Fenton, MS D'Agostino, M Durante, C Russo, D Filetti, S Damante, G AF Passon, Nadia Puppin, Cinzia Lavarone, Elisa Bregant, Elisa Franzoni, Alessandra Hershman, Jerome M. Fenton, Mike S. D'Agostino, Maria Durante, Cosimo Russo, Diego Filetti, Sebastiano Damante, Giuseppe TI Cyclic AMP-Response Element Modulator Inhibits the Promoter Activity of the Sodium Iodide Symporter Gene in Thyroid Cancer Cells SO THYROID LA English DT Article ID SODIUM/IODIDE SYMPORTER; TRANSCRIPTIONAL REPRESSION; UPSTREAM ENHANCER; EXPRESSION; BINDING; PROTEIN; DOMAIN; PAX-8; IDENTIFICATION; CARCINOMA AB Background: Comprehension of the regulatory mechanism involved in the sodium iodide symporter (NIS) expression is of great relevance for thyroid cancer. In fact, restoration of NIS expression would be a strategy to treat undifferentiated thyroid cancer. Previous in vitro findings suggest that the cyclic AMP-response element (CRE) modulator (CREM) is involved in control of NIS expression. In this work, we examined the expression of CREM in a series of thyroid cancer tissues and its action on NIS promoter in human thyroid cancer cells. Methods: Expression of mRNA levels for CREM, PAX8 and NIS was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 6 normal thyroid tissues, 22 papillary, 12 follicular and 4 anaplastic thyroid cancers. The effect of CREM on transcriptional activity of the NIS promoter was investigated by transient transfection of human thyroid cell lines. Results: Compared to normal tissues, NIS and PAX8 mRNA levels were significantly reduced in all types of thyroid cancer. As expected, the maximal decrease was detected in anaplastic thyroid cancer. Conversely, CREM mRNA levels were increased in all types of thyroid cancer, reaching statistical significance for follicular and anaplastic thyroid carcinoma (p = 0.0157 and 0.0045, respectively). Transfection experiments showed an inhibitory effect of CREM on NIS promoter activity in various thyroid cancer cell lines. Conclusions: These data demonstrate that CREM expression is increased in thyroid cancer tissue and may play a role in the downregulation of NIS expression in thyroid cancer acting at the transcriptional level. C1 [Durante, Cosimo; Filetti, Sebastiano] Univ Roma La Sapienza, Dipartimento Med Interna & Specialita Med, I-00161 Rome, Italy. [Passon, Nadia; Puppin, Cinzia; Lavarone, Elisa; Bregant, Elisa; Damante, Giuseppe] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy. [Franzoni, Alessandra; Damante, Giuseppe] St Mary Mercy Univ Hosp, Inst Med Genet, Udine, Italy. [Hershman, Jerome M.; Fenton, Mike S.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [D'Agostino, Maria] Univ Catanzaro, Dept Pharmacobiol Sci, Catanzaro, Italy. RP Filetti, S (reprint author), Univ Roma La Sapienza, Dipartimento Med Interna & Specialita Med, Piazzale Aldo Moro 5, I-00161 Rome, Italy. EM sebastiano.filetti@uniroma1.it RI Lavarone, Elisa/I-4853-2012 FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 10296]; MIUR [20093WAPIK_003]; American Thyroid Association; Umberto Di Mario Foundation; Banca d'Italia FX This work was supported by grants to G.D. from Associazione Italiana per la Ricerca sul Cancro (AIRC) (No. IG 10296) and MIUR (PRIN No. 20093WAPIK_003), to M. F. from the American Thyroid Association, and to S. F. from The Umberto Di Mario Foundation and from the Banca d'Italia. NR 37 TC 1 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2012 VL 22 IS 5 BP 487 EP 493 DI 10.1089/thy.2011.0360 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935UI UT WOS:000303546500007 PM 22510021 ER PT J AU Gershman, B Eisner, BH AF Gershman, Boris Eisner, Brian H. TI Long-term Outcomes of Percutaneous Nephrolithotomy in Patients With Chronic Kidney Disease: A Single-center Experience EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material ID STONES; RISK C1 [Gershman, Boris; Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02215 USA. RP Gershman, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02215 USA. NR 8 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 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2012 VL 79 IS 5 BP 994 EP 995 DI 10.1016/j.urology.2011.10.069 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 934TW UT WOS:000303470600013 PM 22309785 ER PT J AU Ramsey, SD Zeliadt, SB Blough, DK Fedorenko, CR Fairweather, ME McDermott, CL Penson, DF Van Den Eeden, SK Hamilton, AS Arora, NK AF Ramsey, Scott D. Zeliadt, Steven B. Blough, David K. Fedorenko, Catherine R. Fairweather, Megan E. McDermott, Cara L. Penson, David F. Van Den Eeden, Stephen K. Hamilton, Ann S. Arora, Neeraj K. TI Complementary and Alternative Medicine Use, Patient-reported Outcomes, and Treatment Satisfaction Among Men With Localized Prostate Cancer SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; PREVALENCE; THERAPY; CAPSURE; BOTHER AB OBJECTIVE To evaluate the association between complementary and alternative medicine (CAM) use, satisfaction with treatment, and patient-reported outcomes after treatment. METHODS The Prostate CAncer Therapy Selection Study prospectively surveyed patients newly diagnosed with localized prostate cancer about their treatment decision-making process and outcomes. The Prostate CAncer Therapy Selection Study recruited patients from 3 geographic areas through hospital-based urology clinics and community urology practices. RESULTS More than 700 patients completed the baseline and follow-up surveys. More than 50% of respondents reported using CAM; this decreased to 39% if prayer was excluded as a type of CAM. On multivariate analysis, factors related to communication with the treating physician, but not CAM use, were associated with treatment satisfaction. The likelihood of stability or improvement in urinary, bowel, and sexual function at 6 months was related to the choice of primary therapy but was unrelated to CAM use. CONCLUSION In the present prospective observational study, CAM use was highly prevalent but unrelated to treatment satisfaction or changes in functional status. The effect of CAM on these endpoints remains to be established in comparative effectiveness studies. UROLOGY 79: 1034-1041, 2012. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU National Cancer Institute [HHSN261200900582P, N01-PC-35142, N01-PC-35139, N01-PC-35136]; Cancer Surveillance System of the Fred Hutchinson Cancer Research Center; Fred Hutchinson Cancer Research Center; State of Washington FX This publication was supported by the National Cancer Institute (grants HHSN261200900582P, N01-PC-35142, N01-PC-35139, and N01-PC-35136) and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, funded by contract N01-PC-35142 from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. NR 28 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAY PY 2012 VL 79 IS 5 BP 1034 EP 1041 DI 10.1016/j.urology.2012.01.023 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 934TW UT WOS:000303470600022 PM 22546381 ER PT J AU Bauer, KA AF Bauer, Kenneth A. TI Reversal of antithrombotic agents SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review ID DEEP-VEIN-THROMBOSIS; CATHETER-DIRECTED THROMBOLYSIS; QUALITY-OF-LIFE; THROMBOEMBOLIC PULMONARY-HYPERTENSION; VENOUS THROMBOSIS; POSTTHROMBOTIC SYNDROME; PHARMACOMECHANICAL THROMBECTOMY; POSTPHLEBITIC-SYNDROME; COMPRESSION STOCKINGS; RANDOMIZED TRIAL AB Anticoagulants are the mainstay of therapy for thromboembolic diseases. In addition to the more traditional agents, new oral anticoagulants, including dabigatran etexilate, rivaroxaban, and apixaban, have been shown to be effective across several indications. Bleeding is a serious complication associated with any anticoagulant, but many of the traditional parenteral and new oral agents do not currently have specific antidotes. This review describes available and future options for the reversal of the effects of anticoagulants, in particular the new oral agents and discusses current management strategies for bleeding events in clinical practice. Am. J. Hematol. 87: S119-S126, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Bauer, Kenneth A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Bauer, Kenneth A.] VA Boston Healthcare Syst, Boston, MA USA. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM kbauer@bidmc.harvard.edu FU Bayer HealthCare Pharmaceuticals; Janssen Research & Development, LLC FX The author would like to acknowledge Kelly Farrell who provided editorial assistance with funding from Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC. NR 55 TC 48 Z9 49 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S119 EP S126 DI 10.1002/ajh.23165 PG 8 WC Hematology SC Hematology GA 928RB UT WOS:000302999500021 PM 22460529 ER PT J AU Davies, LE Schoch, PH AF Davies, Loren E. Schoch, Patricia H. TI Retrospective Review of PeriProcedures in Warfarin Patients At the Denver Va Medical Center (DVAMC) SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Davies, Loren E.; Schoch, Patricia H.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S153 EP S153 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500046 ER PT J AU Garcia, D Van Cott, EM Kouides, PA AF Garcia, David Van Cott, Elizabeth M. Kouides, Peter A. TI Introductory remarks for the THSNA meeting proceedings: Hemostasis and thrombosis at the cutting edge SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material C1 [Garcia, David] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kouides, Peter A.] Univ Rochester, Sch Med, Dept Hematol & Oncol, Rochester, NY USA. [Kouides, Peter A.] Roswell Pk Mem Canc Inst, Rochester, NY USA. RP Garcia, D (reprint author), Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S1 EP S1 DI 10.1002/ajh.23181 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500001 PM 22473910 ER PT J AU Grabowski, EF Kushak, RI Yam, K Ingelfinger, JR AF Grabowski, Eric F. Kushak, Rafail I. Yam, Kylee Ingelfinger, Julie R. TI Shiga Toxin Upregulates Tissue Factor Gene Expression in Endothelium and Reduces Synthesis, Cell-Surface Association, and Secretion of Tissue Factor Pathway Inhibitor SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Grabowski, Eric F.; Kushak, Rafail I.; Yam, Kylee; Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S186 EP S186 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500131 ER PT J AU Grabowski, EF Yam, K Gerace, M AF Grabowski, Eric F. Yam, Kylee Gerace, Matthew TI Evaluation of hemostasis in flowing blood SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID COAGULATION-LABORATORY-ASSOCIATION; VON-WILLEBRAND-DISEASE; TRANSMISSION PLATELET AGGREGOMETRY; BLEEDING DISORDERS; DIAGNOSIS; MANAGEMENT; SUBCOMMITTEE; GUIDELINES; ASSAY AB Hemostasis and thrombosis are now increasingly recognized as integrally related to blood rheology and blood flow. Platelets, for example, are known to access the vessel wall in ways which depend upon the small-scale motions of neighboring erythrocytes, and access one another via collisions driven by gradients in blood flow velocity. In this context, flow devices have become a subject of great interest in the clinical assessment of bleeding disorders, especially platelet function defects and von Willebrand disease. While these devices currently lack standardization and outcomes measures which establish clear clinical utility, their promise remains great, particularly in the potential to simulate the microenvironment of arteries vs. veins and in their ability to incorporate such intrinsically flow-dependent phenomena as co-localization of tissue-factor-bearing microparticles with platelets, the weakness of the GPIb-vWF bond at very high shear stresses, and even the hemostatic and antithrombotic function of vascular endothelium. In contrast, currently utilized assays are often performed under static conditions that do not involve flow and therefore are not able to simulate the microenvironment of arteries and veins. Am. J. Hematol. 87: S51-S55, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Grabowski, Eric F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA. EM egrabowski@partners.org NR 22 TC 7 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S51 EP S55 DI 10.1002/ajh.23207 PG 5 WC Hematology SC Hematology GA 928RB UT WOS:000302999500010 PM 22495911 ER PT J AU Hayward, CPM Moffat, KA Plumhoff, E Van Cott, EM AF Hayward, Catherine P. M. Moffat, Karen A. Plumhoff, Elizabeth Van Cott, Elizabeth M. TI Approaches to investigating common bleeding disorders: An evaluation of North American coagulation laboratory practices SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID VON-WILLEBRAND-DISEASE; EHLERS-DANLOS-SYNDROME; STORAGE POOL DEFICIENCY; PLATELET-FUNCTION; DIAGNOSTIC EVALUATION; CHILDREN; SYMPTOMS; AGGREGATION; QUESTIONNAIRE; AGGREGOMETRY AB Bleeding disorders commonly result from deficiencies or defects in von Willebrand factor (VWF), platelets, coagulation factors, or fibrinolytic proteins. The primary goal of our study was to assess current North American coagulation laboratory practices for diagnosing bleeding disorders, using an on-line patterns-of-practice survey of diagnostic laboratory members of the North American Specialized Coagulation Laboratory Association. The survey examined laboratory approaches to evaluating bleeding disorders, with specific questions about the tests and test panels offered and compliance to recent guideline recommendations on diagnosing von Willebrand disease (VWD) and platelet function disorders. All laboratories responding to the survey performed a prothrombin time/international normalized ratio, an activated partial thromboplastin time, and coagulation factor assays, and many tested for VWD and platelet disorders. However, few laboratories had test panels that evaluated the more common bleeding disorders and few performed some assays, including VWF multimer assessments and assays for fibrinolytic disorders. Additionally, the cutoffs used by laboratories to diagnose type 1 VWD varied considerably, with only a minority following the National Heart Lung Blood Institute recommendations. In contrast, laboratories that tested for platelet function disorders mostly complied with aggregation testing recommendations, as published in the recent North American guidelines. Our results indicate that there are some gaps in the strategies used by laboratories to diagnose bleeding disorders that might be addressed by development of further guidelines and test algorithms that emphasize evaluations for common bleeding disorders. Laboratories may also benefit from guidelines on test interpretation, and external evaluation of their bleeding disorder testing strategies. Am. J. Hematol. 87: S45-S50, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Hayward, Catherine P. M.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada. [Hayward, Catherine P. M.; Moffat, Karen A.] McMaster Univ, Dept Med, Hamilton, ON L8S 4K1, Canada. [Hayward, Catherine P. M.; Moffat, Karen A.] Hamilton Reg Lab Med Program, Hamilton, ON, Canada. [Hayward, Catherine P. M.; Moffat, Karen A.; Plumhoff, Elizabeth; Van Cott, Elizabeth M.] N Amer Specialized Coagulat Lab Assoc, Rochester, MN USA. [Plumhoff, Elizabeth] Mayo Clin, Rochester, MN USA. [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Hayward, CPM (reprint author), McMaster Univ, Dept Pathol & Mol Med, Room 2N29A,1280 Main St W, Hamilton, ON L8S 4K1, Canada. EM haywrdc@mcmaster.ca OI Hayward, Catherine/0000-0002-2843-0817 FU Heart and Stroke Career Investigator Award FX The participation of NASCOLA members in this study is gratefully acknowledged. Catherine P. M. Hayward is the recipient of a Heart and Stroke Career Investigator Award. NR 34 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S45 EP S50 DI 10.1002/ajh.23124 PG 6 WC Hematology SC Hematology GA 928RB UT WOS:000302999500009 PM 22367923 ER PT J AU Johnson, NV Khor, B Van Cott, EM AF Johnson, Nicholas V. Khor, Bernard Van Cott, Elizabeth M. TI Advances in laboratory testing for thrombophilia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACTIVATED PROTEIN-C; CAMBRIDGE-II A384S; S ASSAYS; FACTOR-V; ANTITHROMBIN DEFICIENCY; LUPUS ANTICOAGULANTS; C4B-BINDING PROTEIN; COAGULATION ASSAYS; VENOUS THROMBOSIS; RESISTANCE AB Testing for hereditary thrombophilia typically includes tests for activated protein C resistance (APC-R) and/or factor V Leiden, protein C, protein S, antithrombin, and prothrombin G20210A. New options for these assays have become available in recent years, with different advantages and disadvantages among the currently available methods. Potential interferences for each assay type are discussed, including lupus anticoagulants, heparin, warfarin, direct thrombin inhibitors (such as argatroban, dabigatran, hirudin, or bivalirudin), rivaroxaban, factor deficiencies or elevations, factor V Leiden, and specific mutations that the assay(s) might not be able to detect. Causes of acquired deficiencies are also described, as these must be carefully excluded before diagnosing a hereditary deficiency of protein C, protein S, or antithrombin. Am. J. Hematol. 87: S108-S112, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, GRJ 235,55 Fruit St, Boston, MA 02114 USA. OI Khor, Bernard/0000-0003-4689-5092 NR 37 TC 11 Z9 11 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S108 EP S112 DI 10.1002/ajh.23186 PG 5 WC Hematology SC Hematology GA 928RB UT WOS:000302999500019 PM 22473489 ER PT J AU Kaatz, S Kouides, PA Garcia, DA Spyropolous, AC Crowther, M Douketis, JD Chan, AKC James, A Moll, S Ortel, TL Van Cott, EM Ansell, J AF Kaatz, Scott Kouides, Peter A. Garcia, David A. Spyropolous, Alex C. Crowther, Mark Douketis, Jim D. Chan, Anthony K. C. James, Andra Moll, Stephan Ortel, Thomas L. Van Cott, Elizabeth M. Ansell, Jack TI Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PARTIAL THROMBOPLASTIN TIME; MONITORING UNFRACTIONATED HEPARIN; VENOUS THROMBOSIS; ANTICOAGULANT-THERAPY; INTRAVENOUS HEPARIN; PULMONARY-EMBOLISM; MAST-CELLS; THROMBOEMBOLISM; REAGENTS; RANGE AB The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed. Am. J. Hematol. 87: S141-S145, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Kaatz, Scott] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Kouides, Peter A.] Mary M Gooley Hemophilia Ctr, Dept Med, New York, NY USA. [Garcia, David A.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Spyropolous, Alex C.] Univ Rochester, Med Ctr, Div Hematol Oncol, Rochester, NY 14642 USA. [Crowther, Mark; Douketis, Jim D.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Chan, Anthony K. C.] McMaster Childrens Hosp, Div Pediat Hematol Oncol, Hamilton, ON, Canada. [James, Andra] Duke Univ, Dept Obstet & Gynecol & Med, Durham, NC USA. [Moll, Stephan] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Ortel, Thomas L.] Duke Univ, Med Ctr, Dept Pathol & Med, Durham, NC USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ansell, Jack] NYU, Sch Med, Dept Med, New York, NY USA. RP Kaatz, S (reprint author), Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. EM skaatz1@hfhs.org OI Chan, Anthony K. C./0000-0003-1551-3995 FU Boehringer-Ingelheim; Bristol Myer Squibb; Bayer/Jansen/Johnson and Johnson; Eisai; National Institute of Health; Canadian Institute of Health Research; Blue Cross/Blue Shield of Michigan; Center for Disease Control; Pfizer; GlaxoSmithKline; Daiichi Sankyo FX Scott Kaatz, DO, MSc: Grant support: Boehringer-Ingelheim, Bristol Myer Squibb, Bayer/Jansen/Johnson and Johnson, Eisai, National Institute of Health, Canadian Institute of Health Research, Blue Cross/Blue Shield of Michigan. Speaker honorarium: Jansen/Johnson and Johnson, Boehringer-Ingelheim, GlaxoSmithKline, Eisai. Consultant: Boehringer Ingelheim, Bristol Myer Squibb/Pfizer, Jansen/Johnson and Johnson. Board membership (non-profit): AC Forum, National Certification Board of Anticoagulation Providers, National Blood Clot Alliance Medical and Scientific Advisory Board. David A. Garcia, MD: Trial Steering Committee: Bristol Myer Squibb. Advisory board: Daiichi Sankyo, Boehringer Ingelheim, Bristol Myer Squibb and CSL Behring. Alex C. Spyropolous, MD: Steering Committee: Jansen/Johnson and Johnson. Data Safety Monitoring Board: Astellas. Advisory board: Boehringer Ingelheim, Johnson & Johnson, Bayer, Pfizer, Bristol Myer Squibb. Mark Crowther, MD, MSc: Educational development: Octapharma and Pfizer. Advisory boards: Octapharma, CSL Behring, Pfizer, Leo, Bayer and Boehringer Ingelheim. Expert testimony: Bayer. Jim D. Douketis, MD: Consultancies: Boehringer Ingelheim, Pfizer/Bristol Myer Squibb. Advisory board: Boehringer Ingelheim, Bayer, Sanofi, Astra-Zeneca. Anthony K. C. Chan, MBBS: Steering Committee: Bayer. Data Safety and Monitoring Board: Boehringer Ingelheim. Adjudication Committee: Bristol Myer Squibb. Advisory board: Baxter. Andra James, MD, MPH: Research funding: CSL Behring, Grifols. Advisory board: CSL Behring. Honoraria: Baxter, Octapharma. Thomas L. Ortel, MD, PhD: Grant support: National Institute of Health, Center for Disease Control, Eisai, Pfizer, GlaxoSmithKline, Daiichi Sankyo. Consultant: Sanofi, Boehringer Ingelheim, GTC Therapeutics, Instrumentation Laboratories. Jack Ansell, MD: Consultant: Bristol Myers Squibb, Pfizer, Janssen, Boehringher Ingelheim, Daiichi Sankyo. NR 34 TC 173 Z9 176 U1 1 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S141 EP S145 DI 10.1002/ajh.23202 PG 5 WC Hematology SC Hematology GA 928RB UT WOS:000302999500025 PM 22473649 ER PT J AU Moffat, KA Van Cott, E Plumhoff, E Hayward, CPM AF Moffat, Karen A. Van Cott, Elizabeth Plumhoff, Elizabeth Hayward, Catherine P. M. TI Are Clinical Laboratories Following Published Guidelines for the Interpretation of Light Transmission Aggregometry? Results from a Nascola Patterns-of-Practice Survey SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Moffat, Karen A.; Hayward, Catherine P. M.] Hamilton Reg Lab Med Program, Hamilton, ON, Canada. [Moffat, Karen A.; Hayward, Catherine P. M.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Moffat, Karen A.; Van Cott, Elizabeth; Plumhoff, Elizabeth; Hayward, Catherine P. M.] N Amer Specialized Coagulat Lab Assoc, Rochester, MN USA. [Van Cott, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Plumhoff, Elizabeth] Mayo Clin, Rochester, MN USA. [Hayward, Catherine P. M.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S173 EP S173 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500097 ER PT J AU Sarode, R Milling, TJ Refaai, MA Mangione, A Durn, BL Goldstein, JN AF Sarode, Ravindra Milling, Truman J. Refaai, Majed A. Mangione, Antoinette Durn, Billie L. Goldstein, Joshua N. TI Integrated Safety Analysis of a Four-Factor Prothrombin Complex Concentrate Versus Plasma in Phase Iii Clinical Trials SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Sarode, Ravindra] UT SW Med Ctr, Dallas, TX USA. [Milling, Truman J.] Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Austin, TX 78701 USA. [Refaai, Majed A.] Univ Rochester, Sch Med Ctr, Rochester, NY 14627 USA. [Mangione, Antoinette; Durn, Billie L.] CSL Behring, King Of Prussia, PA USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S181 EP S181 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500117 ER PT J AU Sarode, R Milling, TJ Refaai, MA Mangione, A Schneider, A Goldstein, JN AF Sarode, Ravindra Milling, Truman J. Refaai, Majed A. Mangione, Antoinette Schneider, Astrid Goldstein, Joshua N. TI Randomized Phase IIIb Study Comparing the Safety and Efficacy of Four-Factor Prothrombin Complex Concentrate with Plasma in Subjects Receiving Vitamin K Antagonists with Major Bleeding SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Sarode, Ravindra] UT SW Med Ctr, Dallas, TX USA. [Milling, Truman J.] Univ Med Ctr Brackenridge, Dell Childrens Med Ctr, Austin, TX USA. [Refaai, Majed A.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Mangione, Antoinette] CSL Behring, King Of Prussia, PA USA. [Schneider, Astrid] CSL Behring GmbH, Marburg, Germany. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S146 EP S146 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500028 ER PT J AU Smock, KJ Ledford-Kraemer, MR Meijer, P Van Cott, EM AF Smock, Kristi J. Ledford-Kraemer, Marlies R. Meijer, Piet Van Cott, Elizabeth M. TI Laboratory Testing for Heparin-Induced Thrombocytopenia: A Report from the North American Specialized Coagulation Laboratory Association (Nascola) SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Ledford-Kraemer, Marlies R.] CLOT ED Inc, Islamorada, FL USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S167 EP S168 PG 2 WC Hematology SC Hematology GA 928RB UT WOS:000302999500083 ER PT J AU Zantek, ND Hsu, PH Refaai, MA Ledford-Kraemer, M Meijer, P Van Cott, EM AF Zantek, Nicole D. Hsu, Peihong Refaai, Majed A. Ledford-Kraemer, Marlies Meijer, Piet Van Cott, Elizabeth M. TI The North American Specialized Coagulation Laboratory Association Experience with Factor VII Proficiency Testing SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hsu, Peihong] Hofstra N Shore Long Isl Jewish Sch Med, Dept Pathol Lab Med, Lake Success, NY USA. [Refaai, Majed A.] Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY 14627 USA. [Ledford-Kraemer, Marlies] CLOT ED, Islamorada, FL USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Div Clin Labs, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2012 VL 87 SU 1 BP S171 EP S171 PG 1 WC Hematology SC Hematology GA 928RB UT WOS:000302999500093 ER PT J AU Bateman, BT Callaghan, WM Kuklina, EV AF Bateman, Brian T. Callaghan, William M. Kuklina, Elena V. TI Safety and efficiency of multiple square sutures to avoid peripartum hysterectomy REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Dept Anesthesia Crit Care & Pain Med,Med Sch, Boston, MA 02114 USA. [Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Kuklina, Elena V.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Obstet Anesthesia, Dept Anesthesia Crit Care & Pain Med,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM BBateman@partners.org FU Intramural CDC HHS [CC999999] NR 3 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 2012 VL 206 IS 5 BP E5 EP E6 DI 10.1016/j.ajog.2012.02.039 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 931JB UT WOS:000303211100007 PM 22459344 ER PT J AU Brown, SD Ecker, JL Ward, JRM Halpern, EF Sayeed, SA Buchmiller, TL Mitchell, C Donelan, K AF Brown, Stephen D. Ecker, Jeffrey L. Ward, Johanna R. M. Halpern, Elkan F. Sayeed, Sadath A. Buchmiller, Terry L. Mitchell, Christine Donelan, Karen TI Prenatally diagnosed fetal conditions in the age of fetal care: does who counsels matter? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE congenital abnormalities; fetal; physician attitudes; pregnancy management; prenatal diagnosis ID LEFT-HEART SYNDROME; LOW GESTATIONAL-AGE; QUALITY-OF-LIFE; DOWN-SYNDROME; ULTRASOUND DIAGNOSIS; HEALTH-PROFESSIONALS; EUROPEAN COUNTRIES; NEONATAL OUTCOMES; CESAREAN-SECTION; PRETERM INFANTS AB OBJECTIVE: We sought to characterize practices and attitudes of maternal- fetal medicine (MFM) and fetal care pediatric (FCP) specialists regarding fetal abnormalities. STUDY DESIGN: This was a self-administered survey of 434 MFMs and FCPs (response rate: MFM 60.9%; FCP 54.2%). RESULTS: For Down syndrome (DS), congenital diaphragmatic hernia (CDH), spina bifida: MFMs were more likely than FCPs to support termination (DS 52% vs 35%, P < .001; CDH 49% vs 36%, P < .001; spina bifida 54% vs 35%, P < .001), and consider offering termination options as highly important (DS 90% vs 70%, P < .001; CDH 88% vs 69%, P < .001; spina bifida 88% vs 70%, P < .001). For DS only, MFMs were less likely than FCPs to think that pediatric specialist consultation should be offered prior to a decision regarding termination (54% vs 75%, P < .001). MFMs reported report higher termination rates among patients only for DS (DS 51% vs 21%, P < .001). CONCLUSION: MFM and FCP specialists' counseling attitudes differ for fetal abnormalities. C1 [Brown, Stephen D.] Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. [Buchmiller, Terry L.] Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Sayeed, Sadath A.] Childrens Hosp Boston, Div Newborn Med, Dept Med, Boston, MA 02115 USA. [Buchmiller, Terry L.] Childrens Hosp Boston, Adv Fetal Care Ctr, Boston, MA 02115 USA. [Mitchell, Christine] Childrens Hosp Boston, Off Eth, Boston, MA 02115 USA. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Ward, Johanna R. M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Sayeed, Sadath A.; Mitchell, Christine] Harvard Univ, Sch Med, Div Med Eth, Dept Global Hlth & Social Med, Boston, MA USA. RP Brown, SD (reprint author), Childrens Hosp Boston, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM Stephen.brown@childrens.harvard.edu FU Greenwall Foundation; Kornfeld Program in Bioethics and Patient Care; Harvard University; American Roentgen Ray Society; Office of Faculty Development, Children's Hospital Boston FX This study was supported by grants from the Greenwall Foundation, the Kornfeld Program in Bioethics and Patient Care, the Harvard University William F. Milton Fund, the American Roentgen Ray Society Leonard Berlin Scholarship in Medical Professionalism, and a Faculty Career Development Award, Office of Faculty Development, Children's Hospital Boston (all to S.D.B.). NR 51 TC 0 Z9 0 U1 0 U2 5 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 2012 VL 206 IS 5 AR 409.e1 DI 10.1016/j.ajog.2012.01.026 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 931JB UT WOS:000303211100015 PM 22340943 ER PT J AU Lehavot, K Hoerster, KD Nelson, KM Jakupcak, M Simpson, TL AF Lehavot, Keren Hoerster, Katherine D. Nelson, Karin M. Jakupcak, Matthew Simpson, Tracy L. TI Health Indicators for Military, Veteran, and Civilian Women SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; US MILITARY; MILLENNIUM COHORT; WAR VETERANS; ACTIVE-DUTY; CARE; OBESITY; DISPARITIES AB Background: Women who have served in the military are a rapidly growing population. No previous studies have compared directly their health status to that of civilians. Purpose: To provide estimates of several leading U.S. health indicators by military service status among women. Methods: Data were obtained from the 2010 Behavioral Risk Factor Surveillance Survey, a U.S. population-based study. Health outcomes were compared by military status using multivariable logistic regression among the female participants (274,399 civilians, 4221 veterans, 661 active duty, and 995 National Guard or Reserves [NG/R]). Data were analyzed in August 2011. Results: Veterans reported poorer general health and greater incidence of health risk behaviors, mental health conditions, and chronic health conditions than civilian women. Active duty women reported better access to health care, better physical health, less engagement in health risk behaviors, and greater likelihood of having had a recent Pap than civilian women. Women from the NG/R were comparable to civilians across most health domains, although they had a greater likelihood of being overweight or obese and reporting a depressive and anxiety disorder. Conclusions: Compared with civilian women, NG/R women rated their health and access to health care similarly and active duty women rated theirs better on several domains, but veterans consistently reported poorer health. (Am J Prev Med 2012;42(5):473-480) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Lehavot, Keren; Hoerster, Katherine D.; Nelson, Karin M.; Jakupcak, Matthew; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Lehavot, Keren; Hoerster, Katherine D.; Jakupcak, Matthew; Simpson, Tracy L.] Univ Washington, Seattle Div, Seattle, WA 98195 USA. [Lehavot, Keren; Hoerster, Katherine D.; Jakupcak, Matthew; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116-POC, Seattle, WA 98108 USA. EM klehavot@uw.edu FU VA Puget Sound Health Care System, Seattle, Washington FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. The views expressed in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 46 TC 57 Z9 57 U1 5 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2012 VL 42 IS 5 BP 473 EP 480 DI 10.1016/j.amepre.2012.01.006 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 928ED UT WOS:000302963300012 PM 22516487 ER PT J AU Rasmussen, J Wilhelm, S AF Rasmussen, Jessica Wilhelm, Sabine TI Obsessive-Compulsive Spectrum Disorders: Refining the Research Agenda for DSM-V SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Rasmussen, Jessica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Wilhelm, Sabine] Massachusetts Gen Hosp, OCD & Related Disorders Program, Boston, MA 02114 USA. RP Rasmussen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 6 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 2012 VL 169 IS 5 BP 542 EP 543 DI 10.1176/appi.ajp.2011.11101600 PG 2 WC Psychiatry SC Psychiatry GA 932LJ UT WOS:000303292300026 ER PT J AU Stoddard, FJ AF Stoddard, Frederick J., Jr. TI Religious and Spiritual Issues in Psychiatric Diagnosis: A Research Agenda for DSM-V SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Book Review C1 [Stoddard, Frederick J., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Stoddard, Frederick J., Jr.] Shriners Hosp Children, Boston, MA USA. RP Stoddard, FJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 1 U2 3 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 2012 VL 169 IS 5 BP 544 EP 545 DI 10.1176/appi.ajp.2011.11111692 PG 2 WC Psychiatry SC Psychiatry GA 932LJ UT WOS:000303292300028 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Unstable Angina and Non-ST Elevation Myocardial Infarction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE antiplatelet drugs; invasive strategy; anticoagulants; coronary revascularization; ST segment deviations ID ACUTE CORONARY SYNDROMES; GLYCOPROTEIN IIB/IIIA INHIBITORS; RANDOMIZED CLINICAL-TRIALS; C-REACTIVE PROTEIN; SEGMENT-ELEVATION; ANTIPLATELET THERAPY; METABOLIC EFFICIENCY; NATRIURETIC PEPTIDE; PLATELET INHIBITION; LESS ISCHEMIA AB Non-ST elevation acute coronary syndromes are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, they are among the most common serious illnesses in adults, and are associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves antiischemic agents (nitrates and beta blockers), antiplatelet drugs (aspirin, P2Y(12), and glycoprotein IIb/IIIa receptor blockers), and anticoagulants (unfractionated and low-molecular-weight heparins). Patients should undergo risk stratification, and those with high-risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated. C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 48 TC 14 Z9 15 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2012 VL 185 IS 9 BP 924 EP 932 DI 10.1164/rccm.201109-1745CI PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 930ZE UT WOS:000303182700007 PM 22205565 ER PT J AU Gervais, DA Arellano, RS AF Gervais, Debra A. Arellano, Ronald S. TI Ablation of Hepatocellular Carcinoma: An Incomplete Review Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Gervais, Debra A.; Arellano, Ronald S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Gervais, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 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 2012 VL 198 IS 5 BP W507 EP W507 DI 10.2214/AJR.11.8262 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 930TG UT WOS:000303162800017 ER PT J AU Chau, N Xin, C Grafals, M Tran, P Castano, AP Linn, G Ren, S Li, J Kersjes, K Chang, A Bhat, B Hartner, J Orkin, S Portilla, D MacKenna, DA Duffield, JS AF Chau, N. Xin, C. Grafals, M. Tran, P. Castano, A. P. Linn, G. Ren, S. Li, J. Kersjes, K. Chang, A. Bhat, B. Hartner, J. Orkin, S. Portilla, D. MacKenna, D. A. Duffield, J. S. TI Inhibition of microRNA-21 as a Therapeutic Strategy for Kidney Fibrosis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Chau, N.; Tran, P.; Li, J.; Kersjes, K.; Chang, A.; Bhat, B.; MacKenna, D. A.] Regulus Pharmaceut, San Diego, CA USA. [Xin, C.; Castano, A. P.; Linn, G.; Ren, S.; Orkin, S.; Duffield, J. S.] Univ Washington, Div Renal, Seattle, WA 98195 USA. [Xin, C.; Castano, A. P.; Linn, G.; Ren, S.; Orkin, S.; Duffield, J. S.] Univ Washington, Dept Med, Ctr Lung Biol, Seattle, WA USA. [Xin, C.; Castano, A. P.; Linn, G.; Ren, S.; Orkin, S.; Duffield, J. S.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. [Grafals, M.] Lahey Clin Fdn, Dept Transplantat, Burlington, MA USA. [Hartner, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp, Boston, MA 02115 USA. [Portilla, D.] Univ Arkansas, Little Rock, AR 72204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 6 BP 28 EP 28 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500007 ER PT J AU Lee, KM Kim, JI Yeh, H Zhao, G Stott, R Soohoo, J Deng, S Markmann, JF AF Lee, K. M. Kim, J. I. Yeh, H. Zhao, G. Stott, R. Soohoo, J. Deng, S. Markmann, J. F. TI Regulatory-B Cell and Regulatory-T Cell Collaborate To Promote Transplantation Tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Lee, K. M.; Kim, J. I.; Yeh, H.; Stott, R.; Soohoo, J.; Deng, S.; Markmann, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhao, G.; Deng, S.] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 85 BP 52 EP 52 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500086 ER PT J AU Kim, JI Lee, KM Stott, R O'Connor, MR Yeh, H Zhao, G Eliades, P Soohoo, J Fox, C Cheng, N Deng, S Markmann, JF AF Kim, J. I. Lee, K. M. Stott, R. O'Connor, M. R. Yeh, H. Zhao, G. Eliades, P. Soohoo, J. Fox, C. Cheng, N. Deng, S. Markmann, J. F. TI Anti-CD45RB/Anti-TIM-1-Induced Tolerance Requires Regulatory B Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Kim, J. I.; Lee, K. M.; Stott, R.; O'Connor, M. R.; Yeh, H.; Zhao, G.; Eliades, P.; Soohoo, J.; Fox, C.; Cheng, N.; Deng, S.; Markmann, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 88 BP 53 EP 53 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500089 ER PT J AU Lee, S Aoyama, A Tonsho, M Boskovic, S Yamada, Y Smith, RN Colvin, RB Cosimi, AB Benichou, G Madsen, JC Kawai, T Allan, JS AF Lee, S. Aoyama, A. Tonsho, M. Boskovic, S. Yamada, Y. Smith, R. -N. Colvin, R. B. Cosimi, A. B. Benichou, G. Madsen, J. C. Kawai, T. Allan, J. S. TI Anti-IL-6R Antibodies Prevent Acute Rejection of Allogeneic Lung Transplants in Monkeys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Lee, S.; Aoyama, A.; Tonsho, M.; Boskovic, S.; Yamada, Y.; Smith, R. -N.; Colvin, R. B.; Cosimi, A. B.; Benichou, G.; Madsen, J. C.; Kawai, T.; Allan, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 235 BP 96 EP 96 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500236 ER PT J AU Wang, L Liu, Y Bradner, JE Hancock, WW AF Wang, L. Liu, Y. Bradner, J. E. Hancock, W. W. TI Selective Inhibition of Epigenetic Readers: Competitive Inhibition of BET Bromodomains Prevents T Cell Activation and Promotes Long-Term Renal and Cardiac Allograft Acceptance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Wang, L.; Liu, Y.; Hancock, W. W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Wang, L.; Liu, Y.; Hancock, W. W.] Univ Penn, Philadelphia, PA 19104 USA. [Bradner, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bradner, J. E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 237 BP 97 EP 97 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500238 ER PT J AU Liu, W Xiao, X Demirci, G Madsen, J Li, XC AF Liu, W. Xiao, X. Demirci, G. Madsen, J. Li, X. C. TI Identification of Alloreactive Macrophages In Vivo That Recognize and Reject Allogeneic Non-Self SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Liu, W.; Xiao, X.; Demirci, G.; Li, X. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplant Res Ctr, Boston, MA 02115 USA. [Liu, W.; Xiao, X.; Demirci, G.; Li, X. C.] Harvard Univ, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA. [Madsen, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 299 BP 115 EP 115 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235500300 ER PT J AU Porcheray, F DeVito, J Dargon, I Helou, Y Fraser, J Nobecourt, P Ferdman, J Germana, S Girouard, T Kawai, T Saidman, S Wong, W Colvin, R Leguern, C Zorn, E AF Porcheray, F. DeVito, J. Dargon, I. Helou, Y. Fraser, J. Nobecourt, P. Ferdman, J. Germana, S. Girouard, T. Kawai, T. Saidman, S. Wong, W. Colvin, R. Leguern, C. Zorn, E. TI Humoral Rejection of Human Kidney Grafts Associates with Polyreactive Antibodies That Bind Apoptotic Cells and Contribute to Their Clearance by Phagocytes SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Porcheray, F.; DeVito, J.; Dargon, I.; Helou, Y.; Fraser, J.; Nobecourt, P.; Ferdman, J.; Germana, S.; Girouard, T.; Kawai, T.; Saidman, S.; Wong, W.; Colvin, R.; Leguern, C.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 471 BP 169 EP 169 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501095 ER PT J AU Ferdman, J Porcheray, F DeVito, J Fraser, J Dougherty, S Kawai, T Wong, W Zorn, E AF Ferdman, J. Porcheray, F. DeVito, J. Fraser, J. Dougherty, S. Kawai, T. Wong, W. Zorn, E. TI In Situ Expansion of Memory B Cell Clones in Rejected Human Kidney Grafts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Ferdman, J.; Porcheray, F.; DeVito, J.; Fraser, J.; Dougherty, S.; Kawai, T.; Wong, W.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 490 BP 175 EP 175 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501114 ER PT J AU Pathiraja, V Tasaki, M Scalea, J Matar, A Duran-Struuck, R Gillon, B Sachs, DH Huang, C Yamada, K AF Pathiraja, V. Tasaki, M. Scalea, J. Matar, A. Duran-Struuck, R. Gillon, B. Sachs, D. H. Huang, C. Yamada, K. TI Successful Induction of Tolerance of Both Islets and Kidneys and Cure of Diabetes Following Vascularized Islet-Kidney Transplantation in Non-Human Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Pathiraja, V.; Tasaki, M.; Scalea, J.; Matar, A.; Duran-Struuck, R.; Gillon, B.; Sachs, D. H.; Huang, C.; Yamada, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 499 BP 178 EP 178 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501123 ER PT J AU Leonard, DA Horner, B Randolph, MA Duran-Struuck, R Crepeau, R Matar, A Mallard, C Sachs, DH Cetrulo, CL Huang, C AF Leonard, D. A. Horner, B. Randolph, M. A. Duran-Struuck, R. Crepeau, R. Matar, A. Mallard, C. Sachs, D. H. Cetrulo, C. L., Jr. Huang, C. TI Induction of Vascularized Skin Tolerance by Establishment of Stable Mixed Chimerism across a Major Histocompatibility Barrier in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Leonard, D. A.; Horner, B.; Duran-Struuck, R.; Crepeau, R.; Matar, A.; Mallard, C.; Sachs, D. H.; Cetrulo, C. L., Jr.; Huang, C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Leonard, D. A.; Horner, B.; Randolph, M. A.; Cetrulo, C. L., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 503 BP 179 EP 179 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501127 ER PT J AU Sondermeijer, HP Buhler, L McMurchy, A Kato, Y Wu, A Griesemer, A Martinez, M Boskovic, S Yamada, Y Kawai, T Cosimi, AB Benichou, G Smith, NR Slate, A Wekerle, T Levings, M Sykes, M AF Sondermeijer, H. P. Buehler, L. McMurchy, A. Kato, Y. Wu, A. Griesemer, A. Martinez, M. Boskovic, S. Yamada, Y. Kawai, T. Cosimi, A. B. Benichou, G. Smith, N. Rex Slate, A. Wekerle, T. Levings, M. Sykes, M. TI Ex Vivo Recipient Expanded Regulatory T-Cells Promote Prolonged Mixed Hematopoietic Chimerism and Renal Allograft Tolerance in a Non-Myeloablative Non-Human Primate Bone Marrow Transplantation Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Sondermeijer, H. P.; Kato, Y.; Wu, A.; Griesemer, A.; Martinez, M.; Slate, A.; Sykes, M.] Columbia Univ, Med Ctr, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boskovic, S.; Yamada, Y.; Kawai, T.; Cosimi, A. B.; Benichou, G.; Smith, N. Rex] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [McMurchy, A.; Levings, M.] Med Univ Vienna, Vienna, Austria. [Wekerle, T.] Univ Hosp Geneva, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 504 BP 179 EP 179 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501128 ER PT J AU Tonsho, M Millington, T Klarin, D Boskovic, S Nadazdin, O Benichou, G Kawai, T Cosimi, AB Smith, NR Colvin, RB Madsen, JC AF Tonsho, M. Millington, T. Klarin, D. Boskovic, S. Nadazdin, O. Benichou, G. Kawai, T. Cosimi, A. B. Smith, N. R. Colvin, R. B. Madsen, J. C. TI Induction of Tolerance to Heart Allografts by Donor Kidney Co-Transplantation in Nonhuman Primates (NHPs) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Tonsho, M.; Millington, T.; Klarin, D.; Boskovic, S.; Nadazdin, O.; Benichou, G.; Kawai, T.; Cosimi, A. B.; Smith, N. R.; Colvin, R. B.; Madsen, J. C.] Harvard Univ, Sch Med, Boston, MA USA. [Tonsho, M.; Millington, T.; Klarin, D.; Boskovic, S.; Nadazdin, O.; Benichou, G.; Kawai, T.; Cosimi, A. B.; Smith, N. R.; Colvin, R. B.; Madsen, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 502 BP 179 EP 179 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501126 ER PT J AU Boneschansker, L Irimia, D Bruneau, S Cho, H Yan, J Wong, E Jain, N Klagsbrun, M Briscoe, DM AF Boneschansker, L. Irimia, D. Bruneau, S. Cho, H. Yan, J. Wong, E. Jain, N. Klagsbrun, M. Briscoe, D. M. TI Netrin-1: A Potent Inhibitor of Lymphocyte Chemotaxis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Boneschansker, L.; Bruneau, S.; Jain, N.; Klagsbrun, M.; Briscoe, D. M.] Childrens Hosp Boston, Boston, MA USA. [Irimia, D.; Cho, H.; Yan, J.; Wong, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boneschansker, L.; Irimia, D.; Bruneau, S.; Cho, H.; Yan, J.; Wong, E.; Jain, N.; Klagsbrun, M.; Briscoe, D. M.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 626 BP 215 EP 215 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235501256 ER PT J AU Albritton, A Leonard, DA Barone, AAL Torabi, R Mallard, C Kurtz, J Sachs, DH Cetrulo, CL AF Albritton, A. Leonard, D. A. Barone, A. A. Leto Torabi, R. Mallard, C. Kurtz, J. Sachs, D. H. Cetrulo, C. L., Jr. TI Lack of Cross-Sensitization between alpha-1,3-Galactosyltransferase Knockout Porcine and Allogeneic Skin Grafts Permits Serial Grafting. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Albritton, A.; Leonard, D. A.; Barone, A. A. Leto; Torabi, R.; Mallard, C.; Kurtz, J.; Sachs, D. H.; Cetrulo, C. L., Jr.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Leonard, D. A.; Barone, A. A. Leto; Cetrulo, C. L., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Kurtz, J.] Univ Cambridge Emmanuel Coll, Dept Biol, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 843 BP 277 EP 277 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235502064 ER PT J AU Ueno, T Dutta, P Gorbatov, R Keliher, E Yeung, M Libby, P Weissleder, R Nahrendorf, M AF Ueno, T. Dutta, P. Gorbatov, R. Keliher, E. Yeung, M. Libby, P. Weissleder, R. Nahrendorf, M. TI Nanoparticle PET-CT Detects Immunosuppression Efficiency in Cardiac Transplants. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Ueno, T.; Dutta, P.; Gorbatov, R.; Keliher, E.; Weissleder, R.; Nahrendorf, M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ueno, T.; Yeung, M.] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 853 BP 279 EP 279 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235502074 ER PT J AU Porcheray, F DeVito, J Dargon, I Helou, Y Fraser, J Nobecourt, P Ferdman, J Germana, S Girouard, T Kawai, T Saidman, S Wong, W Colvin, R Leguern, C Zorn, E AF Porcheray, F. DeVito, J. Dargon, I. Helou, Y. Fraser, J. Nobecourt, P. Ferdman, J. Germana, S. Girouard, T. Kawai, T. Saidman, S. Wong, W. Colvin, R. Leguern, C. Zorn, E. TI Robust Expansion of Memory Polyreactive B Cells Secreting Antibodies Cross-Reactive to HLA and Self Amidst Kidney Graft Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Porcheray, F.; DeVito, J.; Dargon, I.; Helou, Y.; Fraser, J.; Nobecourt, P.; Ferdman, J.; Germana, S.; Girouard, T.; Kawai, T.; Saidman, S.; Wong, W.; Colvin, R.; Leguern, C.; Zorn, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 867 BP 283 EP 283 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235502088 ER PT J AU Duran-Struuck, R Matar, A Crepeau, R Gusha, A Schenk, M Pathiraja, V Hanekamp, I Spitzer, TR Sachs, DH Huang, C AF Duran-Struuck, R. Matar, A. Crepeau, R. Gusha, A. Schenk, M. Pathiraja, V. Hanekamp, I. Spitzer, T. R. Sachs, D. H. Huang, C. TI Host-Versus-Graft Responses Associated with Graft Loss Following Reduced Intensity Haploidentical Hematopoietic Cell Transplantation in a Pre-Clinical Large Animal Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Duran-Struuck, R.; Matar, A.; Crepeau, R.; Gusha, A.; Schenk, M.; Pathiraja, V.; Hanekamp, I.; Sachs, D. H.; Huang, C.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Spitzer, T. R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 902 BP 292 EP 292 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235502123 ER PT J AU Wamala, I Kim, KM Schuetz, C Varma, M Machaidze, Z Martins, P Yeh, H Smith, NR Elias, N Cosimi, BA Sachs, DH Hertl, M AF Wamala, I. Kim, K. M. Schuetz, C. Varma, M. Machaidze, Z. Martins, P. Yeh, H. Smith, N. R. Elias, N. Cosimi, B. A. Sachs, D. H. Hertl, M. TI Aminocaproic Acid Prevents Severe Thrombocytopenia Following Liver Xenotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Wamala, I.; Kim, K. M.; Schuetz, C.; Varma, M.; Machaidze, Z.; Martins, P.; Yeh, H.; Elias, N.; Cosimi, B. A.; Sachs, D. H.; Hertl, M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Smith, N. R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1058 BP 336 EP 337 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235502279 ER PT J AU Villani, V Gillon, B Tasaki, M Hanekamp, I Cormack, T Moran, S Sachs, D Yamada, K AF Villani, V. Gillon, B. Tasaki, M. Hanekamp, I. Cormack, T. Moran, S. Sachs, D. Yamada, K. TI The Thymus Is Required To Break Tolerance of Renal Allografts in a Miniature Swine Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Villani, V.; Gillon, B.; Tasaki, M.; Hanekamp, I.; Cormack, T.; Moran, S.; Sachs, D.; Yamada, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1118 BP 354 EP 354 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235503007 ER PT J AU Ueno, T Yeung, M Jung, K Yun, SH Weissleder, R AF Ueno, T. Yeung, M. Jung, K. Yun, S. H. Weissleder, R. TI The Importance of DC (Dendritic Cell) - T Cell Interplay in Cardiac Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Ueno, T.; Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ueno, T.; Yeung, M.] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1265 BP 399 EP 399 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235503168 ER PT J AU Fraser, JW Hastings, C Porcheray, F DeVito, J Dargon, I Helou, Y Ferdman, J Smith, RN Zorn, E AF Fraser, J. W. Hastings, C. Porcheray, F. DeVito, J. Dargon, I. Helou, Y. Ferdman, J. Smith, R. N. Zorn, E. TI Polyreactive Antibodies Generated Amidst Rejection of Human Kidney Grafts Activate Complement and Deposit C3d/C4d SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Fraser, J. W.; Hastings, C.; Porcheray, F.; DeVito, J.; Dargon, I.; Helou, Y.; Ferdman, J.; Smith, R. N.; Zorn, E.] Mass Gen Hosp, Boston, MA USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1335 BP 419 EP 420 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235503238 ER PT J AU Yamada, Y Boskovic, S Lee, S Nadazdin, O Tonsho, M Aoyama, A Klarin, D Smith, RN Colvin, R Tocco, G Alessandorini, A Madsen, J Sachs, D Cosimi, B Benichou, G Kawai, T AF Yamada, Y. Boskovic, S. Lee, S. Nadazdin, O. Tonsho, M. Aoyama, A. Klarin, D. Smith, R. -N. Colvin, R. Tocco, G. Alessandorini, A. Madsen, J. Sachs, D. Cosimi, B. Benichou, G. Kawai, T. TI In Vivo IL-2 Administration Can Abolish Tolerance to Kidney Allografts Induced Via Mixed Chimerism in Non-Human Primates. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Yamada, Y.; Boskovic, S.; Lee, S.; Nadazdin, O.; Tonsho, M.; Aoyama, A.; Klarin, D.; Smith, R. -N.; Colvin, R.; Tocco, G.; Alessandorini, A.; Madsen, J.; Sachs, D.; Cosimi, B.; Benichou, G.; Kawai, T.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1427 BP 446 EP 446 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504002 ER PT J AU Farkash, E Zhang, P Khawaja, Z Saidman, S Collins, AB Smith, RN Williams, W Hill, G Colvin, R Alessandrini, A AF Farkash, E. Zhang, P. Khawaja, Z. Saidman, S. Collins, A. B. Smith, R. N. Williams, W. Hill, G. Colvin, R. Alessandrini, A. TI Non-Complement-Fixing Antibodies Predominate in C4d-Negative Chronic Antibody Mediated Rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Farkash, E.; Zhang, P.; Khawaja, Z.; Saidman, S.; Collins, A. B.; Smith, R. N.; Williams, W.; Colvin, R.; Alessandrini, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hill, G.] OneLambda, Canoga Pk, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA LB27 BP 450 EP 450 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504018 ER PT J AU Sihag, S Aoyama, A Gottschall, JD Wain, JC Arn, JS Farkash, EA Smith, RN Madsen, JC Rosengard, BR Sachs, DH Allan, JS AF Sihag, S. Aoyama, A. Gottschall, J. D. Wain, J. C. Arn, J. S. Farkash, E. A. Smith, R. N. Madsen, J. C. Rosengard, B. R. Sachs, D. H. Allan, J. S. TI Prolonged Survival of Pulmonary Allografts between Highly Inbred Miniature Swine without Immunosuppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1458 BP 458 EP 458 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504048 ER PT J AU Akiyoshi, T Lee, WM Chase, CM Alessandrini, A Sebastian, DP Della Pelle, P Connoly, SE Farkash, E Yun, SH Russell, PS Colvin, RB AF Akiyoshi, T. Lee, W. M. Chase, C. M. Alessandrini, A. Sebastian, D. P. Della Pelle, P. Connoly, S. E. Farkash, E. Yun, S. -H. Russell, P. S. Colvin, R. B. TI In Vivo Two Photon Microscopy of Aortic Allografts: A New Tool for Investigation of the Dynamics of Graft Vascular Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Lee, W. M.; Yun, S. -H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RI lee, Woei Ming "Steve"/C-7035-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1489 BP 466 EP 466 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504079 ER PT J AU Poznansky, MC Chen, T Duncanson, S Hibert, M Kodish, B Machaidze, Z Deng, S Sachs, DH Markmann, JF Sambanis, T AF Poznansky, M. C. Chen, T. Duncanson, S. Hibert, M. Kodish, B. Machaidze, Z. Deng, S. Sachs, D. H. Markmann, J. F. Sambanis, T. TI Incorporation of CXCL12 in Calcium-LVM Microcapsules Improves Long-Term Function and Delays Rejection of Allogeneic Islet Grafts in NOD/LtJ Mice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Poznansky, M. C.; Chen, T.; Hibert, M.; Kodish, B.] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. [Duncanson, S.; Sambanis, T.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Machaidze, Z.; Deng, S.; Markmann, J. F.] MGH, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1534 BP 479 EP 479 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504124 ER PT J AU Saidi, RF Markmann, J Jabbour, N Li, Y Shah, S Cosimi, AB Bozorgzadeh, A AF Saidi, R. F. Markmann, J. Jabbour, N. Li, Y. Shah, S. Cosimi, A. B. Bozorgzadeh, A. TI The Faltering Solid Organ Donor Pool in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Saidi, R. F.; Jabbour, N.; Li, Y.; Shah, S.; Bozorgzadeh, A.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Markmann, J.; Cosimi, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1706 BP 527 EP 528 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504296 ER PT J AU Gillon, B Scalea, J Cormack, T Moran, S Villani, V Tasaki, M Torabi, R Pathiraja, V Sachs, D Yamada, K AF Gillon, B. Scalea, J. Cormack, T. Moran, S. Villani, V. Tasaki, M. Torabi, R. Pathiraja, V. Sachs, D. Yamada, K. TI The Adoptive Transfer of Long-Term Tolerant Renal Grafts Induced Systemic Infectious Tolerance in MGH Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Gillon, B.; Scalea, J.; Cormack, T.; Moran, S.; Villani, V.; Tasaki, M.; Torabi, R.; Pathiraja, V.; Sachs, D.; Yamada, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1721 BP 531 EP 531 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504311 ER PT J AU Stott, R Soohoo, J Kim, JI Lee, KM O'Connor, MR Yeh, H Deng, S Markmann, JF AF Stott, R. Soohoo, J. Kim, J. I. Lee, K. M. O'Connor, M. R. Yeh, H. Deng, S. Markmann, J. F. TI B Cell-Dependent Antibody Therapy Results in Tolerance in Stringent Allograft Model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Stott, R.; Soohoo, J.; Kim, J. I.; Lee, K. M.; O'Connor, M. R.; Yeh, H.; Deng, S.; Markmann, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA 1729 BP 533 EP 533 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504319 ER PT J AU Yeh, H Markmann, JF Hunsicker, LG AF Yeh, H. Markmann, J. F. Hunsicker, L. G. TI Demographic Factors Simultaneously Associated with Higher Wait List Numbers and Fewer Deceased Donor Livers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Yeh, H.; Markmann, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hunsicker, L. G.] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA LB41 BP 538 EP 538 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504337 ER PT J AU Yeh, H Dong, N Smoot, E Schuetz, C Elias, N Schoenfeld, D Markmann, JF AF Yeh, H. Dong, N. Smoot, E. Schuetz, C. Elias, N. Schoenfeld, D. Markmann, J. F. TI Patients Transplanted for HCC Suffer Less from Geographic Disparities in Access to Liver Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY, 2012 CL Boston, MA C1 [Yeh, H.; Dong, N.; Smoot, E.; Schuetz, C.; Elias, N.; Schoenfeld, D.; Markmann, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 SU 3 SI SI MA LB42 BP 538 EP 539 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QX UT WOS:000303235504338 ER PT J AU Kokko, KE Colvin, RB AF Kokko, K. E. Colvin, R. B. TI Below the WaterlineuThe Danger of De Novo Donor-Specific HLA Antibodies SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE Allocation; antibody mediated rejection; donor specific antibody; kidney transplantation ID LEUKOCYTE ANTIGEN ANTIBODIES; KIDNEY-TRANSPLANT C1 [Kokko, K. E.] Univ Mississippi, Dept Med, Jackson, MS 39216 USA. [Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kokko, KE (reprint author), Univ Mississippi, Dept Med, Jackson, MS 39216 USA. EM kkokko@umc.edu FU NIAID NIH HHS [U19 AI102405] NR 6 TC 4 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 IS 5 BP 1077 EP 1078 DI 10.1111/j.1600-6143.2012.04016.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QT UT WOS:000303235100005 PM 22537262 ER PT J AU Meltzer, AJ Veillette, GR Aoyama, A Kim, KM Cochrane, ME Wain, JC Madsen, JC Sachs, DH Rosengard, BR Allan, JS AF Meltzer, A. J. Veillette, G. R. Aoyama, A. Kim, K. M. Cochrane, M. E. Wain, J. C. Madsen, J. C. Sachs, D. H. Rosengard, B. R. Allan, J. S. TI Donor Brain Death Inhibits Tolerance Induction in Miniature Swine Recipients of Fully MHC-Disparate Pulmonary Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Brain death; lung transplantation; swine; tolerance induction ID GENE-EXPRESSION; TRANSPLANTATION; REJECTION; HISTOCOMPATIBILITY; TRANSCRIPTION; INJURY; PCR AB We have previously shown that a short course of high-dose tacrolimus induces long-term tolerance to fully mismatched lung allografts procured from healthy MHC-inbred miniature swine. Here, we investigate whether donor brain death affects tolerance induction. Four recipient swine were transplanted with fully mismatched lung grafts from donors that were rendered brain dead and mechanically ventilated for 4 h before procurement (Group 1). These recipients were compared to two control groups (Group 2: 4 h of donor ventilation without brain death [n = 5]; and Group 3: no donor brain death with <1 h of ventilation [n = 6]). All recipients were treated with a 12-day course of tacrolimus. In contrast to both groups of control animals, the swine transplanted with lung allografts from brain dead donors all rejected their grafts by postoperative day 45 and showed persistent responsiveness to donor antigen by MLR. Several additional swine underwent brain death induction and/or mechanical ventilation alone to determine the effects of these procedures on the expression of proinflammatory molecules. Significant increases in serum concentrations of IL-1, TNF-a and IL-10 were seen after brain death. Upregulation of IL-1 and IL-6 gene expression was also observed. C1 [Allan, J. S.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cardiothorac Transplantat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Cardiothorac Transplantat Lab, Boston, MA 02114 USA. EM jallan@partners.org FU NIH [R01HL67110, R01HL45211]; Thoracic Surgery Foundation for Research and Education; Yoshida Scholarship Foundation FX Supported by NIH R01HL67110 (J.S.A.), NIH R01HL45211 (J.C.M.) and fellowships from the Thoracic Surgery Foundation for Research and Education (K.M.K.) and the Yoshida Scholarship Foundation (A.A.). NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 IS 5 BP 1290 EP 1295 DI 10.1111/j.1600-6143.2011.03949.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QT UT WOS:000303235100027 PM 22300400 ER PT J AU Koulmanda, M Qipo, A Fan, Z Smith, N Auchincloss, H Zheng, XX Strom, TB AF Koulmanda, M. Qipo, A. Fan, Z. Smith, N. Auchincloss, H. Zheng, X. X. Strom, T. B. TI Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After Short-Term Triple Therapy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Islet allograft; nonhuman primate; transplantation; triple therapy ID REGULATORY T-CELLS; ALLOGRAFT; TRANSPLANTATION; STREPTOZOTOCIN; LYMPHOCYTES; TOLERANCE; PHENOTYPE; RESISTANT; REJECTION; BLOCKADE AB Preclinical studies in nonhuman primates (NHP) are particularly useful to evaluate the safety and efficacy of new therapeutic proteins developed for use in clinical transplantation. We hypothesized that a treatment that selectively destroys activated cytopathic donor reactive T cells while sparing resting and immunoregulatory T cells in a mouse model might also produce long-term drug-free engraftment and tolerance without the hazards of lymphopenia in the challenging nonhuman primate islet allograft model. Short-term treatment with a regimen consisting of rapamycin, and IL-2.Ig plus mutant antagonist-type IL-15.Ig cytolytic fusion proteins (triple therapy) posttransplantation results in prolonged, drug-free engraftment of cynomolgus islet allografts. Moreover slow progressive loss of islet function in some recipients was not associated with obvious pathologic evidence of rejection. C1 [Koulmanda, M.; Qipo, A.; Fan, Z.; Zheng, X. X.; Strom, T. B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Koulmanda, M.; Qipo, A.; Fan, Z.; Zheng, X. X.; Strom, T. B.] Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Dept Med, Transplant Inst, Boston, MA 02114 USA. [Smith, N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Auchincloss, H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Auchincloss, H.] NIAID, Bethesda, MD 20892 USA. [Zheng, X. X.] Univ Pittsburgh, Thomas Starzl Transplant Inst, Pittsburgh, PA USA. RP Koulmanda, M (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM mkoulman@bidmc.harvard.edu FU NIH [PO1 DK53087]; Juvenile Diabetes Research Foundation Center for Islet Transplantation at Harvard Medical School FX We thank Vaja Tchipashivili from the Joslin Diabetes Center for providing monkey islets and Luba Zachachin for expert assistance with tissue processing. This work was funded in part by the NIH PO1 DK53087 and the Juvenile Diabetes Research Foundation Center for Islet Transplantation at Harvard Medical School. NR 21 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2012 VL 12 IS 5 BP 1296 EP 1302 DI 10.1111/j.1600-6143.2012.03973.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 931QT UT WOS:000303235100028 PM 22390179 ER PT J AU Ramos, EM Keagle, P Gillis, T Lowe, P Mysore, JS Leclerc, AL Ratti, A Ticozzi, N Gellera, C Gusella, JF Silani, V Alonso, I Brown, RH Macdonald, ME Landers, JE AF Ramos, Eliana Marisa Keagle, Pamela Gillis, Tammy Lowe, Patrick Mysore, Jayalakshmi S. Leclerc, Ashley Lyn Ratti, Antonia Ticozzi, Nicola Gellera, Cinzia Gusella, James F. Silani, Vincenzo Alonso, Isabel Brown, Robert H., Jr. Macdonald, Marcy E. Landers, John E. TI Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Huntington's disease; amyotrophic lateral sclerosis; trinucleotide repeat; neurodegenerative disease; polyglutamine expansion ID LENGTH POLYGLUTAMINE EXPANSIONS; MOTOR-NEURON DISEASE; HEXANUCLEOTIDE REPEAT; TRINUCLEOTIDE REPEAT; ALS PATIENTS; MUTATIONS; PROTEIN; CHOREA; CHROMOSOMES; OPTINEURIN AB A higher prevalence of intermediate ataxin-2 CAG repeats in amyotrophic lateral sclerosis (ALS) patients has raised the possibility that CAG expansions in other polyglutamine disease genes could contribute to ALS neurodegeneration. We sought to determine whether expansions of the CAG repeat of the HTT gene that causes Huntington's disease, are associated with ALS. We compared the HTT CAG repeat length on a total of 3144 chromosomes from 1572 sporadic ALS patients and 4007 control chromosomes, and also tested its possible effects on ALS-specific parameters, such as age and site of onset and survival rate. Our results show that the CAG repeat in the HTT gene is not a risk factor for ALS nor modifies its clinical presentation. These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders. C1 [Keagle, Pamela; Lowe, Patrick; Leclerc, Ashley Lyn; Brown, Robert H., Jr.; Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01610 USA. [Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S.; Gusella, James F.; Macdonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ramos, Eliana Marisa; Alonso, Isabel] Univ Porto, IBMC Inst Mol & Cell Biol, UnIGENe, P-4100 Oporto, Portugal. [Ratti, Antonia; Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, IRCCS Ist Auxol Italiano, Dino Ferrari Ctr, Dept Neurol, Milan, Italy. [Ratti, Antonia; Ticozzi, Nicola; Silani, Vincenzo] Univ Milan, IRCCS Ist Auxol Italiano, Dino Ferrari Ctr, Neurosci Lab, Milan, Italy. [Gellera, Cinzia] Fdn IRCCS Ist Neurol Carlo Besta, Unit Genet Neurodegenerat & Metab Dis, Milan, Italy. RP Landers, JE (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01610 USA. EM john.landers@umassmed.edu RI Alonso, Isabel/I-4307-2013; Ticozzi, Nicola/K-8094-2016; GELLERA, CINZIA/J-7887-2016; OI Alonso, Isabel/0000-0001-8549-6903; Ticozzi, Nicola/0000-0001-5963-7426; GELLERA, CINZIA/0000-0002-3582-665X; Silani, Vincenzo/0000-0002-7698-3854 FU Fundacao para a Ciencia e a Tecnologia; National Institutes of Health NINDS Huntington's Disease Center; CHDI Foundation, Inc.; NIH/NINDS; Francesco Caleffi donation; AriSLA; Italian Ministry of Health, Ricerca Finalizzata FX EMR is the recipient of a scholarship from Fundacao para a Ciencia e a Tecnologia. Grants were received from the National Institutes of Health NINDS Huntington's Disease Center Without Walls (JFG, MEM) and the CHDI Foundation, Inc. (JFG, MEM). Generous support was provided by the ALS Therapy Alliance, Project ALS, the Angel Fund, the Pierre L. de Bourgknecht ALS Research Foundation, the Al-Athel ALS Research Foundation, the ALS Family Charitable Foundation and the National Institute of Neurological Disorders and Stroke (RHB). JEL acknowledges grant support from NIH/NINDS. NT and VS have been supported by a Francesco Caleffi donation and acknowledge grant support from AriSLA and the Italian Ministry of Health, Ricerca Finalizzata, 2009. NR 30 TC 7 Z9 7 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD MAY PY 2012 VL 13 IS 3 BP 265 EP 269 DI 10.3109/17482968.2011.653573 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 932YD UT WOS:000303325500004 PM 22409360 ER PT J AU Chemali, JJ Van Dort, CJ Brown, EN Solt, K AF Chemali, Jessica J. Van Dort, Christa J. Brown, Emery N. Solt, Ken TI Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate SO ANESTHESIOLOGY LA English DT Article ID STEADY-STATE RESPONSE; ISOFLURANE ANESTHESIA; BISPECTRAL INDEX; RATS; SLEEP; PHYSOSTIGMINE; INVOLVEMENT; SUPPRESSION; DEPRESSION; PATHWAYS AB Background: A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. Methods: Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of methylphenidate to restore righting during a continuous target-controlled infusion (TCI) of propofol was also tested. In a separate group of rats, a TCI of propofol was established and spectral analysis was performed on electroencephalogram recordings taken before and after methylphenidate administration. Results: Methylphenidate decreased median time to emergence after a single dose of propofol from 735 s (95% CI: 598-897 s, n = 6) to 448 s (95% CI: 371-495 s, n = 6). The difference was statistically significant (P = 0.0051). During continuous propofol anesthesia with a median final target plasma concentration of 4.0 mu g/ml (95% CI: 3.2-4.6, n = 6), none of the rats exhibited purposeful movements after injection of normal saline. After methylphenidate, however, all six rats promptly exhibited arousal and had restoration of righting with a median time of 82 s (95% CI: 30-166 s). Spectral analysis of electroencephalogram data demonstrated a shift in peak power from delta (less than 4 Hz) to theta (4-8 Hz) and beta (12-30 Hz) after administration of methylphenidate, indicating arousal in 4/4 rats. Conclusions: Methylphenidate decreases time to emergence after a single dose of propofol, and induces emergence during continuous propofol anesthesia in rats. Further study is warranted to test the hypothesis that methylphenidate induces emergence from propofol general anesthesia in humans. C1 [Chemali, Jessica J.; Van Dort, Christa J.; Brown, Emery N.; Solt, Ken] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Brown, Emery N.; Solt, Ken] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, Maryland [DP1-OD003646, K08-GM094394]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication November 6, 2011. Accepted for publication February 10, 2012. Supported by grant nos. DP1-OD003646 and K08-GM094394 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. Presented in part at annual meetings of the Society for Anesthesia and Sleep Medicine, October 14, 2011, Chicago, Illinois, and the Society for Neuroscience, November 13, 2011, Washington, D.C. Jessica J. Chemali, Emery N. Brown, and Ken Solt submitted a patent application on September 1, 2011, for the use of intravenous methylphenidate to restore arousal during propofol general anesthesia. NR 28 TC 35 Z9 36 U1 1 U2 5 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 2012 VL 116 IS 5 BP 998 EP 1005 DI 10.1097/ALN.0b013e3182518bfc PG 8 WC Anesthesiology SC Anesthesiology GA 931EY UT WOS:000303199600007 PM 22446983 ER PT J AU Pejo, E Ge, R Banacos, N Cotten, JF Husain, SS Raines, DE AF Pejo, Ervin Ge, Rile Banacos, Natalie Cotten, Joseph F. Husain, S. Shaukat Raines, Douglas E. TI Electroencephalographic Recovery, Hypnotic Emergence, and the Effects of Metabolite after Continuous Infusions of a Rapidly Metabolized Etomidate Analog in Rats SO ANESTHESIOLOGY LA English DT Article ID INTRAVENOUS ANESTHESIA; RENAL-FAILURE; PHARMACOKINETICS; REMIFENTANIL; PHARMACODYNAMICS; SUPPRESSION; VOLUNTEERS; ALFENTANIL; ESMOLOL; DESIGN AB Background: Methoxycarbonyl etomidate is an ultrarapidly metabolized etomidate analog. It is metabolized to methoxycarbonyl etomidate carboxylic acid (MOC-ECA), which has a hypnotic potency that is 350-fold less than that of methoxycarbonyl etomidate. The authors explored the relationships between methoxycarbonyl etomidate infusion duration, recovery time, metabolite concentrations in blood and cerebrospinal fluid (CSF), and methoxycarbonyl etomidate metabolism in brain tissue and CSF to test the hypothesis that rapid metabolism of methoxycarbonyl etomidate may lead to sufficient accumulation of MOC-ECA in the brain to produce a pharmacologic effect. Methods: A closed-loop system with burst suppression ratio feedback was used to administer methoxycarbonyl etomidate infusions of varying durations to rats. After infusion, recovery of the electroencephalogram and righting reflexes were assessed. MOC-ECA concentrations were measured in blood and CSF during and after methoxycarbonyl etomidate infusion, and the in vitro half-life of methoxycarbonyl etomidate was determined in rat brain tissue and CSF. Results: Upon termination of continuous methoxycarbonyl etomidate infusions, the burst suppression ratio recovered in a biexponential manner with fast and slow components having time constants that differed by more than 100-fold and amplitudes that varied inversely with infusion duration. MOC-ECA concentrations reached hypnotic concentrations in the CSF with prolonged methoxycarbonyl etomidate infusion and then decreased during a period of several hours after infusion termination. The metabolic half-life of methoxycarbonyl etomidate in brain tissue and CSF was 11 and 20 min, respectively. Conclusion: In rats, methoxycarbonyl etomidate metabolism is sufficiently fast to produce pharmacologically active MOC-ECA concentrations in the brain with prolonged methoxycarbonyl etomidate infusion. C1 [Pejo, Ervin; Ge, Rile; Banacos, Natalie; Cotten, Joseph F.; Husain, S. Shaukat; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cotten, Joseph F.; Husain, S. Shaukat; Raines, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, Maryland [R01-GM087316, R21-DA029253, K08-GM083216]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital FX Received from the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication October 28, 2011. Accepted for publication February 10, 2012. Supported by grants R01-GM087316, R21-DA029253, and K08-GM083216 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. The Massachusetts General Hospital has submitted patent applications for methoxycarbonyl etomidate and related analogues. Three authors (Drs. Raines, Cotten, and Husain) and their respective laboratories, departments, and institutions could receive compensation related to the development or sale of methoxycarbonyl etomidate and related analogs. Dr. Raines is a consultant for and holds an equity interest in Annovation BioPharma Inc., Wayland, Massachusetts, which has licensed this technology for development. E. Pejo and R. Ge contributed equally to this work. NR 21 TC 10 Z9 13 U1 0 U2 2 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 2012 VL 116 IS 5 BP 1057 EP 1065 DI 10.1097/ALN.0b013e3182515403 PG 9 WC Anesthesiology SC Anesthesiology GA 931EY UT WOS:000303199600013 PM 22417966 ER PT J AU Baker, K AF Baker, Keith TI Errors in Assessment of Resident Performance Reply SO ANESTHESIOLOGY LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM khbaker@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2012 VL 116 IS 5 BP 1161 EP 1162 DI 10.1097/ALN.0b013e3182504d1e PG 3 WC Anesthesiology SC Anesthesiology GA 931EY UT WOS:000303199600036 ER PT J AU van Ravesteyn, NT Miglioretti, DL Stout, NK Lee, SJ Schechter, CB Buist, DSM Huang, H Heijnsdijk, EAM Trentham-Dietz, A Alagoz, O Near, AM Kerlikowske, K Nelson, HD Mandelblatt, JS de Koning, HJ AF van Ravesteyn, Nicolien T. Miglioretti, Diana L. Stout, Natasha K. Lee, Sandra J. Schechter, Clyde B. Buist, Diana S. M. Huang, Hui Heijnsdijk, Eveline A. M. Trentham-Dietz, Amy Alagoz, Oguzhan Near, Aimee M. Kerlikowske, Karla Nelson, Heidi D. Mandelblatt, Jeanne S. de Koning, Harry J. TI Tipping the Balance of Benefits and Harms to Favor Screening Mammography Starting at Age 40 Years A Comparative Modeling Study of Risk SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BREAST-CANCER MORTALITY; SWEDISH 2-COUNTY TRIAL; FALSE-POSITIVE RECALL; SERVICES TASK-FORCE; FOLLOW-UP; COST-EFFECTIVENESS; AMERICAN-COLLEGE; WOMEN; DENSITY; IMPACT AB Background: Timing of initiation of screening for breast cancer is controversial in the United States. Objective: To determine the threshold relative risk (RR) at which the harm-benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years. Design: Comparative modeling study. Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature. Target Population: A contemporary cohort of women eligible for routine screening. Time Horizon: Lifetime. Perspective: Societal. Intervention: Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial). Outcome Measures: Benefits: life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm-benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted. Results of Base-Case Analysis: Screening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm-benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate. Results of Sensitivity Analysis: The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions. Limitation: Risk was assumed to influence onset of disease without influencing screening performance. Conclusion: Women aged 40 to 49 years with a 2-fold increased risk have similar harm-benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm-benefit ratios vary by screening method, interval, and outcome measure. C1 [van Ravesteyn, Nicolien T.] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. Univ Washington, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Wisconsin, Madison, WI USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Washington, DC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Providence Hlth & Serv, Providence Canc Ctr, Portland, OR USA. RP van Ravesteyn, NT (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM n.vanravesteyn@erasmusmc.nl FU National Cancer Institute [U01CA086076-10S1, U01CA88283, U01CA152958, KO5CA96940, U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]; BCSC FX The collection of BCSC cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see www.breastscreening.cancer.gov/work/acknowledgement.html. This research was supported by a National Cancer Institute Activities to Promote Research Collaboration supplement (U01CA086076-10S1), and, in part, by National Cancer Institute grants U01CA88283, U01CA152958, and KO5CA96940. Data collection was supported by the BCSC funded by the National Cancer Institute cooperative agreements U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040. NR 49 TC 54 Z9 54 U1 1 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 2012 VL 156 IS 9 BP 609 EP U39 DI 10.7326/0003-4819-156-9-201205010-00002 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 933YR UT WOS:000303403700001 PM 22547470 ER PT J AU Nelson, HD Zakher, B Cantor, A Fu, RW Griffin, J O'Meara, ES Buist, DSM Kerlikowske, K van Ravesteyn, NT Trentham-Dietz, A Mandelblatt, JS Miglioretti, DL AF Nelson, Heidi D. Zakher, Bernadette Cantor, Amy Fu, Rongwei Griffin, Jessica O'Meara, Ellen S. Buist, Diana S. M. Kerlikowske, Karla van Ravesteyn, Nicolien T. Trentham-Dietz, Amy Mandelblatt, Jeanne S. Miglioretti, Diana L. TI Risk Factors for Breast Cancer for Women Aged 40 to 49 Years A Systematic Review and Meta-analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ORAL-CONTRACEPTIVE USE; AFRICAN-AMERICAN WOMEN; HISPANIC WHITE WOMEN; SERVICES-TASK-FORCE; PHYSICAL-ACTIVITY; BODY-SIZE; MAMMOGRAPHIC DENSITY; UNITED-STATES; REPRODUCTIVE FACTORS; CIGARETTE-SMOKING AB Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions. Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor. Data Sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium. Study Selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor. Data Extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U. S. population means. Data Synthesis: Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk. Limitations: Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered. Conclusion: Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening. C1 [Nelson, Heidi D.] Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Portland, OR 97239 USA. Providence Canc Ctr, Portland, OR USA. Grp Hlth Res Inst, Seattle, WA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Erasmus MC, Rotterdam, Netherlands. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Nelson, HD (reprint author), Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Mail Code BICC,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM nelsonh@ohsu.edu FU National Cancer Institute [U01CA086076-10S1]; BCSC [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]; Providence Health Services; Veterans Affairs Fellowship in Health Issues of Women Veterans FX By a National Cancer Institute Activities to Promote Research Collaboration supplement (U01CA086076-10S1). Data collection was supported by the National Cancer Institute-funded BCSC co-operative agreements (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). Providence Health & Services provided additional support for Dr. Nelson, and the Veterans Affairs Fellowship in Health Issues of Women Veterans provided support for Dr. Cantor. The collection of BCSC cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see www.breastscreening.cancer.gov/work/acknowledgement.html. NR 121 TC 101 Z9 108 U1 7 U2 60 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 2012 VL 156 IS 9 BP 635 EP U79 DI 10.7326/0003-4819-156-9-201205010-00006 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 933YR UT WOS:000303403700004 PM 22547473 ER PT J AU Brooks, RC Hasley, PB Jasti, H Macpherson, D AF Brooks, Robert C. Hasley, Peggy B. Jasti, Harish Macpherson, David TI Update in General Internal Medicine: Evidence Published in 2011 SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID AMBULATORY BLOOD-PRESSURE; VENOUS THROMBOEMBOLISM; PRIMARY-CARE; RISK; THERAPY; HOME C1 Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Vet Integrated Serv Network 4, Pittsburgh, PA USA. RP Macpherson, D (reprint author), 323 N Shore Dr,Suite 400, Pittsburgh, PA 15212 USA. EM David.Macpherson@va.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 2012 VL 156 IS 9 BP 649 EP U85 DI 10.7326/0003-4819-156-9-201205010-00410 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 933YR UT WOS:000303403700005 PM 22517813 ER PT J AU Zhang, YY Xu, ZP Wang, H Dong, YL Shi, HN Culley, DJ Crosby, G Marcantonio, ER Tanzi, RE Xie, ZC AF Zhang, Yiying Xu, Zhipeng Wang, Hui Dong, Yuanlin Shi, Hai Ning Culley, Deborah J. Crosby, Gregory Marcantonio, Edward R. Tanzi, Rudolph E. Xie, Zhongcong TI Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSIENT FOREBRAIN ISCHEMIA; PERMEABILITY TRANSITION PORE; BETA-PROTEIN-LEVELS; CYCLOSPORINE-A; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; CELL-DEATH; CASPASE ACTIVATION; BRAIN; INCREASES AB Objective: There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. Methods: We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. Results: Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5'-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. Interpretation: These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation. ANN NEUROL 2012; 71: 687-698 C1 [Zhang, Yiying; Xu, Zhipeng; Wang, Hui; Dong, Yuanlin; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Zhang, Yiying; Xu, Zhipeng; Wang, Hui; Dong, Yuanlin; Shi, Hai Ning; Tanzi, Rudolph E.; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wang, Hui] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China. [Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Culley, Deborah J.; Crosby, Gregory] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Culley, Deborah J.; Crosby, Gregory; Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Dept Neurol, Charlestown, MA 02129 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@partners.org FU NIH [K08 NS048140, R21 AG029856, R01 GM088801, DK082427, P30 DK040561]; American Geriatrics Society; Alzheimer's Association; Cure Alzheimer's Fund FX This study was supported by NIH grants K08 NS048140, (NINDS), R21 AG029856 (NIA), and R01 GM088801 (NINDS) (Z. Xie); American Geriatrics Society Jahnigen Award (Z. Xie); an Investigator-Initiated Research Grant from Alzheimer's Association (Z. Xie); Cure Alzheimer's Fund (Z. Xie); and NIH grant DK082427 (NIDDK) (H. S.). The Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital and Harvard Medical School covered the cost of inhalation anesthetic isoflurane and desflurane. The work was performed at Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. The flow cytometric analysis was performed at the Cell Biology Core of Harvard Clinic Nutrition Research Center [NIH grant P30 DK040561 (NIDDK) to Dr. Allan Walker].; D.J.C.: board membership, American Board of Anesthesiology. G.C.: grants/grants pending, NIH; travel expenses, Emory University, American Board of Anesthesiology. NR 50 TC 87 Z9 97 U1 3 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2012 VL 71 IS 5 BP 687 EP 698 DI 10.1002/ana.23536 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929DF UT WOS:000303040700013 PM 22368036 ER PT J AU Funalot, B Topilko, P Arroyo, MAR Sefiani, A Hedley-Whyte, ET Yoldi, ME Richard, L Touraille, E Laurichesse, M Khalifa, E Chauzeix, J Ouedraogo, A Cros, D Magdelaine, C Sturtz, FG Urtizberea, JA Charnay, P Bragado, FG Vallat, JM AF Funalot, Benoit Topilko, Piotr Ramos Arroyo, Maria Antonia Sefiani, Abdelaziz Hedley-Whyte, E. Tessa Yoldi, Maria E. Richard, Laurence Touraille, Estelle Laurichesse, Mathieu Khalifa, Emmanuel Chauzeix, Jasmine Ouedraogo, Adama Cros, Didier Magdelaine, Corinne Sturtz, Franck G. Urtizberea, J. Andoni Charnay, Patrick Garcia Bragado, Federico Vallat, Jean-Michel TI Homozygous deletion of an EGR2 enhancer in congenital amyelinating neuropathy SO ANNALS OF NEUROLOGY LA English DT Article ID SCHWANN-CELL DEVELOPMENT; GENE-EXPRESSION; COPY NUMBER; KROX20; MECHANISMS; MUTATIONS; DISEASE; SOX10; MYELINATION; CONNEXIN-32 AB The transcription factor EGR2 is expressed in Schwann cells, where it controls peripheral nerve myelination. Mutations of EGR2 have been found in patients with congenital hypomyelinating neuropathy or CharcotMarieTooth disease type 1D. In a patient with congenital amyelinating neuropathy, we observed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice. This patient, born from consanguineous parents, showed no EGR2 immunoreactivity in Schwann cells and harbored a homozygous 10.7-kilobase-long deletion encompassing a myelin-specific enhancer of EGR2. This regulatory mutation is the first genetic abnormality associated with congenital amyelinating neuropathy in humans. ANN NEUROL 2012; C1 [Funalot, Benoit; Vallat, Jean-Michel] Univ Hosp, Natl Referral Ctr Rare Peripheral Neuropathies, Limoges, France. [Funalot, Benoit; Richard, Laurence; Touraille, Estelle; Vallat, Jean-Michel] Univ Hosp, Dept Neurol, Limoges, France. [Funalot, Benoit; Laurichesse, Mathieu; Khalifa, Emmanuel; Chauzeix, Jasmine; Magdelaine, Corinne; Sturtz, Franck G.] Univ Hosp, Dept Biochem & Mol Genet, Limoges, France. [Funalot, Benoit; Richard, Laurence; Khalifa, Emmanuel; Ouedraogo, Adama; Magdelaine, Corinne; Sturtz, Franck G.; Vallat, Jean-Michel] Univ Limoges, Sch Med, Res Team Myelin Maintenance & Peripheral Neuropat, Limoges, France. [Topilko, Piotr; Charnay, Patrick] Ecole Normale Super, Inst Biol, Natl Inst Hlth, F-75231 Paris, France. [Topilko, Piotr; Charnay, Patrick] Natl Ctr Sci Res, Unit 8197, Med Res Unit 1024, Paris, France. [Ramos Arroyo, Maria Antonia] Virgen del Camino Hosp, Navarre Hlth Serv, Dept Med Genet, Pamplona, Spain. [Sefiani, Abdelaziz] Mohamed V Souissi Univ, Sch Med & Pharm, Human Genom Ctr, Rabat, Morocco. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yoldi, Maria E.] Virgen del Camino Hosp, Navarre Hlth Serv, Dept Pediat, Pamplona, Spain. [Cros, Didier] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Urtizberea, J. Andoni] Seaside Hosp Paris, Hendaye, France. [Garcia Bragado, Federico] Virgen del Camino Hosp, Navarre Hlth Serv, Dept Pathol, Pamplona, Spain. RP Funalot, B (reprint author), CHU Limoges, Serv Neurol, 2 Martin Luther King, F-87042 Limoges, France. EM benoit.funalot@unilim.fr FU French Ministry of Health; French Ministry of Education, Research, and Technology; National Institute of Health and Medical Research; National Center for Scientific Research; French Muscular Dystrophy Association; European Leukodystrophy Association Foundation FX This work was supported by the French Ministry of Health; French Ministry of Education, Research, and Technology; National Institute of Health and Medical Research; National Center for Scientific Research; French Muscular Dystrophy Association; and European Leukodystrophy Association Foundation. NR 20 TC 10 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2012 VL 71 IS 5 BP 719 EP 723 DI 10.1002/ana.23527 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 929DF UT WOS:000303040700016 PM 22522483 ER PT J AU Jaffer, FA AF Jaffer, Farouc A. TI Shining Light and Illuminating Murine Atherosclerosis via Optical Coherence Tomography SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID IN-VIVO; CARDIOVASCULAR-DISEASE C1 [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Jaffer, FA (reprint author), MGH Cardiovasc Res Ctr, 185 Cambridge St,Suite 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Howard Hughes Medical Institute; NHLBI NIH HHS [R01 HL108229, R01 HL 108229-01A1] NR 11 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2012 VL 32 IS 5 BP 1068 EP 1069 DI 10.1161/ATVBAHA.112.246439 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 931DL UT WOS:000303195100006 PM 22517362 ER PT J AU Rask-Madsen, C Buonomo, E Li, Q Park, K Clermont, AC Yerokun, O Rekhter, M King, GL AF Rask-Madsen, Christian Buonomo, Erica Li, Qian Park, Kyoungmin Clermont, Allen C. Yerokun, Oluwatobi Rekhter, Mark King, George L. TI Hyperinsulinemia Does Not Change Atherosclerosis Development in Apolipoprotein E Null Mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; diabetes mellitus; genetically altered mice; insulin resistance; signal transduction ID INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; VASCULAR INFLAMMATION; DEFICIENT MICE; HEART-DISEASE; PAI-1 GENE; RECEPTOR; SENSITIVITY; EXPRESSION; DYSFUNCTION AB Objective-To determine the contribution of hyperinsulinemia to atherosclerosis development. Methods and Results-Apolipoprotein E (Apoe) null mice that had knockout of a single allele of the insulin receptor (Insr) gene were compared with littermate Apoe null mice with intact insulin receptors. Plasma insulin levels in Insr haploinsufficient/Apoe null mice were 50% higher in the fasting state and up to 69% higher during a glucose tolerance test, but glucose tolerance was not different in the 2 groups. C-peptide levels, insulin sensitivity, and postreceptor insulin signaling in muscle, liver, fat, and aorta were not different between groups, whereas disappearance in plasma of an injected insulin analog was delayed in Insr haploinsufficient/Apoe null mice, indicating that impaired insulin clearance was the primary cause of hyperinsulinemia. No differences were observed in plasma lipids or blood pressure. Despite the hyperinsulinemia, atherosclerotic lesion size was not different between the 2 groups at time points up to 52 weeks of age when measured as en face lesion area in the aorta, cross-sectional plaque area in the aortic sinus, and cholesterol abundance in the brachiocephalic artery. Conclusion-Hyperinsulinemia, without substantial vascular or whole-body insulin resistance and without changes in plasma lipids or blood pressure, does not change susceptibility to atherosclerosis. (Arterioscler Thromb Vasc Biol. 2012; 32: 1124-1131.) C1 [King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02120 USA. [Rekhter, Mark] Lilly Res Labs, Atherosclerosis & Metab Syndrome Dept, Indianapolis, IN USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 4504, Boston, MA 02120 USA. EM george.king@joslin.harvard.edu FU NIH [K08EY018677, R01DK053105, P30DK036836, U24DK059637] FX The study was supported by NIH grants K08EY018677 to Dr Rask-Madsen and R01DK053105 to Dr King. Measurement of plasma insulin and serum free fatty acids was performed by the Joslin Diabetes Center Specialized Assay Core, blood pressure and dual-energy X-ray absorptiometry scanning by Joslin's Animal Physiology Core, and cryosections made by Joslin's Advanced Microscopy Core, all supported by NIH grant P30DK036836. Plasma lipid profiles were measured at the Lipid, Lipoprotein, and Atherosclerosis Core of the Vanderbilt Mouse Metabolic Phenotype Centers with support from NIH grant U24DK059637. The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 36 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2012 VL 32 IS 5 BP 1124 EP + DI 10.1161/ATVBAHA.111.239558 PG 17 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 931DL UT WOS:000303195100016 PM 22426129 ER PT J AU Hosseini, M Ehrhardt, N Weissglas-Volkov, D Lai, CM Mao, HZ Liao, JL Nikkola, E Bensadoun, A Taskinen, MR Doolittle, MH Pajukanta, P Peterfy, M AF Hosseini, Maryam Ehrhardt, Nicole Weissglas-Volkov, Daphna Lai, Ching-Mei Mao, Hui Z. Liao, Jo-Ling Nikkola, Elina Bensadoun, Andre Taskinen, Marja-Riitta Doolittle, Mark H. Pajukanta, Paeivi Peterfy, Miklos TI Transgenic Expression and Genetic Variation of Lmf1 Affect LPL Activity in Mice and Humans SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hyperlipoproteinemia; lipases; transgenic models; lipoprotein lipase ID FAMILIAL COMBINED HYPERLIPIDEMIA; HUMAN LIPOPROTEIN-LIPASE; LOW-DENSITY LIPOPROTEIN; ADIPOSE-TISSUE; INSULIN-RESISTANCE; HEPATIC LIPASE; SEVERE HYPERTRIGLYCERIDEMIA; ENDOPLASMIC-RETICULUM; ENDOTHELIAL LIPASE; FINNISH FAMILIES AB Objective-Lipoprotein lipase (LPL) is a principal enzyme in lipoprotein metabolism, tissue lipid utilization, and energy metabolism. LPL is synthesized by parenchymal cells in adipose, heart, and muscle tissues followed by secretion to extracellular sites, where lipolyic function is exerted. The catalytic activity of LPL is attained during posttranslational maturation, which involves glycosylation, folding, and subunit assembly within the endoplasmic reticulum. A lipase-chaperone, lipase maturation factor 1 (Lmf1), has recently emerged as a critical factor in this process. Previous studies demonstrated that loss-of-function mutations of Lmf1 result in diminished lipase activity and severe hypertriglyceridemia in mice and human subjects. The objective of this study is to investigate whether, beyond its role as a required factor in lipase maturation, variation in Lmf1 expression is sufficient to modulate LPL activity in vivo. Methods and Results-To assess the effects of Lmf1 overexpression in adipose and muscle tissues, we generated aP2-Lmf1 and Mck-Lmf1 transgenic mice. Characterization of relevant tissues revealed increased LPL activity in both mouse strains. In the omental and subcutaneous adipose depots, Lmf1 overexpression was associated with increased LPL specific activity without changes in LPL mass. In contrast, increased LPL activity was due to elevated LPL protein level in heart and gonadal adipose tissue. To extend these studies to humans, we detected association between LMF1 gene variants and postheparin LPL activity in a dyslipidemic cohort. Conclusion-Our results suggest that variation in Lmf1 expression is a posttranslational determinant of LPL activity. (Arterioscler Thromb Vasc Biol. 2012; 32: 1204-1210.) C1 [Hosseini, Maryam; Ehrhardt, Nicole; Mao, Hui Z.; Liao, Jo-Ling; Peterfy, Miklos] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Hosseini, Maryam; Lai, Ching-Mei; Liao, Jo-Ling; Doolittle, Mark H.; Peterfy, Miklos] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hosseini, Maryam; Lai, Ching-Mei; Doolittle, Mark H.; Peterfy, Miklos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Weissglas-Volkov, Daphna; Nikkola, Elina; Pajukanta, Paeivi] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Bensadoun, Andre] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Taskinen, Marja-Riitta] Helsinki Univ Hosp, Dept Med, Helsinki, Finland. RP Peterfy, M (reprint author), Cedars Sinai Med Ctr, Inst Med Genet, Davis 4091,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM mpeterfy@ucla.edu FU National Institutes of Health [HL095056, HL028481]; Cedars-Sinai Medical Center FX This work was supported by the National Institutes of Health grants HL095056 (to P. P.), HL028481 (to P. P. and M. P.), and the Cedars-Sinai Medical Center. NR 54 TC 5 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2012 VL 32 IS 5 BP 1204 EP + DI 10.1161/ATVBAHA.112.245696 PG 28 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 931DL UT WOS:000303195100025 PM 22345169 ER PT J AU Seok, J Xu, WH Gao, H Davis, RW Xiao, WZ AF Seok, Junhee Xu, Weihong Gao, Hong Davis, Ronald W. Xiao, Wenzhong TI JETTA: junction and exon toolkits for transcriptome analysis SO BIOINFORMATICS LA English DT Article ID EXPRESSION INDEX COMPUTATION; RNA-SEQ; MICROARRAYS; ARRAYS AB High-throughput genome-wide studies of alternatively spliced mRNA transcripts have become increasingly important in clinical research. Consequently, easy-to-use software tools are required to process data from these studies, for example, using exon and junction arrays. Here, we introduce JETTA, an integrated software package for the calculation of gene expression indices as well as the identification and visualization of alternative splicing events. We demonstrate the software using data of human liver and muscle samples hybridized on an exon-junction array. C1 [Seok, Junhee; Xu, Weihong; Gao, Hong; Davis, Ronald W.; Xiao, Wenzhong] Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Seok, Junhee] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Xiao, WZ (reprint author), Stanford Genome Technol Ctr, 855 Calif St, Palo Alto, CA 94304 USA. EM wxiao1@partners.org OI xiao, wenzhong/0000-0003-4944-6380 FU National Institutes of Health [U54-GM062119, P01-HG000205, R01-HG004634] FX Funding: National Institutes of Health U54-GM062119, P01-HG000205 and R01-HG004634. NR 14 TC 17 Z9 17 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 1 PY 2012 VL 28 IS 9 BP 1274 EP 1275 DI 10.1093/bioinformatics/bts134 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 933CY UT WOS:000303338200013 PM 22433281 ER PT J AU Toh, WS Lim, TC Kurisawa, M Spector, M AF Toh, Wei Seong Lim, Teck Chuan Kurisawa, Motoichi Spector, Myron TI Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment SO BIOMATERIALS LA English DT Article DE Hydrogel; Hyaluronic acid; Chondrogenesis; Mesenchymal stem cells; Cartilage; Tissue engineering ID IN-VITRO; INTERVERTEBRAL DISC; CARTILAGE TISSUE; ARTICULAR CHONDROCYTES; SKELETAL DEVELOPMENT; DIFFERENTIATION; DELIVERY; SCAFFOLDS; MATRIX; BONE AB An injectable and biodegradable hydrogel system comprising hyaluronic acid-tyramine (HA-Tyr) conjugates can safely undergo covalent cross-linking in vivo by the addition of small amounts of peroxidase and hydrogen peroxide (H2O2), with the independent tuning of the gelation rate and degree of cross-linking. Such hydrogel networks with tunable mechanical and degradation properties may provide the additional level of control needed to enhance chondrogenesis and overall cartilage tissue formation in vitro and in vivo. In this study, HA-Tyr hydrogels were explored as biomimetic matrices for caprine mesenchymal stem cells (MSCs) in cartilage tissue engineering. The compressive modulus, equilibrium swelling and degradation rate could be controlled by varying the concentration of H2O2 as the oxidant in the oxidative coupling reaction. Cellular condensation reflected by the increase in effective number density of rounded cells in lacunae was greater in softer hydrogel matrices with lower cross-linking that displayed enhanced scaffold contracture. Conversely, within higher cross-linked matrices, cells adopted a more elongated morphology, with a reduced degree of cellular condensation. Furthermore, the degree of hydrogel cross-linking also modulated matrix biosynthesis and cartilage tissue histogenesis. Lower cross-linked matrix enhanced chondrogenesis with increases in the percentage of cells with chondrocytic morphology; biosynthetic rates of glycosaminoglycan and type II collagen; and hyaline cartilage tissue formation. With increasing cross-linking degree and matrix stiffness, a shift in MSC differentiation toward fibrous phenotypes with the formation of fibrocartilage and fibrous tissues was observed. These findings suggest that the tunable three-dimensional microenvironment of the HA-Tyr hydrogels modulates cellular condensation during chondrogenesis and has a dramatic impact on spatial organization of cells, matrix biosynthesis, and overall cartilage tissue histogenesis. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Toh, Wei Seong; Lim, Teck Chuan; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Toh, Wei Seong; Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Lim, Teck Chuan; Spector, Myron] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kurisawa, Motoichi] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore. RP Spector, M (reprint author), VA Boston Healthcare Syst, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Toh, Wei Seong/K-7720-2013; KURISAWA, MOTOICHI/C-1325-2014 OI Toh, Wei Seong/0000-0001-9147-6423; KURISAWA, MOTOICHI/0000-0003-2413-6933 FU Department of Veterans Affairs; Veterans Health Administration; Rehabilitation Research and Development Service; Agency for Science, Technology and Research (A*STAR) Singapore FX The authors thank Dr. Thomas Schmid for his generous gift of lubricin antibody (mAb S6.79). The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service and Agency for Science, Technology and Research (A*STAR) Singapore (WST, TCL and MK). MS is supported by a Research Career Scientist Award from the Department of Veterans Affairs. NR 44 TC 84 Z9 87 U1 11 U2 125 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAY PY 2012 VL 33 IS 15 BP 3835 EP 3845 DI 10.1016/j.biomaterials.2012.01.065 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 932EM UT WOS:000303273200006 PM 22369963 ER PT J AU Choueiri, TK Pal, SK McDermott, DM Ramies, DA Morrissey, S Lee, Y Miles, D Holland, JS Dutcher, JP AF Choueiri, T. K. Pal, S. K. McDermott, D. M. Ramies, D. A. Morrissey, S. Lee, Y. Miles, D. Holland, J. S. Dutcher, J. P. TI Anti-tumor activity observed in an ongoing phase 1 drug-drug interaction study of cabozantinib (XL184) and rosiglitazone in patients (pts) with renal cell carcinoma SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 10th International Kidney Cancer Symposium CY OCT 14-15, 2011 CL Chicago, IL C1 [Choueiri, T. K.; Morrissey, S.] Harvard Univ, Brigham & Womens Hosp, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Pal, S. K.] City Hope Natl Med Ctr, Duarte, CA USA. [McDermott, D. M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ramies, D. A.; Lee, Y.; Miles, D.; Holland, J. S.] Exelixis, San Francisco, CA USA. [Dutcher, J. P.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 2012 VL 109 SU 5 SI SI MA 8 BP 4 EP 4 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 934IS UT WOS:000303438400009 ER PT J AU Yu, Y Sanderson, SR Reyes, M Sharma, A Dunbar, N Srivastava, T Juppner, H Bergwitz, C AF Yu, Y. Sanderson, S. R. Reyes, M. Sharma, A. Dunbar, N. Srivastava, T. Jueppner, H. Bergwitz, C. TI Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several unrelated families: Long-term follow-up in one kindred SO BONE LA English DT Article DE HHRH; SLC34A3; NaPi-IIc; Long-term follow-up; 1,25(OH)(2) vitamin D ID HEREDITARY HYPOPHOSPHATEMIC RICKETS; X-LINKED HYPOPHOSPHATEMIA; PHOSPHATE HOMEOSTASIS; I COTRANSPORTER; SMALL-INTESTINE; SLC34A3; GENE; METABOLISM; EXPRESSION; PDZ AB Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous for two different mutations, c.1046_47del and the intronic mutation c.560+23_561-42del, while the index case in kindred B was homozygous for the nonsense SLC34A3 mutation c.1764C > G (p.Y588X). The patient in kindred C was diagnosed with IH because of bilateral medullary nephrocalcinosis, suppressed PTH levels, and hypercalciuria; she was found to have a novel heterozygous c.1571_1880del mutation. The HHRH patients in kindred A were treated for up to 7 years with oral phosphate, which led to reversal of hypophosphatemia, hypercalciuria, and prevention or healing of the mild bone abnormalities. PTH levels were normal throughout the observation period, while 1,25(OH)(2) vitamin D levels remained elevated and may thus be helpful for assessing treatment efficacy and patient compliance in HHRH. (C) 2012 Elsevier Inc. All rights reserved. C1 [Yu, Y.; Reyes, M.; Jueppner, H.; Bergwitz, C.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Yu, Y.; Reyes, M.; Sharma, A.; Jueppner, H.; Bergwitz, C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sharma, A.; Jueppner, H.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Sanderson, S. R.] Horizon Hlth Network, St John, NB E2L 4L2, Canada. [Dunbar, N.] Baystate Med Ctr, Springfield, MA 01199 USA. [Srivastava, T.] Univ Missouri, Childrens Mercy Hosp & Clin, Sect Pediat Nephrol, Bone & Mineral Disorder Clin, Kansas City, MO 64108 USA. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier Bldg 1055, Boston, MA 02114 USA. EM cbergwitz@partners.org FU Studienstiftung des deutschen Volkes (The German National Merit Foundation); Biomedical Sciences Exchange Program; NIH/NIDDK [5K08DK078361, R37DK46718] FX This work was supported by the Studienstiftung des deutschen Volkes (The German National Merit Foundation) (Y.Y.), Biomedical Sciences Exchange Program (Y.Y.), and NIH/NIDDK 5K08DK078361 (C.B.) and R37DK46718 (H.J.). NR 43 TC 13 Z9 14 U1 0 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD MAY PY 2012 VL 50 IS 5 BP 1100 EP 1106 DI 10.1016/j.bone.2012.02.015 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 932EY UT WOS:000303274400011 PM 22387237 ER PT J AU Yu, Y Sanderson, SR Reyes, M Sharma, A Dunbar, N Srivastava, T Juppner, H Bergwitz, C AF Yu, Y. Sanderson, S. R. Reyes, M. Sharma, A. Dunbar, N. Srivastava, T. Jueppner, H. Bergwitz, C. TI Novel NaPi-IIc mutations causing HHRH and idiopathic hypercalciuria in several unrelated families: Long-term follow-up in one kindred (vol 50, pg 1100, 2012) SO BONE LA English DT Correction C1 [Yu, Y.; Reyes, M.; Jueppner, H.; Bergwitz, C.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Yu, Y.; Reyes, M.; Sharma, A.; Jueppner, H.; Bergwitz, C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sharma, A.; Jueppner, H.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Sanderson, S. R.] Horizon Hlth Network, St John, NB E2L 4L2, Canada. [Dunbar, N.] Baystate Med Ctr, Springfield, MA 01199 USA. [Srivastava, T.] Univ Missouri, Childrens Mercy Hosp & Clin, Sect Pediat Nephrol, Bone & Mineral Disorder Clin, Kansas City, MO 64108 USA. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier Bldg 1055, Boston, MA 02114 USA. EM cbergwitz@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2012 VL 50 IS 5 BP 1206 EP 1206 DI 10.1016/j.bone.2012.03.024 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 932EY UT WOS:000303274400028 ER PT J AU Gallagher, A Beland, R Lassonde, M AF Gallagher, Anne Beland, Renee Lassonde, Maryse TI The contribution of functional near-infrared spectroscopy (fNIRS) to the presurgical assessment of language function in children SO BRAIN AND LANGUAGE LA English DT Article DE Optical imaging; Children; Speech lateralization; Neurological disease; Epilepsy; Surgery; Intracarotid amobarbital test; Functional magnetic resonance imaging; Brain mapping ID INTRACAROTID AMOBARBITAL PROCEDURE; TEMPORAL-LOBE EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL SPEECH DOMINANCE; WADA TEST; BRAIN-FUNCTION; NONINVASIVE ASSESSMENT; OPTICAL TOPOGRAPHY; FRONTAL-LOBE; LATERALIZATION AB Before performing neurosurgery, an exhaustive presurgical assessment is required, usually including an investigation of language cerebral lateralization. Among the available procedures, the intracarotid amobarbital test (IAT) was formerly the most widely used. However, this procedure has many limitations: it is invasive and potentially traumatic, especially for children. To overcome these limitations, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used. Again, these methods are difficult to use with children, who must remain motionless during data acquisition. Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique that is easily applied to pediatric and cognitively limited patients. It has been used recently in epileptic children for presurgical assessment of expressive and receptive language brain lateralization. The aim of this review is to present the contribution of fNIRS to the presurgical assessment of language function in children with neurological diseases. (C) 2011 Elsevier Inc. All rights reserved. C1 [Lassonde, Maryse] Univ Montreal, Dept Psychol, Ctr Rech Neuropsychol & Cognit, Montreal, PQ H3C 3J7, Canada. [Gallagher, Anne] Harvard Univ, Sch Med, Boston, MA USA. [Gallagher, Anne] Carol & James Herscot Ctr Tuberous Sclerosis Comp, Dept Neurol, Boston, MA USA. [Gallagher, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Beland, Renee; Lassonde, Maryse] Ctr Hosp Univ St Justine, Ctr Rech Hop St Justine, Montreal, PQ, Canada. RP Lassonde, M (reprint author), Univ Montreal, Dept Psychol, Ctr Rech Neuropsychol & Cognit, CP 6128,Succ Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM maryse.lassonde@umontreal.ca NR 62 TC 5 Z9 5 U1 5 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 2012 VL 121 IS 2 SI SI BP 124 EP 129 DI 10.1016/j.bandl.2011.03.006 PG 6 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 932KX UT WOS:000303291100005 PM 21511328 ER PT J AU O'Donovan, A Neylan, TC Metzler, T Cohen, BE AF O'Donovan, Aoife Neylan, Thomas C. Metzler, Thomas Cohen, Beth E. TI Lifetime exposure to traumatic psychological stress is associated with elevated inflammation in the Heart and Soul Study SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Aging; Cardiovascular disease; C-reactive protein; Immune system; Inflammation; Interleukin-6; Psychological stress; Resistin; Traumatic psychological stress; Tumor necrosis factor-alpha ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; PRIMARY-CARE PATIENTS; POSTTRAUMATIC-STRESS; CARDIOVASCULAR EVENTS; DEPRESSIVE SYMPTOMS; CIRCULATING INTERLEUKIN-6; MYOCARDIAL-INFARCTION; INDUCIBLE ISCHEMIA; NATIONAL SAMPLE AB Exposure to traumatic psychological stress increases risk for disease events and mortality in patients with cardiovascular disease (CVD). While the biological mechanisms of these effects are not known, inflammation may play a key role as it is both elevated by psychological stress and involved in the development and progression of CVD. In a prospective study of patients with stable CVD (n = 979), we examined if higher lifetime trauma exposure was associated with elevated levels of inflammation at baseline and at five-year follow-up, and with greater increases in inflammation over time. Inflammation was indexed by a composite score incorporating the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP) and resistin. In follow-up analyses, we adjusted for sociodemographic factors, psychiatric disorders and health behaviors that were significantly associated with trauma exposure. Higher trauma exposure was associated with elevated inflammation at baseline (beta = .09, p = .01) and at five-year follow-up (beta = .09, p = .03). While levels of inflammation increased from baseline to follow-up in the sample, there was no significant association between trauma exposure and rate of change in inflammation. Findings were robust to adjustments for sociodemographic factors and psychiatric disorders, but health behaviors appeared to contribute to the association between trauma and inflammation at follow-up. This is the first large-scale demonstration of an association between lifetime trauma exposure and inflammation. High lifetime exposure to traumatic stress may contribute to an accelerated rate of CVD progression through elevated inflammation. (C) 2012 Elsevier Inc. All rights reserved. C1 [O'Donovan, Aoife; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [O'Donovan, Aoife; Neylan, Thomas C.; Metzler, Thomas; Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Donovan, Aoife; Neylan, Thomas C.; Metzler, Thomas; Cohen, Beth E.] No Calif Inst Res & Educ, San Francisco, CA USA. [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP O'Donovan, A (reprint author), Univ Calif San Francisco, Dept Psychiat, 3333 Calif St,Suite 465, San Francisco, CA 94143 USA. EM aoife.odonovan@ucsf.edu FU NIH/NHLBI [K23 HL 094765-01]; Department of Defense/NCIRE [DAMD17-03-1-0532, W81XWH-05-2-0094]; Irene Perstein Foundation; Society in Science: Branco Weiss Fellowship; Department of Veterans Affairs, Washington, DC; National Heart Lung and Blood Institute, Bethesda, MD [R01 HL079235]; American Federation for Aging Research (Paul Beeson Scholars Program), New York, NY; Robert Wood Johnson Foundation, Princeton, NJ; Ischemia Research and Education Foundation, South San Francisco, CA; Nancy Kirwan Heart Research Fund, San Francisco, CA; Department of Defense [W81XWH-10-2-0089]; Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration FX This research was supported in part by NIH/NHLBI Grant K23 HL 094765-01, Department of Defense/NCIRE Grants DAMD17-03-1-0532, W81XWH-05-2-0094, and a Grant from the Irene Perstein Foundation to Dr. Cohen and by a Society in Science: Branco Weiss Fellowship to Dr. O'Donovan. The Heart and Soul Study was funded by the Department of Veterans Affairs, Washington, DC, the National Heart Lung and Blood Institute (R01 HL079235), Bethesda, MD, the American Federation for Aging Research (Paul Beeson Scholars Program), New York, NY, the Robert Wood Johnson Foundation (Faculty Scholars Program), Princeton, NJ, the Ischemia Research and Education Foundation, South San Francisco, CA, and the Nancy Kirwan Heart Research Fund, San Francisco, CA. This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Medical Center, San Francisco, CA. Mr. Metzler is supported in part by Grants from the Department of Defense (W81XWH-10-2-0089), the Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration. The funding organizations had no role in the design or conduct of the study; data collection, management, analysis or interpretation of the data; or preparation, review or approval of the manuscript. The authors would like to thank The Heart and Soul Study team for supporting this manuscript, particular Dr. Mary Whooley, Mathilda Regan and Bee Ya Na. NR 74 TC 27 Z9 27 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAY PY 2012 VL 26 IS 4 BP 642 EP 649 DI 10.1016/j.bbi.2012.02.003 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 929PV UT WOS:000303078800018 PM 22366689 ER PT J AU Hensley, ML Kravetz, S Jia, XY Iasonos, A Tew, W Pereira, L Sabbatini, P Whalen, C Aghajanian, CA Zarwan, C Berlin, S AF Hensley, Martee L. Kravetz, Sara Jia, Xiaoyu Iasonos, Alexia Tew, William Pereira, Lauren Sabbatini, Paul Whalen, Christin Aghajanian, Carol A. Zarwan, Corinne Berlin, Suzanne TI Eribulin mesylate (halichondrin B analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer A 2-Cohort, Phase 2 Study SO CANCER LA English DT Article DE eribulin; ovarian cancer; phase 2; recurrence ID PEGYLATED LIPOSOMAL DOXORUBICIN; 2-STAGE DESIGNS; TRIAL; PACLITAXEL; CARCINOMA AB BACKGROUND: Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. In this study, the authors assessed the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer. METHODS: Patients with recurrent, measurable epithelial ovarian cancer who had received <= 2 prior cytotoxic regimens and who had adequate organ function were enrolled into 2 separate cohorts: 1) platinum-resistant patients (who had a progression-free interval <6 months after their last platinum-based therapy) and 2) platinum-sensitive patients (who had a progression-free interval >= 6 months after their last platinum-based therapy). Eribulin 1.4 mg/m(2) was administered over 15 minutes intravenously on days 1 and 8 every 21 days. Efficacy was determined by objective response on computed tomography studies. RESULTS: In the platinum-resistant cohort, 37 patients enrolled, and 36 patients were evaluable for response and toxicity. Two patients achieved a partial response (5.5%), and 16 patients (44%) had stable disease as their best response. The median progression-free survival was 1.8 months (95% confidence interval, 1.4-2.8 months). In the platinum-sensitive cohort, 37 patients enrolled, and all were evaluable for response. Seven patients achieved a partial response (19%). The median progression-free survival was 4.1 months (95% confidence interval, 2.8-5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% of platinum-resistant patients; 54% of platinum-sensitive patients). CONCLUSIONS: Eribulin produced an objective response in 5.5% of women with platinum-resistant, recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. The median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group. Cancer 2012;118:2403-10. (C) 2011 American Cancer Society. C1 [Hensley, Martee L.; Kravetz, Sara; Tew, William; Sabbatini, Paul; Aghajanian, Carol A.] Mem Sloan Kettering Canc Ctr, Gynecol Med Oncol Serv, Dept Med, New York, NY 10065 USA. [Hensley, Martee L.; Kravetz, Sara; Tew, William; Sabbatini, Paul; Aghajanian, Carol A.] Weill Cornell Med Coll, New York, NY USA. [Jia, Xiaoyu; Iasonos, Alexia] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Pereira, Lauren; Whalen, Christin; Berlin, Suzanne] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zarwan, Corinne] Lahey Clin Fdn, Div Hematol Oncol, Dept Med, Boston, MA USA. RP Hensley, ML (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10065 USA. EM hensleym@mskcc.org FU Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute [NO1-CM62206] FX Funding for this study was provided by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute NO1-CM62206 (Clinicaltrials.gov registration no. NCT00334893). NR 19 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 1 PY 2012 VL 118 IS 9 BP 2403 EP 2410 DI 10.1002/cncr.26569 PG 8 WC Oncology SC Oncology GA 929ES UT WOS:000303044600009 PM 21935916 ER PT J AU Jabaudon, D Shnider, SJ Tischfield, DJ Galazo, MJ Macklis, JD AF Jabaudon, Denis Shnider, Sara J. Tischfield, David J. Galazo, Maria J. Macklis, Jeffrey D. TI ROR beta Induces Barrel-like Neuronal Clusters in the Developing Neocortex SO CEREBRAL CORTEX LA English DT Article DE barrel cortex; cortical patterning; cytoarchitecture; ROR beta; thalamocortical innervation ID DEVELOPING CEREBRAL-CORTEX; VESICULAR GLUTAMATE TRANSPORTERS; CORTICOSPINAL MOTOR-NEURONS; MOUSE SOMATOSENSORY CORTEX; SUBTYPE-SPECIFIC GENES; REELER MUTANT MICE; PROJECTION NEURONS; CORTICAL AREAS; ADULT-RAT; COUP-TFI AB Neurons in layer IV of the rodent whisker somatosensory cortex are tangentially organized in periodic clusters called barrels, each of which is innervated by thalamocortical axons transmitting sensory information from a single principal whisker, together forming a somatotopic map of the whisker pad. Proper thalamocortical innervation is critical for barrel formation during development, but the molecular mechanisms controlling layer IV neuron clustering are unknown. Here, we investigate the role in this mapping of the nuclear orphan receptor ROR beta, which is expressed in neurons in layer IV during corticogenesis. We find that ROR beta protein expression specifically increases in the whisker barrel cortex during barrel formation and that in vivo overexpression of ROR beta is sufficient to induce periodic barrel-like clustering of cortical neurons. Remarkably, this clustering can be induced as early as E18, prior to innervation by thalamocortical afferents and whisker derived-input. At later developmental stages, these ectopic neuronal clusters are specifically innervated by thalamocortical axons, demonstrated by anterograde labeling from the thalamus and by expression of thalamocortical-specific synaptic markers. Together, these data indicate that ROR beta expression levels control cytoarchitectural patterning of neocortical neurons during development, a critical process for the topographical mapping of whisker input onto the cortical surface. C1 [Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Bauer Labs, Cambridge, MA 02138 USA. [Jabaudon, Denis; Shnider, Sara J.; Tischfield, David J.; Galazo, Maria J.; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Shnider, Sara J.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Jabaudon, Denis] Univ Geneva, Dept Basic Neurosci, CH-1211 Geneva, Switzerland. [Jabaudon, Denis] Univ Geneva, Neurol Clin, CH-1211 Geneva, Switzerland. [Jabaudon, Denis; Shnider, Sara J.; Tischfield, David J.; Galazo, Maria J.; Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA. [Jabaudon, Denis; Shnider, Sara J.; Tischfield, David J.; Galazo, Maria J.; Macklis, Jeffrey D.] Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Program Neurosci,Med Sch, Boston, MA 02114 USA. [Jabaudon, Denis; Shnider, Sara J.; Tischfield, David J.; Galazo, Maria J.; Macklis, Jeffrey D.] Harvard Univ, MGH HMS Ctr Nervous Syst Repair, Dept Neurol, Program Neurosci,Med Sch, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Bauer Labs, 7 Divin Ave, Cambridge, MA 02138 USA. EM jeffrey_macklis@hms.harvard.edu FU National Institutes of Health (NIH) [NS49553, NS45523, NS41590]; Harvard Stem Cell Institute; Spastic Paraplegia Foundation; Travis Roy Foundation; Massachusetts Spinal Cord Injury Research Fund; Jane and Lee Seidman Fund for CNS Research; Emily and Robert Pearlstein Fund for Nervous System Repair; Swiss National Science Foundation; Pierre Mercier Science Foundation; NIH predoctoral NRSA [F31 NS063516]; Mary Gordon Roberts Fellowship; Caja Madrid Foundation FX National Institutes of Health (NIH) (NS49553, NS45523 to J.D.M.; additional infrastructure supported by grant number NS41590 to J.D.M.); Harvard Stem Cell Institute; Spastic Paraplegia Foundation; Travis Roy Foundation; Massachusetts Spinal Cord Injury Research Fund; Jane and Lee Seidman Fund for CNS Research; and Emily and Robert Pearlstein Fund for Nervous System Repair to J.D.M. The Swiss National Science Foundation and Pierre Mercier Science Foundation partially supported D.J.; NIH predoctoral NRSA (F31 NS063516) partially supported S.J.S.; Harvard Stem Cell Institute Internship Program and a Mary Gordon Roberts Fellowship partially supported D. T.; a Caja Madrid Foundation fellowship partially supported M.J.G. NR 59 TC 28 Z9 29 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2012 VL 22 IS 5 BP 996 EP 1006 DI 10.1093/cercor/bhr182 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 930SX UT WOS:000303161400002 PM 21799210 ER PT J AU Hedden, T Van Dijk, KRA Shire, EH Sperling, RA Johnson, KA Buckner, RL AF Hedden, Trey Van Dijk, Koene R. A. Shire, Emily H. Sperling, Reisa A. Johnson, Keith A. Buckner, Randy L. TI Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology SO CEREBRAL CORTEX LA English DT Article DE aging; amyloid beta; executive function; fMRI; individual differences; PET ID PREFRONTAL CORTEX FUNCTION; PITTSBURGH COMPOUND-B; AGE-RELATED-CHANGES; INTRINSIC FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; SPATIAL WORKING-MEMORY; ADULT LIFE-SPAN; ALZHEIMERS-DISEASE; OLDER-ADULTS; AMYLOID DEPOSITION AB Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes. C1 [Hedden, Trey; Van Dijk, Koene R. A.; Shire, Emily H.; Sperling, Reisa A.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Hedden, Trey; Johnson, Keith A.; Buckner, Randy L.] Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Van Dijk, Koene R. A.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Van Dijk, Koene R. A.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Shire, Emily H.; Sperling, Reisa A.; Buckner, Randy L.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Sperling, Reisa A.; Johnson, Keith A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Hedden, T (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM hedden@nmr.mgh.harvard.edu RI Van Dijk, Koene/G-3317-2012 OI Van Dijk, Koene/0000-0001-6137-4282 FU National Institute on Aging [R01 AG021910, R01 AG034556, R01 AG037497, P01 AG036694, R01 AG027435-S1, 5 P01 AG04390]; Howard Hughes Medical Institute; Alzheimer's Association; Netherlands Organization for Scientific Research; National Center for Research Resources (NCRR), National Institutes of Health; NCRR [1S10RR023401, 1S10RR019307, 1S10RR023043]; Hebrew SeniorLife Institute for Aging Research; Massachusetts Alzheimer's Disease Research Center [2 P50 AG05134] FX National Institute on Aging (grants R01 AG021910, R01 AG034556, R01 AG037497, P01 AG036694, and R01 AG027435-S1); Howard Hughes Medical Institute; Alzheimer's Association. K. R. A. V. D. was supported by the Netherlands Organization for Scientific Research.; We thank Angel Mehta, Renee Poulin, Betsy Hemphill, Jeremy Carmasin, and Meghan Frey for assistance during data collection and Tanveer Talukdar and Itamar Kahn for technical advice. This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers 1S10RR023401, 1S10RR019307, and 1S10RR023043. The MGH Molecular Imaging PET Core provided assistance with amyloid imaging. Alex Becker, Aaron Schultz, Bill Klunk, and Chet Mathis provided assistance with PiB. Dorene Rentz and the Massachusetts Alzheimer's Disease Research Center provided assistance with clinical and neuropsychological characterization of the participants. Minjie Wu kindly provided software for labeling WMHs. Research participants were recruited with the assistance of resources provided by the Harvard Cooperative Program on Aging (supported by the Hebrew SeniorLife Institute for Aging Research and grants from the National Institute on Aging 5 P01 AG04390 and the Massachusetts Alzheimer's Disease Research Center Subgrant 2 P50 AG05134), the Research Study Volunteer Program for Health at Massachusetts General Hospital and Brigham and Women's Hospital, and the Commonwealth of Massachusetts Executive Office of Elder Affairs. Conflict of Interest: K. A. J. has served as a paid consultant to GE Healthcare, Ltd., which holds a license agreement with the University of Pittsburgh based on the PiB technology described in this article. GE Healthcare provided no grant support for this study and had no role in the design or interpretation of results or preparation of this article. NR 112 TC 29 Z9 30 U1 2 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2012 VL 22 IS 5 BP 1038 EP 1051 DI 10.1093/cercor/bhr172 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 930SX UT WOS:000303161400006 PM 21765181 ER PT J AU Derbyshire, ER Mazitschek, R Clardy, J AF Derbyshire, Emily R. Mazitschek, Ralph Clardy, Jon TI Characterization of Plasmodium Liver Stage Inhibition by Halofuginone SO CHEMMEDCHEM LA English DT Article DE halofuginone; high-throughput screening; malaria; sporozoites; structure-activity relationships ID LIFE-CYCLE; ANTIMALARIAL ACTIVITY; DRUG DISCOVERY; MALARIA; FALCIPARUM; SPOROZOITES; HOST; FEBRIFUGINE; INFECTION; MEROZOITES AB Malaria is a devastating parasitic disease that afflicts one-third of the worlds population. Antimalarial drugs in common use address few targets, and their efficacy is being undermined by parasite resistance. Most therapeutics target blood-stage malaria, whereas only few compounds are active against malarias liver stage, the first stage of the Plasmodium parasites life cycle within the human host. The identification of inhibitors active against liver-stage malaria would benefit the development of chemical probes to elucidate the poorly understood biology of this phase of the parasite life cycle and could provide agents to prevent and eliminate the disease. Herein we report the development of a live-cell parasite traversal assay in 384-well format amenable to high-throughput screening that exploits the wounding of liver cells by the parasite. This method identifies small molecules that may inhibit the parasite's actinmyosin motor system. The traversal assay, in addition to established methods, was used to evaluate the activity of halofuginone, a synthetic halogenated derivative of the natural alkaloid febrifugine, against liver-stage Plasmodium berghei parasites. Halofuginone was found to inhibit P. berghei sporozoite load in HepG2 cells with an IC50 value of 17 nM. While the compound does not affect parasite traversal through human liver cells, an inhibition time course assay indicates that it affects essential processes in both early- and late-stage parasite development. C1 [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Derbyshire, Emily R.; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Mazitschek, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM rmazitschek@mgh.harvard.edu; jon_clardy@hms.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU Harvard Medical School-Portugal; Ruth L. Kirschstein National Research Service Award [F32GM093510] FX This work was supported by a Harvard Medical School-Portugal Collaborative Research Grant to J.C. and a Ruth L. Kirschstein National Research Service Award (F32GM093510) to E.R.D. The authors thank Maria M. Mota (University of Lisbon, Portugal) for critical input and providing the Plasmodium antibody, and Joseph F. Cortese (Broad Institute) for blood-stage assays. The authors also thank the Nikon Imaging Center and the Institute of Chemistry and Cell Biology (ICCB)-Longwood Screening Facility at Harvard Medical School. NR 39 TC 19 Z9 21 U1 0 U2 20 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 2012 VL 7 IS 5 BP 844 EP 849 DI 10.1002/cmdc.201200045 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 931CP UT WOS:000303192300010 PM 22438279 ER PT J AU Jin, JF Sundararaj, KP Samuvel, DJ Zhang, XM Li, YC Lu, ZY Lopes-Virella, MF Huang, Y AF Jin, Junfei Sundararaj, Kamala P. Samuvel, Devadoss J. Zhang, Xiaoming Li, Yanchun Lu, Zhongyang Lopes-Virella, Maria F. Huang, Yan TI Different signaling mechanisms regulating IL-6 expression by LPS between gingival fibroblasts and mononuclear cells: seeking the common target SO CLINICAL IMMUNOLOGY LA English DT Article DE Inflammation; LPS; Cytokine; Gene expression; Signal transduction; Transcription ID NF-KAPPA-B; C-REACTIVE PROTEIN; PERIODONTAL-DISEASE; ENDOTHELIAL-CELLS; MMP-1 EXPRESSION; LIPOPOLYSACCHARIDE; INTERLEUKIN-6; ACTIVATION; RECEPTOR; AP-1 AB To reduce connective tissue IL-6 level stimulated by LPS, it is essential to control IL-6 expression in both mononuclear cells and fibroblasts. However, it is unclear whether the regulatory mechanisms for both cells are similar or not. In this study, we found that signaling pathways mediating LPS-stimulated IL-6 in mononuclear U937 cells and fibroblasts were different. Furthermore, our studies showed that while LPS activated AP-1 and NF kappa B in U937 cells, it only activated NF kappa B in fibroblasts. Analysis of nuclear AP-1 subunits showed that LPS stimulated c-Fos, Fra-1 and Jun D activities in U937 cells, but not fibroblasts. The lack of ERK involvement in LPS-stimulated IL-6 in fibroblasts was further supported by the observations that simvastatin, which is known to target ERK-AP-1, failed to inhibit LPS-stimulated IL-6 by fibroblasts. Finally, we showed that targeting NFKB pathway was highly effective in inhibition of LPS-stimulated IL-6 in coculture of U937 cells and fibroblasts. Published by Elsevier Inc. C1 [Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Jin, Junfei; Sundararaj, Kamala P.; Samuvel, Devadoss J.; Zhang, Xiaoming; Li, Yanchun; Lu, Zhongyang; Lopes-Virella, Maria F.; Huang, Yan] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU Department of Veterans Affairs; NIH [DE16353] FX This work was supported by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs and by NIH grant DE16353 (to Y.H.). NR 38 TC 9 Z9 10 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2012 VL 143 IS 2 BP 188 EP 199 DI 10.1016/j.clim.2012.01.019 PG 12 WC Immunology SC Immunology GA 932KV UT WOS:000303290900010 PM 22386866 ER PT J AU Dooley, KE Bliven-Sizemore, EE Weiner, M Lu, Y Nuermberger, EL Hubbard, WC Fuchs, EJ Melia, MT Burman, WJ Dorman, SE AF Dooley, K. E. Bliven-Sizemore, E. E. Weiner, M. Lu, Y. Nuermberger, E. L. Hubbard, W. C. Fuchs, E. J. Melia, M. T. Burman, W. J. Dorman, S. E. TI Safety and Pharmacokinetics of Escalating Daily Doses of the Antituberculosis Drug Rifapentine in Healthy Volunteers SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ACQUIRED RIFAMYCIN RESISTANCE; HIV-RELATED TUBERCULOSIS; PLASMA-CONCENTRATIONS; RIFAMPICIN; INDUCTION; MIDAZOLAM; TWICE; MOXIFLOXACIN; RIFABUTIN; REGIMENS AB Rifapentine (RPT) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RIF). The maximal tolerated daily dose of RP T and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. In this phase I, dose-escalation study among healthy volunteers, daily doses as high as a prespecified maximum of 20 mg/kg/day were well tolerated. Steady-state RP T concentrations increased with dose from 5 to 15 mg/kg, but area under the plasma concentration-time curve (AUC(0-24)) and maximum concentration (C-max) were similar in the 15- and 20-mg/kg cohorts. Although RP T pharmacokinetics (PK) appeared to be time-dependent, accumulation occurred with daily dosing. The mean AUC(0-12) of oral midazolam (MDZ), a cytochrome 3A (CYP3A) probe drug, was reduced by 93% with the coadministration of RPT and by 74% with the coadministration of RIF (P < 0.01). Changes in the oral clearance of MDZ did not vary by RP T dose. In conclusion, RP T was tolerated at doses as high as 20 mg/kg/day, its PK were less than dose-proportional, and its CYP3A induction was robust. C1 [Dooley, K. E.; Lu, Y.; Hubbard, W. C.; Fuchs, E. J.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Dooley, K. E.; Nuermberger, E. L.; Melia, M. T.; Dorman, S. E.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Bliven-Sizemore, E. E.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. [Weiner, M.] Vet Adm Med Ctr, Div Med & Infect Dis, San Antonio, TX USA. [Burman, W. J.] Denver Publ Hlth, Denver, CO USA. RP Dooley, KE (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. EM kdooley1@jhmi.edu FU Centers for Disease Control and Prevention; CDC Foundation; National Institutes of Health National Center for Research Resources [UL1 RR025005]; NIAID [P30 50410, K23AI080842]; Sanofi-Aventis; [1S10 RR 27733] FX The study team is grateful to the individuals who participated in this study. We appreciate the efforts of the research team at the Drug Development Unit at Johns Hopkins, notably Stephanie Everts and Elizabeth Purdy. We acknowledge the contributions of Namandje Bumpus and Teresa Parsons from the Clinical Pharmacology Analytical Laboratory at Johns Hopkins to the development of the RPT and RIF (and metabolite) assays, and we thank Angela Kashuba and Stephanie Malone at the University of North Carolina for quantifying MDZ and its metabolite. We also acknowledge Carla Jeffries of the Centers for Disease Control and Prevention for her assistance with graphics. We appreciate the thoughtful input and comments of Chad Heilig and Andy Vernon from the Centers for Disease Control and Prevention and Theresa Shapiro from Johns Hopkins. This study was sponsored by the Centers for Disease Control and Prevention and the CDC Foundation and was supported by the following grants: Institutional Clinical and Translational Science Award National Institutes of Health National Center for Research Resources UL1 RR025005, NIAID P30 50410 (UNC Center for AIDS Research (MDZ assays)), and K23AI080842 (K. E. D.). The ABI-Sciex API5500 Quadrupole-Linear Ion Trap console used for quantification of rifapentine and rifampin was purchased from Grant 1S10 RR 27733 awarded to W. C. H. The Waters Acquity ultraperformance liquid chromatography interfaced with the API5500 was purchased with funds from Pendleton Enterprises awarded to Craig W. Hendrix. Rifapentine (Priftin; Anagni, Italy) was provided by Sanofi-Aventis. NR 37 TC 24 Z9 25 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2012 VL 91 IS 5 BP 881 EP 888 DI 10.1038/clpt.2011.323 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 929FT UT WOS:000303047400022 PM 22472995 ER PT J AU Gopal, RK Yamashita, TE Prochazka, AV AF Gopal, Ravi K. Yamashita, Traci E. Prochazka, Allan V. TI Research without results: Inadequate public reporting of clinical trial results SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Publication bias; Food and Drug Administration; Transparency; Clinical trials; Trial registries ID EFFICACY; BIAS AB Objective: In order to increase transparency in the medical literature, the Food and Drug Administration (FDA) Modernization Act of 1997 and the FDA Amendment Act of 2007 required registration of all "applicable trials" with required "basic results" reporting. We evaluated the rate of compliance with the FDA mandatory results reporting in www.clinicaltrials.gov. Methods: All completed registered interventional studies that may be subject to FDA regulation, one year prior to required results reporting (October 2006 to September 2007, n = 1097) and during the two years after required reporting (October 2007 to September 2008 (07-08), n = 2231 and October 2008 to September 2009 (08-09), n = 2923). Results: Downloading all 99,315 records from clinicaltrials.gov, we excluded all non-applicable studies. Results reporting increased from 6.8% (n = 75) prior to mandatory reporting to 19.1% (n = 427, p<.01) in 07-08 and 10.8% (n = 316, p<.01) in 08-09. The odds ratio for results reporting using the 06-07 time period as the reference was 3.31 (95% Cl 2.54-4.32) for 07-08 and 1.74 (1.33-2.28) for 08-09. Of the 818 trials with results in clinicaltrials.gov, the rate of published articles found decreased from 60% (n = 45) in the year prior to required reporting to 33% (n = 140, p<.001) for 07-08 and 20% (n = 63, p<.001) for 08-09 time period. Conclusion: The majority of studies registered in clinicaltrials.gov are not required to report data. Of studies that may be required to report data, compliance with data reporting has improved. The clinicaltrials.gov website is not yet a comprehensive resource for study results. Published by Elsevier Inc. C1 [Gopal, Ravi K.; Prochazka, Allan V.] Univ Colorado Denver Sch Med, Denver Vet Affairs Hosp, Dept Ambulatory Care, Denver, CO USA. [Yamashita, Traci E.] Univ Colorado Denver Sch Med, Dept Gen Internal Med, Dept Ambulatory Care, Denver, CO USA. RP Gopal, RK (reprint author), Denver VAMC, Box 11B,1055 Clermont St, Denver, CO 80220 USA. EM ravi.gopal@va.gov NR 13 TC 12 Z9 12 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2012 VL 33 IS 3 BP 486 EP 491 DI 10.1016/j.cct.2012.02.001 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 930XM UT WOS:000303178100006 PM 22342449 ER PT J AU Mendu, ML Zager, S Gibbons, FK Christopher, KB AF Mendu, Mallika L. Zager, Sam Gibbons, Fiona K. Christopher, Kenneth B. TI Relationship between neighborhood poverty rate and bloodstream infections in the critically ill SO CRITICAL CARE MEDICINE LA English DT Article DE bloodstream infection; critical care; poverty ID DISPARITIES GEOCODING PROJECT; INTENSIVE-CARE-UNIT; SOCIOECONOMIC-STATUS; RISK-FACTORS; COMMON COLD; T-CELLS; CLINICAL-SIGNIFICANCE; PARENTERAL-NUTRITION; ACQUIRED BACTEREMIA; MULTILEVEL ANALYSIS AB Background: Poverty is associated with increased risk of chronic illness, but its contribution to bloodstream infections is not well-defined. Methods: We performed a multicenter observational study of 14,657 patients, aged 18 yrs or older, who received critical care and had blood cultures drawn between 1997 and 2007 in two hospitals in Boston, Massachusetts. Data sources included 1990 U. S. Census and hospital administrative data. Census tracts were used as the geographic units of analysis. The exposure of interest was neighborhood poverty rate categorized as <5%, 5%-10%, 10%-20%, 20%-40%, and >40%. Neighborhood poverty rate is the percentage of residents with income below the federal poverty line. The primary end point was bloodstream infection occurring 48 hrs before critical care initiation to 48 hrs after. Associations between neighborhood poverty rate and bloodstream infection were estimated by logistic regression models. Adjusted odds ratios were estimated by multi-variable logistic regression models. Results: Two thousand four-hundred thirty-five patients had bloodstream infections. Neighborhood poverty rate was a strong predictor of risk of bloodstream infection, with a significant risk gradient across neighborhood poverty rate quintiles. After multi-variable analysis, neighborhood poverty rate in the highest quintiles (20%-40% and >40%) were associated with a 26% and 49% increase in bloodstream infection risk, respectively, relative to patients with neighborhood poverty rate of <5%. Conclusions: Within the limitations of our study design, increased neighborhood poverty rate, a proxy for decreased socioeconomic status, appears to be associated with risk of bloodstream infection among patients who receive critical care. (Crit Care Med 2012; 40: 1427-1436) C1 [Mendu, Mallika L.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Zager, Sam] Harvard Univ, Sch Med, Boston, MA USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Nathan E Hellman Mem Lab, Div Renal, Boston, MA 02115 USA. RP Mendu, ML (reprint author), Brigham & Womens Hosp, Dept Internal Med, 75 Francis St, Boston, MA 02115 USA. EM kbchristopher@partners.org FU National Institutes of Health [K08AI060881] FX Supported, in part, by the National Institutes of Health [Grant K08AI060881]. NR 124 TC 12 Z9 13 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2012 VL 40 IS 5 BP 1427 EP 1436 DI 10.1097/CCM.0b013e318241e51e PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 930AE UT WOS:000303106900004 PM 22511126 ER PT J AU Bajwa, EK Malhotra, CK Thompson, BT Christiani, DC Gong, MN AF Bajwa, Ednan K. Malhotra, Cindy K. Thompson, B. Taylor Christiani, David C. Gong, Michelle N. TI Statin therapy as prevention against development of acute respiratory distress syndrome: An observational study SO CRITICAL CARE MEDICINE LA English DT Article DE ALI/ARDS; critical illness; statin ID ACUTE LUNG INJURY; POPULATION-BASED COHORT; PROPENSITY SCORE; CLINICAL-TRIAL; SEVERE SEPSIS; SIMVASTATIN; OUTCOMES; EXPRESSION; MORTALITY; INFECTION AB Objectives: The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins") have anti-inflammatory properties and are associated with improved outcomes in critically ill patients. We investigated whether previous statin therapy affects outcomes in patients at risk for acute respiratory distress syndrome. Design: Patients were followed-up for the primary outcome of acute respiratory distress syndrome and secondary outcomes of intensive care unit and 60-day mortality, organ dysfunction, and ventilator-free days in a secondary analysis of a prospective cohort study. Receipt of statin therapy was recorded. Propensity score matching was used to adjust for confounding by indication. Setting: Intensive care units at a tertiary care academic medical center. Patients: Critically ill patients (2,743) with acute respiratory distress syndrome risk factors. Interventions: None. Measurements and Main Results: Acute respiratory distress syndrome developed in 738 (26%) patients; 413 patients (15%) received a statin within 24 hrs of intensive care unit admission. Those who had received a statin within 24 hrs had a lower rate of development of acute respiratory distress syndrome (odds ratio 0.56; 95% confidence interval 0.43-0.73; p < .0001). After multivariate adjustment for potential confounders, this association remained significant (odds ratio 0.69; 95% confidence interval 0.51-0.92; p = .01). However, after propensity score matching, the association was not statistically significant (odds ratio 0.79; 95% confidence interval 0.57-1.10; p = .16). Statin use was not associated with reduced acute respiratory distress syndrome mortality, organ dysfunction, or ventilator-free days. Results of the study were presented in accordance with STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Conclusions: Statin therapy at the time of intensive care unit admission was not associated with a lower rate of development of acute respiratory distress syndrome after matching for patient propensity to receive statins. Statin therapy was not associated with improvements in acute respiratory distress syndrome mortality, organ failure, or days free from mechanical ventilation. (CritCare Med 2012; 40:1470-1477) C1 [Bajwa, Ednan K.; Thompson, B. Taylor; Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Malhotra, Cindy K.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Boston, MA 02115 USA. [Gong, Michelle N.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care Med, Bronx, NY 10467 USA. RP Bajwa, EK (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. EM ebajwa@partners.org FU NHBLI [HL60710, HL67197, HL084060, HL086667]; National Institutes of Health FX Supported, in part, by NHBLI grants HL60710, HL67197, HL084060, and HL086667.; Drs. Bajwa, Christiani, and Gong receive grant support from the National Institutes of Health. Dr. Thompson is an investigator for the ARDS Network and Medical Director of the Clinical Coordination Center. Dr. Malhotra has not disclosed any potential conflicts of interest. NR 43 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2012 VL 40 IS 5 BP 1470 EP 1477 DI 10.1097/CCM.0b013e3182416d7a PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 930AE UT WOS:000303106900010 PM 22430234 ER PT J AU Rice, TW Rubinson, L Uyeki, TM Vaughn, FL John, BB Miller, RR Higgs, E Randolph, AG Smoot, BE Thompson, BT AF Rice, Todd W. Rubinson, Lewis Uyeki, Timothy M. Vaughn, Frances L. John, Benjamin B. Miller, Russell R., II Higgs, Elizabeth Randolph, Adrienne G. Smoot, B. Elizabeth Thompson, B. Taylor CA NHLBI ARDS Network TI Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States SO CRITICAL CARE MEDICINE LA English DT Article DE bacterial coinfection; critical illness; mortality; pandemic H1N1 influenza ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; H1N1 VIRUS; A(H1N1) INFECTION; ILL PATIENTS; VENTILATION; PNEUMONIA; FAILURE; MEXICO AB Objectives: The contribution of bacterial coinfection to critical illness associated with 2009 influenza A virus infection remains uncertain. The objective of this study was to determine whether bacterial coinfection increased the morbidity and mortality of 2009 influenza A. Design: Retrospective and prospective cohort study. Setting: Thirty-five adult U. S. intensive care units over the course of 1 yr. Patients: Six hundred eighty-three critically ill adults with confirmed or probable 2009 influenza A. Interventions: None. Measurements and Main Results: A confirmed or probable case was defined as a positive 2009 influenza A test result or positive test for influenza A that was otherwise not subtyped. Bacterial coinfection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hrs of intensive care unit admission. The mean age was 45 +/- 16 yrs, mean body mass index was 32.5 +/- 11.1 kg/m(2), and mean Acute Physiology and Chronic Health Examination II score was 21 +/- 9, with 76% having at least one comorbidity. Of 207 (30.3%) patients with bacterial coinfection on intensive care unit admission, 154 had positive cultures with Staphylococcus aureus (n = 57) and Streptococcus pneumoniae (n = 19), the most commonly identified pathogens. Bacterial coinfected patients were more likely to present with shock (21% vs. 10%; p = .0001), require mechanical ventilation at the time of intensive care unit admission (63% vs. 52%; p = .005), and have longer duration of intensive care unit care (median, 7 vs. 6 days; p = .05). Hospital mortality was 23%; 31% in bacterial coinfected patients and 21% in patients without coinfection (p = .002). Immunosuppression (relative risk 1.57; 95% confidence interval 1.20-2.06; p = .0009) and Staphylococcus aureus at admission (relative risk 2.82; 95% confidence interval 1.76-4.51; p < .0001) were independently associated with increased mortality. Conclusions: Among intensive care unit patients with 2009 influenza A, bacterial coinfection diagnosed within 72 hrs of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality. (Crit Care Med 2012; 40: 1487-1498) C1 [Rice, Todd W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Rubinson, Lewis] HHS ASPR OPEO, Natl Disaster Med Syst, Salt Lake City, UT USA. [Uyeki, Timothy M.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Salt Lake City, UT USA. [Vaughn, Frances L.; John, Benjamin B.] HHS ASPR OPEO, Emergency Care Coordinat Ctr, Salt Lake City, UT USA. [Miller, Russell R., II] Intermt Med Ctr, Salt Lake City, UT USA. [Miller, Russell R., II] Univ Utah, Sch Med, Salt Lake City, UT USA. [Higgs, Elizabeth] NIAID, Div Clin Res, NIH, Boston, MA USA. [Randolph, Adrienne G.] Childrens Hosp, Boston, MA 02115 USA. [Smoot, B. Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. [Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rice, TW (reprint author), Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. EM todd.rice@vanderbilt.edu OI Randolph, Adrienne/0000-0002-3084-3071 FU NHLBI [N01-HR-56179] FX Supported, in part, by NHLBI N01-HR-56179. NR 35 TC 66 Z9 72 U1 2 U2 12 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 2012 VL 40 IS 5 BP 1487 EP 1498 DI 10.1097/CCM.0b013e3182416f23 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA 930AE UT WOS:000303106900012 PM 22511131 ER PT J AU Schmidt, U Coppadoro, A Hess, DR AF Schmidt, Ulrich Coppadoro, Andrea Hess, Dean R. TI To breathe or not to breathe? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; lung-protection; ventilation ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; MECHANICAL VENTILATION; PRESSURE SUPPORT C1 [Schmidt, Ulrich; Hess, Dean R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Dept Resp Care, Boston, MA 02114 USA. [Coppadoro, Andrea] Univ Milano Bicocca, Dept Expt Med, Monza, Italy. RP Schmidt, U (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Dept Resp Care, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2012 VL 40 IS 5 BP 1680 EP 1681 DI 10.1097/CCM.0b013e3182474cd0 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 930AE UT WOS:000303106900052 PM 22511162 ER PT J AU Aft, R Perez, JR Raje, N Hirsh, V Saad, F AF Aft, Rebecca Perez, Jose-Ricardo Raje, Noopur Hirsh, Vera Saad, Fred TI Could targeting bone delay cancer progression? Potential mechanisms of action of bisphosphonates SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Bisphosphonates; Bone metastases; Breast cancer; Disseminated tumor cells; Multiple myeloma; Zoledronic acid ID DISSEMINATED TUMOR-CELLS; EARLY BREAST-CANCER; NITROGEN-CONTAINING BISPHOSPHONATES; RANDOMIZED CONTROLLED-TRIAL; REFRACTORY PROSTATE-CANCER; MESENCHYMAL STEM-CELLS; PLUS ZOLEDRONIC ACID; KAPPA-B LIGAND; DELTA T-CELLS; MULTIPLE-MYELOMA AB Although dissemination may occur early in the course of many cancers, the development of overt metastases depends upon a variety of factors inherent to the cancer cells and the tissue(s) they colonize. The time lag between initial dissemination and established metastases could be several years, during which period the bone marrow may provide an unwitting sanctuary for disseminated tumor cells (DTCs). Survival in a dormant state within the bone marrow may help DTCs weather the effects of anticancer therapies and seed posttreatment relapses. The importance of the bone marrow for facilitating DTC survival may vary depending on the type of cancer and mechanisms of tumor cell dissemination. By altering the bone microenvironment, bisphosphonates may reduce DTC viability. Moreover, some bisphosphonates have demonstrated multiple anticancer activities. These multiple mechanisms may help explain the improvement in disease outcomes with the use of zoledronic acid in malignancies like breast cancer and multiple myeloma. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Aft, Rebecca] Washington Univ, Sch Med, Dept Surg, Div Gen Surg Canc, St Louis, MO 63110 USA. [Perez, Jose-Ricardo] Novartis Pharmaceut, Florham Pk, NJ USA. [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hirsh, Vera] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Saad, Fred] CRCHUM Ctr Hosp Univ Montreal, Montreal, PQ, Canada. RP Aft, R (reprint author), Washington Univ, Sch Med, Dept Surg, Div Gen Surg Canc, 660 S Euclid Ave, St Louis, MO 63110 USA. EM aftr@wustl.edu FU AstraZeneca; Acetylon; Novartis Pharmaceuticals FX R. Aft has received honoraria from Novartis. J.-R. Perez is an employee of Novartis Pharmaceuticals Corporation. N. Raje is a consultant and has participated in advisory boards for Novartis, Amgen, and Celgene, and has received research grants from AstraZeneca and Acetylon. V. Hirsh has participated in advisory boards for Novartis and Amgen. F. Saad has received research funding, attended advisory board meetings, and received honoraria for speaking on behalf of Novartis Oncology.; Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Shalini Murthy, PhD, ProEd Communications, Inc.(R), for her medical editorial assistance with this manuscript. NR 137 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2012 VL 82 IS 2 BP 233 EP 248 DI 10.1016/j.critrevonc.2011.05.009 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 932MG UT WOS:000303294600011 PM 21683613 ER PT J AU Courtney, KD Taplin, ME AF Courtney, Kevin D. Taplin, Mary-Ellen TI The evolving paradigm of second-line hormonal therapy options for castration-resistant prostate cancer SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE abiraterone acetate; ARN-509; castrate-resistant prostate cancer; MDV3100; second-line hormonal therapy; TAK-700; TOK-001 ID INHIBITOR ABIRATERONE ACETATE; ANDROGEN-RECEPTOR GENE; I CLINICAL-TRIAL; INTRATUMORAL ANDROGENS; ANTITUMOR-ACTIVITY; PHASE-II; PROGRESSION; STEROIDOGENESIS; KETOCONAZOLE; ANTIANDROGEN AB Purpose of review The review examines recent advances in second-line hormonal therapy for the treatment of castrate-resistant prostate cancer (CRPC). Recent findings Recent data highlight the continued importance of androgen signaling in CRPC. These findings have spurred the development of novel inhibitors of adrenal and intra-tumoral androgen synthesis and novel androgen signaling inhibitors with activity in CRPC. In the past year abiraterone acetate, a CYP17 (17 alpha-hydroxylase/17,20 lyase) inhibitor, received US FDA approval for use in the treatment of metastatic CRPC in patients previously treated with docetaxel. Additionally, the novel androgen signaling inhibitor MDV3100 has been reported to confer a survival advantage compared to placebo in the same patient population. Here we review the scientific rationale for targeting androgen signaling in CRPC and the recent pivotal trials that support the use of novel second-line hormonal therapies. Additionally, we summarize ongoing preclinical and clinical efforts to ascertain and overcome mechanisms of resistance. Summary Novel inhibitors of extra-gonadal androgen synthesis and androgen receptor function demonstrate the continued importance of androgen signaling in CRPC. These agents have improved clinical outcomes for patients with metastatic CRPC. C1 [Courtney, Kevin D.; Taplin, Mary-Ellen] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. RP Taplin, ME (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM Mary_Taplin@dfci.harvard.edu FU Michael and Sally Fairweather Fund FX Funding: Michael and Sally Fairweather Fund. NR 37 TC 14 Z9 15 U1 0 U2 5 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 2012 VL 24 IS 3 BP 272 EP 277 DI 10.1097/CCO.0b013e328351059d PG 6 WC Oncology SC Oncology GA 931LC UT WOS:000303220400012 PM 22327837 ER PT J AU Willette, AA Bendlin, BB Colman, RJ Kastman, EK Field, AS Alexander, AL Sridharan, A Allison, DB Anderson, R Voytko, ML Kemnitz, JW Weindruch, RH Johnson, SC AF Willette, Auriel A. Bendlin, Barbara B. Colman, Ricki J. Kastman, Erik K. Field, Aaron S. Alexander, Andrew L. Sridharan, Aadhavi Allison, David B. Anderson, Rozalyn Voytko, Mary-Lou Kemnitz, Joseph W. Weindruch, Richard H. Johnson, Sterling C. TI Calorie Restriction Reduces the Influence of Glucoregulatory Dysfunction on Regional Brain Volume in Aged Rhesus Monkeys SO DIABETES LA English DT Article ID DIETARY RESTRICTION; INSULIN-RESISTANCE; ALZHEIMERS-DISEASE; ENERGY-METABOLISM; GLUCOSE; MECHANISMS; TERM; RAT; PATHOGENESIS; HIPPOCAMPUS AB Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity x dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships. Diabetes 61:1036-1042, 2012 C1 [Willette, Auriel A.; Bendlin, Barbara B.; Kastman, Erik K.; Sridharan, Aadhavi; Anderson, Rozalyn; Weindruch, Richard H.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Willette, Auriel A.; Alexander, Andrew L.; Johnson, Sterling C.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI USA. [Willette, Auriel A.; Bendlin, Barbara B.; Kastman, Erik K.; Sridharan, Aadhavi; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Colman, Ricki J.; Anderson, Rozalyn; Kemnitz, Joseph W.; Johnson, Sterling C.] Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Field, Aaron S.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Sridharan, Aadhavi; Johnson, Sterling C.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Voytko, Mary-Lou] Wake Forest Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA. [Kemnitz, Joseph W.] Univ Wisconsin, Dept Cell & Regenerat Biol, Sch Med & Publ Hlth, Madison, WI USA. [Johnson, Sterling C.] Univ Wisconsin, Inst Clin & Translat Res, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. EM scj@medicine.wisc.edu RI Kastman, Erik/N-6645-2016; OI Allison, David/0000-0003-3566-9399; Kastman, Erik/0000-0001-7221-9042; Bendlin, Barbara/0000-0002-0580-9875 FU National Institutes of Health [RR-000167, AG-011915, AG-000213, GM-007507, MH-085051, MH-062015]; William S. Middleton Memorial Veterans Hospital; Research Facilities Improvement Program [RR-15459-01, RR-020141-01] FX This study was supported in part by the National Institutes of Health grants RR-000167, AG-011915, AG-000213, GM-007507, MH-085051, and MH-062015. This study was also supported with resources and facilities at the William S. Middleton Memorial Veterans Hospital. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grants RR-15459-01 and RR-020141-01. NR 48 TC 21 Z9 22 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAY PY 2012 VL 61 IS 5 BP 1036 EP 1042 DI 10.2337/db11-1187 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 930XW UT WOS:000303179100015 PM 22415875 ER PT J AU Aranda, J Motiejunaite, R Im, E Kazlauskas, A AF Aranda, Jorge Motiejunaite, Ruth Im, Eunok Kazlauskas, Andrius TI Diabetes Disrupts the Response of Retinal Endothelial Cells to the Angiomodulator Lysophosphatidic Acid SO DIABETES LA English DT Article ID GROWTH-FACTOR; NADPH OXIDASE; RETINOPATHY; ACTIVATION; ANGIOGENESIS; AUTOTAXIN; PHOTOCOAGULATION; COMPLICATIONS; PATHWAYS; RECEPTOR AB The objectives of this study were to investigate how diabetes mellitus (DM) influences responsiveness of retinal neovessels to lysophosphatidic acid (LPA) and to elucidate the underlying mechanism. To this end, we used an ex vivo assay in which neovessels sprouted from retinal explants (isolated from either control or DM mice) when cultured between two layers of collagen and in the presence of vascular endothelial growth factor-A. While DM had no effect on the formation of neovessels, it prevented LPA-induced regression. High-glucose (HG) treatment of retinal explants mimicked the DM phenotype. Similarly, primary retinal endothelial cells (RECs), which were subjected to HG treatment, organized into tubes that were resistant to LPA. HG caused LPA resistance within RECs by elevating ROS, which activated Src-family kinases that stimulated the extracellular signal-related kinase (Erk) pathway, which antagonized LPA-mediated signaling events that were required for regression. This ROS/Src/Erk pathway mechanism appeared to be the same route by which DM induced LPA resistance of retinal neovessels. We conclude that DM/HG reprograms signaling pathways in RECs to induce a state of LPA resistance. Diabetes 61:1225-1233, 2012 C1 [Aranda, Jorge; Motiejunaite, Ruth; Kazlauskas, Andrius] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. [Motiejunaite, Ruth] Vilnius State Univ, Dept Biochem & Biophys, Vilnius, Lithuania. [Im, Eunok] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. RP Kazlauskas, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. EM ak@eri.harvard.edu FU Juvenile Diabetes Research Foundation [I-2008-905]; National Institutes of Health [DK-083336]; Pew Latin American Fellows Program in the Biomedical Sciences; American Diabetes Association [7-09-MI-04]; Fundacion Mexico en Harvard FX This study was supported by grants from the Juvenile Diabetes Research Foundation (I-2008-905 to A.K.), the National Institutes of Health (DK-083336 to El.), the Pew Latin American Fellows Program in the Biomedical Sciences, the American Diabetes Association Mentor-Based Minority Fellowship (7-09-MI-04), and Fundacion Mexico en Harvard (to J.A.). NR 39 TC 8 Z9 8 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2012 VL 61 IS 5 BP 1225 EP 1233 DI 10.2337/db11-1189 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 930XW UT WOS:000303179100035 PM 22415872 ER PT J AU Scott, RA Chu, AY Grarup, N Manning, AK Hivert, MF Shungin, D Tonjes, A Yesupriya, A Barnes, D Bouatia-Naji, N Glazer, NL Jackson, AU Kutalik, Z Lagou, V Marek, D Rasmussen-Torvik, LJ Stringham, HM Tanaka, T Aadahl, M Arking, DE Bergmann, S Boerwinkle, E Bonnycastle, LL Bornstein, SR Brunner, E Bumpstead, SJ Brage, S Carlson, OD Chen, H Chen, YDI Chines, PS Collins, FS Couper, DJ Dennison, EM Dowling, NF Egan, JS Ekelund, U Erdos, MR Forouhi, NG Fox, CS Goodarzi, MO Grassler, J Gustafsson, S Hallmans, G Hansen, T Hingorani, A Holloway, JW Hu, FB Isomaa, B Jameson, KA Johansson, I Jonsson, A Jorgensen, T Kivimaki, M Kovacs, P Kumari, M Kuusisto, J Laakso, M Lecoeur, C Levy-Marchal, C Li, G Loos, RJF Lyssenko, V Marmot, M Marques-Vidal, P Morken, MA Muller, G North, KE Pankow, JS Payne, F Prokopenko, I Psaty, BM Renstrom, F Rice, K Rotter, JI Rybin, D Sandholt, CH Sayer, AA Shrader, P Schwarz, PEH Siscovick, DS Stancakova, A Stumvoll, M Teslovich, TM Waeber, G Williams, GH Witte, DR Wood, AR Xie, WJ Boehnke, M Cooper, C Ferrucci, L Froguel, P Groop, L Kao, WHL Vollenweider, P Walker, M Watanabe, RM Pedersen, O Meigs, JB Ingelsson, E Barroso, I Florez, JC Franks, PW Dupuis, J Wareham, NJ Langenberg, C AF Scott, Robert A. Chu, Audrey Y. Grarup, Niels Manning, Alisa K. Hivert, Marie-France Shungin, Dmitry Toenjes, Anke Yesupriya, Ajay Barnes, Daniel Bouatia-Naji, Nabila Glazer, Nicole L. Jackson, Anne U. Kutalik, Zoltan Lagou, Vasiliki Marek, Diana Rasmussen-Torvik, Laura J. Stringham, Heather M. Tanaka, Toshiko Aadahl, Mette Arking, Dan E. Bergmann, Sven Boerwinkle, Eric Bonnycastle, Lori L. Bornstein, Stefan R. Brunner, Eric Bumpstead, Suzannah J. Brage, Soren Carlson, Olga D. Chen, Han Chen, Yii-Der Ida Chines, Peter S. Collins, Francis S. Couper, David J. Dennison, Elaine M. Dowling, Nicole F. Egan, Josephine S. Ekelund, Ulf Erdos, Michael R. Forouhi, Nita G. Fox, Caroline S. Goodarzi, Mark O. Graessler, Juergen Gustafsson, Stefan Hallmans, Goeran Hansen, Torben Hingorani, Aroon Holloway, John W. Hu, Frank B. Isomaa, Bo Jameson, Karen A. Johansson, Ingegerd Jonsson, Anna Jorgensen, Torben Kivimaki, Mika Kovacs, Peter Kumari, Meena Kuusisto, Johanna Laakso, Markku Lecoeur, Cecile Levy-Marchal, Claire Li, Guo Loos, Ruth J. F. Lyssenko, Valeri Marmot, Michael Marques-Vidal, Pedro Morken, Mario A. Mueller, Gabriele North, Kari E. Pankow, James S. Payne, Felicity Prokopenko, Inga Psaty, Bruce M. Renstrom, Frida Rice, Ken Rotter, Jerome I. Rybin, Denis Sandholt, Camilla H. Sayer, Avan A. Shrader, Peter Schwarz, Peter E. H. Siscovick, David S. Stancakova, Alena Stumvoll, Michael Teslovich, Tanya M. Waeber, Gerard Williams, Gordon H. Witte, Daniel R. Wood, Andrew R. Xie, Weijia Boehnke, Michael Cooper, Cyrus Ferrucci, Luigi Froguel, Philippe Groop, Leif Kao, W. H. Linda Vollenweider, Peter Walker, Mark Watanabe, Richard M. Pedersen, Oluf Meigs, James B. Ingelsson, Erik Barroso, Ines Florez, Jose C. Franks, Paul W. Dupuis, Josee Wareham, Nicholas J. Langenberg, Claudia TI No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels SO DIABETES LA English DT Article ID DIABETES PREVENTION PROGRAM; LIFE-STYLE INTERVENTION; COMMON VARIANTS; TYPE-2; RISK; MELLITUS; ENVIRONMENT; TRAITS; POLYMORPHISMS; PROGRESSION AB Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP x physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (beta = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 X 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12 mmol/allele, P <= 1.53 X 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P >= 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions. Diabetes 61:1291-1296, 2012 C1 [Scott, Robert A.; Barnes, Daniel; Brage, Soren; Ekelund, Ulf; Forouhi, Nita G.; Loos, Ruth J. F.; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Chu, Audrey Y.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chu, Audrey Y.; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Grarup, Niels; Hansen, Torben; Sandholt, Camilla H.; Pedersen, Oluf] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, Fac Hlth Sci, Copenhagen, Denmark. [Manning, Alisa K.; Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Grarup, Niels; Hansen, Torben; Sandholt, Camilla H.; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Shungin, Dmitry; Renstrom, Frida; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Umea, Sweden. [Shungin, Dmitry; Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany. [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Integriertes Forsch & Behandlungszentrum IFB Adip, Leipzig, Germany. [Yesupriya, Ajay; Dowling, Nicole F.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Bouatia-Naji, Nabila; Lecoeur, Cecile; Froguel, Philippe] Inst Pasteur, CNRS, UMR 8199, F-59019 Lille, France. [Bouatia-Naji, Nabila; Lecoeur, Cecile; Levy-Marchal, Claire; Froguel, Philippe] Univ Lille Nord France, Lille, France. [Glazer, Nicole L.] Boston Univ, Dept Med Prevent Med & Epidemiol, Boston, MA 02215 USA. [Jackson, Anne U.; Stringham, Heather M.; Teslovich, Tanya M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kutalik, Zoltan; Marek, Diana; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Kutalik, Zoltan; Marek, Diana; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland. [Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Lagou, Vasiliki; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Rasmussen-Torvik, Laura J.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Aadahl, Mette; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Arking, Dan E.] Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. [Arking, Dan E.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.; Erdos, Michael R.; Morken, Mario A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Bornstein, Stefan R.; Graessler, Juergen; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany. [Brunner, Eric; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Marmot, Michael] UCL, Dept Epidemiol & Publ Hlth, London, England. [Bumpstead, Suzannah J.] Wellcome Trust Sanger Inst, Cambridge, England. [Carlson, Olga D.; Egan, Josephine S.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [Chen, Yii-Der Ida; Goodarzi, Mark O.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Dennison, Elaine M.; Jameson, Karen A.; Sayer, Avan A.; Cooper, Cyrus] Univ Southampton, MRC, Lifecourse Epidemiol Unit, Southampton, Hants, England. [Fox, Caroline S.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Hu, Frank B.; Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Jonsson, Anna; Lyssenko, Valeri; Groop, Leif] Lund Univ, Diabet & Endocrinol Unit, Dept Clin Sci, Malmo, Sweden. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany. [Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Univ Eastern Finland, Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Levy-Marchal, Claire] Hop Robert Debre, INSERM, CIC EC 05, F-75019 Paris, France. [Li, Guo] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Li, Guo] Univ Washington, Dept Med, Seattle, WA USA. [Marques-Vidal, Pedro] CHU Vaudois, Inst Social & Prevent Med IUMSP, CH-1011 Lausanne, Switzerland. [Mueller, Gabriele] Univ Dresden, Inst Med Informat & Biometry, Med Fac Carl Gustav Carus, Dresden, Germany. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. [Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Shrader, Peter; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Waeber, Gerard; Vollenweider, Peter] CHUV, Dept Internal Med, Lausanne, Switzerland. [Witte, Daniel R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Wood, Andrew R.; Xie, Weijia] Peninsula Coll Med & Dent, Exeter, Devon, England. [Cooper, Cyrus] Univ Oxford, Botnar Res Ctr, Oxford, England. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England. [Barroso, Ines] Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Cambridge, England. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Scott, RA (reprint author), Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. EM robert.scott@mrc-epid.cam.ac.uk RI Marques-Vidal, Pedro/C-9449-2009; Li, Guo/E-5613-2012; Schwarz, Peter/B-5127-2013; Holloway, John/B-5424-2009; Rice, Kenneth/A-4150-2013; Brage, Soren/C-6415-2013; Colaus, PsyColaus/K-6607-2013; Lagou, Vasiliki/N-8451-2013; Witte, Daniel/C-1722-2008; Prokopenko, Inga/H-3241-2014; Grarup, Niels/K-2807-2015; BOUATIA-NAJI, NABILA/D-5863-2013 OI Forouhi, Nita/0000-0002-5041-248X; Chen, Han/0000-0002-9510-4923; Jorgensen, Torben/0000-0001-9453-2830; Marmot, Michael/0000-0002-2431-6419; Payne, Felicity/0000-0003-4228-581X; Pankow, James/0000-0001-7076-483X; Bergmann, Sven/0000-0002-6785-9034; Rybin, Denis/0000-0002-3657-4829; Barnes, Daniel/0000-0002-3781-7570; Marques-Vidal, Pedro/0000-0002-4548-8500; Kivimaki, Mika/0000-0002-4699-5627; Aihie Sayer, Avan/0000-0003-1283-6457; Dupuis, Josee/0000-0003-2871-3603; Kumari, Meena/0000-0001-9716-1035; Schwarz, Peter/0000-0001-6317-7880; Shungin, Dmitry/0000-0001-7900-5856; Holloway, John/0000-0001-9998-0464; Rice, Kenneth/0000-0001-5779-4495; Bouatia-Naji, Nabila/0000-0001-5424-2134; Brage, Soren/0000-0002-1265-7355; Witte, Daniel/0000-0002-0769-2922; Prokopenko, Inga/0000-0003-1624-7457; Grarup, Niels/0000-0001-5526-1070; FU British Heart Foundation [RG/07/008/23674]; Medical Research Council [G0100222, G0701863, G0902037, G1002084, G19/35, G8802774, MC_U106179471, MC_U106179473, MC_UP_A100_1003, MC_UP_A620_1014, MC_UP_A620_1015]; NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [UL1 RR024148, UL1 RR025741]; NHLBI NIH HHS [T32 HL007575]; NIDDK NIH HHS [K24 DK080140, P30 DK020572, P30 DK063491, R01 DK072041] NR 28 TC 5 Z9 5 U1 0 U2 9 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 2012 VL 61 IS 5 BP 1291 EP 1296 DI 10.2337/db11-0973 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 930XW UT WOS:000303179100042 PM 22415877 ER PT J AU Marina, AL Utzschneider, KM Wright, LA Montgomery, BK Marcovina, SM Kahn, SE AF Marina, Anna L. Utzschneider, Kristina M. Wright, Lorena A. Montgomery, Brenda K. Marcovina, Santica M. Kahn, Steven E. TI Colesevelam Improves Oral but Not Intravenous Glucose Tolerance by a Mechanism Independent of Insulin Sensitivity and beta-Cell Function SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; GLYCEMIC CONTROL; BILE-ACIDS; PANCREATIC-SECRETION; DOUBLE-BLIND; CHOLECYSTOKININ; RELEASE; CHOLESTYRAMINE; HYDROCHLORIDE; THERAPY AB OBJECTIVE-To determine the mechanism by which the bile acid sequestrant colesevelam improves glycemic control. RESEARCH DESIGN AND METHODS-We performed a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis and a meal tolerance test (MTT) in 20 subjects with impaired fasting glucose (11 men, 9 women; mean age 60.7 +/- 1.9 years, BM I 29.4 +/- 0.9 kg/m(2)) in a single-blind study after 2 weeks of placebo treatment and 8 weeks of colesevelam 3.75 g daily. From these tests, insulin sensitivity, beta-cell function, and glucose tolerance were determined, along with gastrointestinal peptide levels during the MTT. RESULTS-Fasting plasma glucose and HbA(1c) decreased with colesevelam (from 5.9 +/- 0.1 to 5.7 +/- 0.1 mmol/L, P < 0.05, and from 5.86 +/- 0.06 to 5.76 +/- 0.06%, P = 0.01, respectively), but fasting insulin did not change. Colesevelam had no effect on any FSIGT measures. In contrast, the MTT incremental area under the curve (iAUC) for both glucose (from 249.3 +/- 28.5 to 198.8 +/- 23.6 mmol/L . min, P < 0.01) and insulin (from 20,130 [13,542-35,292] to 13,086 [9,804-21,138] pmol/L . min, P < 0.05) decreased with, colesevelam. However, the ratio of iAUC insulin to iAUC glucose was not changed. iAUC for cholecystokinin (CCK) increased (from 43.2 [0-130.1] to 127.1 [47.2-295.2] pmol/L . min, P < 0.01), while iAUC for fibroblast growth factor 19 decreased (from 11,185 [1,346-17,661] to 2,093 [673-6,707] pg/mL . min, P < 0.01.) with colesevelam. However, iAUC for glucagon, glucose-dependent insulinocropic peptide, and glucagon-like peptide 1 did not change. CONCLUSIONS-Colesevelam improves oral but not intravenous glucose tolerance without changing insulin sensitivity, beta-cell function, or incretins. This effect may be at least partially explained by the colesevelam-induced increase in CCK. C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. EM skahn@u.washington.edu FU U.S. Department of Veterans Affairs, National Institutes of Health [DK-007247, DK-017047]; Daiichi Sankyo FX This study was supported in pan by the U.S. Department of Veterans Affairs, National Institutes of Health Grants DK-007247 and DK-017047.; The study was also supported by an investigator-initiated proposal sponsored by Daiichi Sankyo. No other potential conflicts of interest relevant to this article were reported. NR 30 TC 26 Z9 26 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 2012 VL 35 IS 5 BP 1119 EP 1125 DI 10.2337/dc11-2050 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931KN UT WOS:000303218900033 PM 22446171 ER PT J AU King, GL McNeely, MJ Thorpe, LE Mau, MLM Ko, J Liu, LNL Sun, A Hsu, WC Chow, EA AF King, George L. McNeely, Marguerite J. Thorpe, Lorna E. Mau, Marjorie L. M. Ko, Jocelyn Liu, Lenna L. Sun, Angela Hsu, William C. Chow, Edward A. TI Understanding and Addressing Unique Needs of Diabetes in Asian Americans, Native Hawaiians, and Pacific Islanders SO DIABETES CARE LA English DT Review ID NEW-YORK-CITY; GLUCOSE-INTOLERANCE; MULTIETHNIC COHORT; CHINESE-AMERICANS; CENTRAL ADIPOSITY; DIETARY PATTERNS; SOUTH ASIANS; PREVALENCE; HEALTH; RISK C1 [King, George L.; Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. [McNeely, Marguerite J.] Univ Washington, Dept Med, Seattle, WA USA. [Thorpe, Lorna E.] CUNY, Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Mau, Marjorie L. M.; Ko, Jocelyn] Univ Hawaii Manoa, John A Burns Sch Med, Dept Native Hawaiian Hlth, Ctr Native & Pacific Hlth Dispar Res, Honolulu, HI 96822 USA. [Liu, Lenna L.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Sun, Angela] Chinese Community Hlth Resource Ctr, San Francisco, CA USA. [Chow, Edward A.] Calif Chinese Community Hlth Care Assoc, San Francisco, CA USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. EM george.king@joslin.harvard.edu FU National Institutes of Health [P20-MD-000173, S21-MD-00028]; American Diabetes Association; Asian & Pacific Islander American Health Forum; Association of Asian Pacific Islander Health Care Organizations; Daichii Sankyo, Inc.; Joslin Diabetes Center AADI; Kaiser Permanente; National Council of Asian Pacific Islander Physicians (NCAPIP); Novo Nordisk; sanofi-aventis FX Sponsors who have made possible the State of the Sciences Conference 2011: "Diabetes in Asian Americans, Native Hawaiians & Pacific Islanders: A Call to Action": American Diabetes Association, Asian & Pacific Islander American Health Forum, Association of Asian Pacific Islander Health Care Organizations, Daichii Sankyo, Inc., Joslin Diabetes Center AADI, Kaiser Permanente, National Council of Asian Pacific Islander Physicians (NCAPIP), Novo Nordisk, and sanofi-aventis, U.S. LLC. M.L.M.M. was supported by National Institutes of Health Grants P20-MD-000173 and S21-MD-00028. No other potential conflicts of interest relevant to this article were reported. NR 51 TC 40 Z9 40 U1 0 U2 9 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 2012 VL 35 IS 5 BP 1181 EP 1188 DI 10.2337/dc12-0210 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931KN UT WOS:000303218900042 PM 22517939 ER PT J AU Hsu, WC Boyko, EJ Fujimoto, WY Kanaya, A Karmally, W Karter, A King, GL Look, M Maskarinec, G Misra, R Tavake-Pasi, F Arakaki, R AF Hsu, William C. Boyko, Edward J. Fujimoto, Wilfred Y. Kanaya, Alka Karmally, Wahida Karter, Andrew King, George L. Look, Mele Maskarinec, Gertraud Misra, Ranjita Tavake-Pasi, Fahina Arakaki, Richard TI Pathophysiologic Differences Among Asians, Native Hawaiians, and Other Pacific Islanders and Treatment Implications SO DIABETES CARE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; LIFE-STYLE MODIFICATION; RANDOMIZED-CONTROLLED-TRIAL; VISCERAL ADIPOSE-TISSUE; FASTING GLUCOSE; JAPANESE-AMERICANS; MULTIETHNIC COHORT; ETHNIC-DIFFERENCES; METABOLIC SYNDROME C1 [Hsu, William C.; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. [Boyko, Edward J.] Vet Adm Puget Sound Hlth Care Syst, Gen Internal Med Sect, Seattle, WA USA. [Fujimoto, Wilfred Y.] Univ Washington, Dept Med, Seattle, WA USA. [Kanaya, Alka] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Karmally, Wahida] Columbia Univ, Irving Inst Clin & Translat Res, New York, NY USA. [Karter, Andrew] Kaiser Pennanente No Calif, Ctr Diabet Translat Res, Div Res, Oakland, CA USA. [Look, Mele] Univ Hawaii Manoa, John A Burns Sch Med, Dept Native Hawaiian Hlth, Ctr Native & Pacific Hlth Dispar Res, Honolulu, HI 96822 USA. [Maskarinec, Gertraud] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Misra, Ranjita] Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA. [Tavake-Pasi, Fahina] Natl Tongan Amer Soc, Salt Lake City, UT USA. [Arakaki, Richard] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. RP Hsu, WC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Asian Amer Diabet Initiat, Boston, MA 02115 USA. EM william.hsu@joslin.harvard.edu OI Misra, Ranjita/0000-0001-7314-0184 FU National Center on Minority Health and Health Disparities [P20MD000173]; National Institutes of Health [DK-31170, HL-49293, DK-02654]; VA Puget Sound Health Care System FX This article was made possible in part by Award P20MD000173 from the National Center on Minority Health and Health Disparities. This work was partly supported by National Institutes of Health Grants DK-31170, HL-49293, and DK-02654; by facilities and services provided by the Diabetes and Endocrinology Research Center (DK-17047), Clinical Nutrition Research Unit (DK-35816), and the General Clinical Research Center (RR-00037) at the University of Washington. The VA Puget Sound Health Care System provided support for E.J.B.'s involvement in this research. NR 51 TC 30 Z9 30 U1 1 U2 7 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 2012 VL 35 IS 5 BP 1189 EP 1198 DI 10.2337/dc12-0212 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931KN UT WOS:000303218900043 PM 22517940 ER PT J AU Eda, H Kulig, KM Steiner, TA Shimada, H Patel, K Park, E Kim, E Borenstein, JT Neville, CM Keller, BT AF Eda, Hiroyuki Kulig, Katherine M. Steiner, Toni A. Shimada, Hideaki Patel, Krupali Park, Eric Kim, Ernest S. Borenstein, Jeffrey T. Neville, Craig M. Keller, Bradley T. TI A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatic stellate cell; Nanofiber membrane; Stress fiber; Growth factor; Quiescent ID MESENCHYMAL STEM-CELLS; PEPTIDE-AMPHIPHILE NANOFIBERS; EXTRACELLULAR-MATRIX; LIVER MYOFIBROBLASTS; ROCK INHIBITOR; TGF-BETA; COLLAGEN; RAT; GROWTH; ACTIVATION AB Hepatic stellate cells (HSC) play a major role in the progression of liver fibrosis. The aim of our study was to investigate whether rat HSC cultured on a nanofiber membrane (NM) retain their quiescent phenotype during both short- and long-term culture and whether activated HSC revert to a quiescent form when re-cultured on NM. Rat HSC cultured for 1 day on plastic plates (PP) were used as quiescent HSC, while cells cultured for 1 week on PP were considered to be activated HSC. Quiescent or activated HSC were subsequently plated on PP or NM and cultured for an additional 4 days at which time their gene expression, stress fiber development, and growth factor production were determined. For long-term culture, HSC were grown on NM for 20 days and the cells then replated on PP and cultured for another 10 days. Expression of marker genes for HSC activation, stress fiber development, and growth factor production were significantly lower in both quiescent and activated HSC cultured on NM than in those cultured on PP. After long-term culture on NM, activation marker gene expression and stress fiber development were still significantly lower in HSC than in PP, and HSC still retained the ability to activate when replated onto PP. HSC cultured on NM retained quiescent characteristics after both short- and long-term culture while activated HSC reverted toward a quiescent state when cultured on NM. Cultures of HSC grown on NM are a useful in vitro model to investigate the mechanisms of activation and deactivation. C1 [Eda, Hiroyuki] Ajinomoto Pharmaceut Co Ltd, Exploratory Res Labs, Kawasaki, Kanagawa, Japan. [Eda, Hiroyuki; Steiner, Toni A.; Shimada, Hideaki; Patel, Krupali; Keller, Bradley T.] Pfizer Inc, Pfizer Global Res & Dev, St Louis Labs, Discovery Biol, Chesterfield, MO USA. [Kulig, Katherine M.; Neville, Craig M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Park, Eric] Pfizer Inc, Pfizer Global Res & Dev, Res Technol Ctr, Cambridge, MA USA. [Kim, Ernest S.; Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. RP Eda, H (reprint author), Ajinomoto Pharmaceut Co Ltd, Exploratory Res Labs, Kawasaki, Kanagawa, Japan. EM hiroyuki_eda@ajinomoto.com FU Pfizer Inc. FX This work is supported by Pfizer Inc. NR 46 TC 2 Z9 2 U1 1 U2 4 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 2012 VL 57 IS 5 BP 1152 EP 1162 DI 10.1007/s10620-012-2084-9 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 933TH UT WOS:000303385100007 PM 22359192 ER PT J AU Stearns, AT Balakrishnan, A Radmanesh, A Ashley, SW Rhoads, DB Tavakkolizadeh, A AF Stearns, A. T. Balakrishnan, A. Radmanesh, A. Ashley, S. W. Rhoads, D. B. Tavakkolizadeh, A. TI Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-Induced Obesity SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Vagus; Bariatric surgery; Capsaicin; Vagotomy; Abdominal visceral fat ID VISCERAL ADIPOSE-TISSUE; SENSORY NERVE DESENSITIZATION; METABOLIC RISK-FACTORS; GLUCOSE-TOLERANCE; MORBID-OBESITY; COTRANSPORTER SGLT1; INSULIN-SECRETION; TRUNCAL VAGOTOMY; BODY-WEIGHT; FOOD-INTAKE AB We previously demonstrated vagal neural pathways, specifically subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium-glucose cotransporter SGLT1, the intestinal transporter responsible for absorption of dietary glucose. We hypothesized targeting this pathway could be a novel therapy for obesity. We therefore tested the impact of disrupting vagal signaling by total vagotomy or selective vagal de-afferentation on weight gain and fat content in diet-induced obese rats. Male Sprague-Dawley rats (n = 5-8) underwent truncal vagotomy, selective vagal de-afferentation with capsaicin, or sham procedure. Animals were maintained for 11 months on a high-caloric Western diet. Abdominal visceral fat content was assessed by magnetic resonance imaging together with weight of fat pads at harvest. Glucose homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene expression was assessed by qPCR and immunoblotting and function by glucose uptake in everted jejunal sleeves. At 11-months, vagotomized rats weighed 19% less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams. Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P = 0.039) in visceral abdominal fat, respectively. There were no changes in blood glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged across all cohorts at 11-months postoperatively. Truncal vagotomy led to significant reductions in both diet-induced weight gain and visceral abdominal fat deposition. Vagal de-afferentation led to a more modest, but clinically and statistically significant, reduction in visceral abdominal fat. As increased visceral abdominal fat is associated with excess morbidity and mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery. C1 [Stearns, A. T.; Balakrishnan, A.; Ashley, S. W.; Tavakkolizadeh, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Stearns, A. T.] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [Balakrishnan, A.] Univ Liverpool, Sch Clin Sci, Div Gastroenterol, Liverpool L69 3GE, Merseyside, England. [Radmanesh, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Rhoads, D. B.] Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Tavakkolizadeh, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM atavakkoli@partners.org OI Stearns, Adam/0000-0003-4327-7360 FU Harvard Clinical Nutrition Center [P30-DK040561]; Berkeley Fellowship; George Herbert Hunt Travelling Fellowship; Nutricia Foundation FX Funding sources include: Harvard Clinical Nutrition Center Grant P30-DK040561 (AT); Berkeley Fellowship and George Herbert Hunt Travelling Fellowship (ATS); and Nutricia Foundation Fellowship (AB). We would like to thank Dr Sharon Peled, and Dr Clare Tempany-Afdhal for technical advice and support with magnetic resonance image acquisition, and Jan Rounds for invaluable managerial support. NR 42 TC 23 Z9 23 U1 0 U2 4 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 2012 VL 57 IS 5 BP 1281 EP 1290 DI 10.1007/s10620-011-1968-4 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 933TH UT WOS:000303385100022 PM 22138962 ER PT J AU Carmody, TP Delucchi, K Duncan, CL Banys, P Simon, JA Solkowitz, SN Huggins, J Lee, SK Hall, SM AF Carmody, Timothy P. Delucchi, Kevin Duncan, Carol L. Banys, Peter Simon, Joel A. Solkowitz, Sharon N. Huggins, Joy Lee, Sharon K. Hall, Sharon M. TI Intensive intervention for alcohol-dependent smokers in early recovery: A randomized trial SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Smoking cessation; Tobacco use; Alcohol dependence; Concurrent intervention; Early recovery ID ADDICTION SEVERITY INDEX; POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE-ABUSE TREATMENT; MENTAL-HEALTH-CARE; FAGERSTROM TOLERANCE QUESTIONNAIRE; SMOKING-CESSATION INTERVENTIONS; INTEGRATING TOBACCO CESSATION; NATIONAL EPIDEMIOLOGIC SURVEY; NICOTINE DEPENDENCE; CIGARETTE-SMOKING AB Introduction: The purpose of this study was to investigate the efficacy of an intensive tobacco cessation intervention for alcohol-dependent smokers in early recovery. Methods: A total of 162 alcohol-dependent smokers were randomized to either intensive intervention for smoking cessation or usual care. The intensive intervention consisted of 16 sessions of individual cognitive behavior therapy (CBT) and combination nicotine replacement therapy that lasted 26 weeks. Usual care involved referral to a free-standing smoking cessation program that provided smoking cessation counseling of varying duration and guideline-concordant medications. The primary cessation outcome was verified 7-day point prevalence abstinence (PPA) at 12, 26, 38, and 52 weeks. Results: At 12 and 26 weeks, the verified 7-day point-prevalence quit rate was significantly higher for the intensive intervention group than for the usual care group (both p = 0.03). However, the quit rates for the two treatment groups were not significantly different at 38 or 52 weeks. Verified 30-day alcohol abstinence rates were not significantly different for the two treatment groups at any of the follow-up assessments. Conclusions: The intensive smoking cessation intervention yielded a higher short-term smoking quit rate without jeopardizing sobriety. A chronic care model might facilitate maintenance of smoking cessation during the first year of alcohol treatment and perhaps for longer periods of time. It is hoped that studies such as this will inform the development of more effective interventions for concurrent alcohol and tobacco use disorders. Published by Elsevier Ireland Ltd. C1 [Carmody, Timothy P.; Duncan, Carol L.; Banys, Peter; Solkowitz, Sharon N.; Huggins, Joy; Lee, Sharon K.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Carmody, Timothy P.; Delucchi, Kevin; Duncan, Carol L.; Banys, Peter; Simon, Joel A.; Solkowitz, Sharon N.; Huggins, Joy; Lee, Sharon K.; Hall, Sharon M.] Univ Calif San Francisco, Treatment Res Ctr, San Francisco, CA 94143 USA. [Simon, Joel A.] San Francisco VA Med Ctr, Gen Internal Med Sect, Med Serv, San Francisco, CA 94121 USA. [Simon, Joel A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Simon, Joel A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Carmody, TP (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM Timothy.Carmody@va.gov FU NIDA [P50 DA09253] FX This work is a component of the UCSF Treatment Research Center and was supported by NIDA grant P50 DA09253. NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 66 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2012 VL 122 IS 3 BP 186 EP 194 DI 10.1016/j.drugalcdep.2011.09.026 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 934GQ UT WOS:000303432200003 PM 22014532 ER PT J AU Oliva, EM Harris, AHS Trafton, JA Gordon, AJ AF Oliva, Elizabeth M. Harris, Alex H. S. Trafton, Jodie A. Gordon, Adam J. TI Receipt of opioid agonist treatment in the Veterans Health Administration: Facility and patient factors SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid-related disorders; Buprenorphine; Methadone; United States Department of Veterans Affairs ID OFFICE-BASED TREATMENT; PRIMARY-CARE; OPIATE ADDICTION; BUPRENORPHINE; METHADONE; DEPENDENCE; RETENTION; BARRIERS; NALOXONE; RISK AB Background: Opioid agonist treatment (OAT)-through licensed clinic settings (C-OAT) using methadone or buprenorphine or office-based settings with buprenorphine (O-OAT)-is an evidence-based treatment for opioid dependence. Because of limited availability of on-site C-OAT (n = 28 of 128 facilities) in the Veterans Health Administration (VHA), O-OAT use has been encouraged. This study examined OAT utilization across VHA facilities and the patient and facility factors related to variability in utilization. Method: We examined 12 months of VHA administrative data (fiscal year [FY] 2008, October 2007 through September 2008) for evidence of OAT utilization and substance use disorder program data from an annual VHA survey. Variability in OAT utilization across facilities and patient and facility factors related to OAT utilization were examined using mixed-effects, logistic regression models. Results: Among 128 VHA facilities, 35,240 patients were diagnosed with an opioid use disorder. Of those, 27.3% received OAT: 22.2% received C-OAT and 5.1% received O-OAT with buprenorphine. Substantial facility-level variability in proportions of patients treated with OAT was found, ranging from 0% to 66% with 44% of facilities treating <5%. Significant patient-level predictors of OAT receipt included being male, age >= 56, and without another mental health diagnosis. Significant facility-level predictors included offering any OAT services (C-OAT or O-OAT) and specialty substance abuse treatment services on weekends. Conclusion: In FY2008, prior to the VHA national mandate of access to buprenorphine OAT, substantial variation in the use of OAT existed, partially explained by patient- and facility-level factors. Implementation efforts should focus on increasing access to this evidence-based treatment, especially in facilities at the low end of the distribution. (C) 2011 Published by Elsevier Ireland Ltd. C1 [Gordon, Adam J.] Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr,Ctr Res Hlth Care, Pittsburgh, PA 15206 USA. [Oliva, Elizabeth M.; Harris, Alex H. S.; Trafton, Jodie A.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. RP Gordon, AJ (reprint author), Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr,Ctr Res Hlth Care, 7180 Highland Dr,Mailcode 151-C-H, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov RI Nilsson, Marcus/H-2186-2012 NR 22 TC 9 Z9 9 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2012 VL 122 IS 3 BP 241 EP 246 DI 10.1016/j.drugalcdep.2011.10.004 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 934GQ UT WOS:000303432200011 PM 22115887 ER PT J AU Azadani, AN Chitsaz, S Matthews, PB Jaussaud, N Leung, J Wisneski, A Ge, L Tseng, EE AF Azadani, Ali N. Chitsaz, Sam Matthews, Peter B. Jaussaud, Nicolas Leung, James Wisneski, Andrew Ge, Liang Tseng, Elaine E. TI Biomechanical comparison of human pulmonary and aortic roots SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Biomechanics; Aortic root; Pulmonary root; Ross operation; Stress; Strain ID PORCINE PULMONARY; ASCENDING AORTA; VALVE; ANEURYSM AB Significant dilation of the pulmonary autograft is problematic after the Ross operation and may require reoperation. Pulmonary autograft remodelling occurs in response to the immediate rise in pressure and consequently wall stress. Stress-strain response of the pulmonary root plays an important role in understanding autograft function and remodelling following the Ross procedure. However, limited data are available on mechanical properties of fresh human pulmonary roots. The aim of this study was to compare mechanical properties of fresh human pulmonary and aortic roots prior to the Ross operation. Fresh healthy human hearts (n = 21) were obtained from California Transplant Donor Network (Oakland, CA, USA). Five regions of pulmonary and aortic roots, anterior and posterior artery and three sinuses, were subjected to displacement-controlled equibiaxial stretch testing within 24 h of cross-clamp time. Different regions of pulmonary and aortic roots were compared using a paired-comparison approach based on tissue stiffness at systemic pressure. Furthermore, histologic analysis was performed to compare the fibrous structure of pulmonary and aortic roots. Human pulmonary and aortic roots demonstrated nonlinear response to biaxial loading in both circumferential and longitudinal directions. Pulmonary artery was found to be significantly stiffer than ascending aorta at systemic pressure in the two principal directions (P < 0.001). Similarly, pulmonary sinuses were significantly stiffer than the aortic sinuses at systemic pressure in the two directions (P < 0.001). Histological analysis revealed that aortic roots had tight denser weave of elastin than pulmonary roots. Significant differences were found in the compliance and fibrous structure of human pulmonary and aortic roots. These regional differences may impact pulmonary autograft remodelling and influence late autograft dilation. C1 [Tseng, Elaine E.] Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Div Cardiothorac Surg, Dept Surg, 500 Parnassus Ave,Suite 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 FU American Heart Association FX This research was funded by the American Heart Association administered by the Northern California Institute for Research and Education using resources from the San Francisco VA Medical Center. NR 12 TC 19 Z9 19 U1 5 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD MAY PY 2012 VL 41 IS 5 BP 1111 EP 1116 DI 10.1093/ejcts/ezr163 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 930TA UT WOS:000303161800040 PM 22219450 ER PT J AU Richardson, PG Eng, C Kolesar, J Hideshima, T Anderson, KC AF Richardson, Paul G. Eng, Cathy Kolesar, Jill Hideshima, Teru Anderson, Kenneth C. TI Perifosine, an oral, anti-cancer agent and inhibitor of the Akt pathway: mechanistic actions, pharmacodynamics, pharmacokinetics, and clinical activity SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE Akt; biomarker; colorectal cancer; D-21266; KRX-0401; multiple myeloma; perifosine; targeted agent ID NF-KAPPA-B; MULTIPLE-MYELOMA CELLS; COLORECTAL-CANCER; MOLECULAR-MECHANISMS; PHASE-I; TRIAL; MACROGLOBULINEMIA; CYTOTOXICITY; ACTIVATION; APOPTOSIS AB Introduction: Perifosine is a novel targeted oral Akt inhibitor currently in Phase III clinical development for treatment of colorectal cancer (CRC, in combination with capecitabine) and multiple myeloma (MM, in combination with bortezomib and dexamethasone). Areas covered: The mechanism, preclinical testing, and clinical activity of perifosine in CRC and MM are discussed, with supportive pharmacokinetic information presented. Appropriate literature searches were carried out for background and discussion purposes. Expert opinion: In preclinical models, perifosine has been shown to target phosphatidylinositol 3-kinase-Akt signaling. In CRC cell lines, preclinical studies indicate that perifosine may enhance the cytotoxic effects of fluorouracil, likely primarily through the nuclear transcription factorkappa B pathway. A placebo-controlled Phase II randomized trial of capecitabine +/- perifosine in previously treated patients with metastatic CRC showed the combination to be superior. In MM, Phase I/II clinical trials have established the optimal dosing schedule for perifosine and bortezomib in combination, and demonstrated that perifosine can sensitize to, or overcome resistance to, bortezomib, associated with prolonged responses and a favorable side effect profile. Ultimately, the favorable tolerability of perifosine will allow for its testing in combination with multiple targeted therapies to improve PFS and OS, which represent an important unmet need in these populations. C1 [Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hideshima, Teru] Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. [Kolesar, Jill] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53792 USA. [Eng, Cathy] Univ Texas MD Anderson Canc Ctr, Colorectal Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Heme Malignancy, Dept Adult Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M557, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU Keryx Biopharmaceuticals FX This article was supported by Keryx Biopharmaceuticals. PG Richardson is on the advisory board for Millennium, Celgene, Keryx Biopharmaceuticals and Johnson & Johnson. KC Anderson is on the advisory board for Millennium, Merck & Co. Celgene, Bristol-Myers Squibb and Onyx Pharmaceuticals is also the founder of Acetylon Pharmaceuticals and Oncopep. T Hideshima is a consultant for Acetylon Pharmaceuticals. All other authors have nothing to disclose. NR 45 TC 28 Z9 28 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD MAY PY 2012 VL 8 IS 5 BP 623 EP 633 DI 10.1517/17425255.2012.681376 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 931QM UT WOS:000303234400009 PM 22512706 ER PT J AU Brugge, WR Wallace, MB AF Brugge, William R. Wallace, Michael B. TI FISHing: New Methods to Improve the Diagnostic Sensitivity of Fine Needle Aspiration Cytology SO GASTROENTEROLOGY LA English DT Editorial Material ID SOLID PANCREATIC MASSES; IN-SITU HYBRIDIZATION; ENDOSCOPIC ULTRASONOGRAPHY; EUS-FNA; K-RAS; CANCER; 22-GAUGE C1 [Brugge, William R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wallace, Michael B.] Mayo Clin, Jacksonville, FL 32224 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. EM WBrugge@partners.org NR 15 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2012 VL 142 IS 5 BP 1055 EP 1057 DI 10.1053/j.gastro.2012.03.009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 930CK UT WOS:000303113600015 PM 22446080 ER PT J AU Schaefer, EAK Chung, RT AF Schaefer, Esperance A. K. Chung, Raymond T. TI Anti-Hepatitis C Virus Drugs in Development SO GASTROENTEROLOGY LA English DT Review DE Protease Inhibitors; NS5B Inhibitors; NS5A Inhibitors; Host Targeted Anti-Virals ID GENOTYPE 1 INFECTION; REPLICATION COMPLEX INHIBITOR; NS3/4A PROTEASE INHIBITOR; CHRONIC HCV INFECTION; IN-VITRO RESISTANCE; ANTIVIRAL ACTIVITY; INTERFERON-LAMBDA; RNA REPLICATION; NONNUCLEOSIDE INHIBITORS; COMBINATION THERAPY AB Development of robust cell culture models for hepatitis C viral infection has greatly increased our understanding of this virus and its life cycle. This knowledge has led to the development of many drugs that target specific elements of viral replication, including viral proteins and host factors required for replication. The NS3/4A serine protease inhibitors were the first of these to be used in the clinic, and reagents that target other elements of the viral lifecycle are in advanced stages of clinical development. These include new NS3/4A protease inhibitors, NS5B RNA-dependent RNA polymerase inhibitors, NS5A inhibitors, and host-directed antivirals, such as cyclophilin inhibitors. Alternative interferons with possibly improved tolerability, specifically interferon-lambda 1 (interleukin-29), are also under development. These new reagents against hepatitis C virus should lead to highly effective, well-tolerated, and likely interferon-sparing therapies in the next several years. C1 [Schaefer, Esperance A. K.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Schaefer, EAK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 116 TC 54 Z9 55 U1 1 U2 19 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 2012 VL 142 IS 6 BP 1340 EP + DI 10.1053/j.gastro.2012.02.015 PG 54 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 930RH UT WOS:000303156300011 PM 22537441 ER PT J AU Leung, FW AF Leung, Felix W. TI Magnetic endoscope imaging colonoscope: a new modality for hypothesis testing in unsedated colonoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; PATIENT PAIN; PERFORMANCE; IMPROVEMENT C1 [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Gastroenterol, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Gastroenterol, North Hills, CA USA. NR 10 TC 5 Z9 5 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 2012 VL 75 IS 5 BP 1037 EP 1039 DI 10.1016/j.gie.2012.02.058 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 932GC UT WOS:000303277400015 PM 22520878 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Teaching the endoscopic and paraendoscopic skills of gastroenterology SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2012 VL 75 IS 5 BP 1069 EP 1071 DI 10.1016/j.gie.2012.02.014 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 932GC UT WOS:000303277400020 PM 22520879 ER PT J AU Rodriguez, N Rauh-Hain, JA Shoni, M Berkowitz, RS Muto, MG Feltmate, C Schorge, JO del Carmen, MG Matulonis, UA Horowitz, NS AF Rodriguez, Noah Rauh-Hain, J. Alejandro Shoni, Melina Berkowitz, Ross S. Muto, Michael G. Feltmate, Colleen Schorge, John O. del Carmen, Marcela G. Matulonis, Ursula A. Horowitz, Neil S. TI Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CA 125; Neoadjuvant chemotherapy; Advanced ovarian cancer; Interval debulking; Optimal cytoreduction ID PHASE-III TRIAL; HALF-LIFE; INDUCTION CHEMOTHERAPY; COMPUTED-TOMOGRAPHY; PRIMARY SURGERY; ONCOLOGY-GROUP; CARCINOMA; SURVIVAL; PACLITAXEL; REDUCTION AB Objective. To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC). Methods. Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy,. and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test. Results. One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 <= 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04). Conclusions. Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of <= 100 U/mL were highly likely to be cytoreduced to no residual disease. (C) 2012 Published by Elsevier Inc. C1 [Rodriguez, Noah; Rauh-Hain, J. Alejandro; Shoni, Melina; Berkowitz, Ross S.; Muto, Michael G.; Feltmate, Colleen; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol,Med Sch, Boston, MA 02115 USA. [Rauh-Hain, J. Alejandro] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol,Med Sch, Boston, MA 02115 USA. [Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Horowitz, NS (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol,Med Sch, Francis St, Boston, MA 02115 USA. EM nhorowitz@partners.org NR 27 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2012 VL 125 IS 2 BP 362 EP 366 DI 10.1016/j.ygyno.2012.02.006 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NV UT WOS:000303227500017 PM 22333992 ER PT J AU Dizon, DS Blessing, JA Penson, RT Drake, RD Walker, JL Johnston, CM DiSilvestro, PA Fader, AN AF Dizon, Don S. Blessing, John A. Penson, Richard T. Drake, Richard D. Walker, Joan L. Johnston, Carolyn M. DiSilvestro, Paul A. Fader, Amanda Nickles TI A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: A gynecologic oncology group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Platinum-resistant; Chemotherapy; Ovarian cancer; HIDAC inhibitors; Carboplatin ID HISTONE DEACETYLASE INHIBITOR; SOLID TUMORS; CANCER; TRIAL; GEMCITABINE; PACLITAXEL; THERAPY; PXD101; WOMEN AB Background. Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer. Methods. Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design. Results. Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage. Conclusions. The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer. (C) 2012 Elsevier Inc. All rights reserved. C1 [Dizon, Don S.; DiSilvestro, Paul A.] Brown Univ, Program Womens Oncol, Women & Infants Hosp, Alpert Med Sch, Providence, RI 02905 USA. [Blessing, John A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Buffalo, NY 14263 USA. [Blessing, John A.] Roswell Pk Canc Inst, Stat & Data Ctr, Buffalo, NY 14263 USA. [Penson, Richard T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Drake, Richard D.] Fairview Hosp, Cleveland Clin, Ctr Canc, Cleveland, OH 44111 USA. [Walker, Joan L.] Univ Oklahoma, Oklahoma City, OK 73190 USA. [Johnston, Carolyn M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Fader, Amanda Nickles] Greater Baltimore Med Ctr, Baltimore, MD 21204 USA. RP Dizon, DS (reprint author), Brown Univ, Program Womens Oncol, Women & Infants Hosp, Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA. EM donstevendizon@gmail.com FU National Cancer Institute [CA 27469, CA 37517]; Curagen; Topotarget FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical and Data Center (CA 37517). The following Gynecologic Oncology Group member institutions participated in this study: Roswell Park Cancer Institute, Abington Memorial Hospital, Walter Reed Army Medical Center, University of Mississippi Medical Center, University of Pennsylvania Cancer Center, University of North Carolina School of Medicine, Rush-Presbyterian-St. Luke's Medical Center, The Cleveland Clinic Foundation, Cooper Hospital/University Medical Center, MD Anderson Cancer Center, University of Massachusetts Medical School, University of Oklahoma, 110, Women and Infants Hospital, The Hospital of Central Connecticut and Community Clinical Oncology Program.; Dr. Richard T. Penson received research funding for PXD-Cancer & Leukemia Group B/belinostat studies sponsored by Curagen and Topotarget. All other co-authors have no conflicts of interest to declare. NR 20 TC 20 Z9 20 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2012 VL 125 IS 2 BP 367 EP 371 DI 10.1016/j.ygyno.2012.02.019 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NV UT WOS:000303227500018 PM 22366594 ER PT J AU Rauh-Hain, JA Winograd, D Growdon, WB Schorge, JO Goodman, AK Boruta, DM Berkowitz, RS Horowitz, NS del Carmen, MG AF Rauh-Hain, J. Alejandro Winograd, Dina Growdon, Whitfield B. Schorge, John O. Goodman, A. K. Boruta, David M. Berkowitz, Ross S. Horowitz, Neil S. del Carmen, Marcela G. TI Prognostic determinants in patients with uterine and ovarian clear carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine cancer; Ovarian cancer; Clear cell carcinoma ID ONCOLOGY-GROUP EXPERIENCE; DISTINCT-HISTOLOGIC-TYPE; CELL-CARCINOMA; CLINICAL CHARACTERISTICS; ENDOMETRIAL CANCER; ADJUVANT THERAPY; POOR-PROGNOSIS; ADENOCARCINOMA; MANAGEMENT; RESISTANCE AB Objective. The purpose of this study is to analyze and compare the demographics, treatment, recurrence, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). Methods. A retrospective review of the Cancer Registry database was performed. All patients with UCCC and OCCC who underwent surgical staging at the two participating institutions, between January, 1995 and December, 2007, were identified. Categorical variables were evaluated by Chi square test. Survival estimates were plotted utilizing the Kaplan-Meier method. Results. Analysis of 41 women with UCCC and 121 with OCCC was performed. In patients with OCCC, 48.4% had localized disease, 18.9% had regional spread, 31.1% had distant metastasis, and in 1.6% spread is unknown: compared to UCCC, 41.5% had localized disease, 12.2% regional spread, and 46.3% distant metastasis (p = 0.2). The median progression free survival was 31.4 months in women with UCCC, compared to 145 months in patients with OCCC (p = 0.04). UCCC women had a median overall survival of 39.5 months, compared to 155.8 months in patients with OCCC (p = 0.002). In the multivariate Cox regression model, age > 55 years old, tumor extension, optimal cytoreduction, and platinum-based chemotherapy were identified as independent predictors of overall survival. UCCC vs. OCCC was not associated with decreased overall survival in multivariate analysis. Conclusion. OCCC and UCCC have the same rate of localized disease, regional spread and distant metastasis. After controlling for age, tumor extension, optimal cytoreduction, and platinum based chemotherapy, UCCC was not associated with decreased overall survival compared to OCCC. (C) 2012 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Winograd, Dina; Growdon, Whitfield B.; Schorge, John O.; Goodman, A. K.; Boruta, David M.; Berkowitz, Ross S.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. [Rauh-Hain, J. Alejandro; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Div Gynecol Oncol, Sch Med, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02115 USA. EM mdelcarmen@partners.org NR 32 TC 9 Z9 9 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 2012 VL 125 IS 2 BP 376 EP 380 DI 10.1016/j.ygyno.2012.02.016 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NV UT WOS:000303227500020 PM 22366593 ER PT J AU Rubatt, JM Darcy, KM Tian, CQ Muggia, F Dhir, R Armstrong, DK Bookman, MA Niedernhofer, LJ Deloia, J Birrer, M Krivak, TC AF Rubatt, Jennifer M. Darcy, Kathleen M. Tian, Chunqiao Muggia, Franco Dhir, Rajiv Armstrong, Deborah K. Bookman, Michael A. Niedernhofer, Laura J. Deloia, Julie Birrer, Michael Krivak, Thomas Carl TI Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: A gynecologic oncology group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Biomarker; DNA repair; Platinum-resistance; Prognosis ID NUCLEOTIDE EXCISION-REPAIR; PRIMARY CYTOREDUCTIVE SURGERY; PHASE-III TRIAL; PROTEIN EXPRESSION; DNA-REPAIR; PLATINUM-RESISTANCE; ENDONUCLEASE ERCC1-XPF; GENETIC POLYMORPHISMS; CHEMOTHERAPY; CISPLATIN AB Objective. Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy. Methods. Formalin-fixed, paraffin-embedded tumors were collected from two COG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated. Results. Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p = 0.59), median OS (52.0 months versus 47.0 months, respectively, p = 0.30), risk of disease progression (adjusted hazard ratio [HR] = 0.90, 95% confidence interval (CI): 0.71-1.15, p = 0.41), and risk of death (adjusted HR = 0.81, 95% CI: 0.61-1.07, p = 0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene. Conclusions. ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy. Published by Elsevier Inc. C1 [Rubatt, Jennifer M.; Krivak, Thomas Carl] Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA 15213 USA. [Darcy, Kathleen M.; Tian, Chunqiao] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Muggia, Franco] NYU, Dept Med Oncol, New York, NY 10016 USA. [Dhir, Rajiv] Univ Pittsburgh, Med Ctr Shadyside, Dept Pathol, Pittsburgh, PA 15213 USA. [Armstrong, Deborah K.] John Hopkins Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Bookman, Michael A.] Arizona Canc Ctr, Dept Hematol Oncol, Tucson, AZ 85719 USA. [Niedernhofer, Laura J.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. [Niedernhofer, Laura J.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA. [Deloia, Julie] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. [Birrer, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Krivak, TC (reprint author), Magee Womens Hosp, Div Gynecol Oncol, 300 Halket St,Suite 2130, Pittsburgh, PA 15213 USA. EM tkrivak@mail.magee.edu OI Muggia, Franco/0000-0003-0703-9146 FU National Cancer Institute [CA 27469, CA 37517]; NIEHS [ES016114]; [P30CA047904] FX This study was supported by the National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517). This project used the University of Pittsburgh Cancer Institute Tissue and Research Pathology Services and was supported in part by award P30CA047904. L.J.N. and J.M.R. were supported by NIEHS (ES016114). The following Gynecologic Oncology Group member institutions participated in this study: Roswell Park Cancer Institute, University of Alabama at Birmingham, Duke University Medical Center, Abington Memorial Hospital, Walter Reed Army Medical Center, University of Minnesota Medical School, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington, University of Pennsylvania Cancer Center, Milton S. Hers-hey Medical Center, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center at Dallas, Indiana University School of Medicine, Wake Forest University School of Medicine, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, Magee Women's Hospital, SUNY Downstate Medical Center, University of Kentucky, The Cleveland Clinic Foundation, State University of New York at Stony Brook, Southwestern Oncology Group, Washington University School of Medicine, Cooper Hospital/University Medical Center, Columbus Cancer Council, MD Anderson Cancer Center, University of Massachusetts Medical School, Fox Chase Cancer Center, Women's Cancer Center, University of Oklahoma, University of Virginia Health Sciences Center, University of Chicago, Tacoma General Hospital, Thomas Jefferson University Hospital, Mayo Clinic, Case Western Reserve University, Tampa Bay Cancer Consortium, North Shore University Hospital, Gynecologic Oncology Network, Ellis Fischel Cancer Center, Fletcher Allen Health Care, Australia New Zealand COG, Southern Nevada CCOP, Yale University, University of Wisconsin Hospital, Cancer Trials Support Unit, University of Texas Galveston, Southeast Gynecologic Oncology, Community Clinical Oncology Program, MRC-United Kingdom, and Mario Negri. NR 36 TC 13 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2012 VL 125 IS 2 BP 421 EP 426 DI 10.1016/j.ygyno.2012.01.008 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NV UT WOS:000303227500028 PM 22261301 ER PT J AU Konstantinopoulos, PA Berlin, ST Campos, SM Matulonis, UA Cannistra, SA AF Konstantinopoulos, Panagiotis A. Berlin, Suzanne T. Campos, Susana M. Matulonis, Ursula A. Cannistra, Stephen A. TI Bevacizumab rechallenge after first line maintenance bevacizumab SO GYNECOLOGIC ONCOLOGY LA English DT Letter ID OVARIAN-CANCER C1 [Konstantinopoulos, Panagiotis A.; Cannistra, Stephen A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Gynecol Med Oncol, Cambridge, MA 02138 USA. [Berlin, Suzanne T.; Campos, Susana M.; Matulonis, Ursula A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. RP Konstantinopoulos, PA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Gynecol Med Oncol, Cambridge, MA 02138 USA. EM pkonstan@bidmc.harvard.edu NR 5 TC 1 Z9 1 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 2012 VL 125 IS 2 BP 510 EP 511 DI 10.1016/j.ygyno.2012.02.013 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NV UT WOS:000303227500042 PM 22366591 ER PT J AU Lomonaco, R Ortiz-Lopez, C Orsak, B Webb, A Hardies, J Darland, C Finch, J Gastaldelli, A Harrison, S Tio, F Cusi, K AF Lomonaco, Romina Ortiz-Lopez, Carolina Orsak, Beverly Webb, Amy Hardies, Jean Darland, Celia Finch, Joan Gastaldelli, Amalia Harrison, Stephen Tio, Fermin Cusi, Kenneth TI Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease SO HEPATOLOGY LA English DT Article ID STELLATE CELL ACTIVATION; DEPENDENT DIABETES-MELLITUS; ACID-METABOLISM; PPAR-GAMMA; STEATOHEPATITIS; ADIPONECTIN; GLUCOSE; LIPOTOXICITY; MECHANISMS; SECRETION AB The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 +/- 1, body mass index = 34.1 +/- 0.3 kg/m2) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IRi = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IRi quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[3H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). Conclusion: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. (HEPATOLOGY 2012) C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, Audie L Murphy Vet Adm Med Ctr, San Antonio, TX 78229 USA. [Webb, Amy] Univ Texas Hlth Sci Ctr San Antonio, Div Hepatol, San Antonio, TX 78229 USA. [Hardies, Jean] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Tio, Fermin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Harrison, Stephen] Brooke Army Med Ctr, San Antonio, TX USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, Audie L Murphy Vet Adm Med Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu RI Gastaldelli, Amalia/H-3319-2014; webb, andrew/G-9642-2016 OI Gastaldelli, Amalia/0000-0003-2594-1651; FU Burroughs Wellcome Fund; American Diabetes Association [1-08-CR-08]; Veterans Affairs Merit Award [1 I01 CX000167-01]; Veterans Affairs Medical Research Fund; National Center for Research Resources [UL 1RR025767] FX This work was supported by the Burroughs Wellcome Fund (to K.C.), the American Diabetes Association (1-08-CR-08; to K.C.), and a Veterans Affairs Merit Award (1 I01 CX000167-01; to K.C.), the Veterans Affairs Medical Research Fund, and the National Center for Research Resources (award no.: UL 1RR025767). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources of the National Institutes of Health. NR 47 TC 99 Z9 102 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2012 VL 55 IS 5 BP 1389 EP 1397 DI 10.1002/hep.25539 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929GN UT WOS:000303049400009 PM 22183689 ER PT J AU Singal, AK Bashar, H Anand, BS Jampana, SC Singal, V Kuo, YF AF Singal, Ashwani K. Bashar, Hmoud Anand, Bhupinderjit S. Jampana, Sarat C. Singal, Vineet Kuo, Yong-Fang TI Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis: Exploratory analysis from the UNOS database SO HEPATOLOGY LA English DT Article ID DISEASE; SURVIVAL; GRAFT AB Data on liver transplantation for patients with alcoholic hepatitis are limited. Using the United Network for Organ Sharing database (2004-2010), adults undergoing liver transplantation for a listing diagnosis of alcoholic hepatitis were matched for age, gender, ethnicity, and model for endstage disease (MELD) score, donor risk index, and year of transplantation with three patients transplanted for a listing diagnosis of alcoholic cirrhosis. Study outcomes of graft and patient survival on follow-up were also analyzed for cohorts based on the diagnosis of the explant (46 alcoholic hepatitis and 138 alcoholic cirrhosis) and diagnosis at both listing as well as of the explant (11 alcoholic hepatitis and 33 alcoholic cirrhosis). Five-year graft and patient survival of alcoholic hepatitis and alcoholic cirrhosis patients were 75% and 73% (P = 0.97) and 80% and 78% (P = 0.90), respectively. Five-year graft and patient survival rates were also similar for cohorts based on diagnosis of the explant and diagnosis at listing as well as explant. Cox proportional regression analysis adjusting for other variables showed no impact of the etiology of liver disease (alcoholic hepatitis versus alcoholic cirrhosis) on the graft and patient survival. The causes of graft loss and patient mortality were similar in the two groups, and were not alcohol-related in any patient. Conclusion: Compared with alcoholic cirrhosis, patients with alcoholic hepatitis have similar posttransplantation graft and patient survival. Based on these preliminary findings, liver transplantation may be considered in a select group of patients with alcoholic hepatitis who fail to improve with medical therapy. Prospective studies are needed to assess the long-term outcome after liver transplantation in patients with alcoholic hepatitis. (HEPATOLOGY 2012) C1 [Singal, Ashwani K.; Bashar, Hmoud; Jampana, Sarat C.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Singal, Ashwani K.] Univ Texas Med Branch, Dept Gastroenterol, Galveston, TX USA. [Anand, Bhupinderjit S.] Baylor Coll Med, Michael DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singal, Vineet] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. [Kuo, Yong-Fang] Univ Texas Med Branch, Dept Biostat, Galveston, TX USA. RP Singal, AK (reprint author), Mayo Clin, Dept Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM ashwanisingal.com@gmail.com NR 25 TC 43 Z9 44 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2012 VL 55 IS 5 BP 1398 EP 1405 DI 10.1002/hep.25544 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929GN UT WOS:000303049400010 PM 22213344 ER PT J AU Hariri, LP Mino-Kenudson, M Shea, B Digumarthy, S Onozato, M Yagi, Y Fraire, AE Matsubara, O Mark, EJ AF Hariri, Lida P. Mino-Kenudson, Mari Shea, Barry Digumarthy, Subba Onozato, Maristela Yagi, Yukako Fraire, Armando E. Matsubara, Osamu Mark, Eugene J. TI Distinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis SO HUMAN PATHOLOGY LA English DT Article DE Hypersensitivity pneumonitis; Extrinsic allergic alveolitis; Acute; Interstitial lung disease; Acute fibrinous and organizing pneumonia; Fibrin ID ORGANIZING PNEUMONIA; PULMONARY-FIBROSIS; INTERSTITIAL PNEUMONIA; FARMERS LUNG; SURVIVAL AB Hypersensitivity pneumonitis is an inflammatory lung disease that develops in response to exposure to antigen. Cases can be stratified by the duration of exposure and speed of symptom progression into acute, subacute, and chronic hypersensitivity pneumonitis. Although the pathologic features of subacute hypersensitivity pneumonitis are well established and those of chronic hypersensitivity pneumonitis have been reported, little is known about the histopathology of acute hypersensitivity pneumonitis. We evaluated the pathologic features of 5 patients with clinically confirmed hypersensitivity pneumonitis and rapid onset of symptoms and 3 patients with subacute or chronic hypersensitivity pneumonitis with symptom exacerbation. Histopathologic features assessed in each case included those characteristic of subacute hypersensitivity pneumonitis (bronchiolocentric chronic inflammation, histiocytic aggregates, and bronchiolitis obliterans), those associated with acute inflammation (fibrin deposition and neutrophilic infiltrate), and fibrosis. The classic features of hypersensitivity pneumonitis were identified in all 8 cases, with I also exhibiting fixed fibrosis confirming underlying chronic hypersensitivity pneumonitis. Fibrin deposition was present in 8 (100%) of 8 cases, and its extent was significant (28% surface area fibrin deposition/total disease area on average). Two had intra-alveolar fibrin so marked that it resembled acute fibrinous and organizing pneumonia. In addition, prominent interstitial neutrophilic infiltrate (>= 5 cells/high-power field) was seen in all cases. These features have not been reported as characteristics of subacute or chronic hypersensitivity pneumonitis. Increased fibrin deposition and neutrophilic infiltrate may characterize acute hypersensitivity pneumonitis or abrupt exacerbation of hypersensitivity pneumonitis, and these along with characteristic features of subacute hypersensitivity pneumonitis (granulomatous inflammation and bronchiolocentricity) are sufficient to establish a morphologic diagnosis, particularly in conjunction with clinicoradiologic features. (C) 2012 Elsevier Inc. All rights reserved. C1 [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Pulm Pathol Serv, Boston, MA 02114 USA. [Shea, Barry] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fraire, Armando E.] Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01605 USA. [Matsubara, Osamu] Natl Def Med Coll, Dept Pathol, Tokorozawa, Saitama 359, Japan. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Pulm Pathol Serv, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 23 TC 20 Z9 22 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2012 VL 43 IS 5 BP 660 EP 668 DI 10.1016/j.humpath.2011.06.001 PG 9 WC Pathology SC Pathology GA 932JY UT WOS:000303288600006 PM 21855112 ER PT J AU Levy, M Trivedi, A Zhang, J Miles, L Mattis, AN Kim, GE Lassman, C Anders, RA Misdraji, J Yerian, LM Xu, HD Dhall, D Wang, HLL AF Levy, Mary Trivedi, Anand Zhang, Jun Miles, Lili Mattis, Aras N. Kim, Grace E. Lassman, Charles Anders, Robert A. Misdraji, Joseph Yerian, Lisa M. Xu, Haodong Dhall, Deepti Wang, Hanlin L. TI Expression of glypican-3 in undifferentiated embryonal sarcoma and mesenchymal hamartoma of the liver SO HUMAN PATHOLOGY LA English DT Article DE Glypican-3; Liver; Undifferentiated embryonal sarcoma; Mesenchymal hamartoma; Immunohistochemistry ID HEPATOCELLULAR-CARCINOMA; IMMUNOHISTOCHEMICAL ANALYSIS; CLINICAL-FEATURES; DIAGNOSTIC MARKER; TUMOR; HEPATOBLASTOMA; LESIONS; ADULT AB Glypican-3 (GPC3) is an oncofetal protein that has been demonstrated to be a useful diagnostic immunomarker for hepatocellular carcinoma and hepatoblastoma. Its expression in mesenchymal tumors of the liver, particularly undifferentiated embryonal sarcoma (UES) and mesenchymal hamartoma (MH), has not been investigated. In this study, a total of 24 UESs and 18 MHs were immunohistochemically stained for GPC3 expression. The results showed cytoplasmic staining for GPC3 in 14 (58%) UESs, of which 6 exhibited diffuse immunoreactivity and the remaining 8 showed focal positivity. The patients with GPC3-positive UES tended to be younger (mean 18 years; median 11 years) than those with GPC3-negative tumors (mean 39.4 years; median 27 years), although the difference did not reach statistical significance (P = .06). Eight MHs also exhibited GPC3 immunoreactivity (44%; 4 diffuse and 4 focal). Positive staining in all 8 cases was primarily seen in entrapped nonlesional hepatocytes with a canalicular and cytoplasmic staining pattern. In only 4 cases (22%) was GPC3 immunoreactivity also observed in the mesenchymal component. The patients with positive staining also tended to be younger (mean 2.6 years; median 1.1 years) compared with those with negative staining (mean 16.3 years; median 4.5 years), but the difference was not statistically significant (P = .15). Our data demonstrate that GPC3 is expressed in a subset of UES and MH of the liver. Caution should thus be exercised when evaluating a GPC3-expressing hepatic neoplasm, particularly on a needle biopsy when the differential diagnosis includes poorly differentiated hepatocellular carcinoma or hepatoblastoma. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lassman, Charles; Wang, Hanlin L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Levy, Mary; Trivedi, Anand; Dhall, Deepti; Wang, Hanlin L.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Zhang, Jun] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Miles, Lili] Cincinnati Childrens Hosp Med Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45229 USA. [Mattis, Aras N.; Kim, Grace E.] Univ Calif San Francisco, Med Ctr, Dept Pathol, San Francisco, CA 94143 USA. [Anders, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Misdraji, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Yerian, Lisa M.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44195 USA. [Xu, Haodong] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. RP Wang, HLL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM hanlinwang@mednet.ucla.edu RI Mattis, Aras/C-5558-2014 FU [R01DK080736]; [R01DK081417] FX This work is partly supported by grants R01DK080736 and R01DK081417 (to R.A.A.). NR 28 TC 8 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2012 VL 43 IS 5 BP 695 EP 701 DI 10.1016/j.humpath.2011.06.016 PG 7 WC Pathology SC Pathology GA 932JY UT WOS:000303288600010 PM 21937079 ER PT J AU Attaman, JA Toth, TL Furtado, J Campos, H Hauser, R Chavarro, JE AF Attaman, Jill A. Toth, Thomas L. Furtado, Jeremy Campos, Hannia Hauser, Russ Chavarro, Jorge E. TI Dietary fat and semen quality among men attending a fertility clinic SO HUMAN REPRODUCTION LA English DT Article DE male infertility; semen quality; diet; fat; gas chromatography ID ASTHENOZOOSPERMIC MALES; SEMINAL PLASMA; ACID SUPPLEMENTATION; SPERM CONCENTRATION; LIPID-COMPOSITION; BOAR SPERM; INFERTILITY; SPERMATOZOA; MOTILITY; HUMANS AB The objective of this study was to examine the relation between dietary fats and semen quality parameters. Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n 23). Linear regression was used to determine associations while adjusting for potential confounders. Men were primarily Caucasian (89) with a mean (SD) age of 36.4 (5.3) years; 71 were overweight or obese; and 67 were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43 (95 confidence interval (CI): 6214) lower total sperm count and 38 (95 CI: 5810) lower sperm concentration than men in the lowest third (P-trend 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r 0.53), but saturated fat intake was unrelated to sperm levels (r 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9 (0.43.5) higher normal morphology than men in the lowest third (P-trend 0.02). In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings. C1 [Attaman, Jill A.; Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Attaman, Jill A.; Toth, Thomas L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Furtado, Jeremy; Campos, Hannia; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Attaman, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02115 USA. EM Jill.A.Attaman@hitchcock.org FU National Institute of Environmental Health Sciences [ES009718, ES000002]; National Institute of Diabetes and Digestive Kidney Diseases [DK46200] FX This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences, and DK46200 from National Institute of Diabetes and Digestive Kidney Diseases. NR 52 TC 54 Z9 56 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2012 VL 27 IS 5 BP 1466 EP 1474 DI 10.1093/humrep/des065 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 930TB UT WOS:000303161900029 PM 22416013 ER PT J AU Park, SY Sargent, D Spofford, I Vosburgh, KG A-Rahim, Y AF Park, Sun Young Sargent, Dustin Spofford, Inbar Vosburgh, Kirby G. A-Rahim, Yousif TI A Colon Video Analysis Framework for Polyp Detection SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Colon cancer; conditional random fields (CRFs); eigenimages; polyp detection; quasi-Newton method ID COLORECTAL-CANCER; MISS RATES; ENDOSCOPY; CLASSIFICATION; ADENOMAS; PATTERNS; FEATURES; IMAGES; SYSTEM AB This paper presents an automated video analysis framework for the detection of colonic polyps in optical colonoscopy. Our proposed framework departs from previous methods in that we include spatial frame-based analysis and temporal video analysis using time-course image sequences. We also provide a video quality assessment scheme including two measures of frame quality. We extract colon-specific anatomical features from different image regions using a windowing approach for intraframe spatial analysis. Anatomical features are described using an eigentissue model. We apply a conditional random field to model interframe dependences in tissue types and handle variations in imaging conditions and modalities. We validate our method by comparing our polyp detection results to colonoscopy reports from physicians. Our method displays promising preliminary results and shows strong invariance when applied to both white light and narrow-band video. Our proposed video analysis system can provide objective diagnostic support to physicians by locating polyps during colon cancer screening exams. Furthermore, our system can be used as a cost-effective video annotation solution for the large backlog of existing colonoscopy videos. C1 [Sargent, Dustin] Zigi Solut, San Diego, CA 92037 USA. [Park, Sun Young] Sci & Technol Int Med Syst, San Diego, CA 92037 USA. [Spofford, Inbar] Harvard Univ, Sch Med, Div Pediat Gastroenterol & Nutr, Massachusetts Gen Hosp,Dept Pediat, Boston, MA 02114 USA. [Vosburgh, Kirby G.] Harvard Univ, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. [A-Rahim, Yousif] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA. [A-Rahim, Yousif] Pali Momi Med Ctr, Aiea, HI 96701 USA. RP Park, SY (reprint author), Zigi Solut, San Diego, CA 92037 USA. EM hi2sunyoung@gmail.com; dustysargent@gmail.com; ispofford@partners.org; kvosburgh@partners.org; yousif@hawaii.edu FU U.S. Army Medical Research and Material Command [W81XWH-07-C-0086, W81XWH-07-C-0177] FX This work was supported by the U.S. Army Medical Research and Material Command under Contracts W81XWH-07-C-0086 and W81XWH-07-C-0177. NR 27 TC 21 Z9 21 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAY PY 2012 VL 59 IS 5 BP 1408 EP 1418 DI 10.1109/TBME.2012.2188397 PG 11 WC Engineering, Biomedical SC Engineering GA 931FJ UT WOS:000303201000023 PM 22361654 ER PT J AU Ashworth, LA Billett, A Mitchell, P Nuti, F Siegel, C Bousvaros, A AF Ashworth, Lori A. Billett, Amy Mitchell, Paul Nuti, Federica Siegel, Corey Bousvaros, Athos TI Lymphoma risk in children and young adults with inflammatory bowel disease: Analysis of a large single-center cohort SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; ulcerative colitis; lymphoma; pediatrics; thiopurines; immunomodulators; biologics; anti-TNF antibodies ID T-CELL LYMPHOMA; IMMUNOSUPPRESSIVE THERAPY; CROHNS-DISEASE; AZATHIOPRINE; 6-MERCAPTOPURINE AB Background: Prior studies suggest an increased risk of lymphoma in adults with inflammatory bowel disease (IBD). Cases of lymphoma have also been reported in children with IBD. However, the precise risk of lymphoma in relation to drug exposure has not been ascertained in children. Methods: We conducted a single-center, retrospective study of 1560 children and young adults with IBD evaluated at Children's Hospital Boston between 1979 and 2008. Of this group, 186 patients were excluded due to incorrect diagnosis, one-time second-opinion visits, or missing hospital records. The remaining 1374 patients had charts reviewed to determine whether lymphoma developed while they were receiving their clinical care at our institution and the duration of exposure to various IBD medications. The rate of lymphoma was calculated in patient-years of exposure for each class of medications utilized in IBD. Results: Of 1374 patients (741 male; age at diagnosis 12.1 +/- 4.0 years; 791 Crohn's disease [CD], 535 ulcerative colitis [UC], 48 IBD unclassified), we identified two patients who developed lymphoma (one Hodgkin, one anaplastic large cell), in 6624 patient-years of follow-up (mean duration follow-up 4.8 years per patient). Both patients were males (ages 12 and 18 years at time of lymphoma onset) and were receiving thiopurines but had not yet received biologics at the time of their cancer diagnosis. They were both treated with chemotherapy and are alive without cancer 32+ and 76+ months since diagnosis. The absolute incidence rate of lymphoma for patients having received thiopurines was 4.5 per 10,000 patient-years compared to the expected rate of 0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.51 (95% confidence interval [CI] 0.7441.98). Conclusions: The overall risk of lymphoma in children with IBD is low, with only two cases seen in our hospital over a 30-year period. The lymphoma risk (as estimated by SIR) in children receiving thiopurines is comparable to that reported in studies of adults. While there may be an increased risk of lymphoma in children treated with thiopurines, the risk did not reach statistical significance in this large cohort. (Inflamm Bowel Dis 2011;) C1 [Ashworth, Lori A.; Bousvaros, Athos] Childrens Hosp Boston, Ctr Inflammatory Bowel Dis, Boston, MA 02115 USA. [Billett, Amy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mitchell, Paul] Childrens Hosp Boston, Clin Res Program, Boston, MA 02115 USA. [Nuti, Federica] Univ Roma La Sapienza, Div Pediat Gastroenterol, Rome, Italy. [Siegel, Corey] Dartmouth Hitchcock Med Ctr, Div Gastroenterol, Hanover, NH USA. RP Bousvaros, A (reprint author), Childrens Hosp Boston, Ctr Inflammatory Bowel Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM athos.bousvaros@childrens.harvard.edu FU Macinnes family; Rasmussen family; Wolfman family FX We would like to thank the Macinnes, Rasmussen, & Wolfman families for their support of this work. NR 24 TC 18 Z9 18 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2012 VL 18 IS 5 BP 838 EP 843 DI 10.1002/ibd.21844 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929ZO UT WOS:000303104700007 PM 21887728 ER PT J AU Wei, SC Rosenberg, IM Cao, ZF Huett, AS Xavier, RJ Podolsky, DK AF Wei, Shu-Chen Rosenberg, Ian M. Cao, Zhifang Huett, Alan S. Xavier, Ramnik J. Podolsky, Daniel K. TI Tribbles 2 (Trib2) is a novel regulator of toll-like receptor 5 signaling SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Tribbles 2; Toll-like receptor; IBD; nuclear factor kappa B; MAPK; NF-?B2 ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; CELL-FUNCTION; NEGATIVE REGULATOR; INTESTINAL-MUCOSA; IMMUNE-RESPONSES; ACTIVATION; PATHWAYS; NF-KAPPA-B2; EXPRESSION AB Background: Toll-like receptors (TLRs) are expressed by a variety of cells, including intestinal epithelia. However, the full spectrum of regulators modulating innate responses via TLRs has not been delineated. Tribbles (Trib) have been identified as a highly conserved family of kinase-like proteins. We sought to clarify the role of Trib2 in the TLR signaling pathway. Methods: Trib2 mRNA and protein levels were analyzed by quantitative polymerase chain reaction (PCR) and western blot, respectively. Immunohistochemical staining was used to determine the expression of Trib2 in human tissue. Involvement of Trib2 in nuclear factor kappa B (NF-?B) pathways was assessed in epithelial cells by NF-?B reporter assay. Proteins that interacted with Trib2 were identified by mass spectrometry and confirmed by immunoprecipitation. The domain essential for Trib2 function was mapped using truncated constructs. Results: Trib2 expression is decreased in active inflamed tissue from patients with inflammatory bowel disease (IBD). Trib2 is expressed in human and mouse colonic epithelium as well as immune cells, and its expression in epithelium is inducible in a ligand-dependent manner by TLR5 ligand stimulation. Trib2 inhibits TLR5-mediated activation of NF-?B downstream of TRAF6. Trib2 selectively modulates mitogen-activated protein kinase (MAPK) pathways p38 and Jun N-terminal kinase (JNK) but not p44/p42 (ERK1/2). NF-?B2 (p100) was identified as a Trib2 binding partner in regulating the TLR5 signaling pathway that leads to inhibition of NF-?B activity. Residues 158177 in the Trib2 kinase-like domain are required for Trib2 function. Conclusions: These observations indicate that Trib2 is a novel regulator in the TLR5 signaling pathway and altered expression of Trib2 may play a role in IBD. (Inflamm Bowel Dis 2012;) C1 [Wei, Shu-Chen; Rosenberg, Ian M.; Cao, Zhifang; Huett, Alan S.; Xavier, Ramnik J.; Podolsky, Daniel K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Wei, Shu-Chen; Rosenberg, Ian M.; Cao, Zhifang; Huett, Alan S.; Xavier, Ramnik J.; Podolsky, Daniel K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Wei, Shu-Chen] Natl Taiwan Univ Hosp & Coll Med, Dept Internal Med, Taipei, Taiwan. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Podolsky, Daniel K.] UT SW Med Ctr, Dallas, TX USA. RP Xavier, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu FU NIH [DK060049, DK043351]; Ministry of Education of Taiwan; National Science Council of Taiwan [NSC-095-SAF-I-564-604-TMS, NSC-98-2314-B-002-094-MY2]; National Taiwan University Hospital [NTUH-97-N1038, NTUH-98-N1197]; Liver Disease Prevention & Treatment Research Foundation FX Supported by NIH funds DK060049 and DK043351 (to R.J.X.), the Ministry of Education of Taiwan (Taiwan Study Abroad Scholarship), the National Science Council of Taiwan (NSC-095-SAF-I-564-604-TMS, NSC-98-2314-B-002-094-MY2), the National Taiwan University Hospital (NTUH-97-N1038, NTUH-98-N1197), and by the Liver Disease Prevention & Treatment Research Foundation. NR 36 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2012 VL 18 IS 5 BP 877 EP 888 DI 10.1002/ibd.22883 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929ZO UT WOS:000303104700013 PM 22271508 ER PT J AU Docktor, MJ Paster, BJ Abramowicz, S Ingram, J Wang, YYE Correll, M Jiang, HY Cotton, SL Kokaras, AS Bousvaros, A AF Docktor, Michael J. Paster, Bruce J. Abramowicz, Shelly Ingram, Jay Wang, Yaoyu E. Correll, Mick Jiang, Hongyu Cotton, Sean L. Kokaras, Alexis S. Bousvaros, Athos TI Alterations in diversity of the oral microbiome in pediatric inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; microbiome; oral microbial biomarkers ID MUCOSA-ASSOCIATED MICROBIOTA; CROHNS-DISEASE; INVOLVEMENT; PERIODONTITIS; IMBALANCES; RESPONSES; PROFILES; CHILDREN; HEALTH; CAVITY AB Background: Oral pathology is a commonly reported extraintestinal manifestation of Crohn's disease (CD). The hostmicrobe interaction has been implicated in the pathogenesis of inflammatory bowel disease (IBD) in genetically susceptible hosts, yet limited information exists about oral microbes in IBD. We hypothesize that the microbiology of the oral cavity may differ in patients with IBD. Our laboratory has developed a 16S rRNA-based technique known as the Human Oral Microbe Identification Microarray (HOMIM) to study the oral microbiome of children and young adults with IBD. Methods: Tongue and buccal mucosal brushings from healthy controls, CD, and ulcerative colitis (UC) patients were analyzed using HOMIM. Shannon Diversity Index (SDI) and Principal Component Analysis (PCA) were employed to compare population and phylum-level changes among our study groups. Results: In all, 114 unique subjects from the Children's Hospital Boston were enrolled. Tongue samples from patients with CD showed a significant decrease in overall microbial diversity as compared with the same location in healthy controls (P = 0.015) with significant changes seen in Fusobacteria (P < 0.0002) and Firmicutes (P = 0.022). Tongue samples from patients with UC did not show a significant change in overall microbial diversity as compared with healthy controls (P = 0.418). Conclusions: As detected by HOMIM, we found a significant decrease in overall diversity in the oral microbiome of pediatric CD. Considering the proposed microbehost interaction in IBD, the ease of visualization and direct oral mucosal sampling of the oral cavity, further study of the oral microbiome in IBD is of potential diagnostic and prognostic value. (Inflamm Bowel Dis 2011;) C1 [Docktor, Michael J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Ctr Inflammatory Bowel Dis, Boston, MA 02115 USA. [Paster, Bruce J.; Cotton, Sean L.; Kokaras, Alexis S.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Abramowicz, Shelly] Harvard Univ, Sch Dent Med, Childrens Hosp Boston, Dept Oral & Maxillofacial Surg,Dept Plast & Oral, Boston, MA 02115 USA. [Wang, Yaoyu E.; Correll, Mick] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Jiang, Hongyu] Harvard Univ, Sch Med, Childrens Hosp Boston, Clin Res Program, Boston, MA 02115 USA. RP Docktor, MJ (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Ctr Inflammatory Bowel Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM Michael.docktor@childrens.harvard.edu FU Crohn's & Colitis Foundation of America [5T32DK007477-27, 1832]; Harvard Institute of Translational Immunology (HITI)/Leona M. and Harry B. Helmsley Charitable Trust; Rasmussen family; MacInnes family; Wolfman family FX Supported in part by a T32 training grant (#5T32DK007477-27) in addition to a Senior Research Award (#1832) from the Crohn's & Colitis Foundation of America and from a grant from the Harvard Institute of Translational Immunology (HITI)/Leona M. and Harry B. Helmsley Charitable Trust Pilot Grants Program.; We thank the Rasmussen, Wolfman and MacInnes families for their generous support of the Children's Hospital Interdisciplinary Microbiome Project. NR 43 TC 33 Z9 34 U1 4 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2012 VL 18 IS 5 BP 935 EP 942 DI 10.1002/ibd.21874 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929ZO UT WOS:000303104700018 PM 21987382 ER PT J AU Greenberg, JA Wylie, B Robinson, JN AF Greenberg, James A. Wylie, Blair Robinson, Julian N. TI A pilot study to assess the adequacy of the Brigham 20 Kit for cesarean delivery SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Brigham 20 Kit; Cesarean delivery; Surgical instruments AB Objective: To determine whether a kit of only 20 instruments could be used to perform cesarean deliveries in a consistently safe manner for the purpose of providing better surgical instruments to healthcare providers in limited-resource environments. Methods: In a small pilot study, 10 obstetricians in 2 hospitals in Boston, USA, used and evaluated the adequacy of the Brigham 20 Kit for cesarean delivery among 10 women. Results: On average, the obstetricians rated the Brigham 20 Kit 8.7 out of 10 for adequacy and made some minor suggestions regarding the kit's instrumentation configuration. Conclusion: The limited-instrument Brigham 20 Kit seemed adequate to perform cesarean deliveries safely. Larger clinical trials are needed to assess the value of this new concept for cesarean delivery in limited-resource environments. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Greenberg, James A.; Robinson, Julian N.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Wylie, Blair] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greenberg, JA (reprint author), 1153 Ctr St,Suite 36, Boston, MA 02130 USA. EM jagreenberg@partners.org NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD MAY PY 2012 VL 117 IS 2 BP 157 EP 159 DI 10.1016/j.ijgo.2011.12.007 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 933NG UT WOS:000303368200012 PM 22342056 ER PT J AU Chen, WP Wu, SM AF Chen, Wen-Pin Wu, Sean M. TI Small molecule regulators of postnatal Nkx2.5 cardiomyoblast proliferation and differentiation SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Review DE Nkx2; 5; cardiomyoblast; TGF-ss ID TGF-BETA; MESENCHYMAL TRANSITION; PROGENITOR CELLS; EXPRESSION; MEMBRANE; NUCLEUS; HEART AB While recent data have supported the capacity for a neonatal heart to undergo cardiomyogenesis, it is unclear whether these new cardiomyocytes arise from an immature cardiomyoblast population or from the division of mature cardiomyocytes. By following the expression of enhanced Green Fluorescent Protein (eGFP) in an Nkx2.5 enhancer-eGFP transgenic mice, we have identified a population of immature cells that can undergo cardiomyogenic as well as smooth muscle cell differentiation in the neonatal heart. Here, we examined growth factors and small molecule regulators that potentially regulate the proliferation and cardiomyogenic versus smooth muscle cell differentiation of neonatal Nkx2.5-GFP + cells in vitro. We found that A83-01 (A83), an inhibitor of TGF-beta RI, was able to induce an expansion of neonatal Nkx2.5-eGFP + cells. In addition, the ability of A83 to expand eGFP + cells in culture was dependent on signalling from the mitogen-activated protein kinase kinase (MEK) as treatment with a MEK inhibitor, PD0325901, abolished this effect. On the other hand, activation of neonatal Nkx2.5-eGFP + cells with TGF-beta 1, but not activin A nor BMP2, led to smooth muscle cell differentiation, an effect that can be reversed by treatment with A83. In summary, small molecule inhibition of TGF-beta signalling may be a promising strategy to induce the expansion of a rare population of postnatal cardiomyoblasts. C1 [Wu, Sean M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Chen, Wen-Pin] Natl Taiwan Univ, Coll Med, Inst Pharmacol, Taipei, Taiwan. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Wu, SM (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Div Cardiol, Room 3224 Simches Bldg,185 Cambridge St, Boston, MA 02114 USA. EM smwu@partners.org OI Chen, Wen-Pin/0000-0002-0143-5642 FU NIH/NHLBI [K08 HL081086, U01 HL100408-01]; NIH [DP2 0D004411] FX We thank Dr. Marcus Vallaster and Ms. Rebecca Feistritzerfor for experimental assistance. This work was supported by NIH/NHLBI (K08 HL081086 and U01 HL100408-01) and NIH Director's New Innovator's Award DP2 0D004411 (to S.M.W.). NR 19 TC 8 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD MAY PY 2012 VL 16 IS 5 BP 961 EP 965 DI 10.1111/j.1582-4934.2011.01513.x PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 931SL UT WOS:000303239500002 PM 22212626 ER PT J AU Young, CNJ Brutkowski, W Lien, CF Arkle, S Lochmuller, H Zablocki, K Gorecki, DC AF Young, Christopher N. J. Brutkowski, Wojciech Lien, Chun-Fu Arkle, Stephen Lochmueller, Hanns Zablocki, Krzysztof Gorecki, Dariusz C. TI P2X7 purinoceptor alterations in dystrophic mdx mouse muscles: relationship to pathology and potential target for treatment SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE P2X7; Duchenne muscular dystrophy; mdx; Ca2+influx; ERK signalling; purinoceptor ID SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; P2X(7) RECEPTOR; PURINERGIC RECEPTOR; NUCLEOTIDE RECEPTOR; EXTRACELLULAR ATP; CALCIUM INFLUX; T-CELLS; DIFFERENTIATION; EXPRESSION AB Duchenne muscular dystrophy (DMD) is a lethal inherited muscle disorder. Pathological characteristics of DMD skeletal muscles include, among others, abnormal Ca2+ homeostasis and cell signalling. Here, in the mdx mouse model of DMD, we demonstrate significant P2X7 receptor abnormalities in isolated primary muscle cells and cell lines and in dystrophic muscles in vivo. P2X7 mRNA expression in dystrophic muscles was significantly up-regulated but without alterations of specific splice variant patterns. P2X7 protein was also up-regulated and this was associated with altered function of P2X7 receptors producing increased responsiveness of cytoplasmic Ca2+ and extracellular signal-regulated kinase (ERK) phosphorylation to purinergic stimulation and altered sensitivity to NAD. Ca2+ influx and ERK signalling were stimulated by ATP and BzATP, inhibited by specific P2X7 antagonists and insensitive to ivermectin, confirming P2X7 receptor involvement. Despite the presence of pannexin-1, prolonged P2X7 activation did not trigger cell permeabilization to propidium iodide or Lucifer yellow. In dystrophic mice, in vivo treatment with the P2X7 antagonist Coomassie Brilliant Blue reduced the number of degenerationregeneration cycles in mdx skeletal muscles. Altered P2X7 expression and function is thus an important feature in dystrophic mdx muscle and treatments aiming to inhibit P2X7 receptor might slow the progression of this disease. C1 [Young, Christopher N. J.; Brutkowski, Wojciech; Lien, Chun-Fu; Arkle, Stephen; Gorecki, Dariusz C.] Univ Portsmouth, Sch Pharm & Biomed Sci, Portsmouth, Hants, England. [Lochmueller, Hanns] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zablocki, Krzysztof] M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. RP Gorecki, DC (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM darek.gorecki@port.ac.uk OI Lochmuller, Hanns/0000-0003-2324-8001 FU Interreg IV (AdMiN); Institute of Biomedical and Biomolecular Sciences; Medical Research Council UK through the Centre for Neuromuscular Diseases [G0601943] FX DCG holds the Fulbright Distinguished Scholarship. This work was supported by the Interreg IV (AdMiN) grant to DCG, the Institute of Biomedical and Biomolecular Sciences PhD grant to C.Y. and the Medical Research Council UK through the Centre for Neuromuscular Diseases (G0601943) to H. L. We thank Drs F. Koch-Nolte for providing HEK(P2X7R) cells, D. Blake for 2166 antibody, GlaxoSmithKline, Harlow, UK, for the P2X7 knockout mice, G. Scarlett for advice on qPCR and J. Smith for help with the live cell imaging. NR 59 TC 15 Z9 15 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD MAY PY 2012 VL 16 IS 5 BP 1026 EP 1037 DI 10.1111/j.1582-4934.2011.01397.x PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 931SL UT WOS:000303239500009 PM 21794079 ER PT J AU Hawryluk, EB Linskey, KR Duncan, LM Nazarian, RM AF Hawryluk, Elena B. Linskey, Katy R. Duncan, Lyn M. Nazarian, Rosalynn M. TI Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE drug-induced; interface dermatitis; lupus-like reaction; neutrophilic eccrine hidradenitis; psoriasiform dermatitis ID NECROSIS-FACTOR-ALPHA; LUPUS-LIKE SYNDROME; NEUTROPHILIC ECCRINE HIDRADENITIS; INTERFACE DERMATITIS PATTERN; TOXIC EPIDERMAL NECROLYSIS; INDUCED SWEETS-SYNDROME; DRUG-INDUCED LUPUS; OF-THE-LITERATURE; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE AB Biologic therapies targeting tumor necrosis factor (TNF)-alpha have become a mainstay in the management of a number of autoimmune diseases. We report a series of adverse skin eruptions in six patients (four females, two males, age: 2158 years, mean: 39) receiving 4 months to 10 years (mean 3.1 years) of anti-TNF-alpha therapies (infliximab, n = 4; adalimumab, n = 1 or etanercept, n = 1). The following drug-associated diagnoses were made in eight skin biopsies performed at Massachusetts General Hospital between 3/2007 and 10/2010: pustular folliculitis, psoriasis, interface dermatitis, neutrophilic eccrine hidradenitis, Sweet's syndrome, lupus, vasculitis and palmoplantar pustulosis. The descriptions of neutrophilic eccrine hidradenitis-like and Sweet's-like hypersensitivity eruptions induced by anti-TNF-alpha therapies are the first such cases described in the literature. Each cutaneous eruption improved or resolved with switching to a different TNF-alpha inhibitor, discontinuation of the anti-TNF-alpha agent, and/or topical or systemic steroids. There was a clear chronologic relationship with, and clinical remission upon withdrawal or steroid suppression of the anti-TNF-alpha agents. The mechanism for such diverse cutaneous eruptions among this class of medications remains poorly understood. The cutaneous adverse reaction profile of TNF-alpha inhibitors is broad and should be considered in the histopathologic differential in this clinical setting. C1 [Linskey, Katy R.; Duncan, Lyn M.; Nazarian, Rosalynn M.] Harvard Univ, Dermatopathol Unit, Pathol Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Hawryluk, Elena B.] Harvard Univ, Dept Dermatol, Sch Med, Boston, MA 02114 USA. RP Nazarian, RM (reprint author), Harvard Univ, Dermatopathol Unit, Pathol Serv, Massachusetts Gen Hosp,Med Sch, 55 Fruit St,WRN 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 72 TC 23 Z9 25 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2012 VL 39 IS 5 BP 481 EP 492 DI 10.1111/j.1600-0560.2012.01894.x PG 12 WC Dermatology; Pathology SC Dermatology; Pathology GA 929FD UT WOS:000303045800004 PM 22515220 ER PT J AU Gardner, S Ruchelsman, D Mudgal, C AF Gardner, S. Ruchelsman, D. Mudgal, C. TI Concomitant high-energy fractures of the distal radius and hook of hamate SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Letter ID PATTERNS C1 [Gardner, S.; Ruchelsman, D.; Mudgal, C.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Gardner, S (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. EM cmudgal@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD MAY PY 2012 VL 37E IS 4 BP 366 EP 367 DI 10.1177/1753193411436293 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 930UN UT WOS:000303167400016 PM 22290881 ER PT J AU Ditomassi, M AF Ditomassi, Marianne TI A Multi-instrument Evaluation of the Professional Practice Environment SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID NURSES JOB-SATISFACTION; INTENSIVE-CARE UNITS; PSYCHOMETRIC EVALUATION; REGISTERED NURSES; WORK; OUTCOMES; SCALE; ORGANIZATION; SERVICES; QUALITY AB This study identified organizational characteristics that are highly correlated with the work satisfaction of RNs using 2 practice environment measurement tools. In the sample, the organizational characteristics of autonomy, control over practice, and internal work motivation are critical to RNs' sense of work satisfaction. As care redesign efforts ensue, the need to preserve and strengthen the professional practice environment remains a priority for nurse executives. C1 [Ditomassi, Marianne] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ditomassi, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mditomassi@partners.org NR 46 TC 7 Z9 8 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2012 VL 42 IS 5 BP 266 EP 272 DI 10.1097/NNA.0b013e3182480901 PG 7 WC Nursing SC Nursing GA 933FA UT WOS:000303344000006 PM 22525290 ER PT J AU Chavez, LJ Williams, EC Lapham, G Bradley, KA AF Chavez, Laura J. Williams, Emily C. Lapham, Gwen Bradley, Katharine A. TI Association Between Alcohol Screening Scores and Alcohol-Related Risks Among Female Veterans Affairs Patients SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID BEHAVIORAL-COUNSELING INTERVENTIONS; INTIMATE PARTNER VIOLENCE; IDENTIFICATION TEST AUDIT; PRIMARY-CARE; GENDER-DIFFERENCES; EMERGENCY-DEPARTMENT; PREVENTIVE-SERVICES; DRINKING BEHAVIOR; SUBSTANCE-ABUSE; SEXUAL ASSAULT AB Objective: Evidence-based brief interventions for primary care patients with at-risk drinking include personalized feedback on alcohol-related risks, yet little is known about associations between alcohol screening scores and outcomes among women. This study evaluated associations between scores on the three-item Alcohol Use Disorders Identification Test consumption (AUDIT-C) questionnaire and self-reported alcohol-related risks and consequences among veteran women. Method: Female outpatients from an urban Veterans Affairs facility were mailed annual surveys (1998-2000) (response rates: 65% Years 1 and 2, 55% Year 3). Measures were obtained from each respondent's first completed survey and included a gender-specific AUDIT-C (0-12 points), self-reported alcohol-related consequences, problem drinking or other drug use, and health risks. The prevalence of each outcome across AUDIT-C score groups (0, 1-2, 3, 4, 5-7, 8-12) was estimated using logistic regression, adjusting for age, race, and marital status. Results: Among 2,670 respondents, 23.7% screened positive for alcohol misuse (AUDIT-C >= 3). For three out of the five alcohol-related consequences (tolerance, blackouts, felt needed to cut down), adjusted prevalence increased at AUDIT-C scores of 3 or more. The remaining alcohol-related consequences (morning eye openers, family/friends worried) increased at scores of 4 or more, as did self-reported problem drinking or other drug use. Associations between health risks (two or more sexual partners, sexually transmitted diseases, injuries, domestic violence, hepatitis/cirrhosis) and AUDIT-C scores were less consistent, but prevalence generally increased at scores of 5 or more. Conclusions: Increasing scores on the AUDIT-C reflect increasing prevalence of self-reported alcohol-related risks and consequences among women. These results provide clinicians with gender-specific information on alcohol-related risks that could be incorporated into brief interventions. (J. Stud. Alcohol Drugs, 73, 391-400, 2012) C1 [Chavez, Laura J.; Williams, Emily C.; Lapham, Gwen; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Chavez, Laura J.; Williams, Emily C.; Lapham, Gwen; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. RP Chavez, LJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Laura.Chavez2@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [GEN-97-022]; Substance Use Disorders Quality Enhancement Research Initiative FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (GEN-97-022), and Substance Use Disorders Quality Enhancement Research Initiative. Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the University of Washington. NR 59 TC 11 Z9 11 U1 1 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2012 VL 73 IS 3 BP 391 EP 400 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 929UQ UT WOS:000303091600006 PM 22456244 ER PT J AU Stout, RL Kelly, JF Magill, M Pagano, ME AF Stout, Robert L. Kelly, John F. Magill, Molly Pagano, Maria E. TI Association Between Social Influences and Drinking Outcomes Across Three Years SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID NETWORK SUPPORT; FOLLOW-UP; ALCOHOL TREATMENT; SUBSTANCE-ABUSE AB Objective: Multiple studies have shown social network variables to mediate and predict drinking outcome, but, because of self-selection biases, these studies cannot reliably determine whether the influence is causal or correlational. The goal of this study was to evaluate evidence for a causal role for social network characteristics in determining long-term outcomes using state-of-the-art statistical methods. Method: Outpatient and aftercare clients enrolled in Project MATCH (N = 1,726) were assessed at intake and at 3, 6, 9, 12, and 15 months; the outpatient sample was also followed to 39 months. Generalized linear modeling with propensity stratification tested whether changes in social network ties (i.e., number of pro-abstainers and pro-drinkers) at Month 9 predicted percentage of days abstinent and drinks per drinking day at 15 and 39 months, covarying for Alcoholics Anonymous (AA) attendance at Month 9. Results: An increase in the number of pro-drinkers predicted worse drinking outcomes, measured by percentage of days abstinent and drinks per drinking day, at Months 15 and 39 (p < .0001). An increase in the number of pro-abstainers predicted more percentage of days abstinent for both time periods (p < .01). The social network variables uniquely predicted 5%-12% of the outcome variance; AA attendance predicted an additional 1%-6%. Conclusions: Network composition following treatment is an important and plausibly causal predictor of alcohol outcome across 3 years, adjusting for multiple confounders. The effects are consistent across patients exhibiting a broad range of alcohol-related impairment. Results support the further development of treatments that promote positive social changes and highlight the need for additional research on the determinants of social network changes. (J. Stud. Alcohol Drugs, 73, 489-497, 2012) C1 [Stout, Robert L.] Pacific Inst Res & Evaluat, Decis Sci Inst, Pawtucket, RI 02860 USA. [Kelly, John F.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, John F.] Harvard Univ, Sch Med, Boston, MA USA. [Magill, Molly] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Pagano, Maria E.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Div Child Psychiat, Cleveland, OH 44106 USA. RP Stout, RL (reprint author), Pacific Inst Res & Evaluat, Decis Sci Inst, 1005 Main St, Pawtucket, RI 02860 USA. EM stout@pire.org FU National Institute on Alcohol Abuse and Alcoholism [R21 AA016762] FX This research was supported by National Institute on Alcohol Abuse and Alcoholism Grant R21 AA016762, Mechanisms and Moderators of Behavior Change in Alcoholics Anonymous. Data from Project MATCH were gathered under cooperative agreements with the National Institute on Alcohol Abuse and Alcoholism. The authors would also like to acknowledge collegial contributions from Dr. J. Scott Tonigan of the University of New Mexico. NR 48 TC 22 Z9 22 U1 2 U2 11 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2012 VL 73 IS 3 BP 489 EP 497 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 929UQ UT WOS:000303091600016 PM 22456254 ER PT J AU Putterman, DB Valente, M AF Putterman, Daniel B. Valente, Michael TI Difference between the Default Telecoil (T-Coil) and Programmed Microphone Frequency Response in Behind-the-Ear (BTE) Hearing Aids SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Electromagnetic (EM) field; hearing aid; telecoil (t-coil) ID PERFORMANCE; TELEPHONE AB Background: A telecoil (t-coil) is essential for hearing aid users when listening on the telephone because using the hearing aid microphone when communicating on the telephone can cause feedback due to telephone handset proximity to the hearing aid microphone. Clinicians may overlook the role of the t-coil due to a primary concern of matching the microphone frequency response to a valid prescriptive target. Little has been published to support the idea that the t-coil frequency response should match the microphone frequency response to provide "seamless" and perhaps optimal performance on the telephone. If the clinical goal were to match both frequency responses, it would be useful to know the relative differences, if any, that currently exist between these two transducers. Purpose: The primary purpose of this study was to determine if statistically significant differences were present between the mean output (in dB SPL) of the programmed microphone program and the hearing aid manufacturer's default t-coil program as a function of discrete test frequencies. In addition, pilot data are presented on the feasibility of measuring the microphone and t-coil frequency response with real-ear measures using a digital speech-weighted noise. Research Design: A repeated-measures design was utilized for a 2-cc coupler measurement condition. Independent variables were the transducer (microphone, t-coil) and 11 discrete test frequencies (15 discrete frequencies in the real-ear pilot condition). Study Sample: The study sample was comprised of behind-the-ear (BTE) hearing aids from one manufacturer. Fifty-two hearing aids were measured in a coupler condition, 39 of which were measured in the real-ear pilot condition. Hearing aids were previously programmed and verified using real-ear measures to the NAL-NL1 (National Acoustic Laboratories Non-linear 1) prescriptive target by a licensed audiologist. Data Collection and Analysis: Hearing aid output was measured with a Fonix 7000 hearing aid analyzer (Frye Electronics, Inc.) in a HA-2 2-cc coupler condition using a pure-tone sweep at an input level of 60 dB SPL with the hearing aid in the microphone program and 31.6 mA/M in the t-coil program. A digital speech weighted noise input signal presented at additional input levels was used in the real-ear pilot condition. A mixed-model repeated-measures analysis of variance (ANOVA) and the Tukey Honestly Significant Difference (HSD) post hoc test were utilized to determine if significant differences were present in performance across treatment levels. Results: There was no significant difference between mean overall t-coil and microphone output averaged across 11 discrete frequencies (F(1,102) = 0, p < 0.98). A mixed-model repeated-measures ANOVA revealed a significant transducer by frequency interaction (F(10,102) = 13.0, p < 0.0001). Significant differences were present at 200 and 400 Hz where the mean t-coil output was less than the mean microphone output, and at 4000, 5000, and 6300 Hz where the mean t-coil output was greater than the mean microphone output. Conclusions: The mean t-coil output was significantly lower than the mean microphone output at 400 Hz, a frequency that lies within the typical telephone bandwidth of 300-3300 Hz. This difference may partially help to explain why some patients often complain the t-coil fails to provide sufficient loudness for telephone communication. C1 [Putterman, Daniel B.] Washington Univ, Sch Med, Program Audiol & Commun Sci, St Louis, MO USA. [Valente, Michael] Washington Univ, Sch Med, Div Adult Audiol, St Louis, MO USA. RP Putterman, DB (reprint author), Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. EM Daniel.Putterman@va.gov FU National Center for Research Resources (NCRR) [TL1 RR024995]; National Institutes of Health (NIH); NIH Roadmap for Medical Research FX This publication was made possible by Grant Number TL1 RR024995 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. NR 29 TC 0 Z9 0 U1 0 U2 3 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD MAY PY 2012 VL 23 IS 5 SI SI BP 366 EP 378 DI 10.3766/jaaa.23.5.7 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 931LA UT WOS:000303220200007 PM 22533979 ER PT J AU Favero, M AF Favero, Marcus TI Nurture Shock: New Thinking about Children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Favero, Marcus] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Favero, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mfavero@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2012 VL 51 IS 5 BP 538 EP 539 DI 10.1016/j.jaac.2012.03.012 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 932NH UT WOS:000303297300014 ER PT J AU Meris, A Amigoni, M Verma, A Thune, JJ Kober, L Velazquez, E McMurray, JJV Pfeffer, MA Califf, R Levine, RA Solomon, SD AF Meris, Alessandra Amigoni, Maria Verma, Anil Thune, Jens Jakob Kober, Lars Velazquez, Eric McMurray, John J. V. Pfeffer, Marc A. Califf, Robert Levine, Robert A. Solomon, Scott D. CA Valsartan Acute Myocardial TI Mechanisms and Predictors of Mitral Regurgitation after High-Risk Myocardial Infarction SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Mitral regurgitation; Myocardial infarction; Mitral geometry; Tenting area; Left ventricular remodeling ID LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; DOPPLER ASSESSMENT; INSIGHTS; DETERMINANTS; CAPTOPRIL; VALSARTAN; SHAPE AB Background: Mitral regurgitation (MR) has been associated with adverse outcomes after myocardial infarction (MI). Without structural valve disease, functional MR has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus. The aims of this study were to elucidate the mechanistic components of MR after high-risk MI and to identify predictors of MR progression during follow-up. Methods: The Valsartan in Acute Myocardial Infarction Echo substudy prospectively enrolled 610 patients with LV dysfunction, heart failure, or both after MI. MR at baseline, 1 month, and 20 months was quantified by mapping jet expansion in the left atrium in 341 patients with good-quality echocardiograms. Indices of LV remodeling, left atrial size, and diastolic function and parameters of mitral valve deformation, including tenting area, coaptation depth, anterior leaflet concavity, annular diameters, and contractility, were assessed and related to baseline MR. The progression of MR was further analyzed, and predictors of worsening among the baseline characteristics were identified. Results: Tenting area, coaptation depth, annular dilatation, and left atrial size were all associated with the degree of baseline MR. Tenting area was the only significant and independent predictor of worsening MR; a tenting area of 4 cm(2) was a useful cutoff to identify worsening of MR after MI and moderate to severe MR after 20 months. Conclusions: Increased mitral tenting and larger mitral annular area are determinants of MR degree at baseline, and tenting area is an independent predictor of progression of MR after MI. Although LV remodeling itself contributes to ischemic MR, this influence is directly dependent on alterations in mitral geometry. (J Am Soc Echocardiogr 2012;25:535-42.) C1 [Meris, Alessandra; Amigoni, Maria; Verma, Anil; Thune, Jens Jakob; Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Kober, Lars] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Velazquez, Eric; Califf, Robert] Duke Univ, Med Ctr, Durham, NC USA. [McMurray, John J. V.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. [Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013; OI mcmurray, john/0000-0002-6317-3975 FU Novartis Pharmaceuticals Corporation (East Hanover, NJ); Novartis Pharmaceuticals Corporation FX The VALIANT trial was funded by a grant from Novartis Pharmaceuticals Corporation (East Hanover, NJ). Drs. Kober, Velazquez, McMurray, Pfeffer, Califf, and Solomon have received research support from Novartis Pharmaceuticals Corporation. NR 33 TC 19 Z9 19 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2012 VL 25 IS 5 BP 535 EP 542 DI 10.1016/j.echo.2012.01.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930CE UT WOS:000303112900010 PM 22305962 ER PT J AU Weiner, RB Wang, F Hutter, AM Wood, MJ Berkstresser, B McClanahan, C Neary, J Marshall, JE Picard, MH Baggish, AL AF Weiner, Rory B. Wang, Francis Hutter, Adolph M., Jr. Wood, Malissa J. Berkstresser, Brant McClanahan, Carlene Neary, Jennifer Marshall, Jane E. Picard, Michael H. Baggish, Aaron L. TI The Feasibility, Diagnostic Yield, and Learning Curve of Portable Echocardiography for Out-of-Hospital Cardiovascular Disease Screening SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Athletes; Echocardiography; Screening ID HAND-HELD ECHOCARDIOGRAPHY; EUROPEAN-SOCIETY; AMERICAN-SOCIETY; RECOMMENDATIONS; CARDIOLOGY; ABNORMALITIES; HYPERTROPHY; IMPACT; HEART; ELECTROCARDIOGRAPHY AB Background: The reduction in the size of full-capability echocardiographic machines facilitates "out-of-hospital" transthoracic echocardiography (TTE). Data documenting the feasibility, yield, and logistical considerations of out-of-hospital TTE for preparticipation evaluation of athletes are sparse. Methods: A multiyear study was conducted to examine the role of 12-lead electrocardiography for athlete screening in which TTE was used to document or exclude underlying structural heart disease. Using a commercially available portable transthoracic echocardiographic system, the rate of technically adequate imaging, diagnostic yield, and the time required for the completion of TTE (including setup, performance, and interpretation) were examined. TTE was performed in university medical offices and at "out-of-office" athletic facilities. Measurements were recorded during each year of the study to determine the impact of targeted attempts to improve efficiency. Results: Four hundred sixty-seven of 510 participants had transthoracic echocardiographic images that were technically adequate for complete interpretation (imaging success rate, 92%). Echocardiographic evidence of physiologic, exercise-induced cardiac remodeling was observed in 110 of 510 (22%). Cardiac abnormalities with relevance to sports participation risk were detected in 11 of 508 participants (2.2%). Over 3 years, the average time for the completion of TTE (including setup, imaging, and interpretation) decreased (year 1, 17.4 +/- 3 min; year 2, 14.0 +/- 2.1 min; year 3, 11.0 +/- 1.8 min; P < .001). This was driven by a significant decrease in the time required for TTE at out-of-office athletic facilities. Conclusions: Community-based TTE in athletes is feasible and is associated with a high rate of technically adequate imaging. Importantly, there appears to be a significant learning curve associated with out-of-hospital TTE. (J Am Soc Echocardiogr 2012;25:568-75.) C1 [Weiner, Rory B.; Hutter, Adolph M., Jr.; Wood, Malissa J.; McClanahan, Carlene; Neary, Jennifer; Marshall, Jane E.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wang, Francis; Berkstresser, Brant] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 35 TC 7 Z9 7 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2012 VL 25 IS 5 BP 568 EP 575 DI 10.1016/j.echo.2012.01.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 930CE UT WOS:000303112900015 PM 22326132 ER PT J AU Fintelmann, F Pulli, B Abedi-Tari, F Trombley, M Shore, MT Shepard, JA Rosenthal, DI AF Fintelmann, Florian Pulli, Benjamin Abedi-Tari, Faezeh Trombley, Maureen Shore, Mary-Theresa Shepard, Jo-Anne Rosenthal, Daniel I. TI Repeat Rates in Digital Chest Radiography and Strategies for Improvement SO JOURNAL OF THORACIC IMAGING LA English DT Article DE chest; direct radiography; repeat rate; computed radiography; digital radiography ID REJECT ANALYSIS; QUALITY-ASSURANCE; FILM; HOSPITALS; PROGRAM AB Purpose: To determine the repeat rate (RR) of chest radiographs acquired with portable computed radiography (CR) and installed direct radiography (DR) and to develop and assess strategies designed to decrease the RR. Materials and Methods: The RR and reasons for repeated digital chest radiographs were documented over the course of 16 months while a task force of thoracic radiologists, technologist supervisors, technologists, and information technology specialists continued to examine the workflow for underlying causes. Interventions decreasing the RR were designed and implemented. Results: The initial RR of digital chest radiographs was 3.6% (138/3818) for portable CR and 13.3% (476/3575) for installed DR systems. By combining RR measurement with workflow analysis, targets for technical and teaching interventions were identified. The interventions decreased the RR to 1.8% (81/4476) for portable CR and to 8.2% (306/3748) for installed DR. Conclusions: We found the RR of direct digital chest radiography to be significantly higher than that of computed chest radiography. We believe this is due to the ease with which repeat images can be obtained and discarded, and it suggests the need for ongoing surveillance of RR. We were able to demonstrate that strategies to lower the RR, which had been developed in the era of film-based imaging, can be adapted to the digital environment. On the basis of our findings, we encourage radiologists to assess their own departmental RRs for direct digital chest radiography and to consider similar interventions if necessary to achieve acceptable RRs for this modality. C1 [Fintelmann, Florian; Pulli, Benjamin; Abedi-Tari, Faezeh; Trombley, Maureen; Shore, Mary-Theresa; Shepard, Jo-Anne; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Fintelmann, F (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND II 216,55 Fruit St, Boston, MA 02114 USA. EM ffintelmann@partners.org NR 16 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAY PY 2012 VL 27 IS 3 BP 148 EP 151 DI 10.1097/RTI.0b013e3182455f36 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929LV UT WOS:000303066500010 PM 22331101 ER PT J AU Kropil, P Rojas, CA Ghoshhajra, B Lanzman, RS Miese, FR Scherer, A Kalra, M Abbara, S AF Kroepil, Patric Rojas, Carlos A. Ghoshhajra, Brian Lanzman, Rotem S. Miese, Falk R. Scherer, Axel Kalra, Mannudeep Abbara, Suhny TI Prospectively ECG-triggered High-pitch Spiral Acquisition for Cardiac CT Angiography in Routine Clinical Practice Initial Results SO JOURNAL OF THORACIC IMAGING LA English DT Article DE cardiac computed tomography; flash; dose; pitch; image quality ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; DUAL-SOURCE CT; IMAGE QUALITY; CORONARY-ANGIOGRAPHY; QUANTITATIVE PARAMETERS; RADIATION-EXPOSURE; SHOOT MODE; ARTERIES; SOCIETY AB Purpose: This study was conducted to evaluate the mode of application, image quality (IQ), and radiation exposure resulting from introduction of a prospectively electrocardiogram-triggered high-pitch cardiac computed tomography angiography (CTA) acquisition mode into routine clinical practice. Materials and Methods: A total of 42 prospectively triggered cardiac CTAs were conducted on 34 patients (11 female, 23 male; mean age 56 +/- 15 y) using a high-pitch mode (pitch 3.4) on a dual-source CT. In 8 of these patients with higher heart rates or occasional premature ventricular contractions, 2 immediately subsequent CTAs were performed ("double flash protocol"). Subjective IQ was assessed for coronary arteries using a 4-point scale (1 = unevaluable to 4 = excellent). Contrast-to-noise ratio (CNR) was measured in 9 locations. CT Dose Index and dose-length product were obtained, and the patients' effective dose was calculated. Results: Mean effective doses were 2.6 +/- 1.4 mSv (range: 1.1 to 6.4) for the entire cardiac examination and 1.4 +/- 0.7 mSv (0.4 to 3.1) for individual high-pitch cardiac CTA. z-coverage ranged from 9.9 cm in a native coronary CTA to 31.4 cm in a bypass graft case. The overall subjective IQ was good to excellent (mean score: 3.5), with 1.5% unevaluable coronary segments. The "double flash protocol" resulted in a fully diagnostic CT study in all cases just after taking both scans into consideration. The mean CNR of all locations was 19.7 +/- 2.6. Conclusion: Prospectively electrocardiograph-triggered high-pitch-mode cardiac CTA is a feasible and promising technique in clinical routine, allowing for evaluation of coronaries at good-to-excellent IQ and providing high CNR and minimal radiation doses. The "double flash protocol" might become a more robust tool in patients with elevated heart rates or premature ventricular contractions. C1 [Kroepil, Patric; Lanzman, Rotem S.; Miese, Falk R.; Scherer, Axel] Univ Dusseldorf, Fac Med, Dept Diagnost & Intervent Radiol, D-40225 Dusseldorf, Germany. [Rojas, Carlos A.; Ghoshhajra, Brian; Kalra, Mannudeep; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Imaging Sect, Boston, MA USA. RP Miese, FR (reprint author), Univ Dusseldorf, Fac Med, Dept Diagnost & Intervent Radiol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM Falk.Miese@med.uni-duesseldorf.de FU NHLBI NIH HHS [T32 HL076136, T32 HL076136-07] NR 26 TC 12 Z9 13 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD MAY PY 2012 VL 27 IS 3 BP 194 EP 201 DI 10.1097/RTI.0b013e318228223f PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 929LV UT WOS:000303066500018 PM 21964497 ER PT J AU Pietanza, MC Gadgeel, SM Dowlati, A Lynch, TJ Salgia, R Rowland, KM Wertheim, MS Price, KA Riely, GJ Azzoli, CG Miller, VA Krug, LM Kris, MG Beumer, JH Tonda, M Mitchell, B Rizvi, NA AF Pietanza, M. Catherine Gadgeel, Shirish M. Dowlati, Afshin Lynch, Thomas J. Salgia, Ravi Rowland, Kendrith M., Jr. Wertheim, Michael S. Price, Katharine A. Riely, Gregory J. Azzoli, Christopher G. Miller, Vincent A. Krug, Lee M. Kris, Mark G. Beumer, Jan H. Tonda, Margaret Mitchell, Ben Rizvi, Naiyer A. TI Phase II Study of the Multitargeted Tyrosine Kinase Inhibitor XL647 in Patients with Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE EGFR-sensitizing mutation; EGFR-resistance mutation; Tyrosine kinase inhibitor; Acquired resistance; Molecular analysis ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR GENE-MUTATIONS; ACQUIRED-RESISTANCE; MOLECULAR CHARACTERISTICS; T790M MUTATIONS; EGFR MUTATIONS; SOLID TUMORS; DOUBLE-BLIND; GEFITINIB; ERLOTINIB AB Purpose: XL647 is an oral small-molecule inhibitor of multiple receptor tyrosine kinases, including endothelial growth factor receptor (EGFR), vascular endothelial growth factor receptor 2, HER2 and Ephrin type-B receptor 4 (EphB4). We undertook an open-label, multi-institutional Phase II study to investigate the efficacy and safety of XL647 in treatment-naive non-small-cell lung cancer patients clinically enriched for the presence of EGFR mutations. Methods: Eligibility included patients with advanced-stage treatment-naive lung adenocarcinoma with a known sensitizing mutation of EGFR or patients with at least one of the following criteria: being Asian, female, or having minimal or no smoking history. Two dosing schedules were evaluated; in the "intermittent 5 & 9 dosing" cohort, XL647 350 mg for 5 days every 14 days was given; and in the "daily dosing" cohort, XL647 300 mg daily for 28 days was administered. Tumor EGFR mutation status was determined on available tissue. The primary end point was confirmed objective response rate. Results: Forty-one patients were treated on the intermittent 5 & 9 dosing-and 14 on the daily-dosing schedule. The majority of patients were eligible on the basis of smoking history. The response rate and progression-free survival for the two schedules combined were 20% and 5.3 months (90% confidence interval, 3.7-6.7), respectively. Thirty-eight patients (69%) had material available for mutation testing and 14 EGFR-sensitizing mutations were detected. The response rate and progression-free survival for EGFR-mutation-positive patients were 57% (8/14) and 9.3 months (90% confidence interval, 5.5-11.7). The toxicities were comparable between the two schedules; the most common adverse effects being diarrhea, nausea, and fatigue. Conclusions: XL647 administered on an intermittent or daily-dosing schedule demonstrated antitumor activity in patients with EGFR-activating mutations. The adverse-event profile was similar for the two dosing schedules. C1 [Pietanza, M. Catherine; Price, Katharine A.; Riely, Gregory J.; Azzoli, Christopher G.; Miller, Vincent A.; Krug, Lee M.; Kris, Mark G.; Rizvi, Naiyer A.] Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Thorac Oncol Serv, Dept Med, New York, NY 10065 USA. [Pietanza, M. Catherine; Riely, Gregory J.; Azzoli, Christopher G.; Miller, Vincent A.; Krug, Lee M.; Kris, Mark G.; Rizvi, Naiyer A.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Gadgeel, Shirish M.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Dowlati, Afshin] Case Western Reserve Univ, Dept Med, Div Hematol Oncol, Cleveland, OH 44106 USA. [Lynch, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Lynch, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salgia, Ravi] Univ Chicago, Med Ctr, Dept Med, Thorac Oncol Res Program, Chicago, IL 60637 USA. [Wertheim, Michael S.] Hematol Oncol Associates, Port St Lucie, FL USA. [Rowland, Kendrith M., Jr.] Carle Canc Ctr, Urbana, IL USA. [Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Beumer, Jan H.] Univ Pittsburgh, Mol Therapeut & Drug Discovery Program, Inst Canc, Pittsburgh, PA USA. [Tonda, Margaret; Mitchell, Ben] Exelixis Inc, So San Francisco, CA USA. RP Pietanza, MC (reprint author), Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Thorac Oncol Serv, Dept Med, 300 E 66th St, New York, NY 10065 USA. EM pietanzm@mskcc.org OI Kris, Mark/0000-0002-7317-5341; Beumer, Jan/0000-0002-8978-9401 FU Exelixis, Inc. FX Supported by Exelixis, Inc. Thomas J. Lynch has served as a consultant for Merck, BI, and Supergen; has served on the Board of Directors for Infinity; and holds a patent with Partners Healthcare for EGFR mutations. Gregory J. Riely has received a grant for research or other work related to the topic of this manuscript. Vincent A. Miller has served as a consultant for Boehringer Ingelheim, and has received honoraria from OSI-Astellus, Genentech, and Clovis. Ben Mitchell and Margaret Tonda are employees of the organization and held stock in the organization. NR 39 TC 22 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2012 VL 7 IS 5 BP 856 EP 865 DI 10.1097/JTO.0b013e31824c943f PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 927YT UT WOS:000302947300013 PM 22722787 ER PT J AU Heist, RS Sequist, LV Engelman, JA AF Heist, Rebecca S. Sequist, Lecia V. Engelman, Jeffrey A. TI Genetic Changes in Squamous Cell Lung Cancer A Review SO JOURNAL OF THORACIC ONCOLOGY LA English DT Review DE Squamous cell carcinoma of the lung; Molecular targets; Somatic mutations ID GROWTH-FACTOR RECEPTOR; COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; COPY-NUMBER; TYROSINE KINASE; CHROMOSOMAL IMBALANCES; MUTATIONAL HOTSPOTS; PROTEIN EXPRESSION; SOMATIC MUTATIONS AB Identifying specific somatic mutations that drive tumor growth has transformed the treatment of lung cancer. For example, cancers with sensitizing epidermal growth factor receptor mutations and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocations can have remarkable responses to epidermal growth factor receptor and ALK inhibitors respectively, leading to significant clinical benefit. However, effective molecularly targeted therapies have disproportionately impacted adenocarcinomas compared to squamous cell carcinomas, and never or light smokers compared to heavy smokers. Further progress in non-small-cell lung cancer will require the identification and effective targeting of molecular alterations in all subtypes of lung cancer. Here, we review the current knowledge about the molecular alterations found in squamous cell carcinoma of the lung. First, we will discuss the ongoing efforts to comprehensively assess the squamous cell carcinoma genome. We will then discuss the evidence supporting the role of specific genes in driving squamous cell carcinomas. By describing the landscape of somatic targets in squamous cell lung cancer, we hope to crystallize the current understanding of potential targets, spur development of therapies that can have clinical impact, and underscore the importance of new discoveries in this field. C1 [Heist, Rebecca S.; Sequist, Lecia V.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA 02114 USA. RP Heist, RS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM rheist@partners.org FU SPORE FX Supported in part by SPORE Career Development Award. NR 119 TC 44 Z9 47 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD MAY PY 2012 VL 7 IS 5 BP 924 EP 933 DI 10.1097/JTO.0b013e31824cc334 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 927YT UT WOS:000302947300023 PM 22722794 ER PT J AU Carlen, M Meletis, K Siegle, JH Cardin, JA Futai, K Vierling-Claassen, D Ruhlmann, C Jones, SR Deisseroth, K Sheng, M Moore, CI Tsai, LH AF Carlen, M. Meletis, K. Siegle, J. H. Cardin, J. A. Futai, K. Vierling-Claassen, D. Ruehlmann, C. Jones, S. R. Deisseroth, K. Sheng, M. Moore, C. I. Tsai, L-H TI A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior SO MOLECULAR PSYCHIATRY LA English DT Article DE parvalbumin; interneurons; gamma; NMDAR; optogenetics; oscillations ID WORKING-MEMORY; SYNAPTIC PLASTICITY; FREQUENCY OSCILLATIONS; SELECTIVE IMPAIRMENT; PREFRONTAL CORTEX; DENDRITIC SPINES; SCHIZOPHRENIA; MICE; NEURONS; MODEL AB Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors. Molecular Psychiatry (2012) 17, 537-548; doi:10.1038/mp.2011.31; published online 5 April 2011 C1 [Carlen, M.; Meletis, K.] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Siegle, J. H.; Cardin, J. A.; Vierling-Claassen, D.; Moore, C. I.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Carlen, M.; Meletis, K.; Futai, K.; Ruehlmann, C.; Sheng, M.; Tsai, L-H] MIT, Picower Inst Leaning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Cardin, J. A.] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA. [Vierling-Claassen, D.; Jones, S. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Deisseroth, K.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Tsai, L-H] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Tsai, L-H] Howard Hughes Med Inst, Cambridge, MA USA. RP Carlen, M (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden. EM marie.carlen@ki.se; cim@mit.edu; lhtsai@mit.edu OI Carlen, Marie/0000-0003-1658-1631 FU NARSAD; Knut and Alice Wallenbergs Foundation FX We thank Tracey Petryshen, Erin Berry, Mike Lewis, Nadine Joseph and Ji-Song Guan for their valuable advice on behavioral assays. MC is supported by a NARSAD Young Investigator Award. MC and KM are supported by Knut and Alice Wallenbergs Foundation. NR 66 TC 161 Z9 165 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2012 VL 17 IS 5 BP 537 EP 548 DI 10.1038/mp.2011.31 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 930BN UT WOS:000303110800009 PM 21468034 ER PT J AU Malhotra, D Fletcher, AL Astarita, J Lukacs-Kornek, V Tayalia, P Gonzalez, SF Elpek, KG Chang, SK Knoblich, K Hemler, ME Brenner, MB Carroll, MC Mooney, DJ Turley, SJ AF Malhotra, Deepali Fletcher, Anne L. Astarita, Jillian Lukacs-Kornek, Veronika Tayalia, Prakriti Gonzalez, Santiago F. Elpek, Kutlu G. Chang, Sook Kyung Knoblich, Konstantin Hemler, Martin E. Brenner, Michael B. Carroll, Michael C. Mooney, David J. Turley, Shannon J. CA Immunological Genome Project TI Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks SO NATURE IMMUNOLOGY LA English DT Article ID FIBROBLASTIC RETICULAR CELLS; T-CELLS; DENDRITIC CELLS; CONDUIT SYSTEM; ANTIGEN; EXPRESSION; COLLAGEN; TOLERANCE; TISSUES; INFLAMMATION AB Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly elucidated. Here, comparative transcriptomic analyses of mouse LNSC subsets demonstrated the expression of important immune mediators, growth factors and previously unknown structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of crosstalk. Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of genes relevant to cytokine signaling, relative to their expression in skin and thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of genes encoding chemokines and molecules involved in the acute-phase response and the antigen-processing and antigen-presentation machinery. Poorly studied podoplanin (gp38)-negative CD31-LNSCs showed similarities to FRCs but lacked expression of interleukin 7 (IL-7) and were identified as myofibroblastic pericytes that expressed integrin alpha(7). Together our data comprehensively describe the transcriptional characteristics of LNSC subsets. C1 [Malhotra, Deepali; Fletcher, Anne L.; Astarita, Jillian; Lukacs-Kornek, Veronika; Elpek, Kutlu G.; Knoblich, Konstantin; Hemler, Martin E.; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Malhotra, Deepali; Astarita, Jillian] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Tayalia, Prakriti; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Gonzalez, Santiago F.; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Carroll, Michael C.] Harvard Univ, Sch Med, Div Rheumatol Immunol & Allergy, Immune Dis Inst, Boston, MA USA. [Gonzalez, Santiago F.; Carroll, Michael C.] Harvard Univ, Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Chang, Sook Kyung; Brenner, Michael B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Brenner, Michael B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu RI Knoblich, Konstantin/B-5980-2009; Gautier, Emmanuel L./E-2259-2017; OI Knoblich, Konstantin/0000-0002-5646-837X; Gautier, Emmanuel L./0000-0003-2976-7566; Malhotra, Deepali/0000-0002-8215-7639; Gazit, Roi/0000-0002-0548-2147; Kim, Charles/0000-0001-6474-8227 FU US National Institutes of Health [R01 DK074500, P01 AI045757, R24 AI072073, R01 AI063428-06, R01 DE019917, GM38903]; Dana-Farber Cancer Institute; European Union [220044] FX We thank L. Fisher (US National Institutes of Health) for polyclonal anti-decorin, anti-fibromodulin and anti-biglycan; M. Koch (University of Cologne) for polyclonal anti-collagen XIV; M. Curry for technical assistance in sorting stromal-cell populations; J.B. Lewis for discussions during analysis of microarray data; eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project; and K. W. Wucherpfennig for critical reading of the manuscript. Supported by the US National Institutes of Health (R01 DK074500 and P01 AI045757 to S.J.T.; R24 AI072073 to the ImmGen Consortium; R01 AI063428-06 to M. B. B.; R01 DE019917 to D.J.M.; and GM38903 to M. E. H. and K. K.), the Dana-Farber Cancer Institute (K. K. and V.L.-K.) and the Seventh Framework Programme of the European Union (Marie Curie International Outgoing Fellowship 220044 to S.F.G.). NR 50 TC 126 Z9 126 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2012 VL 13 IS 5 BP 499 EP U107 DI 10.1038/ni.2262 PG 14 WC Immunology SC Immunology GA 929GD UT WOS:000303048400014 PM 22466668 ER PT J AU Buckholtz, JW Marois, R AF Buckholtz, Joshua W. Marois, Rene TI The roots of modern justice: cognitive and neural foundations of social norms and their enforcement SO NATURE NEUROSCIENCE LA English DT Article ID PREFRONTAL CORTEX; DECISION-MAKING; ALTRUISTIC PUNISHMENT; 3RD-PARTY PUNISHMENT; HUMAN COOPERATION; EVOLUTION; RECIPROCITY; MECHANISMS; FAIRNESS; SPITEFUL AB Among animals, Homo sapiens is unique in its capacity for widespread cooperation and prosocial behavior among large and genetically heterogeneous groups of individuals. This ultra-sociality figures largely in our success as a species. It is also an enduring evolutionary mystery. There is considerable support for the hypothesis that this facility is a function of our ability to establish, and enforce through sanctions, social norms. Third-party punishment of norm violations ("I punish you because you harmed him") seems especially crucial for the evolutionary stability of cooperation and is the cornerstone of modern systems of criminal justice. In this commentary, we outline some potential cognitive and neural processes that may underlie the ability to learn norms, to follow norms and to enforce norms through third-party punishment. We propose that such processes depend on several domain-general cognitive functions that have been repurposed, through evolution's thrift, to perform these roles. C1 [Buckholtz, Joshua W.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckholtz, Joshua W.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckholtz, Joshua W.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, Boston, MA 02114 USA. [Marois, Rene] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Marois, Rene] Vanderbilt Univ, Ctr Integrated & Cognit Neurosci, Nashville, TN USA. RP Buckholtz, JW (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM joshuabuckholtz@fas.harvard.edu; rene.marois@vanderbilt.edu FU MacArthur Foundation Research Network on Law and Neuroscience [KK9127, KK1031] FX We thank K. Jan for literature research and O. Jones for comments on an earlier draft of this manuscript, and the MacArthur Foundation Research Network on Law and Neuroscience for support (KK9127 and KK1031). NR 50 TC 53 Z9 59 U1 3 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2012 VL 15 IS 5 BP 655 EP 661 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 932DI UT WOS:000303270200006 PM 22534578 ER EF