FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pruhs, Z Michaud, KD Erickson, AR Sayles, H Kerr, GS Gaffo, AL Caplan, L Cannon, GW Lazaro, DM Reimold, AM Johnson, DS Cherascu, B Schwab, P Khan, NA Mikuls, TR AF Pruhs, Zachary Michaud, Kaleb D. Erickson, Alan R. Sayles, Harlan Kerr, Gail S. Gaffo, Angelo L. Caplan, Liron Cannon, Grant W. Lazaro, Deana M. Reimold, Andreas M. Johnson, Dannette S. Cherascu, Bogdan Schwab, Pascale Khan, Nasim A. Mikuls, Ted R. TI Vascular Calcification On Hand and Wrist Radiographs Are Associated with Comorbidity and Overall Mortality In Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Pruhs, Zachary; Michaud, Kaleb D.] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb D.] Natl Data Bank Rheumat Dis, Omaha, NE USA. [Erickson, Alan R.] UNMC Phys Brentwood, Lavista, NE USA. [Sayles, Harlan] Univ Nebraska, Sch Med, Omaha, NE 68198 USA. [Kerr, Gail S.] Washington DC VA, Washington, DC USA. [Kerr, Gail S.] Georgetown Univ, Washington, DC USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Caplan, Liron] Denver VA, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Aurora, CO USA. [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Lazaro, Deana M.] Brooklyn VA, Brooklyn, NY USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Johnson, Dannette S.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Cherascu, Bogdan] Iowa City VA, Iowa City, IA USA. [Cherascu, Bogdan] Univ Iowa, Iowa City, IA USA. [Schwab, Pascale] Portland VA, Portland, OR USA. [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Khan, Nasim A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Khan, Nasim A.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska, Omaha, NE 68182 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1174 BP S457 EP S458 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501368 ER PT J AU Ramos, PS Oates, JC Kamen, DL Gaffney, PM Langefeld, CD Kelly, JA Kaufman, KM Kimberly, RP Niewold, TB Jacob, CO Tsao, BP Brown, E James, JA Guthridge, J Merrill, JT Boackle, SA Freedman, BI Scofield, RH Stevens, AM Vyse, TJ Criswell, LA Moser, KL Alarcon-Riquelme, ME Harley, JB Gilkeson, GS AF Ramos, Paula S. Oates, James C. Kamen, Diane L. Gaffney, Patrick M. Langefeld, Carl D. Kelly, Jennifer A. Kaufman, Kenneth M. Kimberly, Robert P. Niewold, Timothy B. Jacob, Chaim O. Tsao, Betty P. Brown, Elizabeth James, Judith A. Guthridge, Joel Merrill, Joan T. Boackle, Susan A. Freedman, Barry I. Scofield, R. Hal Stevens, Anne M. Vyse, Timothy J. Criswell, Lindsey A. Moser, Kathy L. Alarcon-Riquelme, Marta E. Harley, John B. Gilkeson, Gary S. CA PROFILE TI Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus (SLE) Varies Across Populations with Different African Ancestries SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Ramos, Paula S.; Langefeld, Carl D.; Freedman, Barry I.] Wake Forest Sch Med, Winston Salem, NC USA. [Oates, James C.; Kamen, Diane L.; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kimberly, Robert P.; Brown, Elizabeth; PROFILE] Univ Alabama, Birmingham, AL USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Boackle, Susan A.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Stevens, Anne M.] Univ Washington, Seattle, WA 98195 USA. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 OCT PY 2011 VL 63 IS 10 SU S MA 641 BP S250 EP S250 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500637 ER PT J AU Robertson, JM Heinlen, L Anderson, J Niewold, TB Keith, MP Harley, JB James, JA AF Robertson, Julie M. Heinlen, Latisha Anderson, Jourdan Niewold, Timothy B. Keith, Michael P. Harley, John B. James, Judith A. TI Interferon-Alpha Activity Levels Increase Immediately Preceding Clinical Classification of Systemic Lupus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Robertson, Julie M.; Anderson, Jourdan; James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Heinlen, Latisha] OUHSC, Oklahoma City, OK USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Keith, Michael P.] Natl Naval Med Ctr, Bethesda, MD USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2601 BP S1022 EP S1022 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503181 ER PT J AU Sakurai, D Zhao, J Deng, Y Kaufman, K Kelly, JA Kimberly, RP Alarcon-Riquelme, ME Harley, JB Bae, SC Jacob, CO Vyse, TJ Niewold, TB Gaffney, PM Moser, KL James, JA Gilkeson, GS Kamen, DL Langefeld, CD Chang, DM Song, YW Yu, CY Grossman, JM Cantor, RM Hahn, BH Tsao, BP AF Sakurai, Daisuke Zhao, Jian Deng, Yun Kaufman, Kenneth Kelly, Jennifer A. Kimberly, Robert P. Alarcon-Riquelme, Marta E. Harley, John B. Bae, Sang-Cheol Jacob, Chaim O. Vyse, Timothy J. Niewold, Timothy B. Gaffney, Patrick M. Moser, Kathy L. James, Judith A. Gilkeson, Gary S. Kamen, Diane L. Langefeld, Carl D. Chang, Deh-Ming Song, Yeong Wook Yu, Chack-Yung Grossman, Jennifer M. Cantor, Rita M. Hahn, Bevra H. Tsao, Betty P. CA PROFILE Investigators BIOLUPUS GENLES Networ TI Risk Alleles of SLE Associated IL10 SNPs Conferred Differential Binding to Transcription Factors SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Sakurai, Daisuke; Zhao, Jian; Deng, Yun; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Alarcon-Riquelme, Marta E.; BIOLUPUS GENLES Networ] Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK 73104 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Immunol, London WC2R 2LS, England. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Kamen, Diane L.] Med Univ SC, Charleston, SC USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong Wook] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Yu, Chack-Yung] Nationwide Childrens Hosp, Ctr Mol & Human Genet, Res Inst, Columbus, OH USA. [Yu, Chack-Yung] Ohio State Univ, Columbus, OH 43210 USA. RI Yu, Chack-Yung/E-4360-2011; Zhao, Jian/E-6292-2012 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2477 BP S966 EP S966 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503048 ER PT J AU Sanchez, E Comeau, ME Freedman, BI Kelly, JA Kaufman, K Langefeld, CD Brown, EE Merrill, JT Tsao, BP Kamen, DL Gilkeson, GS James, JA Vyse, TJ Gaffney, PM Jacob, CO Niewold, TB Richardson, BC Harley, JB Alarcon-Riquelme, ME Sawalha, AH AF Sanchez, Elena Comeau, Mary E. Freedman, Barry I. Kelly, Jennifer A. Kaufman, Kenneth Langefeld, Carl D. Brown, Elizabeth E. Merrill, J. T. Tsao, Betty P. Kamen, Diane L. Gilkeson, Gary S. James, Judith A. Vyse, Tomothy J. Gaffney, Patrick M. Jacob, Chaim O. Niewold, Timothy B. Richardson, Bruce C. Harley, John B. Alarcon-Riquelme, Marta E. Sawalha, Amr H. TI Identification of Novel Genetic Susceptibility Loci In African-American Lupus Patients Using a Candidate Gene Association Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Comeau, Mary E.; Freedman, Barry I.; Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Brown, Elizabeth E.] Univ Alabama, Birmingham, AL USA. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Kamen, Diane L.] Med Univ SC, Charleston, SC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Vyse, Tomothy J.] Guys Hosp, Univ London Kings Coll, London SE1 9RT, England. [Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Richardson, Bruce C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Med Ctr, US Dept Vet Affairs, Cincinnati, OH USA. [Alarcon-Riquelme, Marta E.] Pfizer Univ Granada Junta Andalucia, Oklahoma Med Res Fdn, Ctr Genom & Oncol Res, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 7 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 OCT PY 2011 VL 63 IS 10 SU S MA 2476 BP S965 EP S966 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503047 ER PT J AU Sekine, H Machida, T Suzuki, E Reilly, C Zhang, X Ruiz, P Gilkeson, GS AF Sekine, Hidemaru Machida, Takeshi Suzuki, Eiji Reilly, Christopher Zhang, Xian Ruiz, Phil Gilkeson, Gary S. TI Interferon Regulatory Factor-4 deficient Lupus-Prone MRL/LprMice Show Strong Propensity for Th1 Polarity and Develop Granulomatous Lesions in Multiple Organs SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Sekine, Hidemaru; Machida, Takeshi] Fukushima Med Univ, Fukushima, Japan. [Reilly, Christopher] Virginia Tech, Blacksburg, VA USA. [Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Ruiz, Phil] Univ Miami, Miami, FL USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 557 BP S213 EP S213 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500553 ER PT J AU Shah, N Hannon, MJ Wang, ZJ Kwoh, CK AF Shah, Nehal Hannon, Michael J. Wang Zhijie Kwoh, C. Kent TI Relationship of Specific Pain Patterns in Knee Osteoarthritis with Severity of Pain and Functional Disability. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Hannon, Michael J.; Wang Zhijie] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1983 BP S770 EP S771 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502369 ER PT J AU Stone, JH Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Fessler, BJ Tchao, N Webber, L Ding, LN Sejismundo, LP Mieras, K Ikle, D Phippard, DJ Jepson, B Lail, A Asare, A Lim, N Mueller, M Brunetta, P Allen, NB Fervenza, F Geetha, D Keogh, K Kissin, EY Monach, PA Peikert, T Stegeman, C Ytterberg, SR Specks, U AF Stone, John H. Merkel, Peter A. Seo, Philip Spiera, Robert Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Fessler, Barri J. Tchao, Nadia Webber, Lisa Ding, Linna Sejismundo, Lourdes P. Mieras, Kathleen Ikle, David Phippard, Deborah J. Jepson, Brett Lail, Alice Asare, Adam Lim, Noha Mueller, Mark Brunetta, Paul Allen, Nancy B. Fervenza, Fernando Geetha, Duvuru Keogh, Karina Kissin, Eugene Y. Monach, Paul A. Peikert, Tobias Stegeman, Coen Ytterberg, Steven R. Specks, Ulrich CA RAVE-ITN Res Grp TI Extended Follow-up of Treatment with Rituximab Versus Cyclophosphamide for Remission-Induction of ANCA-Associated Vasculitis: Which Subsets Are At Greatest Risk for Flare? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William; Allen, Nancy B.] Duke Univ, Med Ctr, Durham, NC USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Tchao, Nadia; Phippard, Deborah J.; Asare, Adam; Lim, Noha] Immune Tolerance Network, Bethesda, MD USA. [Webber, Lisa; Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Sejismundo, Lourdes P.] Johns Hopkins Univ, Baltimore, MD USA. [Mieras, Kathleen; Fervenza, Fernando; Keogh, Karina; Peikert, Tobias; Ytterberg, Steven R.; Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Ikle, David; Jepson, Brett; Lail, Alice] Rho, Chapel Hill, NC USA. [Mueller, Mark] US FDA, Bethesda, MD 20014 USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. [Geetha, Duvuru] Johns Hopkins Univ, York, PA USA. NR 0 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2432 BP S946 EP S947 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503003 ER PT J AU Strle, K Shin, JJ Glickstein, L Steere, AC AF Strle, Klemen Shin, Junghee J. Glickstein, Lisa Steere, Allen C. TI A Toll-Like Receptor 1 Polymorphism Is Associated with Heightened T Helper 1 Responses and Antibiotic-Refractory Lyme Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Strle, Klemen; Shin, Junghee J.; Glickstein, Lisa; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 975 BP S382 EP S382 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501170 ER PT J AU Suzuki, E Williams, S Karam, E Gilkeson, GS Zhang, X AF Suzuki, Eiji Williams, Sarah Karam, Eva Gilkeson, Gary S. Zhang, Xian TI Role of Transcription Factor Fli-1 in Regulation of Dendritic Cell and Monocyte Development SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Suzuki, Eiji; Karam, Eva; Gilkeson, Gary S.; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA. [Williams, Sarah; Gilkeson, Gary S.; Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 68 BP S24 EP S24 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500069 ER PT J AU Tjarnlund, A Rider, LG Miller, FW Werth, VP Pilkington, CA de Visser, M Forslund, E Amato, AA Barohn, RJ Bottai, M Finkel, R Paulus, HE Hengstman, GJD Liang, MH Singh, J Lundberg, IE AF Tjarnlund, Anna Rider, Lisa G. Miller, Frederick W. Werth, Victoria P. Pilkington, Clarissa A. de Visser, Marianne Forslund, Elin Amato, Anthony A. Barohn, Richard J. Bottai, Matteo Finkel, Richard Paulus, Harold E. Hengstman, Gerald J. D. Liang, Matthew H. Singh, Jasvinder Lundberg, Ingrid E. TI Ethnic but not Gender Differences in Disease Manifestations in Dermatomyositis Patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Bottai, Matteo] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA. [Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, Dept Rheumatol, London WC1N 3JH, England. [de Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Amato, Anthony A.; Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amato, Anthony A.] Harvard Univ, Sch Med, Boston, MA USA. [Barohn, Richard J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, MO USA. [Finkel, Richard] Univ Penn, Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Paulus, Harold E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hengstman, Gerald J. D.] Catharina Hosp, Dept Neurol, Eindhoven, Netherlands. [Singh, Jasvinder] Univ Alabama, Birmingham, AL USA. [Singh, Jasvinder] VA Med Ctr, Birmingham, AL 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 235 BP S87 EP S87 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500235 ER PT J AU Unizony, S Arias-Urdaneta, L Miloslavsky, E Arvikar, SL Khosroshahi, A Stone, JH AF Unizony, Sebastian Arias-Urdaneta, Luis Miloslavsky, Eli Arvikar, Sheila L. Khosroshahi, Arezou Stone, John H. TI Tocilizumab for the Treatment of Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis) and Polymyalgia Rheumatica: A Case Series. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Unizony, Sebastian; Arias-Urdaneta, Luis; Miloslavsky, Eli; Arvikar, Sheila L.; Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 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 OCT PY 2011 VL 63 IS 10 SU S MA 1507 BP S589 EP S589 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501701 ER PT J AU Vashisht, P Sayles, H Cannon, GW Kerr, GS Schwab, P Lazaro, DM Reimold, AM Khan, NA Cherascu, B Gaffo, AL Johnson, DS Mikuls, TR Michaud, K AF Vashisht, Priyanka Sayles, Harlan Cannon, Grant W. Kerr, Gail S. Schwab, Pascale Lazaro, Deana M. Reimold, Andreas M. Khan, Nasim A. Cherascu, Bogdan Gaffo, Angelo L. Johnson, Dannette S. Mikuls, Ted R. Michaud, Kaleb TI Generalizability of Patients with Rheumatoid Arthritis in Biologic Clinical Trials SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Vashisht, Priyanka] Creighton Univ, Med Ctr, Omaha, NE USA. [Sayles, Harlan; Mikuls, Ted R.; Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Cannon, Grant W.] Salt Lake City VA, Salt Lake City, UT USA. [Kerr, Gail S.] Washington DC VA, Washington, DC USA. [Schwab, Pascale] Portland VA, Portland, OR USA. [Lazaro, Deana M.] Brooklyn VA, Brooklyn, NY USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Khan, Nasim A.] Univ Arkansas Med Sci & Cent Arkansas Vet Healthc, Little Rock, AR USA. [Cherascu, Bogdan] Iowa City VA, Iowa City, IA USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Dannette S.] Jackson VA, Jackson, MS USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Omaha, NE USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT USA. [Kerr, Gail S.] Georgetown Univ, Washington, DC USA. [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Cherascu, Bogdan] Univ Iowa, Iowa City, IA USA. [Johnson, Dannette S.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 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 OCT PY 2011 VL 63 IS 10 SU S MA 1200 BP S467 EP S467 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621501394 ER PT J AU Vudattu, NK Drouin, EE Steere, AC AF Vudattu, Nalini K. Drouin, Elise E. Steere, Allen C. TI High Expression of GITR and OX-40 Receptors on Memory CD4+25+T Cells in the Joint Fluid of Patients with Antibiotic-Refractory Lyme Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Vudattu, Nalini K.] Massachusetts Gen Hosp, Charlestown, MA USA. [Vudattu, Nalini K.] Harvard Univ, Sch Med, Charlestown, MA USA. [Drouin, Elise E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 1939 BP S755 EP S755 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621502325 ER PT J AU Zhao, J Sakurai, D Deng, Y Sestak, AL Langefeld, CD Kaufman, KM Kelly, JA Gaffney, PM Moser, KL Alarcon-Riquelme, ME Harley, JB Bae, SC Vyse, TJ Jacob, CO Kimberly, RP Criswell, LA James, JA Gilkeson, GS Anaya, JM Chang, DM Song, YW Grossman, JM Hahn, BH Cantor, RM Tsao, BP AF Zhao, Jian Sakurai, Daisuke Deng, Yun Sestak, Andrea L. Langefeld, Carl D. Kaufman, Kenneth M. Kelly, Jennifer A. Gaffney, Patrick M. Moser, Kathy L. Alarcon-Riquelme, Marta E. Harley, John B. Bae, Sang-Cheol Vyse, Timothy J. Jacob, Chaim O. Kimberly, Robert P. Criswell, Lindsey A. James, Judith A. Gilkeson, Gary S. Anaya, Juan-Manuel Chang, Deh-Ming Song, Yeong W. Grossman, Jennifer M. Hahn, Bevra H. Cantor, Rita M. Tsao, Betty P. CA BIOLUPUS GENLES Network PROFILE Investigators TI SLE-Risk Alleles of SNPs in the NMNAT2/SMG7 Region Are Associated with Lower mRNA Levels of SMG7 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Zhao, Jian; Sakurai, Daisuke; Deng, Yun; Grossman, Jennifer M.; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sestak, Andrea L.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Kaufman, Kenneth M.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Alarcon-Riquelme, Marta E.; BIOLUPUS GENLES Network] Pfizer Univ Granada Junda de Andalucia GENYO, Ctr Genom & Invest Oncol, Granada, Spain. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Bae, Sang-Cheol] Hanyang Univ, Hosp Rheumat Dis, CRCRA, Seoul 133791, South Korea. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kimberly, Robert P.; PROFILE Investigators] Univ Alabama, Birmingham, AL USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosaling Russell Med Res Ctr Arthrit, San Francisco, CA USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Anaya, Juan-Manuel] Univ Rosario, Corp Invest Biol, Bogota, Colombia. [Chang, Deh-Ming] Natl Def Med Ctr, Taipei, Taiwan. [Song, Yeong W.] Seoul Natl Univ, Seoul, South Korea. RI Zhao, Jian/E-6292-2012; Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 1 U2 3 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 OCT PY 2011 VL 63 IS 10 SU S MA 639 BP S249 EP S249 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500635 ER PT J AU Zhu, XX Wang, MM Qiu, JH Zou, HJ AF Zhu, Xiaoxia Wang, Meimei Qiu, Jianhua Zou, Hejian TI Resveratrol Deacetylating Rela/p65 Contributes to Inhibit Transforming Growth Factor-Alpha Induced Inflammation Via a Sirt1 Dependent Manner SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Professionals C1 [Zhu, Xiaoxia; Zou, Hejian] Fudan Univ, Div Rheumatol, Huashan Hosp, Shanghai 200433, Peoples R China. [Wang, Meimei] Dongnan Univ, Div Rheumatol, Zhongda Hosp, Nanjing, Peoples R China. [Qiu, Jianhua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, 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 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 69 BP S24 EP S24 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500070 ER PT J AU Walunas, TL Lenschow, DJ Bakker, CY Linsley, PS Freeman, GJ Green, JM Thompson, CB Bluestone, JA AF Walunas, Theresa L. Lenschow, Deborah J. Bakker, Christina Y. Linsley, Peter S. Freeman, Gordon J. Green, Jonathan M. Thompson, Craig B. Bluestone, Jeffrey A. TI CTLA-4 Can Function as a Negative Regulator of T Cell SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID LYMPHOCYTES-T; COUNTER-RECEPTOR; CD28 RECEPTOR; ACTIVATION; EXPRESSION; ANTIGEN; MOLECULE; ANTIBODY; LIGAND; MICE AB CD28 and CTLA-4 are related glycoprotiens found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor in murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 MAbs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function. C1 [Walunas, Theresa L.; Lenschow, Deborah J.; Bakker, Christina Y.; Bluestone, Jeffrey A.] Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. [Green, Jonathan M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Freeman, Gordon J.; Thompson, Craig B.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Linsley, Peter S.] Bristol Myers Squibb Co, Pharmaceut Res Labs, Seattle, WA 98121 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Div Hematol Malignaacies, Dept Med,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Walunas, TL (reprint author), Univ Chicago, Comm Immunol, Chicago, IL 60637 USA. NR 36 TC 8 Z9 9 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2011 VL 187 IS 7 BP 3466 EP 3474 PG 9 WC Immunology SC Immunology GA 822IB UT WOS:000295036400003 PM 21934098 ER PT J AU Onoe, T Kalscheuer, H Danzl, N Chittenden, M Zhao, GL Yang, YG Sykes, M AF Onoe, Takashi Kalscheuer, Hannes Danzl, Nichole Chittenden, Meredith Zhao, Guiling Yang, Yong-Guang Sykes, Megan TI Human Natural Regulatory T Cell Development, Suppressive Function, and Postthymic Maturation in a Humanized Mouse Model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; HUMAN IMMUNE-SYSTEM; SCID-HU MOUSE; MHC CLASS-II; HEMATOPOIETIC STEM-CELLS; SELF-ANTIGEN; HOMEOSTATIC PROLIFERATION; PHENOTYPIC CONVERSION; IMMUNODEFICIENT MICE; NEONATAL MICE AB CD4(+) regulatory T cells (Tregs) control adaptive immune responses and promote self-tolerance. Various humanized mouse models have been developed in efforts to reproduce and study a human immune system. However, in models that require T cell differentiation in the recipient murine thymus, only low numbers of T cells populate the peripheral immune systems. T cells are positively selected by mouse MHC and therefore do not function well in an HLA-restricted manner. In contrast, cotransplantation of human fetal thymus/liver and i.v. injection of CD34(+) cells from the same donor achieves multilineage human lymphohematopoietic reconstitution, including dendritic cells and formation of secondary lymphoid organs, in NOD/SCID mice. Strong Ag-specific immune responses and homeostatic expansion of human T cells that are dependent on peripheral human APCs occur. We now demonstrate that FOXP3(+)Helios(+) "natural" Tregs develop normally in human fetal thymic grafts and are present in peripheral blood, spleen, and lymph nodes of these humanized mice. Humanized mice exhibit normal reversal of CD45 isoform expression in association with thymic egress, postthymic "naive" to "activated" phenotypic conversion, and suppressive function. These studies demonstrate the utility of this humanized mouse model for the study of human Treg ontogeny, immunobiology and therapy. The Journal of Immunology, 2011, 187: 3895-3903. C1 [Kalscheuer, Hannes; Danzl, Nichole; Zhao, Guiling; Yang, Yong-Guang; Sykes, Megan] Columbia Univ, Columbia Ctr Translat Immunol, Coll Phys & Surg, New York, NY 10032 USA. [Onoe, Takashi; Kalscheuer, Hannes; Chittenden, Meredith; Zhao, Guiling; Yang, Yong-Guang; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Kalscheuer, Hannes; Danzl, Nichole; Zhao, Guiling; Yang, Yong-Guang; Sykes, Megan] Columbia Univ, Dept Med, New York, NY 10032 USA. [Sykes, Megan] Columbia Univ, Dept Surg, New York, NY 10032 USA. [Sykes, Megan] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA. RP Sykes, M (reprint author), Columbia Univ, Columbia Ctr Translat Immunol, Coll Phys & Surg, 650 W 168th St,BB1512, New York, NY 10032 USA. EM megan.sykes@columbia.edu FU National Institutes of Health [R01 AI084903, PO1 AI045897]; Japan Society for the Promotion of Science; Juvenile Diabetes Research Foundation FX This work was supported by National Institutes of Health Grants R01 AI084903 and PO1 AI045897. T.O. was supported in part by a Postdoctoral Fellowship for Research Abroad of the Japan Society for the Promotion of Science. H. K. was supported by a postdoctoral fellowship from the Juvenile Diabetes Research Foundation. NR 68 TC 19 Z9 20 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2011 VL 187 IS 7 BP 3895 EP 3903 DI 10.4049/jimmunol.1100394 PG 9 WC Immunology SC Immunology GA 822IB UT WOS:000295036400049 PM 21876039 ER PT J AU Hatzenbuehler, ML O'Cleirigh, C Mayer, KH Mimiaga, MJ Safren, SA AF Hatzenbuehler, Mark L. O'Cleirigh, Conall Mayer, Kenneth H. Mimiaga, Matthew J. Safren, Steven A. TI Prospective Associations Between HIV-Related Stigma, Transmission Risk Behaviors, and Adverse Mental Health Outcomes in Men Who Have Sex with Men SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE HIV-related stigma; HIV risk behaviors; Depression; Anxiety; MSM ID UNITED-STATES; POSITIVE MEN; SUBSTANCE USE; INFECTED MEN; CARE; DEPRESSION; PEOPLE; PREVALENCE; HIV/AIDS; DISCRIMINATION AB Background The vast majority of research on HIV-related stigma has been cross sectional, and few studies have examined whether experiencing stigma is associated with sexual risk behaviors. Purpose The purpose of this study is to examine the prospective relationships between experiencing HIV-related stigma and symptoms of anxiety and depression, as well as sexual transmission risk behavior. Methods The sample included HIV-infected men who have sex with men (n=314) who participated in a secondary HIV-prevention study at their primary care site. Participants were assessed at baseline, and then completed follow-up assessments at 3, 6, 9, and 12 months. Results Experiencing HIV-related stigma was prospectively associated with symptoms of depression (beta=0.16, p<.001), panic (beta=0.11, p=.01), and generalized anxiety (beta=0.05, p=.05). In addition, perceiving HIV-related stigma was prospectively associated with transmission risk behaviors, including unprotected receptive or insertive anal intercourse with HIV-seronegative or status unknown partners (beta=0.06, p=.047). Conclusions Experiencing HIV-related stigma may increase risk for sexual transmission risk behavior and mental health problems. C1 [Hatzenbuehler, Mark L.; O'Cleirigh, Conall; Mimiaga, Matthew J.; Safren, Steven A.] Fenway Inst, Boston, MA USA. [Hatzenbuehler, Mark L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Hatzenbuehler, Mark L.; O'Cleirigh, Conall; Mayer, Kenneth H.; Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mayer, Kenneth H.] Brown Univ, Dept Med, Providence, RI 02912 USA. [Mayer, Kenneth H.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Hatzenbuehler, ML (reprint author), Fenway Inst, Boston, MA USA. EM mlh2101@columbia.edu FU NIMH NIH HHS [5R01MH068746-05, R01 MH068746]; PHS HHS [H97HA01293] NR 39 TC 36 Z9 39 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2011 VL 42 IS 2 BP 227 EP 234 DI 10.1007/s12160-011-9275-z PG 8 WC Psychology, Multidisciplinary SC Psychology GA 849YE UT WOS:000297160700008 PM 21533623 ER PT J AU Wang, DB Gitcho, MA Kraemer, BC Klein, RL AF Wang, David B. Gitcho, Michael A. Kraemer, Brian C. Klein, Ronald L. TI Genetic strategies to study TDP-43 in rodents and to develop preclinical therapeutics for amyotrophic lateral sclerosis SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE adeno-associated virus; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; gene therapy; gene transfer ID FRONTOTEMPORAL LOBAR DEGENERATION; ADENOASSOCIATED VIRUS VECTORS; SPINAL MUSCULAR-ATROPHY; MOTOR-NEURON DISEASE; TRANSGENIC ALS MICE; BINDING PROTEIN 43; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE AB The neuropathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) and a class of frontotemporal lobar degeneration is ubiquitinated cytoplasmic aggregates composed of transactive response DNA binding protein 43 kDa (TDP-43). Genetic manipulation of TDP-43 in animal models has been used to study the proteins role in pathogenesis. Transgenic rodents for TDP-43 have recapitulated key aspects of ALS such as paralysis, loss of spinal motor neurons and muscle atrophy. Viral vectors are an alternate approach to express pathological proteins in animals. Use of the recombinant adeno-associated virus vector serotype 9 has permitted widespread transgene expression throughout the central nervous system after intravenous administration. Expressing TDP-43 in rats with this method produced a phenotype that was consistent with and similar to TDP-43 transgenic lines. Increased levels of TDP-43 in the nucleus are toxic to neurons and sufficient to produce ALS-like symptoms. Animal models based on TDP-43 will address the relationships between TDP-43 expression levels, pathology, neuronal loss, muscle atrophy, motor function and causative mechanisms of disease. New targets that modify TDP-43 function, or targets from previous ALS models and other models of spinal cord diseases, could be tested for efficacy in the recent rodent models of ALS based on TDP-43. The vector approach could be an important therapeutic channel because the entire spinal cord can be affected from a one-time peripheral administration. C1 [Wang, David B.; Klein, Ronald L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA. [Gitcho, Michael A.] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI USA. [Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Klein, RL (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol Toxicol & Neurosci, Shreveport, LA 71105 USA. EM klein@lsuhsc.edu FU Department of Veterans Affairs [1147891]; NIH/NINDS [R01 NS048450] FX David Knight and R. Waleed Naseem critiqued the manuscript. This work was supported by Department of Veterans Affairs Merit Review Grant 1147891 (B.C.K.) and NIH/NINDS R01 NS048450 (R.L.K.). NR 112 TC 9 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2011 VL 34 IS 8 BP 1179 EP 1188 DI 10.1111/j.1460-9568.2011.07803.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 847ZC UT WOS:000297014000001 PM 21777407 ER PT J AU Sangwaiya, MJ Kalra, MK Roddie, M AF Sangwaiya, M. J. Kalra, M. K. Roddie, M. TI Venienti occurrite morbo: Knowledge and Prevention of Errors in Radiology SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article ID VOICE RECOGNITION; RATES C1 [Sangwaiya, M. J.; Kalra, M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sangwaiya, M. J.; Roddie, M.] Univ London Imperial Coll Sci Technol & Med, London, England. RP Sangwaiya, MJ (reprint author), Charing Cross Hosp, Dept Imaging, Fulham Palace Rd, London W6 8RF, England. EM drminaljagtiani@yahoo.co.uk NR 11 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD OCT PY 2011 VL 65 SU 173 SI SI BP 1 EP 2 DI 10.1111/j.1742-1241.2011.02782.x PG 2 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 851FJ UT WOS:000297253500002 ER PT J AU Raeisossadati, R Farshchian, M Ganji, A Tavassoli, A Velayati, A Dadkhah, E Chavoshi, S Bahar, MM Memar, B Mashhadi, MTR Naseh, H Forghanifard, MM Moghbeli, M Moaven, O Abbaszadegan, MR AF Raeisossadati, Reza Farshchian, Moein Ganji, Azita Tavassoli, Alieza Velayati, Arash Dadkhah, Ezzat Chavoshi, Somaye Bahar, Mostafa Mehrabi Memar, Bahram Mashhadi, Mohammad Taghi Rajabi Naseh, Hossein Forghanifard, Mohammad Mahdi Moghbeli, Meysam Moaven, Omeed Abbaszadegan, Mohammad Reza TI Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE Colon cancer; Real-time PCR; Tumor markers; TEM-8; CEA; TEM-8; Q-PCR; Colorectal cancer ID POLYMERASE-CHAIN-REACTION; TIME RT-PCR; MOLECULAR-DETECTION; MESSENGER-RNA; COLON-CANCER; METASTASIS; RISK AB Background Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection. Methods A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control. Results TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p = 0.009 and 30/40 vs 11/40, p = 0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p = 0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values. Conclusions TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread. C1 [Raeisossadati, Reza; Velayati, Arash; Dadkhah, Ezzat; Chavoshi, Somaye; Moghbeli, Meysam; Abbaszadegan, Mohammad Reza] MUMS, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. [Ganji, Azita] MUMS, Imam Reza Hosp, Dept Internal Med, Mashhad 9196773117, Iran. [Raeisossadati, Reza] Islamic Azad Univ, Fac Sci, Sci & Res Branch, Dept Biol, Tehran, Iran. [Tavassoli, Alieza] Qaem Hosp, Endoscop & Minimally Invas Res Ctr, Mashhad, Iran. [Bahar, Mostafa Mehrabi] MUMS, Imam Reza Hosp, Dept Surg, Mashhad 9196773117, Iran. [Memar, Bahram; Naseh, Hossein] MUMS, Omid Hosp, Dept Pathol, Mashhad 9196773117, Iran. [Mashhadi, Mohammad Taghi Rajabi] Omid Hosp, Dept Surg, Mashhad, Iran. [Moaven, Omeed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Farshchian, Moein] Ferdowsi Univ Mashhad, Dept Biol, Fac Sci, Mashhad, Iran. [Forghanifard, Mohammad Mahdi] Islamic Azad Univ, Damghan Branch, Dept Biol Sci, Damghan, Iran. RP Abbaszadegan, MR (reprint author), MUMS, Avicenna Res Inst, Immunol Res Ctr, Div Human Genet, Mashhad 9196773117, Iran. EM abbaszadeganmr@mums.ac.ir RI Memar, Bahram/F-6572-2012; Moghbeli, Meysam/Q-6582-2016; OI Moghbeli, Meysam/0000-0001-9680-0309; Ganji, Azita/0000-0002-8161-6629; Moaven, Omeed/0000-0002-0560-0457 FU National Science Foundation at Mashhad University of Medical Sciences [85122/68] FX This study was supported by a grant from the Iran National Science Foundation (#85122/68) at Mashhad University of Medical Sciences. The authors sincerely thank all of their colleagues at the Human Genetics Division of the Avicenna Research Institute who contributed in this study. NR 25 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD OCT PY 2011 VL 26 IS 10 BP 1265 EP 1270 DI 10.1007/s00384-011-1230-8 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 851CZ UT WOS:000297247200005 PM 21573768 ER PT J AU Shi, P Scott, MA Ghosh, B Wan, DP Wissner-Gross, Z Mazitschek, R Haggarty, SJ Yanik, MF AF Shi, Peng Scott, Mark A. Ghosh, Balaram Wan, Dongpeng Wissner-Gross, Zachary Mazitschek, Ralph Haggarty, Stephen J. Yanik, Mehmet Fatih TI Synapse microarray identification of small molecules that enhance synaptogenesis SO NATURE COMMUNICATIONS LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; ADHESION MOLECULES; ALZHEIMERS-DISEASE; NEURONS; NEUROLIGINS; PLASTICITY; DISORDERS; PLATFORM; BIOLOGY; PROTEIN AB Synaptic function is affected in many brain diseases and disorders. Technologies for large-scale synapse assays can facilitate identification of drug leads. Here we report a 'synapse microarray' technology that enables ultra-sensitive, high-throughput and quantitative screening of synaptogenesis. Our platform enables the induction of synaptic structures in regular arrays by precise positioning of non-neuronal cells expressing synaptic proteins, while allowing neurites to grow freely around these cells. The technology increases by tenfold the sensitivity of the traditional assays, and simultaneously decreases the time required to capture synaptogenic events by an order of magnitude. It is readily incorporated into multiwell formats compatible with industrial high-throughput screening platforms. Using this technology, we screened a chemical library, and identified novel histone deacetylase (HDAC) inhibitors that improve neuroligin-1-induced synaptogenesis by modulating class-I HDACs. We also found a structure-activity relationship for designing novel potent histone deacetylase inhibitors, which can be applied towards development of new therapeutics. C1 [Shi, Peng; Scott, Mark A.; Yanik, Mehmet Fatih] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Ghosh, Balaram; Wan, Dongpeng; Mazitschek, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Wissner-Gross, Zachary] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Haggarty, Stephen J.; Yanik, Mehmet Fatih] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Yanik, Mehmet Fatih] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Yanik, MF (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM yanik@mit.edu RI Mazitschek, Ralph/E-3741-2013; OI Mazitschek, Ralph/0000-0002-1105-689X; SHI, Peng/0000-0003-0629-4161 FU NIH [R01 NS066352]; NIH/NIDA [R01 DA028301]; Packard Fellowship; Stanley Medical Research Institute; Simons Foundation; Fannie and John Hertz Foundation FX We thank Peter Scheiffele (University of Basel) for NLG1 and AChE plasmid and Lance Kam (Columbia University, NY) for providing HEK293 cells. We thank Somponnat Sampattavanich and Joel Voldman for help with fabrication, and Matthew Angel for his comments on the manuscript. We thank Dan Fass, Thomas Nieland and Li-Huei Tsai for discussing the role of HDACs in synaptogenesis. This work is supported by NIH EUREKA Award (R01 NS066352), NIH/NIDA R01 DA028301, Packard Fellowship and the Stanley Medical Research Institute. P.S. is supported by a Simons Foundation research fellowship. Z.W.G. is supported by a Fannie and John Hertz Foundation fellowship. NR 49 TC 50 Z9 50 U1 3 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD OCT PY 2011 VL 2 AR 510 DI 10.1038/ncomms1518 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 844XV UT WOS:000296787300023 PM 22027590 ER PT J AU Cianfrocca, M Lee, S Von Roenn, J Rudek, MA Dezube, BJ Krown, SE Sparano, JA AF Cianfrocca, Mary Lee, Sandra Von Roenn, Jamie Rudek, Michelle A. Dezube, Bruce J. Krown, Susan E. Sparano, Joseph A. TI Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi's sarcoma: an Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE HIV infection; AIDS; Kaposi's sarcoma; Paclitaxel; Protease inhibitors ID ACTIVE ANTIRETROVIRAL THERAPY; NON-HODGKINS-LYMPHOMA; DRUG-INTERACTIONS; ADVANCED CANCER; HIV-1 PROTEASE; DNA-SEQUENCES; PHARMACOKINETICS; HERPESVIRUS; PHARMACODYNAMICS; CHEMOTHERAPY AB Purpose Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Methods Patients with advanced HIV-associated KS received paclitaxel (100 mg/m(2)) by intravenous infusion over 3 h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Results Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30%) had an objective response and median progression-free survival was 7.8 months (95% confidence interval, 5.6, 21.0 months). Conclusion Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy. C1 [Cianfrocca, Mary; Von Roenn, Jamie] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Lee, Sandra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Dezube, Bruce J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Krown, Susan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sparano, Joseph A.] Albert Einstein Coll Med, Montefiore Einstein Canc Ctr, Bronx, NY 10467 USA. RP Cianfrocca, M (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM m-cianfrocca@northwestern.edu FU Department of Health and Human Services; National Institutes of Health [CA23318, CA66636, CA21115, U01 CA121947] FX The authors thank Dr. Fayez Hamzeh for performing the pharmacokinetic analysis when he was a faculty member at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Baltimore, MD), Dr. Michelle Till for her scientific contributions leading to the design of the study and Dr. David Scadden for contributing patients to the study. Supported in part by grants from the Department of Health and Human Services and the National Institutes of Health CA23318 to the Eastern Cooperative Oncology Group (ECOG) statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center and chairman's office, U01 CA121947 to the AIDS Malignancy Consortium. NR 39 TC 12 Z9 12 U1 0 U2 4 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 OCT PY 2011 VL 68 IS 4 BP 827 EP 833 DI 10.1007/s00280-010-1509-4 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 849JR UT WOS:000297122300001 PM 21207228 ER PT J AU Yoon, HH Catalano, P Gibson, MK Skaar, TC Philips, S Montgomery, EA Hafez, MJ Powell, M Liu, G Forastiere, AA Benson, AB Kleinberg, LR Murphy, KM AF Yoon, H. H. Catalano, P. Gibson, M. K. Skaar, T. C. Philips, S. Montgomery, E. A. Hafez, M. J. Powell, M. Liu, G. Forastiere, A. A. Benson, A. B. Kleinberg, L. R. Murphy, K. M. TI Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Chemoradiation; Esophageal cancer; Radiation toxicity prediction; Single nucleotide polymorphism; Trimodality ID STRAND BREAK REPAIR; CELL LUNG-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; S-TRANSFERASE POLYMORPHISMS; NORMAL TISSUE COMPLICATIONS; ADVANCED COLORECTAL-CANCER; DNA-REPAIR; EXCISION-REPAIR; XPD POLYMORPHISMS; CHEMOTHERAPY AB Purpose Germline genetic variations may partly explain the clinical observation that normal tissue tolerance to radiochemotherapy varies by individual. Our objective was to evaluate the association between single-nucleotide polymorphisms (SNPs) in radiation/platinum pathways and serious treatment-related toxicity in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy. Methods In a multicenter clinical trial (E1201), 81 eligible treatment-naive subjects with resectable esophageal adenocarcinoma received cisplatin-based chemotherapy concurrent with radiotherapy, with planned subsequent surgical resection. Toxicity endpoints were defined as grade >3 radiation-related or myelosuppressive events probably or definitely related to therapy, occurring during or up to 6 weeks following the completion of radiochemotherapy. SNPs were analyzed in 60 subjects in pathways related to nucleotide/base excision- or double stranded break repair, or platinum influx, efflux, or detoxification. Results Grade >= 3 radiation-related toxicity (mostly dysphagia) and myelosuppression occurred in 18 and 33% of subjects, respectively. The variant alleles of the XRCC2 5' Xanking SNP (detected in 28% of subjects) and of GST-Pi Ile-105-Val (detected in 65% of subjects) were each associated with higher odds of serious radiation-related toxicity compared to the major allele homozygote (47% vs. 9%, and 31% vs. 0%, respectively; P = 0.005). No SNP was associated with myelosuppression. Conclusions This novel finding in a well-characterized cohort with robust endpoint data supports further investigation of XRCC2 and GST-Pi as potential predictors of radiation toxicity. C1 [Yoon, H. H.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. [Catalano, P.; Powell, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gibson, M. K.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Skaar, T. C.; Philips, S.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Montgomery, E. A.; Hafez, M. J.; Forastiere, A. A.; Kleinberg, L. R.; Murphy, K. M.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. [Liu, G.] Univ Toronto, Princess Margaret Hosp, Toronto, ON M5G 2C4, Canada. [Benson, A. B.] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. RP Yoon, HH (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM yoon.harry@mayo.edu RI Liu, Geoffrey/N-4421-2016 FU American Society of Clinical Oncology; National Institutes of Health [CA 90628-08U, CA 23318, CA 66636, CA 21115, CA 13650, CA 16116, CA 49883, CA 17145, CA39229] FX We thank M. Eileen Dolan, MD, for helpful discussion, and Karen J. Hanson, Candace Kostelec, and Carol Chami for administrative assistance. This work was supported by the American Society of Clinical Oncology [Young Investigator Award to H.H.Y.]; and National Institutes of Health [CA 90628-08U to H.H.Y., and CA 23318, CA 66636, CA 21115, CA 13650, CA 16116, CA 49883, CA 17145, and CA39229 to the Eastern Cooperative Oncology Group]. NR 52 TC 4 Z9 4 U1 0 U2 7 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 OCT PY 2011 VL 68 IS 4 BP 863 EP 870 DI 10.1007/s00280-011-1556-5 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 849JR UT WOS:000297122300005 PM 21286719 ER PT J AU Minturn, JE Evans, AE Villablanca, JG Yanik, GA Park, JR Shusterman, S Groshen, S Hellriegel, ET Bensen-Kennedy, D Matthay, KK Brodeur, GM Maris, JM AF Minturn, Jane E. Evans, Audrey E. Villablanca, Judith G. Yanik, Gregory A. Park, Julie R. Shusterman, Suzanne Groshen, Susan Hellriegel, Edward T. Bensen-Kennedy, Debra Matthay, Katherine K. Brodeur, Garrett M. Maris, John M. TI Phase I trial of lestaurtinib for children with refractory neuroblastoma: a new approaches to neuroblastoma therapy consortium study SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Neuroblastoma; Receptor tyrosine kinase; Targeted therapy; Lestaurtinib; Signal transduction ID TYROSINE-KINASE INHIBITOR; HIGH-RISK NEUROBLASTOMA; ACUTE MYELOID-LEUKEMIA; INTENSIVE CHEMOTHERAPY; ANTITUMOR EFFICACY; CEP-751 KT-6587; FLT3 INHIBITOR; EXPRESSION; TRANSPLANTATION; INVASIVENESS AB Purpose TrkB acts as an oncogenic kinase in a subset of human neuroblastomas. Lestaurtinib, a multi-kinase inhibitor with potent activity against Trk kinases, has demonstrated activity in preclinical models of neuroblastoma. Methods Patients with refractory high-risk neuroblastoma received lestaurtinib twice daily for 5 days out of seven in 28-day cycles, starting at 70% of the adult recommended Phase 2 dose. Lestaurtinib dose was escalated using a 3 + 3 design. Pharmacokinetics and plasma phospho-TrkB inhibitory activity were evaluated in the first cycle. Results Forty-seven subjects were enrolled, and 10 dose levels explored starting at 25 mg/M(2)/dose BID. Forty-six subjects were evaluable for response, and 42 subjects were fully evaluable for determination of dose escalation. Asymptomatic and reversible grade 3-4 transaminase elevation was dose limiting in 4 subjects. Reversible pancreatitis (grade 2) was observed in 3 subjects after prolonged treatment at higher dose levels. Other toxicities were mild and reversible. Pharmacokinetic analyses revealed rapid drug absorption, however inter-patient variability was large. Plasma inhibition of phospho-TrkB activity was observed 1 h post-dosing at 85 mg/M(2) with uniform inhibition at 120 mg/M(2). There were two partial responses and nine subjects had prolonged stable disease at dose levels >= 5, (median: 6 cycles). A biologically effective and recommended phase 2 dose of 120 mg/M(2)/dose BID was established. Conclusions Lestaurtinib was well tolerated in patients with refractory neuroblastoma, and a dose level sufficient to inhibit TrkB activity was established. Safety and signs of activity at the higher dose levels warrant further evaluation in neuroblastoma. C1 [Brodeur, Garrett M.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Minturn, Jane E.; Evans, Audrey E.; Brodeur, Garrett M.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Minturn, Jane E.; Evans, Audrey E.; Brodeur, Garrett M.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Villablanca, Judith G.; Groshen, Susan] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Villablanca, Judith G.; Groshen, Susan] Univ So Calif, Keck Sch Med, Dept Biostat, Los Angeles, CA 90033 USA. [Villablanca, Judith G.; Groshen, Susan] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Yanik, Gregory A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Yanik, Gregory A.] CS Mott Childrens Hosp, Ann Arbor, MI USA. [Park, Julie R.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Park, Julie R.] Univ Washington, Seattle, WA 98195 USA. [Shusterman, Suzanne] Childrens Hosp Boston, Dept Pediat, Boston, MA USA. [Shusterman, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hellriegel, Edward T.; Bensen-Kennedy, Debra] Cephalon Inc, Dept Drug Safety & Disposit, Frazer, PA USA. [Hellriegel, Edward T.; Bensen-Kennedy, Debra] Cephalon Inc, Dept Clin Res, Frazer, PA USA. [Hellriegel, Edward T.; Bensen-Kennedy, Debra] Cephalon Inc, Dept Oncol, Frazer, PA USA. [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. RP Maris, JM (reprint author), Childrens Hosp Philadelphia, Div Oncol, 3501 Civ Ctr Blvd,CTRB 3060, Philadelphia, PA 19104 USA. EM brodeur@email.chop.edu; maris@chop.edu FU NIH [P01-CA81403, P01-CA97323, R01-CA-094194]; Giulio D'Angio Endowed Chair in Neuroblastoma Research (Maris); NIH/NCRR UCSF-CTSI [UL1 RR024131]; Alex's Lemonade Stand Foundation; Children's Neuroblastoma Cancer Foundation; Dougherty Family Foundation; Evan T.J. Dunbar Memorial Foundation; Neuroblastoma Children's Cancer Society FX This work was supported by NIH Program Project Grants P01-CA81403 (Childrens Hospital Los Angeles, PI: Seeger) and P01-CA97323 (Brodeur), R01-CA-094194 (Brodeur), and the Giulio D'Angio Endowed Chair in Neuroblastoma Research (Maris), NIH/NCRR UCSF-CTSI Grant UL1 RR024131, Alex's Lemonade Stand Foundation, Children's Neuroblastoma Cancer Foundation, Dougherty Family Foundation, Evan T.J. Dunbar Memorial Foundation, Neuroblastoma Children's Cancer Society. NR 26 TC 36 Z9 37 U1 0 U2 2 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 OCT PY 2011 VL 68 IS 4 BP 1057 EP 1065 DI 10.1007/s00280-011-1581-4 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 849JR UT WOS:000297122300026 PM 21340605 ER PT J AU Rader, F Van Wagoner, DR Ellinor, PT Gillinov, AM Chung, MK Costantini, O Blackstone, EH AF Rader, Florian Van Wagoner, David R. Ellinor, Patrick T. Gillinov, A. Marc Chung, Mina K. Costantini, Otto Blackstone, Eugene H. TI Influence of Race on Atrial Fibrillation After Cardiac Surgery SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; race/ethnicity; cardiac surgery; epidemiology; risk factors ID CONGESTIVE-HEART-FAILURE; RACIAL-DIFFERENCES; EUROPEAN ANCESTRY; RANDOMIZED-TRIAL; RISK; PREVALENCE; VARIANTS; PREDICTORS; PREVENTION; MORTALITY AB Background-Despite having fewer risk factors for atrial fibrillation (AF), white patients have a greater prevalence of AF in the community than black patients, and a genetic basis has been postulated. However, it is unknown whether occurrence of new-onset AF after cardiac surgery is different in white versus black patients, and secondarily, other non-Caucasian patients. Methods and Results-From 1995 through 2005, 20 282 white, 1323 black, and 1919 other non-Caucasian patients in sinus rhythm underwent coronary artery bypass grafting with or without valve surgery. To adjust for clinical and socioeconomic confounders, we performed propensity-adjusted analyses; 7093 white patients (35%) had postoperative AF, compared with 255 (22%) black patients and 550 (29%) other non-Caucasians (P<0.0001). Whites were older than black patients, had higher socioeconomic position, and greater left atrial size but were less likely to have hypertension or congestive heart failure. In 847 propensity-matched patient pairs, postoperative AF occurred more frequently in white than in black patients (odds ratio, 1.74; 95% confidence interval, 1.7-1.78). Other than higher occurrence of bradycardia requiring pacing and reintubation in white patients, occurrence of other postoperative complications, hospital mortality, and length of postoperative stay were similar. Age and valvular surgery were the strongest predictors of AF irrespective of race. Conclusions-White patients had a markedly higher risk of postoperative AF than black and other non-Caucasian patients. The cause for racial differences of arrhythmic risk is unknown, but a genetic predisposition is plausible. Our results have implications for risk stratification and mechanistic understanding of postoperative AF. (Circ Arrhythm Electrophysiol. 2011;4:644-652.) C1 [Rader, Florian; Costantini, Otto] Case Western Reserve Univ, Heart & Vasc Ctr, Cleveland, OH 44118 USA. [Van Wagoner, David R.; Chung, Mina K.] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 USA. [Van Wagoner, David R.; Chung, Mina K.] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Blackstone, Eugene H.] Cleveland Clin, Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Blackstone, Eugene H.] Cleveland Clin, Inst Heart & Vasc, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. RP Rader, F (reprint author), Case Western Reserve Univ, Heart & Vasc Ctr, MetroHlth Campus,2500 MetroHlth Dr, Cleveland, OH 44118 USA. EM frader@metrohealth.org RI Van Wagoner, David/C-6783-2008 OI Van Wagoner, David/0000-0001-8250-9828 FU National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [RR024990]; NIH [HL092577, DA027021, HL104156, HL105780]; Fondation Leducq (European-North American Atrial Fibrillation Research Alliance, ENAFRA) [07/CVD-03]; [NIH-HL090620] FX This publication was made possible in part by grant No. RR024990 (Dr Rader) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Information on NCRR is available at http://www.ncrr.nih.gov. This work was also supported by grants from the NIH to Dr Ellinor (HL092577, DA027021, HL104156, HL105780) and Dr Chung (NIH-HL090620) and by a grant to Drs Van Wagoner and Chung from the Fondation Leducq (European-North American Atrial Fibrillation Research Alliance, ENAFRA, 07/CVD-03). NR 35 TC 13 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD OCT PY 2011 VL 4 IS 5 BP 644 EP U107 DI 10.1161/CIRCEP.111.962670 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841QB UT WOS:000296526400015 PM 21841189 ER PT J AU Ademi, Z Reid, CM Hollingsworth, B Stoelwinder, J Steg, PG Bhatt, DL Vale, M Liew, D AF Ademi, Zanfina Reid, Christopher M. Hollingsworth, Bruce Stoelwinder, Johannes Steg, Ph Gabriel Bhatt, Deepak L. Vale, Margarite Liew, Danny CA Reach Registry Investigators TI Cost-Effectiveness of Optimizing Use of Statins in Australia: Using Outpatient Data From the REACH Registry SO CLINICAL THERAPEUTICS LA English DT Article DE coronary artery disease; cost-effectiveness analysis; registries; statins ID PHARMACEUTICAL BENEFITS SCHEME; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; EVENT RATES; ATHEROTHROMBOTIC DISEASE; ECONOMIC-IMPLICATIONS; POPULATION; METAANALYSIS; PERSPECTIVE; PERSISTENCE AB Background: Although few cardiovascular registries report the costs of illness or cost-effectiveness of health interventions, such information is critical to inform the effective and cost-effective management of cardiovascular disease, particularly if drawn from population-based registries, which more accurately reflect clinical practice and follow up patients for much longer than clinical trials. Objective: The goal of this study was to estimate the cost-effectiveness of closing the statin "treatment gap" in the secondary prevention of coronary artery disease (CAD) in Australia. Methods: A decision analysis Markov model was developed with yearly cycles and the health states of alive or dead. Using data from the Australian Reduction of Atherothrombosis for Continued Health Registry, the model compared current statin coverage (82%) in the secondary prevention of CAD (the current group) with a hypothetical situation of 100% coverage (the improved group). The 18% gap was filled with use of generic statins. Data from a recent meta-analysis were used to estimate the benefits of statin use in terms of reducing recurrent cardiovascular events and death. Government reimbursement data from 2011 were used to calculate direct health care costs. The cost of the intervention to improve statin coverage was assumed to be $250 per person. Years of life lived and costs were discounted at 5% annually. All values are given in Australian dollars. Results: Among the 2058 subjects in the current group, the model estimated that there would be 106 nonfatal myocardial infractions, 68 nonfatal strokes, and 275 deaths over 5 years. In the improved group, all of whom took statins, the corresponding numbers were 101, 65, and 259, equating to numbers needed to treat of 426, 639, and 127, respectively. Over the 5 years, there would be 0.018 life-years gained (discounted) at a net cost of $546 (discounted) per person. These equated to an incremental cost-effectiveness ratio of $29,717 per life-year gained. Conclusion: The results suggest that for patients with CAD, maximizing coverage with statins, in line with evidence-based recommendations, represents a cost-effective means of secondary prevention. (Clin Ther. 2011;33:1456-1465) (C) 2011 Elsevier HS Journals, Inc. All rights reserved. C1 [Ademi, Zanfina; Liew, Danny] Univ Melbourne, Dept Med RMH, Melbourne EpiCtr, Melbourne, Vic, Australia. [Ademi, Zanfina; Reid, Christopher M.; Stoelwinder, Johannes] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Hollingsworth, Bruce] Monash Univ, Ctr Hlth Econ, Melbourne, Vic 3004, Australia. [Steg, Ph Gabriel] Univ Paris 07, INSERM, U698, AP HP, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Vale, Margarite] Univ Melbourne, St Vincents Hosp, Melbourne, Vic, Australia. RP Ademi, Z (reprint author), Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne EpiCtr, 7 East, Parkville, Vic 3050, Australia. EM zademi@unimelb.edu.au OI Hollingsworth, Bruce/0000-0002-4314-6523; Liew, Danny/0000-0002-0131-623X FU Monash University; Australian Research Council [LP077532]; sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan) FX This work was supported by Monash University. In addition, it was supported in part by the Australian Research Council Linkage Project LP077532. The international REACH registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan) and is endorsed by the World Heart Federation. The REACH registry enforces a no-ghost-writing policy. A complete list of the REACH Registry Investigators appears in JAMA (2006;295:180-189). NR 45 TC 3 Z9 3 U1 2 U2 7 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD OCT PY 2011 VL 33 IS 10 BP 1456 EP 1465 DI 10.1016/j.clinthera.2011.08.004 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848GE UT WOS:000297037800013 PM 21982384 ER PT J AU Alexander, BM Mehta, MP AF Alexander, Brian M. Mehta, Minesh P. TI Role of isocitrate dehydrogenase in glioma SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE cancer metabolism; glioma; isocitrate dehydrogenase ID INTEGRATED GENOMIC ANALYSIS; PROLYL HYDROXYLASE REACTION; ACUTE MYELOID-LEUKEMIA; CODON 132 MUTATION; IDH2 MUTATIONS; D-2-HYDROXYGLUTARIC ACIDURIA; OXIDATIVE DAMAGE; CELLULAR DEFENSE; ONCOMETABOLITE 2-HYDROXYGLUTARATE; NEURONAL APOPTOSIS AB Recently, the isocitrate dehydrogenase (IDH) enzymes have become a focal point for research aimed at understanding the biology of glioma and identifying novel targets for therapy. Following the publication of a landmark genetic sequencing study in 2008, which identified IDH1 as a frequently mutated gene in glioblastoma, much work has been carried out to further characterize the frequency, associations and clinical implications of IDH1/2 mutations. Mutations in IDH genes are thought to occur early in tumorigenesis and define a subgroup of glioma that are characterized by specific metabolic changes and improved prognosis. At present, assays identifying tumors with IDH1 mutations are clinically useful as prognostic markers. While the mechanisms linking IDH1/2 mutations to tumor development are still under investigation, the cellular milieu created by these mutations offers potential targets for the development of novel therapeutics. C1 [Mehta, Minesh P.] Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, Chicago, IL 60611 USA. [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Mehta, MP (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Radiat Oncol, NMH Arkes Family Pavil Suite 1820,676 N St Clair, Chicago, IL 60611 USA. EM mineshpmehta@gmail.com OI mehta, minesh/0000-0002-4812-5713 NR 95 TC 9 Z9 10 U1 0 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD OCT PY 2011 VL 11 IS 10 BP 1399 EP 1409 DI 10.1586/ERN.11.134 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 838KO UT WOS:000296289300013 PM 21955197 ER PT J AU Wilens, TE Morrison, NR Prince, J AF Wilens, Timothy E. Morrison, Nicholas R. Prince, Jefferson TI An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE adult; amphetamine; antidepressants; atomoxetine; attention-deficit/hyperactivity disorder; methylphenidate; pharmacotherapy; stimulants ID DEFICIT HYPERACTIVITY DISORDER; PLACEBO-CONTROLLED TRIAL; MIXED AMPHETAMINE SALTS; RANDOMIZED CONTROLLED-TRIAL; MINIMAL-BRAIN-DYSFUNCTION; SUBSTANCE USE DISORDERS; DOUBLE-BLIND TRIAL; LONG-TERM SAFETY; EXTENDED-RELEASE METHYLPHENIDATE; ADJUNCT OROS-METHYLPHENIDATE AB Adults with attention-deficit/hyperactivity disorder (ADHD) are more frequently presenting for diagnosis and treatment. Medication is considered to be appropriate among available treatments for ADHD; however, the evidence supporting the use of pharmacotherapeutics for adults with ADHD remains less established. In this article, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. In adults with ADHD, short-term improvements in symptomatology have been documented through the use of stimulants and antidepressants. Studies suggest that methylphenidate and amphetamine maintained an immediate onset of action, whereas the ADHD response to the nonstimulants appeared to be delayed. At a group level, there appears to be some, albeit not entirely consistent, dose-dependent responses to amphetamine and methylphenidate. Generally speaking, variability in diagnostic criteria, dosing parameters and response rates between the various studies was considerable, and most studies were of a relatively short duration. The aggregate literature shows that the stimulants and catecholaminergic nonstimulants investigated had a clinically significant beneficial effect on treating ADHD in adults. C1 [Wilens, Timothy E.; Morrison, Nicholas R.; Prince, Jefferson] Massachusetts Gen Hosp, Child Psychiat Serv, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Wilens, Timothy E.; Prince, Jefferson] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Prince, Jefferson] N Shore Childrens Hosp, Salem, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. EM twilens@partners.org FU NIH; Abbott; Lilly; McNeil; Merck; NIH (NIDA); American Psychiatric Association; MGH Psychiatric Academy; Tower Foundation; Norman H. Read Trust; Shire; American Academy of Child and Adolescent Psychiatry; GlaxoSmithKline; Forest; [K24 DA016264] FX This work was supported by the NIH and by K24 DA016264 to Timothy Wilens. Timothy Wilens receives or has received grant support from the following sources: Abbott, Lilly, McNeil, Merck, NIH (NIDA) and Shire. He has also been a speaker for the following: Lilly, McNeil, Novartis and Shire, and is or has been a consultant for: Abbott, Astra-Zeneca, Euthymics, Lilly, McNeil, Merck, NIH, Novartis and Shire. Timothy Wilens has a published book with Guilford Press: Straight Talk About Psychiatric Medications for Kids.; In the last 18 months, Jefferson Prince has received support from the American Academy of Child and Adolescent Psychiatry, the American Psychiatric Association and the MGH Psychiatric Academy. Jefferson Prince has also received grant monies from the Tower Foundation and the Norman H. Read Trust, and has received monies for a CME program sponsored by Shire and Lilly. Over Jefferson Prince's professional career he was at one time on the speaker's bureau for Ortho-McNeil, Celltech, Lilly and Forest; has acted as a consultant for Ortho-McNeil, Shire, Lilly, Forest, Abbott, Pfizer and GlaxoSmithKline; and has received grant monies from the American Academy of Child and Adolescent Psychiatry, Lilly, GlaxoSmithKline and Forest. NR 188 TC 45 Z9 48 U1 6 U2 26 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD OCT PY 2011 VL 11 IS 10 BP 1443 EP 1465 DI 10.1586/ERN.11.137 PG 23 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 838KO UT WOS:000296289300017 PM 21955201 ER PT J AU Kohlschutter, A Eichler, F AF Kohlschuetter, Alfried Eichler, Florian TI Childhood leukodystrophies: a clinical perspective SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE brain white matter; children; degenerative brain disease; metabolic genetic disease; MRI ID X-LINKED ADRENOLEUKODYSTROPHY; MERZBACHER-LIKE-DISEASE; GLOBOID-CELL LEUKODYSTROPHY; BONE-MARROW-TRANSPLANTATION; AICARDI-GOUTIERES-SYNDROME; INFANTILE KRABBES-DISEASE; WHITE-MATTER DISEASE; UMBILICAL-CORD BLOOD; METACHROMATIC LEUKODYSTROPHY; FOLLOW-UP AB Leukodystrophies are white matter disorders that are genetic in nature. In the young, they represent an important cause of progressive neurological disability. They are frequently recognized on MRI, but their identification remains a challenge. Their diagnosis is important for prognostication, palliative and experimental treatment, as well as family screening. The diagnostic strategy rests upon clinical clues and MRI patterns, complemented by appropriately selected electrophysiological and laboratory testing. Considerable overlap exists between white and gray matter disease, as neuronal degeneration will result in myelin loss. An understanding of the pathophysiology and natural disease evolution is necessary to understand the risks and benefits of experimental and palliative treatments. C1 [Kohlschuetter, Alfried] Childrens Hosp Univ Med Ctr, Hamburg, Germany. [Eichler, Florian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kohlschutter, A (reprint author), Childrens Hosp Univ Med Ctr, Hamburg, Germany. EM kohlschuetter@uke.uni-hamburg.de FU EU FX Alfried Kohlschutter receives financial support from LeukoTreat (http://leukotreat.eu), a project of the EU to develop treatment strategies for leukodystrophies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 79 TC 25 Z9 26 U1 0 U2 12 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD OCT PY 2011 VL 11 IS 10 BP 1485 EP 1496 DI 10.1586/ERN.11.135 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 838KO UT WOS:000296289300019 PM 21955203 ER PT J AU Hideshima, T Anderson, KC AF Hideshima, Teru Anderson, Kenneth C. TI Novel therapies in MM: from the aspect of preclinical studies SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Multiple myeloma; Novel therapy; Microenvironment ID MULTIPLE-MYELOMA CELLS; REGULATES AGGRESOME FORMATION; DEPENDENT KINASE INHIBITOR; FIBROBLAST-GROWTH-FACTOR; KAPPA-B PATHWAY; PROTEASOME INHIBITOR; ANTIMYELOMA ACTIVITY; IN-VITRO; MONOCLONAL-ANTIBODY; HEMATOLOGIC MALIGNANCIES AB During the last decade, thalidomide, lenalidomide, and bortezomib have been approved by the US Food and Drug Administration for the treatment of MM; however, MM remains incurable. The development and progression of multiple myeloma (MM) is a complex multi-step process involving genetic abnormalities in tumor cells at both early and late stages. Moreover, soluble factors and cell-cell contact within the tumor bone marrow (BM) microenvironment promotes MM cell growth, survival, and drug resistance. A number of novel agents targeting both tumor cells and growth factors in the BM milieu have been developed. Currently they are under evaluation in preclinical studies, as single agents and/or in combination, to improve outcome of MM patients. C1 [Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hideshima, Teru; Anderson, Kenneth C.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM teru_hideshima@dfci.harvard.edu NR 77 TC 19 Z9 20 U1 1 U2 2 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD OCT PY 2011 VL 94 IS 4 BP 344 EP 354 DI 10.1007/s12185-011-0917-5 PG 11 WC Hematology SC Hematology GA 850OQ UT WOS:000297205400005 PM 21881879 ER PT J AU Chaux, A Amin, M Cubilla, AL Young, RH AF Chaux, Alcides Amin, Mahul Cubilla, Antonio L. Young, Robert H. TI Metastatic Tumors to the Penis: A Report of 17 Cases and Review of the Literature SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE penile cancer; penile metastasis; penile secondary tumor; priapism; outcome ID SQUAMOUS-CELL CARCINOMA; RECTAL-CARCINOMA; METACHRONOUS METASTASIS; RADIATION-THERAPY; BLADDER-CANCER; GLANS-PENIS; SECONDARY; PRIAPISM; ADENOCARCINOMA; MALIGNANCIES AB This study presents clinicopathologic and outcome features of 17 patients with metastatic tumor to the penis. Primary sites and histological types were as follows: 6 urothelial carcinomas of urinary bladder, 4 prostatic carcinomas (2 adenocarcinomas and 2 adenosquamous carcinomas), 2 colorectal adenocarcinomas, 2 pulmonary carcinomas (1 squamous cell carcinoma and 1 small cell carcinoma), 1 squamous cell carcinoma of base of the tongue, 1 cutaneous malignant melanoma, and 1 acute myeloid leukemia. Literature review revealed similar distribution of organ sites in 437 cases. Most of our tumors were metachronous. Interval between primary and penile metastasis ranged from 3 to 60 months (mean 16 months). Most of the patients presented with a penile mass. Priapism was observed in 4 patients. The shaft was the commonest anatomical site involved (12 cases). Tumor emboli were usually found in the erectile tissues (14 cases), mainly corpora cavernosa. A total of 14 patients died of disseminated disease. Time interval between primary tumor and penile metastasis ranged from 3 to 60 months (mean 19 months) and between diagnosis of penile metastasis and death ranged from 0.25 to 18 months (mean 6 months), significantly shorter (P = .0058). Patients presented a median survival of 18 months from primary treatment and 5 months after diagnosis of penile metastasis. None of the patients who died of disseminated cancer lived more than 18 months after pathological diagnosis. Clinical evidence of penile involvement in a patient with a known malignancy is an ominous sign and should alert the clinicians to the dismal prognosis. C1 [Chaux, Alcides; Cubilla, Antonio L.] Inst Patol & Invest, Asuncion, Paraguay. [Amin, Mahul] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Cubilla, AL (reprint author), Inst Patol & Invest, Martin Brizuela 325, Asuncion, Paraguay. EM acubilla@institutodepatologia.com.py OI Chaux, Alcides/0000-0002-5824-9867 NR 69 TC 21 Z9 23 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2011 VL 19 IS 5 BP 597 EP 606 DI 10.1177/1066896909350468 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 848TL UT WOS:000297077900007 PM 20075023 ER PT J AU Bonilha, VL Rayborn, ME Li, Y Grossman, GH Berson, EL Hollyfield, JG AF Bonilha, Vera L. Rayborn, Mary E. Li, Yong Grossman, Gregory H. Berson, Eliot L. Hollyfield, Joe G. TI Histopathology and Functional Correlations in a Patient with a Mutation in RPE65, the Gene for Retinol Isomerase SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LEBER CONGENITAL AMAUROSIS; THERAPY RESTORES VISION; VISUAL CYCLE; PIGMENT EPITHELIUM; RETINITIS-PIGMENTOSA; CHILDHOOD BLINDNESS; CANINE MODEL; BRIARD DOGS; MOUSE MODEL; VITAMIN-A AB PURPOSE. Here the authors describe the structural features of the retina and retinal pigment epithelium (RPE) in postmortem donor eyes of a 56-year-old patient with a homozygous missense RPE65 mutation (Ala132Thr) and correlate the pathology with the patient's visual function last measured at age 51. METHODS. Eyes were enucleated within 13.5 hours after death. Representative areas from the macula and periphery were processed for light and electron microscopy. Immunofluorescence was used to localize the distribution of RPE65, rhodopsin, and cone arrestin. The autofluorescence in the RPE was compared with that of two normal eyes from age-similar donors. RESULTS. Histologic examination revealed the loss of rods and cones across most areas of the retina, attenuated retinal vessels, and RPE thinning in both eyes. A small number of highly disorganized cones were present in the macula that showed simultaneous labeling with cone arrestin and red/green or blue opsin. RPE65 immunoreactivity and RPE autofluorescence were reduced compared with control eyes in all areas studied. Rhodopsin labeling was observed in rods in the far periphery. The optic nerve showed a reduced number of axons. CONCLUSIONS. The clinical findings of reduced visual acuity, constricted fields, and reduced electroretinograms (ERGs) 5 years before death correlated with the small number of cones present in the macula and the extensive loss of photoreceptors in the periphery. The absence of autofluorescence in the RPE suggests that photoreceptor cells were probably missing across the retina for extended periods of time. Possible mechanisms that could lead to photoreceptor cell death are discussed. (Invest Ophthalmol Vis Sci. 2011;52:8381-8392) DOI: 10.1167/iovs.117973 C1 [Bonilha, Vera L.; Rayborn, Mary E.; Li, Yong; Grossman, Gregory H.; Hollyfield, Joe G.] Cleveland Clin Lerner Coll Med, Cole Eye Inst, Dept Ophthalmol, Cleveland, OH USA. [Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Bonilha, VL (reprint author), Cleveland Clin, Dept Ophthalm Res, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bonilhav@ccf.org OI Grossman, Gregory/0000-0003-1511-7028 FU Foundation Fighting Blindness Histopathology [F-OH01-1102-0231]; Foundation Fighting Blindness; Research to Prevent Blindness; National Institutes of Health [R01EY014240-08, 3R21EY017153-02S1] FX Supported by The Foundation Fighting Blindness Histopathology Grant F-OH01-1102-0231 (JGH), Research Center Grants from The Foundation Fighting Blindness (JGH, ELB), Research to Prevent Blindness Unrestricted Grants (JGH), and National Institutes of Health Grants R01EY014240-08 (JGH) and 3R21EY017153-02S1 (VLB). NR 62 TC 3 Z9 3 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2011 VL 52 IS 11 BP 8381 EP 8392 DI 10.1167/iovs.11-7973 PG 12 WC Ophthalmology SC Ophthalmology GA 846MN UT WOS:000296907700020 PM 21931134 ER PT J AU Hu, YQ Ledoux, WR Fassbind, M Rohr, ES Sangeorzan, BJ Haynor, D AF Hu, Yangqiu Ledoux, William R. Fassbind, Michael Rohr, Eric S. Sangeorzan, Bruce J. Haynor, David TI Multi-Rigid Image Segmentation and Registration for the Analysis of Joint Motion From Three-Dimensional Magnetic Resonance Imaging SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE joint motion; MRI; segmentation; registration; visualization ID ANKLE JOINT; SUBTALAR; KINEMATICS; FOOT; MR; COMPLEX AB We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo magnetic resonance imaging (MRI) scans and its application to the analysis of foot and ankle joint motion. Using an MRI-compatible positioning device, a foot was scanned in a single neutral and seven other positions ranging from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. A segmentation method combining graph cuts and level set was developed. In the subsequent registration step, a separate rigid body transformation for each bone was obtained by registering the neutral position dataset to each of the other ones, which produced an accurate description of the motion between them. The segmentation algorithm allowed a user to interactively delineate 14 foot bones in the neutral position volume in less than 30 min total (user and computer processing unit [CPU]) time. Registration to the seven other positions took approximately 10 additional minutes of user time and 5.25 h of CPU time. For validation, our results were compared with those obtained from 3DViewnix, a semiautomatic segmentation program. We achieved excellent agreement, with volume overlap ratios greater than 88% for all bones excluding the intermediate cuneiform and the lesser metatarsals. For the registration of the neutral scan to the seven other positions, the average overlap ratio is 94.25%, while the minimum overlap ratio is 89.49% for the tibia between the neutral position and position 1, which might be due to different fields of view (FOV). To process a single foot in eight positions, our tool requires only minimal user interaction time (less than 30 min total), a level of improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications. [DOI: 10.1115/1.4005175] C1 [Hu, Yangqiu; Haynor, David] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Hu, Yangqiu; Haynor, David] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Ledoux, William R.; Fassbind, Michael; Rohr, Eric S.; Sangeorzan, Bruce J.] VA Ctr Excellence Limb Loss Prevent & Prosthet En, Seattle, WA 98108 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.; Sangeorzan, Bruce J.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [5P60AR048093-03]; Department of Veterans Affairs [A2661C] FX This research was partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases under Grant 5P60AR048093-03, and by the Department of Veterans Affairs, Rehabilitation Research and Development Grant A2661C. NR 34 TC 6 Z9 6 U1 1 U2 8 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 2011 VL 133 IS 10 AR 101005 DI 10.1115/1.4005175 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 846CN UT WOS:000296874900005 PM 22070330 ER PT J AU Keating, AM Jacobs, DS AF Keating, Anne M. Jacobs, Deborah S. TI Anti-VEGF Treatment of Corneal Neovascularization SO OCULAR SURFACE LA English DT Article DE anti-VEGF agents; bevacizumab; corneal neovascularization; intravitreal injection; ranibizumab; subconjunctival injection; vascular endothelial growth factor (VEGF); VEGF inhibitors ID ENDOTHELIAL GROWTH-FACTOR; SCLERAL CONTACT-LENS; SUBCONJUNCTIVAL BEVACIZUMAB; TOPICAL BEVACIZUMAB; MACULAR DEGENERATION; GRAFT FAILURE; SOLID TUMORS; THERAPY; ANGIOGENESIS; DISEASE AB Vascular endothelial growth factor (VEGF) is an angiogenic factor shown to be a critical secreted cytokine in tumorigenesis and retinal neovascularization (NV). Currently, there are two anti-VEGF agents, pegaptanib and ranizumab, approved by the United States Food and Drug Administration (FDA) for intravitreal use in the treatment of wet age-related macular degeneration (AMD). Bevacizumab is FDA-approved for intravenous administration in the treatment of several cancers and is in widespread use, off-label, as an intravitreal injection to treat a variety of retinal pathologies. Animal studies demonstrate the role of VEGF in corneal NV. There are now a number of human case series reporting the use of anti-VEGF agents, primarily bevacizumab, to treat corneal NV. This review summarizes reports to date on the use of anti-VEGF agents in the treatment of corneal NV in humans, noting the limitations of current data and the need for further studies. The experience of one clinician with the use of an anti-VEGF drug in the treatment of active corneal NV is presented. C1 [Jacobs, Deborah S.] Boston Fdn Sight, Needham, MA 02494 USA. [Keating, Anne M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Jacobs, DS (reprint author), Boston Fdn Sight, 464 Hillside Ave,Suite 205, Needham, MA 02494 USA. EM djacobs@bostonsight.org FU Boston Foundation for Sight FX Financial Disclosures: None. Dr. Jacobs is a salaried, full-time employee of 501(c)3 Boston Foundation for Sight. Dr. Keating is employed by Essentia Health, Department of Ophthalmology, Fargo, ND. Neither author has any financial or proprietary interest in any contact lens or prosthetic device, or in any concept or product discussed in this article. NR 48 TC 15 Z9 18 U1 0 U2 9 PU ETHIS COMMUNICATINS, INC PI NEW YORK PA 75 MAIDEN LANE, STE 408, NEW YORK, NY 10038 USA SN 1542-0124 J9 OCUL SURF JI Ocul. Surf. PD OCT PY 2011 VL 9 IS 4 BP 227 EP 238 PG 12 WC Ophthalmology SC Ophthalmology GA 841CF UT WOS:000296489200005 PM 22023817 ER PT J AU Hetz, C Martinon, F Rodriguez, D Glimcher, LH AF Hetz, Claudio Martinon, Fabio Rodriguez, Diego Glimcher, Laurie H. TI THE UNFOLDED PROTEIN RESPONSE: INTEGRATING STRESS SIGNALS THROUGH THE STRESS SENSOR IRE1 alpha SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ENDOPLASMIC-RETICULUM-STRESS; TRANSCRIPTION FACTOR XBP-1; PLASMA-CELL DIFFERENTIATION; MARINESCO-SJOGREN-SYNDROME; PANCREATIC BETA-CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; INFLAMMATORY-BOWEL-DISEASE; MESSENGER-RNA TRANSLATION; ER-STRESS; MITOCHONDRIAL APOPTOSIS AB Hetz C, Martinon F, Rodriguez D, Glimcher LH. The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1 alpha. Physiol Rev 91: 1219-1243, 2011; doi: 10.1152/physrev.00001.2011.-Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the nucleus and cytosol to restore ER homeostasis. Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1 alpha), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). IRE1 alpha signaling is a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, here referred to as the UPRosome. Here we provide an overview of the signaling and regulatory mechanisms underlying IRE1 alpha function and discuss the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis. C1 [Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Harvard Sch Publ Hlth,Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. Univ Chile, Ctr Mol Studies Cell, Inst Biomed Sci, Santiago, Chile. Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago 7, Chile. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Ctr Infect & Immun Lausanne, Epalinges, Switzerland. RP Glimcher, LH (reprint author), Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Harvard Sch Publ Hlth,Dept Med, FXB Bldg,Rm 205,651 Huntington Ave, Boston, MA 02115 USA. EM chetz@med.uchile.cl; lglimche@hsph.harvard.edu RI Martinon, Fabio/A-5575-2009; Hetz, Claudio/I-1900-2013 OI Martinon, Fabio/0000-0002-6969-822X; Hetz, Claudio/0000-0001-7724-1767 FU FONDECYT [1100176, 3100033]; Millennium Institute [P09-015-F]; Michael J. Fox Foundation for Parkinson's Research; ICGEB; Alzheimer's Disease Foundation; CHDI Foundation; FONDAP [15010006]; Swiss National Science Foundation [31003A_130476]; National Institute on Aging [AI-32412]; Leila and Harold Mathers Foundation FX This work was supported by the following: FONDECYT Grant 1100176, Millennium Institute Grant P09-015-F, Michael J. Fox Foundation for Parkinson's Research, ICGEB, Alzheimer's Disease Foundation, CHDI Foundation, and FONDAP Grant 15010006 (to C. Hetz); FONDECYT Grant 3100033 (to D. Rodriguez); Swiss National Science Foundation Grant 31003A_130476 (to F. Martinon); and National Institute on Aging Grant AI-32412, the Leila and Harold Mathers Foundation, and an anonymous foundation (to L. H. Glimcher). NR 207 TC 184 Z9 189 U1 3 U2 36 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 EI 1522-1210 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 2011 VL 91 IS 4 BP 1219 EP 1243 DI 10.1152/physrev.00001.2011 PG 25 WC Physiology SC Physiology GA 842BM UT WOS:000296561600003 PM 22013210 ER PT J AU Buzon, MJ Codoner, FM Frost, SDW Pou, C Puertas, MC Massanella, M Dalmau, J Llibre, JM Stevenson, M Blanco, J Clotet, B Paredes, R Martinez-Picado, J AF Buzon, Maria J. Codoner, Francisco M. Frost, Simon D. W. Pou, Christian Puertas, Maria C. Massanella, Marta Dalmau, Judith Llibre, Josep M. Stevenson, Mario Blanco, Julia Clotet, Bonaventura Paredes, Roger Martinez-Picado, Javier TI Deep Molecular Characterization of HIV-1 Dynamics under Suppressive HAART SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; IN-VIVO; INFECTED INDIVIDUALS; MITOCHONDRIAL-DNA; ANTIVIRAL THERAPY; EXTENDED PERIODS; DRUG-RESISTANCE; PLASMA VIREMIA AB In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART) is required. In this regard, most studies have focused on integrated (proviral) HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication-defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal) viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC) samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse-transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM)) in order to determine molecular compartmentalization. We observed low molecular variance (mean variability <= 0.042). Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10(-6) AMOVA test; P = 0.001 SM test), suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10(-6)) suggesting that episomal and proviral DNA forms originated from different anatomical compartments. Collectively, this suggests the presence of a chronic viral reservoir in which there is stochastic release of infectious virus and in which there are limited rounds of de novo infection. This could be explained by the existence of different reservoirs with unique pharmacological accessibility properties, which will require strategies that improve drug penetration/ retention within these reservoirs in order to minimise maintenance of the viral reservoir by de novo infection. C1 [Buzon, Maria J.; Codoner, Francisco M.; Pou, Christian; Puertas, Maria C.; Massanella, Marta; Dalmau, Judith; Blanco, Julia; Clotet, Bonaventura; Paredes, Roger; Martinez-Picado, Javier] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, IrsiCaixa, Inst Recerca,SIDA, Badalona, Spain. [Frost, Simon D. W.] Univ Cambridge, Dept Vet Med, Cambridge, England. [Llibre, Josep M.; Clotet, Bonaventura; Paredes, Roger] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Unitat VIH, Badalona, Spain. [Stevenson, Mario] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Martinez-Picado, Javier] ICREA, Barcelona, Spain. RP Buzon, MJ (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jmpicado@irsicaixa.es RI Frost, Simon/F-3648-2010; Blanco, Julia/A-5347-2008; Martinez-Picado, Javier/G-5507-2012; Pou, Christian/B-2932-2015; Buzon, Maria J/G-8286-2015; Puertas, Maria /G-3251-2016; Massanella, Marta/P-8619-2016 OI Frost, Simon/0000-0002-5207-9879; Blanco, Julia/0000-0002-2225-0217; Martinez-Picado, Javier/0000-0002-4916-2129; Pou, Christian/0000-0003-3932-788X; Buzon, Maria J/0000-0003-4427-9413; Puertas, Maria /0000-0002-6750-2318; Massanella, Marta/0000-0002-3326-151X FU Spanish AIDS network [RD06/0006]; HIVACAT; European Community [FP7/2007-2013]; NIH; Merck Sharp Dohme (MSD); AGAUR; Marie Curie European Reintegration Grant; Royal Society FX This study was supported by the Spanish AIDS network (RD06/0006), by the HIVACAT program, by funding from the European Community's FP7/2007-2013, under the project CHAIN, by funding from the NIH to M. Stevenson and by an unrestricted grant from Merck Sharp & Dohme (MSD). J Blanco is a researcher from IGTP. MJ Buzon and M. Massanella were supported by AGAUR. FM Codoner was supported by the Marie Curie European Reintegration Grant. SDW Frost was supported in part by a Royal Society Wolfson Merit Research Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 39 Z9 39 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2011 VL 7 IS 10 AR e1002314 DI 10.1371/journal.ppat.1002314 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 844FY UT WOS:000296734300043 PM 22046128 ER PT J AU Feeley, EM Sims, JS John, SP Chin, CR Pertel, T Chen, LM Gaiha, GD Ryan, BJ Donis, RO Elledge, SJ Brass, AL AF Feeley, Eric M. Sims, Jennifer S. John, Sinu P. Chin, Christopher R. Pertel, Thomas Chen, Li-Mei Gaiha, Gaurav D. Ryan, Bethany J. Donis, Ruben O. Elledge, Stephen J. Brass, Abraham L. TI IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry SO PLOS PATHOGENS LA English DT Article ID WEST NILE VIRUS; GENE-EXPRESSION; EARLY ENDOSOMES; DENGUE VIRUS; CELLS; PROTEIN; ENDOCYTOSIS; AUTOPHAGY; RIBONUCLEOPROTEINS; HEMAGGLUTININ AB To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. C1 [Feeley, Eric M.; Sims, Jennifer S.; John, Sinu P.; Chin, Christopher R.; Pertel, Thomas; Gaiha, Gaurav D.; Ryan, Bethany J.; Brass, Abraham L.] MIT, Ragon Inst, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Feeley, Eric M.; Sims, Jennifer S.; John, Sinu P.; Chin, Christopher R.; Pertel, Thomas; Gaiha, Gaurav D.; Ryan, Bethany J.; Brass, Abraham L.] Harvard Univ, Charlestown, MA USA. [Chen, Li-Mei; Donis, Ruben O.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Elledge, Stephen J.] Harvard Univ, Brigham & Womens Hosp, Dept Genet, Sch Med, Boston, MA 02115 USA. [Elledge, Stephen J.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Brass, Abraham L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. RP Feeley, EM (reprint author), MIT, Ragon Inst, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM abrass@partners.org OI Pertel, Thomas/0000-0002-2286-6011 FU Charles H. Hood Foundation; Phillip T. and Susan M. Ragon Institute Foundation FX The source of funding for this work was from the Charles H. Hood Foundation and the Phillip T. and Susan M. Ragon Institute Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 122 Z9 132 U1 2 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD OCT PY 2011 VL 7 IS 10 AR e1002337 DI 10.1371/journal.ppat.1002337 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 844FY UT WOS:000296734300058 PM 22046135 ER PT J AU Hermann, M Joung, JK Maeder, ML Becher, B Burki, K Aguzzi, A Buch, T Pelczar, P AF Hermann, Mario Joung, J. Keith Maeder, Morgan L. Becher, Burkhard Buerki, Kurt Aguzzi, Adriano Buch, Thorsten Pelczar, Pawel TI Targeted transgene integration in mouse embryos using "open source" zinc finger nucleases SO TRANSGENIC RESEARCH LA English DT Meeting Abstract C1 [Hermann, Mario; Buerki, Kurt; Pelczar, Pawel] Univ Zurich, Inst Lab Anim Sci, Zurich, Switzerland. [Joung, J. Keith; Maeder, Morgan L.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Joung, J. Keith; Maeder, Morgan L.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Becher, Burkhard; Buch, Thorsten] Univ Zurich, Inst Expt Immunol, CH-8091 Zurich, Switzerland. [Hermann, Mario; Aguzzi, Adriano] Univ Zurich, Inst Neuropathol, Zurich, Switzerland. [Buch, Thorsten] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany. RI Aguzzi, Adriano/A-3351-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD OCT PY 2011 VL 20 IS 5 MA 60 BP 1164 EP 1164 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 844XS UT WOS:000296786900074 ER PT J AU Tassa, C Shaw, SY Weissleder, R AF Tassa, Carlos Shaw, Stanley Y. Weissleder, Ralph TI Dextran-Coated Iron Oxide Nanoparticles: A Versatile Platform for Targeted Molecular Imaging, Molecular Diagnostics, and Therapy SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID MAGNETIC-RELAXATION; NONINVASIVE DETECTION; LIVING CELLS; CANCER-CELLS; ATHEROSCLEROSIS; PROBES; INFLAMMATION; NANOSENSORS; NANOCRYSTALS; TELOMERASE AB Advances in our understanding of the genetic basis of disease susceptibility coupled with prominent successes for molecular targeted therapies have resulted in an emerging strategy of personalized medicine. This approach envisions risk stratification and therapeutic selection based on an individual's genetic makeup and physiologic state (the latter assessed through cellular or molecular phenotypes). Molecularly targeted nanoparticles can play a key role in this vision through noninvasive assessments of molecular processes and specific cell populations in vivo, sensitive molecular diagnostics, and targeted delivery of therapeutics. A superparamagnetic iron oxide nanoparticle with a cross-linked dextran coating, or CLIO, is a powerful and illustrative nanoparticle platform for these applications. These structures and their derivatives support diagnostic imaging by magnetic resonance (MRI), optical, and positron emission tomography (PET) modalities and constitute a versatile platform for conjugation to targeting ligands. A variety of conjugation methods exist to couple the dextran surface to different functional groups; in addition, a robust bioorthogonal [4 + 2] cycloaddition reaction between 1,2,4,5-tetrazene (Tz) and trans-cyclooctene (TCO) can conjugate nanoparticles to targeting ligands or label pretargeted cells. The ready availability of conjugation methods has given rise to the synthesis of libraries of small molecule modified nanoparticles, which can then be screened for nanoparticles with specificity for a specific cell type. Since most nanoparticles display their targeting ligands In a multivalent manner, a detailed understanding of the kinetics and affinity of a nanoparticle's interaction with Its target (as determined by surface plasmon resonance) can yield functionally Important insights Into nanoparticle design. In this Account, we review applications of the CLIO platform In several areas relevant to the mission of personalized medicine. We demonstrate rapid and highly sensitive molecular profiling of cancer markers ex vivo, as part of detailed, individualized molecular phenotyping. The CLIO platform also facilitates targeted magnetic resonance and combined modality imaging (such as MR/PET/fluorescence/CT) to enable multiplexed measurement of molecular phenotypes In vivo for early diagnosis and disease classification. Finally, the targeted delivery of a photodynamic therapy agent as Part of a theranostic nanoparticle successfully Increased local cell toxicity and minimized systemic side effects. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH/NHLBI [HHSN268201000044C] FX The authors gratefully acknowledge the contributions from all researchers whose work has been described in this Account. This work was funded by Contract Number HHSN268201000044C (NIH/NHLBI) to S.Y.S. and R.W. NR 73 TC 289 Z9 295 U1 34 U2 316 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD OCT PY 2011 VL 44 IS 10 SI SI BP 842 EP 852 DI 10.1021/ar200084x PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 843OT UT WOS:000296682400002 PM 21661727 ER PT J AU Mendez-Navarro, J Ortiz-Olvera, NX Villegas-Rios, M Mendez-Tovar, LJ Andersson, KL Moreno-Alcantar, R Gallardo-Cabrera, VE Felix, S Galvan, C Vargas, G Gomez, LM Dehesa-Violante, M AF Mendez-Navarro, Jorge Ortiz-Olvera, Nayeli X. Villegas-Rios, Margarita Mendez-Tovar, Luis J. Andersson, Karin L. Moreno-Alcantar, Rosalba Gallardo-Cabrera, Victor E. Felix, Sergio Galvan, Carlos Vargas, Gilka Gomez, Luz M. Dehesa-Violante, Margarita TI Hepatotoxicity from ingestion of wild mushrooms of the genus Amanita section Phalloideae collected in Mexico City: two case reports SO ANNALS OF HEPATOLOGY LA English DT Article DE Mushroom poisoning; Amanita; Acute liver failure; Treatment; MARS; Amatoxins; Mushroom hepatotoxicity; Fulminant hepatitis ID FULMINANT HEPATIC-FAILURE; LIVER-TRANSPLANTATION; AMATOXINS; TOXINS; FUNGI AB We present two cases of acute liver injury resulting from consumption of wild mushrooms. The first case was a male who developed acute hepatitis after ingestion of diverse mushrooms including Amanita species. His clinical course was favorable with complete recovery of liver function. The second case was a male who developed acute liver failure (ALF) after ingestion of Amanita bisporigera. He required MARS therapy as a bridge to liver transplantation but transplantation was not performed because he succumbed to multiorgan failure. There are few trials demonstrating the efficacy of the different treatments for mushroom poisoning. These cases demonstrate that the consumption of wild mushrooms without proper knowledge of toxic. species represents a serious and under recognized health problem. C1 [Mendez-Navarro, Jorge; Ortiz-Olvera, Nayeli X.; Moreno-Alcantar, Rosalba; Gallardo-Cabrera, Victor E.; Felix, Sergio; Galvan, Carlos; Vargas, Gilka; Dehesa-Violante, Margarita] Hosp Especialidades Ctr Med La Raza, CMN Siglo 21, Dept Gastroenterol, Natl Med Ctr,IMSS, Mexico City 06725, DF, Mexico. [Villegas-Rios, Margarita] Univ Nacl Autonoma Mexico, Fac Sci, Comparat Biol Dept, Mycol Area, Mexico City 04510, DF, Mexico. [Mendez-Tovar, Luis J.] Hosp Especialidades Ctr Med La Raza, CMN Siglo 21, Med Res Lab Dermatol & Mycol, Natl Med Ctr,IMSS, Mexico City 06725, DF, Mexico. [Andersson, Karin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Gomez, Luz M.] Hosp Especialidades Ctr Med La Raza, CMN Siglo 21, Dept Pathol, Natl Med Ctr,IMSS, Mexico City 06725, DF, Mexico. RP Mendez-Navarro, J (reprint author), Hosp Especialidades Ctr Med La Raza, CMN Siglo 21, Dept Gastroenterol, Natl Med Ctr,IMSS, Av Cuauhtemoc 330, Mexico City 06725, DF, Mexico. EM jmndoc@yahoo.com NR 29 TC 2 Z9 2 U1 0 U2 2 PU MEXICAN ASSOC HEPATOLOGY PI MEXICO PA PUNTE DE PIEDRA 150, COLONIA TORIELLO GUERRA, MEXICO, DF CP 14040, MEXICO SN 1665-2681 J9 ANN HEPATOL JI Ann. Hepatol. PD OCT-DEC PY 2011 VL 10 IS 4 BP 568 EP 574 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 843LF UT WOS:000296672600023 PM 21911902 ER PT J AU Cyganek, K Hebda-Szydlo, A Skupien, J Katra, B Janas, I Borodako, A Kaim, I Klupa, T Reron, A Malecki, MT AF Cyganek, Katarzyna Hebda-Szydlo, Alicja Skupien, Jan Katra, Barbara Janas, Izabela Borodako, Alicja Kaim, Irena Klupa, Tomasz Reron, Alfred Malecki, Maciej T. TI Glycemic control and pregnancy outcomes in women with type 2 diabetes from Poland. The impact of pregnancy planning and a comparison with type 1 diabetes subjects SO ENDOCRINE LA English DT Article DE Pregnancy; Type 2 diabetes; Type 1 diabetes; Outcomes ID CONGENITAL-ANOMALIES; PERINATAL-MORTALITY; INSULIN-TREATMENT; UNITED-STATES; BIRTH-WEIGHT; MELLITUS; CARE; POPULATION; COMPLICATIONS; MALFORMATIONS AB The number of pregnancies complicated by type 2 diabetes mellitus (T2DM) is growing; however, their clinical characteristics remain incomplete. We aimed to assess clinical characteristics, glycemic control, and selected pregnancy outcomes in pregestational T2DM from Poland and to compare them with those of T1DM. We analyzed 415 consecutive singleton pregnancies; among them, there were 70 women with T2DM and 345 with T1DM. As compared to T1DM patients, women with T2DM were older (mean age 33.1 years vs. 27.8, respectively), heavier before pregnancy (mean BMI 30.8 kg/m(2) vs. 23.9), and had a shorter duration of diabetes (mean 3.3 years vs. 11.4); (P < 0.0001 for all comparisons). The gestational age at the first visit was higher in T2DM (mean 11.4 weeks vs. 8.6; P = 0.0004). Nevertheless, they had better glycemic control in the first trimester (mean HbA1c 6.2% vs. 7.0; P = 0.003); in subsequent months, the differences in HbA1c were no longer significant. T2DM women gained less weight during pregnancy (mean 9.9 kgs vs. 14.1; P < 0.0001). The proportion of miscarriages (10.0 vs. 7.3%; P = 0.32), preterm deliveries (12.7 vs. 17.8%; P = 0.32), combined infant deaths, and congenital malformations were similar in both groups (9.5 vs. 8.8%; P = 0.4) as was the frequency of caesarean sections (58.7 vs. 64.1%; P = 0.30). Macrosomic babies were more than twice less frequent in T2DM and the difference reached borderline significance (7.9 vs. 17.5%, P = 0.07). Pregnancy planning in T2DM had a significant impact on HbA1c in the first trimester (5.7 vs. 6.4% in the planning vs. the not planning group, P = 0.02); the difference was not significant in the second and third trimester. T2DM women had better glycemic control in the first trimester than T1DM subjects and gained less weight during pregnancy. This could have been the reason for the slightly lower number of macrosomic babies but did not affect other outcomes. In T2DM, pregnancy planning had a beneficial glycemic effect in the first trimester. C1 [Cyganek, Katarzyna; Hebda-Szydlo, Alicja; Katra, Barbara; Janas, Izabela; Borodako, Alicja; Klupa, Tomasz; Malecki, Maciej T.] Jagiellonian Univ, Dept Metab Dis, Coll Med, PL-31511 Krakow, Poland. [Kaim, Irena; Reron, Alfred] Jagiellonian Univ, Coll Med, Dept Obstet & Perinatol, PL-31511 Krakow, Poland. [Cyganek, Katarzyna; Hebda-Szydlo, Alicja; Katra, Barbara; Kaim, Irena; Klupa, Tomasz; Reron, Alfred; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. [Skupien, Jan] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Malecki, MT (reprint author), Jagiellonian Univ, Dept Metab Dis, Coll Med, 15 Kopernika St, PL-31511 Krakow, Poland. EM mmalecki@cm-uj.krakow.pl FU Polish Ministry of Science [N N407 414436]; Jagiellonian University Medical College FX This study was supported by the Polish Ministry of Science Grant No. N N407 414436 and by the Jagiellonian University Medical College. The authors would like to express their gratefulness to The Great Orchestra of Christmas Charity; a non-governmental aid organization in Poland, which provided help in medical care to many women participating in this study. NR 48 TC 12 Z9 13 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD OCT PY 2011 VL 40 IS 2 BP 243 EP 249 DI 10.1007/s12020-011-9475-0 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 844XZ UT WOS:000296787800013 PM 21528433 ER PT J AU Rahman, SH Kuhle, J Riedel, H Maeder, M Joung, JK Schambach, A Cathomen, T AF Rahman, S. H. Kuehle, J. Riedel, H. Maeder, M. Joung, J. K. Schambach, A. Cathomen, T. TI Zinc-finger nuclease-mediated correction of the cellular RS-SCID phenotype SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 [Rahman, S. H.; Kuehle, J.; Schambach, A.; Cathomen, T.] Hannover Med Sch, Inst Expt Hematol, D-3000 Hannover, Germany. [Riedel, H.] Robert C Byrd Hlth Sci Ctr, Dept Biochem, Morgantown, WV USA. [Maeder, M.; Joung, J. K.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2011 VL 22 IS 10 BP A27 EP A27 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843WS UT WOS:000296707900088 ER PT J AU Medalia, C Chang, VW AF Medalia, Carla Chang, Virginia W. TI Gender equality, development, and cross-national sex gaps in life expectancy SO INTERNATIONAL JOURNAL OF COMPARATIVE SOCIOLOGY LA English DT Article DE cross-national; development; gender equality; life expectancy; sex differences ID WOMENS HEALTH; FEMALE MORTALITY; RISK-FACTOR; COUNTRIES; SMOKING; CONVERGENCE; INEQUALITY; EMPLOYMENT; COHORT; MEN AB Female life expectancy exceeds male life expectancy in almost every country throughout the world. Nevertheless, cross-national variation in the sex gap suggests that social factors, such as gender equality, may directly affect or mediate an underlying biological component. In this article, we examine the association between gender equality and the sex gap in mortality. Previous research has not addressed this question from an international perspective with countries at different levels of development. We examine 131 countries using a broad measure of national gender equality that is applicable in both Less Developed Countries (LDCs) and Highly Developed Countries (HDCs). We find that the influence of gender equality is conditional on level of development. While gender equality is associated with divergence between female and male life expectancies in LDCs, it is associated with convergence in HDCs. The relationship between gender equality and the sex gap in mortality in HDCs strongly relates to, but is not explained by, sex differences in lung cancer mortality. Finally, we find that divergence in LDCs is primarily driven by a strong positive association between gender equality and female life expectancy. In HDCs, convergence is potentially related to a weak negative association between gender equality and female life expectancy, though findings are not statistically significant. C1 [Medalia, Carla] Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Medalia, C (reprint author), Univ Penn, Dept Sociol, McNeil Bldg,Ste 113,3718 Locust Walk, Philadelphia, PA 19104 USA. EM medalia@sas.upenn.edu NR 58 TC 5 Z9 5 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0020-7152 J9 INT J COMP SOCIOL JI Int. J. Comp. Sociol. PD OCT PY 2011 VL 52 IS 5 BP 371 EP 389 DI 10.1177/0020715211426177 PG 19 WC Sociology SC Sociology GA 846TA UT WOS:000296924900001 ER PT J AU Kamnaksh, A Kovesdi, E Kwon, SK Wingo, D Ahmed, F Grunberg, NE Long, J Agoston, DV AF Kamnaksh, Alaa Kovesdi, Erzsebet Kwon, Sook-Kyung Wingo, Daniel Ahmed, Farid Grunberg, Neil E. Long, Joseph Agoston, Denes V. TI Factors Affecting Blast Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavior; inflammation; traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; INDUCED NEUROTRAUMA; CEREBRAL-ISCHEMIA; INFLAMMATION; NEUROPROTECTION; MECHANISMS; EXPRESSION; CYTOKINES; EXPOSURE; IMMUNE AB The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI) and stress-related neurobehavioral disorders like post-traumatic stress disorder (PTSD) are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis and treatment as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naive rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I, C II, and C III animals exhibited increased anxiety, but serum corticosterone levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in ionized calcium-binding adapter molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL-positive cells in the VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors in the development of post-traumatic symptoms, and to establish a differential diagnosis for PTSD and bTBI. C1 [Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Grunberg, Neil E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Kamnaksh, Alaa; Kwon, Sook-Kyung; Ahmed, Farid; Grunberg, Neil E.; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Kovesdi, Erzsebet] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC USA. [Long, Joseph] Walter Reed Army Inst Res, Ctr Mil Psychiat & Neurotrauma, Blast Induced Neurotrauma Branch, Silver Spring, MD USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu FU Center for Neuroscience and Regenerative Medicine (CNRM) [G1703F] FX We thank the Neurotrauma Team (WRAIR) for their technical help during the exposures. This work was supported by Center for Neuroscience and Regenerative Medicine (CNRM) grant no. G1703F. NR 46 TC 42 Z9 42 U1 1 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2011 VL 28 IS 10 BP 2145 EP 2153 DI 10.1089/neu.2011.1983 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 839OX UT WOS:000296378500015 PM 21861635 ER PT J AU Bakitas, M Kryworuchko, J Matlock, DD Volandes, AE AF Bakitas, Marie Kryworuchko, Jennifer Matlock, Dan D. Volandes, Angelo E. TI Palliative Medicine and Decision Science: The Critical Need for a Shared Agenda To Foster Informed Patient Choice in Serious Illness SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE DECISIONS; OF-LIFE DISCUSSIONS; DRUG FACTS BOX; BREAST-CANCER; PATIENTS PREFERENCES; HEART-FAILURE; END; AIDS; COMMUNICATION AB Assisting patients and their families in complex decision making is a foundational skill in palliative care; however, palliative care clinicians and scientists have just begun to establish an evidence base for best practice in assisting patients and families in complex decision making. Decision scientists aim to understand and clarify the concepts and techniques of shared decision making (SDM), decision support, and informed patient choice in order to ensure that patient and family perspectives shape their health care experience. Patients with serious illness and their families are faced with myriad complex decisions over the course of illness and as death approaches. If patients lose capacity, then surrogate decision makers are cast into the decision-making role. The fields of palliative care and decision science have grown in parallel. There is much to be gained in advancing the practices of complex decision making in serious illness through increased collaboration. The purpose of this article is to use a case study to highlight the broad range of difficult decisions, issues, and opportunities imposed by a life-limiting illness in order to illustrate how collaboration and a joint research agenda between palliative care and decision science researchers, theorists, and clinicians might guide best practices for patients and their families. C1 [Bakitas, Marie] Dartmouth Hitchcock Med Ctr, Sect Palliat Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Kryworuchko, Jennifer] Univ Saskatchewan, Saskatoon, SK, Canada. [Matlock, Dan D.] Univ Colorado Denver, Aurora, CO USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bakitas, M (reprint author), Dartmouth Hitchcock Med Ctr, Sect Palliat Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. EM marie.bakitas@hitchcock.org OI Bakitas, Marie/0000-0002-2913-2053 FU National Palliative Care Research Center; Foundation for Informed Medical Decision Making; Hartford Geriatrics Health Outcomes Research Scholar; Agency for Healthcare Research and Quality; National Institute for Nursing Research [R01-NR011871-01] FX The authors thank Daphne Ellis for assistance with preparation of the manuscript. The authors acknowledge the following sources of funding: National Palliative Care Research Center Junior Career Award (MB), Foundation for Informed Medical Decision Making (MB, JK, DDM, AV), Hartford Geriatrics Health Outcomes Research Scholar (DDM), and Agency for Healthcare Research and Quality K08 Award (AEV) and National Institute for Nursing Research (R01-NR011871-01) (MB). NR 82 TC 16 Z9 16 U1 3 U2 9 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 OCT PY 2011 VL 14 IS 10 BP 1109 EP 1116 DI 10.1089/jpm.2011.0032 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 842BG UT WOS:000296560600008 PM 21895453 ER PT J AU Whitlock, SN Goldberg, IP Singh, JP AF Whitlock, Sandra N. Goldberg, Ilan P. Singh, Jagmeet P. TI Is Pacemaker Deactivation at the End of Life Unique?: A Case Study and Ethical Analysis SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; TERMINALLY-ILL PATIENTS; OF-LIFE; SUSTAINING TREATMENT; THERAPY; DEVICES; ATTITUDES; CARE; AGORAPHOBIA; MANAGEMENT AB Although there has been considerable controversy regarding the deactivation of pacemakers near the end of life, clinicians can expect to facemore requests for pacemaker withdrawal as the number of implants grows. Despite a clear ethical and legal precedent, these requests may elicit significant psychological and moral distress on the part of the clinical team. We illustrate some of the difficulties clinicians may face by describing the case of a patient with end-stage heart failure who asked to have her pacemaker turned off near the end of life. We discuss the challenges in determining pacemaker dependency, differing attitudes toward deactivating pacemakers versus other cardiac devices, and how the issues of perceived burden and timing of death may contribute to a clinician's sense of moral distress. C1 [Whitlock, Sandra N.] Four Seasons, Palliat Care, Flat Rock, NC 28731 USA. [Singh, Jagmeet P.] Harvard Univ, Sch Med, Boston, MA USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Whitlock, SN (reprint author), Four Seasons, Palliat Care, 571 S Allen Rd, Flat Rock, NC 28731 USA. EM swhitlock@fourseasonscfl.org NR 33 TC 3 Z9 3 U1 1 U2 5 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 OCT PY 2011 VL 14 IS 10 BP 1184 EP 1188 DI 10.1089/jpm.2011.0084 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 842BG UT WOS:000296560600020 PM 21882901 ER PT J AU Avery, CL He, QC North, KE Ambite, JL Boerwinkle, E Fornage, M Hindorff, LA Kooperberg, C Meigs, JB Pankow, JS Pendergrass, SA Psaty, BM Ritchie, MD Rotter, JI Taylor, KD Wilkens, LR Heiss, G Lin, DY AF Avery, Christy L. He, Qianchuan North, Kari E. Ambite, Jose L. Boerwinkle, Eric Fornage, Myriam Hindorff, Lucia A. Kooperberg, Charles Meigs, James B. Pankow, James S. Pendergrass, Sarah A. Psaty, Bruce M. Ritchie, Marylyn D. Rotter, Jerome I. Taylor, Kent D. Wilkens, Lynne R. Heiss, Gerardo Lin, Dan Yu TI A Phenomics-Based Strategy Identifies Loci on APOC1, BRAP, and PLCG1 Associated with Metabolic Syndrome Phenotype Domains SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; GENETIC-LOCI; SIGNAL-TRANSDUCTION; DIABETES RISK; HEART; OBESITY AB Despite evidence of the clustering of metabolic syndrome components, current approaches for identifying unifying genetic mechanisms typically evaluate clinical categories that do not provide adequate etiological information. Here, we used data from 19,486 European American and 6,287 African American Candidate Gene Association Resource Consortium participants to identify loci associated with the clustering of metabolic phenotypes. Six phenotype domains (atherogenic dyslipidemia, vascular dysfunction, vascular inflammation, pro-thrombotic state, central obesity, and elevated plasma glucose) encompassing 19 quantitative traits were examined. Principal components analysis was used to reduce the dimension of each domain such that >55% of the trait variance was represented within each domain. We then applied a statistically efficient and computational feasible multivariate approach that related eight principal components from the six domains to 250,000 imputed SNPs using an additive genetic model and including demographic covariates. In European Americans, we identified 606 genome-wide significant SNPs representing 19 loci. Many of these loci were associated with only one trait domain, were consistent with results in African Americans, and overlapped with published findings, for instance central obesity and FTO. However, our approach, which is applicable to any set of interval scale traits that is heritable and exhibits evidence of phenotypic clustering, identified three new loci in or near APOC1, BRAP, and PLCG1, which were associated with multiple phenotype domains. These pleiotropic loci may help characterize metabolic dysregulation and identify targets for intervention. C1 [Avery, Christy L.; North, Kari E.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [He, Qianchuan; Lin, Dan Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Ambite, Jose L.] Univ So Calif, Inst Informat Sci, Los Angeles, CA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Hindorff, Lucia A.] NHGRI, Off Populat Gen, NIH, Bethesda, MD 20892 USA. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Pendergrass, Sarah A.; Ritchie, Marylyn D.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Wilkens, Lynne R.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. RP Avery, CL (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM christy_avery@unc.edu RI Ritchie, Marylyn/C-1114-2012; OI Pankow, James/0000-0001-7076-483X FU NIH/NHGRI [U01 HG004798]; NIH/NHLBI, 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, U01 HG004790]; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]; National Heart, Lung, and Blood Institute; NHLBI [K99-HL-098458]; NIDDK [K24 DK080140, R01 DK078616] FX PAGE: Support for the Genetic Epidemiology of Causal Variants Across the Life Course (CALiCo) was provided through the National Human Genome Research Institute's Population Architecture Using Genomics and Epidemiology (PAGE) network (U01 HG004803). EAGLE work was funded by NIH/NHGRI grant U01 HG004798. The WHI program is funded by NIH/NHLBI, 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, 44221, and U01 HG004790. Funding support for the Multiethnic Cohort study was provided through the National Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and U01CA98758) and NHGRI (U01 HG004802). CARe: The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research. The following five parent studies contributed parent study data, ancillary study data, and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype data base for wide dissemination to the biomedical research community: Atherosclerosis Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California Davis (N01-HC-85083), University of California Irvine (N01-HC85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California Irvine (N01-HC45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169). CLA was supported by grant K99-HL-098458 from the NHLBI. JBM was supported by grants K24 DK080140 and R01 DK078616 from the NIDDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 61 TC 40 Z9 43 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002322 DI 10.1371/journal.pgen.1002322 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400023 PM 22022282 ER PT J AU Janas, MM Khaled, M Schubert, S Bernstein, JG Golan, D Veguilla, RA Fisher, DE Shomron, N Levy, C Novina, CD AF Janas, Maja M. Khaled, Mehdi Schubert, Steffen Bernstein, Jacob G. Golan, David Veguilla, Rosa A. Fisher, David E. Shomron, Noam Levy, Carmit Novina, Carl D. TI Feed-Forward Microprocessing and Splicing Activities at a MicroRNA-Containing Intron SO PLOS GENETICS LA English DT Article ID MESSENGER-RNAS; HOST GENES; HNRNP A1; COMPLEX; BIOGENESIS; EXPRESSION; MELANOMA; IDENTIFICATION; SPLICEOSOME; PRECURSORS AB The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6-exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5' splice site (5'SS), but not in the 3'SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5'SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs. C1 [Janas, Maja M.; Khaled, Mehdi; Schubert, Steffen; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Microbiol & Immunob, Boston, MA 02115 USA. [Janas, Maja M.; Khaled, Mehdi; Schubert, Steffen; Novina, Carl D.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Khaled, Mehdi; Veguilla, Rosa A.; Fisher, David E.] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Bernstein, Jacob G.] MIT, MIT Media Lab, Cambridge, MA 02139 USA. [Golan, David; Shomron, Noam] Tel Aviv Univ, Sackler Fac Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel. [Levy, Carmit] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Janas, MM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Microbiol & Immunob, 44 Binney St, Boston, MA 02115 USA. EM carmitlevy@post.tau.ac.il; carl_novina@dfci.harvard.edu RI khaled, mehdi/C-4854-2012 FU NIH; Melanoma Research Alliance; Doris Duke Medical Foundation; Sheldon and Dr. Miriam Adelson Medical Research Foundation; American Cancer Society; Cash Memorial Fund FX This work was funded by grants from the NIH, the Melanoma Research Alliance, the Doris Duke Medical Foundation, and the Sheldon and Dr. Miriam Adelson Medical Research Foundation to DEF and by grants from the American Cancer Society and the Cash Memorial Fund to CDN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 31 Z9 31 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD OCT PY 2011 VL 7 IS 10 AR e1002330 DI 10.1371/journal.pgen.1002330 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 843IL UT WOS:000296665400031 PM 22028668 ER PT J AU Sadik, CD Kim, ND Luster, AD AF Sadik, Christian D. Kim, Nancy D. Luster, Andrew D. TI Neutrophils cascading their way to inflammation SO TRENDS IN IMMUNOLOGY LA English DT Review ID OBSTRUCTIVE PULMONARY-DISEASE; INFL AMMATORY ARTHRITIS; SPINAL-CORD-INJURY; BONE-MARROW; WHIM-SYNDROME; G-CSF; RHEUMATOID-ARTHRITIS; AIRWAY INFLAMMATION; DEFICIENT MICE; RECRUITMENT AB Neutrophils are pivotal effector cells of innate immunity. Their recruitment into peripheral tissues is indispensable for host defense. Given their destructive potential, neutrophil entry into tissue must be tightly regulated in vivo to avoid damage to the host. An array of chemically diverse chemoattractants is active on neutrophils and participates in recruitment. Neutrophil chemoattractants were thought redundant in the control of neutrophil recruitment into peripheral tissue, based on their often indistinguishable effects on neutrophils in vitro and their frequently overlapping patterns of expression at inflammatory sites in vivo. Recent data, however, suggest that neutrophil chemoattractants have unique functions in the recruitment of neutrophils into inflammatory sites in vivo, dictated by their distinct patterns of temporal and spatial expression. C1 [Sadik, Christian D.; Kim, Nancy D.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02114 USA. EM aluster@mgh.harvard.edu RI Sadik, Christian/E-8404-2012 FU Deutsche Forschungsgemeinschaft [Sa1960/1-1]; National Institutes of Health [R01-AI050892, K08-AR054094] FX This work was supported by grants of the Deutsche Forschungsgemeinschaft (Sa1960/1-1 to C.D.S.) and of the National Institutes of Health (R01-AI050892 to A.D.L. and K08-AR054094 to N.D.K.). NR 75 TC 161 Z9 164 U1 3 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD OCT PY 2011 VL 32 IS 10 BP 452 EP 460 DI 10.1016/j.it.2011.06.008 PG 9 WC Immunology SC Immunology GA 847QJ UT WOS:000296987300002 PM 21839682 ER PT J AU Mazo, IB Massberg, S von Andrian, UH AF Mazo, Irina B. Massberg, Steffen von Andrian, Ulrich H. TI Hematopoietic stem and progenitor cell trafficking SO TRENDS IN IMMUNOLOGY LA English DT Review ID UMBILICAL-CORD BLOOD; BONE-MARROW NICHE; SECONDARY LYMPHOID ORGANS; PRE-B-CELL; IN-VIVO; STEM/PROGENITOR CELLS; AORTIC ENDOTHELIUM; CD34(+) CELLS; CHEMOKINE RECEPTORS; ADHESION MOLECULES AB Migration of hematopoietic stem cells (HSCs) is essential during embryonic development and throughout adult life. During embryogenesis, trafficking of HSCs is responsible for the sequential colonization of different hematopoietic organs by blood-producing cells. In adulthood, circulation of HSCs maintains homeostasis of the hematopoietic system and participates in innate immune responses. HSC trafficking is also crucial in clinical settings such as bone marrow (BM) and stem cell transplantation. This review provides an overview of the molecular and cellular signals that control and fine-tune trafficking of HSCs and hematopoietic progenitor cells in embryogenesis and during postnatal life. We also discuss the potential clinical utility of therapeutic approaches to modulate HSC trafficking in patients. C1 [Massberg, Steffen] Tech Univ Munich, Klinikum Rechts Isar, Deutsch Herzzentrum Munchen, D-8000 Munich, Germany. [Massberg, Steffen] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 1, D-8000 Munich, Germany. [Mazo, Irina B.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mazo, Irina B.; von Andrian, Ulrich H.] Immune Dis Inst, Boston, MA 02115 USA. RP Massberg, S (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Deutsch Herzzentrum Munchen, D-8000 Munich, Germany. EM massberg@dhm.mhn.de; uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL056949-11, P01 HL056949]; NIAID NIH HHS [P01 AI078897, P01 AI078897-03, R01 AI069259, R01 AI069259-06] NR 124 TC 50 Z9 50 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD OCT PY 2011 VL 32 IS 10 BP 493 EP 503 DI 10.1016/j.it.2011.06.011 PG 11 WC Immunology SC Immunology GA 847QJ UT WOS:000296987300007 PM 21802990 ER PT J AU Flanagan, ME Welsh, CA Kiess, C Hoke, S Doebbeling, BN AF Flanagan, Mindy E. Welsh, Catherine Amber Kiess, Chris Hoke, Shawn Doebbeling, Bradley N. CA HAI Collaborative TI A national collaborative for reducing health care-associated infections: Current initiatives, challenges, and opportunities SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Hospital-acquired infections; infection prevention and control ID HOSPITAL-ACQUIRED INFECTIONS; BLOOD-STREAM INFECTIONS; NOSOCOMIAL INFECTIONS; EDUCATION-PROGRAM; STAY; INTERVENTION; SAFETY; LENGTH; IMPACT; COSTS AB There has been increasing interest and an upsurge in efforts to prevent hospital-associated infections (HAIs), a leading cause of death in the United States. This study was conducted to assess current strategies and efforts of HAI reduction initiatives in hospitals. HAI reduction initiatives and factors influencing institutional participation in these initiatives were categorized. Data were collected via open-ended questions on surveys performed in 5 different HAI collaboratives. Thematic analysis of the coded qualitative data was conducted. A total of 1,212 health care professionals from 33 different hospitals participated. Improving hand hygiene was the most frequently mentioned HAI reduction initiative implemented in the previous year. Initiatives for reducing central line or central venous catheter infections and ventilator-associated pneumonia also were commonly cited. The most frequently mentioned challenges to implementing HAI reduction initiatives included poor adherence, insufficient resources, staffing problems, lack of culture change, no impetus to change, and issues related to staff and patient education. Many respondents identified engaging physicians as particularly challenging. These findings suggest that consistently improving hand hygiene remains a widespread problem for reducing HAIs and sustaining this type of behavioral change is difficult. Furthermore, ensuring staff and physician engagement and compliance in HAI reduction efforts remains challenging for most hospitals. C1 [Flanagan, Mindy E.; Doebbeling, Bradley N.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Welsh, Catherine Amber; Doebbeling, Bradley N.] Regenstrief Inst Inc, Indianapolis, IN USA. [Kiess, Chris; Hoke, Shawn; Doebbeling, Bradley N.] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Indianapolis, IN USA. [Doebbeling, Bradley N.] Roudebush VAMC, VA HSR&D Ctr Implementing Evidence Based Practice, Indianapolis, IN USA. [Doebbeling, Bradley N.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. RP Flanagan, ME (reprint author), 10 W 10th St,Suite 2000, Indianapolis, IN 46202 USA. EM meflanag@iupui.edu FU Agency for Heathcare Research and Quality [HHSA290200600013I] FX This research was supported by the Agency for Heathcare Research and Quality (Contract HHSA290200600013I, Task Order 4). NR 18 TC 16 Z9 16 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD OCT PY 2011 VL 39 IS 8 BP 685 EP 689 DI 10.1016/j.ajic.2010.12.013 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 841TH UT WOS:000296535700013 PM 21665329 ER PT J AU Schnabel, RB Kerr, KF Lubitz, SA Alkylbekova, EL Marcus, GM Sinner, MF Magnani, JW Wolf, PA Deo, R Lloyd-Jones, DM Lunetta, KL Mehra, R Levy, D Fox, ER Arking, DE Mosley, TH Muller-Nurasyid, M Young, TR Wichmann, HE Seshadri, S Farlow, DN Rotter, JI Soliman, EZ Glazer, NL Wilson, JG Breteler, MMB Sotoodehnia, N Newton-Cheh, C Kaab, S Ellinor, PT Alonso, A Benjamin, EJ Heckbert, SR AF Schnabel, Renate B. Kerr, Kathleen F. Lubitz, Steven A. Alkylbekova, Ermeg L. Marcus, Gregory M. Sinner, Moritz F. Magnani, Jared W. Wolf, Philip A. Deo, Rajat Lloyd-Jones, Donald M. Lunetta, Kathryn L. Mehra, Reena Levy, Daniel Fox, Ervin R. Arking, Dan E. Mosley, Thomas H. Mueller-Nurasyid, Martina Young, Taylor R. Wichmann, H. -Erich Seshadri, Sudha Farlow, Deborah N. Rotter, Jerome I. Soliman, Elsayed Z. Glazer, Nicole L. Wilson, James G. Breteler, Monique M. B. Sotoodehnia, Nona Newton-Cheh, Christopher Kaeaeb, Stefan Ellinor, Patrick T. Alonso, Alvaro Benjamin, Emelia J. Heckbert, Susan R. CA Candidate Gene Assoc Resource CARe TI Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) Project SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atrial fibrillation; single nucleotide polymorphism; epidemiology; cohort study; race/ethnicity ID C-REACTIVE PROTEIN; CHROMOSOME 4Q25; ATHEROSCLEROSIS RISK; EUROPEAN ANCESTRY; ISCHEMIC-STROKE; INFLAMMATION; VARIANTS; INTERLEUKIN-6; DISEASE; DESIGN AB Background-The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. Methods and Results-We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n = 18 524; 2260 cases) or African American descent (n = 3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n = 906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n = 19 602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P = 0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P = 0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P = 0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P = 0.0005). Conclusions-In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans. (Circ Cardiovasc Genet. 2011; 4: 557-564.) C1 [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98101 USA. [Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Schnabel, Renate B.; Sinner, Moritz F.; Magnani, Jared W.; Wolf, Philip A.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Schnabel, Renate B.] Univ Med Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Kerr, Kathleen F.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98101 USA. [Lubitz, Steven A.; Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Alkylbekova, Ermeg L.; Fox, Ervin R.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Marcus, Gregory M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA USA. [Sinner, Moritz F.; Mueller-Nurasyid, Martina; Kaeaeb, Stefan] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Wolf, Philip A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Deo, Rajat] Univ Penn, Div Cardiol, Electrophysiol Sect, Philadelphia, PA 19104 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mehra, Reena] Case Sch Med, Dept Med, Cleveland, OH USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS 39216 USA. [Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Mueller-Nurasyid, Martina; Wichmann, H. -Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Young, Taylor R.; Farlow, Deborah N.; Newton-Cheh, Christopher] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Glazer, Nicole L.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Breteler, Monique M. B.] Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands. [Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Sch Med, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Sch Med, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Ctr Human Genet Res, Boston, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Dept Cardiol, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Prevent Med, Boston, MA 02215 USA. RP Heckbert, SR (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Sch Publ Hlth, Dept Epidemiol, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM schnabelr@gmx.de; emelia@bu.edu; heckbert@u.washington.edu RI Alonso, Alvaro/A-4917-2010; Lloyd-Jones, Donald/C-5899-2009; Kerr, Kathleen/A-2893-2013; Schnabel, Renate/F-6527-2014; Breteler, Monique /J-5058-2014; OI Seshadri, Sudha/0000-0001-6135-2622; Mehra, Reena/0000-0002-6222-2675; Benjamin, Emelia/0000-0003-4076-2336; Alonso, Alvaro/0000-0002-2225-8323; Lunetta, Kathryn/0000-0002-9268-810X FU NIH/NHLBI [RC1HL099452]; American Heart Association [09SDG2280087, 09FTF2190028]; CHS (Cardiovascular Health Study); National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, HHSN268200625226C, HHSN268200900055C, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 R01HL087641, R01HL59367, R01HL086694, R01HL093029]; FHS (Framingham Heart Study) [R01-HL080295]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; NIH [HHSN268200625226C, 1R01HL092577, RC1HL101056, AG028321, T32 HL007575, DA027021, HL104156, HL105780]; Deutsche Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1]; FHS [SCHN 1149/3-1]; German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung); German National Genome Research Network (NGFN); German National Competence Network on Atrial Fibrillation (AFNET); Leducq Foundation [07-CVD 03]; German Heart Foundation; Helmholtz Zentrum Munchen; State of Bavaria; German National Genome Research Network; LMUinnovativ; National Human Genome Research Institute [U01HG004402]; NIH Roadmap for Medical Research [UL1RR025005]; National Institute on Aging [R01AG027002]; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Affymetrix [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; NINDS [NS17950]; National Institute of Aging [AG08122, AG031287, AG033193]; Netherlands Organization of Scientific Research [175.010.2005.011]; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing [050-060-810]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Ministry of Education, Culture, and Science; Ministry for Health, Welfare, and Sports; European Commission; Municipality of Rotterdam to the Rotterdam Study; [01GS0499]; [01GI0204]; [01GS0838] FX We acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the all research institutions, study investigators, field staff, and study participants in creating the Candidate Gene Association Resource for Biomedical Research (CARe). The following 3 parent studies have specifically contributed phenotype data and DNA samples through the Massachusetts Institute of Technology, Broad Institute (N01-HC-65226) to create this genotype/phenotype database that will become publically available: ARIC (Atherosclerosis Risk in Communities), University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022), and University of North Carolina, Forsyth County (N01-HC-55018). This study was additionally supported by grants RC1HL099452 (NIH/NHLBI) and 09SDG2280087 (American Heart Association); CHS (Cardiovascular Health Study). This research was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, HHSN268200625226C, and HHSN268200900055C from the National Heart, Lung, and Blood Institute, and by grant R01-HL080295; FHS (Framingham Heart Study). This research was conducted using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Framingham Heart Study research was supported by NIH grants 1R01HL092577 (P.T.E., E.J.B.); RC1HL101056 (E.J.B., A.A.); AG028321 (E.J.B.); T32 HL007575 (S.A.L.); DA027021, HL104156, and HL105780 (P.T.E.); The Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 and Emmy Noether Program SCHN 1149/3-1 supported FHS research (R. B. S.). JWM was supported by American Heart Association award No. 09FTF2190028; AFNET/KORA S4: The study was also supported by the German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung) in the context of the German National Genome Research Network (NGFN), the German National Competence Network on Atrial Fibrillation (AFNET), the Leducq Foundation (07-CVD 03) by grants to Dr Kaab (01GS0499, 01GI0204, and 01GS0838). Dr Sinner is supported by the German Heart Foundation.; KORA S4: The KORA platform is funded by the Helmholtz Zentrum Munchen, the BMBF partly in the context of the German National Genome Research Network, and the State of Bavaria, and as part of LMUinnovativ; CHARGE Stroke Consortium: Supported by grants or contracts from the National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 R01HL087641, R01HL59367, and R01HL086694, R01HL093029), the National Human Genome Research Institute (U01HG004402), and NIH (HHSN268200625226C) and the NIH Roadmap for Medical Research (UL1R025005) to the Atherosclerosis Risk in Communities study; contracts and grants from the National Heart, Lung, and Blood Institute (N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01HL080295, and R01HL087652), the National Institute on Aging (R01AG027002), the National Center for Research Resources (M01RR00069, that partially supported the genotyping), and the National Institute of Diabetes and Digestive and Kidney Diseases (DK063491) to the Cardiovascular Health Study; grants from the National Heart, Lung, and Blood Institute (N01-HC-25195) and its contract with Affymetrix for genotyping services (N02-HL-6-4278), the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center for the use of the Linux Cluster for Genetic Analysis; and by grants from the NINDS (NS17950) and the National Institute of Aging (AG08122, AG031287, and AG033193 to the Framingham Heart Study), the Netherlands Organization of Scientific Research (175.010.2005.011), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Ageing (050-060-810), the Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture, and Science, the Ministry for Health, Welfare, and Sports, the European Commission, and the Municipality of Rotterdam to the Rotterdam Study. We thank the staff and participants of the above-mentioned studies for their important contributions. NR 45 TC 27 Z9 29 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2011 VL 4 IS 5 BP 557 EP U188 DI 10.1161/CIRCGENETICS.110.959197 PG 28 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 841RB UT WOS:000296529200017 PM 21846873 ER PT J AU Barrett, LF Mesquita, B Gendron, M AF Barrett, Lisa Feldman Mesquita, Batja Gendron, Maria TI Context in Emotion Perception SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article DE emotion; emotion recognition; emotion perception; language; context; culture ID FACIAL EXPRESSIONS; CULTURAL-DIFFERENCES; CATEGORICAL PERCEPTION; AMYGDALA RESPONSE; FEARFUL FACES; RECOGNITION; LANGUAGE AB We review recent work demonstrating consistent context effects during emotion perception. Visual scenes, voices, bodies, other faces, cultural orientation, and even words shape how emotion is perceived in a face, calling into question the still-common assumption that the emotional state of a person is written on and can be read from the face like words on a page. Incorporating context during emotion perception appears to be routine, efficient, and, to some degree, automatic. This evidence challenges the standard view of emotion perception represented in psychology texts, in the cognitive neuroscience literature, and in the popular media and points to a necessary change in the basic paradigm used in the scientific study of emotion perception. C1 [Barrett, Lisa Feldman; Gendron, Maria] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mesquita, Batja] Univ Leuven, Dept Psychol, Louvain, Belgium. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. EM barretli@bc.edu NR 24 TC 124 Z9 131 U1 12 U2 82 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD OCT PY 2011 VL 20 IS 5 BP 286 EP 290 DI 10.1177/0963721411422522 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 841JU UT WOS:000296509400003 ER PT J AU Palileo, C Kaunitz, JD AF Palileo, Coleen Kaunitz, Jonathan D. TI Gastrointestinal defense mechanisms SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE lipopolysaccharides; matrix metalloproteinase; prostaglandin E synthase; proton pump inhibitor; trefoil factors ID GASTRODUODENAL MUCOSAL DEFENSE; BICARBONATE SECRETION; SENSORY NEURONS; GASTRIC-ULCERS; INDOMETHACIN; INJURY; ANGIOGENESIS; LANSOPRAZOLE; INHIBITORS; MELATONIN AB Purpose of review We have highlighted the recent findings relating to gastroduodenal mucosal defense, including elements that may contribute to the failure of defense systems and factors that enhance mucosal healing, focusing on findings that elucidate new pathophysiological mechanisms. Recent findings Bicarbonate secretion is mediated by multiple types of prostaglandin E synthases, including membrane-bound prostaglandin E synthase-1. Mucins, growth factors, and trefoil factors are involved in accelerating gastric injury healing through epithelial reconstruction. A combination of NSAIDs and bile induce greater damage on the mucosa than if the two agents were acting alone. Proton pump inhibitors defend the mucosa from injury by promoting cellular restitution as well as inhibiting gastric acid secretion and reactive oxygen species (ROS) damage. Roxatidine, a novel H-2 receptor antagonist, acts through a mechanism that involves nitric oxide. Melatonin enhances angiogenesis through the upregulation of plasma levels of gastrin and matrix metalloproteinase expression. The mucosal protective drug polaprezinc exhibits ROS-quenching activities. Lipopolysaccharides induce oxidative stress mediated by p38 mitogen-activated protein kinase (p38 MAPK). Aging weakens gastroduodenal mucosal defense mechanisms. Summary There is a wide array of pathways leading to gastroduodenal mucosal injury in addition to protective defense mechanisms that counteract them to maintain homeostasis. Increased understanding of these systems may help identify novel molecular targets for the prevention and treatment of mucosal injury. C1 [Palileo, Coleen; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Palileo, Coleen] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Palileo, Coleen; Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, David Geffen Sch Med, Bldg 114,Suite 217E,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU VA Merit Review; NIH/NIDDK [R01 DK54221] FX This study was supported by VA Merit Review funding and NIH/NIDDK R01 DK54221 (J.D.K.). NR 39 TC 22 Z9 25 U1 0 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD OCT PY 2011 VL 27 IS 6 BP 543 EP 548 DI 10.1097/MOG.0b013e32834b3fcb PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 836WN UT WOS:000296148000010 PM 21897225 ER PT J AU Tena, G Boudsocq, M Sheen, J AF Tena, Guillaume Boudsocq, Marie Sheen, Jen TI Protein kinase signaling networks in plant innate immunity SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Review ID PATTERN-RECOGNITION RECEPTORS; DEFENSE GENE-EXPRESSION; ARABIDOPSIS-THALIANA; MAP KINASE; TRANSCRIPTION FACTOR; MOLECULAR-PATTERNS; NITRIC-OXIDE; PHYTOALEXIN BIOSYNTHESIS; NICOTIANA-BENTHAMIANA; NADPH OXIDASE AB In plants and animals, innate immunity is triggered through pattern recognition receptors (PRRs) in response to microbe-associated molecular patterns (MAMPs) to provide the first line of inducible defense. Plant receptor protein kinases (RPKs) represent the main plasma membrane PRRs perceiving diverse MAMPs. RPKs also recognize secondary danger-inducible plant peptides and cell-wall signals. Both types of RPKs trigger rapid and convergent downstream signaling networks controlled by calcium-activated PKs and mitogen-activated PK (MAPK) cascades. These PK signaling networks serve specific and overlapping roles in controlling the activities and synthesis of a plethora of transcription factors (TFs), enzymes, hormones, peptides and antimicrobial chemicals, contributing to resistance against bacteria, oomycetes and fungi. C1 [Tena, Guillaume; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Tena, Guillaume; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Tena, Guillaume; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Boudsocq, Marie] INRA CNRS UEVE, Unite Rech Genom Vegetale, F-91057 Evry, France. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIH; NSF; European Community FX We thank Fred Ausubel, Sang-Dong Yoo, Libo Shan, Ping He, Thorsten Nurnberger, Gerry Berkowitz, John Mundy, Shugun Zhang, Kazuo Shinozaki, Cyril Zipfel and Scott Peck for sharing ideas, insights and preprints. We apologize for limited literature coverage owing to space limitation. The projects on innate immunity, MAPK and CDPK signaling have been supported by the NIH and NSF grants. MB was supported by a Marie Curie International fellowship within the 6th European Community Framework Program. NR 85 TC 147 Z9 153 U1 14 U2 109 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 EI 1879-0356 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD OCT PY 2011 VL 14 IS 5 BP 519 EP 529 DI 10.1016/j.pbi.2011.05.006 PG 11 WC Plant Sciences SC Plant Sciences GA 843QA UT WOS:000296685900007 PM 21704551 ER PT J AU Iezzoni, LI Frakt, AB Pizer, SD AF Iezzoni, Lisa I. Frakt, Austin B. Pizer, Steven D. TI Uninsured persons with disability confront substantial barriers to health care services SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Health insurance; Disability; Access; Barriers to care ID HARD-OF-HEARING; PREVENTIVE SERVICES; BREAST-CANCER; PHYSICAL-DISABILITIES; INSURANCE COVERAGE; INTERVIEW SURVEY; NATIONAL-HEALTH; CERVICAL-CANCER; WOMEN; ACCESS AB Background: Despite social "safety net" programs, many U.S. residents with disabilities lack insurance coverage and thus risk financial barriers to accessing care. The study objectives were to characterize working-age adults with disabilities who lack health insurance and to examine their self-reported barriers to care. Methods: The authors conducted analyses of nationally representative Medical Expenditure Panel Survey data from 2000 through 2006. Results: During this time period, 14.8% of working-age U.S. residents lacked health insurance, including 11.6% of persons with disabilities. Focusing only on uninsured individuals, persons with disabilities were significantly (p = .001) more likely than those without disabilities to have a usual source of care. However, on 6 other access measures (those that comprised our composite indicator of access barriers), uninsured persons with disabilities reported barriers significantly (p = .001) more often than did individuals without disabilities: 36.0% of uninsured persons with disabilities reported being unable to get necessary medical care, compared with 9.5% of uninsured, nondisabled persons; and 26.9% of uninsured persons with disabilities reported being unable to get necessary medications, compared with 5.3% of uninsured individuals without disabilities. Having a cognitive impairment produced the largest adjusted odds ratio (AOR) of reporting any access barrier (1.64, 95% CI 144-1.87), while having lower body functional limitations or hearing deficits also produced relatively high AORs (1.47, 1.32-1.65 and 1.48, 1.11-1.98, respectively). Conclusions: Uninsured individuals with disabilities confront significantly more barriers to accessing care than do nondisabled persons without health insurance. Certain types of disabilities appear especially associated with experiencing access barriers, suggesting areas requiring particular attention. (C) 2011 Elsevier Inc. All rights reserved. C1 [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frakt, Austin B.; Pizer, Steven D.] US Dept Vet Affairs, Boston, MA 02130 USA. [Frakt, Austin B.; Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Iezzoni, LI (reprint author), 50 Staniford St,Room 901B, Boston, MA USA. EM liezzoni@partners.org FU Agency for Healthcare Research and Quality [R01 HS015941] FX This work was funded by the Agency for Healthcare Research and Quality (Grant No. R01 HS015941). The authors have no conflicts of interest to declare. NR 60 TC 29 Z9 30 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD OCT PY 2011 VL 4 IS 4 BP 238 EP 244 DI 10.1016/j.dhjo.2011.06.001 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 841XX UT WOS:000296549600005 PM 22014671 ER PT J AU Gorgun, G Anderson, KC AF Goerguen, Guellue Anderson, Kenneth C. TI Intrinsic modulation of lymphocyte function by stromal cell network: advance in therapeutic targeting of cancer SO IMMUNOTHERAPY LA English DT Review DE bone marrow stromal cells; hematologic malignancies; immunomodulatory drugs; immunotherapy; lymphocytes; macrophages; multiple myeloma; solid tumors; tumor microenvironment; tumor stromal cells ID HUMAN MULTIPLE-MYELOMA; REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; MESENCHYMAL STEM-CELLS; NF-KAPPA-B; DEXAMETHASONE-INDUCED APOPTOSIS; ARTHRITIS SYNOVIAL FIBROBLASTS; BLOOD MONONUCLEAR-CELLS; NATURAL-KILLER-CELL; SUPPRESSOR-CELLS AB Advances in tumor biology have demonstrated a point of critical importance: tumor are established as an intersection of malignant clone cells and surrounding stromal cells. The stroma is composed of nonhematopoietic cells, including connective tissue cells, blood vessels, nerves, fat and smooth muscle cells, in the extracellular matrix niche. Recent studies have demonstrated that stromal cells regulate immune responses by: coordinating lymphocyte homing, differentiation, activation and antigen responses; inducing tolerance; and maintaining immunologic memory. Hence, elucidation of the interaction between stromal cells and lymphocytes is essential for generating effective immunotherapies. In this article, we summarize what is currently known about the interactions between stromal cells and lymphocytes in the tumor microenvironment, as well as potential immunotherapeutic approaches targeting stroma-lymphocyte interactions; both in the context of our work on multiple myeloma, and of recent literature in both solid tumors and hematologic malignancies. C1 [Goerguen, Guellue; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gorgun, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gullu_gorgun@dfci.harvard.edu FU Celgene; Millennium; Novartis; Onyx; BMS; Merck FX Kennith C Anderson has recieved funding from Celgene, Millennium, Novartis, Onyx, BMS and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 155 TC 5 Z9 5 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD OCT PY 2011 VL 3 IS 10 BP 1253 EP 1264 DI 10.2217/IMT.11.124 PG 12 WC Immunology SC Immunology GA 843XX UT WOS:000296711800012 PM 21995575 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Chronic rhinosinusitis: Epidemiology and medical management SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE Rhinosinusitis; sinusitis; nasal polyposis; epidemiology; medical management; treatment ID ENDOSCOPIC SINUS SURGERY; ALLERGIC FUNGAL RHINOSINUSITIS; PLACEBO-CONTROLLED TRIAL; CHRONIC HYPERPLASTIC SINUSITIS; MESSENGER-RNA EXPRESSION; AQUEOUS NASAL SPRAY; QUALITY-OF-LIFE; DOUBLE-BLIND; ASPIRIN DESENSITIZATION; MUCOCILIARY CLEARANCE AB Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author's personal experience. (J Allergy Clin Immunol 2011; 128:693-707.) C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org NR 131 TC 116 Z9 119 U1 3 U2 30 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 OCT PY 2011 VL 128 IS 4 BP 693 EP 709 DI 10.1016/j.jaci.2011.08.004 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA 841UA UT WOS:000296538100001 PM 21890184 ER PT J AU Stoddard, FJ Luthra, R Sorrentino, EA Saxe, GN Drake, J Chang, YC Levine, JB Chedekel, DS Sheridan, RL AF Stoddard, Frederick J., Jr. Luthra, Rohini Sorrentino, Erica A. Saxe, Glenn N. Drake, Jennifer Chang, Yuchiao Levine, John B. Chedekel, David S. Sheridan, Robert L. TI A Randomized Controlled Trial of Sertraline to Prevent Posttraumatic Stress Disorder in Burned Children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ANXIETY DISORDER; PART I; ADOLESCENTS; DEPRESSION; PTSD; EFFICACY; TRAUMA AB Background: This study evaluated the potential benefits of a centrally acting selective serotonin reuptake inhibitor, sertraline, versus placebo for prevention of symptoms of posttraumatic stress disorder (PTSD) and depression in burned children. This is the first controlled investigation based on our review of the early use of a medication to prevent PTSD in children. Methods: Twenty-six children aged 6-20 were assessed in a 24-week double-blind placebo-controlled design. Each child received either flexibly dosed sertraline between 25-150 mg/day or placebo. At each reassessment, information was collected in compliance with the study medication, parental assessment of the child's symptomatology and functioning, and the child's self-report of symptomatology. The protocol was approved by the Human Studies Committees of Massachusetts General Hospital and Shriners Hospitals for Children. Results: The final sample was 17 subjects who received sertraline versus 9 placebo control subjects matched for age, severity of injury, and type of hospitalization. There was no significant difference in change from baseline with child-reported symptoms; however, the sertraline group demonstrated a greater decrease in parent-reported symptoms over 8 weeks (-4.1 vs. -0.5, p = 0.005), over 12 weeks (-4.4 vs. -1.2, p = .008), and over 24 weeks (-4.0 vs. -0.2, p = 0.017). Conclusions: Sertraline was a safe drug, and it was somewhat more effective in preventing PTSD symptoms than placebo according to parent report but not child report. Based on this study, sertraline may prevent the emergence of PTSD symptoms in children. C1 [Stoddard, Frederick J., Jr.; Luthra, Rohini; Sorrentino, Erica A.; Saxe, Glenn N.; Drake, Jennifer; Levine, John B.; Chedekel, David S.; Sheridan, Robert L.] Shriners Hosp Children, Boston, MA 02114 USA. [Stoddard, Frederick J., Jr.; Luthra, Rohini; Sorrentino, Erica A.; Saxe, Glenn N.; Drake, Jennifer; Levine, John B.; Chedekel, David S.; Sheridan, Robert L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Saxe, Glenn N.] NYU, Sch Med, Ctr Child Study, New York, NY USA. [Levine, John B.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Shriners Hosp Children, 55 Fruit St, Boston, MA 02114 USA. EM fstoddard@partners.org OI Saxe, Glenn/0000-0002-4756-1169 FU Shriners Hospitals for Children [8840]; Centers for Disease Control and Prevention [5R01DP000339]; John Henry Foundation; Shriners Hospital for Children-Boston [5R01DP000339]; Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital FX This study was supported by Grant # 8840 from the Shriners Hospitals for Children to Dr. Stoddard. Grant Support for Dr. Levine includes the Shriners Hospital for Children-Boston- and Centers for Disease Control and Prevention, Grant number 5R01DP000339, and the John Henry Foundation, The Benson-Henry Institute for Mind Body Medicine, Massachusetts General Hospital. NR 61 TC 19 Z9 19 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2011 VL 21 IS 5 BP 469 EP 477 DI 10.1089/cap.2010.0133 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 842OG UT WOS:000296608200011 PM 22040192 ER PT J AU Hayes, TB Anderson, LL Beasley, VR de Solla, SR Iguchi, T Ingraham, H Kestemont, P Kniewald, J Kniewald, Z Langlois, VS Luque, EH Mccoy, KA Munoz-de-Toro, M Oka, T Oliveira, CA Orton, F Ruby, S Suzawa, M Tavera-Mendoza, LE Trudeau, VL Victor-Costa, AB Willingham, E AF Hayes, Tyrone B. Anderson, Lloyd L. Beasley, Val R. de Solla, Shane R. Iguchi, Taisen Ingraham, Holly Kestemont, Patrick Kniewald, Jasna Kniewald, Zlatko Langlois, Valerie S. Luque, Enrique H. McCoy, Krista A. Munoz-de-Toro, Monica Oka, Tomohiro Oliveira, Cleida A. Orton, Frances Ruby, Sylvia Suzawa, Miyuki Tavera-Mendoza, Luz E. Trudeau, Vance L. Victor-Costa, Anna Bolivar Willingham, Emily TI Demasculinization and feminization of male gonads by atrazine: Consistent effects across vertebrate classes SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Atrazine; Gonads; Endocrine disruptor ID SPRAGUE-DAWLEY RATS; NORTHERN LEOPARD FROG; ADRENOCORTICAL CARCINOMA-CELLS; AROMATASE CYP19 ACTIVITY; TADPOLE XENOPUS-LAEVIS; S-TRIAZINE HERBICIDES; MALE WISTAR RATS; RANA-PIPIENS; IN-VITRO; SEXUAL-DIFFERENTIATION AB Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called "Hill criteria" (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause-effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis - demonstrated in fish, amphibians, reptiles, and mammals - represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the "Hill criteria". (C) 2011 Published by Elsevier Ltd. C1 [Hayes, Tyrone B.] Univ Calif Berkeley, Museum Vertebrate Zool, Lab Integrat Studies Amphibian Biol, Energy & Resources Grp,Grp Endocrinol, Berkeley, CA 94720 USA. [Hayes, Tyrone B.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Anderson, Lloyd L.] Iowa State Univ Sci & Technol, Coll Vet Med, Dept Anim Sci, Coll Agr & Life, Ames, IA 50011 USA. [Beasley, Val R.] Univ Illinois, Coll Vet Med, Dept Comparat Biosci, Envirovet Program Wildlife & Ecosyst Hlth, Urbana, IL 61802 USA. [de Solla, Shane R.] Environm Canada, Wildlife & Landscape Sci Directorate, Burlington, ON L7R 4A6, Canada. [Iguchi, Taisen] Natl Inst Basic Biol, Okazaki, Aichi 4448787, Japan. [Ingraham, Holly; Suzawa, Miyuki] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kestemont, Patrick] Univ Namur FUNDP, Unit Res Organism Biol, B-5000 Namur, Belgium. [Kniewald, Jasna; Kniewald, Zlatko] Univ Zagreb, Fac Food Technol & Biotechnol, Zagreb 41000, Croatia. [Langlois, Valerie S.] Royal Mil Coll Canada, Dept Chem & Chem Engn, Kingston, ON K7K 7B4, Canada. [Luque, Enrique H.; Munoz-de-Toro, Monica] Univ Nacl Litoral, Sch Biochem & Biol Sci, Lab Endocrinol & Tumores Hormonodependientes, Santa Fe, Argentina. [McCoy, Krista A.] Univ S Florida, Dept Integrat Biol, Tampa, FL 33620 USA. [Oka, Tomohiro] IDEA Consultants Inc, Inst Environm Ecol, Shizuoka 4210212, Japan. [Oliveira, Cleida A.; Victor-Costa, Anna Bolivar] Univ Fed Minas Gerais, Dept Morphol, BR-31270901 Belo Horizonte, MG, Brazil. [Orton, Frances] Univ London, Sch Pharm, Ctr Toxicol, London WC1N 1AX, England. [Ruby, Sylvia] Concordia Univ, Dept Biol, Montreal, PQ H3G 1M8, Canada. [Tavera-Mendoza, Luz E.] Harvard Univ, Sch Med, Dana Faber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tavera-Mendoza, Luz E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Trudeau, Vance L.] Univ Ottawa, Dept Biol, Ctr Adv Res Environm Genom, Ottawa, ON K1N 6N5, Canada. RP Hayes, TB (reprint author), Univ Calif Berkeley, Museum Vertebrate Zool, Lab Integrat Studies Amphibian Biol, Energy & Resources Grp,Grp Endocrinol, Berkeley, CA 94720 USA. EM tyrone@berkeley.edu RI Orton, Frances/L-8213-2014; Oliveira, Cleida/C-4966-2013; OI Oliveira, Cleida/0000-0001-9610-7846; Trudeau, Vance/0000-0002-0845-9444 FU TBH; Novartis; Syngenta Crop Protection; Ecorisk; National Science Foundation; World Wildlife Fund; Alton Jones Foundation; Homeland Foundation; Rose Foundation, Park-Water Company; Biofaculty Award [UCB]; Distinguished Mentor Award [UCB]; Distinguished Teaching Award [UCB]; Mitchell Kapor Foundation; David Foundation; Cornell-Douglas Foundation; Wallace Global Fund; Class of '43 Endowed Chair (UCB); Toxic Substances Research and Teaching Program (UCB), Hewlett Packard; Howard Hughes Medical Institute; McNair Scholars Program (UCB); Amgen Scholars Program (UCB); Mentored Research fellowship program (UCB); Center for Designing Foods to Improve Nutrition; Dr. Scholl Foundation; SRdS (Environment Canada); Ministry of the Environment, Japan; National Institutes of Health; National Science Funds, FNRS, Belgium; Ministry of Science and Technology of the Republic of Croatia; Ford Foundation; Universidad Nacional del Litoral; Argentine National Council for Science and Technology (CONICET); Argentine National Agency for the Promotion of Science and Technology; National Institute of Environmental Health Sciences; University of Florida Institute of Food and Agricultural Sciences; CO & ABV-C (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq/Brazil; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES/Brazil; Declining Amphibian Population Task Force and Depertment for Environmental, Food and Rural Affairs, UK; Toxic Substances Research Initiative, Government of Canada; Environment Canada; Canadian Water Network; Texas State University, San Marcos FX We thank Donald Tillitt and Diana Papoulias, USGS, for the photograph featured in Fig. 2, panel A. Primary research on atrazine was supported as follows: TBH (Novartis, Syngenta Crop Protection, Ecorisk, the National Science Foundation, the World Wildlife Fund, the Alton Jones Foundation, the Homeland Foundation, the Rose Foundation, Park-Water Company, the Biofaculty Award [UCB], the Distinguished Mentor Award [UCB], the Distinguished Teaching Award [UCB], the Mitchell Kapor Foundation, the David Foundation, the Cornell-Douglas Foundation, the Wallace Global Fund, the Class of '43 Endowed Chair (UCB), the Toxic Substances Research and Teaching Program (UCB), Hewlett Packard, the Biology Fellows Program (Howard Hughes Medical Institute), the McNair Scholars Program (UCB), the Amgen Scholars Program (UCB), and the Mentored Research fellowship program (UCB); LA (USDA grant through the Center for Designing Foods to Improve Nutrition; VRB (John G. Shedd Aquarium Funding through support from the Dr. Scholl Foundation); SRdS (Environment Canada); TI & TO (Ministry of the Environment, Japan); HI & MS (National Institutes of Health), PK (National Science Funds, FNRS, Belgium); JK & ZK (Ministry of Science and Technology of the Republic of Croatia, Former Yu-USA Joint Fund for S&T Coop, and the Ford Foundation; VSL (NSERC-PGSD program), EHL & MMT (Universidad Nacional del Litoral, CAI+D program, the Argentine National Council for Science and Technology (CONICET), and the Argentine National Agency for the Promotion of Science and Technology; KAM (National Institute of Environmental Health Sciences to L Guillette, Rewald, Olowo, Society for Integrative and Comparative Biology, Sigma Xi grants in aid of research and the University of Florida Institute of Food and Agricultural Sciences Women's Club Fellowship; CO & ABV-C (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq/Brazil, grant and research fellowship to CAO, Master fellowship to ABVC supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES/Brazil); FO (Declining Amphibian Population Task Force and Depertment for Environmental, Food and Rural Affairs, UK); SR & LET-M (Toxic Substances Research Initiative, Government of Canada; VLT (Environment Canada and the Canadian Water Network); EW (Texas State University, San Marcos). NR 142 TC 85 Z9 90 U1 29 U2 241 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 2011 VL 127 IS 1-2 SI SI BP 64 EP 73 DI 10.1016/j.jsbmb.2011.03.015 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 841WV UT WOS:000296546800010 PM 21419222 ER PT J AU Sher, L AF Sher, Leo TI Teaching medical staff in general hospitals about suicide prevention SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Letter ID INPATIENT SUICIDE C1 James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, Bronx, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, Dept Psychiat, Mt Sinai Sch Med, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM DrLeoSher@gmail.com NR 4 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER TAIWAN PI TAIPEI PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2, TAIPEI, 10449, TAIWAN SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD OCT PY 2011 VL 110 IS 10 BP 664 EP 664 DI 10.1016/j.jfma.2011.08.011 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 843IM UT WOS:000296665500011 PM 21982473 ER PT J AU Factor, SA Steenland, NK Higgins, DS Molho, ES Kay, DM Montimurro, J Rosen, AR Zabetian, CP Payami, H AF Factor, Stewart A. Steenland, N. Kyle Higgins, Donald S. Molho, Eric S. Kay, Denise M. Montimurro, Jennifer Rosen, Ami R. Zabetian, Cyrus P. Payami, Haydeh TI Disease-Related and Genetic Correlates of Psychotic Symptoms in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; psychosis; depression; sleep; freezing of gait; genetics; risk factors ID VISUAL HALLUCINATIONS; RISK-FACTORS; LEWY BODIES; DEMENTIA; POLYMORPHISMS; ASSOCIATION; FREQUENCY; LEVODOPA; CHOLECYSTOKININ; PREVALENCE AB Our aim was to examine disease-related and genetic correlates of the development of psychotic symptoms in a large population of patients with Parkinson's disease. We studied 500 patients with Parkinson's disease from the NeuroGenetics Research Consortium using logistic regression models. Predictors were demographic, clinical (motor/nonmotor features), and genetic, measured as continuous or dichotomous variables. Continuous measures were divided into population-based tertiles. Results are given as odds ratios (95% confidence intervals) for dichotomous variables and by ascending tertile for continuous variables. Psychotic symptoms were associated with increasing age: 4.86 (1.62-14.30) and 6.25 (2.09-18.74) (test for trend: P = 0.01); and duration of disease: 3.81 (1.23-11.76) and 5.33 (1.68-16.89) (test for trend: P = 0.03). For nonmotor features, we demonstrated positive trends with depression: 1.31 (0.47-3.61) and 5.01 (2.04-12.33) (test for trend: P < 0.0001); cognitive dysfunction: 0.69 (0.26-1.84) and 2.51 (1.00-6.29) (test for trend: P 5 0.03); and an excess for those with sleep disorders: 2.00 (1.03-3.89) (P = 0.04). Psychotic symptoms were not associated with tremor or postural instability scores, but there was an association with freezing of gait: 3.83 (1.67-8.75) (P < 0.002). Psychotic symptoms were not associated with the presence of any examined polymorphisms in the apolipoprotein, alpha-synuclein, or microtubule associated protein tau genes. This is the largest study to examine correlates of psychotic symptoms in Parkinson's disease. We discovered a novel association with freezing of gait. We demonstrated an association with depression and duration of disease, both of which were inconsistently related in previous studies, and confirmed the association with age, cognitive dysfunction, and sleep disorders. (C) 2011 Movement Disorder Society C1 [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30329 USA. [Higgins, Donald S.] Samuel Stratton Vet Affairs Med Ctr, Albany, NY USA. [Molho, Eric S.] Albany Med Ctr, Albany, NY USA. [Kay, Denise M.; Montimurro, Jennifer; Payami, Haydeh] New York State Dept Hlth, Albany, NY USA. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Seattle, WA USA. RP Factor, SA (reprint author), Emory Univ, Sch Med, Dept Neurol, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM sfactor@emory.edu OI Kay, Denise/0000-0002-9928-2698; Zabetian, Cyrus/0000-0002-7739-4306 FU Michael J. Fox Foundation; Close to a Cure Foundation; NIH [R01-NS36960]; Department of Veterans Affairs; New York State Department of Health Wadsworth Center; Sartain Lanier Family Foundation; Riley Family Chair in Parkinson's Disease; Teva Neurosciences; Ipsen; Ceregene; Consolidated Anti-aging Foundation; Allergan; EMD Serono; Impax Pharmaceuticals; Acadia Pharmaceuticals; Merz Pharmaceuticals FX Funding agencies: Michael J. Fox Foundation: Edmond J. Safra Global Genetics Consortia Grant; Close to a Cure Foundation: A Fund for Parkinson's Research of Foundation for the Carolinas; NIH: R01-NS36960, Department of Veterans Affairs Merit Review Award; New York State Department of Health Wadsworth Center; The Sartain Lanier Family Foundation; and the Riley Family Chair in Parkinson's Disease.; Stewart A. Factor has research grants from Teva Neurosciences, Ipsen, Ceregene, the Michael J. Fox Foundation, and the Consolidated Anti-aging Foundation and also was a consultant for Boehringer-Ingelheim. Eric S. Molho has received research grants from Teva Neurosciences, Allergan, EMD Serono, Impax Pharmaceuticals, and Acadia Pharmaceuticals and has received consulting fees from Allergan, Merz Pharmaceuticals, and Ipsen. NR 49 TC 19 Z9 19 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 IS 12 BP 2190 EP 2195 DI 10.1002/mds.23806 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 842PH UT WOS:000296610900012 PM 21714002 ER PT J AU Palacios, N Gao, X McCullough, ML Jacobs, EJ Patel, AV Mayo, T Schwarzschild, MA Ascherio, A AF Palacios, Natalia Gao, Xiang McCullough, Marjorie L. Jacobs, Eric J. Patel, Alpa V. Mayo, Tinisha Schwarzschild, Michael A. Ascherio, Alberto TI Obesity, Diabetes, and Risk of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE obesity; diabetes; Parkinson's disease; body mass index ID CORONARY HEART-DISEASE; BODY-MASS INDEX; PHYSICAL-ACTIVITY; PROSPECTIVE COHORT; FAT DISTRIBUTION; CANCER; INSULIN; WOMEN; HYPOTHALAMUS; METAANALYSIS AB The aim of this work was to investigate whether obesity and diabetes are related to risk of Parkinson's disease. We prospectively followed 147,096 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2005. Participants provided information on anthropometric variables and medical history at baseline and on waist circumference in 1997. Incident cases of Parkinson's disease (n = 656) were confirmed by treating neurologists and medical record review. Relative risks were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Neither body mass index nor waist circumference significantly predicted Parkinson's disease risk. Relative risk comparing individuals with a baseline body mass index of >= 30 to those with a body mass index <23 was 1.00 (95% confidence interval: 0.75, 1.34; P trend: 0.79), and that comparing individuals with a waist circumference in the top category (>= 40.3 inches in men and >= 35 inches in women) to those in the bottom category (<34.5 inches in men and <28 inches in women) was 1.35 (95% confidence interval: 0.95, 1.93; P trend: 0.08). History of diabetes was not significantly associated with Parkinson's disease risk (combined relative risks = 0.88; 95% confidence interval: 0.62, 1.25; P heterogeneity = 0.96). In addition, neither body mass index at age 18 nor changes in weight between age 18 and baseline were significantly associated with Parkinson's disease risk. The results did not differ significantly by gender. Our results do not provide evidence for a relationship between body mass index, weight change, waist circumference, or baseline diabetes and risk of Parkinson's disease. (C) 2011 Movement Disorder Society C1 [Palacios, Natalia; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [McCullough, Marjorie L.; Jacobs, Eric J.; Patel, Alpa V.; Mayo, Tinisha] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Palacios, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM palacios@hsph.harvard.edu FU National Institutes of Health [R01 NS048517, T32 ES07069] FX This work was funded by the National Institutes of Health (R01 NS048517; to A.A.) and the Training Program in Environmental Epidemiology, NIH Kirshstein National Research Service Award (T32 ES07069; to N.P.). NR 30 TC 41 Z9 42 U1 1 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 IS 12 BP 2253 EP 2259 DI 10.1002/mds.23855 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 842PH UT WOS:000296610900021 PM 21739472 ER PT J AU Ding, HL Sarokhan, AK Roderick, SS Bakshi, R Maher, NE Ashourian, P Kan, CG Chang, S Santarlasci, A Swords, KE Ravina, BM Hayes, MT Sohur, US Wills, AM Flaherty, AW Unni, VK Hung, AY Selkoe, DJ Schwarzschild, MA Schlossmacher, MG Sudarsky, LR Growdon, JH Ivinson, AJ Hyman, BT Scherzer, CR AF Ding, Hongliu Sarokhan, Alison K. Roderick, Sarah S. Bakshi, Rachit Maher, Nancy E. Ashourian, Paymon Kan, Caroline G. Chang, Sunny Santarlasci, Andrea Swords, Kyleen E. Ravina, Bernard M. Hayes, Michael T. Sohur, U. Shivraj Wills, Anne-Marie Flaherty, Alice W. Unni, Vivek K. Hung, Albert Y. Selkoe, Dennis J. Schwarzschild, Michael A. Schlossmacher, Michael G. Sudarsky, Lewis R. Growdon, John H. Ivinson, Adrian J. Hyman, Bradley T. Scherzer, Clemens R. TI Association of SNCA with Parkinson: Replication in the Harvard NeuroDiscovery Center Biomarker Study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; alpha-synuclein; GATA transcription factors; biomarker; genome-wide association study ID ALPHA-SYNUCLEIN; DISEASE; TRANSCRIPTION AB Background: Mutations in the alpha-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson's disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. Methods: We genotyped a prioritized noncoding variant in SNCA intron 4 in 344 patients with Parkinson's disease and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. Results: The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio, 1.40; P = .0032). Conclusions: This result increases confidence in the notion that in many clinically well-characterized patients, genetic variation in SNCA contributes to "sporadic" disease. (C) 2011 Movement Disorder Society C1 [Ding, Hongliu; Sarokhan, Alison K.; Roderick, Sarah S.; Bakshi, Rachit; Maher, Nancy E.; Ashourian, Paymon; Kan, Caroline G.; Chang, Sunny; Selkoe, Dennis J.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Lab Neurogen, Ctr Neurol Dis, Cambridge, MA 02139 USA. [Hayes, Michael T.; Hung, Albert Y.; Sudarsky, Lewis R.; Scherzer, Clemens R.] Brigham & Womens Hosp, Dept Neurol, Cambridge, MA 02139 USA. [Sarokhan, Alison K.; Roderick, Sarah S.; Maher, Nancy E.; Kan, Caroline G.; Chang, Sunny; Santarlasci, Andrea; Swords, Kyleen E.; Ivinson, Adrian J.; Hyman, Bradley T.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Biomarker Program, Cambridge, MA 02139 USA. [Ashourian, Paymon] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Santarlasci, Andrea; Sohur, U. Shivraj; Wills, Anne-Marie; Flaherty, Alice W.; Unni, Vivek K.; Schwarzschild, Michael A.; Growdon, John H.; Hyman, Bradley T.; Scherzer, Clemens R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Swords, Kyleen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ravina, Bernard M.] Biogen Idec Inc, Translat Neurol, Cambridge, MA USA. [Schlossmacher, Michael G.] Univ Ottawa, Ottawa, ON, Canada. RP Scherzer, CR (reprint author), Harvard Univ, Sch Med, Lab Neurogen, Ctr Neurol Dis, 65 Landsdowne St,Suite 307A, Cambridge, MA 02139 USA. EM cscherzer@rics.bwh.harvard.edu RI Bakshi, Rachit/D-6960-2012 FU NIH [R01 NS064155, R21 NS060227, K24 NS060991]; Harvard NeuroDiscovery Center; Michael J. Fox Foundation; M.E.M.O. Hoffman Foundation; RJG Foundation; Neurologix, Inc. FX This study was funded by NIH grants R01 NS064155 (to C.R.S.), R21 NS060227 (to C.R.S.), K24 NS060991 (to M.A.S.), the Harvard NeuroDiscovery Center (to C.R.S. and B.T.H.), the Michael J. Fox Foundation (grants to C.R.S., M.G.S., and J.H.G.), the M.E.M.O. Hoffman Foundation (to C.R.S.), and the RJG Foundation (to C.R.S.).; Clemens R. Scherzer is a consultant for Link Medicine Corp and the Michael J. Fox Foundation and a scientific collaborator of DiaGenic and Pfizer. Alice W. Flaherty has a contract with Neurologix, Inc. NR 7 TC 10 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 IS 12 BP 2283 EP 2286 DI 10.1002/mds.23934 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 842PH UT WOS:000296610900026 PM 21953863 ER PT J AU Seppi, K Weintraub, D Coelho, M Perez-Lloret, S Fox, SH Katzenschlager, R Hametner, EM Poewe, W Rascol, O Goetz, CG Sampaio, C AF Seppi, Klaus Weintraub, Daniel Coelho, Miguel Perez-Lloret, Santiago Fox, Susan H. Katzenschlager, Regina Hametner, Eva-Maria Poewe, Werner Rascol, Olivier Goetz, Christopher G. Sampaio, Cristina TI The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the Non-Motor Symptoms of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; evidence-based medicine; dopamine agonists; tricyclic antidepressants; selective serotonin reuptake inhibitors (SSRIs); omega-3 fatty-acids; transcranial magnetic stimulation ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; BOTULINUM-TOXIN-A; DOPAMINERGIC-INDUCED HALLUCINATIONS; TRANSCRANIAL MAGNETIC STIMULATION; QUALITY STANDARDS SUBCOMMITTEE; DRUG-INDUCED PSYCHOSIS; ACADEMY-OF-NEUROLOGY; SCALE MDS-UPDRS; DOUBLE-BLIND AB The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Omega-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not usful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. (C) 2011 Movement Disorder Society C1 [Sampaio, Cristina] Univ Lisbon, Inst Med Mol, P-1699 Lisbon, Portugal. [Seppi, Klaus; Hametner, Eva-Maria; Poewe, Werner] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis & Mental Illness Res Educ & Clin C, Philadelphia, PA USA. [Seppi, Klaus] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA. [Coelho, Miguel] Hosp Santa Maria, Neurol Clin Res Unit, Inst Med Mol, Lisbon, Portugal. [Perez-Lloret, Santiago; Rascol, Olivier] Toulouse Univ Hosp, Dept Clin Pharmacol, Toulouse, France. [Fox, Susan H.] Toronto Western Hosp, Movement Disorder Clin, Toronto, ON, Canada. [Katzenschlager, Regina] Danube Hosp SMZ Ost, Dept Neurol, Vienna, Austria. [Goetz, Christopher G.] Rush Univ Med Ctr, Dept Neurol Sci, Chicago, IL USA. RP Sampaio, C (reprint author), Univ Lisbon, Inst Med Mol, P-1699 Lisbon, Portugal. EM klaus.seppi@uki.at; crissampaio@mac.com OI Coelho, Miguel/0000-0002-4008-8110 FU MDS; Teva pharmaceuticals FX This work was supported by the MDS and an unrestricted educational grant from Teva pharmaceuticals. NR 118 TC 261 Z9 271 U1 19 U2 95 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2011 VL 26 SU 3 BP S42 EP S80 DI 10.1002/mds.23884 PG 39 WC Clinical Neurology SC Neurosciences & Neurology GA 842PN UT WOS:000296611500003 PM 22021174 ER PT J AU McCarthy, JR Jaffer, FA AF McCarthy, Jason R. Jaffer, Farouc A. TI The role of nanomedicine in the imaging and therapy of thrombosis SO NANOMEDICINE LA English DT Editorial Material DE imaging; iron oxide; therapy; thrombolysis; thrombosis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE MYOCARDIAL-INFARCTION; ACUTE ISCHEMIC-STROKE; CONTRAST AGENT; TARGETED THROMBOLYSIS; NANOPARTICLES C1 [McCarthy, Jason R.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [McCarthy, Jason R.; Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. RP McCarthy, JR (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, 185 Cambridge St,Suite 5-210, Boston, MA 02114 USA. EM mccarthy@hms.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [R21 HL093607, R01 HL108229-02, R01 HL108229, 1R01HL108229, R21HL093607, R21 HL093607-02, HHSN268201000044C]; PHS HHS [HHSN268201000044C] NR 13 TC 3 Z9 3 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD OCT PY 2011 VL 6 IS 8 BP 1291 EP 1293 DI 10.2217/NNM.11.128 PG 3 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 842NJ UT WOS:000296605900001 PM 22026372 ER PT J AU Hsu, FC Sides, EG Mychaleckyj, JC Worrall, BB Elias, GA Liu, Y Chen, WM Coull, BM Toole, JF Rich, SS Furie, KL Sale, MM AF Hsu, F. -C. Sides, E. G. Mychaleckyj, J. C. Worrall, B. B. Elias, G. A. Liu, Y. Chen, W. -M. Coull, B. M. Toole, J. F. Rich, S. S. Furie, K. L. Sale, M. M. TI Transcobalamin 2 variant associated with poststroke homocysteine modifies recurrent stroke risk SO NEUROLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLASMA TOTAL HOMOCYSTEINE; FALSE DISCOVERY RATE; BETA-SYNTHASE GENE; METHYLENETETRAHYDROFOLATE REDUCTASE; VITAMIN INTERVENTION; VASCULAR-DISEASE; ISCHEMIC-STROKE; MYOCARDIAL-INFARCTION AB Objectives: The Vitamin Intervention for Stroke Prevention trial found an association between baseline poststroke homocysteine (Hcy) and recurrent stroke. We investigated genes for enzymes and cofactors in the Hcy metabolic pathway for association with Hcy and determined whether associated single nucleotide polymorphisms (SNPs) influenced recurrent stroke risk. Methods: Eighty-six SNPs in 9 candidate genes (BHMT1, BHMT2, CBS, CTH, MTHFR, MTR, MTRR, TCN1, and TCN2) were genotyped in 2,206 subjects (83% European American). Associations with Hcy measures were assessed using linear regression models assuming an additive genetic model, adjusting for age, sex, and race and additionally for baseline Hcy when postmethionine load change was assessed. Associations with recurrent stroke were evaluated using survival analyses. Results: Five SNPs in the transcobalamin 2 (TCN2) gene were associated with baseline Hcy (false discovery rate [FDR]-adjusted p = 0.049). TCN2 SNP rs731991 was associated with recurrent stroke risk in the low-dose arm of the trial under a recessive model (log-rank test p = 0.009, hazard ratio 0.34). Associations with change in postmethionine load Hcy levels were found with 5 SNPs in the cystathionine beta-synthase (CBS) gene (FDR-adjusted p < 0.031). Conclusions: TCN2 variants contribute to poststroke Hcy levels, whereas variants in the CBS gene influence Hcy metabolism. Variation in the TCN2 gene also affects recurrent stroke risk in response to cofactor therapy. Neurology (R) 2011;77:1543-1550 C1 [Mychaleckyj, J. C.; Worrall, B. B.; Elias, G. A.; Chen, W. -M.; Rich, S. S.; Sale, M. M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. [Hsu, F. -C.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Sides, E. G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27103 USA. [Sides, E. G.; Liu, Y.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Mychaleckyj, J. C.; Worrall, B. B.; Chen, W. -M.; Rich, S. S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Worrall, B. B.] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA. [Rich, S. S.; Sale, M. M.] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. [Sale, M. M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Coull, B. M.] Univ Arizona, Dept Neurol, Tucson, AZ USA. [Furie, K. L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Furie, K. L.] Harvard Univ, Dept Neurol, Boston, MA 02115 USA. RP Sale, MM (reprint author), Univ Virginia, Ctr Publ Hlth Genom, POB 800717, Charlottesville, VA 22908 USA. EM msale@virginia.edu FU NIH [NS034447, HG005160]; Wake Forest University General Clinical Research Center [M01-RR07122]; Abbott; Bill and Melinda Gates Foundation; NIH (NHGRI, NHLBI, NINDS); University of Virginia; Wake Forest University; NIH/NINDS; American Heart Association; Deane Institute FX Supported by the NIH (grants NS034447 to J.F.T. and HG005160 to M. M. S. and B. B. W.) and the Wake Forest University General Clinical Research Center (M01-RR07122).; Dr. Hsu and E. G. Sides report no disclosures. Dr. Mychaleckyj receives research support from Abbott, the NIH, and the Bill and Melinda Gates Foundation. Dr. Worrall serves as an Associate Editor of Neurology (R) and on the editorial board of Seminars in Neurology; receives royalties from the publication of Merritt's Neurology, 10th, 11th, and 12th eds. (chapter author); receives/has received research support from the NIH (NHGRI, NHLBI, NINDS) and from the University of Virginia-CTSA Pilot Project. G. Elias, Dr. Liu, and Dr. Chen report no disclosures. Dr. Coull serves on data safety monitoring boards for the NIH/NINDS and on a scientific advisory board for Neurobiological Technologies; and serves on the editorial boards of Stroke and Journal of Stroke and Cerebrovascular Diseases. Dr. Toole reports no disclosures. Dr. Rich receives research support from the NIH and Wake Forest University. Dr. Furie serves on a data safety monitoring board for the NIH/NINDS; serves as Vice Editor of Stroke; receives publishing royalties from UpToDate, Inc.; and receives research support from the NIH/NINDS, the American Heart Association, and the Deane Institute. Dr. Sale receives research support from the NIH. NR 40 TC 15 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2011 VL 77 IS 16 BP 1543 EP 1550 DI 10.1212/WNL.0b013e318233b1f9 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 839TL UT WOS:000296392000011 PM 21975197 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Self-Plagiarism SO ONCOLOGIST LA English DT Editorial Material ID RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; TARGETED THERAPY; BIOLOGY C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Chabner, Bruce A.] Harvard Univ, Sch Med, Boston, MA USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RI Inov Farmaceutica, Inct/K-2313-2013 NR 9 TC 2 Z9 3 U1 2 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2011 VL 16 IS 10 BP 1347 EP 1348 DI 10.1634/theoncologist.2011-0312 PG 2 WC Oncology SC Oncology GA 842AK UT WOS:000296557500001 PM 22016495 ER PT J AU Kamal, AH Loprinzi, CL Reynolds, C Dueck, AC Geiger, XJ Ingle, JN Carlson, RW Hobday, TJ Winer, EP Goetz, MP AF Kamal, Arif H. Loprinzi, Charles L. Reynolds, Carol Dueck, Amylou C. Geiger, Xochiquetzal J. Ingle, James N. Carlson, Robert W. Hobday, Timothy J. Winer, Eric P. Goetz, Matthew P. TI Breast Medical Oncologists' Use of Standard Prognostic Factors to Predict a 21-Gene Recurrence Score SO ONCOLOGIST LA English DT Article DE Breast cancer; recurrence disease management ID GENE-EXPRESSION; CANCER; CHEMOTHERAPY; ASSAY; TAMOXIFEN; MARKERS AB Background. Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX (R); Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit. We explored the ability of oncologists to predict the RS using standard prognostic criteria. Methods. Standard demographic and tumor prognostic criteria were obtained from patients with an available RS. Two academic pathologists provided tumor grade, histologic type, and hormone receptor status. Six academic oncologists predicted the RS category (low, intermediate, or high) and provided a recommendation for therapy. The oncologists were then given the actual RS and provided recommendations for therapy. Analysis for agreement was performed. Results. Thirty-one cases, including nine additional cases with variant pathology reads, were presented. There was substantial agreement in oncologists' ability to discriminate between true low or true intermediate and true high (kappa = 0.75; p < .0001). Predictions between low and intermediate were not consistent. The most common discrepancies were predictions of a low RS risk when cases were true intermediate and predictions of an intermediate RS risk when cases were true low. The actual RS resulted in a change in the treatment recommendations in 19% of cases. Of the 186 scenarios and six oncologists in aggregate, five fewer chemotherapy recommendations resulted with the actual RS. Conclusions. Oncologists are able to differentiate between a low or intermediate RS and a high RS using standard prognostic criteria. However, provision of the actual RS changed the treatment recommendations in nearly 20% of cases, suggesting that the RS may reduce chemotherapy use. This effect was observed in particular in intermediate-risk cases. Prospective clinical trials are necessary to determine whether decisions based on the RS change outcomes. The Oncologist 2011; 16: 1359-1366 C1 [Kamal, Arif H.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Div Med Oncol, Durham, NC 27710 USA. [Loprinzi, Charles L.; Ingle, James N.; Hobday, Timothy J.; Goetz, Matthew P.] Mayo Clin, Ctr Canc, Div Med Oncol, Rochester, MN USA. [Reynolds, Carol] Mayo Clin, Ctr Canc, Dept Pathol, Rochester, MN USA. [Dueck, Amylou C.] Mayo Clin, Ctr Canc, Div Biomed Stat & Informat, Rochester, MN USA. [Geiger, Xochiquetzal J.] Mayo Clin Florida, Dept Pathol, Jacksonville, FL USA. [Carlson, Robert W.] Stanford Comprehens Canc Ctr, Div Med Oncol, Palo Alto, CA USA. [Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Goetz, MP (reprint author), 200 1st St SW, Rochester, MN 55905 USA. EM goetz.matthew@mayo.edu RI Inov Farmaceutica, Inct/K-2313-2013 FU NCI NIH HHS [K05 CA124477] NR 21 TC 15 Z9 15 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2011 VL 16 IS 10 BP 1359 EP 1366 DI 10.1634/theoncologist.2011-0048 PG 8 WC Oncology SC Oncology GA 842AK UT WOS:000296557500003 PM 21934103 ER PT J AU Park, ER Japuntich, SJ Traeger, L Cannon, S Pajolek, H AF Park, Elyse R. Japuntich, Sandra J. Traeger, Lara Cannon, Sheila Pajolek, Hannah TI Disparities Between Blacks and Whites in Tobacco and Lung Cancer Treatment SO ONCOLOGIST LA English DT Article DE Racial disparities; Blacks; Lung cancer; Tobacco treatment; Treatment outcomes ID NICOTINE REPLACEMENT THERAPY; MAJOR PULMONARY MORBIDITY; AFRICAN-AMERICAN SMOKERS; QUALITY-OF-LIFE; SMOKING-CESSATION; RACIAL-DIFFERENCES; HEALTH-CARE; UNITED-STATES; DEPRESSIVE SYMPTOMS; ETHNIC DISPARITIES AB Racial disparities exist in lung cancer incidence, morbidity, and mortality. Smoking is responsible for the majority of lung cancers, and racial disparities also exist in smoking outcomes. Black smokers are less likely than white smokers to engage in evidence-based tobacco treatment, and black smokers are less likely than white smokers to stop smoking. Continued smoking following a lung cancer diagnosis is a potential indicator of poor lung cancer treatment outcomes, yet lung cancer patients who smoke are unlikely to receive evidence-based tobacco treatment. The risks from continued smoking after diagnosis deserve attention as a modifiable factor toward lessening racial disparities in lung cancer outcomes. The Oncologist 2011; 16: 1428-1434 C1 [Park, Elyse R.; Japuntich, Sandra J.; Pajolek, Hannah] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra J.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Park, Elyse R.; Japuntich, Sandra J.; Traeger, Lara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Cannon, Sheila] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. RP Park, ER (reprint author), Inst Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM epark@partners.org RI Inov Farmaceutica, Inct/K-2313-2013 NR 95 TC 7 Z9 7 U1 2 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2011 VL 16 IS 10 BP 1428 EP 1434 DI 10.1634/theoncologist.2011-0114 PG 7 WC Oncology SC Oncology GA 842AK UT WOS:000296557500011 PM 21964005 ER PT J AU Kesselheim, JC Norden, AD Wen, PY Joffe, S AF Kesselheim, Jennifer C. Norden, Andrew D. Wen, Patrick Y. Joffe, Steven TI Discontinuing Bevacizumab in Patients with Glioblastoma: An Ethical Analysis SO ONCOLOGIST LA English DT Article DE Bevacizumab; Ethics; Glioblastoma multiforme ID RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS; PHASE-II TRIAL; PLUS IRINOTECAN; HEALTH; TEMOZOLOMIDE; MULTIFORME; CHEMOTHERAPY; MULTICENTER; PATTERNS AB Glioblastoma (GBM) is a highly lethal malignant brain tumor that expresses proangiogenic factors, including vascular endothelial growth factor (VEGF). Bevacizumab (Avastin (R); Genentech, Inc., South San Francisco, CA), a monoclonal antibody against VEGF, is routinely used in the U.S. to treat GBM patients whose tumors have progressed following initial therapy. The Ethics Advisory Committee at the Dana-Farber Cancer Institute was asked to provide consultation on two cases involving patients with recurrent GBM who were receiving bevacizumab. Despite evidence of disease progression, family members advocated for the continued use of bevacizumab because of its mild toxicity profile and concern that discontinuation would impair quality of life. However, continuing bevacizumab in this setting posed physical and financial risks to the patients and raised ethical concerns about resource allocation and justice. We analyze the ethical questions regarding bevacizumab discontinuation in the setting of progressive GBM. We articulate the potential benefits and harms of continuing the drug and identify guiding principles for drug discontinuation that should be made transparent to patients and families. With the increasing availability of new, modestly toxic, expensive drugs for patients with advanced cancer, questions of when to stop these drugs will become increasingly relevant. The Oncologist 2011; 16: 1435-1439 C1 [Kesselheim, Jennifer C.; Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Kesselheim, Jennifer C.; Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Kesselheim, JC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_kesselheim@dfci.harvard.edu RI Inov Farmaceutica, Inct/K-2313-2013; OI Joffe, Steven/0000-0002-0667-7384 FU Exelixis; AstraZeneca; Eisai; Boehringer-Ingelheim; Merck; Genentech; Novartis FX Jennifer C. Kesselheim: None; Andrew D. Norden: None; Patrick Y. Wen: Consultant/advisory role: Agios, Lilly/ImClone, Novartis; Honoraria: Merck; Research funding/contracted research: Exelixis, AstraZeneca, Eisai, Boehringer-Ingelheim, Merck, Genentech, Novartis; Steven Joffe: None. NR 32 TC 7 Z9 7 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD OCT PY 2011 VL 16 IS 10 BP 1435 EP 1439 DI 10.1634/theoncologist.2011-0047 PG 5 WC Oncology SC Oncology GA 842AK UT WOS:000296557500012 PM 21948651 ER PT J AU Walensky, RP Bassett, IV AF Walensky, Rochelle P. Bassett, Ingrid V. TI HIV Self-testing and the Missing Linkage SO PLOS MEDICINE LA English DT Editorial Material ID SOUTH-AFRICA C1 [Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Bassett, Ingrid V.] Ctr AIDS Res, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIMH NIH HHS [R01 MH073445, R01 MH090326, R01 MH65869, R01 MH065869] NR 12 TC 15 Z9 16 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD OCT PY 2011 VL 8 IS 10 AR e1001101 DI 10.1371/journal.pmed.1001101 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 841YZ UT WOS:000296552400002 PM 21990965 ER PT J AU Hess, DR AF Hess, Dean R. TI Approaches to Conventional Mechanical Ventilation of the Patient With Acute Respiratory Distress Syndrome SO RESPIRATORY CARE LA English DT Article DE acute lung injury; ALI; acute respiratory distress syndrome; ARDS; lung-protective ventilation strategies; mechanical ventilation; PEEP; ventilator-induced lung injury ID ACUTE LUNG INJURY; END-EXPIRATORY PRESSURE; INVERSE RATIO VENTILATION; TIDAL VOLUME VENTILATION; RANDOMIZED CONTROLLED-TRIAL; ELECTRICAL-IMPEDANCE TOMOGRAPHY; CHEST-WALL MECHANICS; DEAD-SPACE FRACTION; PROTECTIVE-VENTILATION; INSPIRATORY FLOW AB To minimize ventilator-induced lung injury, attention should be directed toward avoidance of alveolar over-distention and cyclical opening and closure of alveoli. The most impressive study of mechanical ventilation to date is the Acute Respiratory Distress Syndrome (ARDS) Network study of higher versus lower tidal volume (V(T)), which reported a reduction in mortality from 39.8% to 31.0% with 6 mL/kg ideal body weight rather than 12 mL/kg ideal body weight (number-needed-to-treat of 12 patients). To achieve optimal lung protection, the lowest plateau pressure and V(T) possible should be selected. What is most important is limitation of V(T) and alveolar distending pressure, regardless of the mode set on the ventilator. Accumulating observational evidence suggests that V(T) should be limited in all mechanically ventilated patients-even those who do not have ALI/ARDS. Evidence does not support the use of pressure controlled inverse-ratio ventilation. Although zero PEEP is probably injurious, an area of considerable controversy is the optimal setting of PEEP. Available evidence does not support the use of higher PEEP, compared to lower PEEP, in unselected patients with acute lung injury (ALI)/ARDS. However, results of a meta-analysis using individual patients from 3 randomized controlled trials suggest that higher PEEP should be used for ARDS, whereas lower PEEP may be more appropriate in patients with ALI. PEEP should be set to maximize alveolar recruitment while avoiding over-distention. Many approaches for setting PEEP have been described, but evidence is lacking that any one approach is superior to any other. In most, if not all, cases of ALI/ARDS, conventional ventilation strategies can be used effectively to provide lung-protective ventilation strategies. C1 Harvard Univ, Resp Care Serv, Massachusetts Gen Hosp, Sch Boston, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Resp Care Serv, Massachusetts Gen Hosp, Sch Boston, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 125 TC 18 Z9 20 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 OCT PY 2011 VL 56 IS 10 BP 1555 EP 1572 DI 10.4187/respcare.01387 PG 18 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 841XJ UT WOS:000296548200010 PM 22008397 ER PT J AU Won, SJ Tang, XN Suh, SW Yenari, MA Swanson, RA AF Won, Seok Joon Tang, Xian Nan Suh, Sang Won Yenari, Midori A. Swanson, Raymond A. TI Hyperglycemia Promotes Tissue Plasminogen Activator-Induced Hemorrhage by Increasing Superoxide Production SO ANNALS OF NEUROLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; GLOBAL CEREBRAL-ISCHEMIA; BRAIN LACTIC-ACIDOSIS; NADPH OXIDASE; INTRACEREBRAL HEMORRHAGE; CANADIAN ALTEPLASE; OXIDATIVE STRESS; GLUCOSE LEVEL; INFARCT SIZE; CELL-DAMAGE AB Objective: Risk of intracerebral hemorrhage is the primary factor limiting use of tissue plasminogen activator (tPA) for stroke. Clinical studies have established an association between admission hyperglycemia and the risk of hemorrhage with tPA use, independent of prior diabetes. Here we used an animal model of tPA-induced reperfusion hemorrhage to determine if this clinical association reflects a true causal relationship. Methods: Rats underwent 90 minutes of focal ischemia, and tPA infusion was begun 10 minutes prior to vessel reperfusion. Glucose was administered during ischemia to generate blood levels ranging from 5.9 +/- 1.8mM (normoglycemia) to 21 +/- 2.3mM. In some studies, apocynin was administered to block superoxide production by nicotinamide adenine dinucleotide phosphate (NADPH). Brains were harvested 1 hour or 3 days after reperfusion to evaluate the effects of hyperglycemia and apocynin on oxidative stress, blood-brain barrier breakdown, infarct volume, and hemorrhage volume. Results: Rats that were hyperglycemic during tPA infusion had diffusely increased blood-brain barrier permeability in the postischemic territory, and a 3- to 5-fold increase in intracerebral hemorrhage volumes. The hyperglycemic rats also showed increased superoxide formation in the brain parenchyma and vasculature during reperfusion. The effects of hyperglycemia on superoxide production, blood-brain barrier disruption, infarct size, and hemorrhage were all attenuated by apocynin. Interpretation: These findings demonstrate a causal relationship between hyperglycemia and hemorrhage in an animal model of tPA stroke treatment, and suggest that this effect of hyperglycemia is mediated through an increase in superoxide production by NADPH oxidase. ANN NEUROL 2011;70:583-590 C1 San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Swanson, RA (reprint author), 127 Neurol VAMC, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU US Department of Veterans Affairs; National Institutes of Health [P50 NS14543] FX This work was supported by the US Department of Veterans Affairs and National Institutes of Health (P50 NS14543; R. A. S. and M.A.Y.). S.J.W. and X.N.T. contributed equally to this work. NR 47 TC 48 Z9 51 U1 0 U2 4 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 OCT PY 2011 VL 70 IS 4 BP 583 EP 590 DI 10.1002/ana.22538 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700011 PM 22002675 ER PT J AU Tang, XN Zheng, Z Giffard, RG Yenari, MA AF Tang, Xian N. Zheng, Zhen Giffard, Rona G. Yenari, Midori A. TI Significance of Marrow-Derived Nicotinamide Adenine Dinucleotide Phosphate Oxidase in Experimental Ischemic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; BRAIN-BARRIER PERMEABILITY; NADPH OXIDASE; REPERFUSION INJURY; MILD HYPOTHERMIA; IN-VIVO; APOCYNIN; MICE; RATS; IRRADIATION AB Objective: Reperfusion after stroke leads to infiltration of inflammatory cells into the ischemic brain. Nicotinamide adenine dinucleotide phosphate oxidase (NOX2) is a major enzyme system that generates superoxide in immune cells. We studied the effect of NOX2 derived from the immune cells in the brain and in blood cells in experimental stroke. Methods: To establish whether NOX2 plays a role in brain ischemia, strokes were created in mice, then mice were treated with the NOX2 inhibitor apocynin or vehicle and compared to mice deficient in NOX2's gp91 subunit and their wild-type littermates. To determine whether NOX2 in circulating cells versus brain resident cells contribute to ischemic injury, bone marrow chimeras were generated by transplanting bone marrow from wild-type or NOX2-deficient mice into NOX2 or wild-type hosts, respectively. Results: Apocynin and NOX2 deletion both significantly reduced infarct size, blood-brain barrier disruption, and hemorrhagic transformation of the infarcts, compared to untreated wild-type controls. This was associated with decreased matrix metalloproteinase 9 expression and reduced loss of tight junction proteins. NOX2-deficient mice receiving wild-type marrow had better outcomes compared to the wild-type mice receiving wild-type marrow. Interestingly, wild-type mice receiving NOX2-deficient marrow had even smaller infarct sizes and less hemorrhage than NOX2-deficient mice receiving wild-type marrow. Interpretation: This indicates that NOX2, whether present in circulating cells or brain resident cells, contributes to ischemic brain injury and hemorrhage. However, NOX2 from the circulating cells contributed more to the exacerbation of stroke than that from brain resident cells. These data suggest the importance of targeting the peripheral immune system for treatment of stroke. ANN NEUROL 2011;70:606-615 C1 [Yenari, Midori A.] UCSF, Neurol VAMC 127, Dept Neurol, San Francisco, CA 94121 USA. [Tang, Xian N.; Zheng, Zhen; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Tang, Xian N.; Giffard, Rona G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. RP Yenari, MA (reprint author), UCSF, Neurol VAMC 127, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu FU NIH [NINDS R01 NS40516, NINDS P50 NS014543, NIGMS R01 GM 49831]; American Heart Association FX This work was supported by NIH grants NINDS R01 NS40516 (M.A.Y.), NINDS P50 NS014543 (M.A.Y., R. G. G.), and NIGMS R01 GM 49831 (R. G. G.), an American Heart Association Established Investigator Award (M.A.Y.). Grants to M.A.Y. were administered by the Northern California Institute for Research and Education and the Department of Veterans Affairs. NR 42 TC 29 Z9 30 U1 0 U2 2 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 OCT PY 2011 VL 70 IS 4 BP 606 EP 615 DI 10.1002/ana.22476 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700014 PM 22028221 ER PT J AU Desikan, RS McEvoy, LK Thompson, WK Holland, D Roddey, JC Blennow, K Aisen, PS Brewer, JB Hyman, BT Dale, AM AF Desikan, Rahul S. McEvoy, Linda K. Thompson, Wesley K. Holland, Dominic Roddey, J. Cooper Blennow, Kaj Aisen, Paul S. Brewer, James B. Hyman, Bradley T. Dale, Anders M. CA Alzheimers Dis Neuroimaging TI Amyloid-beta Associated Volume Loss Occurs Only in the Presence of Phospho-Tau SO ANNALS OF NEUROLOGY LA English DT Article ID DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; ELDERLY SUBJECTS; A-BETA(42) AB The relationship between neurodegeneration and the 2 hallmark proteins of Alzheimer's disease, amyloid-beta (A beta) and tau, is still unclear. Here, we examined 286 nondemented participants (107 cognitively normal older adults and 179 memory impaired individuals) who underwent longitudinal magnetic resonance (MR) imaging and lumbar puncture. Using mixed effects models, we investigated the relationship between longitudinal entorhinal cortex atrophy rate, cerebrospinal fluid (CSF) p-tau(181p) and CSF A beta(1-42). We found a significant relationship between elevated entorhinal cortex atrophy rate and decreased CSF A beta(1-42) only with elevated CSF p-tau(181p). Our findings indicate that neurodegeneration-associated volume loss occurs only in the presence of phospho-tau in humans at risk for dementia. ANN NEUROL 2011;70:657-661 C1 [Desikan, Rahul S.; McEvoy, Linda K.; Brewer, James B.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Thompson, Wesley K.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Holland, Dominic; Roddey, J. Cooper; Aisen, Paul S.; Brewer, James B.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Blennow, Kaj] Goteburg Univ, Sahlgrenska Acad, Clin Neurochem Lab, Gothenburg, Sweden. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Dale, AM (reprint author), Univ Calif San Diego, Dept Radiol, 8950 Villa La Jolla Dr,Suite C101, La Jolla, CA 92037 USA. EM amdale@ucsd.edu FU National Institutes of Health [R01AG031224, K01AG029218, K02 NS067427, T32 EB005970, P30 AG010129, K01 AG030514]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; AFAR-GE Junior Investigator Award for Excellence in Imaging and Aging Research (RSD); NIH NIA; NSF; SFARI; Janssen Alzheimer Immunotherapy; Innogenetics; Bristol-Myers Squibb; Swedish Research Council; Swedish Brain Power project; Swedish Council for Working Life and Social Research; Swedish Alzheimer Foundation; Stiftelsen for Gamla Tjanarinnor; King Gustaf V's and Queen Victoria's Foundation; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation; General Electric Medical Foundation FX This research was supported by grants from the National Institutes of Health (R01AG031224 (AMD); K01AG029218 (LKM); K02 NS067427 (JBB); T32 EB005970 (PI: Robert Mattrey; Trainee: RSD)) and an AFAR-GE Junior Investigator Award for Excellence in Imaging and Aging Research (RSD)). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904 (PI: Michael Weiner)).; A.M.D. is a founder and holds equity in CorTechs Labs, Inc. and serves on the Scientific Advisory Board (the terms of this arrangement have been reviewed and approved by the University of California at San Diego in accordance with its conflict of interest policies); has received grant(s) from the NIH NIA; has grants/grants pending from the NIH, NSF, and SFARI; and with DH has filed a patent application for a method for longitudinal image registration (Quarc) at UCSD. J.B.B. has received grants from the NIH, NIA; and has grants/grants pending from Janssen Alzheimer Immunotherapy and General Electric Medical Foundation. K. B. has consulted for Innogenetics, AdLyfe Corporation, Bayer Schering Pharma, Bristol-Myers Squibb, Merz Pharmaceuticals, LLC, AstraZeneca, and sanofi-aventis; has grants/grants pending with Innogenetics, Bristol-Myers Squibb, the Swedish Research Council, the Swedish Brain Power project, the Swedish Council for Working Life and Social Research, the Swedish Alzheimer Foundation, Stiftelsen for Gamla Tjanarinnor, and the King Gustaf V's and Queen Victoria's Foundation; and has received payment for lectures including service on speakers bureaus from Janssen Immunotherapy. L. K. M. has received grant(s) from the NIH, and her spouse is CEO of CorTechs Labs, Inc.; ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U. S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). 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 for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 20 TC 52 Z9 53 U1 0 U2 5 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 OCT PY 2011 VL 70 IS 4 BP 657 EP 661 DI 10.1002/ana.22509 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 839VD UT WOS:000296396700019 PM 22002658 ER PT J AU Sperling, R AF Sperling, Reisa TI Derek Denny-Brown Neurological Scholar Award: Can We Detect Alzheimer's Disease a Decade Before Dementia, and Why Would We Want To? SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 136th Annual Meeting of the American-Neurological-Association (ANA) CY SEP 25-27, 2011 CL San Diego, CA SP Amer Neurol Assoc (ANA) C1 [Sperling, Reisa] Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Med Sch, Cambridge, MA 02138 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2011 VL 70 SU 15 BP S1 EP S1 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 840DW UT WOS:000296419500002 ER PT J AU Baig, S Cunningham, MJ AF Baig, Samir Cunningham, Michael J. TI Otolaryngology Education in Family Medicine and Communication Sciences Training SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OTITIS-MEDIA AB Objectives: To characterize the extent and format of otolaryngology instruction during family medicine and communication disorders training and to determine the comfort level of graduate trainees to assess specific hearing disorders. Design: Online surveys were sent to program directors in the fields of family medicine, audiology, and speech pathology. Directors were asked to delineate methods of teaching otolaryngology-related material and to define how often otolaryngologists were involved in their curricula. They were also asked to rate their graduate trainees' ability to manage 3 clinical scenarios involving pediatric hearing impairment. Participants: A total of 682 surveys were sent using e-mail addresses from the American Medical Association and the Council of Academic Programs in Communication Sciences and Disorders. Results: Response rates were 20% for family medicine programs and 30% for each of the communication science disciplines. Virtually all respondent family medicine programs have dedicated instruction in otolaryngology, typically in the form of a clinical rotation (98%). Ninety-five percent of audiology programs involve an otolaryngologist in teaching compared with 55% of speech pathology programs. Otolaryngology-related diagnostic examination skills are taught by most programs in all 3 disciplines; confirmation of skills acquisition, however, is lacking. Directors rated the competence of their trainees to manage hearing disorders at an average of 3.4 for audiology, 2.7 for speech pathology, and 2.6 for family medicine graduates on a 4-point scale. Conclusions: Respondent directors from all 3 disciplines make a concerted effort to teach otolaryngology-related topics. A greater emphasis on those otolaryngology disorders requiring multidisciplinary care appears necessary, as does more formal instruction in and competency evaluation of diagnostic examination skills. C1 [Baig, Samir] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Childrens Hosp Boston, 300 Longwood Ave,Lo 367, Boston, MA 02115 USA. EM michael.cunningham@childrens.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2011 VL 137 IS 10 BP 984 EP 988 DI 10.1001/archoto.2011.159 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 834DU UT WOS:000295940400002 PM 21930974 ER PT J AU Roylance, R Endesfelder, D Gorman, P Burrell, RA Sander, J Tomlinson, I Hanby, AM Speirs, V Richardson, AL Birkbak, NJ Eklund, AC Downward, J Kschischo, M Szallasi, Z Swanton, C AF Roylance, Rebecca Endesfelder, David Gorman, Patricia Burrell, Rebecca A. Sander, Jil Tomlinson, Ian Hanby, Andrew M. Speirs, Valerie Richardson, Andrea L. Birkbak, Nicolai J. Eklund, Aron C. Downward, Julian Kschischo, Maik Szallasi, Zoltan Swanton, Charles TI Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IN-SITU HYBRIDIZATION; EXPRESSION SIGNATURE; ANEUPLOIDY; PROGNOSIS; CELLS; LUNG; ADENOCARCINOMAS; HETEROGENEITY; CHEMOTHERAPY; SENSITIVITY AB Background: Chromosomal instability (CIN) is thought to be associated with poor prognosis in solid tumors; however, evidence from preclinical and mouse tumor models suggest that CIN may paradoxically enhance or impair cancer cell fitness. Breast cancer prognostic expression signature sets, which reflect tumor CIN status, efficiently delineate outcome in estrogen receptor ER-positive breast cancer in contrast to ER-negative breast cancer, suggesting that the relationship of CIN with prognosis differs in these two breast cancer subtypes. Methods: Direct assessment of CIN requires single-cell analysis methods, such as centromeric FISH, aimed at determining the variation around the modal number of two or more chromosomes within individual tumor nuclei. Here, we document the frequency of tumor CIN by dual centromeric FISH analysis in a retrospective primary breast cancer cohort of 246 patients with survival outcome. Results: There was increased CIN and clonal heterogeneity in ER-negative compared with ER-positive breast cancer. Consistent with a negative impact of CIN on cellular fitness, extreme CIN in ER-negative breast cancer was an independent variable associated with improved long-term survival in multivariate analysis. In contrast, a linear relationship of increasing CIN with poorer prognosis in ER-positive breast cancer was observed, using three independent measures of CIN. Conclusions: The paradoxical relationship between extreme CIN and cancer outcome in the ER-negative cohorts may explain why prognostic expression signatures, reflecting tumor CIN status, fail to predict outcome in this subgroup. Impact: Assessment of tumor CIN status may support risk stratification in ER-negative breast cancer and requires prospective validation. Cancer Epidemiol Biomarkers Prev; 20(10); 2183-94. (C) 2011 AACR. C1 [Roylance, Rebecca; Endesfelder, David; Gorman, Patricia; Burrell, Rebecca A.; Sander, Jil; Downward, Julian; Swanton, Charles] London Res Inst, Canc Res UK, London WC2A 3LY, England. [Roylance, Rebecca; Gorman, Patricia] Barts & London Queen Marys Sch Med & Dent, Inst Canc, London, England. [Kschischo, Maik] Univ Appl Sci, Remagen, Germany. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Hanby, Andrew M.; Speirs, Valerie] St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England. [Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Richardson, Andrea L.; Birkbak, Nicolai J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA. [Birkbak, Nicolai J.; Eklund, Aron C.; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Swanton, Charles] Royal Marsden Hosp, Dept Med, Breast Unit, Sutton, Surrey, England. [Swanton, Charles] Royal Marsden Hosp, Dept Med, Drug Dev Unit, Sutton, Surrey, England. RP Swanton, C (reprint author), London Res Inst, Canc Res UK, 44 Lincolns Inn Fields, London WC2A 3LY, England. EM charles.swanton@cancer.org.uk OI Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001; Downward, Julian/0000-0002-2331-4729 FU Cancer Research UK; MRC; Inflammatory Breast Cancer UK; NIH [NCI SPORE P50 CA 89393, R21LM008823-01A1]; Breast Cancer Research Foundation FX This work was funded by Cancer Research UK, MRC, Inflammatory Breast Cancer UK, NIH (grants NCI SPORE P50 CA 89393 and R21LM008823-01A1) and by the Breast Cancer Research Foundation. NR 49 TC 58 Z9 60 U1 0 U2 8 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 OCT PY 2011 VL 20 IS 10 BP 2183 EP 2194 DI 10.1158/1055-9965.EPI-11-0343 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900024 PM 21784954 ER PT J AU Milne, RL Goode, EL Garca-Closas, M Couch, FJ Severi, G Hein, R Fredericksen, Z Malats, N Zamora, MP Perez, JIA Benitez, J Dork, T Schurmann, P Karstens, JH Hillemanns, P Cox, A Brock, IW Elliot, G Cross, SS Seal, S Turnbull, C Renwick, A Rahman, N Shen, CY Yu, JC Huang, CS Hou, MF Nordestgaard, BG Bojesen, SE Lanng, C Alnaes, GG Kristensen, V Borrensen-Dale, AL Hopper, JL Dite, GS Apicella, C Southey, MC Lambrechts, D Yesilyurt, BT Floris, G Leunen, K Sangrajrang, S Gaborieau, V Brennan, P McKay, J Chang-Claude, J Wang-Gohrke, S Radice, P Peterlongo, P Manoukian, S Barile, M Giles, GG Baglietto, L John, EM Miron, A Chanock, SJ Lissowska, J Sherman, ME Figueroa, JD Bogdanova, NV Antonenkova, NN Zalutsky, IV Rogov, YI Fasching, PA Bayer, CM Ekici, AB Beckmann, MW Brenner, H Muller, H Arndt, V Stegmaier, C Andrulis, IL Knight, JA Glendon, G Mulligan, AM Mannermaa, A Kataja, V Kosma, VM Hartikainen, JM Meindl, A Heil, J Bartram, CR Schmutzler, RK Thomas, GD Hoover, RN Fletcher, O Gibson, LJ Silva, ID Peto, J Nickels, S Flesch-Janys, D Anton-Culver, H Ziogas, A Sawyer, E Tomlinson, I Kerin, M Miller, N Schmidt, MK Broeks, A Van't Veer, LJ Tollenaar, RAEM Pharoah, PDP Dunning, AM Pooley, KA Marme, F Schneeweiss, A Sohn, C Burwinkel, B Jakubowska, A Lubinski, J Jaworska, K Durda, K Kang, D Yoo, KY Noh, DY Ahn, SH Hunter, DJ Hankinson, SE Kraft, P Lindstrom, S Chen, XQ Beesley, J Hamann, U Harth, V Justenhoven, C Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Hooning, M Hollestelle, A Oldenburg, RA Tilanus-Linthorst, M Khusnutdinova, E Bermisheva, M Prokofieva, D Farahtdinova, A Olson, JE Wang, XS Humphreys, MK Wang, Q Chenevix-Trench, G Easton, DF AF Milne, Roger L. Goode, Ellen L. Garca-Closas, Montserrat Couch, Fergus J. Severi, Gianluca Hein, Rebecca Fredericksen, Zachary Malats, Nuria Pilar Zamora, M. Arias Perez, Jose Ignacio Benitez, Javier Doerk, Thilo Schuermann, Peter Karstens, Johann H. Hillemanns, Peter Cox, Angela Brock, Ian W. Elliot, Graeme Cross, Simon S. Seal, Sheila Turnbull, Clare Renwick, Anthony Rahman, Nazneen Shen, Chen-Yang Yu, Jyh-Cherng Huang, Chiun-Sheng Hou, Ming-Feng Nordestgaard, Borge G. Bojesen, Stig E. Lanng, Charlotte Alnaes, Grethe Grenaker Kristensen, Vessela Borrensen-Dale, Anne-Lise Hopper, John L. Dite, Gillian S. Apicella, Carmel Southey, Melissa C. Lambrechts, Diether Yesilyurt, Betul T. Floris, Giuseppe Leunen, Karin Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul McKay, James Chang-Claude, Jenny Wang-Gohrke, Shan Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Giles, Graham G. Baglietto, Laura John, Esther M. Miron, Alexander Chanock, Stephen J. Lissowska, Jolanta Sherman, Mark E. Figueroa, Jonine D. Bogdanova, Natalia V. Antonenkova, Natalia N. Zalutsky, Iosif V. Rogov, Yuri I. Fasching, Peter A. Bayer, Christian M. Ekici, Arif B. Beckmann, Matthias W. Brenner, Hermann Mueller, Heiko Arndt, Volker Stegmaier, Christa Andrulis, Irene L. Knight, Julia A. Glendon, Gord Mulligan, Anna Marie Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M. Meindl, Alfons Heil, Joerg Bartram, Claus R. Schmutzler, Rita K. Thomas, Gilles D. Hoover, Robert N. Fletcher, Olivia Gibson, Lorna J. Silva, Isabel dos Santos Peto, Julian Nickels, Stefan Flesch-Janys, Dieter Anton-Culver, Hoda Ziogas, Argyrios Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Schmidt, Marjanka K. Broeks, Annegien Van't Veer, Laura J. Tollenaar, Rob A. E. M. Pharoah, Paul D. P. Dunning, Alison M. Pooley, Karen A. Marme, Frederik Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Hunter, David J. Hankinson, Susan E. Kraft, Peter Lindstrom, Sara Chen, Xiaoqing Beesley, Jonathan Hamann, Ute Harth, Volker Justenhoven, Christina Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Hooning, Maartje Hollestelle, Antoinette Oldenburg, Rogier A. Tilanus-Linthorst, Madeleine Khusnutdinova, Elza Bermisheva, Marina Prokofieva, Darya Farahtdinova, Albina Olson, Janet E. Wang, Xianshu Humphreys, Manjeet K. Wang, Qin Chenevix-Trench, Georgia Easton, Douglas F. CA GENICA Network KConFab Investigators AOCS Grp TI Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; SUBTYPES; ALLELES; RISK AB Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 x 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR 1.07, 95% CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 x 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) 2 x 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend 5 x 10(-7)]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222-31. (C) 2011 AACR. C1 [Milne, Roger L.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 28029, Spain. [Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain. [Milne, Roger L.; Severi, Gianluca; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Severi, Gianluca; Giles, Graham G.; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Goode, Ellen L.; Fredericksen, Zachary; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Gibson, Lorna J.; Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London, England. [Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust Partnership Kings, Div Canc Studies, NIHR Comprehens Biomed Res Ctr, London, England. [Hein, Rebecca; Chang-Claude, Jenny; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany. [Heil, Joerg; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Marme, Frederik; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, Heidelberg, Germany. [Arias Perez, Jose Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain. [Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany. [Karstens, Johann H.; Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany. [Cox, Angela; Brock, Ian W.; Elliot, Graeme] Univ Sheffield, Dept Oncol, Inst Canc Studies, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England. [Elliot, Graeme] Univ Manchester, Manchester, Lancs, England. [Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, Surrey, England. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan. [Huang, Chiun-Sheng] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ Chung Ho Mem Hosp, Ctr Canc, Kaohsiung, Taiwan. [Hou, Ming-Feng] Kaohsiung Med Univ Chung Ho Mem Hosp, Dept Surg, Kaohsiung, Taiwan. [Nordestgaard, Borge G.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Nordestgaard, Borge G.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Lanng, Charlotte] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark. [Alnaes, Grethe Grenaker; Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway. [Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Fac Med, Fac Div Ahus, Uio, Norway. [Floris, Giuseppe; Leunen, Karin] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand. [Gaborieau, Valerie; Brennan, Paul; McKay, James] Int Agcy Res Canc, F-69372 Lyon, France. [Chang-Claude, Jenny; Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Radice, Paolo; Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Tumori, Italy. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Tumori, Italy. [Barile, Monica] IEO, Div Canc Prevent & Genet, Milan, Italy. [John, Esther M.] Fremont & Stanford Univ, Sch Med, Canc Prevent Inst Calif, Stanford, CA USA. [Miron, Alexander] Dana Farber Canc Inst, Boston, MA USA. [Hunter, David J.; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Hunter, David J.; Hankinson, Susan E.; Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Chanock, Stephen J.; Sherman, Mark E.; Figueroa, Jonine D.; Thomas, Gilles D.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Antonenkova, Natalia N.; Zalutsky, Iosif V.; Rogov, Yuri I.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Fasching, Peter A.; Bayer, Christian M.; Beckmann, Matthias W.] Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen Nuremberg, Dept Gynecol & Obstet, Univ Breast Ctr Franconia, Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, New York, NY USA. [Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, New York, NY USA. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Sch Med, Inst Clin Med Pathol & Forens Med, Helsinki, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Bioctr Kuopio, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Obstet & Gynecol, D-8000 Munich, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, CMMC, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX1 2JD, England. [Kerin, Michael; Miller, Nicola] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland. [Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Pharoah, Paul D. P.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Pharoah, Paul D. P.; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Pharoah, Paul D. P.; Dunning, Alison M.; Pooley, Karen A.; Humphreys, Manjeet K.; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Seoul, South Korea. [Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Harth, Volker] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. [Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Justenhoven, Christina] Univ Tubingen, Tubingen, Germany. [Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet, Oulu, Finland. [Winqvist, Robert; Pylkas, Katri; GENICA Network] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. [Grip, Mervi] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland. [Hooning, Maartje] Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Oldenburg, Rogier A.] Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands. [Tilanus-Linthorst, Madeleine] Family Canc Clin, Dept Surg Oncol, Rotterdam, Netherlands. [Hollestelle, Antoinette] Erasmus Univ, Med Ctr, Dept Med Oncol, Josephine Nefkens Inst, Rotterdam, Netherlands. [Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya; Farahtdinova, Albina] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia. RP Milne, RL (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM rmilne@cnio.es RI Jakubowska, Anna/O-8050-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Hartikainen, Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Khusnutdinova, Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Rahman, Nazneen/D-2802-2013; Noh, Dong-Young/G-5531-2011; Andrulis, Irene/E-7267-2013; Radice, Paolo/O-3119-2013; Knight, Julia/A-6843-2012; Shen, CY/F-6271-2010; Verdrengh, Evelien/H-4571-2012; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Kerin, Michael/D-6748-2013; Rahman, Nazneen/B-8890-2012; Dork, Thilo/J-8620-2012; Ekici, Arif/C-3971-2013 OI Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison Margaret/0000-0001-6651-7166; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Bowtell, David/0000-0001-9089-7525; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Hollestelle, Antoinette/0000-0003-1166-1966; Rahman, Nazneen/0000-0003-4376-0440; Dite, Gillian/0000-0002-2448-2548; Huang, Chiun-Sheng/0000-0002-6557-211X; Cross, Simon/0000-0003-2044-1754; FU European Community [223175, HEALTH-F2-2009-223175]; CR-UK [C1287/A10118, C1287/A12014]; European Union COST [BM0606]; Dutch Cancer Society [NKI 2001-2423, 2007-3839, DDHK 2004-3124, DDHK 2009-4318]; Dutch National Genomics Initiative; United States National Cancer Institute, NIH [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR); Cancer Care Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania; Cancer Foundation of Western Australia; NHMRC [199600, 145684, 288704, 454508]; ELAN-Fond of the University Hospital of Erlangen; Cancer Research UK [C1287/A10118, C8620/A8372, C8620/A8857, C490/A10124, C8197/A10123]; Breakthrough Breast Cancer; NHS; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Herlev Hospital; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; Baden Wurttemberg Ministry of Science, Research and Arts; German Cancer Aid (Deutsche Krebshilfe); US Military Acquisition (ACQ)Activity, Era of Hope Award [W81XWH-05-1-0204]; Institute of Cancer Research (UK); Medical Research Council (UK); Deutsche Krebshilfe [107054]; German Cancer Research Centre (DKFZ); Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany; Deutsche Krebshilfe e. V. [70492, 70-2892-BR I]; Hannover Medical School; German Academic Exchange Program; German Federal Ministry of Research and Education [RUS08/017]; Kuopio University Hospital; Cancer Fund of North Savo; Finnish Cancer Organizations; Academy of Finland; University of Eastern Finland; National Breast Cancer Foundation; Queensland Cancer Fund; Cancer Councils of New South Wales; Cancer Councils of Victoria; Cancer Councils of Tasmania; Cancer Councils of South Australia; Stichting tegen Kanker [232-2008, 196-2010]; Hamburg Cancer Society; German Cancer Research Center; Ministero della Salute; Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sul Cancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori [5 x 1000]; NIH [CA122340, CA128978, CA87969, CA58860, CA92044]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; VicHealth; Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711]; Norwegian Research council [155218/V40, 175240/S10]; Borrensen-Dale; FUGE-NFR [181600/V11]; Swizz Bridge Award; Finnish Cancer Foundation; Sigrid Juselius Foundation; University of Oulu; Oulu University Hospital; National Cancer Institute, Department of Health and Human Services, USA; Yorkshire Cancer Research; Breast Cancer Campaign; Ministry of Health and Welfare, Republic of Korea [AO30001]; Polish Foundation of Science; National Cancer Institute Thailand; Institute of Biomedical Sciences, Academia Sinica, Taiwan; Lon V Smith Foundation [LVS39420]; NIHR Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation; King's College London, United Kingdom; Oxford Biomedical Research Centre; [PBZ_KBN_122/P05/2004] FX Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175; COGS). The BCAC is funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST Programme (BM0606). D.F. Easton is a Principal Research Fellow of CR-UK. The ABCS was supported by the Dutch Cancer Society (grants NKI 2001-2423, 2007-3839) and the Dutch National Genomics Initiative. The ABCFS, NC-BCFR, and OFBCR work was supported by the United States National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and principal investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L. Hopper is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. M.C. Southey is an NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G. Chenevix-Trench is supported by the NHMRC. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev Hospital. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer, and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The FBCS is supported by funds from Cancer Research UK (C8620/A8372 and C8620/A8857), a US Military Acquisition (ACQ) Activity, Era of Hope Award (W81XWH-05-1-0204), and the Institute of Cancer Research (UK). C. Turnbull is funded by a Medical Research Council (UK) Clinical Research Fellowship. The FBCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The GC-HBOC was supported by Deutsche Krebshilfe (107054), the Dietmar-Hopp Foundation, the Helmholtz society, and the German Cancer Research Centre (DKFZ).; The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Isurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. (70492) and genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P.685). The HABCS study was supported by an intramural grant from Hannover Medical School. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to N.V. Bogdanova), and the Friends of Hannover Medical School (to N.V. Bogdanova). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017). The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, The Academy of Finland, and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, 454508). LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e. V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center, and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). MBCSG was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to PR), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Peterlongo), and by funds from Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. SEE ABCFS. The NBCS was supported by grants from the Norwegian Research council, 155218/V40, 175240/S10 to A.-L. Borrensen-Dale, FUGE-NFR 181600/V11 to V.-M. Kosma, and a Swizz Bridge Award to A.-L. Borrensen-Dale. The NHS was funded by NIH grant CA87969. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318).; The SBCS was suppoted by Yorkshire Cancer Research and the Breast Cancer Campaign. SEARCH is funded by program grants from Cancer Research UK (C490/A10124, C8197/A10123, C1287/A10118). The SEBCS was supported by the Korea Health 21 R&D Project (AO30001), Ministry of Health and Welfare, Republic of Korea. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004; K. Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TBCS was funded by The National Cancer Institute Thailand. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH (CA58860, CA92044) and the Lon V Smith Foundation (LVS39420). E. Sawyer is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. I. Tomlinson is supported by the Oxford Biomedical Research Centre. NR 14 TC 23 Z9 23 U1 1 U2 13 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 OCT PY 2011 VL 20 IS 10 BP 2222 EP 2231 DI 10.1158/1055-9965.EPI-11-0569 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900028 PM 21795498 ER PT J AU Davidsson, S Fiorentino, M Andren, O Fang, F Mucci, LA Varenhorst, E Fall, K Rider, JR AF Davidsson, Sabina Fiorentino, Michelangelo Andren, Ove Fang, Fang Mucci, Lorelei A. Varenhorst, Eberhard Fall, Katja Rider, Jennifer R. TI Inflammation, Focal Atrophic Lesions, and Prostatic Intraepithelial Neoplasia with Respect to Risk of Lethal Prostate Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POPULATION-BASED COHORT; HIGH-GRADE; POSTATROPHIC HYPERPLASIA; PROPIONIBACTERIUM-ACNES; RADICAL PROSTATECTOMY; EPITHELIAL-CELLS; FOLLOW-UP; CARCINOGENESIS; CARCINOMA; PREVALENCE AB Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR. C1 [Davidsson, Sabina; Andren, Ove; Rider, Jennifer R.] Orebro Univ Hosp, Dept Urol, S-70185 Orebro, Sweden. [Fiorentino, Michelangelo] Univ Bologna, Mol Pathol Lab, Addarii Inst Oncol, Dept Hematol Oncol, Bologna, Italy. [Mucci, Lorelei A.; Fall, Katja] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fiorentino, Michelangelo; Rider, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Brigham & Womens Hosp & Adult Oncol, Boston, MA 02115 USA. [Fang, Fang; Mucci, Lorelei A.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Varenhorst, Eberhard] Linkoping Univ Hosp, Dept Urol, S-58185 Linkoping, Sweden. [Fang, Fang; Fall, Katja] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Davidsson, S (reprint author), Orebro Univ Hosp, Dept Urol, S-70185 Orebro, Sweden. EM sabina.davidsson@orebroll.se RI Fall, Katja/A-9186-2012; OI Fang, Fang/0000-0002-3310-6456; Rider, Jennifer/0000-0002-2637-6036; Fall, Katja/0000-0002-3649-2639 FU Department of Defense [PC060389]; DF/HCC [NIH/NCIP50 CA90381]; Prostate Cancer Foundation; Swedish Cancer Society [CAN2006/1341] FX This study was supported by Department of Defense Prostate Cancer Idea Development Award PC060389, DF/HCC Prostate SPORE Career Development Award NIH/NCIP50 CA90381 (J.R. Rider), Prostate Cancer Foundation (L.A. Mucci), and by Swedish Cancer Society, CAN2006/1341 (K. Fall) NR 37 TC 22 Z9 24 U1 0 U2 3 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 OCT PY 2011 VL 20 IS 10 BP 2280 EP 2287 DI 10.1158/1055-9965.EPI-11-0373 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 831GR UT WOS:000295717900034 PM 21953116 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; acute radiation syndrome management; treatment of ARS; narrative review of countermeasures for ARS ID MESENCHYMAL STEM-CELLS; RESPIRATORY-DISTRESS-SYNDROME; MEDICAL-MANAGEMENT; CRITICALLY-ILL; GLUCOSE CONTROL; PUBLIC-HEALTH; CRITICAL-CARE; SEPTIC SHOCK; DOUBLE-BLIND; LUNG INJURY AB Objectives: The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results: No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. Conclusions: High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future. C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to Richard Hatchett and the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 181 TC 28 Z9 28 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 183 EP 201 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300007 PM 21986999 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; cytokines and radiation injury; transplantation for ARS; acute radiation syndrome management; hematopoietic syndrome management ID COLONY-STIMULATING FACTOR; MEDICAL-MANAGEMENT; PROGENITOR CELLS; RHESUS-MONKEYS; RECOMMENDATIONS; ACCIDENT; MYELOSUPPRESSION; RADIOSENSITIVITY; TRANSPLANTATION; GROWTH AB Objective: Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with >1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary. Results: Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation. Conclusions: Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence. (Disaster Med Public Health Preparedness. 2011;5:202-212) C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 44 TC 32 Z9 34 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 202 EP 212 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300008 PM 21987000 ER PT J AU Faupel-Badger, JM Staff, AC Thadhani, R Powe, CE Potischman, N Hoover, RN Troisi, R AF Faupel-Badger, Jessica M. Staff, Anne Cathrine Thadhani, Ravi Powe, Camille E. Potischman, Nancy Hoover, Robert N. Troisi, Rebecca TI Maternal angiogenic profile in pregnancies that remain normotensive SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Pregnancy; Angiogenic factors; sFlt1; PlGF; Soluble endoglin; Maternal ID PLACENTAL GROWTH-FACTOR; SOLUBLE ENDOGLIN; HYPERTENSIVE DISORDERS; ANTIANGIOGENIC FACTORS; TYROSINE KINASE-1; PREECLAMPSIA; RISK; SFLT1; VASCULOGENESIS; PATHOGENESIS AB Objective: We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies. Study design: Circulating levels of maternal placental like growth factor (PIGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis. Results: In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (p = 0.06) and second (p = 0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (p = 0.004) and second trimester (p = 0.008), but significantly lower sEng concentrations in both trimesters (p = 0.002 for first trimester and p = 0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p = 0.05 and p = 0.007, respectively) and second trimesters (p = 0.003 and p = 0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (r(s) = 0.18, p = 0.03) and MAP (r(s) = 0.16, p = 0.04). Second trimester sEng levels were inversely associated with second trimester MAP (r(s) = -0.17, p = 0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics. Conclusions: These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population. Published by Elsevier Ireland Ltd. C1 [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD USA. [Faupel-Badger, Jessica M.; Hoover, Robert N.; Troisi, Rebecca] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Rockville, MD USA. [Staff, Anne Cathrine] Oslo Univ Hosp, Dept Obstet & Gynaecol, Ulleval, Norway. [Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway. [Thadhani, Ravi; Powe, Camille E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thadhani, Ravi; Powe, Camille E.] Harvard Univ, Sch Med, Boston, MA USA. [Potischman, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Troisi, Rebecca] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. RP Faupel-Badger, JM (reprint author), NIH, 6120 Execut Blvd,Suite 150E,MSC 7105, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov FU NIH; National Cancer Institute; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; Division Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; [HD 39223] FX Funding support: This research was supported in part by the Intramural Research Program of the NIH and the National Cancer Institute. The Divisions of Cancer Epidemiology and Genetics and Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services provided funding for the data analysis and manuscript preparation. HD 39223 provided funding for the collection of original data and laboratory assays. NR 25 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD OCT PY 2011 VL 158 IS 2 BP 189 EP 193 DI 10.1016/j.ejogrb.2011.05.001 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 838OK UT WOS:000296301900012 PM 21641103 ER PT J AU Chen, XY Wu, MX AF Chen, Xinyuan Wu, Mei X. TI Laser vaccine adjuvant for cutaneous immunization SO EXPERT REVIEW OF VACCINES LA English DT Article DE adjuvant; cell motility; cutaneous vaccination; laser; noninflammation ID INTRADERMAL INFLUENZA VACCINATION; MONOPHOSPHORYL-LIPID-A; ANTHRAX VACCINE; MICROINJECTION SYSTEM; DNA DELIVERY; HEPATITIS-B; IMMUNOGENICITY; ADULTS; SAFETY; TRIAL AB Simple and efficient technologies for intradermal immunization have recently been developed, making cutaneous vaccination a valid alternative for vaccine delivery. This raises an urgent need for safe and potent adjuvants suitable for cutaneous vaccination. Many traditional adjuvants like aluminum-based adjuvants may not be appropriate for boosting cutaneous immunization because they evoke strong and persistent inflammation in the skin that would potentially breach its integrity with serious consequences. Laser vaccine adjuvant is induced by brief illumination of a small area of the skin with a safe, noninvasive laser prior to intradermal injection of the vaccine into the site of illumination. It does not stimulate overt inflammation or reactogenicity in the skin and boosts immune responses via enhancing the motility of antigen-presenting cells. Laser vaccine adjuvant is convenient, safe and ideal for augmentation of cutaneous immunization and has distinct advantages over conventional adjuvants, in particular when encountering vaccine shortages during an unpredictable event. C1 [Wu, Mei X.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Chen, Xinyuan; Wu, Mei X.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Chen, Xinyuan; Wu, Mei X.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wu, MX (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM mwu2@partners.org FU NIH [AI070785, RC1 DA028378]; Boston Biocom LLC. [2008A25652]; Bill & Melinda Gates Foundation [53273] FX This work is supported in part by the NIH grants AI070785 and RC1 DA028378, Sponsored Research agreement grant #2008A25652 from Boston Biocom LLC., and Grand Challenges Explorations grant #53273 from the Bill & Melinda Gates Foundation (to Mei X Wu). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 48 TC 15 Z9 15 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 EI 1744-8395 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD OCT PY 2011 VL 10 IS 10 BP 1397 EP 1403 DI 10.1586/ERV.11.112 PG 7 WC Immunology SC Immunology GA 840GL UT WOS:000296427100012 PM 21988305 ER PT J AU Morgenroth, DC Segal, AD Zelik, KE Czerniecki, JM Klute, GK Adamczyk, PG Orendurff, MS Hahn, ME Collins, SH Kuo, AD AF Morgenroth, David C. Segal, Ava D. Zelik, Karl E. Czerniecki, Joseph M. Klute, Glenn K. Adamczyk, Peter G. Orendurff, Michael S. Hahn, Michael E. Collins, Steven H. Kuo, Art D. TI The effect of prosthetic foot push-off on mechanical loading associated with knee osteoarthritis in lower extremity amputees SO GAIT & POSTURE LA English DT Article DE Prosthesis; Amputation; Osteoarthritis; Biomechanics; Rehabilitation ID TO-STEP TRANSITIONS; HUMAN WALKING; ADDUCTION MOMENT; INVERTED PENDULUM; STATIC ALIGNMENT; DISEASE SEVERITY; GAIT; ENERGY; PREVALENCE; ANKLE AB Lower extremity amputation not only limits mobility, but also increases the risk of knee osteoarthritis of the intact limb. Dynamic walking models of non-amputees suggest that pushing-off from the trailing limb can reduce collision forces on the leading limb. These collision forces may determine the peak knee external adduction moment (EAM), which has been linked to the development of knee OA in the general population. We therefore hypothesized that greater prosthetic push-off would lead to reduced loading and knee EAM of the intact limb in unilateral transtibial amputees. Seven unilateral transtibial amputees were studied during gait under three prosthetic foot conditions that were intended to vary push-off. Prosthetic foot-ankle push-off work, intact limb knee EAM and ground reaction impulses for both limbs during step-to-step transition were measured. Overall, trailing limb prosthetic push-off work was negatively correlated with leading intact limb 1st peak knee EAM (slope = .72 +/- .22; p = .011). Prosthetic push-off work and 1st peak intact knee EAM varied significantly with foot type. The prosthetic foot condition with the least push-off demonstrated the largest knee EAM, which was reduced by 26% with the prosthetic foot producing the most push-off. Trailing prosthetic limb push-off impulse was negatively correlated with leading intact limb loading impulse (slope = .34 +/- .14; p = .001), which may help explain how prosthetic limb push-off can affect intact limb loading. Prosthetic feet that perform more prosthetic push-off appear to be associated with a reduction in 1st peak intact knee EAM, and their use could potentially reduce die risk and burden of knee osteoarthritis in this population. Published by Elsevier B.V. C1 [Morgenroth, David C.; Segal, Ava D.; Czerniecki, Joseph M.; Klute, Glenn K.; Hahn, Michael E.] RR&D Ctr, Dept Vet Affairs, Seattle, WA USA. [Klute, Glenn K.; Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Klute, Glenn K.] Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. [Morgenroth, David C.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Zelik, Karl E.; Adamczyk, Peter G.; Kuo, Art D.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Collins, Steven H.] Carnegie Mellon Univ, Dept Mech Engn, Pittsburgh, PA 15213 USA. [Adamczyk, Peter G.; Collins, Steven H.] Intelligent Prosthet Syst LLC, Ann Arbor, MI USA. [Orendurff, Michael S.] Texas Scottish Rite Hosp Children, Movement Sci Lab, Dallas, TX 75219 USA. RP Morgenroth, DC (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. EM dmorgen@u.washington.edu RI Kuo, Arthur/L-3359-2013; Adamczyk, Peter/P-5928-2014; OI Kuo, Arthur/0000-0001-5233-9709; Adamczyk, Peter/0000-0001-5374-7691; Morgenroth, David/0000-0002-0226-7775 FU U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation [A4372R, A4843C]; Rehabilitation Medicine Scientist Training Program; NIH [K12 HD001097] FX This work was supported by the U.S. Department of Veterans Affairs, Office of Research and Development Rehabilitation, R&D Program (Grants A4372R and A4843C). Additionally, Dr. Morgenroth's work was supported by the Rehabilitation Medicine Scientist Training Program and the NIH (grant K12 HD001097). Statistical analyses were performed by Jane B. Shofer, MS. Prosthetic adjustments were performed by Wayne Biggs, CPO. NR 34 TC 32 Z9 36 U1 7 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD OCT PY 2011 VL 34 IS 4 BP 502 EP 507 DI 10.1016/j.gaitpost.2011.07.001 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 841AQ UT WOS:000296484800011 PM 21803584 ER PT J AU Badanich, KA Doremus-Fitzwater, TL Mulholland, PJ Randall, PK Delpire, E Becker, HC AF Badanich, K. A. Doremus-Fitzwater, T. L. Mulholland, P. J. Randall, P. K. Delpire, E. Becker, H. C. TI NR2B-deficient mice are more sensitive to the locomotor stimulant and depressant effects of ethanol SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Alcohol; locomotor activity; loss of righting; mice; NMDA receptor ID D-ASPARTATE RECEPTORS; NMDA RECEPTOR; GLUTAMATE RECEPTORS; INSULAR CORTEX; NR2B SUBUNITS; C57BL/6J MICE; MOUSE-BRAIN; RAT; EXPRESSION; IFENPRODIL AB The NR2B subunit of N-methyl D-aspartate glutamate receptors influences pharmacological properties and confers greater sensitivity to the modulatory effects of ethanol. This study examined behavioral responses to acute ethanol in a conditional knockout mouse model that allowed for a delayed genetic deletion of the NR2B subunit to avoid mouse lethality. Mice lacking the NR2B gene (knockout) were produced by mating NR2B[f/f] mice with CAMKIIa-driven tTA transgenic mice and the tetO-CRE transgenic mice. Adult male and female offspring representing each of the resultant genotypes (knockout, CAM, CRE and wildtype mice) were tested for open-field locomotor activity following acute low- and high-dose ethanol challenge as well as loss of righting reflex. Findings indicate that male and female mice lacking the NR2B subunit exhibited greater overall activity in comparison to other genotypes during the baseline locomotor activity test. NR2B knockout mice exhibited an exaggerated stimulant response to 1.5 g/kg (i.p.) and an exaggerated depressant response to 3.0 g/kg (i.p.) ethanol challenge. In addition, NR2B knockout mice slept longer following a high dose of ethanol (4.0 g/kg, i.p.). To evaluate pharmacokinetics, clearance rates of ethanol (1.5, 4.0 g/kg, i.p.) were measured and showed that female NR2B knockouts had a faster rate of metabolism only at the higher ethanol dose. Western blot analyses confirmed significant reduction in NR2B expression in the forebrain of knockout mice. Collectively, these data indicate that the NR2B subunit of the N-methyl D-aspartate glutamate receptor is involved in regulating low-dose stimulant effects of ethanol and the depressant/hypnotic effects of ethanol. C1 [Badanich, K. A.; Doremus-Fitzwater, T. L.; Mulholland, P. J.; Randall, P. K.; Becker, H. C.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. [Delpire, E.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA. [Becker, H. C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Becker, HC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, 67 President St,IOP 456N, Charleston, SC 29425 USA. EM beckerh@musc.edu FU NIAAA [AA13514, AA14095] FX This work was supported by NIAAA grants AA13514 to E.D. and AA14095 to H.C.B. The authors would like to thank Dr John J. Woodward for insightful comments during the preparation of this manuscript. A special thanks to Kay Fernandez, Josh Sanchez, Michelle Cunningham and Catherine Hindman for their technical assistance. NR 55 TC 18 Z9 18 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD OCT PY 2011 VL 10 IS 7 BP 805 EP 816 DI 10.1111/j.1601-183X.2011.00720.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 837WD UT WOS:000296238100013 PM 21762461 ER PT J AU Pidala, J Kurland, BF Chai, XY Vogelsang, G Weisdorf, DJ Pavletic, S Cutler, C Majhail, N Lee, SJ AF Pidala, Joseph Kurland, Brenda F. Chai, Xiaoyu Vogelsang, Georgia Weisdorf, Daniel J. Pavletic, Steven Cutler, Corey Majhail, Navneet Lee, Stephanie J. TI Sensitivity of changes in chronic graft-versus-host disease activity to changes in patient-reported quality of life: results from the Chronic Graft-versus-Host Disease Consortium SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE chronic graft versus host disease; quality of life; sensitivity to change ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; FORM HEALTH SURVEY; RECOMMENDATIONS; RELIABILITY; SURVIVORS; RECOVERY; VALIDITY; TRIALS; TESTS AB Background The 2005 National Institute of Health Chronic Graft-versus-Host Disease Consensus Conference recommended collection of patient-reported outcomes in clinical trials on chronic graft-versus-host disease. We assessed whether changes in chronic graft-versus-host disease severity, determined using National Institute of Health criteria, clinicians' assessment or patients' self-evaluation, correlated with patient-reported quality of life as measured by the Short Form-36 and Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) instruments. Design and Methods Three-hundred and thirty-six adult patients (median age 52 years; range, 19 - 79) with chronic graft-versus-host disease from six transplant centers contributed baseline and follow-up data (from 936 visits overall). Results While the majority of the patients had stable chronic graft-versus-host disease, improvement or worsening was noted in approximately 40% of follow-up visits. Multivariable analysis demonstrated no association between change in chronic graft-versus-host disease severity evaluated by National Institute of Health criteria and change in quality of life, while clinician-reported changes in severity were associated with changes in some quality of life measures. Patient-reported changes in the severity of chronic graft-versus-host disease were associated with changes in all quality of life measures. Comparison of the Short Form-36 and the FACT-BMT suggested that the data collected in the Functional Assessment of Cancer Therapy - General (FACT-G) core survey are sufficient without the need for the Short Form-36 or the FACT-BMT subscale. Conclusions We conclude that serial National Institute of Health and clinician-reported chronic graft-versus-host disease severity assessments cannot substitute for patient-reported outcomes in clinical trials. Collection of just the FACT-G instead of the Short Form-36 and the full FACT-BMT will decrease respondent burden without compromising quality of life assessment. C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Kurland, Brenda F.; Chai, Xiaoyu; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vogelsang, Georgia] Johns Hopkins Univ, Baltimore, MD USA. [Weisdorf, Daniel J.; Majhail, Navneet] Univ Minnesota, Minneapolis, MN USA. [Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pidala, J (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,FOB 3308, Tampa, FL 33612 USA. EM joseph.pidala@moffitt.org OI Kurland, Brenda/0000-0002-5669-0595 NR 26 TC 20 Z9 21 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2011 VL 96 IS 10 BP 1528 EP 1535 DI 10.3324/haematol.2011.046367 PG 8 WC Hematology SC Hematology GA 837XR UT WOS:000296245000020 PM 21685473 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI ANALYSIS & COMMENTARY Eliminating Health And Health Care Disparities Among The Growing Population Of People With Disabilities SO HEALTH AFFAIRS LA English DT Editorial Material ID BREAST-CANCER; MOBILITY IMPAIRMENTS; ADA; CALIFORNIA; DIAGNOSIS; BARRIERS; OBESITY; ADULTS; WOMEN AB Fifty-four million people in the United States are now living with disabilities. That number will grow substantially in the next thirty years, as the "baby-boom" generation ages and many of today's children and young adults mature and experience complications related to overweight and obesity. This reality poses a major challenge to the health care and policy communities. People with disabilities confront disadvantages from social and environmental determinants of health, including lower educational levels, lower incomes, and higher unemployment, than people without disabilities. Those with disabilities are also much more likely to report being in fair or poor health; to use tobacco; to forgo physical activity; and to be overweight or obese. People with disabilities also experience health care disparities, such as lower rates of screening and more difficulty accessing services, compared to people without disabilities. Eliminating these multifaceted disadvantages among people with disabilities should be a critical national priority. C1 Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM liezzoni@partners.org NR 38 TC 50 Z9 50 U1 2 U2 8 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 OCT PY 2011 VL 30 IS 10 BP 1947 EP 1954 DI 10.1377/hlthaff.2011.0613 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 833GZ UT WOS:000295872500019 PM 21976339 ER PT J AU Zisook, S Lesser, IM Lebowitz, B Rush, AJ Kallenberg, G Wisniewski, SR Nierenberg, AA Fava, M Luther, JF Morris, DW Trivedi, MH AF Zisook, Sidney Lesser, Ira M. Lebowitz, Barry Rush, A. John Kallenberg, Gene Wisniewski, Stephen R. Nierenberg, Andrew A. Fava, Maurizio Luther, James F. Morris, David W. Trivedi, Madhukar H. TI Effect of Antidepressant Medication Treatment on Suicidal Ideation and Behavior in a Randomized Trial: An Exploratory Report From the Combining Medications to Enhance Depression Outcomes Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITORS; MEASUREMENT-BASED CARE; DIAGNOSTIC SCREENING QUESTIONNAIRE; BRIEF SELF-REPORT; BODY-MASS INDEX; REPORT QIDS-SR; MAJOR DEPRESSION; QUICK INVENTORY; PSYCHOMETRIC EVALUATION AB Objective: To explore relationships between baseline sociodemographic and clinical features and baseline suicidal ideation, and treatment effects on suicidal ideation and behavior, in depressed outpatients. Method: From March 2008 to September 2009, the Combining Medications to Enhance Depression Outcomes study, a single-blind, 7-month randomized trial, enrolled outpatients with nonpsychotic chronic and/or recurrent major depressive disorder (DSM-IV-TR criteria) in primary and psychiatric care (N=665). Participants received escitalopram plus placebo, bupropion sustained release (SR) plus escitalopram, or venlafaxine extended release (XR) plus mirtazapine. The primary outcome measure for this report is presence of suicidal ideation assessed by the Concise Health Risk Tracking Self-Report, which measures suicidal ideation and behaviors over the last 24 hours. Sociodemographic and clinical features were compared in those with versus without baseline ideation. At 4, 12, and 28 weeks, treatment effects on suicidality were assessed, and unadjusted and adjusted outcomes were compared among those with and without baseline ideation using linear, logistic, ordinal logistic, and negative binomial regression models. Results: Baseline suicidal ideation was associated with greater depressive severity, childhood neglect, childhood abuse, early major depressive disorder onset, greater psychiatric comorbidity, and worse functioning and quality of life. After adjustment for treatment, gender, age at first depressive episode, obsessive-compulsive symptoms, and depressive severity, depressive symptom outcomes did not differ between ideation groups at 12 or 28 weeks or between treatments. Overall, 79% of participants with baseline suicidal ideation had none at week 4,83% had none at week 12, and 86% had none at week 28. All treatments reduced ideation, with bupropion-SR plus escitalopram the most effective at week 12 (P < .01). In participants without baseline ideation, emergent ideation did not differ between treatments: 2.5% had ideation at 4 weeks, 1.3% had ideation at 12 weeks, and only 1.7% had ideation at 28 weeks. Four patients (all receiving venlafaxine-XR plus mirtazapine) attempted suicide (P=.0162). Conclusion: Baseline ideation did not affect depressive symptom outcome. Bupropion-SR plus escitalopram most effectively reduced ideation. Ideation emergence was uncommon. Venlafaxine-XR plus mirtazapine may pose a higher risk of suicide attempts. C1 [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Zisook, Sidney] VA Healthcare Syst, La Jolla, CA USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Lebowitz, Barry] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Kallenberg, Gene] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Morris, David W.; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Zisook, S (reprint author), VA Healthcare Syst, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM szisook@ucsd.edu OI Rush, Augustus/0000-0003-2004-2382; Wisniewski, Stephen/0000-0002-3877-9860 FU National Institute of Mental Health [N01MH90003]; American Foundation for Suicide Prevention; Department of Veterans Affairs; PamLab; University of Michigan and Brain Resource; Bristol-Myers Squibb; Cederroth; Cyberonics; Forest; Eli Lilly; GlaxoSmithKline; Janssen; Lichtwer; NARSAD; NIMH; Pfizer; Stanley Foundation; Wyeth-Ayerst; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; Cephalon; Johnson Johnson; Lichtwer Pharma GmbH; Lorex; Novartis; Organon; Pharmavite; Roche; Sanofi/Synthelabo; Solvay; Corcept; Merck; National Alliance for Research on Schizophrenia and Depression; Pharmacia; Upjohn; Predix FX Dr Zisook has received grant support from National Institute of Mental Health, American Foundation for Suicide Prevention, the Department of Veterans Affairs, and PamLab. Dr Lesser has received grant support from the National Institute of Mental Health. Dr Rush has received consultant fees from University of Michigan and Brain Resource; research support from National Institute of Mental Health; and royalties from Guilford Publications and the University of Texas Southwestern Medical Center. Dr Wisniewski has been a consultant for Cyberonics (2005-2006), ImaRx Therapeutics (2006), Bristol-Myers Squibb (2007), Organon (2007), and Case Western Reserve University (2007). Dr Nierenberg has received research support from Bristol-Myers Squibb, Cederroth, Cyberonics, Forest, Eli Lilly, GlaxoSmithKline, Janssen, Lichtwer, NARSAD, NIMH, Pfizer, Stanley Foundation, and Wyeth-Ayerst; has served on speakers bureaus for Bristol-Myers Squibb, Cyberonics, Forest, Eli Lilly, GlaxoSmithKline, and Wyeth-Ayerst; and has provided advisory/consulting services to Abbott, Brain Cells Inc, Bristol-Myers Squibb, Cederroth, Eli Lilly, GlaxoSmithKline, Genaissance, Innapharma, Janssen, Novartis, Pfizer, Sepracor, Shire, and Somerset. Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Eli Lilly, Lorex, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay, and Wyeth-Ayerst; has been an advisor/consultant to Aspect Medical Systems, AstraZeneca, Bayer AG, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Compellis, Cypress, Dov, EPIX, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmBH, Johnson & Johnson, Janssen, Jazz, Knoll, Eli Lilly, Lundbeck, MedAvante, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay, Somerset, and Wyeth-Ayerst; has been on speaking bureaus for AstraZeneca, Bristol-Myers Squibb, Cephalon, Forest, GlaxoSmithKline, Eli Lilly, Novartis, Organon, Pfizer, PharmaStar, and WyethAyerst; and has equity holdings (excluding mutual funds/blinded trusts) with Compellis and MedAvante. Dr Trivedi has been a consultant for Abbott, Akzo (Organon Pharmaceuticals Inc), AstraZeneca, Bayer, Bristol-Myers Squibb, Cephalon, Cyberonics, Eli Lilly, Fabre-Kramer, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Eli Lilly, Mead-Johnson, Neuronetics, Parke-Davis, Pfizer, Pharmacia & Upjohn, Sepracor, Solvay, VantagePoint, and Wyeth-Ayerst; has served on speakers bureaus for Abdi Brahim, Akzo (Organon Pharmaceuticals Inc), Bristol-Myers Squibb, Cephalon, Cyberonics, Forest, GlaxoSmithKline, Janssen, Eli Lilly, Pharmacia & Upjohn, Solvay, and Wyeth-Ayerst; and has received grant support from Bristol-Myers Squibb, Cephalon, Corcept, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Merck, National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression, Novartis, Pfizer, Pharmacia & Upjohn, Predix, Solvay, and Wyeth-Ayerst. Drs Lebowitz, Kallenberg, and Morris and Mr Luther report no additional financial or other relationships relevant to the subject of this article.; This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (principal investigators: Drs Rush and Trivedi). NR 68 TC 15 Z9 15 U1 1 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2011 VL 72 IS 10 BP 1322 EP 1332 DI 10.4088/JCP.10m06724 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 839XL UT WOS:000296402700003 PM 22075098 ER PT J AU Sachs, GS Ice, KS Chappell, PB Schwartz, JH Gurtovaya, O Vanderburg, DG Kasuba, B AF Sachs, Gary S. Ice, Kathleen S. Chappell, Phillip B. Schwartz, Jeffrey H. Gurtovaya, Oksana Vanderburg, Douglas G. Kasuba, Bryce TI Efficacy and Safety of Adjunctive Oral Ziprasidone for Acute Treatment of Depression in Patients With Bipolar I Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; RATING-SCALE; STEP-BD; DSM-IV; SCHIZOPHRENIA; QUETIAPINE; MANIA; LAMOTRIGINE; COMBINATION; VALIDITY AB Objective: To assess efficacy and safety of adjunctive ziprasidone in subjects with bipolar depression treated with lithium, lamotrigine, or valproate. Method: 298 adult outpatients with bipolar I disorder (DSM-IV criteria) were randomized to receive ziprasidone, 20-80 mg twice a day, or placebo twice a day for 6 weeks plus their preexisting mood stabilizer. The primary efficacy variable was change in Montgomery-Asberg Depression Rating Scale (MADRS) total scores from baseline to 6 weeks. The key secondary efficacy endpoint was change from baseline to week 6 in Clinical Global Impressions-Severity (CGI-S) scores. Computer-administered assessments for diagnostic confidence were included for quality control and to evaluate study performance. The study was conducted between October 2007 and December 2008. Results: The mean +/- SD daily dose of ziprasidone was 89.8 +/- 29.1 mg. Least squares mean +/- standard error changes from baseline to week 6 on MADRS total score for ziprasidone and placebo treatment groups were -13.2 +/- 1.2 and -12.9 +/- 1.1, respectively, with a 2-sided P value of .792. There was no significant difference on the key secondary variable (CGI-S). Adjunctive ziprasidone was well tolerated. Poor quality ratings at baseline were associated with a trend for better improvement on placebo than ziprasidone. Among 43 placebo-treated subjects with poor baseline quality ratings, 29 (67.4%) had baseline MADRS scores >10 points higher on the computer-administered assessment than the MADRS administered by the site-based rater. The response favoring placebo over ziprasidone observed in this subgroup suggests that poor signal detection in some clinical trials can be a consequence of "subject inflation" as well as "rater inflation." Conclusions: Adjunctive ziprasidone treatment failed to separate from mood stabilizer alone on primary and secondary endpoints. Possible contributions to this result include enrollment of a substantial number of subjects with low diagnostic confidence, low quality ratings on the MADRS, and overzealous reporting of symptoms by subjects. C1 [Sachs, Gary S.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Kasuba, Bryce] Concordant Rater Syst, Boston, MA USA. [Ice, Kathleen S.; Chappell, Phillip B.; Schwartz, Jeffrey H.] Pfizer Pharmaceut Grp, New London, CT USA. [Vanderburg, Douglas G.] Pfizer Pharmaceut Grp, New York, NY USA. [Gurtovaya, Oksana] Quintiles Inc, St Laurent, PQ, Canada. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM SachsG@aol.com FU Pfizer; Concordant Rater Systems; Pfizer Inc. FX This study was sponsored by Pfizer.; Pfizer contracted with Concordant Rater Systems to conduct the analysis of computer-based ratings independent of the efficacy analysis.; The authors would like to acknowledge the essential contribution of Balarama Gundapaneni, MS (Pfizer Inc), in performing the statistical analyses reported within the article. The authors would also like to acknowledge the editorial assistance provided by Hilary Bennett, MSc, of PAREXEL (Worthing, United Kingdom), which was funded by Pfizer Inc. NR 38 TC 44 Z9 44 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2011 VL 72 IS 10 BP 1413 EP 1422 DI 10.4088/JCP.09m05934 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 839XL UT WOS:000296402700017 PM 21672493 ER PT J AU Peters, AT Nierenberg, AA AF Peters, Amy T. Nierenberg, Andrew A. TI Stepping Back to Step Forward: Lessons From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; DEPRESSED-PATIENTS; DOUBLE-BLIND; ADD-ON; LAMOTRIGINE; ANTIDEPRESSANTS; METAANALYSIS; LITHIUM; DESIGN; SAFETY C1 [Peters, Amy T.; Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Peters, AT (reprint author), 50 Staniford St,Ste 580, Boston, MA 02114 USA. EM apeters4@partners.org NR 18 TC 5 Z9 5 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2011 VL 72 IS 10 BP 1429 EP 1431 DI 10.4088/JCP.11ac07357 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 839XL UT WOS:000296402700019 PM 22075103 ER PT J AU Sadhu, JM Beresin, EV AF Sadhu, Julie M. Beresin, Eugene V. TI Handling Children's Aggression Constructively: Toward Taming Human Destructiveness SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Book Review C1 [Sadhu, Julie M.; Beresin, Eugene V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Sadhu, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM julie.sadhu@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2011 VL 72 IS 10 BP 1432 EP 1432 DI 10.4088/JCP.11bk07281 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 839XL UT WOS:000296402700020 ER PT J AU Levine, M Adler, J AF Levine, Michael Adler, Jonathan TI ACUTE DIAPHRAGMATIC RUPTURE IN A PATIENT WITH EHLERS-DANLOS SYNDROME SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Ehlers Danlos syndrome; EDS; diaphragmatic rupture; diaphragm; chest pain ID HERNIA AB Ehlers-Danlos syndrome (EDS) is a rare connective tissue disorder, usually characterized by the triad of hypermobility of the joints, hyperextensibility of the skin, and tissue fragility. Numerous gastrointestinal complications have been reported with this syndrome. However, spontaneous diaphragmatic rupture remains a very rare complication. We report a case of a 22-year-old woman with EDS who presented to the Emergency Department complaining of shortness of breath and left-sided chest pain. She was ultimately found to have a spontineous diaphragmatic rupture after forceful emesis. (C) 2011 Elsevier Inc. C1 [Levine, Michael] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Adler, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Levine, M (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House,2nd Floor, Boston, MA 02115 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2011 VL 41 IS 4 BP 366 EP 368 DI 10.1016/j.jemermed.2008.03.004 PG 3 WC Emergency Medicine SC Emergency Medicine GA 841VF UT WOS:000296542600004 PM 18439794 ER PT J AU Kleweno, CP Jawa, A Wells, JH O'Brien, TG Higgins, LD Harris, MB Warner, JJP AF Kleweno, Conor P. Jawa, Andrew Wells, Jessica H. O'Brien, Travis G. Higgins, Laurence D. Harris, Mitchel B. Warner, Jon J. P. TI Midshaft clavicular fractures: comparison of intramedullary pin and plate fixation SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Clavicle; Rockwood pin; plating; midclavicular; trauma; intramedullary pin ID MIDCLAVICULAR FRACTURES; NONOPERATIVE TREATMENT; CLINICAL-TRIAL; COMPLICATIONS; NAIL AB Background: Intramedullary pin and plate fixation for midshaft clavicular fractures both have their proponents, but little comparative data are available. We performed a retrospective comparison of these 2 techniques. Materials and methods: A retrospective review was performed on 40 consecutive patients with closed, simple, or wedge-type midshaft clavicular fractures that were identified from a prospectively collected orthopedic trauma database. Eight patients were excluded due to incomplete follow-up. Intramedullary pins were used in 18 patients and plates in 14; of these, 7 plates were placed superiorly, 6 anteriorly, and 1 inferiorly. Treatment method was determined by preference of the treating surgeon. Results: Among the patients treated with intramedullary pin fixation, all 18 fractures healed, and each underwent a planned procedure for pin removal. Complications included 1 intraoperative pin breakage, 1 superficial wound infection, 2 prominent symptomatic pins, and 1 transient brachial plexopathy. Among the patients treated with plating, delayed union occurred in 1, and refractures occurred in 2 (1 required a second procedure). Three patients underwent plate removal for symptomatic hardware. No patients in either group had significant loss of shoulder motion. Conclusion: Intramedullary pin fixation for acute, simple, or wedge-type midshaft clavicular fractures provides a safe and predictable alternative to plate and screw fixation. Level of evidence: Level III, Retrospective Case Control Study, Treatment Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Kleweno, Conor P.] Harvard Combined Orthopaed Surg Residency Program, Boston, MA USA. [Jawa, Andrew] Boston Univ, Med Ctr, Dept Orthopaed Surg, Boston, MA USA. [Wells, Jessica H.; O'Brien, Travis G.; Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Higgins, Laurence D.; Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Harvard Shoulder Serv, Yawkey Ctr Outpatient Care, 55 Fruit St,Ste 3200,3G,Rm 3-046, Boston, MA 02114 USA. EM jwarner@partners.org NR 21 TC 12 Z9 14 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 OCT PY 2011 VL 20 IS 7 BP 1114 EP 1117 DI 10.1016/j.jse.2011.03.022 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 839RM UT WOS:000296386600019 PM 21723149 ER PT J AU Wenger, NS Roth, CP Martin, D Nickels, L Beckman, R Kamberg, C Mach, J Ganz, DA AF Wenger, Neil S. Roth, Carol P. Martin, David Nickels, Lorraine Beckman, Robin Kamberg, Caren Mach, John Ganz, David A. TI Quality of Care Provided in a Special Needs Plan Using a Nurse Care Manager Model SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE special needs plan; quality of care; vulnerable elders; nurse care manager ID VULNERABLE OLDER PATIENTS; HOME RESIDENTS; EVERCARE; DEMENTIA; SERVICES AB OBJECTIVES: To comprehensively evaluate the quality of care provided in special needs plans (SNPs; Medicare Advantage plans that aim to provide specialized care for complex older adults) and specifically the nurse care management model in the community setting. DESIGN: We adapted 107 process-of-care quality measures across 12 conditions from the Assessing Care of Vulnerable Elders set to obtain a clinically detailed evaluation of the quality of care received by complex older enrollees in a dual eligible Evercare SNP. We abstracted 13 months of primary care medical records to delineate quality of care provided by physicians and whether there was value added from the nurse care manager model. SETTING: Dual eligible Evercare SNP located in central Florida. PARTICIPANTS: Two-hundred thirty-one vulnerable older enrollees in the SNP who had complex disease. RESULTS: Based on physician medical records alone, the 231 high-risk participants (mean age 77, 67% women) received recommended care for 53% of 5,569 evaluated clinical circumstances, ranging from 12% for end-of-life care to 78% for diabetes mellitus. In fewer than 40% of these clinical circumstances was recommended care provided for dementia, falls, and urinary incontinence. In a second analysis accounting for care provided by both the Evercare nurse and the physician, recommended care was provided to patients in 69% of the 5,684 evaluated clinical circumstances. CONCLUSION: Comprehensive quality measurement applied to vulnerable older adults enrolled in one mature SNP showed that the Evercare nurse model addresses important deficits in physician care for geriatric conditions. Such measurement should be applied to other SNP models and to compare SNP care with that for complex, older, fee-for-service Medicare cohorts. J Am Geriatr Soc 59:1810-1822, 2011. C1 [Wenger, Neil S.] Univ Calif Los Angeles, Div GIM, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Wenger, Neil S.; Roth, Carol P.; Beckman, Robin; Ganz, David A.] RAND Hlth, Santa Monica, CA USA. [Kamberg, Caren] RAND Hlth, Arlington, VA USA. [Martin, David; Nickels, Lorraine] UnitedHlth Grp, Minnetonka, MN USA. [Mach, John] Univita Hlth, Eden Prairie, MN USA. [Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Wenger, NS (reprint author), Univ Calif Los Angeles, Div GIM, David Geffen Sch Med, 911 Broxton Plaza 309, Los Angeles, CA 90024 USA. EM nwenger@mednet.ucla.edu FU UnitedHealthcare; United-Health Group FX Conflict of Interest: For NW, CR, RB, CK, and DG, UnitedHealthcare funded the project. DM and LN are employed by UnitedHealthcare and retain stock. JM was an employee of UnitedHeathcare at the time of the study and still owns stock.; This project was supported by a contract from United-Health Group to RAND. NR 21 TC 6 Z9 6 U1 0 U2 7 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 OCT PY 2011 VL 59 IS 10 BP 1810 EP 1822 DI 10.1111/j.1532-5415.2011.03599.x PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 840OE UT WOS:000296449300005 PM 22091494 ER PT J AU Doornberg, JN Buijze, GA Ham, SJ Ring, D Bhandari, M Poolman, RW AF Doornberg, Job N. Buijze, Geert A. Ham, S. John Ring, David Bhandari, Mohit Poolman, Rudolf W. TI Nonoperative Treatment for Acute Scaphoid Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review DE Scaphoid; Fractures; Nonoperative treatment; Cast immobilization; Systematic review ID CAST IMMOBILIZATION; DISPLACED FRACTURES; MANAGEMENT; RECOMMENDATIONS; FIXATION; QUALITY; THUMB; WAIST; BONE AB Background: Recommendations for cast immobilization of acute scaphoid fractures vary substantially. We reviewed data from randomized controlled trials comparing nonoperative treatment methods for acute scaphoid fractures to determine the best available evidence. Methods: A systematic search of the medical literature from 1966 to 2010 was performed. Two authors independently screened titles and abstracts, reviewed articles, assessed methodological quality according to the Grading of Recommendations Assessment Development and Evaluation system, and extracted data. The primary outcome parameter was nonunion. Data were pooled using random-effects models with standard mean differences for continuous and risk ratios for dichotomous variables, respectively. Heterogeneity across studies was assessed with calculation of the I(2) statistic. Results: The search resulted in five potentially eligible trials of which four met our inclusion criteria. In total, 523 patients were included in four trials including two evaluating below-elbow casting versus above-elbow casting; one trial comparing below-elbow casting including the thumb versus excluding the thumb; and one trial comparing fractures with a below-elbow cast with the wrist in 20-degrees flexion to 20-degrees extension, with both types excluding the thumb. There were no significant differences in union rate, pain, grip strength, time to union, or osteonecrosis for the various nonoperative treatment methods. Conclusions: There is no evidence from randomized controlled trials on physician-based or patient-based outcome to favor any nonoperative treatment method for acute scaphoid fractures. C1 [Doornberg, Job N.; Buijze, Geert A.] Acad Med Ctr, Dept Orthopaed Surg, NL-1100 DD Amsterdam, Netherlands. [Ham, S. John; Poolman, Rudolf W.] Onze Lieve Vrouw Hosp, Dept Orthopaed Surg, Amsterdam, Netherlands. [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Bhandari, Mohit] Hamilton Hlth Sci Gen Hosp, Dept Orthopaed Surg, Hamilton, ON, Canada. RP Buijze, GA (reprint author), Acad Med Ctr, Dept Orthopaed Surg, POB 22660, NL-1100 DD Amsterdam, Netherlands. EM gbuijze@partners.org FU Netherlands Organisation for Scientific Research (NWO); Marti-Keuning-Eckhardt Foundatio; Canada Research Chair FX Supported by the Netherlands Organisation for Scientific Research (NWO) (to G. A. B.).; Supported by the Marti-Keuning-Eckhardt Foundation (to J.N.D.), and MB was partially funded as a Canada Research Chair. NR 28 TC 10 Z9 10 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2011 VL 71 IS 4 BP 1073 EP 1081 DI 10.1097/TA.0b013e318222f485 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 833ZT UT WOS:000295925700059 PM 21986747 ER PT J AU Yanover, C Jain, N Pierce, G Howard, TE Sauna, ZE AF Yanover, Chen Jain, Nisha Pierce, Glenn Howard, Tom E. Sauna, Zuben E. TI Pharmacogenetics and the immunogenicity of protein therapeutics SO NATURE BIOTECHNOLOGY LA English DT Letter ID FACTOR-VIII; RISK-FACTORS; IMMUNE-RESPONSES; INHIBITORS; PREVENTION; HEMOPHILIA; PREDICTION C1 [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Jain, Nisha] US FDA, Clin Review Branch, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Pierce, Glenn] Biogen Idec Hemophilia, Waltham, MA USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Yanover, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Computat Biol, 1124 Columbia St, Seattle, WA 98104 USA. EM Zuben.Sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 NR 20 TC 13 Z9 13 U1 0 U2 9 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 OCT PY 2011 VL 29 IS 10 BP 870 EP 873 DI 10.1038/nbt.2002 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 838FQ UT WOS:000296273000009 PM 21997623 ER PT J AU Clarke, JL Ennis, MM Yung, WKA Chang, SM Wen, PY Cloughesy, TF DeAngelis, LM Robins, HI Lieberman, FS Fine, HA Abrey, L Gilbert, MR Mehta, M Kuhn, JG Aldape, KD Lamborn, KR Prados, MD AF Clarke, Jennifer L. Ennis, Michele M. Yung, W. K. Alfred Chang, Susan M. Wen, Patrick Y. Cloughesy, Timothy F. DeAngelis, Lisa M. Robins, H. Ian Lieberman, Frank S. Fine, Howard A. Abrey, Lauren Gilbert, Mark R. Mehta, Minesh Kuhn, John G. Aldape, Kenneth D. Lamborn, Kathleen R. Prados, Michael D. CA N Amer Brain Tumor Consortium TI Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; PFS6; prognosis; recurrence; surgery ID II CLINICAL-TRIALS; PHASE-II; GLIOMA; THERAPY AB Historically, the North American Brain Tumor Consortium used 6-month progression-free survival (PFS6) as the primary outcome for recurrent glioma phase II clinical trials. In some trials, a subset of patients received the trial treatment before surgery to assess tumor uptake and biological activity. We compared PFS6 and overall survival (OS) for patients with glioblastoma undergoing surgery at progression to results for those without surgery to evaluate the impact of surgical intervention on these outcomes. Two data sets were analyzed. The first included 511 patients enrolled during the period 1998-2005, 105 of whom had surgery (excluding biopsies) during the study or <= 30 days prior to registration. Analysis was stratified on the basis of whether temozolomide was part of the protocol treatment regimen. The second data set included 247 patients enrolled during 2005-2008, 103 of whom underwent surgery during the clinical trial or immediately prior to study registration. A combined data set consisting of all patients who did not receive temozolomide was also compiled. No statistically significant difference in PFS6 or OS was found between the surgery and nonsurgery groups in either data set alone or in the combined data set (P > .45). We conclude that PFS6 and OS results for patients with and without surgical intervention at the time of progression are similar, allowing data from these patients to be combined in assessing the benefit of new treatments without the need for stratification or other statistical adjustment. C1 [Clarke, Jennifer L.; Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Yung, W. K. Alfred; Gilbert, Mark R.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeAngelis, Lisa M.; Abrey, Lauren] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robins, H. Ian] Univ Wisconsin Hosp, Madison, WI USA. [Lieberman, Frank S.] Univ Pittsburgh, Med Ctr Canc Pavil, Div Neurooncol, Pittsburgh, PA USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Minesh] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. RP Clarke, JL (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,A-808, San Francisco, CA 94143 USA. EM clarkej@neurosurg.ucsf.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU North American Brain Tumor Consortium [CA62399] FX This work was supported by the North American Brain Tumor Consortium [CA62399]. NR 5 TC 30 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2011 VL 13 IS 10 BP 1118 EP 1124 DI 10.1093/neuonc/nor110 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 835YB UT WOS:000296071900007 PM 21813511 ER PT J AU Rudner, LA Brown, KH Dobrinski, KP Bradley, DF Garcia, MI Smith, ACH Downie, JM Meeker, ND Look, AT Downing, JR Gutierrez, A Mullighan, CG Schiffman, JD Lee, C Trede, NS Frazer, JK AF Rudner, L. A. Brown, K. H. Dobrinski, K. P. Bradley, D. F. Garcia, M. I. Smith, A. C. H. Downie, J. M. Meeker, N. D. Look, A. T. Downing, J. R. Gutierrez, A. Mullighan, C. G. Schiffman, J. D. Lee, C. Trede, N. S. Frazer, J. K. TI Shared acquired genomic changes in zebrafish and human T-ALL SO ONCOGENE LA English DT Article DE T-cell acute lymphoblastic leukemia (T-ALL); array comparative genome hybridization (aCGH); zebrafish; copy number aberration (CNA); leukemogenesis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSGENIC ZEBRAFISH; CELL TRANSPLANTATION; MODEL; ARRAY; HYBRIDIZATION; MUTATIONS; DELETION; MYC; SELECTION AB T-cell acute lymphoblastic leukemia (T-ALL) is a challenging clinical entity with high rates of induction failure and relapse. To discover the genetic changes occurring in T-ALL, and those contributing to relapse, we studied zebrafish (Danio rerio) T-ALL samples using array comparative genomic hybridization (aCGH). We performed aCGH on 17 T-ALLs from four zebrafish T-ALL models, and evaluated similarities between fish and humans by comparing all D. rerio genes with copy number aberrations (CNAs) with a cohort of 75 published human T-ALLs analyzed by aCGH. Within all D. rerio CNAs, we identified 893 genes with human homologues and found significant overlap (67%) with the human CNA dataset. In addition, when we restricted our analysis to primary T-ALLs (14 zebrafish and 61 human samples), 10 genes were recurrently altered in 43 zebrafish cancers and >= 4 human cases, suggesting a conserved role for these loci in T-ALL transformation across species. We also conducted iterative allo-transplantation with three zebrafish malignancies. This technique selects for aggressive disease, resulting in shorter survival times in successive transplant rounds and modeling refractory and relapsed human T-ALL. Fifty-five percent of original CNAs were preserved after serial transplantation, demonstrating clonality between each primary and passaged leukemia. Cancers acquired an average of 34 new CNAs during passaging. Genes in these loci may underlie the enhanced malignant behavior of these neoplasias. We also compared genes from CNAs of passaged zebrafish malignancies with aCGH results from 50 human T-ALL patients who failed induction, relapsed or would eventually relapse. Again, many genes (88/164) were shared by both datasets. Further, nine recurrently altered genes in passaged D. rerio T-ALL were also found in multiple human T-ALL cases. These results suggest that zebrafish and human T-ALLs are similar at the genomic level, and are governed by factors that have persisted throughout evolution. Oncogene (2011) 30, 4289-4296; doi: 10.1038/onc.2011.138; published online 9 May 2011 C1 [Schiffman, J. D.; Trede, N. S.; Frazer, J. K.] Univ Utah, Dept Pediat, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Brown, K. H.; Dobrinski, K. P.; Lee, C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Garcia, M. I.] Univ Texas Brownsville, Brownsville, TX 78520 USA. [Look, A. T.; Gutierrez, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Look, A. T.; Gutierrez, A.] Childrens Hosp, Boston, MA 02115 USA. [Downing, J. R.; Mullighan, C. G.] St Jude Childrens Hosp, Memphis, TN 38105 USA. RP Frazer, JK (reprint author), Univ Utah, Dept Pediat, Dept Oncol Sci, Huntsman Canc Inst, 2000 Circle Hope,HCI 4264, Salt Lake City, UT 84112 USA. EM kimble.frazer@hsc.utah.edu OI Gutierrez, Alejandro/0000-0002-0249-9007; Mullighan, Charles/0000-0002-1871-1850; Frazer, John Kimble/0000-0003-2936-2817; Downie, Jonathan/0000-0002-5424-4401 FU NIAID [R21-AI079784]; Huntsman Cancer Foundation; Eunice Kennedy Shriver NICHD [K08-HD053350]; CHRC at the University of Utah; PCMC Foundation FX We thank Brett Milash for bioinformatics analyses, Ken Boucher for statistical expertise, and Bradley Demarest for assistance with figure preparation. NST was supported by NIAID award R21-AI079784 and the Huntsman Cancer Foundation. JKF was supported by Eunice Kennedy Shriver NICHD award K08-HD053350, the CHRC at the University of Utah, and the PCMC Foundation. Huntsman Cancer Institute core facilities supported by NCI P30-CA042014 also contributed to this work. NR 33 TC 18 Z9 18 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2011 VL 30 IS 41 BP 4289 EP 4296 DI 10.1038/onc.2011.138 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 839HO UT WOS:000296356300006 PM 21552289 ER PT J AU Holleman, A Chung, I Olsen, RR Kwak, B Mizokami, A Saijo, N Parissenti, A Duan, Z Voest, EE Zetter, BR AF Holleman, A. Chung, I. Olsen, R. R. Kwak, B. Mizokami, A. Saijo, N. Parissenti, A. Duan, Z. Voest, E. E. Zetter, B. R. TI miR-135a contributes to paclitaxel resistance in tumor cells both in vitro and in vivo SO ONCOGENE LA English DT Article DE paclitaxel resistance; miRNA-135a; APC; carcinoma ID MICRORNA EXPRESSION PROFILES; SPINDLE ASSEMBLY CHECKPOINT; BREAST-CANCER CELLS; LUNG-CANCER; ALKYLATING-AGENTS; DRUG-RESISTANCE; SUPPRESSOR GENE; SENSITIVITY; PROSTATE; APC AB Cancer cell resistance to paclitaxel continues to be a major clinical problem. In this study, we utilized microRNA (miRNA) arrays to screen for differentially expressed miRNAs in paclitaxel-resistant cell lines established in vitro. We observed concordant upregulation of miR-135a in paclitaxel-resistant cell lines representing three human malignancies. Subsequently, the role of miRNA-135a was evaluated in an in vivo model of paclitaxel resistance. In this model, mice were inoculated subcutaneously with a non-small cell lung carcinoma cell line and treated with paclitaxel for a prolonged period. In paclitaxel-resistant cell lines, established either in vitro or in vivo, blockage of miR-135a sensitized resistant cell lines to paclitaxel-induced cell death. We further demonstrated a correlation between paclitaxel response and miR-135a expression in paclitaxel-resistant subclones that were established in vivo. The paclitaxel-resistant phenotype of these subclones was maintained upon retransplantation in new mice, as shown by decreased tumor response upon paclitaxel treatment compared with controls. Upregulation of miR-135a was associated with reduced expression of the adenomatous polyposis coli gene (APC). APC knockdown increased paclitaxel resistance in parental cell lines. Our results indicate that paclitaxel resistance is associated with upregulation of miR-135a, both in vitro and in vivo, and is in part determined by miR-135a-mediated downregulation of APC. Oncogene (2011) 30, 4386-4398; doi:10.1038/onc.2011.148; published online 9 May 2011 C1 [Holleman, A.; Chung, I.; Olsen, R. R.; Kwak, B.; Zetter, B. R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA. [Holleman, A.] Meander Med Ctr, Dept Internal Med, Amersfoort, Netherlands. [Mizokami, A.] Kanazawa Univ, Grad Sch Med Sci, Dept Integrat Canc Therapy & Urol, Kanazawa, Ishikawa, Japan. [Saijo, N.] Natl Canc Ctr, Res Inst, Div Med Oncol, Tokyo 104, Japan. [Parissenti, A.] Hop Reg Sudbury Reg Hosp, Reg Canc Program, Sudbury, ON, Canada. [Duan, Z.] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. [Voest, E. E.] Utrecht Med Ctr, Dept Med Oncol, Utrecht, Netherlands. RP Zetter, BR (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, 300 Longwood Ave,Karp Bldg,Room 11-125, Boston, MA 02115 USA. EM bruce.zetter@childrens.harvard.edu RI Chung, Ivy/C-3804-2012 FU National Institutes of Health; Kendle; KWF Cancer Foundation; Stichting Fonds Catherine van Tussenbroek; US Department of Defense FX We sincerely thank Dr John Heymach of MD Anderson Cancer Institute, Houston, TX and Jeremy Force, Children's Hospital Boston, for kindly providing us with the A549TR cells. This work was supported in part by grant CA37393 from the National Institutes of Health (BRZ), Kendle (AH), KWF Cancer Foundation (AH), the Stichting Fonds Catherine van Tussenbroek (AH), and a US Department of Defense PCRP fellowship (IC). NR 54 TC 48 Z9 55 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 2011 VL 30 IS 43 BP 4386 EP 4398 DI 10.1038/onc.2011.148 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 839HQ UT WOS:000296356500002 PM 21552288 ER PT J AU de Oliveira, MA Martins, FME Wang, Q Sonis, S Demetri, G George, S Butrynski, J Treister, NS AF de Oliveira, Marcio Augusto Martins e Martins, Fabiana Wang, Qian Sonis, Stephen Demetri, George George, Suzanne Butrynski, James Treister, Nathaniel S. TI Clinical presentation and management of mTOR inhibitor-associated stomatitis SO ORAL ONCOLOGY LA English DT Article DE Aphthous stomatitis; Cancer; Mammalian target of rapamycin inhibitor; mTOR; Mucositis ID RENAL-CELL CARCINOMA; RECURRENT APHTHOUS STOMATITIS; ADVANCED SOLID TUMORS; SINGLE-AGENT TEMSIROLIMUS; PHASE-I TRIAL; EVERY 2 WEEKS; MAMMALIAN TARGET; RAPAMYCIN INHIBITOR; ADVANCED MALIGNANCIES; DEFOROLIMUS AP23573 AB Anti-cancer agents that inhibit the mTOR pathway are associated with a number of unique toxicities, with one of the most significant and potentially dose-limiting being stomatitis. The objective of this study was to report the clinical features and management outcomes of a series of cancer patients who developed painful mTOR inhibitor-associated stomatitis (mIAS). Seventeen cancer patients developed mIAS while being treated with everolimus-or ridaforolimus-containing protocols at the Dana-Farber Cancer Institute and were referred to the oral medicine clinic for evaluation and management. Clinical characteristics, toxicity management, and outcomes were summarized. In addition, the frequency and rationale for dose reductions and therapy discontinuation were assessed. The median duration of mTOR inhibitor therapy was 80 days (range 9-187 days). The median time to development of mouth ulcers was 10 days (range 4-25 days). Five patients required protocol-directed dose reductions due to grades 2 and 3 stomatitis and one patient discontinued cancer treatment due to mouth ulcers. Clinical improvement and pain relief was reported in 86.6% of patients following topical, intralesional, or systemic corticosteroid therapy, with side effects limited to secondary candidiasis (n = 2). Mouth ulcers are a common and potentially dose limiting toxicity associated with the use of mTOR inhibitors in cancer treatment. This case series demonstrates that local and systemic corticosteroid therapy is an effective approach to managing patients with symptomatic mIAS. Prospective studies are necessary to evaluate the effectiveness of treatment and prevention strategies with the ultimate goal of improving overall cancer treatment outcomes. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sonis, Stephen; Treister, Nathaniel S.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [de Oliveira, Marcio Augusto; Martins e Martins, Fabiana] Univ Sao Paulo, Sch Dent, Dept Oral Pathol, Sao Paulo, Brazil. [Wang, Qian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sonis, Stephen; Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Demetri, George; George, Suzanne; Butrynski, James] Dana Farber Canc Inst, Dept Med Oncol, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC-3-028, Boston, MA 02120 USA. EM ntreister@partners.org NR 43 TC 36 Z9 36 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD OCT PY 2011 VL 47 IS 10 BP 998 EP 1003 DI 10.1016/j.oraloncology.2011.08.009 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 841YY UT WOS:000296552300014 PM 21890398 ER PT J AU Bartzokis, G Lu, PH Amar, CP Raven, EP Detore, NR Altshuler, LL Mintz, J Ventura, J Casaus, LR Luo, JS Subotnik, KL Nuechterlein, KH AF Bartzokis, George Lu, Po H. Amar, Chetan P. Raven, Erika P. Detore, Nicole R. Altshuler, Lori L. Mintz, Jim Ventura, Joseph Casaus, Laurie R. Luo, John S. Subotnik, Kenneth L. Nuechterlein, Keith H. TI Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Antipsychotic; Medication; Dopamine; Second generation; Atypical; Myelin; White matter; Gray matter; Oligodendrocyte; Development; Aging ID SCHIZOAFFECTIVE DISORDER; TREATMENT RESPONSE; INTRACORTICAL MYELINATION; ATYPICAL ANTIPSYCHOTICS; PREFRONTAL CORTEX; 1ST EPISODE; BRAIN; ABNORMALITIES; CHOLESTEROL; PREDICTORS AB Context: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. Objectives: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N = 11; and RisO, N = 13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measure: WM volume change scores. Results: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. Conclusions: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions. Published by Elsevier B.V. C1 [Bartzokis, George; Amar, Chetan P.; Raven, Erika P.; Detore, Nicole R.; Altshuler, Lori L.; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA 90095 USA. [Bartzokis, George; Amar, Chetan P.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Bartzokis, G (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIH [MH 0266029, AG027342, MH51928, MH6357, MH037705, P50 MH066286]; Ortho-McNeil Janssen Scientific Affairs, LLC.; Department of Veterans Affairs; Janssen Pharmaceutical Inc. FX Funding for this study was supported in part by NIH grants (MH 0266029; AG027342; MH51928; MH6357; MH037705; P50 MH066286) and two investigator-initiated grants from Ortho-McNeil Janssen Scientific Affairs, LLC.; and the Department of Veterans Affairs. The NIH, Janssen Pharmaceutical Inc., and the Department of Veterans Affairs had no 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.; George Bartzokis and Keith Nuechterlein have received funding from Janssen Pharmaceutical Inc. George Bartzokis has consulted for Janssen Pharmaceutical Inc. NR 53 TC 32 Z9 34 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2011 VL 132 IS 1 BP 35 EP 41 DI 10.1016/j.schres.2011.06.029 PG 7 WC Psychiatry SC Psychiatry GA 833VJ UT WOS:000295912700006 PM 21767934 ER PT J AU Dyckman, KA Lee, AKC Agam, Y Vangel, M Goff, DC Barton, JJS Manoach, DS AF Dyckman, Kara A. Lee, Adrian K. C. Agam, Yigal Vangel, Mark Goff, Donald C. Barton, Jason J. S. Manoach, Dara S. TI Abnormally persistent fMRI activation during antisaccades in schizophrenia: A neural correlate of perseveration? SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Antisaccade; Frontal eye field; Functional MRI; Perseveration; Inhibition ID EVENT-RELATED FMRI; FRONTAL EYE-FIELD; HEMODYNAMIC-RESPONSES; ANTI-SACCADES; TRIAL HISTORY; PRO-SACCADES; TASKS; VARIABILITY; INHIBITION; PLASTICITY AB Objective: Impaired antisaccade performance is a consistent cognitive finding in schizophrenia. Antisaccades require both response inhibition and volitional motor programming, functions that are essential to flexible responding. We investigated whether abnormal timing of hemodynamic responses (HDRs) to antisaccades might contribute to perseveration of ocular motor responses in schizophrenia. We focused on the frontal eye field (FEF), which has been implicated in the persistent effects of antisaccades on subsequent responses in healthy individuals. Method: Eighteen chronic, medicated schizophrenia outpatients and 15 healthy controls performed antisaccades and prosaccades during functional MRI. Finite impulse response models provided unbiased estimates of event-related HDRs. We compared groups on the peak amplitude, time-to-peak, and full-width half-max of the HDRs. Results: In patients, HDRs in bilateral FEF were delayed and prolonged but ultimately of similar amplitude to that of controls. These abnormalities were present for antisaccades, but not prosaccades, and were not seen in a control region. More prolonged HDRs predicted slower responses in trials that followed an antisaccade. This suggests that persistent FEF activity following an antisaccade contributes to inter-trial effects on latency. Conclusions: Delayed and prolonged HDRs for antisaccades in schizophrenia suggest that the functions necessary for successful antisaccade performance take longer to implement and are more persistent. If abnormally persistent neural responses on cognitively demanding tasks are a more general feature of schizophrenia, they may contribute to response perseveration, a classic behavioral abnormality. These findings also underscore the importance of evaluating the temporal dynamics of neural activity to understand cognitive dysfunction in schizophrenia. (C) 2011 Elsevier B.V. All rights reserved. C1 [Dyckman, Kara A.; Lee, Adrian K. C.; Agam, Yigal; Goff, Donald C.; Manoach, Dara S.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. [Lee, Adrian K. C.; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vangel, Mark] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol, Vancouver, BC V6T 1Z4, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol, Vancouver, BC V6T 1Z4, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Visual Sci, Vancouver, BC V6T 1Z4, Canada. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; OI Lee, Adrian KC/0000-0002-7611-0500 FU Canadian Institutes of Health Research [MOP-81270]; NCRR NIH HHS [P41RR14075, P41 RR014075, P41 RR014075-13]; NIMH NIH HHS [R01 MH067720, F32 MH088081, R01 MH67720, F32 MH088081-01, F32 MH082514-02, R01 MH067720-08, F32 MH082514] NR 40 TC 15 Z9 15 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2011 VL 132 IS 1 BP 62 EP 68 DI 10.1016/j.schres.2011.07.026 PG 7 WC Psychiatry SC Psychiatry GA 833VJ UT WOS:000295912700010 PM 21831602 ER PT J AU Zeitels, SM Barbu, AM Landau-Zemer, T Lopez-Guerra, G Burns, JA Friedman, AD Freeman, MW Halvorsen, YD Hillman, RE AF Zeitels, Steven M. Barbu, Anca M. Landau-Zemer, Tali Lopez-Guerra, Gerardo Burns, James A. Friedman, Aaron D. Freeman, Mason W. Halvorsen, Yuan-Di Hillman, Robert E. TI Local Injection of Bevacizumab (Avastin) and Angiolytic KTP Laser Treatment of Recurrent Respiratory Papillomatosis of the Vocal Folds: A Prospective Study SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Avastin; bevacizumab; glottis; KTP laser; larynx; laser; papilloma; papillomatosis; recurrent respiratory papillomatosis; RRP; vocal cord; vocal fold; voice ID TUMOR ANGIOGENESIS; ANESTHESIA; DYSPLASIA; CANCER; SAFETY AB Objectives: Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a negative impact on the voice and whether there were local or systemic complications. Methods: A prospective open-label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained. Results: All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range. Conclusions: This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary. C1 [Zeitels, Steven M.; Barbu, Anca M.; Landau-Zemer, Tali; Lopez-Guerra, Gerardo; Burns, James A.; Friedman, Aaron D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Zeitels, Steven M.; Barbu, Anca M.; Landau-Zemer, Tali; Lopez-Guerra, Gerardo; Burns, James A.; Friedman, Aaron D.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Freeman, Mason W.; Halvorsen, Yuan-Di] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Freeman, Mason W.; Halvorsen, Yuan-Di] Massachusetts Gen Hosp, Translat Med Grp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. FU Eugene B. Casey Foundation; V Foundation; Institute of Laryngology and Voice Restoration; Harvard Catalyst Program FX This work was supported in part by the Eugene B. Casey Foundation, the V Foundation, the Institute of Laryngology and Voice Restoration, and the Harvard Catalyst Program. NR 29 TC 18 Z9 18 U1 0 U2 5 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 OCT PY 2011 VL 120 IS 10 BP 627 EP 634 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 837MY UT WOS:000296209100001 PM 22097147 ER PT J AU Quin, JA Sheng, SB O'Brien, SM Welke, KF Grover, FL Shroyer, AL AF Quin, Jacquelyn A. Sheng, Shubin O'Brien, Sean M. Welke, Karl F. Grover, Frederick L. Shroyer, A. Laurie TI Regional Variation in Patient Risk Factors and Mortality After Coronary Artery Bypass Grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC-SURGERY DATABASE; NEW-YORK-STATE; NATIONAL DATABASE; HEALTH-CARE; OUTCOMES; SERVICES; MEDICARE; SOCIETY; DISEASE AB Background. Geographic variations in patient risk factors and operative mortality after coronary artery bypass graft surgery have not been well studied. Methods. Using The Society of Thoracic Surgeons National Cardiac Database, a retrospective cohort study was performed of patients undergoing isolated coronary artery bypass graft surgery from 2004 to 2007 (n = 504,608). Records were sorted into four major geographic regions (Northeast, Midwest, South, and West) and compared with respect to patient risk profiles and outcomes. Using marginal and hierarchical logistic regression, risk-adjusted operative mortality rates were compared across regions and variation assessed within regions, states and hospital referral regions. Results. Patient risk profiles in the Northeast and West appeared similar, as did profiles in the Midwest and South. Risk-adjusted mortality rates were as follows: Northeast 1.63%, Midwest 2.01%, South 2.25%, and West 1.82%. Compared with the Northeast, mortality rates in the Midwest and South were higher, with the following odds ratios (95% confidence intervals): Midwest 1.26 (1.12 to 1.42), South 1.44 (1.27 to 1.62), and West 1.12 (0.98 to 1.28). Major geographic regions accounted for 16.5% of the variation observed in mortality rates; states and hospital referral regions accounted for 17.8% and 65.7%, respectively. Conclusions. Variations in absolute coronary artery bypass graft surgery mortality rates across large regions were subtle, although rates within the Northeast were comparatively lower. Most of the variation was seen at the hospital referral region level. Given that geographic location has not been routinely incorporated into statistical risk model predictions, additional research appears warranted to identify regional "best care" practices and to advance nationwide improvements in cardiac surgical patient outcomes. (Ann Thorac Surg 2011;92:1277-83) (C) 2011 by The Society of Thoracic Surgeons C1 [Quin, Jacquelyn A.] VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA. Duke Clin Res Inst, Durham, NC USA. Multicare Hlth Syst, Tacoma, WA USA. Univ Colorado, Hlth & Sci Ctr, Denver, CO 80202 USA. SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. RP Quin, JA (reprint author), VA Boston Healthcare Syst, Surg Serv, Mail Code 112, W Roxbury, MA 02132 USA. EM jacquelyn.quin@va.gov RI O'Brien, Sean/H-6268-2013; Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 33 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2011 VL 92 IS 4 BP 1277 EP 1282 DI 10.1016/j.athoracsur.2011.05.062 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 833ZI UT WOS:000295924400035 PM 21855853 ER PT J AU Baker, JN Sundt, T AF Baker, Joshua N. Sundt, Thoralf, III TI Mortality in Acute Type A Aortic Dissection: Validation of the Penn Classification INVITED COMMENTARY SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 [Baker, Joshua N.; Sundt, Thoralf, III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Baker, JN (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox 652, Boston, MA 02114 USA. EM tsundt@partners.org NR 2 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2011 VL 92 IS 4 BP 1382 EP 1383 DI 10.1016/j.athoracsur.2011.06.014 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 833ZI UT WOS:000295924400059 PM 21958784 ER PT J AU Sareyyupoglu, B Sundt, TM AF Sareyyupoglu, Basar Sundt, Thoralf M., III TI The Surgical Treatment of Acute Pulmonary Embolism SO ANNALS OF THORACIC SURGERY LA English DT Letter ID EMBOLECTOMY; SUPPORT C1 [Sareyyupoglu, Basar] Scott & White Mem Hosp & Clin, Texas A&M Hlth Sci Ctr, Coll Med, Div Cardiothorac Surg, Temple, TX 76508 USA. [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sareyyupoglu, B (reprint author), Scott & White Mem Hosp & Clin, Texas A&M Hlth Sci Ctr, Coll Med, Div Cardiothorac Surg, 2401 S 31st St, Temple, TX 76508 USA. EM tsundt@partners.org NR 6 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 OCT PY 2011 VL 92 IS 4 BP 1552 EP 1552 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 833ZI UT WOS:000295924400114 PM 21958828 ER PT J AU Wang, ZR Duran-Struuck, R Crepeau, R Matar, A Hanekamp, I Srinivasan, S Neville, DM Sachs, DH Huang, CA AF Wang, Zhirui Duran-Struuck, Raimon Crepeau, Rebecca Matar, Abraham Hanekamp, Isabel Srinivasan, Srimathi Neville, David M., Jr. Sachs, David H. Huang, Christene A. TI Development of a Diphtheria Toxin Based Antiporcine CD3 Recombinant Immunotoxin SO BIOCONJUGATE CHEMISTRY LA English DT Article ID T-CELL DEPLETION; SINGLE-CHAIN IMMUNOTOXIN; LARGE-ANIMAL-MODEL; PICHIA-PASTORIS; MIXED CHIMERISM; MINIATURE SWINE; OPTIMIZATION; EXPRESSION; TOLERANCE; PCD3-CRM9 AB Anti-CD3 immunotoxins, which induce profound but transient T-cell depletion in vivo by inhibiting eukaryotic protein synthesis in CD3+ cells, are effective reagents in large animal models of transplantation tolerance and autoimmune disease therapy. A diphtheria toxin based antiporcine CD3 recombinant immunotoxin was constructed by fusing the truncated diphtheria toxin DT390 with two identical tandem single chain variable fragments (scFv) derived from the antiporcine CD3 mono-clonal antibody 898H2-6715. The recombinant immunotoxin was pressed in a diphtheria-toxin resistant yeast Pichia pastoris strain under the control of the alcohol oxidase-promoter. The secreted recombinant immunotoxin was purified sequentially With hydrophobic interaction chromatography (Butyl 660 M) followed by strong anion exchange (Poros 50 HQ) The purified antiporcine CD3 immunotoxin was tested in vivo in four-animals; peripheral blood CP3+,T-cell numbers were reduced by 80% and lymph node T-Cells decreased from 74% CD3+ cells pretreatment to 24% CD3+ cells remaining in the lymph node following 4 days of immunotoxin treatment. No clinical toxicity was observed in any of the experimental swine. We anticipate that this conjugate will provide an important tool for in vivo depletion of T-cells in swine transplantation models. C1 [Wang, Zhirui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH East, Boston, MA 02129 USA. [Wang, Zhirui; Sachs, David H.; Huang, Christene A.] DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA USA. [Neville, David M., Jr.] Angimmune LLC, Bethesda, MD 20814 USA. RP Wang, ZR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH East, Bldg 149-6113 13th St, Boston, MA 02129 USA. EM zhirui.wang@tbrc.mgh.harvard.edu FU National Institutes of Health [R01AI084657-02]; Dana Farber/Harvard Cancer Center FX The work was supported by National Institutes of Health (R01AI084657-02 to CAR) and Dana Farber/Harvard Cancer Center Core development grant. We thank Christina Hermanrud, Prashanth Vallabhajosyula, and Lauren L. Springett for their excellent technical assistance, and Bob Hawley and Sharon Germana for intensive manuscript review. NR 20 TC 21 Z9 21 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD OCT PY 2011 VL 22 IS 10 BP 2014 EP 2020 DI 10.1021/bc200230h PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 833WE UT WOS:000295915100015 PM 21866954 ER PT J AU Zeglis, BM Mohindra, P Weissmann, GI Divilov, V Hilderbrand, SA Weissleder, R Lewis, JS AF Zeglis, Brian M. Mohindra, Priya Weissmann, Gabriel I. Divilov, Vadim Hilderbrand, Scott A. Weissleder, Ralph Lewis, Jason S. TI Modular Strategy for the Construction of Radiometalated Antibodies for Positron Emission Tomography Based on Inverse Electron Demand Diels-Alder Click Chemistry SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; BREAST-CANCER; IMMUNO-PET; IMMUNOREACTIVE FRACTION; GROWING APPLICATIONS; IN-VIVO; HER2; BIODISTRIBUTION; MICE; RADIOPHARMACEUTICALS AB A modular system for the construction of radio-metalated antibodies was developed based on the bioorthogonal cycloaddition reaction between 3-(4-benzylamino)-1,2,4, 5-tetrazine and the strained dienophile norbomene. The well-characterized, HER2-specific antibody trastuzumab and the positron emitting radioisotopes Cu-64 and Zr-89 were employed as a model system. The antibody was first covalently coupled to norbomene, and this stock of norbornene-modified antibody was then reacted with tetrazines bearing the chelators 1,4,7,10-tetraazacyclo-dodecane:1,4,7,10-tetiaacetic acid (DOTA) or desferrioxamine (DFO) and subsequently radiometalated with Cu-64 and Zr-89, respectively. The modification strategy is simple and robust, and the resultant radiometalated constructs were obtained in high specific (2.7-75.3 mCi/mg). For a given initial stoichiometric ratio of norbornene to antibody, the Cu-64-DOTA- and Zr-89-DFO-based probes Were shown to be nearly identical in terms of stability, the number of chelates per antibody, and immunoreactivity (9356 hi all cases). In vivo PET imaging and acute biodistribution experiments revealed significant, specific uptake of the Cu-64- and Zr-89-trastuzumab bioconjugates in HER2-positive BT-474 xenografts, with little background uptake in HER2-negative MDA-M-408 xenografts or other tissues. This modular system-one in which the divergent point is a single covalently modified antibody stock that can be reacted selectively with various chelators-will allow for both greater versatility and more facile cross-comparisons in the development of antibody-based radiopharmaceuticals. C1 [Zeglis, Brian M.; Mohindra, Priya; Weissmann, Gabriel I.; Divilov, Vadim; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Zeglis, Brian M.; Mohindra, Priya; Weissmann, Gabriel I.; Divilov, Vadim; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10021 USA. [Hilderbrand, Scott A.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. RP Lewis, JS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. EM lewisj2@mskcc.org FU NIH [R24 CA83084, P30 CA08748, 1F32CA1440138-01, R01EB010011]; DOE [DE-SC0002184] FX The authors thank Dr. Jason P. Holland for insight and helpful conversations, Valerie Longo for aid with animal imaging experiments, Nicholas Ramos for aid in the purification of 85Zr, and Alexander Veach for technical assistance. Services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by NIH grants R24 CA83084 and P30 CA08748. The authors also thank the NIH (Award 1F32CA1440138-01, BMZ; Award R01EB010011, RW) and the DOE (Award DE-SC0002184, JSL) for their generous funding. NR 66 TC 65 Z9 65 U1 3 U2 50 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD OCT PY 2011 VL 22 IS 10 BP 2048 EP 2059 DI 10.1021/bc200288d PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 833WE UT WOS:000295915100020 PM 21877749 ER PT J AU Xu, P Alam, MM Kalsy, A Charles, RC Calderwood, SB Qadri, F Ryan, ET Kovac, P AF Xu, Peng Alam, Mohammad Murshid Kalsy, Anuj Charles, Richelle C. Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. Kovac, Pavol TI Simple, Direct Conjugation of Bacterial O-SP-Core Antigens to Proteins: Development of Cholera Conjugate Vaccines SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SQUARIC ACID DIESTER; VIBRIO-CHOLERAE; SEROTYPE INABA; DETOXIFIED LIPOPOLYSACCHARIDE; ANTIBODY-RESPONSE; DIETHYL SQUARATE; SIDE-CHAIN; POLYSACCHARIDE; INFECTION; CARRIER AB Bacterial O-SP core antigens can be conjugated to proteins in the same, simple way as synthetic, linker-equipped carbohydrates by applying squaric acid chemistry. Introduction of spacers (linkers) to either O-SP core antigens or protein carriers, which is involved in commonly applied protocols, is not required. The newly developed method described here consists of preparation of a squaric acid monoester derivative of O-SP core antigen, utilizing the amino group inherent in the core, and reaction of the monoester with the carrier protein. The intermediate monoester can be easily purified; its conjugation can be monitored by SELDI-TOF mass spectrometry and, thus, readily controlled, since the conjugation can be terminated when the desired carbohydrate protein ratio is reached. Here, we describe production of conjugates containing the O-SP core antigen of Vibrio cholerae 01, the major cause of cholera, a severe dehydrating diarrheal disease of humans. The resultant products are recognized by convalescent phase sera from patients recovering from cholera in Bangladesh, and anti-O-SP-core-protein responses correlate with plasma antilipopolysaccharide and vibriocidal responses, which are the primary markers of protection from cholera. The results suggest that such conjugates have potential as vaccines for cholera and other bacterial diseases. C1 [Alam, Mohammad Murshid; Kalsy, Anuj; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Alam, Mohammad Murshid; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org; kpn@helix.nih.gov RI Xu, Peng/K-7036-2012; Kovac, Pavol/B-8813-2008 OI Kovac, Pavol/0000-0001-5044-3449 FU NIH, NIDDK; International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (ICDDR, B); Fogarty International Center (FIC) [TW05572] FX This research was supported by the Intramural Research Program of the NIH, NIDDK, as well the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (ICDDR, B), and NIAID AI077883 (ETR), AI058935 (SBC, FQ), AI089721 (RCC), and the Fogarty International Center (FIC) TW05572 (MMA, FQ). NR 35 TC 18 Z9 18 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD OCT PY 2011 VL 22 IS 10 BP 2179 EP 2185 DI 10.1021/bc2001984 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 833WE UT WOS:000295915100034 PM 21899371 ER PT J AU Forrester, AM Grabher, C McBride, ER Boyd, ER Vigerstad, MH Edgar, A Kai, FB Da'as, SI Payne, E Look, AT Berman, JN AF Forrester, A. Michael Grabher, Clemens McBride, Eileen R. Boyd, Ellen R. Vigerstad, Marta H. Edgar, Alexander Kai, Fui-Boon Da'as, Sahar I. Payne, Elspeth Look, A. Thomas Berman, Jason N. TI NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE NUP98-HOXA9; acute myeloid leukaemia; myeloproliferative disease; zebrafish; apoptosis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSGENIC ZEBRAFISH; GENE-EXPRESSION; CELL FATE; STEM-CELLS; HOXA9; BCL-2; MODEL; DIFFERENTIATION; TRANSCRIPTION AB NUP98-HOXA9 [t(7;11) (p15;p15)] is associated with inferior prognosis in de novo and treatment-related acute myeloid leukaemia (AML) and contributes to blast crisis in chronic myeloid leukaemia (CML). We have engineered an inducible transgenic zebrafish harbouring human NUP98-HOXA9 under the zebrafish spi1(pu.1) promoter. NUP98-HOXA9 perturbed zebrafish embryonic haematopoiesis, with upregulated spi1expression at the expense of gata1a. Markers associated with more differentiated myeloid cells, lcp1, lyz, and mpx were also elevated, but to a lesser extent than spi1, suggesting differentiation of early myeloid progenitors may be impaired by NUP98-HOXA9. Following irradiation, NUP98-HOXA9-expressing embryos showed increased numbers of cells in G2-M transition compared to controls and absence of a normal apoptotic response, which may result from an upregulation of bcl2. These data suggest NUP98-HOXA9-induced oncogenesis may result from a combination of defects in haematopoiesis and an aberrant response to DNA damage. Importantly, 23% of adult NUP98-HOXA9-transgenic fish developed a myeloproliferative neoplasm (MPN) at 19-23 months of age. In summary, we have identified an embryonic haematopoietic phenotype in a transgenic zebrafish line that subsequently develops MPN. This tool provides a unique opportunity for high-throughput in vivo chemical modifier screens to identify novel therapeutic agents in high risk AML. C1 [Berman, Jason N.] IWK Hlth Ctr, Aquat Lab, Halifax, NS B3K 6R8, Canada. [Forrester, A. Michael; Boyd, Ellen R.; Vigerstad, Marta H.; Edgar, Alexander; Kai, Fui-Boon; Berman, Jason N.] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 3J5, Canada. [McBride, Eileen R.; Berman, Jason N.] Dalhousie Univ, Dept Pediat, Halifax, NS B3H 3J5, Canada. [Grabher, Clemens; Payne, Elspeth; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Grabher, Clemens] Karlsruhe Inst Technol, Inst Toxicol & Genet, Karlsruhe, Germany. RP Berman, JN (reprint author), IWK Hlth Ctr, Aquat Lab, 5850-5980 Univ Ave, Halifax, NS B3K 6R8, Canada. EM Jason.Berman@iwk.nshealth.ca RI Grabher, Clemens/H-2064-2013 FU Nova Scotia Health Research Foundation (NSHRF); Dalhousie Clinical Research Scholar Award; Canadian Institutes of Health Research (CIHR); Canadian Cancer Society; Beatrice Hunter Cancer Research Institute; IWK Summer Studentship FX We would like to thank DG Gilliland for the gift of human NUP98-HOXA9 cDNA and critical review of the manuscript. We thank D Traver for assistance with FACS protocols, CA Jette and S Carbonneau with embryonic apoptosis assays and RNA probes, and U Pyati with qRT-PCR primer design. We thank L Gillis, D Corkery, A Coombs, A Young, and J Jaques for technical and administrative support; C Isenor and M Melanson for histology; C McCormick and TJ Lin for use of equipment; and TB Balci, E Gjini, and LI Zon for critical review of the manuscript. This work was supported by a Nova Scotia Health Research Foundation (NSHRF) Operating Grant and Dalhousie Clinical Research Scholar Award (J.N.B.); Graduate Awards from the Canadian Institutes of Health Research (CIHR) and The Canadian Cancer Society, in conjunction with The Beatrice Hunter Cancer Research Institute (A.M.F.); IWK Summer Studentship (E.R.B.); and Norah Stephen Oncology Scholar (F.B.K.). NR 51 TC 29 Z9 30 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2011 VL 155 IS 2 BP 167 EP 181 DI 10.1111/j.1365-2141.2011.08810.x PG 15 WC Hematology SC Hematology GA 835VD UT WOS:000296063400003 PM 21810091 ER PT J AU Guo, DL Reinitz, F Youssef, M Hong, C Nathanson, D Akhavan, D Kuga, D Amzajerdi, AN Soto, H Zhu, SJ Babic, I Tanaka, K Dang, JL Iwanami, A Gini, B DeJesus, J Lisiero, DD Huang, TT Prins, RM Wen, PY Robins, HI Prados, MD DeAngelis, LM Mellinghoff, IK Mehta, MP James, CD Chakravarti, A Cloughesy, TF Tontonoz, P Mischel, PS AF Guo, Deliang Reinitz, Felicia Youssef, Mary Hong, Cynthia Nathanson, David Akhavan, David Kuga, Daisuke Amzajerdi, Ali Nael Soto, Horacio Zhu, Shaojun Babic, Ivan Tanaka, Kazuhiro Dang, Julie Iwanami, Akio Gini, Beatrice DeJesus, Jason Lisiero, Dominique D. Huang, Tiffany T. Prins, Robert M. Wen, Patrick Y. Robins, H. Ian Prados, Michael D. DeAngelis, Lisa M. Mellinghoff, Ingo K. Mehta, Minesh P. James, C. David Chakravarti, Arnab Cloughesy, Timothy F. Tontonoz, Peter Mischel, Paul S. TI An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR-Dependent Pathway SO CANCER DISCOVERY LA English DT Article ID GROWTH-FACTOR RECEPTOR; FATTY-ACID SYNTHASE; LDL RECEPTOR; LIPID RAFTS; PROSTATE-CANCER; KINASE INHIBITORS; SIGNALING PATHWAY; NUCLEAR RECEPTORS; PROTEIN-KINASE; IN-VIVO AB Glioblastoma (GBM) is the most common malignant primary brain tumor of adults and one of the most lethal of all cancers. Epidermal growth factor receptor (EGFR) mutations (EGFRvIII) and phosphoinositide 3-kinase (PI3K) hyperactivation are common in GBM, promoting tumor growth and survival, including through sterol regulatory element-binding protein 1 (SREBP-1)-dependent lipogenesis. The role of cholesterol metabolism in GBM pathogenesis, its association with EGFR/PI3K signaling, and its potential therapeutic targetability are unknown. In our investigation, studies of GBM cell lines, xenograft models, and GBM clinical samples, including those from patients treated with the EGFR tyrosine kinase inhibitor lapatinib, uncovered an EGFRvIII-activated, PI3K/SREBP-1-dependent tumor survival pathway through the low-density lipoprotein receptor (LDLR). Targeting LDLR with the liver X receptor (LXR) agonist GW3965 caused inducible degrader of LDLR (IDOL)-mediated LDLR degradation and increased expression of the ABCA1 cholesterol efflux transporter, potently promoting tumor cell death in an in vivo GBM model. These results show that EGFRvIII can promote tumor survival through PI3K/SREBP-1-dependent upregulation of LDLR and suggest a role for LXR agonists in the treatment of GBM patients. SIGNIFICANCE: This study reveals that GBM cells have devised a mechanism to subvert the normal pathways for feedback inhibition of cholesterol homeostasis via EGFRvIII and PI3K-dependent activation of SREBP-1. We show that an LXR agonist causes IDOL-mediated LDLR degradation and increases expression of the ABCA1 cholesterol efflux transporter, potently promoting GBM cell death in vivo. These results suggest a role for LXR agonists in the treatment of GBM patients. Cancer Discovery;1(5):442-56. (C) 2011 AACR. C1 [Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Guo, Deliang; Chakravarti, Arnab] Ohio State Univ, Sch Med, Dept Radiat Oncol, Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA. [Soto, Horacio; Lisiero, Dominique D.; Prins, Robert M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Prins, Robert M.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Henry Singleton Brain Tumor Program, Los Angeles, CA 90095 USA. [Prins, Robert M.; Cloughesy, Timothy F.; Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Hong, Cynthia; Tontonoz, Peter] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. [Prados, Michael D.; James, C. David] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Robins, H. Ian] Univ Wisconsin, Dept Med, Madison, WI USA. [DeAngelis, Lisa M.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mehta, Minesh P.] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. RP Mischel, PS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci, Dept Pathol & Lab Med, 10833 Le Conte Ave,Room 13-321, Los Angeles, CA 90095 USA. EM pmischel@mednet.ucla.edu RI James, Charles/E-2721-2012; Guo, Deliang/I-3735-2014; OI James, Charles/0000-0002-1027-203X; Guo, Deliang/0000-0002-8359-390X; Nael, Ali/0000-0002-9671-5531; Prins, Robert/0000-0002-6282-6583; mehta, minesh/0000-0002-4812-5713 FU Rose DiGangi American Brain Tumor Association; NIH [NS072838, CA119347]; California Institute of Regenerative Medicine [6054]; Accelerate Brain Cancer Cure; STOP Cancer; John W. Carson Foundation; The Lya and Harrison Latter endowed Chair; Ziering Family Foundation in memory of Sigi Ziering FX This work was supported by Rose DiGangi American Brain Tumor Association Translational Grant (D. Guo), NIH Grant NS072838 (D. Guo), NIH Grant CA119347 (P. S. Mischel), California Institute of Regenerative Medicine 6054 (P. S. Mischel), Accelerate Brain Cancer Cure (P. S. Mischel), STOP Cancer (P. S. Mischel), John W. Carson Foundation (P. S. Mischel), The Lya and Harrison Latter endowed Chair (P. S. Mischel), and the Ziering Family Foundation in memory of Sigi Ziering (T. F. Cloughesy and P. S. Mischel). NR 65 TC 90 Z9 97 U1 2 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD OCT PY 2011 VL 1 IS 5 BP 442 EP 456 DI 10.1158/2159-8290.CD-11-0102 PG 15 WC Oncology SC Oncology GA 836UX UT WOS:000296140600022 PM 22059152 ER PT J AU Schroen, AT Petroni, GR Wang, HK Thielen, MJ Sargent, D Benedetti, JK Cronin, WM Wickerham, DL Wang, XFF Gray, R Cohn, WF Slingluff, CL Djulbegovic, B AF Schroen, Anneke T. Petroni, Gina R. Wang, Hongkun Thielen, Monika J. Sargent, Daniel Benedetti, Jacqueline K. Cronin, Walter M. Wickerham, Donald L. Wang, Xiaofei F. Gray, Robert Cohn, Wendy F. Slingluff, Craig L., Jr. Djulbegovic, Benjamin TI Challenges to accrual predictions to phase III cancer clinical trials: a survey of study chairs and lead statisticians of 248 NCI-sponsored trials SO CLINICAL TRIALS LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; BARRIERS; PARTICIPATION; ENROLLMENT AB Background Research on barriers to accrual has typically emphasized factors influencing participation after trial activation. Purpose We sought to identify factors influencing trial design and accrual predictions prior to trial activation associated with sufficient accrual. Methods A 30-question web-based survey was sent to the study chair and lead statistician for all 248 phase III trials open in 1993-2002 by five Clinical Trials Cooperative Groups. Questions addressed prior trial experience, trial design elements, accrual predictions, and perceived accrual influences. Accrual sufficiency categorization was derived from Clinical Trials Cooperative Group records: sufficient accrual included trials closed with complete accrual or at interim analysis, insufficient accrual included trials closed with inadequate accrual. Responses were analyzed by respondent role (study chair/lead statistician) and accrual sufficiency. Results Three hundred and nine eligible responses were included (response rate, 63%; lead statisticians, 81%; and study chairs, 45%), representing trials with sufficient (63%) and insufficient accruals (37%). Study chair seniority or lead statistician experience was not linked to accrual sufficiency. Literature review, study chair's personal experience, and expert opinion within Clinical Trials Cooperative Group most commonly influenced control arm selection. Clinical Trials Cooperative Group experience most influenced accrual predictions. These influences were not associated with accrual sufficiency. Among respondents citing accrual difficulties (41%), factors negatively influencing accrual were not consistently identified. Respondents credited three factors with positively influencing accrual: clinical relevance of study, lack of competing trials, and protocol paralleling normal practice. Limitations Perceptions of lead statisticians and study chairs may not accurately reflect accrual barriers encountered by participating physicians or patients. Survey responses may be subject to recall bias. Conclusion Consistent factors explaining poor accrual were not identified, suggesting reasons for poor accrual are not well understood and warrant further study. Alternate strategies for accrual prediction are needed since Clinical Trials Cooperative Group experience is linked to successful and unsuccessful accrual. Clinical Trials 2011; 8: 591-600. http://ctj.sagepub.com C1 [Schroen, Anneke T.; Thielen, Monika J.; Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Charlottesville, VA 22908 USA. [Petroni, Gina R.; Wang, Hongkun; Cohn, Wendy F.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Sargent, Daniel] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Benedetti, Jacqueline K.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Cronin, Walter M.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Wickerham, Donald L.] Natl Surg Breast & Bowel Project NSABP, Pittsburgh, PA USA. [Wang, Xiaofei F.] Duke Univ, Dept Biostatist, Durham, NC USA. [Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Djulbegovic, Benjamin] Univ S Florida, Dept Med, CTSI, Ctr EBM, Tampa, FL USA. RP Schroen, AT (reprint author), Univ Virginia, Dept Surg, POB 800709, Charlottesville, VA 22908 USA. EM ats2x@virginia.edu RI Djulbegovic, Benjamin/I-3661-2012; OI Djulbegovic, Benjamin/0000-0003-0671-1447; Sargent, Daniel/0000-0002-2684-4741 FU National Institutes of Health [R01 CA118232]; NCI, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, U24-CA-114732] FX This study was supported by National Institutes of Health [R01 CA118232] and NCI, Department of Health and Human Services [U10CA-12027, U10CA-69974, U10CA-37377, U10CA-69651, and U24-CA-114732]. NR 17 TC 8 Z9 8 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 591 EP 600 DI 10.1177/1740774511419683 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500005 PM 21878447 ER PT J AU Grant, RW James, BM Florez, JC Park, ER Green, RC Waxler, JL Delahanty, LM O'Brien, KE AF Grant, Richard W. Meigs, James B. Florez, Jose C. Park, Elyse R. Green, Robert C. Waxler, Jessica L. Delahanty, Linda M. O'Brien, Kelsey E. TI Design of a randomized trial of diabetes genetic risk testing to motivate behavior change: The Genetic Counseling/Lifestyle Change (GC/LC) Study for Diabetes Prevention SO CLINICAL TRIALS LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; METABOLIC SYNDROME; GENOMIC MEDICINE; WEIGHT-LOSS; LIFE-STYLE; HEALTH; DISEASE; INTERVENTION; INFORMATION; COMMUNITY AB Background The efficacy of diabetes genetic risk testing to motivate behavior change for diabetes prevention is currently unknown. Purpose This paper presents key issues in the design and implementation of one of the first randomized trials (The Genetic Counseling/Lifestyle Change (GC/LC) Study for Diabetes Prevention) to test whether knowledge of diabetes genetic risk can motivate patients to adopt healthier behaviors. Methods Because individuals may react differently to receiving 'higher' vs 'lower' genetic risk results, we designed a 3-arm parallel group study to separately test the hypotheses that: (1) patients receiving 'higher' diabetes genetic risk results will increase healthy behaviors compared to untested controls, and (2) patients receiving 'lower' diabetes genetic risk results will decrease healthy behaviors compared to untested controls. In this paper we describe several challenges to implementing this study, including: (1) the application of a novel diabetes risk score derived from genetic epidemiology studies to a clinical population, (2) the use of the principle of Mendelian randomization to efficiently exclude 'average' diabetes genetic risk patients from the intervention, and (3) the development of a diabetes genetic risk counseling intervention that maintained the ethical need to motivate behavior change in both 'higher' and 'lower' diabetes genetic risk result recipients. Results Diabetes genetic risk scores were developed by aggregating the results of 36 diabetes-associated single nucleotide polymorphisms. Relative risk for type 2 diabetes was calculated using Framingham Offspring Study outcomes, grouped by quartiles into 'higher', 'average' (middle two quartiles) and 'lower' genetic risk. From these relative risks, revised absolute risks were estimated using the overall absolute risk for the study group. For study efficiency, we excluded all patients receiving 'average' diabetes risk results from the subsequent intervention. This post-randomization allocation strategy was justified because genotype represents a random allocation of parental alleles ('Mendelian randomization'). Finally, because it would be unethical to discourage participants to participate in diabetes prevention behaviors, we designed our two diabetes genetic risk counseling interventions (for 'higher' and 'lower' result recipients) so that both groups would be motivated despite receiving opposing results. Limitations For this initial assessment of the clinical implementation of genetic risk testing we assessed intermediate outcomes of attendance at a 12-week diabetes prevention course and changes in self-reported motivation. If effective, longer term studies with larger sample sizes will be needed to assess whether knowledge of diabetes genetic risk can help patients prevent diabetes. Conclusions We designed a randomized clinical trial designed to explore the motivational impact of disclosing both higher than average and lower than average genetic risk for type 2 diabetes. This design allowed exploration of both increased risk and false reassurance, and has implications for future studies in translational genomics. Clinical Trials 2011; 8: 609-615. http://ctj.sagepub.com C1 [Grant, Richard W.; Meigs, James B.; O'Brien, Kelsey E.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grant, Richard W.; Meigs, James B.; Park, Elyse R.; Waxler, Jessica L.; Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Green, Robert C.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Waxler, Jessica L.] Partners Ctr Human Genet, Boston, MA USA. RP Grant, RW (reprint author), Kaiser Permanente, Div Res, 2101 Webster St, Oakland, CA 94612 USA. EM Rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK [R21 DK84527-01, K24 DK080140] FX This study was funded by NIDDK R21 DK84527-01. Dr Meigs received support from NIDDK K24 DK080140. ClinicalTrials. gov identifier: NCT01034319. NR 41 TC 11 Z9 11 U1 0 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 609 EP 615 DI 10.1177/1740774511414159 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500007 PM 22013171 ER PT J AU Truong, TH Weeks, JC Cook, EF Joffe, S AF Truong, Tony H. Weeks, Jane C. Cook, E. Francis Joffe, Steven TI Altruism among participants in cancer clinical trials SO CLINICAL TRIALS LA English DT Article ID PHASE-I; INFORMED-CONSENT; THERAPEUTIC MISCONCEPTION; PATIENT; RISKS; PERCEPTIONS; BENEFITS; CHILDREN; PHYSICIANS; DISCOURSE AB Background Patients' motivations for participation in cancer clinical trials are incompletely understood. Even less is known about the factors that influence participants' motivations for enrolling in trials. Purpose We studied the reasons why adult patients and parents of pediatric patients agree to participate in cancer trials. We focused on the role of altruism across all phases of trial. Methods We surveyed adult patients and parents of pediatric patients participating in phase I, II, or III cancer clinical trials. We asked respondents why they agreed to enroll, and examined correlates of altruistic motivation using univariate and multivariate analyses. Results Among 205 adults and 48 parents of children participating in cancer trials, 47% reported that altruistic motivations were 'very important' to their decisions to enroll. In multivariate analysis with phase III trial participants as the reference group, phase I trial participants least often identified altruism as a 'very important' motivation for enrolling (phase I OR 0.4, 95% CI (confidence interval) 0.2-0.8; phase II OR 0.9, 95% CI 0.5-1.5, overall P = 0.017). Thirty-three respondents (13%) reported being motivated primarily by altruism. In multivariate analysis, participants with poor prognoses-defined as an expected 5-year disease-free survival of <= 10%-reported altruism as their primary motivation less often than those with better prognoses (OR 0.2, 95% CI 0.1-0.5, P = 0.001). Altruistic motivations did not differ between adult patients and parents of pediatric participants. Limitations The data are derived from related academic medical centers in one city, and the study sample reflects limited sociodemographic diversity, thereby limiting generalizability to other settings. Conclusions Although cancer trial participants commonly report that altruism contributed to their decision to enroll, it is rarely their primary motivation for study participation. Participants in early phase trials and those with poor prognoses are least often motivated by altruism. Clinical Trials 2011; 8: 616-623. http://ctj.sagepub.com C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Truong, Tony H.] Univ Toronto, Hosp Sick Children, Div Haematol Oncol, Dept Paediat, Toronto, ON, Canada. [Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 28 TC 22 Z9 23 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 616 EP 623 DI 10.1177/1740774511414444 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500008 PM 21813584 ER PT J AU Kernan, W Viscoli, C Brass, L Amatangelo, M Birch, A Clark, W Conwit, R Furie, K Gorman, M Pesapane, B Kleindorfer, D Lovejoy, A Osborne, J Silliman, S Zweifler, R Horwitz, R AF Kernan, W. Viscoli, C. Brass, L. Amatangelo, M. Birch, A. Clark, W. Conwit, R. Furie, K. Gorman, M. Pesapane, B. Kleindorfer, D. Lovejoy, A. Osborne, J. Silliman, S. Zweifler, R. Horwitz, R. TI Boosting enrolment in clinical trials: validation of a regional network model SO CLINICAL TRIALS LA English DT Article ID STROKE; RECRUITMENT; SYSTEM AB Background Clinical trials of stroke therapy have been hampered by slow rates of enrolment. Purpose Our purpose is to validate a previously developed model for accelerating enrolment in clinical trials by replicating it at new locations. The model employs coordinators who travel from a host institution to enrol participants from a network of participating hospitals. Active surveillance assures identification of all eligible patients. Methods Among 70 U. S. investigators participating in National Institutes of Health-funded trial of stroke prevention, five investigators were invited to develop local identification and outreach networks (LIONs). Each LION comprised a LION coordinating centre servicing multiple hospitals. Hospitals provided names of patients with stroke or transient ischaemic attack to researchers at the LION coordinating centre who initiated contact; patients were offered home visits for consent and randomization. Outcomes were feasibility, enrolment, data quality, and cost. Results Five LIONs varied in size from two to eight hospitals. All 24 hospitals we approached agreed to participate. The average monthly rate of enrolment at the research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean change = 2.1, range 0.9-3.7). Monthly performance improved over time. Data quality was similar for LIONs and non-LION sites, except for drug adherence which was lower at LIONs. The average cost to randomize and follow one participant during the study interval was 2.4 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. Limitations The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. Conclusion LIONs are a practical, reproducible method to increase enrolment in trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LIONs was higher than conventional sites but declined over time. Clinical Trials 2011; 8: 645-653. http://ctj.sagepub.com C1 [Kernan, W.] IRIS Coordinating Ctr, New Haven, CT USA. [Viscoli, C.; Brass, L.; Pesapane, B.; Lovejoy, A.] Yale Univ, Sch Med, New Haven, CT USA. [Amatangelo, M.; Birch, A.; Furie, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, W.] Oregon Hlth & Sci Univ, Portland, OR USA. [Conwit, R.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Gorman, M.] Univ Vermont, Burlington, VT USA. [Kleindorfer, D.; Osborne, J.] Univ Cinncinati, Cinncinati, OH USA. [Silliman, S.] Univ Florida, Coll Medicine Jacksonville, Jacksonville, FL USA. [Zweifler, R.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Horwitz, R.] Glaxo Smithkline, Philadelphia, PA USA. RP Kernan, W (reprint author), IRIS Coordinating Ctr, Suite 515 2 Church St S, New Haven, CT USA. EM walter.kernan@yale.edu RI Zweifler, Richard/K-1314-2015 FU National Institutes of Neurological Disorders and Stroke (NINDS) [U01 NS044876] FX This work was supported by the National Institutes of Neurological Disorders and Stroke (NINDS) (U01 NS044876). Placebo and pioglitazone tablets were supplied by Takeda Pharmaceuticals North America, Inc. NR 14 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2011 VL 8 IS 5 BP 645 EP 653 DI 10.1177/1740774511414925 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500011 PM 21824978 ER PT J AU Piette, EW Werth, VP AF Piette, Evan W. Werth, Victoria P. TI Dapsone in the Management of Autoimmune Bullous Diseases SO DERMATOLOGIC CLINICS LA English DT Article DE Dapsone; Autoimmune bullous disease; Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DERMATITIS-HERPETIFORMIS; ACQUISITA; PEMPHIGUS; DIAGNOSIS; ERUPTION; COLCHICINE; DERMATOSIS; THERAPY; WOMAN AB Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD. C1 [Piette, Evan W.; Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [NIH K24-AR 02207] FX National Institutes of Health, including NIH K24-AR 02207 (V.P.W.). NR 41 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2011 VL 29 IS 4 BP 561 EP + DI 10.1016/j.det.2011.06.018 PG 5 WC Dermatology SC Dermatology GA 831UB UT WOS:000295755500005 PM 21924998 ER PT J AU Murrell, DF Werth, VP Segall, J Zrnchik, W Stuart, M Sirois, D AF Murrell, Dedee F. Werth, Victoria P. Segall, Janet Zrnchik, Will Stuart, Molly Sirois, David TI The International Pemphigus and Pemphigoid Foundation SO DERMATOLOGIC CLINICS LA English DT Article DE International Pemphigus Pemphigoid Foundation; Pemphigus; Pemphigoid; Pemphigus vulgaris AB The International Pemphigus Pemphigoid Foundation (IPFF) was founded in 1997. The IPPF lists more than 4500 members. The IPPF provides peer health coaches to aid patients in the navigation of the health care system and recommends dermatologists and other specialists in their area who are experts in autoimmune bullous disease. The IPPF hosts the largest worldwide registry of pemphigus/pemphigoid patients with biospecimen collection opportunities are planned. Twice a year the IPPF hosts formal meetings with invited speakers. C1 [Segall, Janet; Zrnchik, Will; Stuart, Molly; Sirois, David] Int Pemphigus Pemphigoid Fdn, Sacramento, CA 95825 USA. [Sirois, David] NYU, Dept Dent, New York, NY 10022 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Div Dermatol, Philadelphia, PA USA. [Werth, Victoria P.] Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Murrell, Dedee F.] Univ New S Wales, St George Hosp, Dept Dermatol, Sydney, NSW 2217, Australia. RP Sirois, D (reprint author), Int Pemphigus Pemphigoid Fdn, 2701 Cottage Way 16, Sacramento, CA 95825 USA. EM david.sirois@nyu.edu FU NIAMS NIH HHS [K24 AR002207] NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2011 VL 29 IS 4 BP 655 EP + DI 10.1016/j.det.2011.06.019 PG 5 WC Dermatology SC Dermatology GA 831UB UT WOS:000295755500020 PM 21925013 ER PT J AU Amati, F Dube, JJ Alvarez-Carnero, E Edreira, MM Chomentowski, P Coen, PM Switzer, GE Bickel, PE Stefanovic-Racic, M Toledo, FGS Goodpaster, BH AF Amati, Francesca Dube, John J. Alvarez-Carnero, Elvis Edreira, Martin M. Chomentowski, Peter Coen, Paul M. Switzer, Galen E. Bickel, Perry E. Stefanovic-Racic, Maja Toledo, Frederico G. S. Goodpaster, Bret H. TI Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance Another Paradox in Endurance-Trained Athletes? SO DIABETES LA English DT Article ID INTRAMUSCULAR LIPID-METABOLISM; STEAROYL-COA DESATURASE-1; SPHINGOLIPID METABOLISM; OBESE HUMANS; WEIGHT-LOSS; EXERCISE; PROTEIN; DIET; SPHINGOSINE-1-PHOSPHATE; SENSITIVITY AB OBJECTIVE-Chronic exercise and obesity both increase intra-myocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS-A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS-DAG content in the NWA group was approximately twofold higher than in the OBS group and similar to 50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, DAGs, and insulin sensitivity. CONCLUSIONS-Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. Diabetes 60:2588-2597, 2011 C1 [Amati, Francesca; Dube, John J.; Alvarez-Carnero, Elvis; Chomentowski, Peter; Coen, Paul M.; Stefanovic-Racic, Maja; Toledo, Frederico G. S.; Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. [Amati, Francesca] Univ Lausanne, Dept Physiol, Sch Biol & Med, Lausanne, Switzerland. [Edreira, Martin M.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Bickel, Perry E.] Univ Texas Hlth Sci Ctr Houston, Ctr Metab & Degenerat Dis, Brown Fdn Inst Mol Med, Houston, TX USA. [Bickel, Perry E.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Endocrinol Diabet & Metab, Houston, TX USA. RP Goodpaster, BH (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA. EM bgood@pitt.edu RI Toledo, Frederico/G-9071-2013; Carnero, Elvis/A-5815-2014; OI Carnero, Elvis/0000-0003-0442-4217; Alvarez Carnero, Elvis/0000-0002-7464-228X; Amati, Francesca/0000-0002-1731-0262; Coen, Paul/0000-0002-2805-2115 FU National Institutes of Health (NIH) [R01-AG20128, R01-DK068046]; American College of Sports Medicine Foundation; University of Pittsburgh; NIH/National Center for Research Resources/Clinical and Translational Science [UL1 RR024153]; University of Pittsburgh Obesity and Nutrition Research Center [1P30DK46204] FX This study was supported by National Institutes of Health (NIH) Grants (R01-AG20128 to B.H.G. and R01-DK068046 to P.E.B.), funding from the American College of Sports Medicine Foundation (to F.A.), University of Pittsburgh Student and Faculty Grants (to B.H.G. and F.A.), an NIH/National Center for Research Resources/Clinical and Translational Science Award (UL1 RR024153), and University of Pittsburgh Obesity and Nutrition Research Center Grant 1P30DK46204. NR 53 TC 143 Z9 148 U1 4 U2 38 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2588 EP 2597 DI 10.2337/db10-1221 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700018 PM 21873552 ER PT J AU Strawbridge, RJ Dupuis, J Prokopenko, I Barker, A Ahlqvist, E Rybin, D Petrie, JR Travers, ME Bouatia-Naji, N Dimas, AS Nica, A Wheeler, E Chen, H Voight, BF Taneera, J Kanoni, S Peden, JF Turrini, F Gustafsson, S Zabena, C Almgren, P Barker, DJP Barnes, D Dennison, EM Eriksson, JG Eriksson, P Eury, E Folkersen, L Fox, CS Frayling, TM Goel, A Gu, HF Horikoshi, M Isomaa, B Jackson, AU Jameson, KA Kajantie, E Kerr-Conte, J Kuulasmaa, T Kuusisto, J Loos, RJF Luan, JA Makrilakis, K Manning, AK Martinez-Larrad, MT Narisu, N Mannila, MN Ohrvik, J Osmond, C Pascoe, L Payne, F Sayer, AA Sennblad, B Silveira, A Stancakova, A Stirrups, K Swift, AJ Syvanen, AC Tuomi, T van 't Hooft, FM Walker, M Weedon, MN Xie, WJ Zethelius, B Ongen, H Malarstig, A Hopewell, JC Saleheen, D Chambers, J Parish, S Danesh, J Kooner, J Ostenson, CG Lind, L Cooper, CC Serrano-Rios, M Ferrannini, E Forsen, TJ Clarke, R Franzosi, MG Seedorf, U Watkins, H Froguel, P Johnson, P Deloukas, P Collins, FS Laakso, M Dermitzakis, ET Boehnke, M McCarthy, MI Wareham, NJ Groop, L Pattou, F Gloyn, AL Dedoussis, GV Lyssenko, V Meigs, JB Barroso, I Watanabe, RM Ingelsson, E Langenberg, C Hamsten, A Florez, JC AF Strawbridge, Rona J. Dupuis, Josee Prokopenko, Inga Barker, Adam Ahlqvist, Emma Rybin, Denis Petrie, John R. Travers, Mary E. Bouatia-Naji, Nabila Dimas, Antigone S. Nica, Alexandra Wheeler, Eleanor Chen, Han Voight, Benjamin F. Taneera, Jalal Kanoni, Stavroula Peden, John F. Turrini, Fabiola Gustafsson, Stefan Zabena, Carina Almgren, Peter Barker, David J. P. Barnes, Daniel Dennison, Elaine M. Eriksson, Johan G. Eriksson, Per Eury, Elodie Folkersen, Lasse Fox, Caroline S. Frayling, Timothy M. Goel, Anuj Gu, Harvest F. Horikoshi, Momoko Isomaa, Bo Jackson, Anne U. Jameson, Karen A. Kajantie, Eero Kerr-Conte, Julie Kuulasmaa, Teemu Kuusisto, Johanna Loos, Ruth J. F. Luan, Jian'an Makrilakis, Konstantinos Manning, Alisa K. Teresa Martinez-Larrad, Maria Narisu, Narisu Mannila, Maria Nastase Ohrvik, John Osmond, Clive Pascoe, Laura Payne, Felicity Sayer, Avan A. Sennblad, Bengt Silveira, Angela Stancakova, Alena Stirrups, Kathy Swift, Amy J. Syvanen, Ann-Christine Tuomi, Tiinamaija van 't Hooft, Ferdinand M. Walker, Mark Weedon, Michael N. Xie, Weijia Zethelius, Bjorn Ongen, Halit Malarstig, Anders Hopewell, Jemma C. Saleheen, Danish Chambers, John Parish, Sarah Danesh, John Kooner, Jaspal Ostenson, Claes-Goran Lind, Lars Cooper, Cyrus C. Serrano-Rios, Manuel Ferrannini, Ele Forsen, Tom J. Clarke, Robert Franzosi, Maria Grazia Seedorf, Udo Watkins, Hugh Froguel, Philippe Johnson, Paul Deloukas, Panos Collins, Francis S. Laakso, Markku Dermitzakis, Emmanouil T. Boehnke, Michael McCarthy, Mark I. Wareham, Nicholas J. Groop, Leif Pattou, Francois Gloyn, Anna L. Dedoussis, George V. Lyssenko, Valeriya Meigs, James B. Barroso, Ines Watanabe, Richard M. Ingelsson, Erik Langenberg, Claudia Hamsten, Anders Florez, Jose C. CA DIAGRAM Consortium GIANT Consortium MuTHER Consortium CARDIoGRAM Consortium C4D Consortium TI Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes SO DIABETES LA English DT Article ID CORONARY HEART-DISEASE; BETA-CELL FUNCTION; SUSCEPTIBILITY LOCI; GLUCOSE-HOMEOSTASIS; INSULIN SENSITIVITY; POPULATION; TCF7L2; RISK; OBESITY; METAANALYSIS AB OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS-We have conducted a meta-analysis of genome-wide association tests of similar to 2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS-Nine SNPs at eight loci were associated with proinsulin levels (P < 5 x 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC3OA8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 x 10(-4)), improved beta-cell function (P = 1.1 x 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 x 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS-We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis. Diabetes 60:2624-2634, 2011 C1 [Voight, Benjamin F.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Strawbridge, Rona J.; Eriksson, Per; Mannila, Maria Nastase; Ohrvik, John; Sennblad, Bengt; Silveira, Angela; van 't Hooft, Ferdinand M.; Malarstig, Anders; Hamsten, Anders] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Dupuis, Josee; Chen, Han; Manning, Alisa K.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Prokopenko, Inga; Travers, Mary E.; Horikoshi, Momoko; Johnson, Paul; McCarthy, Mark I.; Gloyn, Anna L.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Prokopenko, Inga; Dimas, Antigone S.; Peden, John F.; Goel, Anuj; Horikoshi, Momoko; Ongen, Halit; Watkins, Hugh; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Barker, Adam; Barnes, Daniel; Loos, Ruth J. F.; Luan, Jian'an; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Ahlqvist, Emma; Taneera, Jalal; Turrini, Fabiola; Almgren, Peter; Groop, Leif; Lyssenko, Valeriya] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Univ Hosp & Malmo, Malmo, Sweden. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Petrie, John R.] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Bouatia-Naji, Nabila; Eury, Elodie; Kerr-Conte, Julie; Froguel, Philippe; Pattou, Francois] Univ Lille Nord France, Lille, France. [Bouatia-Naji, Nabila; Eury, Elodie; Froguel, Philippe] Inst Pasteur, CNRS UMR 8199, Lille, France. [Dimas, Antigone S.; Nica, Alexandra; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Wheeler, Eleanor; Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, England. [Voight, Benjamin F.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Kanoni, Stavroula; Dedoussis, George V.] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Peden, John F.; Goel, Anuj; Ongen, Halit; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Turrini, Fabiola] Univ Verona, Dept Med, I-37100 Verona, Italy. [Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Zabena, Carina; Teresa Martinez-Larrad, Maria; Serrano-Rios, Manuel] CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid, Spain. [Zabena, Carina; Teresa Martinez-Larrad, Maria; Serrano-Rios, Manuel] Hosp Clin San Carlos, Fdn Invest Biomed, Madrid, Spain. [Barker, David J. P.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. [Dennison, Elaine M.; Jameson, Karen A.; Osmond, Clive; Sayer, Avan A.; Cooper, Cyrus C.] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Eriksson, Johan G.; Kajantie, Eero] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.] Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.; Forsen, Tom J.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Folkersen, Lasse] Karolinska Inst, Dept Med Solna, Expt Cardiovasc Res Unit, Stockholm, Sweden. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Frayling, Timothy M.; Weedon, Michael N.; Xie, Weijia] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Gu, Harvest F.; Ostenson, Claes-Goran] Karolinska Inst, Endocrinol & Diabet Unit, Dept Mol Med & Surg, Stockholm, Sweden. [Isomaa, Bo] Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland. [Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kajantie, Eero] Helsinki Univ Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Kerr-Conte, Julie; Pattou, Francois] INSERM, UMR 859, F-59045 Lille, France. [Kuulasmaa, Teemu; Kuusisto, Johanna; Stancakova, Alena; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuulasmaa, Teemu; Kuusisto, Johanna; Stancakova, Alena; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Makrilakis, Konstantinos] Univ Athens, Sch Med, Laiko Gen Hosp, Dept Propaedeut Med 1, GR-11527 Athens, Greece. [Narisu, Narisu; Swift, Amy J.] Natl Human Genome Res Inst, NIH, Bethesda, MD USA. [Pascoe, Laura] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Syvanen, Ann-Christine; Lind, Lars] Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Tuomi, Tiinamaija] Helsinki Univ Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Zethelius, Bjorn] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Ongen, Halit] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Chambers, John; Kooner, Jaspal] Ealing Hosp NHS Trust, Middlesex, England. [Ferrannini, Ele] Univ Pisa, Sch Med, Dept Internal Med, I-56100 Pisa, Italy. [Ferrannini, Ele] Univ Pisa, Sch Med, CNR Inst Clin Physiol, I-56100 Pisa, Italy. [Forsen, Tom J.] Vaasa Hlth Care Ctr, Vaasa, Finland. [Franzosi, Maria Grazia] Mario Negri Inst Pharmacol Res, Dept Cardiovasc Res, Milan, Italy. [Seedorf, Udo] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Hammersmith Hosp, Dept Genom Common Dis, London, England. [Johnson, Paul] Univ Oxford, DRWF Human Islet Isolat Facil, Oxford, England. [Johnson, Paul] Univ Oxford, Oxford Islet Transplant Programme, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. RP Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. EM claudia.langenberg@mrc-epid.cam.ac.uk; anders.hamsten@ki.se; jcflorez@partners.org RI Tang, Wai Hong/I-1238-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Kiemeney, Lambertus/D-3357-2009; Stark, Klaus/D-3813-2009; Aihie Sayer, Avan/A-4359-2012; Willenborg, Christina/D-2668-2012; Ridderstrale, Martin/F-7678-2012; Elliott, Amanda/G-5120-2012; Rudan, Igor/I-1467-2012; Barker, David/A-5671-2013; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; Zondervan, Krina/M-1143-2013; Cooper, Matthew/J-4420-2014; Strawbridge, Rona/H-5422-2012; Palmer, Lyle/K-3196-2014; Witte, Daniel/C-1722-2008; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Aben, Katja/G-9686-2016; Smith, Albert Vernon/K-5150-2015; Erdmann, Jeanette/P-7513-2014; Aulchenko, Yurii/M-8270-2013; Visvikis-Siest, Sophie/H-2324-2014; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Schwarz, Peter/B-5127-2013; Leander, Karin/C-7261-2017; Feitosa, Mary/K-8044-2012; OI Kaprio, Jaakko/0000-0002-3716-2455; Lawlor, Debbie A/0000-0002-6793-2262; Payne, Felicity/0000-0003-4228-581X; Pankow, James/0000-0001-7076-483X; de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; Dehghan, Abbas/0000-0001-6403-016X; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Kiemeney, Lambertus/0000-0002-2368-1326; Stark, Klaus/0000-0002-7832-1942; Willenborg, Christina/0000-0001-5217-6882; Rudan, Igor/0000-0001-6993-6884; Deloukas, Panos/0000-0001-9251-070X; Coin, Lachlan/0000-0002-4300-455X; Chen, Han/0000-0002-9510-4923; Nothen, Markus/0000-0002-8770-2464; Tuomi, Tiinamaija/0000-0002-8306-6202; Karpe, Fredrik/0000-0002-2751-1770; Yang, Jian/0000-0003-2001-2474; Jorgensen, Torben/0000-0001-9453-2830; Small, Kerrin/0000-0003-4566-0005; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Jones, Gregory T/0000-0002-6950-4210; Ouwehand, Willem/0000-0002-7744-1790; Zondervan, Krina/0000-0002-0275-9905; Cooper, Matthew/0000-0003-1139-3682; Strawbridge, Rona/0000-0001-8506-3585; Palmer, Lyle/0000-0002-1628-3055; Witte, Daniel/0000-0002-0769-2922; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862; Prokopenko, Inga/0000-0003-1624-7457; Aben, Katja/0000-0002-0214-2147; Folkersen, Lasse/0000-0003-0708-9530; Gieger, Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614; Ziegler, Andreas/0000-0002-8386-5397; Hide, Winston/0000-0002-8621-3271; Scherag, Andre/0000-0002-9406-4704; Rivadeneira, Fernando/0000-0001-9435-9441; Palmer, Colin/0000-0002-6415-6560; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Aihie Sayer, Avan/0000-0003-1283-6457; Esko, Tonu/0000-0003-1982-6569; Smith, Albert Vernon/0000-0003-1942-5845; Stewart, Alexandre/0000-0003-2673-9164; Manunta, Paolo/0000-0003-3976-9696; Zeggini, Eleftheria/0000-0003-4238-659X; Erdmann, Jeanette/0000-0002-4486-6231; Dupuis, Josee/0000-0003-2871-3603; Peyvandi, Flora/0000-0001-7423-9864; Luben, Robert/0000-0002-5088-6343; van Dam, Rob/0000-0002-7354-8734; Sijbrands, Eric/0000-0001-8857-7389; Goddard, Michael/0000-0001-9917-7946; Griffin, Simon/0000-0002-2157-4797; Marre, Michel/0000-0002-3071-1837; Barnes, Daniel/0000-0002-3781-7570; Johnson, Toby/0000-0002-5998-3270; Cappuccio, Francesco Paolo/0000-0002-7842-5493; Macciardi, Fabio/0000-0003-0537-4266; Lango Allen, Hana/0000-0002-7803-8688; Bouatia-Naji, Nabila/0000-0001-5424-2134; Magi, Reedik/0000-0002-2964-6011; Zgaga, Lina/0000-0003-4089-9703; Rybin, Denis/0000-0002-3657-4829; Willer, Cristen/0000-0001-5645-4966; Meisinger, Christa/0000-0002-9026-6544; Beckmann, Jacques S /0000-0002-9741-1900; Pichler, Irene/0000-0001-8251-0757; ELOSUA, ROBERTO/0000-0001-8235-0095; Aulchenko, Yurii/0000-0002-7899-1575; Visvikis-Siest, Sophie/0000-0001-8104-8425; Hayward, Caroline/0000-0002-9405-9550; Schwarz, Peter/0000-0001-6317-7880; Leander, Karin/0000-0002-1404-9222; Feitosa, Mary/0000-0002-0933-2410; Seedorf, Udo/0000-0003-4652-5358; Thiering, Elisabeth/0000-0002-5429-9584; Kaakinen, Marika/0000-0002-9228-0462 FU British Heart Foundation [RG/08/014/24067]; Diabetes UK [08/0003775]; Medical Research Council [81696, G0601261, G0601966, G0700222, G0700222(81696), G0700931, G0801056, MC_PC_U127561128, MC_PC_U127592696, MC_U106188470, MC_U127561128, MC_U137686857, MC_UP_A620_1014, MC_UP_A620_1015]; NHLBI NIH HHS [R01 HL087647, U01 HL054527]; NIDDK NIH HHS [DK062370, K24 DK080140, R01 DK078616]; Wellcome Trust [077016/Z/05/Z, 083270/Z/07/Z, 090532] NR 47 TC 128 Z9 134 U1 2 U2 49 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2011 VL 60 IS 10 BP 2624 EP 2634 DI 10.2337/db11-0415 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 834XV UT WOS:000295998700022 PM 21873549 ER PT J AU Park, BJ Pappas, PG Wannemuehler, KA Alexander, BD Anaissie, EJ Andes, DR Baddley, JW Brown, JM Brumble, LM Freifeld, AG Hadley, S Herwaldt, L Ito, JI Kauffman, CA Lyon, GM Marr, KA Morrison, VA Papanicolaou, G Patterson, TF Perl, TM Schuster, MG Walker, R Wingard, JR Walsh, TJ Kontoyiannis, DP AF Park, Benjamin J. Pappas, Peter G. Wannemuehler, Kathleen A. Alexander, Barbara D. Anaissie, Elias J. Andes, David R. Baddley, John W. Brown, Janice M. Brumble, Lisa M. Freifeld, Alison G. Hadley, Susan Herwaldt, Loreen Ito, James I. Kauffman, Carol A. Lyon, G. Marshall Marr, Kieren A. Morrison, Vicki A. Papanicolaou, Genovefa Patterson, Thomas F. Perl, Trish M. Schuster, Mindy G. Walker, Randall Wingard, John R. Walsh, Thomas J. Kontoyiannis, Dimitrios P. TI Invasive Non-Aspergillus Mold Infections in Transplant Recipients, United States, 2001-2006 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMATOPOIETIC STEM-CELL; CARE CANCER CENTER; SURVEILLANCE NETWORK TRANSNET; FUNGAL-INFECTIONS; HEMATOLOGIC MALIGNANCIES; BREAKTHROUGH ZYGOMYCOSIS; SCEDOSPORIUM-PROLIFICANS; RECEIVING VORICONAZOLE; ANTIFUNGAL THERAPY; EPIDEMIOLOGY AB Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001-2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HOT recipients increased substantially during the surveillance period. C1 [Park, Benjamin J.] Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Anaissie, Elias J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Andes, David R.] Univ Wisconsin, Madison, WI USA. [Brown, Janice M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Brumble, Lisa M.] Mayo Clin, Jacksonville, FL 32224 USA. [Freifeld, Alison G.] Univ Nebraska Med Ctr, Omaha, NE USA. [Hadley, Susan] Tufts Med Ctr, Boston, MA USA. [Herwaldt, Loreen] Univ Iowa Hosp, Iowa City, IA USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst Med, Ann Arbor, MI USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA USA. [Marr, Kieren A.; Perl, Trish M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Marr, Kieren A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Morrison, Vicki A.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Papanicolaou, Genovefa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Schuster, Mindy G.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Walker, Randall] Mayo Clin, Rochester, MN USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Walsh, Thomas J.] NIH, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Park, BJ (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE,Mailstop C09, Atlanta, GA 30333 USA. EM bpark1@cdc.gov OI Papanicolaou, Genovefa/0000-0002-2891-079X; Patterson, Thomas /0000-0002-9513-7127 FU Centers for Disease Control and Prevention [5U01CI000286-05]; Merck Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; Enzon Pharmaceuticals, Inc. FX This study was supported through Centers for Disease Control and Prevention Grant 5U01CI000286-05 and grants from Merck & Co., Inc.; Astellas U.S., Inc.; Pfizer, Inc.; Schering-Plough Research Institute; and Enzon Pharmaceuticals, Inc. NR 35 TC 74 Z9 74 U1 0 U2 8 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2011 VL 17 IS 10 BP 1855 EP 1864 DI 10.3201/eid1710.110087 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 833PL UT WOS:000295897300009 PM 22000355 ER PT J AU Wasterlain, C Baldwin, R Naylor, DE Thompson, KW Suchomelova, L Niquet, J AF Wasterlain, ClaudeG. Baldwin, Roger Naylor, David E. Thompson, Kerry W. Suchomelova, Lucie Niquet, Jerome TI Rational polytherapy in the treatment of acute seizures and status epilepticus SO EPILEPSIA LA English DT Article DE Status epilepticus; Acute seizures; Cholinergic seizures; Drug toxicity; GABA(A) receptors; NMDA receptors; Neuronal injury; Monotherapy ID GABA(A) RECEPTORS; TRAFFICKING AB We used a model of severe cholinergic status epilepticus (SE) to study polytherapy aimed at reversing the effects of seizure-induced loss of synaptic GABA(A) receptors and seizure-induced gain of synaptic NMDA receptors. Combinations of a benzodiazepine with ketamine and valproate, or with ketamine and brivaracetam, were more effective and less toxic than benzodiazepine monotherapy in this model of SE. C1 [Wasterlain, ClaudeG.; Baldwin, Roger; Naylor, David E.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] VA Greater Angeles Hlth Care Syst, Epilepsy Res Lab, Los Angeles, CA USA. [Wasterlain, ClaudeG.; Naylor, David E.; Thompson, Kerry W.; Suchomelova, Lucie; Niquet, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wasterlain, ClaudeG.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Wasterlain, C (reprint author), UCLA Geffen Sch Med, Dept Neurol, W LA VA Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU Research Service of VHA; NINDS [NS13515, NS 05974]; James and Debbie Cho Foundation FX Supported by the Research Service of VHA, by grants NS13515 and NS 05974 from NINDS, and by the James and Debbie Cho Foundation. NR 5 TC 23 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2011 VL 52 SU 8 SI SI BP 70 EP 71 DI 10.1111/j.1528-1167.2011.03243.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 835VR UT WOS:000296065200023 PM 21967369 ER PT J AU Gold, MR Birgersdotter-Green, U Singh, JP Ellenbogen, KA Yu, YH Meyer, TE Seth, M Tchou, PJ AF Gold, Michael R. Birgersdotter-Green, Ulrika Singh, Jagmeet P. Ellenbogen, Kenneth A. Yu, Yinghong Meyer, Timothy E. Seth, Milan Tchou, Patrick J. TI The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy SO EUROPEAN HEART JOURNAL LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Electrical dyssynchrony; Left ventricular reverse remodelling; Outcomes ID HEART-FAILURE PATIENTS; LEAD POSITION; OUTCOMES; TRIAL; DEFIBRILLATOR; MORTALITY; IMPACT; SITES AB The aim of the present study was to evaluate the relationship between left ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes in a prospectively designed substudy of the SMART-AV Trial. This was a multicentre study of patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) defibrillator implantation. In 426 subjects, QLV was measured as the interval from the onset of the QRS from the surface ECG to the first large peak of the LV electrogram. Left ventricular volumes were measured by echocardiography at baseline and after 6 months of CRT by a blinded core laboratory. Quality of life (QOL) was assessed by a standardized questionnaire. When separated by quartiles based on QLV duration, reverse remodelling response rates (15 reduction in LV end systolic volume) increased progressively from 38.7 to 68.4 and QOL response rate (10 points reduction) increased from 50 to 72. Patients in the highest quartile of QLV had a 3.21-fold increase (1.586.50, P 0.001) in their odds of a reverse remodelling response after correcting for QRS duration, bundle branch block type, and clinical characteristics by multivariate logistic regression analysis. Electrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement. C1 [Gold, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Birgersdotter-Green, Ulrika] Univ Calif San Diego, San Diego, CA 92103 USA. [Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Yu, Yinghong; Meyer, Timothy E.; Seth, Milan] Boston Sci, St Paul, MN USA. [Tchou, Patrick J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Gold, MR (reprint author), Med Univ S Carolina, 25 Courtenay Dr,ART 7031, Charleston, SC 29425 USA. EM goldmr@musc.edu FU Boston Scientific Corporation; Medtronic; Boston Scientific; St Jude; Biotronik FX This study was funded by Boston Scientific Corporation. Funding to pay the Open Access publication charges for this article was provided by Boston Scientific Corporation.; M.G. reported receiving research grants from Medtronic, Boston Scientific and St Jude, fees for fellowship support from Medtronic and Biotronik, honoraria and consulting fees from Medtronic, Boston Scientific, St Jude and Biotronik. U.B. reported receiving research grants from Medtronic, Boston Scientific and St Jude, honoraria/speakers bureau from Medtronic, Boston Scientific and St Jude. J.S. reported receiving research grants from St Jude, Medtronic, Boston Scientific and Biotronik, fees for advisory board/steering committee/consultant from Boston Scientific, Biotronik, St Jude, Medtronic, CardioInsight, Thoratec and Biosense Webster. K.E. reported receiving research grants from Medtronic, Boston Scientific, St Jude, fees for fellowship support from Medtronic, Boston Scientific, and Biotronik, honoraria and consulting fees from Medtronic, Boston Scientific, St Jude and Biotronik. P.T. reported receiving consulting fees from Medtronic, Inc., Y.Y., T.M., and M.S. are employees of Boston Scientific. NR 30 TC 91 Z9 95 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2011 VL 32 IS 20 BP 2516 EP 2524 DI 10.1093/eurheartj/ehr329 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834DK UT WOS:000295939400018 PM 21875862 ER PT J AU Xu, H Becker, CM Lui, WT Chu, CY Davis, TN Kung, AL Birsner, AE D'Amato, RJ Man, GCW Wang, CC AF Xu, Hui Becker, Christian M. Lui, Wai Ting Chu, Ching Yan Davis, Tina N. Kung, Andrew L. Birsner, Amy E. D'Amato, Robert J. Man, Gene Chi Wai Wang, Chi Chiu TI Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo SO FERTILITY AND STERILITY LA English DT Article DE Endometriosis; green tea catechins; antiangiogenesis ID VEGF-C; MOLECULAR-MECHANISMS; MOUSE MODEL; THERAPY; LESIONS; CELLS; VITRO; MICE AB Objective: To investigate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo. Design: Animal studies. Setting: University laboratory. Animal(s): Human endometrium from women with endometriosis (n = 10) was transplanted into immunocompromised mice. Intervention(s): Mice (n 30) were randomly treated with EGCG, vitamin E (antioxidant control), or vehicle (negative control) for microvessel imaging. Main Outcome Measure(s): Endometriotic implants were collected for angiogenesis microarray and pathway analysis. Differentially expressed angiogenesis molecules were confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Effects of EGCG on angiogenesis signal transduction were further characterized in a human endothelial cell line. Microvessel parameters and the angiogenesis signaling pathway in endometriotic implants and endothelial cells were studied. Result(s): EGCG, but not vitamin E, inhibited microvessels in endometriotic implants. EGCG selectively suppressed vascular endothelial growth factor C (VEGFC) and tyrosine kinase receptor VEGF receptor 2 (VEGFR2) expression. EGCG down-regulated VEGFC/VEGFR2 signaling through c-JUN, interferon-gamma, matrix metalloproteinase 9, and chemokine (C-X-C motif) ligand 3 pathways for endothelial proliferation, inflammatory response, and mobility. EGCG also suppressed VEGFC expression and reduced VEGFR2 and ERK activation in endothelial cells. VEGFC supplementation attenuated the inhibitory effects by EGCG. Conclusion(s): EGCG inhibited angiogenesis and suppressed VEGFC/VEGFR2 expression and signaling pathway in experimental endometriosis in vivo and endothelial cells in vitro. (Fertil Steril (R) 2011; 96: 1021-8. (C)2011 by American Society for Reproductive Medicine.) C1 [Xu, Hui; Lui, Wai Ting; Chu, Ching Yan; Man, Gene Chi Wai; Wang, Chi Chiu] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynaecol, Shatin, Hong Kong, Peoples R China. [Becker, Christian M.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England. [Davis, Tina N.; Kung, Andrew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Birsner, Amy E.; D'Amato, Robert J.] Harvard Univ, Childrens Hosp, Sch Med, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. [Wang, Chi Chiu] Chinese Univ Hong Kong, Prince Wales Hosp, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. RP Wang, CC (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynaecol, 1st Floor,Block E, Shatin, Hong Kong, Peoples R China. EM ccwang@cuhk.edu.hk RI Wang, Ronald/C-6541-2014; OI Kung, Andrew/0000-0002-9091-488X FU Chinese University of Hong Kong [3029821, 3029476]; Obstetrical and Gynaecological Society of Hong Kong; MRC [G0601458]; Oxford Partnership Comprehensive Biomedical Research Centre from the Department of Health's NIHR Biomedical Research Centres FX Supported by the Global Scholarship Programme for Research Excellence-CNOOC grant 2008-2009 from the Chinese University of Hong Kong to H. X. and C. C. W. to study at Harvard and Oxford Universities; two Academic Equipment grants (3029821 and 3029476) from the Chinese University of Hong Kong to C. C. W. for an in vivo cellular imaging system and a microarray-based gene expression and comparative genomic hybridization platform; a Hong Kong Obstetrical and Gynaecological Trust Fund 2010 grant from the Obstetrical and Gynaecological Society of Hong Kong to C. C. W. and G. C. W. M.; an MRC New Investigator Award (G0601458) and the Oxford Partnership Comprehensive Biomedical Research Centre from the Department of Health's NIHR Biomedical Research Centres scheme to C. M. B. NR 36 TC 27 Z9 30 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2011 VL 96 IS 4 BP 1021 EP U488 DI 10.1016/j.fertnstert.2011.07.008 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 834DF UT WOS:000295938800054 PM 21821246 ER PT J AU van Rooyen, DM Larter, CZ Haigh, WG Yeh, MM Ioannou, G Kuver, R Lee, SP Teoh, NC Farrell, GC AF van Rooyen, Derrick M. Larter, Claire Z. Haigh, W. Geoffrey Yeh, Matthew M. Ioannou, George Kuver, Rahul Lee, Sum P. Teoh, Narci C. Farrell, Geoffrey C. TI Hepatic Free Cholesterol Accumulates in Obese, Diabetic Mice and Causes Nonalcoholic Steatohepatitis SO GASTROENTEROLOGY LA English DT Article DE Lipotoxicity; LRH-1; Bsep; Liver Damage ID FATTY LIVER-DISEASE; TRANSCRIPTIONAL REGULATION; MESSENGER-RNA; EXPRESSION; HEPATOCYTES; ASSOCIATION; SUPPRESSION; RESISTANCE; ROLES; RAT AB BACKGROUND & AIMS: Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. METHODS: Alms1 mutant (foz/foz) and wild-type NOD. B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. RESULTS: Hepatic cholesterol accumulation was attributed to upregulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. CONCLUSIONS: In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. C1 [Farrell, Geoffrey C.] Canberra Hosp, Gastroenterol & Hepatol Unit, Liver Res Grp, ANU Med Sch, Garran, ACT 2605, Australia. [Haigh, W. Geoffrey; Kuver, Rahul; Lee, Sum P.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Ioannou, George] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Farrell, GC (reprint author), Canberra Hosp, Gastroenterol & Hepatol Unit, Liver Res Grp, ANU Med Sch, Yamba Dr, Garran, ACT 2605, Australia. EM geoff.farrell@anu.edu.au FU Australian National Health and Medical Research Council (NHMRC) [418101, 585411]; NHMRC [585539]; National Institutes of Health [RO1CA114403] FX Supported by project grants 418101 and 585411 of the Australian National Health and Medical Research Council (NHMRC), NHMRC scholarship 585539, and National Institutes of Health grant RO1CA114403. NR 29 TC 98 Z9 98 U1 4 U2 18 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 OCT PY 2011 VL 141 IS 4 BP 1393 EP U850 DI 10.1053/j.gastro.2011.06.040 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700046 PM 21703998 ER PT J AU Goyal, RK AF Goyal, Raj K. TI Evidence for beta-Nicotinamide Adenine Dinucleotide as a Purinergic, Inhibitory Neurotransmitter in Doubt SO GASTROENTEROLOGY LA English DT Letter C1 [Goyal, Raj K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goyal, Raj K.] VA Boston Healthcare, W Roxbury, MA USA. RP Goyal, RK (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK062867] NR 7 TC 13 Z9 13 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2011 VL 141 IS 4 BP E27 EP E27 DI 10.1053/j.gastro.2011.07.047 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829OQ UT WOS:000295593700009 PM 21888906 ER PT J AU Chavalitdhamrong, D Jensen, DM Kovacs, TOG Jutabha, R Dulai, G Ohning, G Machicado, GA AF Chavalitdhamrong, Disaya Jensen, Dennis M. Kovacs, Thomas O. G. Jutabha, Rome Dulai, Gareth Ohning, Gordon Machicado, Gustavo A. TI Ischemic colitis as a cause of severe hematochezia: risk factors and outcomes compared with other colon diagnoses SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID URGENT COLONOSCOPY; SPECTRUM AB Background: Risk factors and outcomes of severe hematochezia from ischemic colitis compared with other colonic diagnoses have not been well studied. Objective: Our purposes were (1) to compare demographics and outcomes of patients hospitalized with severe hematochezia from ischemic colitis compared with other colonic diagnoses, (2) to compare inpatient and outpatient start of bleeding from ischemic colitis, and (3) to describe potential risk factors. Design: Prospective cohort study. Setting: Tertiary referral academic centers. Patients: Patients referred for gastroenterology consultation for severe hematochezia. Interventions: Colonoscopic therapy was provided as indicated. Main Outcome Measurements: Rebleeding, surgery, and length of hospital stay after colonoscopy. Results: Of 550 patients in the past 12 years with severe hematochezia from colonic sources, the cause in 65 patients (11.8%) was ischemia. Ischemic colitis was found more often in females, in patients taking anticoagulant agents, in patients with severe lung disease, those with higher creatinine levels, those with higher glucose levels, and those with more fresh frozen plasma transfusions. Five patients with focal lesions had colonoscopic hemostasis. Major 30-day outcomes of ischemic colitis patients were significantly worse than patients with other colonic diagnoses. Patients with inpatient (vs outpatient) ischemic colitis had significantly more and more severe comorbidities at baseline and significantly higher rates of rebleeding, surgery, and more days spent in hospital and in the intensive care unit. Limitations: Two-center study. Conclusions: Major 30-day outcomes in ischemic colitis patients were significantly worse than in patients with other colonic diagnoses. Comparing outpatient and inpatient start of ischemic colitis, inpatients had significantly worse outcomes. (Gastrointest Endosc 2011;74:852-7.) C1 [Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] Greater Los Angeles VA Healthcare Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. [Chavalitdhamrong, Disaya; Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] CURE, Hemostasis Res Unit, Los Angeles, CA USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Machicado, Gustavo A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Jutabha, Rome; Machicado, Gustavo A.] Univ Calif Los Angeles, Div Digest Dis, Ronald Reagan Med Ctr, Los Angeles, CA 90095 USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Dulai, Gareth; Ohning, Gordon; Machicado, Gustavo A.] Greater Los Angeles VA Healthcare Ctr, GI Hepatol Sect, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), Greater Los Angeles VA Healthcare Ctr, CURE Digest Dis Res Ctr, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIH [K24 DK002650]; CURE Digestive Diseases Research Center [P30 DK041301] FX All authors disclosed no financial relationships relevant to this publication. This study was partially supported by research funds from an NIH grant (K24 DK002650) and CURE Digestive Diseases Research Center Human Studies Core grant (P30 DK041301). NR 14 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2011 VL 74 IS 4 BP 852 EP 857 DI 10.1016/j.gie.2011.05.039 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 834ME UT WOS:000295963900017 PM 21839438 ER PT J AU Day, LW Kwon, A Inadomi, JM Walter, LC Somsouk, M AF Day, Lukejohn W. Kwon, Annette Inadomi, John M. Walter, Louise C. Somsouk, Ma TI Adverse events in older patients undergoing colonoscopy: a systematic review and meta-analysis SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID COLORECTAL-CANCER; OUTPATIENT COLONOSCOPY; SCREENING COLONOSCOPY; CLINICAL-PRACTICE; DIAGNOSTIC YIELD; GI ENDOSCOPY; RISK-FACTORS; COMPLICATIONS; PERFORATION; POPULATION AB Background: Studies suggest that advancing age is an independent risk factor for experiencing adverse events during colonoscopy. Yet many of these studies are limited by small sample sizes and/or marked variation in reported outcomes. Objective: To determine the incidence rates for specific adverse events in elderly patients undergoing colonoscopy and calculate incidence rate ratios for selected comparison groups. Setting and Patients: Elderly patients undergoing colonoscopy. Design: Systematic review and meta-analysis. Main Outcome Measurements: Perforation, bleeding, cardiovascular (CV)/pulmonary complications, and mortality. Results: Our literature search yielded 3328 articles, of which 20 studies met our inclusion criteria. Pooled incidence rates for adverse events (per 1000 colonoscopies) in patients 65 years of age and older were 26.0 (95% CI, 25.0-27.0) for cumulative GI adverse events, 1.0 (95% CI, 0.9-1.5) for perforation, 6.3 (95% CI, 5.7-7.0) for GI bleeding, 19.1 (95% CI, 18.0-20.3) for CV/pulmonary complications, and 1.0 (95% CI, 0.7-2.2) for mortality. Among octogenarians, adverse events (per 1000 colonoscopies) were as follows: cumulative GI adverse event rate of 34.9 (95% CI, 31.9-38.0), perforation rate of 1.5 (95% CI, 1.1-1.9), GI bleeding rate of 2.4 (95% CI, 1.1-4.6), CV/pulmonary complication rate of 28.9 (95% CI, 26.2-31.8), and mortality rate of 0.5 (95% CI, 0.06-1.9). Patients 80 years of age and older experienced higher rates of cumulative GI adverse events (incidence rate ratio 1.7; 95% CI, 1.5-1.9) and had a greater risk of perforation (incidence rate ratio 1.6, 95% CI, 1.2-2.1) compared with younger patients (younger than 80 years of age). There was an increased trend toward higher rates of GI bleeding and CV/pulmonary complications in octogenarians but neither was statistically significant. Limitations: Heterogeneity of studies included and not all complications related to colonoscopy were captured. Conclusions: Elderly patients, especially octogenarians, appear to have a higher risk of complications during and after colonoscopy. These data should inform clinical decision making, the consent process, public health policy, and comparative effectiveness analyses. (Gastrointest Endosc 2011;74:885-96.) C1 [Day, Lukejohn W.; Somsouk, Ma] San Francisco Gen Hosp, Div Gastroenterol, San Francisco, CA 94110 USA. [Day, Lukejohn W.; Somsouk, Ma] Univ Calif San Francisco, Dept Med, GI Hlth Outcomes, Policy & Econ HOPE Res Program, San Francisco, CA USA. [Kwon, Annette] Calif Pacific Med Ctr, Dept Gastroenterol, San Francisco, CA USA. [Inadomi, John M.] Univ Washington, Dept Med, Div Gastroenterol & Hepatol, Seattle, WA USA. [Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. RP Day, LW (reprint author), San Francisco Gen Hosp, Div Gastroenterol, 1001 Potrero Ave,3D-5, San Francisco, CA 94110 USA. EM lukejohn.day@ucsf.edu RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 FU Mount Zion Health Fund; American Society for Gastrointestinal Endoscopy; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080941]; VA Health Services Research and Development grant [IIR-04-427]; National Cancer Institute [1R01CA134425] FX The authors disclosed no financial relationships relevant to this publication. This work was funded in part by grants from the Mount Zion Health Fund and American Society for Gastrointestinal Endoscopy Cook Career Development Award (M.S.) and from the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080941) (J.M.I.). Dr. Walter is supported by a VA Health Services Research and Development grant IIR-04-427 and by grant 1R01CA134425 from the National Cancer Institute. NR 67 TC 46 Z9 47 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2011 VL 74 IS 4 BP 885 EP 896 DI 10.1016/j.gie.2011.06.023 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 834ME UT WOS:000295963900021 PM 21951478 ER PT J AU Schild-Prufert, K Saito, TT Smolikov, S Gu, YJ Hincapie, M Hill, DE Vidal, M McDonald, K Colaiacovo, MP AF Schild-Pruefert, Kristina Saito, Takamune T. Smolikov, Sarit Gu, Yanjie Hincapie, Marina Hill, David E. Vidal, Marc McDonald, Kent Colaiacovo, Monica P. TI Organization of the Synaptonemal Complex During Meiosis in Caenorhabditis elegans SO GENETICS LA English DT Article ID STRAND BREAK REPAIR; CENTRAL REGION; CHROMOSOME SYNAPSIS; CENTRAL ELEMENT; C-ELEGANS; MEIOTIC CHROMOSOMES; BLAPS CRIBROSA; CROSSING-OVER; PROTEIN ZYP1; RECOMBINATION AB Four different SYP proteins (SYP-1, SYP-2, SYP-3, and SYP-4) have been proposed to form the central region of the synaptonemal complex (SC) thereby bridging the axes of paired meiotic chromosomes in Caenorhabditis elegans. Their interdependent localization suggests that they may interact within the SC. Our studies reveal for the first time how these SYP proteins are organized in the central region of the SC. Yeast two-hybrid and co-immunoprecipitation studies show that SYP-1 is the only SYP protein that is capable of homotypic interactions, and is able to interact with both SYP-2 and SYP-3 directly, whereas SYP-2 and SYP-3 do not seem to interact with each other. Specifically, the coiled-coil domain of SYP-1 is required both for its homotypic interactions and its interaction with the C-terminal domain of SYP-2. Meanwhile, SYP-3 interacts with the C-terminal end of SYP-1 via its N-terminal domain. Immunoelectron microscopy analysis provides insight into the orientation of these proteins within the SC. While the C-terminal domain of SYP-3 localizes in close proximity to the chromosome axes, the N-terminal domains of both SYP-1 and SYP-4, as well as the C-terminal domain of SYP-2, are located in the middle of the SC. Taking into account the different sizes of these proteins, their interaction abilities, and their orientation within the SC, we propose a model of how the SYP proteins link the homologous axes to provide the conserved structure and width of the SC in C. elegans. C1 [Schild-Pruefert, Kristina; Saito, Takamune T.; Smolikov, Sarit; Gu, Yanjie; Hincapie, Marina; Hill, David E.; Vidal, Marc; Colaiacovo, Monica P.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [McDonald, Kent] Univ Calif Berkeley, Electron Microscope Lab, Berkeley, CA 94720 USA. RP Colaiacovo, MP (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,NRB 334, Boston, MA 02115 USA. EM mcolaiacovo@genetics.med.harvard.edu RI Hill, David/B-6617-2011; Saito, Takamune/G-2294-2014; OI Saito, Takamune/0000-0002-4447-4115; Schild, Kristina/0000-0002-0154-7310 FU Deutsche Forschungsgemeinschaft German Research Foundation [PR1057/1-1]; March of Dimes Birth Defects Foundation [5-FY05-1214]; National Institutes of Health [R01GM072551] FX We thank Scott Hawley for critical reading of this manuscript and Monique Zetka for the HTP-3 antibody. K.S.-P. was supported by a Deutsche Forschungsgemeinschaft German Research Foundation postdoctoral research fellowship (PR1057/1-1). This work was supported by research grant 5-FY05-1214 from the March of Dimes Birth Defects Foundation and by National Institutes of Health grant R01GM072551 to M.P.C. NR 38 TC 26 Z9 31 U1 1 U2 10 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2011 VL 189 IS 2 BP 411 EP U437 DI 10.1534/genetics.111.132431 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 836ZH UT WOS:000296158500002 PM 21840865 ER PT J AU Spencer, RJ del Rosario, BC Pinter, SF Lessing, D Sadreyev, RI Lee, JT AF Spencer, Rebecca J. del Rosario, Brian C. Pinter, Stefan F. Lessing, Derek Sadreyev, Ruslan I. Lee, Jeannie T. TI A Boundary Element Between Tsix and Xist Binds the Chromatin Insulator Ctcf and Contributes to Initiation of X-Chromosome Inactivation SO GENETICS LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; IMPRINTING CONTROL REGION; BETA-GLOBIN LOCUS; DOSAGE COMPENSATION; PROTEIN CTCF; GENE; TRANSCRIPTION; CHOICE; GENOME; MOUSE AB In mammals, X-chromosome inactivation (XCI) equalizes X-linked gene expression between XY males and XX females and is controlled by a specialized region known as the X-inactivation center (Xic). The Xic harbors two chromatin interaction domains, one centered around the noncoding Xist gene and the other around the antisense Tsix counterpart. Previous work demonstrated the existence of a chromatin transitional zone between the two domains. Here, we investigate the region and discover a conserved element, RS14, that presents a strong binding site for Ctcf protein. RS14 possesses an insulatory function suggestive of a boundary element and is crucial for cell differentiation and growth. Knocking out RS14 results in compromised Xist induction and aberrant XCI in female cells. These data demonstrate that a junction element between Tsix and Xist contributes to the initiation of XCI. C1 [Spencer, Rebecca J.; del Rosario, Brian C.; Pinter, Stefan F.; Lessing, Derek; Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St, Boston, MA 02115 USA. EM lee@molbio.mgh.harvard.edu OI Pinter, Stefan/0000-0003-4750-1403 FU Harvard Medical School; Deutche Forschungsgemeinschaft; National Institutes of Health [RO1-GM58839] FX We are grateful to all lab members for discussion and support. R.J.S. is supported by the Medical Scientist Training Program at Harvard Medical School. S.F.P. is supported by a Deutche Forschungsgemeinschaft research fellowship. This work is funded by a grant from the National Institutes of Health (RO1-GM58839). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 76 TC 24 Z9 26 U1 1 U2 5 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2011 VL 189 IS 2 BP 441 EP U470 DI 10.1534/genetics.111.132662 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 836ZH UT WOS:000296158500004 PM 21840866 ER PT J AU Plass, A Emmert, MY Gaemperli, O Alkadhi, H Kaufmann, P Falk, V Grunenfelder, J AF Plass, Andre Emmert, Maximilian Y. Gaemperli, Oliver Alkadhi, Hatem Kaufmann, Philipp Falk, Volkmar Gruenenfelder, Juerg TI The Potential Value of Hybrid Positron Emission Tomography/Dual-Source Computed Tomography Imaging in Coronary Bypass Surgery SO HEART SURGERY FORUM LA English DT Article ID MYOCARDIAL-PERFUSION SPECT; ARTERY-DISEASE; CT ANGIOGRAPHY; FLOW RESERVE; DIAGNOSTIC PERFORMANCE; 64-SLICE CT; REVASCULARIZATION; STRESS; FUSION; INTERVENTION AB Background: We evaluated how comprehensive assessment of coronary artery lesions and their hemodynamic relevance by means of hybrid positron emission tomography (PET) and computed tomography (CT) imaging would affect decision-making in coronary artery bypass surgery (CABG), compared with using invasive coronary angiography (ICA) alone. Methods: After undergoing ICA, 27 patients (21 men and 6 women; mean SD age, 66 +/- 10 years) planned for cardiac surgery were scheduled for myocardial perfusion stress/rest evaluation with [13N] ammonia PET and CT coronary angiography. Only ICA was available to the surgeon. Postoperatively, the performed CABG was compared with the hypothetical strategy based on hybrid PET/CT findings (regional coronary flow reserve [CFR], myocardial perfusion defects). Procedures included CABG (n = 18) alone, CABG combined with valve replacement (n = 6), and CABG combined with isolated valve replacement (n = 3). A total of 56 bypass grafts (28 venous and 28 arterial) and 66 distal anastomoses were placed. Results: CT evaluation showed 93% concordance (66/71) with ICA regarding significant stenoses, with sensitivity, specificity, positive predictive value, and negative predictive value of 93.1%, 98.7%, 94.4%, and 98.4%, respectively. In the PET scan, 16 patients had 1 ischemic region, and 12 patients had 1 scar region, including 5 patients who presented with mixed conditions (scar and ischemia). One patient had a completely normal myocardium. Compared with the performed surgery, PET/CT fusion evaluation showed that of the performed anastomoses, 48% had documented ischemia (with a CFR < 2 in 86%), 38% were nonischemic (although a CFR value < 2 was found in 78%), and 14% had scar tissue (fixed perfusion defect). Conclusions: Although < 50% of bypasses were placed to areas with myocardial ischemia, the CFR was low in the majority of nonischemic regions, a finding that may have important prognostic relevance. PET/CT fusion imaging could potentially influence planning for CABG and provide incremental prognostic information. C1 [Plass, Andre; Emmert, Maximilian Y.; Falk, Volkmar; Gruenenfelder, Juerg] Univ Zurich Hosp, Clin Cardiovasc Surg, CH-8091 Zurich, Switzerland. [Gaemperli, Oliver; Kaufmann, Philipp] Univ Zurich Hosp, Clin Nucl Med, CH-8091 Zurich, Switzerland. [Gaemperli, Oliver] Univ Zurich Hosp, Clin Cardiol, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. RP Plass, A (reprint author), Univ Zurich Hosp, Clin Cardiovasc Surg, Ramistr 100, CH-8091 Zurich, Switzerland. EM Andre.Plass@usz.ch NR 36 TC 0 Z9 0 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PD OCT PY 2011 VL 14 IS 5 BP E283 EP E290 DI 10.1532/HSF98.20111045 PG 8 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 839CH UT WOS:000296341700003 PM 21997649 ER PT J AU Tawakol, A Finn, AV AF Tawakol, Ahmed Finn, Aloke V. TI Imaging Inflammatory Changes in Atherosclerosis Multimodal Imaging Hitting Stride SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE atherosclerosis; diabetes; inflammation; MRI; pioglitazone; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; PLAQUE INFLAMMATION; ACTIVATED MACROPHAGES; VASCULAR INFLAMMATION; FDG-PET; FLUORODEOXYGLUCOSE; GLUCOSE; ARTERIES; DISEASE; RISK C1 [Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA. [Finn, Aloke V.] Emory Univ, Sch Med, Dept Internal Med, Atlanta, GA USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac MR PET CT Program, 55 Fruit St,YAW 5904, Boston, MA 02114 USA. EM atawakol@partners.org NR 26 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2011 VL 4 IS 10 BP 1119 EP 1122 DI 10.1016/j.jcmg.2011.09.001 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 835VP UT WOS:000296065000010 PM 21999872 ER PT J AU Faber, JJ Anderson, DF Louey, S Thornburg, KL Giraud, GD AF Faber, J. J. Anderson, D. F. Louey, S. Thornburg, K. L. Giraud, G. D. TI Insignificant response of the fetal placental circulation to arterial hypotension in sheep SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE enalaprilat; somatic blood flow; vascular resistance; plasma renin activity; blood gases; growth ID BLOOD-FLOW; HEMODYNAMICS; ANGIOTENSIN; PRESSURE; LAMB AB Faber JJ, Anderson DF, Louey S, Thornburg KL, Giraud GD. Insignificant response of the fetal placental circulation to arterial hypotension in sheep. J Appl Physiol 111: 1042-1047, 2011. First published June 30, 2011; doi:10.1152/japplphysiol.00345.2011.-Infusion of the angiotensin-converting enzyme inhibitor enalaprilat into fetal sheep caused a profound arterial hypotension within days. Five fetal lambs were infused with enalaprilat for 8 days starting at day 128 of gestation. Total accumulated dose was 0.30 +/- 0.11 mg/kg. Arterial pressure decreased from 43.6 to 25.6 mmHg; venous pressure did not change. Biventricular output was not statistically significantly changed; placental blood flow decreased almost in proportion to the decrease in pressure but the increase in somatic flow was not statistically significant. There were no significant changes in pressure 30 min after the initial 50-mu g loading dose of enalaprilat. However, the arterial pressure responses to test doses of ANG I were largely abolished. After 1 day, however, there was a significant decrease in somatic vascular resistance, which became stronger with time, but almost no decrease in the placental resistance. We conclude that the fetal somatic circulation exhibits a slow but strong decrease in resistance but that the response to hypotension is weak or absent in the fetal placenta, possibly because it is already fully relaxed. C1 [Faber, J. J.; Anderson, D. F.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Faber, J. J.; Anderson, D. F.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97239 USA. [Giraud, G. D.] Portland VA Med Ctr, Portland, OR USA. RP Giraud, GD (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr CH15H, Div Cardiovasc Med, Portland, OR 97239 USA. EM giraudg@ohsu.edu FU National Institutes of Health [P01-HD-34430]; Department of Veterans Affairs; M. Lowell Edwards Endowment FX This research was funded by a National Institutes of Health Program Project Grant (P01-HD-34430), the Department of Veterans Affairs, and the M. Lowell Edwards Endowment. NR 18 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2011 VL 111 IS 4 BP 1042 EP 1047 DI 10.1152/japplphysiol.00345.2011 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 834OR UT WOS:000295972000013 PM 21719727 ER PT J AU Armoundas, A Merchant, F Armoundas, A AF Armoundas, A. Merchant, F. Armoundas, Antonis TI A NOVEL PACING METHOD TO SUPPRESS REPOLARIZATION ALTERNANS SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. 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 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2011 VL 22 SU 1 SI SI BP S118 EP S118 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837ZP UT WOS:000296255000316 ER PT J AU Mela, T Chung, M Gottipaty, V Borge, R Shinn, T Dan, D Uslan, D Gleva, MJ Holcomb, R Poole, J AF Mela, T. Chung, M. Gottipaty, V. Borge, R. Shinn, T. Dan, D. Uslan, D. Gleva, M. J. Holcomb, R. Poole, J. CA REPLACE Investigators TI THE EFFECT OF PHYSICIAN PRACTICE AND SPECIALTY ON OUTCOMES AFTER PACEMAKER AND IMPLANTABLE DEFIBRILLATOR REPLACEMENT: RESULTS FROM THE REPLACE REGISTRY SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. S Carolina Heart Ctr, Columbia, SC USA. Abington Med Specialists, Abington, PA USA. Michigan Heart, Ann Arbor, MI USA. Piedmont Heart Inst, Atlanta, GA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Washington, Sch Med, Seattle, WA 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 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2011 VL 22 SU 1 SI SI BP S72 EP S72 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837ZP UT WOS:000296255000191 ER PT J AU Pappalardo, A Forleo, G Avella, A De Girolamo, P Laurenzi, F Ruskin, J Tondo, C Mansour, M AF Pappalardo, A. Forleo, G. Avella, A. De Girolamo, P. Laurenzi, F. Ruskin, J. Tondo, C. Mansour, M. TI COMBINED USE OF CRYO-BALLOON AND FOCAL OPEN-IRRIGATION RADIOFREQUENCY ABLATION FOR THE TREATMENT OF PERSISTENT ATRIAL FIBRILLATION: ACUTE AND LONG TERM RESULTS SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract C1 San Camillo Hosp, Cardiovasc Dept, Rome, Italy. Tor Vergata Hosp, Cardiovasc Dept, Rome, Italy. Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. Ctr Cardiol Monzino, Milan, Italy. RI Forleo, Giovanni/G-8788-2012 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 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2011 VL 22 SU 1 SI SI BP S47 EP S47 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837ZP UT WOS:000296255000125 ER PT J AU Tondo, C Dello Russo, A Fassini, G Riva, S Heist, K Barrett, C Danik, S Moltrasio, M Casella, M Tundo, F Al-Mohani, G Ruskin, J Mansour, M AF Tondo, C. Dello Russo, A. Fassini, G. Riva, S. Heist, K. Barrett, C. Danik, S. Moltrasio, M. Casella, M. Tundo, F. Al-Mohani, G. Ruskin, J. Mansour, M. TI INCIDENCE OF ISOLATED PULMONARY VEIN POTENTIALS IDENTIFIED DURING LASER BALLOON PULMONARY VEIN ISOLATION SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract CT Venice Arrhythmias Conference CY OCT 09-12, 2011 CL Venice, ITALY C1 IRCCS, Ctr Cardiol Monzino, Milan, Italy. Massachusetts Gen Hosp, Ctr Heart, 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 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2011 VL 22 SU 1 SI SI BP S110 EP S110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837ZP UT WOS:000296255000295 ER PT J AU Tondo, C Fassini, G Dello Russo, A Casella, M Al-Mohani, G Tundo, F Riva, S Moltrasio, M Barrett, C Danik, S Ruskin, J Mansour, M AF Tondo, C. Fassini, G. Dello Russo, A. Casella, M. Al-Mohani, G. Tundo, F. Riva, S. Moltrasio, M. Barrett, C. Danik, S. Ruskin, J. Mansour, M. TI EXTENT AND LEVEL OF PULMONARY VEIN ISOLATION WITH THE LASER BALLOON ABLATION IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Meeting Abstract CT Venice Arrhythmias Conference CY OCT 09-12, 2011 CL Venice, ITALY C1 IRCCS, Ctr Cardiol Monzino, Milan, Italy. Massachusetts Gen Hosp, Ctr Heart, 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 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2011 VL 22 SU 1 SI SI BP S110 EP S110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 837ZP UT WOS:000296255000294 ER PT J AU Frutos-Vivar, F Esteban, A Apezteguia, C Gonzalez, M Arabi, Y Restrepo, MI Gordo, F Santos, C Alhashemi, JA Perez, F Penuelas, O Anzueto, A AF Frutos-Vivar, Fernando Esteban, Andres Apezteguia, Carlos Gonzalez, Marco Arabi, Yaseen Restrepo, Marcos I. Gordo, Federico Santos, Cristina Alhashemi, Jamal A. Perez, Fernando Penuelas, Oscar Anzueto, Antonio TI Outcome of reintubated patients after scheduled extubation SO JOURNAL OF CRITICAL CARE LA English DT Article DE Weaning; Extubation; Outcome; Epidemiology; Noninvasive positive pressure ventilation ID INTENSIVE-CARE-UNIT; POSITIVE-PRESSURE VENTILATION; MECHANICAL VENTILATION; NONINVASIVE VENTILATION; RESPIRATORY-FAILURE; ENDOTRACHEAL INTUBATION; TRACHEAL INTUBATIONS; NOSOCOMIAL PNEUMONIA; MULTIPLE-CENTER; RISK AB Purpose: The main objective of study was to evaluate the outcome of patients who require reintubation after elective extubation. Materials and Methods: This is an observational, prospective cohort study including mechanically ventilated patients who passed successfully a spontaneous breathing trial. Patients were observed for 48 hours after extubation. During this time, reintubation or use of noninvasive positive pressure ventilation was considered as a failure. Reintubated patients were followed after the reintubation to register complications and outcome. Results: A total of 1,152 extubated patients were included in the analysis. Three hundred thirty-six patients (29%) met the criteria for extubation failure. Extubation failure was independently associated with mortality (odds ratio, 3.29; 95% confidence interval, 2.19-4.93). One hundred eighty patients (16% of overall cohort) required reintubation within 48 hours after extubation. Median time from extubation to reintubation was 13 hours (interquartile range, 6-24 hours). Reintubation was independently associated with mortality (odds ratio, 5.18; 95% confidence interval, 3.38-7.94; P < .001). Higher mortality of reintubated patients was due to the development of complications after the reintubation. Conclusions: In a large cohort of scheduled extubated patients, one third of patients developed extubation failure, of whom half needed reintubation. Reintubation was associated with increased mortality due to the development of new complications after reintubation. (C) 2011 Elsevier Inc. All rights reserved. C1 [Esteban, Andres] Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. [Frutos-Vivar, Fernando; Esteban, Andres; Penuelas, Oscar] CIBER Enfermedades Respiratorias, Madrid, Spain. [Apezteguia, Carlos] Hosp Profesor A Posadas, Buenos Aires, DF, Argentina. [Gonzalez, Marco] Clin Medellin, Medellin, Colombia. [Gonzalez, Marco] Univ Pontificia Bolivariana, Medellin, Colombia. [Arabi, Yaseen] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX USA. [Gordo, Federico] Hosp Henares, Madrid, Spain. [Santos, Cristina] Hosp Clin Montevideo, Montevideo, Uruguay. [Alhashemi, Jamal A.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Perez, Fernando] Hosp Clin Caracas, Caracas, Venezuela. RP Esteban, A (reprint author), Hosp Univ Getafe, Intens Care Unit, Madrid 28905, Spain. EM aesteban@ucigetafe.com RI Restrepo, Marcos/H-4442-2014; OI Frutos-Vivar, Fernando/0000-0002-4648-9636 FU CIBER Enfermedades Respiratorias from Instituto Carlos III, Spain FX This work was supported by the CIBER Enfermedades Respiratorias from Instituto Carlos III, Spain. NR 28 TC 42 Z9 43 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2011 VL 26 IS 5 BP 502 EP 509 DI 10.1016/j.jcrc.2010.12.015 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 834NP UT WOS:000295968800013 PM 21376523 ER PT J AU Finn, KM Greenwald, J AF Finn, Kathleen M. Greenwald, Jeff TI Hospitalists and Alcohol Withdrawal: Yes, Give Benzodiazepines but Is That the Whole Story? SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID SYMPTOM-TRIGGERED THERAPY; SCALE CIWA-AR; UNHEALTHY ALCOHOL; PRACTICE GUIDELINE; MANAGEMENT; LORAZEPAM; PREVALENCE; INPATIENTS; DELIRIUM; TRIAL C1 [Finn, Kathleen M.; Greenwald, Jeff] Massachusetts Gen Hosp, Clinician Educ Program, Boston, MA 02114 USA. RP Finn, KM (reprint author), Massachusetts Gen Hosp, Clinician Educ Program, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM Kfinn@partners.org NR 32 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2011 VL 6 IS 8 BP 435 EP 437 DI 10.1002/jhm.966 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 836DX UT WOS:000296090700002 PM 21990171 ER PT J AU Tamuz, M Giardina, TD Thomas, EJ Menon, S Singh, H AF Tamuz, Michal Giardina, Traber Davis Thomas, Eric J. Menon, Shailaja Singh, Hardeep TI Rethinking Resident Supervision to Improve Safety: From Hierarchical to Interprofessional Models SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID SERIOUS MEDICAL ERRORS; INTENSIVE-CARE; ADVERSE EVENTS; PATIENT SAFETY; PHARMACISTS; PREVENTION; TRAINEES; TEAMWORK; IMPACT; UNITS AB BACKGROUND: Inadequate supervision is a significant contributing factor to medical errors involving trainees, but supervision in high-risk settings such as the intensive care unit (ICU) is not well studied. OBJECTIVE: We explored how residents in the ICU experienced supervision related to medication safety, not only from supervising physicians but also from other professionals. DESIGN, SETTING, MEASUREMENTS: Using qualitative methods, we examined in-depth interviews with 17 residents working in ICUs of three tertiary-care hospitals. We analyzed residents' perspectives on receiving and initiating supervision from physicians within the traditional medical hierarchy, and from other professionals, including nurses, staff pharmacists, and clinical pharmacists ("interprofessional supervision"). RESULTS: While initiating their own supervision within the traditional hierarchy, residents believed in seeking assistance from fellows and attendings, and articulated rules of thumb for doing so; however, they also experienced difficulties. Some residents were concerned that their questions would reflect poorly on them; others were embarrassed by their mistaken decisions. Conversely, residents described receiving interprofessional supervision from nurses and pharmacists, who proactively monitored, intervened in, and guided residents' decisions. Residents relied on nurses and pharmacists for nonjudgmental answers to their queries, especially after-hours. To enhance both types of supervision, residents emphasized the importance of improving interpersonal communication skills. CONCLUSIONS: Residents depended on interprofessional supervision when making decisions regarding medications in the ICU. Improving interprofessional supervision, which thus far has been underrecognized and underemphasized in graduate medical education, can potentially improve medication safety in high-risk settings. Journal of Hospital Medicine 2011;6:445-452. (C) 2011 Society of Hospital Medicine C1 [Tamuz, Michal] Suny Downstate Med Ctr, Sch Publ Hlth, Dept Hlth Policy & Management, Brooklyn, NY 11203 USA. [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Mem Hermann Ctr Healthcare Qual & Safety, Med Sch Houston, Div Gen Med,Dept Med, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Davis Giardina, Traber/0000-0002-9184-6524 FU AHRQ [1PO1HS1154401]; Houston VA HSR&D Center of Excellence [HFP90-020] FX Project supported by AHRQ grant #1PO1HS1154401, and in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 40 TC 6 Z9 6 U1 1 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2011 VL 6 IS 8 BP 445 EP 452 DI 10.1002/jhm.919 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 836DX UT WOS:000296090700004 PM 21990173 ER PT J AU Wei, JN Kneeland, PP Dhaliwal, G AF Wei, Jennie Kneeland, Patrick P. Dhaliwal, Gurpreet TI Cracking the Case SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID LEVAMISOLE; AGRANULOCYTOSIS C1 [Wei, Jennie; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Kneeland, Patrick P.] Providence Reg Med Ctr, Div Hosp Med, Everett, WA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Wei, JN (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Room M987, San Francisco, CA 94143 USA. EM jennie.wei@ucsf.edu NR 16 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2011 VL 6 IS 8 BP 480 EP 483 DI 10.1002/jhm.902 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 836DX UT WOS:000296090700009 PM 21990177 ER PT J AU Kieff, DA Busaba, NY AF Kieff, D. A. Busaba, N. Y. TI Negative predictive value of normal nasal endoscopy for sinus disease as a cause of isolated facial pain SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article DE Sinusitis; Facial Pain; Computed Tomography; Nasal Endoscopy; Diagnosis ID CHRONIC RHINOSINUSITIS; CT EVALUATION; MACROLIDE; HEADACHE; MIGRAINE; SURGERY AB Objective: To determine the negative predictive value of normal nasal endoscopy in assessing paranasal sinus disease as the cause of isolated facial pain in the sinus regions. Subjects and methods: The study group comprised 42 consecutive adult patients presenting with the isolated symptom of facial pain, and a negative nasal endoscopy. Patients underwent sinus computed tomography to determine whether radiographic findings indicated a sinugenic aetiology. Results: Patients comprised 27 women and 15 men, with a median age of 38 years. Twenty patients had unilateral pain, 33 per cent had sinus radiographic findings that might explain their facial pain, and 10 per cent had imaging demonstrating mucosal disease in one or more sinuses correlating with the location of the facial pain. Thirty-one per cent had anatomical radiographic findings that could potentially obstruct the osteomeatal unit. Conclusion: Normal nasal endoscopy had a negative predictive value of 67 per cent in excluding a sinugenic cause of isolated facial pain, if radiographically determined anatomical factors and mucosal disease were both included as positive findings; this rose to more than 90 per cent if only those patients with mucosal sinus disease were considered as true positive patients. C1 [Kieff, D. A.; Busaba, N. Y.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Kieff, D. A.; Busaba, N. Y.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Busaba, N. Y.] VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Nicolas_busaba@meei.harvard.edu NR 12 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD OCT PY 2011 VL 125 IS 10 BP 1038 EP 1041 DI 10.1017/S0022215111001678 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 834OI UT WOS:000295971000008 PM 21791156 ER PT J AU Guan, D Higgs, MH Horton, LR Spain, WJ Foehring, RC AF Guan, D. Higgs, M. H. Horton, L. R. Spain, W. J. Foehring, R. C. TI Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE linopirdine; M current; motor cortex; somatosensory cortex; XE-991 ID NEUROTRANSMITTER-RELEASE ENHANCER; SPIKE FREQUENCY ADAPTATION; PERSISTENT NA+ CURRENT; AREA DOPAMINE NEURONS; LINOPIRDINE DUP 996; HIPPOCAMPAL-NEURONS; K+ CURRENT; SYMPATHETIC NEURONS; CORTICAL-NEURONS; MAMMALIAN-CELLS AB Guan D, Higgs MH, Horton LR, Spain WJ, Foehring RC. Contributions of Kv7-mediated potassium current to sub-and suprathreshold responses of rat layer II/III neocortical pyramidal neurons. J Neurophysiol 106: 1722-1733, 2011. First published June 22, 2011; doi: 10.1152/jn.00211.2011.-After block of Kv1- and Kv2-mediated K+ currents in acutely dissociated neocortical pyramidal neurons from layers II/III of rat somatosensory and motor cortex, the remaining current is slowly activating and persistent. We used whole cell voltage clamp to show that the Kv7 blockers linopirdine and XE-991 blocked a current with similar kinetics to the current remaining after combined block of Kv1- and Kv2 channels. This current was sensitive to low doses of linopirdine and activated more slowly and at more negative potentials than Kv1- or Kv2-mediated current. The Kv7-mediated current decreased in amplitude with time in whole cell recordings, but in most cells the current was stable for several minutes. Current in response to a traditional M-current protocol was blocked by muscarine, linopirdine, and XE-991. Whole cell slice recordings revealed that the Q 10 for channel deactivation was similar to 2.5. Sharp electrode current-clamp recordings from adult pyramidal cells demonstrated that block of Kv7-mediated current with XE-991 reduced rheobase, shortened the latency to firing to near rheobase current, induced more regular firing at low current intensity, and increased the rate of firing to a given current injection. XE-991 did not affect single action potentials or spike frequency adaptation. Application of XE-991 also eliminated subthreshold voltage oscillations and increased gain for low-frequency inputs (<10 Hz) without affecting gain for higher frequency inputs. These data suggest important roles for Kv7 channels in subthreshold regulation of excitability, generation of theta-frequency subthreshold oscillations, regulation of interspike intervals, and biasing selectivity toward higher frequency inputs. C1 [Guan, D.; Horton, L. R.; Foehring, R. C.] Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38163 USA. [Higgs, M. H.; Spain, W. J.] Vet Affairs Puget Sound Hlth Care Syst, Neurol, Seattle, WA USA. RP Foehring, RC (reprint author), Univ Tennessee, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA. EM rfoehrin@uthsc.edu FU National Institute of Neurological Disorders and Stroke [NS044163]; Veterans Affairs Merit Award; Veterans Affairs Epilepsy Center of Excellence FX This work was funded by National Institute of Neurological Disorders and Stroke Grant NS044163 (to R. C. Foehring) and a Veterans Affairs Merit Award and Veterans Affairs Epilepsy Center of Excellence ( to W. J. Spain). NR 86 TC 16 Z9 16 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2011 VL 106 IS 4 BP 1722 EP 1733 DI 10.1152/jn.00211.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 836EJ UT WOS:000296092000014 PM 21697446 ER PT J AU Day, ML Semple, MN AF Day, Mitchell L. Semple, Malcolm N. TI Frequency-dependent interaural delays in the medial superior olive: implications for interaural cochlear delays SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE interaural time delay; interaural time difference; sound localization; gerbil; superior olivary complex ID AUDITORY-NERVE FIBERS; TIME DIFFERENCE SENSITIVITY; SOUND LOCALIZATION; BRAIN-STEM; INFERIOR COLLICULUS; NEURAL SYNCHRONIZATION; GLYCINERGIC INHIBITION; COINCIDENCE DETECTION; PRINCIPAL NEURONS; MONGOLIAN GERBIL AB Day ML, Semple MN. Frequency-dependent interaural delays in the medial superior olive: implications for interaural cochlear delays. J Neurophysiol 106: 1985-1999, 2011. First published July 20, 2011; doi: 10.1152/jn.00131.2011.-Neurons in the medial superior olive (MSO) are tuned to the interaural time difference (ITD) of sound arriving at the two ears. MSO neurons evoke a strongest response at their best delay (BD), at which the internal delay between bilateral inputs to MSO matches the external ITD. We performed extracellular recordings in the superior olivary complex of the anesthetized gerbil and found a majority of single units localized to the MSO to exhibit BDs that shifted with tone frequency. The relation of best interaural phase difference to tone frequency revealed nonlinearities in some MSO units and others with linear relations with characteristic phase between 0.4 and 0.6 cycles. The latter is usually associated with the interaction of ipsilateral excitation and contralateral inhibition, as in the lateral superior olive, yet all MSO units exhibited evidence of bilateral excitation. Interaural cochlear delays and phase-locked contralateral inhibition are two mechanisms of internal delay that have been suggested to create frequency-dependent delays. Best interaural phase-frequency relations were compared with a cross-correlation model of MSO that incorporated interaural cochlear delays and an additional frequency-independent delay component. The model with interaural cochlear delay fit phase-frequency relations exhibiting frequency-dependent delays with precision. Another model of MSO incorporating inhibition based on realistic biophysical parameters could not reproduce observed frequency-dependent delays. C1 [Day, Mitchell L.; Semple, Malcolm N.] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Day, ML (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM day@meei.harvard.edu OI Day, Mitchell/0000-0002-2754-234X NR 58 TC 31 Z9 31 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2011 VL 106 IS 4 BP 1985 EP 1999 DI 10.1152/jn.00131.2011 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 836EJ UT WOS:000296092000033 PM 21775710 ER PT J AU Schulman-Green, D Bradley, EH Knobf, MT Prigerson, H DiGiovanna, MP McCorkle, R AF Schulman-Green, Dena Bradley, Elizabeth H. Knobf, M. Tish Prigerson, Holly DiGiovanna, Michael P. McCorkle, Ruth TI Self-Management and Transitions in Women With Advanced Breast Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Breast cancer; self-management; transitions; qualitative; exploratory; oncology; metastatic ID END-OF-LIFE; THEMES; HEALTH; CARE AB Context. Self-management involves behaviors that individuals perform to handle health conditions. Self-management may be particularly challenging during transitions-shifts from one life phase or status to another, for example, from cure-to noncure-oriented care-because they can be disruptive and stressful. Little is known about individuals' experiences with self-management, especially during transitions. Objectives. Our purpose was to describe experiences of self-management in the context of transitions among women with advanced breast cancer. Methods. We interviewed a purposive sample of 15 women with metastatic breast cancer about their self-management preferences, practices, and experiences, including how they managed transitions. Interviews were recorded and transcribed. The qualitative method of interpretive description was used to code and analyze the data. Results. Participants' mean age was 52 years (range 37-91 years); most were White (80%), married (80%), and college educated (60%). Self-management practices related to womens' health and to communication with loved ones and providers. Participants expressed a range of preferences for participation in self-management. Self-management included developing skills, becoming empowered, and creating supportive networks. Barriers to self-management included symptom distress, difficulty obtaining information, and lack of knowledge about the cancer trajectory. Women identified transitions as shifts in physical, emotional, and social well-being, as when their cancer progressed and there was a need to change therapy. Transitions often prompted changes in how actively women self-managed and were experienced as positive, negative, and neutral. Conclusion. Self-management preferences can vary. Providers should explore and revisit patients' preferences and ability to self-manage over time, particularly during transitions. J Pain Symptom Manage 2011;42:517-525. (C) 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Schulman-Green, Dena; Knobf, M. Tish; McCorkle, Ruth] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Bradley, Elizabeth H.; McCorkle, Ruth] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [DiGiovanna, Michael P.] Yale Univ, Sch Med, New Haven, CT USA. [Prigerson, Holly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prigerson, Holly] Harvard Univ, Sch Med, Boston, MA USA. RP Schulman-Green, D (reprint author), 100 Church St S,POB 9740, New Haven, CT 06536 USA. EM dena.schulman-green@yale.edu FU National Institute of Nursing Research [P20NR07806]; American Cancer Society [MRSG08-292-01-CPPB] FX This work was supported by the National Institute of Nursing Research (P20NR07806, M. Grey, Principal Investigator). Dr. Schulman-Green is supported by the American Cancer Society (MRSG08-292-01-CPPB, D. Schulman-Green, Principal Investigator). The authors declare no conflicts of interest. NR 20 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2011 VL 42 IS 4 BP 517 EP 525 DI 10.1016/j.jpainsymman.2010.12.007 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 836VO UT WOS:000296144300006 PM 21444183 ER PT J AU Schuster, J Park, CL Frisman, LK AF Schuster, Jennifer Park, Crystal L. Frisman, Linda K. TI TRAUMA EXPOSURE AND PTSD SYMPTOMS AMONG HOMELESS MOTHERS: PREDICTING COPING AND MENTAL HEALTH OUTCOMES SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; LOW-INCOME; WOMEN; DEPRESSION; ADULTS; STRATEGIES; DISTRESS; ABUSE; VICTIMIZATION; METAANALYSIS AB This longitudinal study investigated associations of posttraumatic stress disorder (PTSD) symptoms from prior trauma with coping with a subsequent stressor and with psychological symptoms. Seventy homeless mothers provided information about previous trauma history and posttraumatic stress symptoms at baseline; coping and psychological symptoms were assessed 15 months later. Results revealed moderately high levels of PTSD in this sample. PTSD symptomatology was related to increased avoidant coping, which mediated the relationship between previous trauma and subsequent psychological symptom severity. Implications for future research and interventions to reduce the negative impact of trauma in homeless women are discussed. C1 [Schuster, Jennifer; Frisman, Linda K.] Univ Connecticut, Connecticut Dept Mental Hlth & Addict Serv, Storrs, CT 06269 USA. RP Schuster, J (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM jennifer.schuster@va.gov NR 37 TC 3 Z9 3 U1 1 U2 5 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD OCT PY 2011 VL 30 IS 8 BP 887 EP 904 PG 18 WC Psychology, Clinical; Psychology, Social SC Psychology GA 835UA UT WOS:000296060300005 ER PT J AU Ng, K Ogino, S Meyerhardt, JA Chan, JA Chan, AT Niedzwiecki, D Hollis, D Saltz, LB Mayer, RJ Benson, AB Schaefer, PL Whittom, R Hantel, A Goldberg, RM Bertagnolli, MM Venook, AP Fuchs, CS AF Ng, Kimmie Ogino, Shuji Meyerhardt, Jeffrey A. Chan, Jennifer A. Chan, Andrew T. Niedzwiecki, Donna Hollis, Donna Saltz, Leonard B. Mayer, Robert J. Benson, Al B., III Schaefer, Paul L. Whittom, Renaud Hantel, Alexander Goldberg, Richard M. Bertagnolli, Monica M. Venook, Alan P. Fuchs, Charles S. TI Relationship Between Statin Use and Colon Cancer Recurrence and Survival: Results From CALGB 89803 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRANSFERASE INHIBITOR R115777; KRAS MUTATION DETECTION; COLORECTAL-CANCER; PHASE-II; CHOLESTEROL LEVELS; GROWTH-FACTOR; FOLLOW-UP; RISK; DISEASE; PREVENTION AB Background Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown. Methods We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided. Results Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (P(trend) = .63, .63, and .59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (P(interaction) = .84, .67, and .98 for DFS, RFS, and OS, respectively). Conclusion Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status. J Natl Cancer Inst 2011; 103: 1540-1551 C1 [Ng, Kimmie; Ogino, Shuji; Meyerhardt, Jeffrey A.; Chan, Jennifer A.; Mayer, Robert J.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg Oncol, Boston, MA 02115 USA. [Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Niedzwiecki, Donna; Hollis, Donna] Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Benson, Al B., III] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Schaefer, Paul L.] Toledo Community Hosp Oncol Program, Toledo, OH USA. [Whittom, Renaud] Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, Canada. [Hantel, Alexander] Edward Canc Ctr, Naperville, IL USA. [Goldberg, Richard M.] Univ N Carolina, Dept Hematol Oncol, Chapel Hill, NC USA. [Venook, Alan P.] Univ Calif San Francisco, Dept Med, Div Med Oncol, San Francisco, CA USA. RP Ng, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM kng4@partners.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute at the National Institutes of Health [P50CA127003, T32CA009001-34, CA31946, CA33601]; American Society of Clinical Oncology; Bank of America; Pharmacia & Upjohn Company (now Pfizer Oncology); [CA71323]; [CA45418]; [CA04326]; [CA47577]; [CA77597]; [CA29165]; [CA45389]; [CA35279]; [CA32291]; [CA77651]; [CA04457]; [CA35421]; [CA08025]; [CA59518]; [CA45808]; [CA21060]; [CA77658]; [CA11789]; [CA41287]; [CA74811]; [CA47642]; [CA31983]; [CA37135]; [CA16450]; [CA12046]; [CA77298]; [CA47559]; [CA47555]; [CA77406]; [CA03927]; [CA26806]; [CA77440] FX This work was supported by the National Cancer Institute at the National Institutes of Health (P50CA127003 and T32CA009001-34 to K.N.); American Society of Clinical Oncology Career Development Award (K.N.); The Charles A. King Trust Postdoctoral Fellowship Award, Bank of America, Co-Trustee (K.N.); as well as by Pharmacia & Upjohn Company (now Pfizer Oncology). The research for CALGB 89803 was also supported, in part, by grants from the National Cancer Institute at the National Institutes of Health (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, Chairman) and to the CALGB Statistical Center (Stephen George, CA33601).; Primary contacts and clinical centers that participated in the CALGB clinical trial included Lee S. Schwartzberg, Baptist Cancer Institute Community Clinical Oncology Program, TN (supported by CA71323); Stephen Grubbs, Christiana Care Health Services, Inc, Community Clinical Oncology Program, Wilmington, DE (supported by CA45418); Harold J. Burstein, Dana-Farber Cancer Institute, Boston, MA (supported by CA32291); Konstantin Dragnev, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH (supported by CA04326); Jeffrey Crawford, Duke University Medical Center, Durham, NC (supported by CA47577); Minetta C. Liu, Georgetown University Medical Center, Washington, DC (supported by CA77597); Jeffrey K. Giguere, Cancer Centers of the Carolinas, Greenville, SC (supported by CA29165); Jeffrey Kirshner, Hematology-Oncology Associates of Central New York Community Clinical Oncology Program, Syracuse, NY (supported by CA45389); Kanti R. Rai, Long Island Jewish Medical Center, Lake Success, NY (supported by CA35279); Jeffrey W. Clark, Massachusetts General Hospital, Boston, MA (supported by CA32291); Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY (supported by CA77651); Lewis R. Silverman,. D., Mount Sinai School of Medicine, New York, NY (supported by CA04457); John A. Ellerton, Nevada Cancer Research Foundation CCOP, Las Vegas, NV (supported by CA35421); William Sikov, Rhode Island Hospital, Providence, RI (supported by CA08025); Ellis Levine, Roswell Park Cancer Institute, Buffalo, NY (supported by CA59518); James N. Atkins, Southeast Cancer Control Consortium, Inc, CCOP, Goldsboro, NC (supported by CA45808); Stephen L. Graziano, State University of New York Upstate Medical University, Syracuse, NY (supported by CA21060); Clara D. Bloomfield, The Ohio State University Medical Center, Columbus, OH (supported by CA77658); Barbara A. Parker, University of California at San Diego, San Diego, CA (supported by CA11789); Hedy L. Kindler, University of Chicago, Chicago, IL (supported by CA41287); David J. Peace, University of Illinois MBCCOP, Chicago, IL (supported by CA74811); Daniel A. Vaena, University of Iowa, Iowa City, IA (supported by CA47642); Martin Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD (supported by CA31983); William V. Walsh, University of Massachusetts Medical School, Worcester, MA (supported by CA37135); Bruce A. Peterson, University of Minnesota, Minneapolis, MN (supported by CA16450); Michael C. Perry, University of Missouri/Ellis Fischel Cancer Center, Columbia, MO (supported by CA12046); Anne Kessinger, University of Nebraska Medical Center, Omaha, NE (supported by CA77298); Thomas C. Shea, University of North Carolina at Chapel Hill, Chapel Hill, NC (supported by CA47559); Harvey B. Niell, University of Tennessee Memphis, Memphis, TN (supported by CA47555); Marc S. Greenblatt, University of Vermont, Burlington, VT (supported by CA77406); David D. Hurd, Wake Forest University School of Medicine, Winston-Salem, NC (supported by CA03927); Brendan M. Weiss, Walter Reed Army Medical Center, Washington, DC (supported by CA26806); Nancy Bartlett, Washington University School of Medicine, St. Louis, MO (supported by CA77440); John Leonard, Weill Medical College of Cornell University, New York, NY (supported by CA07968). NR 51 TC 32 Z9 34 U1 0 U2 3 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 OCT PY 2011 VL 103 IS 20 BP 1540 EP 1551 DI 10.1093/jnci/djr307 PG 12 WC Oncology SC Oncology GA 836JJ UT WOS:000296107700011 PM 21849660 ER PT J AU Jackson, JC Sinnott, PL Marx, BP Murdoch, M Sayer, NA Alvarez, JM Greevy, RA Schnurr, PP Friedman, MJ Shane, AC Owen, RR Keane, TM Speroff, T AF Jackson, James C. Sinnott, Patricia L. Marx, Brian P. Murdoch, Maureen Sayer, Nina A. Alvarez, JoAnn M. Greevy, Robert A. Schnurr, Paula P. Friedman, Matthew J. Shane, Andrea C. Owen, Richard R. Keane, Terence M. Speroff, Theodore TI Variation in Practices and Attitudes of Clinicians Assessing PTSD-Related Disability Among Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; US VETERANS; EXPOSURE AB One hundred thirty-eight Veterans Affairs mental health professionals completed a 128-item Posttraumatic Stress Disorder (PTSD) Practice Inventory that asked about their practices and attitudes related to disability assessment of PTSD. Results indicate strikingly wide variation in the attitudes and practices of clinicians conducting disability assessments for PTSD. In a high percentage of cases, these attitudes and practices conflict with best-practice guidelines. Specifically, 59% of clinicians reported rarely or never using testing, and only 17% indicated routinely using standardized clinical interviews. Less than 1% of respondents reported using functional assessment scales. C1 [Jackson, James C.] Vanderbilt Univ, Sch Med, Div Allergy Pulm Crit Care Med,Ctr Hlth Serv Res, VA Tennessee Valley Healthcare Syst,GRECC, Nashville, TN 37203 USA. [Sinnott, Patricia L.; Shane, Andrea C.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, San Francisco, CA USA. [Sinnott, Patricia L.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. [Marx, Brian P.; Keane, Terence M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Murdoch, Maureen; Sayer, Nina A.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Murdoch, Maureen; Sayer, Nina A.] Minneapolis VA Med Ctr, Gen Internal Med Sect, Minneapolis, MN USA. [Murdoch, Maureen] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Alvarez, JoAnn M.; Greevy, Robert A.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN USA. [Schnurr, Paula P.] Dartmouth Med Sch, Dept Psychiat, Dartmouth, NS, Canada. [Friedman, Matthew J.] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Dartmouth, NS, Canada. [Owen, Richard R.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Speroff, Theodore] VA Tennessee Valley Healthcare Syst, Ctr Hlth Serv Res, GRECC, Dept Biostat, Nashville, TN USA. [Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN USA. RP Jackson, JC (reprint author), Vanderbilt Univ Sch Med, Div Allergy Pulm Crit Care Med, 6th Floor MCE,Suite 6100, Nashville, TN 37232 USA. EM james.c.jackson@vanderbilt.edu RI Schueter, nicos/A-3625-2014; Sayer, Nina/E-3249-2016 NR 14 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2011 VL 24 IS 5 SI SI BP 609 EP 613 DI 10.1002/jts.20688 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 835IS UT WOS:000296030700019 PM 21913226 ER PT J AU Bonsignori, M Hwang, KK Chen, X Tsao, CY Morris, L Gray, E Marshall, DJ Crump, JA Kapiga, SH Sam, NE Sinangil, F Pancera, M Yang, YP Zhang, BS Zhu, J Kwong, PD O'Dell, S Mascola, JR Wu, L Nabel, GJ Phogat, S Seaman, MS Whitesides, JF Moody, MA Kelsoe, G Yang, XZ Sodroski, J Shaw, GM Montefiori, DC Kepler, TB Tomaras, GD Alam, SM Liao, HX Haynes, BF AF Bonsignori, Mattia Hwang, Kwan-Ki Chen, Xi Tsao, Chun-Yen Morris, Lynn Gray, Elin Marshall, Dawn J. Crump, John A. Kapiga, Saidi H. Sam, Noel E. Sinangil, Faruk Pancera, Marie Yang Yongping Zhang, Baoshan Zhu, Jiang Kwong, Peter D. O'Dell, Sijy Mascola, John R. Wu, Lan Nabel, Gary J. Phogat, Sanjay Seaman, Michael S. Whitesides, John F. Moody, M. Anthony Kelsoe, Garnett Yang, Xinzhen Sodroski, Joseph Shaw, George M. Montefiori, David C. Kepler, Thomas B. Tomaras, Georgia D. Alam, S. Munir Liao, Hua-Xin Haynes, Barton F. TI Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; EPSTEIN-BARR-VIRUS; B-CELL RESPONSES; CRYSTAL-STRUCTURE; PG16; PG9; INDIVIDUALS; DIVERSITY; INFECTION AB V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B. 9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies. C1 [Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Crump, John A.] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA. [Montefiori, David C.; Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Kelsoe, Garnett] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Kepler, Thomas B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC 27710 USA. [Morris, Lynn; Gray, Elin] Natl Inst Communicable Dis, Johannesburg, South Africa. [Crump, John A.] Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA. [Crump, John A.; Sam, Noel E.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Crump, John A.] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania. [Kapiga, Saidi H.] London Sch Hyg & Trop Med, London WC1, England. [Sinangil, Faruk] Global Solut Infect Dis, San Francisco, CA USA. [Pancera, Marie; Yang Yongping; Zhang, Baoshan; Zhu, Jiang; Kwong, Peter D.; O'Dell, Sijy; Mascola, John R.; Wu, Lan; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Phogat, Sanjay] IAVI, AIDS Vaccine Design & Dev Lab, Brooklyn, NY USA. [Seaman, Michael S.; Yang, Xinzhen] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Bonsignori, M (reprint author), Duke Univ, Med Ctr, Dept Med, Duke Human Vaccine Inst, MSRB 2,POB 103020,2 Genome Court, Durham, NC 27710 USA. EM mattia.bonsignori@duke.edu; barton.haynes@duke.edu RI Tomaras, Georgia/J-5041-2016; OI Kepler, Thomas/0000-0002-1383-6865; Moody, Tony/0000-0002-3890-5855; Gray, Elin/0000-0002-8613-3570 FU NIH [AI64518]; NIH, NIAID, the Division of AIDS with the Center for HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; Bill and Melinda Gates Foundation; Vaccine Research Center, NIAID, NIH; International AIDS Vaccine Initiative FX Single-cell sorting was performed in the Research Flow Cytometry Core Facility at the Duke Human Vaccine Institute, partly supported by the NIH-funded Duke Center for AIDS Research (CFAR) (grant AI64518), and directed by J.F.W. This work was supported by the NIH, NIAID, the Division of AIDS with the Center for HIV/AIDS Vaccine Immunology (CHAVI) (grant U19 AI067854); by a Collaboration for AIDS Vaccine Discovery grant to B.F.H. from the Bill and Melinda Gates Foundation; in part by a grant from the intramural research program of the Vaccine Research Center, NIAID, NIH, to J.R.M., P.D.K., and G.J.N.; and by a grant from the International AIDS Vaccine Initiative to J.R.M., P.D.K., and S.P. NR 63 TC 216 Z9 219 U1 0 U2 20 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 OCT PY 2011 VL 85 IS 19 BP 9998 EP 10009 DI 10.1128/JVI.05045-11 PG 12 WC Virology SC Virology GA 837ZH UT WOS:000296253900032 PM 21795340 ER PT J AU Moldt, B Schultz, N Dunlop, DC Alpert, MD Harvey, JD Evans, DT Poignard, P Hessell, AJ Burton, DR AF Moldt, Brian Schultz, Niccole Dunlop, D. Cameron Alpert, Michael D. Harvey, Jackson D. Evans, David T. Poignard, Pascal Hessell, Ann J. Burton, Dennis R. TI A Panel of IgG1 b12 Variants with Selectively Diminished or Enhanced Affinity for Fc gamma Receptors To Define the Role of Effector Functions in Protection against HIV SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIBODY-MEDIATED PROTECTION; DEPENDENT CELLULAR CYTOTOXICITY; MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES; IN-VITRO; PASSIVE TRANSFER; IMMUNOGLOBULIN-G; INFECTION; MACAQUES AB Passive transfer of neutralizing antibodies is effective in protecting rhesus macaques against simian/human immunodeficiency virus (SHIV) challenge. In addition to neutralization, effector functions of the crystallizable fragment (Fc) of antibodies are involved in antibody-mediated protection against a number of viruses. We recently showed that interaction between the Fc fragment of the broadly neutralizing antibody IgG1 b12 and cellular Fc gamma receptors (Fc gamma Rs) plays an important role in protection against SHIV infection in rhesus macaques. The specific nature of this Fc-dependent protection is largely unknown. To investigate, we generated a panel of 11 IgG1 b12 antibody variants with selectively diminished or enhanced affinity for the two main activating Fc gamma Rs, Fc gamma RIIa and Fc gamma RIIIa. All 11 antibody variants bind gp120 and neutralize virus as effectively as does wild-type b12. Binding studies using monomeric (enzyme-linked immunosorbent assay [ELISA] and surface plasmon resonance [SPR]) and cellularly expressed Fc gamma receptors show decreased (up to 5-fold) and increased (up to 90-fold) binding to Fc gamma RIIa and Fc gamma RIIIa with this newly generated panel of antibodies. In addition, there was generally a good correlation between b12 variant affinity for Fc gamma receptor and variant function in antibody-dependent cell-mediated virus inhibition (ADCVI), phagocytosis, NK cell activation assays, and antibody-dependent cellular cytotoxicity (ADCC) assays. In future studies, these b12 variants will enable the investigation of the protective role of individual Fc gamma Rs in HIV infection. C1 [Moldt, Brian; Schultz, Niccole; Dunlop, D. Cameron; Poignard, Pascal; Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Moldt, Brian; Schultz, Niccole; Dunlop, D. Cameron; Poignard, Pascal; Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Alpert, Michael D.; Harvey, Jackson D.; Evans, David T.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Primate Res Ctr, Southborough, MA 01772 USA. [Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY USA. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Burton, Dennis R.] Harvard, Boston, MA USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu RI poignard, pascal/N-6678-2013 FU Alfred Benzon Foundation; NIH [AI055332]; International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium; Ragon Institute of MGH, MIT, and Harvard FX This work was funded by a fellowship to B. M. from the Alfred Benzon Foundation and grants from NIH (AI055332), the International AIDS Vaccine Initiative through the Neutralizing Antibody Consortium, and the Ragon Institute of MGH, MIT, and Harvard to D.R.B. NR 50 TC 29 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2011 VL 85 IS 20 BP 10572 EP 10581 DI 10.1128/JVI.05541-11 PG 10 WC Virology SC Virology GA 837ZJ UT WOS:000296254100014 PM 21849450 ER PT J AU Andrabi, S Hwang, JH Choe, JK Roberts, TM Schaffhausen, BS AF Andrabi, Shaida Hwang, Justin H. Choe, Jennifer Kean Roberts, Thomas M. Schaffhausen, Brian S. TI Comparisons between Murine Polyomavirus and Simian Virus 40 Show Significant Differences in Small T Antigen Function SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN PHOSPHATASE 2A; SV40 SMALL-T; HUMAN CELL-TRANSFORMATION; SMALL TUMOR-ANTIGEN; FORKHEAD TRANSCRIPTION FACTOR; CYCLIN-A PROMOTER; MIDDLE-T; PHOSPHATIDYLINOSITOL 3-KINASE; MOUSE FIBROBLASTS; SUBUNIT INTERACTION AB Although members of a virus family produce similar gene products, those products may have quite different functions. Simian virus 40 (SV40) large T antigen (LT), for example, targets p53 directly, but murine polyomavirus LT does not. SV40 small T antigen (SVST) has received considerable attention because of its ability to contribute to transformation of human cells. Here, we show that there are major differences between SVST and polyomavirus small T antigen (POLST) in their effects on differentiation, transformation, and cell survival. Both SVST and POLST induce cell cycle progression. However, POLST also inhibits differentiation of 3T3-L1 preadipocytes and C2C12 myoblasts. Additionally, POLST induces apoptosis of mouse embryo fibroblasts. SVST reduces the proapoptotic transcriptional activity of FOXO1 through phosphorylation. On the other hand, SVST complements large T antigen and Ras for the transformation of human mammary epithelial cells (HMECs), but POLST does not. Mechanistically, the differences between SVST and POLST may lie in utilization of protein phosphatase 2A (PP2A). POLST binds both A alpha and A beta scaffolding subunits of PP2A while SVST binds only A alpha. Knockdown of A beta could mimic POLST-induced apoptosis. The two small T antigens can target different proteins for dephosphorylation. POLST binds and dephosphorylates substrates, such as lipins, that SVST does not. C1 [Andrabi, Shaida; Hwang, Justin H.; Choe, Jennifer Kean; Schaffhausen, Brian S.] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Roberts, Thomas M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Schaffhausen, BS (reprint author), Tufts Univ, Sch Med, Dept Biochem, 136 Harrison Ave, Boston, MA 02111 USA. EM brian.schaffhausen@tufts.edu FU NIH [CA34722, CA50661] FX This work was supported by NIH grants to B. S. S. (CA34722 and CA50661) and T. M. R. (CA50661). NR 79 TC 14 Z9 14 U1 1 U2 5 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 OCT PY 2011 VL 85 IS 20 BP 10649 EP 10658 DI 10.1128/JVI.05034-11 PG 10 WC Virology SC Virology GA 837ZJ UT WOS:000296254100021 PM 21835797 ER PT J AU Kopcow, H Cerdeira, S Burke, S Lo, A Royle, C Thadhani, R Karumanchi, A AF Kopcow, Hernan Cerdeira, Sofia Burke, Suzanne Lo, Agnes Royle, Caroline Thadhani, Rabi Karumanchi, Ananth TI Natural Killer Cells and Preeclampsia SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Kopcow, Hernan; Cerdeira, Sofia; Burke, Suzanne; Lo, Agnes; Royle, Caroline; Karumanchi, Ananth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Thadhani, Rabi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Karumanchi, Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1394 EP 1395 PG 2 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 833IQ UT WOS:000295877900033 ER PT J AU Mahalingaiah, S Missmer, SA Maity, A Williams, PL Meeker, JD Berry, K Ehrlich, S Perry, MJ Cramer, DW Hauser, R AF Mahalingaiah, Shruthi Missmer, Stacey A. Maity, Arnab Williams, Paige L. Meeker, John D. Berry, Katharine Ehrlich, Shelley Perry, Melissa J. Cramer, Daniel W. Hauser, Russ TI Association of Hexachlorobenzene (HCB), Dichlorodiphenyltrichloroethane (DDT), and Dichlorodiphenyldichloroethane (DDE) with In Vitro Fertilization (IVF) Outcomes. SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Mahalingaiah, Shruthi] Boston Univ, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Mahalingaiah, Shruthi; Missmer, Stacey A.; Berry, Katharine; Cramer, Daniel W.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Missmer, Stacey A.; Hauser, Russ] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Maity, Arnab] N Carolina State Univ, Dept Stat, Raleigh, NC USA. [Williams, Paige L.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Ehrlich, Shelley; Perry, Melissa J.; Hauser, Russ] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Perry, Melissa J.] George Washington Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA. [Hauser, Russ] Harvard Univ, Sch Med, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Cambridge, MA 02138 USA. [Hauser, Russ] Harvard Univ, Sch Med, In Vitro Fertilizat Unit, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2011 VL 20 IS 10 BP 1396 EP 1396 PG 1 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 833IQ UT WOS:000295877900038 ER PT J AU Lawson, EA Miller, KK Blum, JI Meenaghan, E Misra, M Eddy, KT Herzog, DB Klibanski, A AF Lawson, Elizabeth A. Miller, Karen K. Blum, Justine I. Meenaghan, Erinne Misra, Madhusmita Eddy, Kamryn T. Herzog, David B. Klibanski, Anne TI Hypoleptinemia in Anorexia Nervosa and Hypothalamic Amenorrhea is Associated with Symptoms of Depression, Independent of Body Mass Index SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Lawson, Elizabeth A.; Miller, Karen K.; Blum, Justine I.; Meenaghan, Erinne; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.; Herzog, David B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2011 VL 20 IS 10 BP 1405 EP 1405 PG 1 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 833IQ UT WOS:000295877900071 ER PT J AU Holsen, LM Lee, JH Spaeth, SB Ogden, LA Klibanski, A Whitfield-Gabrieli, S Sloan, R Goldstein, JM AF Holsen, Laura M. Lee, Jong-Hwan Spaeth, Sarah B. Ogden, Lauren A. Klibanski, Anne Whitfield-Gabrieli, Susan Sloan, Richard Goldstein, Jill M. TI Hypoactivation of the Stress Response Circuitry in Depression Associated with Loss of Parasympathetic Control of the Heart and Dysfunction in the HPG Axis: A Combined Analysis of fMRI and Heart Rate Variability SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Holsen, Laura M.; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Holsen, Laura M.; Spaeth, Sarah B.; Ogden, Lauren A.; Goldstein, Jill M.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Lee, Jong-Hwan] Korea Univ, Dept Brain & Cognit Engn, Seoul, South Korea. [Klibanski, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan] MIT, Athinoula Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA. [Sloan, Richard] Columbia Univ, Med Ctr, Dept Behav Med, New York, NY 10027 USA. [Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2011 VL 20 IS 10 BP 1408 EP 1409 PG 2 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 833IQ UT WOS:000295877900081 ER PT J AU Bae, J Carrasco, R Lee, AH Prabhala, R Tai, YT Anderson, KC Munshi, NC AF Bae, J. Carrasco, R. Lee, A-H Prabhala, R. Tai, Y-T Anderson, K. C. Munshi, N. C. TI Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma SO LEUKEMIA LA English DT Article DE myeloma; XBP1; immunotherapy ID UNFOLDED PROTEIN RESPONSE; PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; MESSENGER-RNA; B-CELL; REACTIVE CTL; TRANSPLANTATION; IMMUNOTHERAPY; INDUCTION; PROMOTER AB The purpose of these studies was to identify human leukocyte antigen (HLA)-A2(+) immunogenic peptides derived from XBP1 antigens to induce a multiple myeloma (MM)-specific immune response. Six native peptides from non-spliced XBP1 antigen and three native peptides from spliced XBP1 antigen were selected and evaluated for their HLA-A2 specificity. Among them, XBP1(184-192), XBP1 SP196-204 and XBP1 SP367-375 peptides showed the highest level of binding affinity, but not stability to HLA-A2 molecules. Novel heteroclitic XBP1 peptides, YISPWILAV or YLFPQLISV, demonstrated a significant improvement in HLA-A2 stability from their native XBP1(184-192) or XBP1 SP367-375 peptide, respectively. Cytotoxic T lymphocytes generated by repeated stimulation of CD3(+) T cells with each HLA-A2-specific heteroclitic peptide showed an increased percentage of CD8(+) (cytotoxic) and CD69(+)/ CD45RO(+) (activated memory) T cells and a lower percentage of CD4(+) (helper) and CD45RA(+)/CCR7(+) (naive) T cells, which were distinct from the control T cells. Functionally, the cytotoxic T lymphocytes (CTL) demonstrated MM-specific and HLA-A2-restricted proliferation, interferon-gamma secretion and cytotoxic activity in response to MM cell lines and importantly, cytotoxicity against primary MM cells. These data demonstrate the distinct immunogenic characteristics of unique heteroclitic XBP1 peptides, which induce MM-specific CTLs and highlights their potential application for immunotherapy to treat the patients with MM or its pre-malignant condition. Leukemia (2011) 25, 1610-1619; doi:10.1038/leu.2011.120; published online 10 June 2011 C1 [Bae, J.; Carrasco, R.; Prabhala, R.; Tai, Y-T; Anderson, K. C.; Munshi, N. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bae, J.; Carrasco, R.; Lee, A-H; Prabhala, R.; Tai, Y-T; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Boston, MA USA. [Prabhala, R.; Munshi, N. C.] VA Boston Healthcare Syst, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU NIH [PO1-155258, P50-100707, PO1-78378, RO1-129295]; Department of Veteran's Affairs; [RO1-50947] FX This work is supported by NIH grants PO1-155258 (NCM); P50-100707, and PO1-78378, (KCA and NCM), RO1-129295 and Department of Veteran's Affairs merit review award (NCM) and RO1-50947 (KCA). NR 48 TC 20 Z9 22 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2011 VL 25 IS 10 BP 1610 EP 1619 DI 10.1038/leu.2011.120 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 836WG UT WOS:000296147300011 PM 21660045 ER PT J AU Herzog, GF Caffee, MW Faestermann, T Hertenberger, R Korschinek, G Leya, I Reedy, RC Sisterson, JM AF Herzog, Gregory F. Caffee, Marc W. Faestermann, Thomas Hertenberger, R. Korschinek, Gunther Leya, Ingo Reedy, Robert C. Sisterson, J. M. TI Cross sections from 5 to 35 MeV for the reactions Mg-nat(He-3,x)Al-26, Al-27(He-3,x)Al-26, Ca-nat(He-3,x)Ca-41, and Ca-nat(He-3,x)Cl-36: Implications for early irradiation in the solar system SO METEORITICS & PLANETARY SCIENCE LA English DT Article ID COSMIC-RAY PARTICLES; SHORT-LIVED NUCLIDES; ALUMINUM-RICH INCLUSIONS; COSMOGENIC NUCLIDES; LOW-ENERGY; AL-26; METEORITES; ELEMENTS; BE-10; AL AB Cross sections were measured for the nuclear reactions Mg-nat(He-3,x)Al-26, Al-27(He-3,x) Al-26, Ca-nat(He-3,x)Ca-41, and Ca-nat(He-3,x)Cl-36 in the energy region from approximately 5-35 MeV. The rates of these reactions are important for studies of early solar system irradiation scenarios. The Al-26, Cl-36, and Ca-41 were separated chemically, and the numbers of atoms produced in each reaction channel were measured using accelerator mass spectrometry (AMS). From these results, 26 cross sections were determined and compared with predictions of the TALYS code. Agreement is within 40% for most cross sections. Our measurements were used to model the production of Be-7, Be-10, Al-26, and Ca-41 in the early solar system. For projectiles H-1, He-3, and He-4, we assumed energy spectra of the general form E-alpha. For a wide range of parameterizations, the modeled ratios of Be-7/Be and Be-10/Be on the one hand and of Al-26/Al-27 and Ca-41/Ca on the other are coupled because the excitation functions for the relevant nuclear reactions have similar shapes. Modeling of a closed system with the constraint that Be-10/Be-9 = 0.001 fails to reproduce simultaneously the range of Be-7/Be-9, Al-26/Al-27, and Ca-41/Ca ratios inferred for the early solar system from studies of meteorites. C1 [Herzog, Gregory F.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Caffee, Marc W.] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Faestermann, Thomas; Korschinek, Gunther] Tech Univ Munich, Fak Phys, D-85748 Garching, Germany. [Hertenberger, R.] Univ Munich, Fak Phys, D-85748 Garching, Germany. [Leya, Ingo] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland. [Reedy, Robert C.] Planetary Sci Inst, Los Alamos, NM 87544 USA. [Sisterson, J. M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Herzog, GF (reprint author), Rutgers State Univ, Dept Chem & Chem Biol, 610 Taylor Rd, Piscataway, NJ 08854 USA. EM herzog@rutchem.rutgers.edu RI Caffee, Marc/K-7025-2015; OI Caffee, Marc/0000-0002-6846-8967; Reedy, Robert/0000-0002-2189-1303 FU NASA [NNG05GJ28G, NNG06GF66G]; Swiss National Science Foundation FX We thank Gene Hall for assistance with target preparation and Jean Duprat for sharing results from his TALYS calculations. We thank Tim Jull and an anonymous reviewer for helpful comments. This work was supported in part by NASA Origins grant NNG05GJ28G (G. F. H., J. M. S., M. W. C.), Cosmochemistry grant NNG06GF66G (R. C. R.), and the Swiss National Science Foundation (I. L.). NR 61 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1086-9379 J9 METEORIT PLANET SCI JI Meteorit. Planet. Sci. PD OCT PY 2011 VL 46 IS 10 BP 1427 EP 1446 DI 10.1111/j.1945-5100.2011.01236.x PG 20 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 837YB UT WOS:000296247400001 ER PT J AU Chan, AT AF Chan, Andrew T. TI Turning up the heat on colorectal cancer SO NATURE MEDICINE LA English DT Editorial Material ID MICROSATELLITE-INSTABILITY; COLON-CANCER; ADJUVANT CHEMOTHERAPY; MISMATCH REPAIR; PROGNOSIS; SURVIVAL; THERAPY; BENEFIT; GENE C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM achan@partners.org NR 12 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1186 EP 1188 DI 10.1038/nm.2500 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100027 PM 21988992 ER PT J AU Walker, BD Ahmed, R Plotkin, S AF Walker, Bruce D. Ahmed, Rafi Plotkin, Stanley TI Moving ahead an HIV vaccine Use both arms to beat HIV SO NATURE MEDICINE LA English DT Editorial Material ID NEUTRALIZING ANTIBODIES; INFECTION; TRIAL; CHALLENGE; IMMUNITY; BROAD; SIV C1 [Walker, Bruce D.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Massachusetts Gen Hosp, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Plotkin, Stanley] Univ Penn & Vaxconsult, Doylestown, PA USA. RP Walker, BD (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Massachusetts Gen Hosp, Boston, MA USA. EM bwalker@partners.org NR 17 TC 29 Z9 29 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2011 VL 17 IS 10 BP 1194 EP 1195 DI 10.1038/nm.2529 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 835FW UT WOS:000296022100031 PM 21988996 ER PT J AU van Es, ACGM van der Grond, J de Craen, AJM Westendorp, RGJ Bollen, ELEM Blauw, GJ Greenberg, SM van Buchem, MA AF van Es, A. C. G. M. van der Grond, J. de Craen, A. J. M. Westendorp, R. G. J. Bollen, E. L. E. M. Blauw, G. J. Greenberg, S. M. van Buchem, M. A. CA PROSPER Study Grp TI Cerebral microbleeds and cognitive functioning in the PROSPER study SO NEUROLOGY LA English DT Article ID MR-IMAGES; INTRACEREBRAL HEMORRHAGE; BRAIN MICROBLEEDS; STROKE; DYSFUNCTION; DESIGN AB Objectives: Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. Methods: For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. Results: We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. Conclusions: Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning. Neurology (R) 2011;77:1446-1452 C1 [van Es, A. C. G. M.; van der Grond, J.; van Buchem, M. A.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [de Craen, A. J. M.; Westendorp, R. G. J.; Blauw, G. J.] Leiden Univ, Med Ctr, Dept Gen Internal Med, Sect Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. [Bollen, E. L. E. M.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. [Greenberg, S. M.] Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. RP van Es, ACGM (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C2-S,POB 9600, NL-2300 RC Leiden, Netherlands. EM A.C.G.M.van_Es@LUMC.nl FU National Genomics Initiative; EC; IOP; NWO; NIH; Alzheimer's Association FX A. C. G. M. van Es, Dr. van der Grond, and Dr. J.M. de Craen report no disclosures. Dr. Westendorp serves on the editorial boards of Experimental Gerontology, Ageing Research Reviews, The Netherlands Journal of Internal Medicine, and Age and Ageing; and receives research support from National Genomics Initiative, EC/FP6, IOP, and NWO; and is executive director of Leyden Academy on Vitality and Ageing. Dr. Bollen and Dr. Blauw report no disclosures. Dr. Greenberg serves on a data safety monitoring board for the NIH/NINDS; has received speaker honoraria from Esteve, Medtronics, Inc., and Pfizer Inc; serves on the editorial boards of Neurology (R), Stroke, Cerebrovascular Disease, and the Journal of Alzheimer's Disease and Other Dementias; has served as a consultant for Roche, Janssen Alzheimer Immunotherapy, and Bristol-Myers Squibb; and has received/receives research support from the NIH and the Alzheimer's Association. Dr. van Buchem reports no disclosures. NR 23 TC 28 Z9 28 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2011 VL 77 IS 15 BP 1446 EP 1452 DI 10.1212/WNL.0b013e318232ab1d PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 835PI UT WOS:000296047900010 PM 21956727 ER PT J AU Vaishnaw, AK Cervantes, A Alsina, M Tabernero, J Infante, JR LoRusso, P Shapiro, GI Paz-Ares, L Schwartz, G Weiss, G Falzone, R Hill, J Cehelsky, J White, A Toudjarska, I Bumcrot, D Meyers, R Hinkle, G Svrzikapa, N Sah, DW Burris, HA Gollob, JA AF Vaishnaw, A. K. Cervantes, A. Alsina, M. Tabernero, J. Infante, J. R. LoRusso, P. Shapiro, G. I. Paz-Ares, L. Schwartz, G. Weiss, G. Falzone, R. Hill, J. Cehelsky, J. White, A. Toudjarska, I. Bumcrot, D. Meyers, R. Hinkle, G. Svrzikapa, N. Sah, D. W. Burris, H. A. Gollob, J. A. TI RNAi IN HUMANS: PHASE I DOSE-ESCALATION STUDY OF ALN-VSP02, A NOVEL RNAi THERAPEUTIC FOR SOLID TUMORS WITH LIVER INVOLVEMENT SO NUCLEIC ACID THERAPEUTICS LA English DT Meeting Abstract CT 7th Annual Meeting of the Oligonucleotide-Therapeutics-Society CY SEP 08-10, 2011 CL Copenhagen, DENMARK SP Oligonucleotide Therapeut Soc C1 [Vaishnaw, A. K.; Falzone, R.; Hill, J.; Cehelsky, J.; White, A.; Toudjarska, I.; Bumcrot, D.; Meyers, R.; Hinkle, G.; Svrzikapa, N.; Sah, D. W.; Gollob, J. A.] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA. [Cervantes, A.] Hosp Clin Univ Valencia, Valencia, Spain. [Alsina, M.; Tabernero, J.] Hosp Univ Vall dHebron, Barcelona, Spain. [Infante, J. R.; Burris, H. A.] Sarah Cannon Res Inst, Nashville, TN USA. [LoRusso, P.] Karmanos Canc Ctr, Detroit, MI USA. [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paz-Ares, L.] Hosp Virgen del Rocio, Seville, Spain. [Schwartz, G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Weiss, G.] Scottsdale Healthcare, TGen Clin Res Serv, Scottsdale, AZ USA. EM avaishnaw@alnylam.com RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2159-3337 J9 NUCLEIC ACID THER JI Nucl. Acid Ther. PD OCT PY 2011 VL 21 IS 5 BP A44 EP A44 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Research & Experimental Medicine GA 837UZ UT WOS:000296231700096 ER PT J AU Ligibel, J AF Ligibel, Jennifer TI Obesity and Breast Cancer SO ONCOLOGY-NEW YORK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SURVIVAL; BODY-MASS INDEX; GROWTH-FACTOR-I; PHYSICAL-ACTIVITY; WEIGHT-GAIN; LOW-FAT; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; FASTING INSULIN AB Obesity is a growing health problem in the United States and, increasingly, around the world. Excess body weight has been linked to an increased risk of postmenopausal breast cancer, and growing evidence also suggests that obesity is associated with poor prognosis in women diagnosed with early-stage breast cancer. Dozens of studies demonstrate that women who are overweight or obese at the time of breast cancer diagnosis are at increased risk of cancer recurrence and death compared with leaner women, and some evidence suggests that women who gain weight after breast cancer diagnosis may also be at increased risk of poor outcomes. In this review, we describe the evidence linking obesity to breast cancer recurrence, discuss the potential biological mechanisms through which weight could impact breast cancer prognosis, and review the weight-loss intervention studies that have been performed in breast cancer populations to date. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Ligibel, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jligibel@partners.org NR 50 TC 40 Z9 41 U1 0 U2 6 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2011 VL 25 IS 11 BP 994 EP 1000 PG 7 WC Oncology SC Oncology GA 838BP UT WOS:000296261800001 PM 22106549 ER PT J AU Grunwald, L Newcomb, CW Daniel, E Kacmaz, RO Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Kempen, JH AF Grunwald, Lili Newcomb, Craig W. Daniel, Ebenezer Kacmaz, R. Oktay Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Kempen, John H. CA Syst Immunosuppressive Therapy Eye TI Risk of Relapse in Primary Acute Anterior Uveitis SO OPHTHALMOLOGY LA English DT Article ID OCULAR INFLAMMATION; CLINICAL-FEATURES; HLA-B27 UVEITIS; DISEASES; OUTCOMES AB Purpose: To evaluate the risk of and risk factors for a second episode (relapse) among patients with remitted primary anterior uveitis. Design: Retrospective cohort study. Participants: Patients with primary anterior uveitis presenting to 1 of 4 academic ocular inflammation subspecialty practices achieving remission of the primary episode within 90 days of initial uveitis diagnosis. Methods: Data were obtained by standardized chart review. Main Outcome Measures: Time to relapse of anterior uveitis and risk factors for relapse. Results: We included 102 patients with a first episode of anterior uveitis who were seen within 90 days of first-ever uveitis onset and followed for 165 person-years after achieving remission of the initial episode. Most patients were female (60%) and white (78%). Forty patients had a recurrence of anterior uveitis. The incidence of relapse was 24% per person-year (95% confidence interval [CI], 17%-33%). At 1.5 years after remission, 61% (95% CI, 48%-71%) were still in remission. Younger adults had significantly higher relapse risk than middle-aged adults (hazard ratio [18-to 35-year-old persons vs. 35-to 55-year-old persons], 2.7; 95% CI, 1.3-6.0). Conclusions: Our results suggest that many patients with remitted primary anterior uveitis presenting for tertiary uveitis care will relapse. Age in the young adult range was associated with higher risk of relapse. Given the high relapse risk, management of patients with primary anterior uveitis should include an explicit plan for detecting and managing relapses. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118: 1911-1915 (C) 2011 by the American Academy of Ophthalmology. C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Univ Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol & Ophthalmol, Philadelphia, PA 19104 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept & Epidemiol, Baltimore, MD USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute [EY014943]; National Eye Institute; Department of Veterans' Affairs FX Supported primarily by National Eye Institute Grant EY014943 (Dr. Kempen). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. During part of the conduct of this project, Dr Kempen was an RPB James S. Adams Special Scholar Award recipient, Dr. Thorne was an RPB Harrington Special Scholar Award recipient, and Drs. Jabs and Rosenbaum were Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Levy-Clarke was previously supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. Dr. Suhler receives support from the Department of Veterans' Affairs. NR 23 TC 6 Z9 6 U1 0 U2 7 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 OCT PY 2011 VL 118 IS 10 BP 1911 EP 1915 DI 10.1016/j.ophtha.2011.02.044 PG 5 WC Ophthalmology SC Ophthalmology GA 835WG UT WOS:000296066900004 PM 21680024 ER PT J AU Ikeda, A Schwartz, J Peters, JL Fang, SN Spiro, A Sparrow, D Vokonas, P Kubzansky, LD AF Ikeda, Ai Schwartz, Joel Peters, Junenette L. Fang, Shona Spiro, Avron, III Sparrow, David Vokonas, Pantel Kubzansky, Laura D. TI Optimism in Relation to Inflammation and Endothelial Dysfunction in Older Men: The VA Normative Aging Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE optimism; pessimism; inflammation; endothelial dysfunction; biomarkers ID AMBULATORY BLOOD-PRESSURE; CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; POSITIVE AFFECT; HEALTHY-MEN; PESSIMISM; ATHEROSCLEROSIS; STRESS; WOMEN; RISK AB Background: Recent research suggests that optimism may reduce the risk of incident cardiovascular disease, but the mechanisms have not been determined. This study examines the association of optimism with change in inflammation and endothelial function over time in men. Methods: Longitudinal data were obtained from the Normative Aging Study excluding men with preexisting coronary heart disease or active infection at the time optimism was assessed (n = 340; mean [standard deviation] age = 70.9 [6.7] years). The Life Orientation Test was used to measure optimism, and serum markers were used to measure inflammation and endothelial dysfunction and were obtained repeatedly during the course of the study (1999-2008). These markers included high-sensitivity C-reactive protein, interleukin 6, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and soluble tumor necrosis factor receptor II. Within this sample, 243 men (71%) had two or more repeated measures of each outcome, resulting in a total of 746 observations for analysis. Linear mixed-effects models with a random subject intercept were used to estimate associations. Results: Higher overall optimism scores were associated with lower levels of interleukin 6 and soluble intercellular adhesion molecule 1 pooled across multiple time points in multivariable models but were not associated with rate of change in these markers over time. Analyses considering separate effects of optimism and pessimism subscales with each outcome indicated stronger effects of a pessimistic orientation versus an optimistic orientation. Conclusions: Higher overall optimism scores were associated with lower levels of inflammation and endothelial dysfunction in older men free of coronary heart disease. C1 [Ikeda, Ai; Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Schwartz, Joel; Peters, Junenette L.; Fang, Shona] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, Avron, III; Sparrow, David] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Kubzansky, LD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM Lkubzans@hsph.harvard.edu OI Spiro III, Avron/0000-0003-4080-8621; Peters, Junenette L./0000-0003-4542-4563 FU Robert Wood Johnson Foundation [63597]; US Department of Veterans Affairs, Massachusetts Veterans Epidemiology Research and Information Center; Japan Society for the Promotion of Science (Tokyo, Japan); US Department of Veterans Affairs; National Institute on Aging [R01-AG013006, R01-AG018436] FX This study was supported by the Robert Wood Johnson Foundation Grant ID 63597, Positive Health: The Copenhagen-Medici Model. The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center. Dr Ikeda was also supported by the Postdoctoral Fellowship for Research Abroad of Japan Society for the Promotion of Science (Tokyo, Japan). Dr Spiro is supported by a VA Merit Review and VA Research Career Scientist Award from the US Department of Veterans Affairs. The Normative Aging Study also has been supported by grants from the National Institute on Aging, including R01-AG013006 and R01-AG018436. The views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 35 TC 29 Z9 29 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD OCT PY 2011 VL 73 IS 8 BP 664 EP 671 DI 10.1097/PSY.0b013e3182312497 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 835QP UT WOS:000296051200005 PM 21949417 ER PT J AU Semenas, E Nozari, A Thiblin, I Rubertsson, S Wildund, L AF Semenas, Egidijus Nozari, Ala Thiblin, Ingemar Rubertsson, Sten Wildund, Lars TI Modulation of nitric oxide expression with methylene blue does not improve outcome after hypovolemic cardiac arrest SO RESUSCITATION LA English DT Article DE Cardiopulmonary resuscitation; Haemorrhage; Methylene blue; Sex ID ISCHEMIA-REPERFUSION INJURY; CARDIOPULMONARY-RESUSCITATION; VENTRICULAR-FIBRILLATION; SEVERE HEMORRHAGE; SEX-DIFFERENCES; PIGS; INHIBITION; SYNTHASE AB Aim of the study: We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals. Methods: Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35 mmHg, and were subjected to 2 min of untreated CA followed by 8 min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3 ml kg(-1) hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5 mg kg(-1) over 20 min, followed by 1.5 mg kg(-1) infusion over 40 min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed. Results: There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes. Conclusions: After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Semenas, Egidijus; Rubertsson, Sten; Wildund, Lars] Uppsala Univ, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, SE-75185 Uppsala, Sweden. [Nozari, Ala] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Thiblin, Ingemar] Dept Surg Sci, SE-75237 Uppsala, Sweden. RP Semenas, E (reprint author), Uppsala Univ, Dept Surg Sci Anesthesiol & Intens Care, Fac Med, SE-75185 Uppsala, Sweden. EM egidijus.semenas@gmail.com FU Laerdal Foundation for Acute Medicine, Stavanger, Norway FX The research was supported, in part, by the Laerdal Foundation for Acute Medicine, Stavanger, Norway. NR 22 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD OCT PY 2011 VL 82 IS 10 BP 1344 EP 1349 DI 10.1016/j.resuscitation.2011.04.027 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 837CM UT WOS:000296168700020 PM 21636201 ER PT J AU Bauman, WA Biering-Sorensen, F Krassioukov, A AF Bauman, W. A. Biering-Sorensen, F. Krassioukov, A. TI The International Spinal Cord Injury Endocrine and Metabolic Function Basic Data Set SO SPINAL CORD LA English DT Article DE spinal cord injury; international data set; endocrine; metabolic; diabetes; osteoporosis ID BONE; TESTOSTERONE; MORTALITY; DIAGNOSIS; MEN AB Objective: To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. Setting: International. Methods: The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. Results: The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org). Spinal Cord (2011) 49, 1068-1072; doi:10.1038/sc.2011.51; published online 17 May 2011 C1 [Bauman, W. A.] James J Peters Vet Affairs Med Ctr, Vet Affairs Rehabil Res & Dev Ctr Excellence Med, Bronx, NY 10468 USA. [Bauman, W. A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, W. A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Biering-Sorensen, F.] Univ Copenhagen, Rigshosp, Clin Spinal Cord Injuries, Ctr Neurosci, DK-2100 Copenhagen, Denmark. [Biering-Sorensen, F.] Univ Copenhagen, Fac Hlth Sci, DK-2100 Copenhagen, Denmark. [Krassioukov, A.] Univ British Columbia, ICORD, Dept Med, Vancouver, BC V5Z 1M9, Canada. [Krassioukov, A.] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. EM william.bauman@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [B4162C] FX We are thankful for the comments and suggestions received from Susan Charlifue, Lawrence Vogel, Vanessa Noonan, Marcalee Sipski Alexander, Inge Eriks-Hoogland, and Michael DeVivo. We wish to thank the Department of Veterans Affairs Rehabilitation Research and Development Service for their support (grant B4162C). NR 26 TC 5 Z9 5 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 OCT PY 2011 VL 49 IS 10 BP 1068 EP 1072 DI 10.1038/sc.2011.51 PG 5 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 833YY UT WOS:000295923200009 PM 21577217 ER PT J AU Wood, KB Fritzell, P Dettori, JR Hashimoto, R Lund, T Shaffrey, C AF Wood, Kirkham B. Fritzell, Peter Dettori, Joseph R. Hashimoto, Robin Lund, Teija Shaffrey, Chris TI Effectiveness of Spinal Fusion Versus Structured Rehabilitation in Chronic Low Back Pain Patients With and Without Isthmic Spondylolisthesis A Systematic Review SO SPINE LA English DT Article DE fusion; heterogeneity of treatment effect; isthmic spondylolisthesis; low back pain; rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; LUMBAR FUSION; CONSERVATIVE TREATMENT; POSTEROLATERAL FUSION; INSTRUMENTED FUSION; INTERBODY FUSION; SURGERY; DISC; CLASSIFICATION; DEGENERATION AB Study Design. Systematic review. Objective. To determine if the presence of isthmic spondylolisthesis modifies the effect of treatment (fusion vs. multidimensional supervised rehabilitation) in patients with chronic low back pain (CLBP). Summary of Background Data. Results of spinal surgery for CLBP are variable. It is unclear whether patients with CLBP and isthmic spondylolisthesis have more success with surgery versus a multidimensional supervised rehabilitation program when compared with those with CLBP but without spondylolisthesis. Methods. A systematic search was conducted in MEDLINE and the Cochrane Collaboration Library for articles published through January 2011. Randomized controlled trials (RCTs) were included that compared spine fusion versus multidimensional supervised rehabilitation in patients with and without isthmic spondylolisthesis. Standardized mean differences (SMDs) and risk differences were calculated for common outcomes, and then compared to determine potential heterogeneity of treatment effect. The final strength of the body of literature was expressed as "high," "moderate," or "low" confidence that the evidence reflects the true effect. Results. No studies were found that directly compared the two subgroups. Three RCTs compared fusion with supervised nonoperative care in patients with CLBP without isthmic spondylolisthesis; one RCT evaluated these treatments in patients with isthmic spondylolisthesis. There were study differences in patient characteristics, type of fusion, the nature of the rehabilitation, outcomes assessed, and length of follow-up. The SMDs for pain in favor of fusion were modest at 2 years for those without isthmic spondylolisthesis, but large in favor of fusion for those with isthmic spondylolisthesis compared with rehabilitation. Similarly, the SMDs for function in patients without isthmic spondylolisthesis compared with rehabilitation was small at 2 years, but appreciably higher in favor of fusion in patients with isthmic spondylolisthesis. Conclusion. The overall strength of evidence evaluating whether the presence of isthmic spondylolisthesis modifies the effect of fusion compared with rehabilitation patients with CLBP is "low." Fusion should be considered for patients with low back pain and isthmic spondylolisthesis who have failed nonoperative treatment. Clinical Recommendations. We recommend considering fusion for patients with isthmic spondylolisthesis and lower back pain who have failed nonoperative treatment. Recommendation: Weak. C1 [Wood, Kirkham B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wood, Kirkham B.] Massachusetts Gen Hosp, Spine Serv, Boston, MA 02114 USA. [Fritzell, Peter] Falun Cent Hosp, Clin Res Ctr, Dept Orthoped Surg, Falun, Sweden. [Dettori, Joseph R.; Hashimoto, Robin] Spectrum Res Inc, Tacoma, WA USA. [Lund, Teija] ORTON Orthopaed Hosp, Invalid Fdn, Helsinki, Finland. [Shaffrey, Chris] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Wood, KB (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Gray 502, Boston, MA 02114 USA. EM kbwood@partners.org RI AOCID, AO Foundation/R-6455-2016 FU AOSpine North America FX AOSpine North America and Foundation funds were received to support this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. NR 32 TC 6 Z9 7 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 1 PY 2011 VL 36 IS 21 SU S BP S110 EP S119 DI 10.1097/BRS.0b013e31822ef8c5 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 835WN UT WOS:000296067700010 PM 21952183 ER PT J AU Mrnak-Meyer, J Tate, SR Tripp, JC Worley, MJ Jajodia, A McQuaid, JR AF Mrnak-Meyer, Jennifer Tate, Susan R. Tripp, Jessica C. Worley, Matthew J. Jajodia, Archana McQuaid, John R. TI Predictors of Suicide-Related Hospitalization among U.S. Veterans Receiving Treatment for Comorbid Depression and Substance Dependence Who is the Riskiest of the Risky? SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID PERSIAN-GULF-WAR; US VETERANS; MOOD REGULATION; DISORDERS; MORTALITY; ABUSERS AB This study examined whether widely accepted suicide risk factors are useful in predicting suicide-related hospitalization, beyond history of a suicide attempt, in high-risk treatment-seeking veterans with depression and substance dependence. Negative mood regulation expectancies were the only significant predictor of hospitalization during 6-months of outpatient treatment. History of a suicide attempt was the only significant predictor of hospitalization during the one-year follow-up period. Results suggest that within high-risk populations, standard suicide risk factors may not identify individuals who will engage in suicidal behaviors resulting in hospitalization. Assessing negative mood regulation expectations may assist in identifying those most at risk. C1 [Mrnak-Meyer, Jennifer; Tate, Susan R.; Tripp, Jessica C.; Jajodia, Archana] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Worley, Matthew J.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. [McQuaid, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [McQuaid, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Tate, SR (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr 116B, San Diego, CA 92161 USA. EM srtate@ucsd.edu FU NIAAA NIH HHS [T32 AA013525]; NIDA NIH HHS [F31 DA030861] NR 38 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD OCT PY 2011 VL 41 IS 5 BP 532 EP 542 DI 10.1111/j.1943-278X.2011.00051.x PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 834DG UT WOS:000295938900006 PM 21815915 ER PT J AU Azadzoi, KM Yalla, SV Siroky, MB AF Azadzoi, Kazem M. Yalla, Subbarao V. Siroky, Mike B. TI Human Bladder Smooth Muscle Cell Damage in Disturbed Oxygen Tension SO UROLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; LOWER URINARY-TRACT; ENDOPLASMIC-RETICULUM STRESS; PARTIAL OUTLET OBSTRUCTION; INDUCED OXIDATIVE STRESS; BLOOD-FLOW; CHRONIC ISCHEMIA; CORONARY-ARTERY; SYMPTOMS; MEN AB OBJECTIVE To characterize human bladder smooth muscle cell reactions to disturbed oxygen tension. Clinical studies have shown a close correlation between bladder ischemia and lower urinary tract symptoms in elderly patients. MATERIALS AND METHODS Confluent cultured human bladder smooth muscle cells were incubated under normoxia, continuous hypoxia, and oxidative stress (hypoxia/reoxygenation) conditions using a computerized oxycycler system. After 48 hours, cell samples were collected and processed for fluorometric assessment of oxidative injury, enzyme immunoassay of antioxidant capacity, and transmission electron microscopy. RESULTS Lipid peroxidation was found in cell hypoxia and oxidative stress, whereas protein oxidation was evident in oxidative stress only. Cell antioxidant capacity decreased in oxidative stress but remained unchanged in hypoxia. Oxidative products were present in cell oxidative stress only, whereas nitrosative products increased in both hypoxia and oxidative stress conditions. Forty-eight hours of hypoxia and oxidative stress had no effect on cell senescence. Thickened deformed cell membrane, swollen mitochondria, and enlarged endoplasmic reticulum (ER) were found in cell hypoxia. Partially lost cell membrane with increased caveolae, swollen mitochondria with degraded cristae, splintered ER, and increased lysosomes were evident in cell oxidative stress. CONCLUSION Human bladder smooth muscle cells are highly reactive to nonconforming oxygen tension. Reactions to hypoxia are consistent with cell survival signaling to cope with lack of oxygen. Changes in oxidative stress indicate extensive damage and deterioration of the subcellular elements. Hypoxic and oxidative damage may be an important mechanism of smooth muscle degeneration in bladder conditions with disturbed oxygen tension. UROLOGY 78: 967.e9-967.e15, 2011. Published by Elsevier Inc. C1 VA Boston Healthcare Syst, Dept Urol, Boston, MA USA. VA Boston Healthcare Syst, Dept Pathol, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Azadzoi, KM (reprint author), Surg Urol 151,Bldg 1A,Room 315,150 S Huntington A, Boston, MA 02130 USA. EM kazadzoi@bu.edu FU Department of Veterans Affairs FX Supported by a Merit Review Grant from the Department of Veterans Affairs. NR 30 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2011 VL 78 IS 4 AR 967.e9 DI 10.1016/j.urology.2011.06.034 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 835GE UT WOS:000296023000067 PM 21872910 ER PT J AU Tamber-Rosenau, BJ Esterman, M Chiu, YC Yantis, S AF Tamber-Rosenau, Benjamin J. Esterman, Michael Chiu, Yu-Chin Yantis, Steven TI Cortical Mechanisms of Cognitive Control for Shifting Attention in Vision and Working Memory SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HUMAN PARIETAL CORTEX; SHORT-TERM-MEMORY; SELECTIVE VISUAL-ATTENTION; OBJECT-BASED ATTENTION; SPATIAL ATTENTION; PREFRONTAL CORTEX; BASAL GANGLIA; NEURAL MECHANISMS; INFORMATION; TASK AB Organisms operate within both a perceptual domain of objects and events, and a mnemonic domain of past experiences and future goals. Each domain requires a deliberate selection of task-relevant information, through deployments of external (perceptual) and internal (mnemonic) attention, respectively. Little is known about the control of attention shifts in working memory, or whether voluntary control of attention in these two domains is subserved by a common or by distinct functional networks. We used human fMRI to examine the neural basis of cognitive control while participants shifted attention in vision and in working memory. We found that these acts of control recruit in common a subset of the dorsal fronto-parietal attentional control network, including the medial superior parietal lobule, intraparietal sulcus, and superior frontal sulcus/gyrus. Event-related multivoxel pattern classification reveals, however, that these regions exhibit distinct spatio-temporal patterns of neural activity during internal and external shifts of attention, respectively. These findings constrain theoretical accounts of selection in working memory and perception by showing that populations of neurons in dorsal fronto-parietal network regions exhibit selective tuning for acts of cognitive control in different cognitive domains. C1 [Tamber-Rosenau, Benjamin J.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Tamber-Rosenau, Benjamin J.; Yantis, Steven] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Esterman, Michael] VA Boston Healthcare Syst, Boston, MA USA. [Esterman, Michael] Boston Univ, Sch Med, Boston, MA 02215 USA. [Chiu, Yu-Chin] Univ Calif San Diego, San Diego, CA 92103 USA. RP Tamber-Rosenau, BJ (reprint author), Vanderbilt Univ, Dept Psychol, 427 Wilson Hall,111 21st Ave S, Nashville, TN 37240 USA. EM benjamin.j.tamber-rosenau@vanderbilt.edu FU National Institutes of Health [R01-DA13165] FX We thank Amy Shelton and John Serences for statistical and technical advice, and Jared Abrams, Terri Brawner, and Kathleen Kahl for excellent technical assistance. This work was supported by the National Institutes of Health grant R01-DA13165 to S. Y. NR 69 TC 39 Z9 39 U1 4 U2 19 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD OCT PY 2011 VL 23 IS 10 BP 2905 EP 2919 DI 10.1162/jocn.2011.21608 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 809KZ UT WOS:000294055600022 PM 21291314 ER PT J AU Wang, KD Brown, K Shen, SY Tucker, J AF Wang, Kaidi Brown, Katherine Shen, Song-Ying Tucker, Joseph TI Social Network-Based Interventions to Promote Condom Use: A Systematic Review SO AIDS AND BEHAVIOR LA English DT Review DE Social network; HIV prevention intervention; Condom use; Condom promotion ID FEMALE SEX WORKERS; HIV-PREVENTION; UNITED-STATES; RISK BEHAVIORS; DRUG-USERS; YOUNG MEN; NORMS; BULGARIA; THAILAND; PROGRAM AB Effective sexually transmitted infection (STIs)/HIV prevention programs are urgently needed, but translating evidence-based methods of STI/HIV prevention into sustainable programs has been difficult. Social influences are critical for establishing condom use norms. This study systematically reviewed social network-based interventions focused on condom promotion. Social networks were defined as groups who self-identified prior to the research study. Eleven eligible research studies were identified and included in this review. Only three studies measured biological endpoints and five studies used validated measures of condom use. Among the nine studies with control groups, eight showed significant improvements in at least one measure of condom use. There were large differences in how social network members were identified and involved in the interventions. This systematic review highlights the potential utility of social network-based condom promotion programs. More research is needed to show how these promising studies can be expanded. C1 [Tucker, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Wang, Kaidi] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Brown, Katherine] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Shen, Song-Ying] Guangzhou Women & Childrens Med Ctr, Guangzhou Birth Cohort Off, Guangzhou 510623, Guangdong, Peoples R China. RP Tucker, J (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jtucker4@partners.org FU FIC NIH HHS [K01 TW008200-02, K01 TW008200]; NICHD NIH HHS [R24 HD056670, R24 HD056670-04] NR 29 TC 17 Z9 17 U1 0 U2 19 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2011 VL 15 IS 7 BP 1298 EP 1308 DI 10.1007/s10461-011-0020-1 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 825KA UT WOS:000295271200002 PM 21811843 ER PT J AU Miller, CL Bangsberg, DR Tuller, DM Senkungu, J Kawuma, A Frongillo, EA Weiser, SD AF Miller, Cari L. Bangsberg, David R. Tuller, David M. Senkungu, Jude Kawuma, Annet Frongillo, Edward A. Weiser, Sheri D. TI Food Insecurity and Sexual Risk in an HIV Endemic Community in Uganda SO AIDS AND BEHAVIOR LA English DT Article DE Food insecurity; HIV/AIDS; Uganda; Sexual-risk behavior; Gender; Transactional sex; Violence ID SUB-SAHARAN AFRICA; GENDER-BASED VIOLENCE; DAR-ES-SALAAM; TRANSACTIONAL SEX; PARTNER VIOLENCE; AGE-DISPARATE; PREVENTION; HIV/AIDS; INTERVENTION; WOMEN AB Food insecurity has been linked to high-risk sexual behavior in sub-Saharan Africa, but there are limited data on these links among people living with HIV/AIDS, and on the mechanisms for how food insecurity predisposes individuals to risky sexual practices. We undertook a series of in-depth open-ended interviews with 41 individuals living with HIV/AIDS to understand the impact of food insecurity on sexual-risk behaviors. Participants were recruited from the Immune Suppression Clinic at the Mbarara University of Science and Technology in Mbarara, Uganda. Interviews were recorded, transcribed verbatim, translated, and coded following the strategy of grounded theory. Four major themes emerged from the interview data: the relationship between food insecurity and transactional sex for women; the impact of a husband's death from HIV on worsening food insecurity among women and children; the impact of food insecurity on control over condom use, and the relationship between food insecurity and staying in violent/abusive relationships. Food insecurity led to increased sexual vulnerability among women. Women were often compelled to engage in transactional sex or remain in violent or abusive relationships due to their reliance on men in their communities to provide food for themselves and their children. There is an urgent need to prioritize food security programs for women living with HIV/AIDS and address broader gender-based inequities that are propelling women to engage in risky sexual behaviors based on hunger. Such interventions will play an important role in improving the health and wellbeing of people living with HIV/AIDS, and preventing HIV transmission. C1 [Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94110 USA. [Miller, Cari L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Bangsberg, David R.; Senkungu, Jude; Kawuma, Annet] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard,Ctr Global Hlth, Boston, MA USA. [Tuller, David M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Tuller, David M.] Univ Calif Berkeley, Grad Sch Journalism, Berkeley, CA 94720 USA. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. RP Weiser, SD (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, 995 Potrero St,Bldg 80,Box 0874, San Francisco, CA 94110 USA. EM sheri.weiser@ucsf.edu FU NIMH NIH HHS [K23 MH079713, K23 MH079713-01, K24 MH087227, K24 MH87227, R01 MH054907]; PHS HHS [R0-1 54907] NR 39 TC 39 Z9 40 U1 3 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2011 VL 15 IS 7 BP 1512 EP 1519 DI 10.1007/s10461-010-9693-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 825KA UT WOS:000295271200024 PM 20405316 ER PT J AU Markowitz, SM O'Cleirigh, C Hendriksen, ES Bullis, JR Stein, M Safren, SA AF Markowitz, Sarah M. O'Cleirigh, Conall Hendriksen, Ellen S. Bullis, Jacqueline R. Stein, Michael Safren, Steven A. TI Childhood Sexual Abuse and Health Risk Behaviors in Patients with HIV and a History of Injection Drug Use SO AIDS AND BEHAVIOR LA English DT Article DE Childhood sexual abuse; HIV transmission risk; Injection drug use; Adherence ID SELF-REPORTED CHILDHOOD; BISEXUAL MEN; MEDICATION ADHERENCE; NATIONAL-SURVEY; PREVALENCE; WOMEN; ADULTS; DEPRESSION; SAMPLE; CIRCUMSTANCES AB Childhood sexual abuse (CSA) is related to poorer health outcomes, associated with increased risk for HIV acquisition, and prevalent among HIV risk groups. Links between CSA and health behavior are an important health concern. We examined the relationship between CSA and transmission risk behavior and medication adherence in 119 HIV-infected individuals with an injection drug use history. 47% reported CSA, with no gender difference. Individuals who experienced CSA were more likely to report sexual HIV transmission risk behavior in the past 6 months, more sexual partners, use of heroin in the past 30 days, and worse adherence to HIV medication than those who did not. These findings confirm that rates of CSA are high in this population, and suggest that a history of CSA may place people managing both HIV and opioid dependence at increased risk for HIV transmission, poor adherence to medication, and vulnerability to substance use relapse. C1 [O'Cleirigh, Conall; Hendriksen, Ellen S.; Bullis, Jacqueline R.; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Markowitz, Sarah M.] Wells Coll, Aurora, NY USA. [O'Cleirigh, Conall; Hendriksen, Ellen S.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Stein, Michael] Butler Hosp, Dept Gen Med, Providence, RI 02906 USA. [Stein, Michael] Brown Univ, Dept Med, Providence, RI 02912 USA. RP Hendriksen, ES (reprint author), Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ehendriksen@partners.org FU NIDA NIH HHS [DA018603-03, R01 DA018603]; NIMH NIH HHS [K24 MH094214] NR 37 TC 14 Z9 14 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2011 VL 15 IS 7 BP 1554 EP 1560 DI 10.1007/s10461-010-9857-y PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 825KA UT WOS:000295271200029 PM 21161362 ER PT J AU Radebe, MA Nair, K Chonco, F Bishop, K Bishop, K Wright, JK van der Stok, M Mncube, Z Altfeld, M Walker, BD Ndung'u, T AF Radebe, M. A. Nair, K. Chonco, F. Bishop, K. Bishop, K. Wright, J. K. van der Stok, M. Mncube, Z. Altfeld, M. Walker, B. D. Ndung'u, T. TI Control of Acute HIV-1 Subtype C Viremia Is Associated with Limited CD8+T-Cell Immunogenicity SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Radebe, M. A.; Nair, K.; Chonco, F.; Bishop, K.; Bishop, K.; Wright, J. K.; van der Stok, M.; Mncube, Z.; Ndung'u, T.] Univ KwaZulu Natal, Durban, South Africa. [Altfeld, M.; Walker, B. D.] Massachusetts Gen Hosp, Massachusetts Inst, Ragon Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A11 EP A11 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500024 ER PT J AU Simmons, RP Groden, E Chang, JJ Lindsay, R Fadda, L Lifson, JD Lane, K Axten, K Rosenberg, E Allen, T Altfeld, M AF Simmons, R. P. Groden, E. Chang, J. J. Lindsay, R. Fadda, L. Lifson, J. D. Lane, K. Axten, K. Rosenberg, E. Allen, T. Altfeld, M. TI Different Cytokine Profiles Induced by HIV-1 and HIV-1-Derived TLR Ligands in Monocytes and mDCs SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Simmons, R. P.; Groden, E.; Chang, J. J.; Lindsay, R.; Fadda, L.; Lane, K.; Axten, K.; Allen, T.; Altfeld, M.] MIT & Harvard, Ragon Inst MGH, Charlestown, MA USA. [Lifson, J. D.] NCI, AIDS & Canc Virus Program, Frederick, MD 21701 USA. [Rosenberg, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A63 EP A63 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500158 ER PT J AU Soghoian, DZ Jessen, H Cutler, S Flanders, M Ranasinghe, S Lindqvist, M Davis, I Lane, K Rychert, J Rosenberg, ES Walker, BD Streeck, H AF Soghoian, D. Z. Jessen, H. Cutler, S. Flanders, M. Ranasinghe, S. Lindqvist, M. Davis, I. Lane, K. Rychert, J. Rosenberg, E. S. Walker, B. D. Streeck, H. TI HIV-Specific Cytolytic CD4+T-Cell Responses During Acute HIV-1 Infection Predict Disease Outcome SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Soghoian, D. Z.; Cutler, S.; Flanders, M.; Ranasinghe, S.; Lindqvist, M.; Davis, I.; Lane, K.; Walker, B. D.; Streeck, H.] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Rychert, J.; Rosenberg, E. S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A10 EP A11 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500023 ER PT J AU Wang, YE Oniangue-Nzda, C Schneidewind, A Kemper, M Mellors, E Qi, Y Gladden, AD Power, KA Pereyra, F Walker, BD Carrington, M Allen, TM AF Wang, Y. E. Oniangue-Nzda, C. Schneidewind, A. Kemper, M. Mellors, E. Qi, Y. Gladden, A. D. Power, K. A. Pereyra, F. Walker, B. D. Carrington, M. Allen, T. M. TI Control of HIV Viral Replication Mediated by the Synergistic Effects of Unique Combinations of HLA Class I Alleles SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on AIDS Vaccine CY SEP 12-15, 2011 CL Bangkok, THAILAND C1 [Wang, Y. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oniangue-Nzda, C.; Kemper, M.; Mellors, E.; Gladden, A. D.; Power, K. A.; Pereyra, F.; Walker, B. D.; Allen, T. M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Schneidewind, A.] Univ Regensburg, Regensburg, Germany. [Carrington, M.] NCI Frederick, SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2011 VL 27 IS 10 BP A60 EP A60 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 832GD UT WOS:000295790500150 ER PT J AU Chen, G Carlson, VCC Wang, J Beck, A Heinz, A Ron, D Lovinger, DM Buck, KJ AF Chen, Gang Carlson, Verginia C. Cuzon Wang, Jun Beck, Anne Heinz, Andreas Ron, Dorit Lovinger, David M. Buck, Kari J. TI Striatal Involvement in Human Alcoholism and Alcohol Consumption, and Withdrawal in Animal Models SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE c-Fos; Electrophysiology; fMRI; Fyn Kinase; PET; Self-Administration ID NR2B-CONTAINING NMDA RECEPTORS; ETHANOL WITHDRAWAL; PREFRONTAL CORTEX; DORSAL STRIATUM; STRIATOPALLIDAL NEURONS; MACACA-FASCICULARIS; CHROMOSOME-4 LOCUS; VENTRAL STRIATUM; BASAL GANGLIA; C57BL/6J MICE AB Background: Different regions of the striatum may have distinct roles in acute intoxication, alcohol seeking, dependence, and withdrawal. Methods: The recent advances are reviewed and discussed in our understanding of the role of the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum in behavioral responses to alcohol, including alcohol craving in abstinent alcoholics, and alcohol consumption and withdrawal in rat, mouse, and nonhuman primate models. Results: Reduced neuronal activity as well as dysfunctional connectivity between the ventral striatum and the dorsolateral prefrontal cortex is associated with alcohol craving and impairment of new learning processes in abstinent alcoholics. Within the DLS of mice and nonhuman primates withdrawn from alcohol after chronic exposure, glutamatergic transmission in striatal projection neurons is increased, while GABAergic transmission is decreased. Glutamatergic transmission in DMS projection neurons is also increased in ethanol withdrawn rats. Ex vivo or in vivo ethanol exposure and withdrawal causes a long-lasting increase in NR2B subunit-containing NMDA receptor activity in the DMS, contributing to ethanol drinking. Analyses of neuronal activation associated with alcohol withdrawal and site-directed lesions in mice implicate the rostroventral caudate putamen, a ventrolateral segment of the DMS, in genetically determined differences in risk for alcohol withdrawal involved in physical association of the multi-PDZ domain protein, MPDZ, with 5-HT(2C) receptors and/or NR2B. Conclusions: Alterations of dopaminergic, glutamatergic, and GABAergic signaling within different regions of the striatum by alcohol is critical for alcohol craving, consumption, dependence, and withdrawal in humans and animal models. C1 [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA. [Chen, Gang; Buck, Kari J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Carlson, Verginia C. Cuzon; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Wang, Jun; Ron, Dorit] Univ Calif San Francisco, Dept Neurol, Ernest Gallo Res Ctr, San Francisco, CA USA. [Beck, Anne; Heinz, Andreas] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. RP Chen, G (reprint author), Univ Minnesota, Inst Translat Neurosci, RM 4-140,MBB 2101 6th SE,East Campus, Minneapolis, MN 55455 USA. EM hdn_2001@yahoo.com RI Wang, Jun/N-8472-2015; Wang, Jun/M-2337-2016 OI Wang, Jun/0000-0002-0085-4722; Wang, Jun/0000-0002-0085-4722 FU division of Intramural Clinical and Basic Research NIAAA [AA13510, AA13641]; State of California for medical research on alcohol and substance abuse through the University of California, San Francisco; Department of Veterans Affairs; German Research Foundation (Deutsche Forschungsgemeinschaft) [HE2597/4-3, 7-3]; Bernstein Center for Computational Neuroscience Berlin [01GQ0411, 01GS08159]; [R01AA014366]; [MH13438]; [AA011114]; [AA10760]; [DA05228] FX The work described in this review was supported by the division of Intramural Clinical and Basic Research NIAAA, AA13510, AA13641 (VCCC, DML); R01AA014366, MH13438, and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (DR); AA011114, AA10760, DA05228, and the Department of Veterans Affairs (KJB); the German Research Foundation (Deutsche Forschungsgemeinschaft, HE2597/4-3 and 7-3) and the Bernstein Center for Computational Neuroscience Berlin (Bundesministerium fur Bildung und Forschung Grants 01GQ0411 and 01GS08159) (AH). NR 80 TC 34 Z9 36 U1 1 U2 13 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 OCT PY 2011 VL 35 IS 10 BP 1739 EP 1748 DI 10.1111/j.1530-0277.2011.01520.x PG 10 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200006 PM 21615425 ER PT J AU Anacker, AMJ Loftis, JM Ryabinin, AE AF Anacker, Allison M. J. Loftis, Jennifer M. Ryabinin, Andrey E. TI Alcohol Intake in Prairie Voles is Influenced by the Drinking Level of a Peer SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Prairie Voles; Social Behavior; Alcohol Self-Administration; Peer Influence; Microtus ochrogaster ID ETHANOL-CONSUMPTION; SOCIAL INFLUENCES; RATS; MICE; BEHAVIOR; SOCIALIZATION; ADOLESCENTS; EXPRESSION; FRIENDSHIP; SELECTION AB Background: Peer interactions can have important effects on alcohol-drinking levels, in some cases increasing use, and in other cases preventing it. In a previous study, we have established the prairie vole as a model animal for the effects of social relationships on alcohol intake and have observed a correlation of alcohol intake between individual voles housed together as pairs. Here, we investigated this correlated drinking behavior, hypothesizing that 1 animal alters its alcohol intake to match the drinking of its partner. Methods: Adult prairie voles were tested for baseline drinking levels with continuous access to 10% alcohol and water for 4 days. In Experiment 1, high alcohol drinkers (> 9 g/kg/d) were paired with low alcohol drinkers (< 5 g/kg/d) of the same sex on either side of a mesh divider for 4 days with continuous access to the same 2-bottle choice test. In Experiment 2, high drinkers were paired with high drinkers and low drinkers paired with low drinkers. In both experiments, animals were again separated following pairing, and drinking was retested in isolation. In Experiment 3, alcohol-naive animals were tested for saccharin consumption (0.05%) first in isolation and then in high saccharin drinkers paired with low saccharin drinkers, and then in another isolation period. Results: In Experiment 1, high drinkers paired with low drinkers significantly decreased their alcohol intake and preference from baseline drinking in isolation, and drinking levels remained significantly lower during isolation following pairing. Interestingly, there was variability between pairs in whether the high drinker decreased or the low drinker increased intake. In Experiment 2, high drinkers paired with high drinkers did not significantly change their intake level or preference, nor did low drinkers paired with low drinkers, and no changes occurred during the subsequent isolation. In Experiment 3, there was no change in saccharin intake or preference when high drinkers were paired with high drinkers or low paired with low, or in the subsequent isolation. Conclusions: Alcohol drinking of prairie voles can be altered under social conditions, such that 1 animal changes its alcohol intake to more closely match the intake of the other animal, helping to explain previous findings of correlated alcohol drinking. The effect does not extend to saccharin, a naturally rewarding sweet substance. This behavior can be used to model the peer pressure that can often affect alcohol intake in humans. C1 [Anacker, Allison M. J.; Loftis, Jennifer M.; Ryabinin, Andrey E.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Ryabinin, AE (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code L470, Portland, OR 97239 USA. EM ryabinin@ohsu.edu FU NIH [AA016886, AA02013601, AA007468]; ARCS Foundation Portland Chapter; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development FX This work was supported by NIH grants AA016886 to AER, AA02013601 to AMJA, institutional training grant AA007468.23, and the ARCS Foundation Portland Chapter M&M award to AMJA. The authors also thank the PVAMC VMU staff for their contributions to the colony management and animal care. This material is the result of work supported with resources and the use of facilities at the Portland Veterans Affairs Medical Center. JML is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Clinical Sciences Research and Development. NR 33 TC 25 Z9 25 U1 1 U2 14 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 OCT PY 2011 VL 35 IS 10 BP 1884 EP 1890 DI 10.1111/j.1530-0277.2011.01533.x PG 7 WC Substance Abuse SC Substance Abuse GA 824QX UT WOS:000295218200020 PM 21575019 ER PT J AU O'Donoghue, ML Braunwald, E White, HD Serruys, P Steg, PG Hochman, J Maggioni, AP Bode, C Weaver, D Johnson, JL Cicconetti, G Lukas, MA Tarka, E Cannon, CP AF O'Donoghue, Michelle L. Braunwald, Eugene White, Harvey D. Serruys, Patrick Steg, Ph. Gabriel Hochman, Judith Maggioni, Aldo P. Bode, Christoph Weaver, Douglas Johnson, Joel L. Cicconetti, Greg Lukas, Mary Ann Tarka, Elizabeth Cannon, Christopher P. TI Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID ACTIVATING-FACTOR ACETYLHYDROLASE; PHOSPHOLIPASE A(2) ACTIVITY; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC PLAQUE; HEART-DISEASE; PLASMA; MACROPHAGES; LESIONS; RISK; INHIBITOR AB Background Higher levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with a higher risk of cardiovascular events and may play a causal role in atherogenesis. Darapladib inhibits Lp-PLA(2) activity in plasma and in arterial plaques and may confer clinical benefit in preventing cardiovascular events. Study Design The SOLID-TIMI 52 trial is a randomized, double-blind, placebo-controlled, multicenter, event-driven trial. Approximately 13,000 subjects are being randomized to darapladib (160 mg enteric-coated tablet daily) or matching placebo within 30 days of hospitalization with an acute coronary syndrome. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points include major and total coronary events, individual components of the primary end point, and all-cause mortality. The study will continue until approximately 1,500 primary end point events have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be approximately 3 years, with a total study duration of approximately 4.1 years. Conclusions The SOLID-TIMI 52 trial will determine the clinical benefit of direct inhibition of Lp-PLA(2) activity with darapladib in patients after an acute coronary syndrome. (Am Heart J 2011;162:613-619.e1.) C1 [O'Donoghue, Michelle L.; Braunwald, Eugene; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. [Johnson, Joel L.; Cicconetti, Greg; Lukas, Mary Ann; Tarka, Elizabeth] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Serruys, Patrick] Erasmus Univ, Thoraxctr, NL-3000 DR Rotterdam, Netherlands. [Steg, Ph. Gabriel] Univ Paris Diderot, INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, Assistance Publ Hop Paris, F-75877 Paris 18, France. [Hochman, Judith] NYU, Sch Med, New York, NY USA. [Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy. [Bode, Christoph] Med Univ Klin, Freiburg, Germany. [Weaver, Douglas] Henry Ford Hosp, Henry Ford Heart & Vasc Inst, Detroit, MI 48202 USA. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. OI Hochman, Judith/0000-0002-5889-5981; Maggioni, Aldo Pietro/0000-0003-2764-6779 NR 21 TC 57 Z9 60 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2011 VL 162 IS 4 BP 613 EP U62 DI 10.1016/j.ahj.2011.07.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833ZO UT WOS:000295925100008 PM 21982651 ER PT J AU Lewis, WR Fonarow, GC Grau-Sepulveda, MV Smith, EE Bhatt, DL Hernandez, AF Olson, D Peterson, ED Schwamm, LH AF Lewis, William R. Fonarow, Gregg C. Grau-Sepulveda, Maria V. Smith, Eric E. Bhatt, Deepak L. Hernandez, Adrian F. Olson, DaiWai Peterson, Eric D. Schwamm, Lee H. TI Improvement in use of anticoagulation therapy in patients with ischemic stroke: Results from Get With The Guidelines-Stroke SO AMERICAN HEART JOURNAL LA English DT Article ID ATRIAL-FIBRILLATION; PREVENTION; WARFARIN; ASPIRIN; CARE; ATTACK; RISK; METAANALYSIS; ASSOCIATION; CLOPIDOGREL AB Background Anticoagulation therapy reduces thromboembolic events in patients with atrial fibrillation (AF) and has a class I indication for ischemic stroke patients with AF and no contraindications. We determined the patient and hospital level characteristics associated with an increased use of anticoagulation, including participation in the Get With The Guidelines-Stroke (GWTG-Stroke) Program. Methods We assessed the use of anticoagulation at hospital discharge in eligible AF patients with stroke or transient ischemic attack (TIA) at 1,354 participating hospitals between April 1, 2003, and April 1, 2010. Results Patients with AF (n = 197,778) represented 20.5% of patients with ischemic stroke/TIA. Among patients with AF, 47.6% (n = 94,119) were deemed eligible for anticoagulation, and of these, 94.0% were discharged on therapy. Older patients, African American or Hispanic patients, and those with diabetes were less likely to receive anticoagulation. Hospitals with a higher volume of patients with stroke were more likely to treat with anticoagulation. The Joint Commission Primary Stroke Centers were also more likely to treat eligible patients (odds ratio 2.16, 95% CI 1.82-2.56, P < .0001). From 2003 to 2010, contraindications to anticoagulation therapy declined from 69.7% to 28.4% (P < .0001 for trend). Anticoagulation among eligible patients improved from 88.4% to 95.2% (P < .0001) for 7 years of participation. Time in GWTG-Stroke was associated with improved anticoagulation use (adjusted odds ratio per year in program, 1.11, 95% CI 1.06-1.16, P < .001). Conclusions Use of anticoagulation among stroke patients with AF has increased to very high levels overall in GWTG-Stroke over time. Future efforts should focus on improving use among selected populations. (Am Heart J 2011;162:692-699.e2.) C1 [Lewis, William R.] Case Western Reserve Univ, Heart & Vasc Ctr, Cleveland, OH 44109 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Olson, DaiWai; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lewis, WR (reprint author), Case Western Reserve Univ, Heart & Vasc Ctr, MetroHlth Campus,2500 MetroHlth Dr, Cleveland, OH 44109 USA. EM wlewis@metrohealth.org RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association/American Stroke Association; Ortho-McNeil; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable; NHLBI; National Institutes of Health [R01 NS062028]; Alberta Heritage Foundation for Medical Research; Alberta Innovates-Health Solutions; Canadian Institutes for Health Research; Heart and Stroke Foundation of Canada; Canadian Stroke Network; Hotchkiss Brain Institute; Astra Zeneca; Bristol-Myers Squibb; Eisai; Sanofi Aventis; Medicines Company; Johnson and Johnson; American Heart Association; Eli Lilly; Ortho-McNeil Pharmaceuticals FX Funding/Support: The Get With The Guidelines-Stroke (GWTG-Stroke) Program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke Program is currently supported, in part, by a charitable contribution from Ortho-McNeil. The GWTG-Stroke has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the American Heart Association Pharmaceutical Roundtable.; Conflicts of interest: William Lewis, MD, received honoraria from Boston Scientific and Boehringer Ingelheim (Modest). Gregg C. Fonarow, MD, received research grants from NHLBI (significant) and honoraria from Medtronic (modest) and is a consultant of Novartis (significant) and Pfizer (modest). Eric E. Smith, MD, MPH, received a research grant: from the National Institutes of Health (R01 NS062028), Alberta Innovates-Health Solutions (funded by the Alberta Heritage Foundation for Medical Research), Canadian Institutes for Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, and the Hotchkiss Brain Institute, as well as honoraria from BMJ Group, QuantiaMD, and Canadian Conference on Dementia; he is also a member of the advisory board of Genentech. Deepak L. Bhatt, MD, MPH, received research grants from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis, and The Medicines Company. Adrian F. Hernandez, MD, received research grants from Johnson and Johnson. Eric D. Peterson, MD, MPH, is a principal investigator of a data analysis center for GWTG-Stroke, funded by the American Heart Association; received a research grant from Merck, Bristol-Myers Squibb, Sanofi Aventis, Eli Lilly, and Ortho-McNeil Pharmaceuticals; and is a consultant of Boehringer Ingleheim. DaiWai Olson, PhD, RN, received a research grant from Bristol-Myers Squibb. Other authors report no conflicts. NR 23 TC 13 Z9 13 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2011 VL 162 IS 4 BP 692 EP U147 DI 10.1016/j.ahj.2011.07.019 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833ZO UT WOS:000295925100019 PM 21982662 ER PT J AU Wiviott, SD Desai, N Murphy, SA Musumeci, G Ragosta, M Antman, EM Braunwald, E AF Wiviott, Stephen D. Desai, Nihar Murphy, Sabina A. Musumeci, Guiseppe Ragosta, Michael Antman, Elliott M. Braunwald, Eugene TI Efficacy and Safety of Intensive Antiplatelet Therapy With Prasugrel from TRITON-TIMI 38 in a Core Clinical Cohort Defined by Worldwide Regulatory Agencies SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; STENT THROMBOSIS; CLOPIDOGREL; TRIAL; THROMBOLYSIS; INHIBITION; ASPIRIN; STROKE AB TRITON-TIMI 38 showed that in patients with acute coronary syndrome undergoing percutaneous coronary intervention prasugrel decreased ischemic events compared to standard clopidogrel, but with more bleeding. The United States Food and Drug Administration and the European Medicines Agency approved prasugrel but provided contraindications in patients with previous stroke or transient ischemic attack and recommended limited use or reduced dose in patients >= 75 years old and weighing < 60 kg. This defined 3 clinically relevant groups of patients for use of prasugrel at the studied dose regimen: group I (core clinical cohort), group II (noncore cohort), and group III (contraindicated). We assessed clinical outcomes of patients within these cohorts in the TRITON-TIMI 38 trial. Survival analysis methods were used to compare outcomes by treatment assignment (prasugrel vs clopidogrel) and by cohort (groups I and II or III). Patients in group I (n = 10,804, 79%) treated with prasugrel had a clinically significant and robust decrease in the primary end point of cardiovascular death, myocardial infarction, or stroke (8.3 vs 11.0%, hazard ratio [HR] 0.74, 95% confidence interval 0.66 to 0.84, p < 0.0001), whereas patients in group II (n = 2149, 16%) had limited efficacy (15.3% vs 16.3%, HR 0.94, 0.76 to 1.18, p = 0.61, p for interaction = 0.07). For Thrombolysis In Myocardial Infarction major bleeding not related to coronary artery bypass grafting, there were tendencies to higher rates with prasugrel in group I(1.9% vs 1.5%, HR 1.24, 0.91 to 1.69, p = 0.17) and group II (4.1% vs 3.4%, HR 1.23, 0.77 to 1.97, p = 0.40); however, the absolute difference was greater for group II. The net clinical outcome (all-cause death/myocardial infarction/stroke/Thrombolysis In Myocardial Infarction major bleeding) in group I patients was highly favorable (10.2% vs 12.5%, HR 0.80, 0.71 to 0.89, p < 0.0001) and neutral in group II (19.5% vs 19.7%, HR 0.98, 0.81 to 1.20, p for interaction = 0.07). Patients in group III (n = 518, 4%) did poorly with regard to efficacy and safety. In TRITON-TIMI 38 patients without previous stroke, < 75 years old, and weighing > 60 kg had substantial decreases in ischemic events with prasugrel compared to clopidogrel. Although relative bleeding excess exists in this population, absolute rates and differences in bleeding were attenuated. In conclusion, these data indicate that use of prasugrel in a core clinical cohort that has been defined by regulatory action will maximize the benefit of prasugrel and limit the risk of adverse outcomes. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:905-911) C1 [Wiviott, Stephen D.; Desai, Nihar; Murphy, Sabina A.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wiviott, Stephen D.; Desai, Nihar; Murphy, Sabina A.; Antman, Elliott M.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. [Musumeci, Guiseppe] Osped Riuniti Bergamo, Cardiovasc Dept, I-24100 Bergamo, Italy. [Ragosta, Michael] Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. EM swiviott@partners.org FU Daiichi Sankyo Company, Limited; Eli Lilly and Company; Daiichi Sankyo, Parsippany, New Jersy; Eli Lilly, Indianapolis, Indiana; Sanofi-Aventis; Merck; Schering Plough FX The TRITON-TIMI 38 trial was supported by Daiichi Sankyo Company, Limited and Eli Lilly and Company. Drs. Wiviott, Antman, and Braunwald report receiving research grants from Daiichi Sankyo, Parsippany, New Jersy, Eli Lilly, Indianapolis, Indiana, Sanofi-Aventis, Merck, and Schering Plough. NR 19 TC 31 Z9 37 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2011 VL 108 IS 7 BP 905 EP 911 DI 10.1016/j.amjcard.2011.05.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833DY UT WOS:000295863200001 PM 21816379 ER PT J AU Cheng, S Fox, CS Larson, MG Massaro, JM McCabe, EL Khan, AM Levy, D Hoffmann, U O'Donnell, CJ Miller, KK Newton-Cheh, C Coviello, AD Bhasin, S Vasan, RS Wang, TJ AF Cheng, Susan Fox, Caroline S. Larson, Martin G. Massaro, Joseph M. McCabe, Elizabeth L. Khan, Abigail May Levy, Daniel Hoffmann, Udo O'Donnell, Christopher J. Miller, Karen K. Newton-Cheh, Christopher Coviello, Andrea D. Bhasin, Shalender Vasan, Ramachandran S. Wang, Thomas J. TI Relation of Visceral Adiposity to Circulating Natriuretic Peptides in Ambulatory Individuals SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; METABOLIC RISK-FACTORS; INSULIN-RESISTANCE; BODY-MASS; ASSOCIATION; ATRIAL; SENSITIVITY; DIAGNOSIS; IMPACT; AGE AB Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeostasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese individuals may underlie the greater cardiovascular risk associated with obesity. Thus the aim of this study was to determine whether lower natriuretic peptide levels in obesity are attributable to differences in regional fat distribution. We investigated the relation of plasma N-terminal pro B-type natriuretic peptide (NT pro-BNP) to regional adiposity in 1,873 community-based individuals (46% women, mean age 45 years). Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured by multidetector computed tomography. In gender-specific multivariable analyses adjusting for age and blood pressure, log NT pro-BNP was inversely associated with VAT in men (beta -0.11 per standard deviation increment, p < 0.001) and women (beta -0.19, p < 0.001). Log NT pro-BNP was inversely associated with SAT in women only (beta -0.14, p < 0.001). In models containing VAT and SAT, only VAT was significantly associated with log NT pro-BNP (men, beta -0.137, p < 0.001; women, beta -0.184, p < 0.001). VAT remained associated with log NT pro-BNP even after adjustment for body mass index and waist circumference (beta -0.119, p < 0.001) and in analyses restricted to nonobese patients (beta -0.165, p < 0.001). Adjustment for insulin resistance attenuated the associations of NT pro-BNP with VAT and SAT. In conclusion, this study demonstrates that circulating NT pro-BNP is related to variations in regional and particularly visceral adiposity. These findings suggest that excess visceral adiposity and concomitant hyperinsulinemia may contribute to the natriuretic peptide "deficiency" observed in obesity. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:979-984) C1 [Cheng, Susan; Fox, Caroline S.; Larson, Martin G.; Massaro, Joseph M.; McCabe, Elizabeth L.; Levy, Daniel; O'Donnell, Christopher J.; Newton-Cheh, Christopher; Coviello, Andrea D.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Cheng, Susan; McCabe, Elizabeth L.; Khan, Abigail May; O'Donnell, Christopher J.; Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Miller, Karen K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02115 USA. [Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA. [Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Larson, Martin G.; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel; Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Levy, Daniel; Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Coviello, Andrea D.; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Newton-Cheh, Christopher] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. EM tjwang@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland [N01-HC-25195, R01-HL-086875]; Ellison Foundation, Bethesda, Maryland FX This work was supported in part by Contracts N01-HC-25195 and R01-HL-086875 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland (Dr. Wang and Dr. Newton-Cheh) and the Ellison Foundation, Bethesda, Maryland (Dr. Cheng). NR 30 TC 23 Z9 23 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2011 VL 108 IS 7 BP 979 EP 984 DI 10.1016/j.amjcard.2011.05.033 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 833DY UT WOS:000295863200014 PM 21813106 ER PT J AU Keenan, RT Pillinger, MH AF Keenan, Robert T. Pillinger, Michael H. TI Steroid for Gout: Myth or Elixir? Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID COLCHICINE; GUIDELINES; TOXICITY C1 [Keenan, Robert T.] Duke Univ, Sch Med, Div Rheumatol & Immunol, Durham, NC 27708 USA. [Pillinger, Michael H.] NYU, New York Harbor Hlth Care Syst, US Dept Vet Affairs, Sect Rheumatol,Div Rheumatol,Sch Med, New York, NY USA. RP Keenan, RT (reprint author), Duke Univ, Sch Med, Div Rheumatol & Immunol, Durham, NC 27708 USA. NR 8 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2011 VL 124 IS 10 BP E19 EP E19 DI 10.1016/j.amjmed.2011.04.029 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 831EZ UT WOS:000295712800014 ER PT J AU Khosroshahi, A Carruthers, MD Deshpande, V Leb, L Reed, JI Stone, JH AF Khosroshahi, Arezou Carruthers, Mollie D. Deshpande, Vikram Leb, Leon Reed, John I. Stone, John H. TI Cutaneous Immunoglobulin G4-Related Systemic Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Clin, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org NR 3 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2011 VL 124 IS 10 BP E7 EP E8 DI 10.1016/j.amjmed.2011.03.011 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 831EZ UT WOS:000295712800004 PM 21722865 ER PT J AU Perlis, RH AF Perlis, Roy H. TI Hard Outcomes: Clinical Trials to Reduce Suicide SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID DISORDER; BIPOLAR; RISK C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Perlis, Roy H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM rperlis@partners.org NR 8 TC 16 Z9 16 U1 1 U2 4 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 OCT PY 2011 VL 168 IS 10 BP 1009 EP 1011 DI 10.1176/appi.ajp.2011.11081250 PG 3 WC Psychiatry SC Psychiatry GA 828DL UT WOS:000295481200001 PM 21969041 ER PT J AU Duncan, LE Keller, MC AF Duncan, Laramie E. Keller, Matthew C. TI A Critical Review of the First 10 Years of Candidate Gene-by-Environment Interaction Research in Psychiatry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID GENOME-WIDE ASSOCIATION; STRESSFUL LIFE EVENTS; COMPLEX DISEASES; METAANALYSIS; DEPRESSION; EPIDEMIOLOGY; MODERATION; GENOTYPE; 5-HTTLPR; PSYCHOPATHOLOGY AB Objective: Gene-by-environment interaction (GxE) studies in psychiatry have typically been conducted using a candidate GxE (cGxE) approach, analogous to the candidate gene association approach used to test genetic main effects. Such cGxE research has received widespread attention and acclaim, yet cGxE findings remain controversial. The authors examined whether the many positive cGxE findings reported in the psychiatric literature were robust or if, in aggregate, cGxE findings were consistent with the existence of publication bias, low statistical power, and a high false discovery rate. Method: The authors conducted analyses on data extracted from all published studies (103 studies) from the first decade (2000-2009) of cGxE research in psychiatry. Results: Ninety-six percent of novel cGxE studies were significant compared with 27% of replication attempts. These findings are consistent with the existence of publication bias among novel cGxE studies, making cGxE hypotheses appear more robust than they actually are. There also appears to be publication bias among replication attempts because positive replication attempts had smaller average sample sizes than negative ones. Power calculations using observed sample sizes suggest that cGxE studies are underpowered. Low power along with the likely low prior probability of a given cGxE hypothesis being true suggests that most or even all positive cGxE findings represent type I errors. Conclusions: In this new era of big data and small effects, a recalibration of views about groundbreaking findings is necessary. Well-powered direct replications deserve more attention than novel cGxE findings and indirect replications. C1 [Duncan, Laramie E.] Harvard Univ, McLean Hosp, Sch Med, Massachusetts Gen Hosp,Sch Publ Hlth, Belmont, MA 02178 USA. Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. RP Duncan, LE (reprint author), Harvard Univ, McLean Hosp, Sch Med, Massachusetts Gen Hosp,Sch Publ Hlth, Belmont, MA 02178 USA. EM laramied@gmail.com; matthew.c.keller@gmail.com OI KELLER, MATTHEW/0000-0002-6075-9882 FU NIMH [MH085812]; National Institute of Child Health and Human Development [HD007289] FX Presented at the World Congress of Psychiatric Gene tics in Athens, Greece, October 4-8, 2010, and at the Behavior Gene tics Association Conference, New port, R. I., June 6-9, 2011. Supported by NIMH g rant MH085812 to Dr. Keller and by National Institute of Child Health and Human Development T32 grant HD007289 to Dr. Duncan. The authors thank Gary McClelland for his help with statistical concepts and John Hewitt, Soo Rhee, and Matthew McQueen for comments and suggestions on the manuscript. NR 43 TC 344 Z9 345 U1 16 U2 131 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 OCT PY 2011 VL 168 IS 10 BP 1041 EP 1049 DI 10.1176/appi.ajp.2011.11020191 PG 9 WC Psychiatry SC Psychiatry GA 828DL UT WOS:000295481200011 PM 21890791 ER PT J AU Sepehr, A Chao, E Trefrey, B Blackford, A Duncan, LM Flotte, TJ Sober, A Mihm, MC Tsao, H AF Sepehr, Alireza Chao, Elizabeth Trefrey, Brie Blackford, Amanda Duncan, Lyn McDivitt Flotte, Thomas J. Sober, Arthur Mihm, Martin C., Jr. Tsao, Hensin TI Long-term Outcome of Spitz-Type Melanocytic Tumors SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SENTINEL LYMPH-NODE; EPITHELIOID CELL NEVI; MALIGNANT-MELANOMA; PEDIATRIC MELANOMA; BIOPSY; MUTATIONS; FEATURES; DIAGNOSIS; CHILDREN; SPINDLE AB Objective: Despite recent advances in our molecular understanding of Spitz-type tumors, the clinical behavior of these lesions remains unclear. We thus set out to define the clinical outcome of classic Spitz nevi, atypical Spitz tumors (ASTs), and spitzoid melanomas. Design: From 1987 through 2002, data on all lesions containing the term "Spitz" or "Spitz" [AND] "melanoma" were retrieved from the pathology database at Massachusetts General Hospital, and the cases were followed up for their outcome. Setting: The study was performed at a university-affiliated tertiary health care center in Boston, Massachusetts. Patients: A total of 157 patients with Spitz-type melanocytic lesions and follow-up information were identified. Main Outcome Measures: Sentinel lymph node biopsy results, metastases, or fatality were assessed. Results: There were 68 classic Spitz nevi, 76 ASTs, 10 spitzoid melanomas, and 3 melanomas that arose in Spitz nevi. Spitz nevi were diagnosed at a younger age than ASTs (mean age, 26.4 years vs 33.7 years) (P = .01), though both occurred earlier than melanomas (mean age, 50.4 years, P < .001). Sentinel lymph node biopsy findings were positive in 1 of 6 and 4 of 8 patients with ASTs and spitzoid melanomas, respectively. After a median follow-up of 9.1 years, only 1 patient with an AST, who had a separate intermediate-thickness melanoma, developed distant metastasis. There were 6 documented invasive melanomas among 144 patients with classic Spitz nevi or ASTs (observed/expected ratio, 8.03) (P = .01). Conclusions: Atypical Spitz tumors are associated with minimal lethal potential, an increased melanoma risk, and a moderate risk of metastasis to regional nodes. It makes clinical sense to minimize aggressive treatment but to offer careful surveillance for rare relapses and subsequent melanomas. C1 [Sepehr, Alireza; Chao, Elizabeth; Trefrey, Brie; Duncan, Lyn McDivitt; Sober, Arthur; Mihm, Martin C., Jr.; Tsao, Hensin] Harvard Univ, Sch Med, Boston, MA USA. [Sepehr, Alireza] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Boston, MA 02114 USA. [Duncan, Lyn McDivitt; Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Duncan, Lyn McDivitt; Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Blackford, Amanda] Johns Hopkins Sch Med, Dept Oncol Biostat, Baltimore, MD USA. [Flotte, Thomas J.] Mayo Clin, Dept Pathol, Rochester, MN USA. [Flotte, Thomas J.] Mayo Clin, Dept Dermatol, Rochester, MN USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, 50 Blossom St,Bartlett 622, Boston, MA 02114 USA. EM htsao@partners.org FU American Cancer Society [RSG-07-085-01-MGO]; National Institutes of Health [K24 CA149202-01]; MGH FX This research was supported in part by grant RSG-07-085-01-MGO from the American Cancer Society, grant K24 CA149202-01 from the National Institutes of Health, and by the MGH Millennium Fund for Melanoma Research (Dr Tsao). NR 30 TC 24 Z9 24 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 2011 VL 147 IS 10 BP 1173 EP 1179 DI 10.1001/archdermatol.2011.170 PG 7 WC Dermatology SC Dermatology GA 834FH UT WOS:000295944300008 PM 21680758 ER PT J AU Gamble, RG Dellavalle, RP AF Gamble, Ryan G. Dellavalle, Robert P. TI Ion-Exchange Water Softener Use and Eczema SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID ATOPIC-DERMATITIS SEVERITY; 6 AREA; HARDNESS; PREVALENCE; SCORE C1 [Dellavalle, Robert P.] Denver VA Med Ctr, Dept Veteran Affairs, Denver, CO 80220 USA. [Gamble, Ryan G.] Univ Colorado Denver, Dept Dermatol, Sch Med, Aurora, CO USA. RP Dellavalle, RP (reprint author), Denver VA Med Ctr, Dept Veteran Affairs, 1055 Clermont St,POB 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 10 TC 1 Z9 1 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 2011 VL 147 IS 10 BP 1208 EP 1210 PG 3 WC Dermatology SC Dermatology GA 834FH UT WOS:000295944300015 PM 22006138 ER PT J AU Norweg, A Ni, PS Garshick, E O'Connor, G Wilke, K Jette, AM AF Norweg, Anna Ni, Pengsheng Garshick, Eric O'Connor, George Wilke, Kira Jette, Alan M. TI A Multidimensional Computer Adaptive Test Approach to Dyspnea Assessment SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Dyspnea; Outcome assessment (health care); Pulmonary disease, chronic obstructive; Rehabilitation; Reproducibility of results ID OBSTRUCTIVE PULMONARY-DISEASE; COGNITIVE-BEHAVIORAL THERAPY; QUALITY-OF-LIFE; SELF-MANAGEMENT; HEALTH-STATUS; COPD; ANXIETY; QUESTIONNAIRE; OUTCOMES; MODEL AB Norweg A, Ni P, Garshick E, O'Connor G, Wilke K, Jette AM. A multidimensional computer adaptive test approach to dyspnea assessment. Arch Phys Med Rehabil 2011; 92:1561-9. Objectives: To develop and test a prototype dyspnea computer adaptive test (CAT). Design: Prospective study. Setting: Two outpatient medical facilities. Participants: A convenience sample of adults (N=292) with chronic obstructive pulmonary disease (COPD). Interventions: Not applicable. Main Outcome Measure: We developed a modified and expanded item bank and CAT for the Dyspnea Management Questionnaire (DMQ), an outcome measure consisting of 4 dyspnea dimensions: dyspnea intensity, dyspnea anxiety, activity avoidance, and activity self-efficacy. Results: Factor analyses supported a 4-dimensional model underlying the 71 DMQ items. The DMQ item bank achieved acceptable Rasch model fit statistics, good measurement breadth with minimal floor and ceiling effects, and evidence of high internal consistency reliability (alpha=.92.98). With the use of CAT simulation analyses, the DMQ-CAT showed high measurement accuracy compared with the total item pool (r=.83-.97, P<.0001) and evidence of good to excellent concurrent validity (r=-.61 to -.80, P<.0001). All DMQ-CAT domains showed evidence for known-groups validity (P <=.001). Conclusions: The DMQ-CAT reliably and validly captured 4 distinct dyspnea domains. Multidimensional dyspnea assessment in COPD is needed to better measure the effectiveness of pharmacologic, pulmonary rehabilitation, and psychosocial interventions in not only alleviating the somatic sensation of dyspnea but also reducing dysfunctional emotions, cognitions, and behaviors associated with dyspnea, especially for anxious patients. C1 [Norweg, Anna; Ni, Pengsheng; Wilke, Kira; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [O'Connor, George] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. RP Norweg, A (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St T5W, Boston, MA 02118 USA. EM anorweg@bu.edu OI Jette, Alan/0000-0002-2117-9973; O'Connor, George/0000-0002-6476-3926; Ni, Pengsheng/0000-0003-1774-2185 FU National Heart, Lung, and Blood Institute, National Institutes of Health [1R21HL091237-01] FX Supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (grant no. 1R21HL091237-01). NR 53 TC 8 Z9 8 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2011 VL 92 IS 10 BP 1561 EP 1569 DI 10.1016/j.apmr.2011.05.020 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 833DE UT WOS:000295861200005 PM 21963123 ER PT J AU Greenberg, CC Lipsitz, SR Neville, B In, H Hevelone, N Porter, SA Weeks, C Jha, AK Gawande, AA Schrag, D Weeks, JC AF Greenberg, Caprice C. Lipsitz, Stuart R. Neville, Bridget In, Haejin Hevelone, Nathanael Porter, Stacy A. Weeks, Christine Jha, Ashish K. Gawande, Atul A. Schrag, Deborah Weeks, Jane C. TI Receipt of Appropriate Surgical Care for Medicare Beneficiaries With Cancer SO ARCHIVES OF SURGERY LA English DT Article ID QUALITY; CLAIMS AB Objective: To investigate receipt of appropriate surgical care in Medicare beneficiaries with cancer. Design: Retrospective cohort study. Setting: National Surveillance, Epidemiology, and End Results registry linked to Medicare claims data. Patients: Fee-for-service Medicare patients aged 65 years or older who underwent a definitive surgical resection for breast, colon, gastric, rectal, or thyroid cancer diagnosed between January 2000 and December 2005. Claims data were available from January 1999 through December 2007. Main Outcome Measures: Receipt of care concordant with established practice guidelines in surgical oncology in the aggregate and by hospital. Results: Concordance with guidelines was greater than 90% for 7 of 11 measures. All guidelines regarding adjuvant therapy had concordance rates greater than 90%. Only 2 of 5 measures for nodal management had concordance rates greater than 90%. At least 50% of hospitals provided guideline-concordant care to 100% of their patients for 6 of 11 guidelines. Patients receiving appropriate care tended to be younger, healthier, white, and more affluent, to have less advanced disease, and to live in the Midwest. Conclusions: We found a high level of concordance with guidelines in some domains of surgical oncology care but far less so in others, particularly for gastric and colon nodal management. Given the current national focus on improving the quality of health care, surgeons must focus on generating data to define appropriate care and translating those data into everyday practice. C1 [Greenberg, Caprice C.; Lipsitz, Stuart R.; In, Haejin; Hevelone, Nathanael; Weeks, Christine; Gawande, Atul A.] Harvard Univ, Ctr Surg & Publ Hlth, Brigham & Womens Hosp, Sch Publ Hlth,Dept Surg, Boston, MA 02115 USA. [Greenberg, Caprice C.; Neville, Bridget; In, Haejin; Schrag, Deborah; Weeks, Jane C.] Harvard Univ, Sch Publ Hlth, Ctr Outcomes & Policy Res, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Jha, Ashish K.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Porter, Stacy A.] Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, CC (reprint author), Harvard Univ, Ctr Surg & Publ Hlth, Brigham & Womens Hosp, Sch Publ Hlth,Dept Surg, 1 Brigham Circle,1620 Tremont St,4-020, Boston, MA 02115 USA. EM ccgreenberg@partners.org OI Gawande, Atul/0000-0002-1824-9176; Hevelone, Nathanael/0000-0003-4740-2085 FU American Surgical Association Foundation FX Funding/Support: This work was supported in part by a grant from the American Surgical Association Foundation. NR 20 TC 19 Z9 19 U1 1 U2 1 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 OCT PY 2011 VL 146 IS 10 BP 1128 EP 1134 DI 10.1001/archsurg.2011.141 PG 7 WC Surgery SC Surgery GA 834EN UT WOS:000295942300004 PM 21690439 ER PT J AU Goldschmidt, A Wilfley, DE Eddy, KT Boutelle, K Zucker, N Peterson, CB Celio-Doyle, A Le Grange, D AF Goldschmidt, Andrea Wilfley, Denise E. Eddy, Kamryn T. Boutelle, Kerri Zucker, Nancy Peterson, Carol B. Celio-Doyle, Angela Le Grange, Daniel TI Overvaluation of shape and weight among overweight children and adolescents with loss of control eating SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Binge eating; Loss of control; Overvaluation of shape and weight ID RANDOMIZED CONTROLLED-TRIAL; SELF-ESTEEM SCALE; BULIMIA-NERVOSA; DISORDER EXAMINATION; CLINICAL-SIGNIFICANCE; RISK-FACTORS; GIRLS; BEHAVIORS; PSYCHOPATHOLOGY; ATTITUDES AB Little is known about the phenomenology of pediatric loss of control (LOC) eating. Overvaluation of shape and weight, however, appears to be diagnostically meaningful among binge eating adults. We explored the significance of shape and weight overvaluation among children and adolescents with LOC eating. Participants (n = 526) included 149 overweight youth with LOC eating and 377 overweight controls (CON). Participants were categorized as those reporting at least moderate overvaluation (LOC-Mod, n = 74; CON-Mod, n = 106) or less than moderate overvaluation (LOC-Low, n = 75; CON-Low, n = 271), and compared on measures of eating-related and general psychopathology. LOC-Mod evidenced lower self-esteem than CON-Low, and greater behavioral problems than CON-Mod and CON-Low, but did not differ from LOC-Low in these domains. With the exception of LOC-Low and CON-Mod, all groups differed on global eating-disorder severity, with LOC-Mod scoring the highest. Overvaluation of shape and weight appears to be of questionable importance in defining subtypes of youth with LOC eating. However, as overvaluation and LOC eating each independently predicts eating-disorder onset, their confluence may confer even further risk for eating-disorder development. Longitudinal studies should address this possibility. Developmentally appropriate discussion about body image disturbance may be indicated in interventions targeting pediatric LOC eating and/or obesity. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Goldschmidt, Andrea; Celio-Doyle, Angela; Le Grange, Daniel] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Wilfley, Denise E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Boutelle, Kerri] Univ Calif San Diego, Dept Pediat & Psychiat, La Jolla, CA 92037 USA. [Zucker, Nancy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Peterson, Carol B.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55454 USA. RP Goldschmidt, A (reprint author), Univ Chicago, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC 3077, Chicago, IL 60637 USA. EM goldschmidta@uchicago.edu; wilfleyd@psychiatry.wustl.edu; keddy@partners.org; kboutelle@ucsd.edu; zucke001@mc.duke.edu; peter161@umn.edu; acdoyle@uchicago.edu; legrange@uchicago.edu FU NICHD NIH HHS [R01 HD036904, R01 HD036904-01A1, R01-HD036904]; NIDDK NIH HHS [P30 DK050456, P30 DK050456-06, P30-DK50456]; NIMH NIH HHS [T32-MH082761, F31 MH071019, F31 MH071019-01A1, F31-MH071019, K24 MH070446, K24 MH070446-01, K24-MH070446, T32 MH082761, T32 MH082761-01A1] NR 52 TC 5 Z9 5 U1 1 U2 15 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 OCT PY 2011 VL 49 IS 10 BP 682 EP 688 DI 10.1016/j.brat.2011.07.011 PG 7 WC Psychology, Clinical SC Psychology GA 827QO UT WOS:000295443200013 PM 21835393 ER PT J AU Farwell, WR Lourenco, C Holmberg, E Hall, RB D'Avolio, L Lawler, EV Gaziano, JM AF Farwell, Wildon R. Lourenco, Christopher Holmberg, Erika Hall, Robert B. D'Avolio, Leonard Lawler, Elizabeth V. Gaziano, J. Michael TI The association between height and prostate cancer grade in the Early Stage Prostate Cancer Cohort Study SO CANCER CAUSES & CONTROL LA English DT Article DE Prostatic neoplasms; Body height; Epidemiology ID GROWTH-FACTOR-I; FACTOR BINDING PROTEIN-3; LIFE-STYLE FACTORS; INCREASED RISK; PLASMA-LEVELS; ELDERLY-MEN; SURVIVAL; WHITE; AGE AB Objective We examined the relationship between height and prostate cancer grade. Methods The Early Stage Prostate Cancer Cohort Study is an observational cohort of 1,037 men diagnosed with early-stage prostate cancer, T0-3NxM0. High-grade prostate cancer was defined as a biopsy Gleason score >= 7 (4 + 3). Logistic regression models were created to calculate odds ratios (OR) and 95% confidence intervals (CI) for the cross-sectional relationship between height and prostate cancer grade in the overall cohort and subpopulations. Results We identified 939 participants with a biopsy Gleason score. High-grade prostate cancer was diagnosed in 138 participants. Overall, participants in the highest quartile of height were more than twice as likely to have a Gleason score >= 7 (4 + 3) than participants in the lowest quartile of height, OR 2.14 (95% CI 1.11, 4.14), after multivariate adjustment. Participants in the highest quartile of height were more likely to be diagnosed with high-grade prostate cancer than participants in the lowest quartile of height among participants who were black, OR 8.00 (95% CI 1.99, 32.18), and participants who had diabetes mellitus, OR 5.09 (95% CI 1.30, 19.98). Conclusions Height is associated with increased risk of high-grade prostate cancer overall and perhaps among certain subpopulations. C1 [Farwell, Wildon R.; Gaziano, J. Michael] VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA. [Farwell, Wildon R.; Lourenco, Christopher; Holmberg, Erika; Hall, Robert B.; D'Avolio, Leonard; Lawler, Elizabeth V.; Gaziano, J. Michael] Vet Affairs Med Ctr, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Farwell, Wildon R.; D'Avolio, Leonard; Lawler, Elizabeth V.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Farwell, Wildon R.; D'Avolio, Leonard; Lawler, Elizabeth V.; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Farwell, WR (reprint author), VA Boston Healthcare Syst, Dept Med, 150 S Huntington Ave, Boston, MA 02130 USA. EM wfarwell@gmail.com FU Department of Defense [W81XWH-08-2-0168]; Department of Veterans Affairs Office of Research and Development [601, 96] FX Supported by research award W81XWH-08-2-0168 from the Department of Defense and grants 601 and 96 from the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. NR 30 TC 2 Z9 3 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2011 VL 22 IS 10 BP 1453 EP 1459 DI 10.1007/s10552-011-9820-x PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 834VJ UT WOS:000295992000011 PM 21773817 ER PT J AU Jagannath, AD Johri, AM Liberthson, R Larobina, M Passeri, J Tighe, D Agnihotri, AK AF Jagannath, Anand D. Johri, Amer M. Liberthson, Richard Larobina, Marco Passeri, Jonathan Tighe, Dennis Agnihotri, Arvind K. TI Quadricuspid Aortic Valve: A Report of 12 Cases and a Review of the Literature SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE aortic valve; quadricuspid; echocardiography ID SURGICAL-TREATMENT; RARE CAUSE; REGURGITATION; ENDOCARDITIS; STENOSIS; ANEURYSM; REPAIR AB Quadricuspid aortic valve (QAV) is rare and its diagnosis, clinical course, and management are less well defined relative to other aortic valve abnormalities. Advances in diagnostic imaging, notably in ultrasound, have increased clinical awareness of this anomaly and prompted this review of our experience with 12 new patients and a compilation of previously reported patients to further characterize this condition. (Echocardiography 2011;28:1035-1040) C1 [Jagannath, Anand D.; Larobina, Marco; Agnihotri, Arvind K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Johri, Amer M.; Passeri, Jonathan] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Liberthson, Richard] Massachusetts Gen Hosp, Div Cardiol, Congenital Heart Dis Program, Boston, MA 02114 USA. [Tighe, Dennis] Univ Massachusetts Mem Hosp, Dept Cardiol, Worcester, MA USA. RP Johri, AM (reprint author), Kingston Gen Hosp, FAPC 3, 76 Stuart St, Kingston, ON K7L 2V7, Canada. EM amerjohri@gmail.com NR 25 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD OCT PY 2011 VL 28 IS 9 BP 1035 EP 1040 DI 10.1111/j.1540-8175.2011.01477.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834OQ UT WOS:000295971900023 PM 21854429 ER PT J AU Margey, R Roy, A Tobin, S O'Keane, CJ McGorrian, C Morris, V Jennings, S Galvin, J AF Margey, Ronan Roy, Andrew Tobin, Sandra O'Keane, Conor J. McGorrian, Catherine Morris, Valerie Jennings, Siobhan Galvin, Joseph TI Sudden cardiac death in 14-to 35-year olds in Ireland from 2005 to 2007: a retrospective registry SO EUROPACE LA English DT Article DE Sudden cardiac death; Sudden arrhythmic death syndrome; Hypertrophic cardiomyopathy; Post-mortem; Autopsy ID LONG-QT SYNDROME; TEMPORAL TRENDS; HEART-DISEASE; UNITED-STATES; POPULATION; YOUNG; NATIONWIDE AB Introduction Sudden cardiac death (SCD) in young people is a rare but devastating event for families and communities. Ireland has previously had no measure of the incidence of SCD in young people. We report the incidence and causes of SCD in persons <35 years of age. Methods and results We undertook a retrospective study of SCD between 2005 and 2007 in persons aged 15-35 years in the Republic of Ireland. We identified potential cases of out of hospital SCD through the Central Statistics Office (CSO) death certificate records. Autopsy, toxicology, and inquest reports were then obtained and analysed by an expert panel who adjudicated on the cause of death. A total of 342 potential SCD cases were identified through the CSO. Fifty were younger than 15 years of age, and 86 had either incomplete or unavailable post-mortem reports. Of 206 full reports obtained, 116 were adjudicated as cases of SCD. Cases were predominantly male (75%), with a mean age of 25.8 years (standard deviation 6.3). The incidence of SCD in this age range was 2.85 per 100 000 person-years (4.36 for males and 1.30 for females) and the incidence of sudden arrhythmic death syndrome (SADS) was 0.76 per 100 000 person-years. The commonest causes were SADS, 26.7% (31 of 116), followed by coronary artery disease, 20.7% (24 of 116), hypertrophic cardiomyopathy (HCM), 14.7% (17 of 116), and idiopathic left ventricular hypertrophy not fulfilling criteria for HCM, 10.3% (12 of 116). Conclusions The incidence of SCD in the young in Ireland was 4.96 (95% CI 3.06, 6.4) for males and 1.3 (95% CI 0.62, 2.56) for females per 100 000 person-years. Sudden arrhythmic death syndrome was the commonest cause of SCD in the young, and the incidence of SADS was more than five times that in official reports of the Irish CSO. C1 [Margey, Ronan; Roy, Andrew; McGorrian, Catherine; Galvin, Joseph] Mater Misericordiae Univ Hosp, Sudden Cardiac Death Young Registry, Dublin 7, Ireland. [Margey, Ronan] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Margey, Ronan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tobin, Sandra] Cent Stat Off, Cork, Ireland. [O'Keane, Conor J.] Mater Misericordiae Univ Hosp, Dept Pathol, Dublin 7, Ireland. [Morris, Valerie] Royal Coll Surgeons Ireland, Dublin 2, Ireland. RP Galvin, J (reprint author), Mater Misericordiae Univ Hosp, Sudden Cardiac Death Young Registry, Eccles St, Dublin 7, Ireland. EM joseph.galvin1@gmail.com OI Roy, Andrew/0000-0001-5677-1048 FU Mater Foundation; Health Service Executive of Ireland FX Funding for the National Sudden Cardiac Death in the Young Registry has been provided by the Mater Foundation and the Health Service Executive of Ireland. NR 24 TC 46 Z9 50 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD OCT PY 2011 VL 13 IS 10 BP 1411 EP 1418 DI 10.1093/europace/eur161 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 827GA UT WOS:000295415200011 PM 21798877 ER PT J AU Beinart, R Guy, ML Ellinor, PT AF Beinart, Roy Guy, Mary L. Ellinor, Patrick T. TI Intermittent, erratic behaviour of an implantable cardioverter defibrillator secondary to a hidden magnetic source of interference SO EUROPACE LA English DT Article C1 [Beinart, Roy; Guy, Mary L.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Beinart, R (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM rbeinart@partners.org FU National Institutes of Health [R01HL092577, R01HL104156, R21DA027021, K24HL105780] FX National Institutes of Health (R01HL092577, R01HL104156, R21DA027021, and K24HL105780 to P.T.E.) NR 3 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD OCT PY 2011 VL 13 IS 10 BP 1508 EP 1509 DI 10.1093/europace/eur152 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 827GA UT WOS:000295415200027 PM 21576126 ER PT J AU Elkin, EB Marshall, DA Kulin, NA Ferrusi, IL Hassett, MJ Ladabaum, U Phillips, KA AF Elkin, Elena B. Marshall, Deborah A. Kulin, Nathalie A. Ferrusi, Ilia L. Hassett, Michael J. Ladabaum, Uri Phillips, Kathryn A. TI Economic evaluation of targeted cancer interventions: Critical review and recommendations SO GENETICS IN MEDICINE LA English DT Review DE breast cancer; economic analysis; cost-effectiveness analysis; targeted therapy; personalized medicine; BRCA; trastuzumab; gene expression profiling ID COST-EFFECTIVENESS ANALYSIS; STAGE BREAST-CANCER; ADJUVANT TRASTUZUMAB THERAPY; RT-PCR ASSAY; LYNCH-SYNDROME; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; MUTATION CARRIERS; AMERICAN-SOCIETY; OVARIAN-CANCER AB Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting. Genet Med 2011:13(10):853-860. C1 [Elkin, Elena B.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Marshall, Deborah A.; Kulin, Nathalie A.] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Marshall, Deborah A.; Ferrusi, Ilia L.] McMaster Univ, Ctr Evaluat Med, Hamilton, ON, Canada. [Hassett, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ladabaum, Uri] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Phillips, Kathryn A.] Univ Calif San Francisco, Inst Hlth Policy Studies, Ctr Comprehens Canc, Ctr Translat & Policy Res Personalized Med TRANSP, San Francisco, CA 94143 USA. [Phillips, Kathryn A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave,Box 44, New York, NY 10065 USA. EM elkine@mskcc.org RI Marshall, Deborah/J-7248-2015 OI Marshall, Deborah/0000-0002-8467-8008 FU National Cancer Institute [P01CA130818, K07CA118189]; Center for Translational and Policy Research on Personalized Medicine (TRANSPERS Center), University of California-San Francisco; Canada Research Chair in Health Systems and Services Research; Epigenomics; Abbott Molecular FX Dr. Ladabaum has consulted for Given Imaging, Quest Diagnostics, and Abbott Molecular. Dr. Ladabaum has received grants from Epigenomics and Abbott Molecular and has stock options with GeneNews. Dr. Marshall has consulted for i3 Innovus. Drs. Elkin, Hassett and Phillips, and Ms. Kulin and Ms. Ferrusi have no commercial associations to disclose.; This work was supported by a grant from the National Cancer Institute (P01CA130818), PI: Phillips) and by the Center for Translational and Policy Research on Personalized Medicine (TRANSPERS Center), University of California-San Francisco. Dr. Elkin is supported by a career development award from the National Cancer Institute (K07CA118189). Dr. Marshall is supported by a Canada Research Chair in Health Systems and Services Research. NR 67 TC 5 Z9 5 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2011 VL 13 IS 10 BP 853 EP 860 DI 10.1097/GIM.0b013e31821f3e64 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 833KN UT WOS:000295884200001 PM 21637102 ER PT J AU Sultan, I Rodriguez-Galindo, C Al-Sharabati, S Guzzo, M Casanova, M Ferrari, A AF Sultan, Iyad Rodriguez-Galindo, Carlos Al-Sharabati, Sereen Guzzo, Marco Casanova, Michela Ferrari, Andrea TI SALIVARY GLAND CARCINOMAS IN CHILDREN AND ADOLESCENTS: A POPULATION-BASED STUDY, WITH COMPARISON TO ADULT CASES SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE salivary glands; carcinoma; children; adolescents; SEER; prognosis ID MUCOEPIDERMOID CARCINOMA; TREP PROJECT; RARE TUMORS; NEOPLASMS; CHILDHOOD; EXPERIENCE; CLASSIFICATION; CANCER AB Background. Salivary gland carcinomas are rare malignancies, particularly in young individuals in whom only scanty data are available from published studies. Methods. We searched the SEER database (1973-2006) for patients with a reported diagnosis of salivary gland carcinoma; children/adolescents (< 20 years old) were compared with adults. Results. We identified 263 children/adolescents (58% girls) and 12,571 adults (43% women). The most common histology was mucoepidermoid carcinoma in both groups, but the percentages of other histologies were different. Children/adolescents had more favorable features with most tumors being localized, with no extension to adjacent tissues or lymphatic spread (76% vs 50% in adults, p < .001). Also most tumors were well differentiated or moderately differentiated (88% vs 49% in adults, p < .001). The 5-year overall survival for children/adolescents was 95% +/- 1.5%, compared with 59% +/- 0.5% for adults (p < .001). Conclusion. When compared with adults, salivary gland carcinomas in children/adolescents are less advanced, and have more favorable features and better outcome. Head Neck 33: 1476-1481, 2011 C1 [Sultan, Iyad] King Hussein Canc Ctr, Dept Pediat Oncol, Amman, Jordan. [Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Al-Sharabati, Sereen] Private Dent Clin, Amman, Jordan. [Guzzo, Marco] Ist Nazl Tumori, Otorhinolaryngol Unit, I-20133 Milan, Italy. [Casanova, Michela; Ferrari, Andrea] Ist Nazl Tumori, Pediat Oncol Unit, I-20133 Milan, Italy. RP Sultan, I (reprint author), King Hussein Canc Ctr, Dept Pediat Oncol, Amman, Jordan. EM isultan@khcc.jo RI Casanova, Michela/K-8436-2016; OI Casanova, Michela/0000-0003-0368-7883; Ferrari, Andrea/0000-0002-4724-0517 NR 23 TC 33 Z9 33 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 IS 10 BP 1476 EP 1481 DI 10.1002/hed.21629 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KH UT WOS:000295883400013 PM 21928420 ER PT J AU Kent, RD Robbins, J AF Kent, Ray D. Robbins, JoAnne TI INTRODUCTION TO THE SPECIAL ISSUE, INTEGRATIVE NEURAL SYSTEMS UNDERLYING VITAL AERODIGESTIVE TRACT FUNCTIONS SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article ID MUSCLES; SPEECH; DYNAMICS; NETWORK; TONGUE AB This special issue is an outgrowth of the conference, "Integrative Neural Systems Underlying Vital Aerodigestive Tract Functions,'' held in Madison, Wisconsin, June 17-19, 2010. The program included 3 plenary lectures, 4 keynote lectures, and 15 scientific papers. In addition, workgroup presentations, and panel discussions provided opportunities for general discussion and integration of information in a multidisciplinary context. This special issue is intended to disseminate major conclusions, potential directions for research, and unique approaches for consideration of application to clinical practice arising from the conference. The contributions assembled in this issue include 7 articles based on the plenary or keynote lectures, an invited perspective on laryngeal function, and a summary of workgroup discussions held at the conference. In this introductory article, names printed in upper case refer to articles in this special issue. C1 [Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Kent, Ray D.] Univ Wisconsin, Waisman Ctr, Dept Communicat Disorders, Madison, WI 53705 USA. [Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. EM jrobbin2@wisc.edu FU NIDCD NIH HHS [#1R13DC009556-01A109] NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S1 EP S4 DI 10.1002/hed.21900 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700001 PM 21901778 ER PT J AU Malandraki, GA Johnson, S Robbins, J AF Malandraki, Georgia A. Johnson, Sterling Robbins, JoAnne TI FUNCTIONAL MRI OF SWALLOWING: FROM NEUROPHYSIOLOGY TO NEUROPLASTICITY SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE fMRI; swallowing; neuroimaging; neuroplasticity; dysphagia ID CEREBRAL CORTICAL REPRESENTATION; PENETRATION-ASPIRATION SCALE; MAGNETIC-RESONANCE; BRAIN-FUNCTION; SENSORY STIMULATION; NEURAL PLASTICITY; OLDER-ADULTS; ACTIVATION; DYSPHAGIA; FMRI AB Swallowing is a complex neurogenic sensorimotor process involving all levels of the neuraxis and a vast number of muscles and anatomic structures. Disruption of any of these anatomic or functional components can lead to swallowing disorders (also known as dysphagia). Understanding the neural pathways that govern swallowing is necessary in diagnosing and treating patients with dysphagia. Functional MRI (fMRI) is a prevalent and effective neuroimaging method that has been used to study the complex neurophysiologic control of swallowing in vivo. This article presents a summary of the research studies that have used fMRI to study the neural control of swallowing in normal subjects and dysphagic patients, and to investigate the effects of swallowing treatments on neuroplasticity. Methodologic challenges and caveats are discussed, and a case study of a pre-posttreatment paradigm is presented to highlight potential future directions of fMRI applications in swallowing research and clinical practice. (C) 2011 Wiley Periodicals, Inc. Head Neck 33: S14-S20, 2011 C1 [Malandraki, Georgia A.] Columbia Univ, Teachers Coll, Program Speech & Language Pathol, Dept Biobehav Sci, New York, NY 10027 USA. [Malandraki, Georgia A.; Johnson, Sterling; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Malandraki, Georgia A.; Johnson, Sterling; Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Malandraki, GA (reprint author), Columbia Univ, Teachers Coll, Program Speech & Language Pathol, Dept Biobehav Sci, New York, NY 10027 USA. EM malandraki@tc.columbia.edu OI Johnson, Sterling/0000-0002-8501-545X FU NIA NIH HHS [P50 AG033514]; NICHD NIH HHS [P30 HD003352]; NIDCD NIH HHS [#1R13DC009556-01A1S1, R13 DC009556] NR 62 TC 6 Z9 9 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S14 EP S20 DI 10.1002/hed.21903 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700004 PM 21901779 ER PT J AU Robbins, J AF Robbins, JoAnne TI UPPER AERODIGESTIVE TRACT NEUROFUNCTIONAL MECHANISMS: LIFELONG EVOLUTION AND EXERCISE SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE dysphagia; dysarthria; obstructive sleep apnea; sarcopenia; exercise; neural maturation; neuromuscular plasticity ID LINGUAL EXERCISE; ORAL-PHARYNGEAL; DYSPHAGIA; STRENGTH; AGE; PLASTICITY; SARCOPENIA; PRESSURE; MUSCLE; ADULTS AB The transformation of the upper aerodigestive tract - oral cavity, pharynx, and larynx - serves the functions of eating, speaking, and breathing during sleeping and waking hours. These life-sustaining functions may be produced by a central neural sensorimotor system that shares certain neuroanatomic networks while maintaining separate neural functional systems and network structures. Current understanding of development, maturation, underlying neural correlates, and integrative factors are discussed in light of currently available imaging modalities and recently emerging interventions. Exercise and an array of additional treatments together seem to provide promising translational pathways for evidence-based innovation, novel habilitation, and rehabilitation strategies and delay, or even prevent neuromuscular decline cross-cutting functions and supporting quality of life throughout increasingly enduring lifespans. (C) 2011 Wiley Periodicals, Inc. Head Neck 33: S30-S36, 2011 C1 [Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Robbins, JoAnne] Univ Wisconsin, Dept Med, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. EM jrobbin2@wisc.edu FU NIDCD NIH HHS [#1R13DC009556-01A1S1, R13 DC009556] NR 51 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2011 VL 33 SU 1 SI SI BP S30 EP S36 DI 10.1002/hed.21902 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 833KS UT WOS:000295884700007 PM 21910155 ER PT J AU Federman, AD Keyhani, S AF Federman, Alex D. Keyhani, Salomeh TI Physicians' participation in the Physicians' Quality Reporting Initiative and their perceptions of its impact on quality of care SO HEALTH POLICY LA English DT Article DE Quality improvement; Reporting; Physician incentives; Health care reform ID PAY-FOR-PERFORMANCE; HEALTH-CARE; PROGRAMS; IMPROVEMENT; PROSPECTS; MEDICARE; VIEWS; COST AB Background: Medicare established the Physicians Quality Reporting Initiative (PQRI, recently renamed the Physicians Quality Reporting System) to increase reporting of quality metrics and promote healthcare quality. Objective: To identify characteristics of PQRI participants and examine their beliefs about its impact. Design: National survey of 4934 U.S. physicians, conducted June through October 2009. Setting: All practice settings. Participants: Randomly selected physicians categorized as primary care, medical specialists, surgeons, other specialists. Measurements: Beliefs about impact of PQRI reporting on quality. Results: The response rate was 49.8%. There were no significant differences between respondents and non-respondents by age, gender, specialty, and region. Thirty-eight percent participated in the PQRI, and were more likely than non-participants to be practice owners (69.0% vs. 57.1%, p < .0001) and to receive performance bonuses through their employer or practice (50.4% vs. 37.0%, p < .0001). Half of PQRI participants believed it had no impact on quality. Medical specialists (57.0%) and surgeons (55.1%) were more likely than primary care (40.4%) and other physicians (45.7%) to say that PQRI has no impact on quality (p = .004). Conclusions: Most PQRI participants believed it had little if any impact on quality. Medicare should identify the reasons behind physicians' negative views while it works to expand the Physicians Quality Reporting System. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Federman, Alex D.; Keyhani, Salomeh] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Bronx, NY USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. [Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, Box 1087,1 Gustave L Levy Pl, New York, NY 10029 USA. EM alex.federman@mssm.edu FU Robert Wood Johnson Foundation; National Institute on Aging; American Federation on Aging Research; Veterans Administration Health Services Research and Development Service FX This study was supported by a grant from the Robert Wood Johnson Foundation. Additionally, Dr. Federman is supported in part by a Paul B. Beeson career development award in aging related research from the National Institute on Aging and the American Federation on Aging Research, and Dr. Keyhani is supported by a career development award from the Veterans Administration Health Services Research and Development Service. NR 28 TC 16 Z9 16 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD OCT PY 2011 VL 102 IS 2-3 BP 229 EP 234 DI 10.1016/j.healthpol.2011.05.003 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 831BR UT WOS:000295704200014 PM 21628079 ER PT J AU Kroy, DC Ciuffreda, DB Hauck, G Tomlinson, M Tanabe, KK Elias, N Misdraji, J Lauer, GM AF Kroy, Daniela C. Ciuffreda, Donatella B. Hauck, Garrett Tomlinson, Michelle Tanabe, Kenneth K. Elias, Nahel Misdraji, Joseph Lauer, Georg M. TI LIVER-TISSUE-SPECIFIC VERSUS DISEASE-SPECIFIC EXPRESSION OF T-CELL INHIBITORY RECEPTORS AND LIGANDS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kroy, Daniela C.; Ciuffreda, Donatella B.; Hauck, Garrett; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Tomlinson, Michelle; Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Elias, Nahel] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 380A EP 381A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002041 ER PT J AU Kumthip, K Maneekarn, N O'Brien, A Thongsawat, S Pantip, C Chusri, P Zhao, H Goto, K Jilg, N Cheng, D Peng, LF Fusco, DN Schaefer, EA Chung, RT Lin, WY AF Kumthip, Kattareeya Maneekarn, Niwat O'Brien, Amornrat Thongsawat, Satawat Pantip, Chansom Chusri, Pattranuch Zhao, Hong Goto, Kaku Jilg, Nikolaus Cheng, Du Peng, Lee F. Fusco, Dahlene N. Schaefer, Esperance A. Chung, Raymond T. Lin, Wenyu TI HCV NS5A DISRUPTED STAT1 PHOSPHORYLATION AND ASSOCIATED WITH SUPPRESSION OF IFN SIGNALING SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kumthip, Kattareeya; Pantip, Chansom; Chusri, Pattranuch; Zhao, Hong; Goto, Kaku; Jilg, Nikolaus; Cheng, Du; Peng, Lee F.; Fusco, Dahlene N.; Schaefer, Esperance A.; Chung, Raymond T.; Lin, Wenyu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Kumthip, Kattareeya; Maneekarn, Niwat; O'Brien, Amornrat; Thongsawat, Satawat; Pantip, Chansom] Chiang Mai Univ, Fac Med, Chiang Mai 50000, Thailand. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 406A EP 407A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002095 ER PT J AU Kanwal, F Kramer, JR Buchanan, P Asch, S Assioun, Y Gary, J Li, J Bacon, BR El-Serag, H AF Kanwal, Fasiha Kramer, Jennifer R. Buchanan, Paula Asch, Steven Assioun, Youssef Gary, Julie Li, Juan Bacon, Bruce R. El-Serag, Hashem TI THE QUALITY OF CARE PROVIDED TO PATIENTS WITH CIRRHOSIS AND ASCITES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kanwal, Fasiha; Gary, Julie; Li, Juan] St Louis VA Med Ctr, St Louis, MO USA. [Kanwal, Fasiha; Buchanan, Paula; Assioun, Youssef; Gary, Julie; Bacon, Bruce R.] St Louis Univ, Sch Med, St Louis, MO USA. [Kramer, Jennifer R.; El-Serag, Hashem] Houston VA, Houston, TX USA. [Kramer, Jennifer R.; El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Asch, Steven] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 408A EP 408A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002098 ER PT J AU Rongey, C Hamilton, N Asch, S Knight, S AF Rongey, Catherine Hamilton, Nathan Asch, Steven Knight, Sara TI GEOGRAPHIC DIFFERENCES IN ACCESS TO AND QUALITY OF LIVER CARE AMONG A NATIONAL COHORT OF VETERAN HEALTH ADMINISTRATION PATIENTS WITH HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rongey, Catherine; Hamilton, Nathan; Knight, Sara] San Francisco VA Med Ctr, San Francisco, CA USA. [Rongey, Catherine; Knight, Sara] UCSF, San Francisco, CA USA. [Asch, Steven] Univ Calif Los Angeles, Los Angeles, CA USA. [Asch, Steven] WLA VAMC, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 410A EP 410A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002102 ER PT J AU Zhu, NL Liu, JC Machida, K Tsukamoto, H AF Zhu, Nian-Ling Liu, Jian-Chang Machida, Keigo Tsukamoto, Hidekazu TI DLK1 AS AN ANTI-ADIPOGENIC MEDIATOR FOR ACTIVATION OF HEPATIC STELLATE CELLS IN LIVER FIBROSIS, REGENERATION, AND CANCER SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Zhu, Nian-Ling; Liu, Jian-Chang; Machida, Keigo; Tsukamoto, Hidekazu] Univ So Calif, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. [Zhu, Nian-Ling] Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. [Liu, Jian-Chang; Machida, Keigo] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA USA. [Tsukamoto, Hidekazu] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 424A EP 424A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002132 ER PT J AU Chan, K Lai, MN Groessl, EJ Hanchate, AD Hernandez, L Wong, JB Clark, J Asch, S Gifford, AL Ho, SB AF Chan, Kee Lai, Mai-Ngan Groessl, Erik J. Hanchate, Amresh D. Hernandez, Leilani Wong, John B. Clark, Jack Asch, Steven Gifford, Allen L. Ho, Samuel B. TI LONG TERM CLINICAL IMPACT OF DIRECT ANTIVIRAL AGENT (DAA) THERAPY FOR UNTREATED CHRONIC HEPATITIS C GENOTYPE 1 INFECTION IN THE VETERANS HEALTH ADMINISTRATION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lai, Mai-Ngan; Groessl, Erik J.; Ho, Samuel B.] VA San Diego Healthcare Syst, Gastroenterol, San Diego, CA USA. [Chan, Kee; Hanchate, Amresh D.; Hernandez, Leilani; Clark, Jack; Gifford, Allen L.] Boston Univ, Boston, MA 02215 USA. [Lai, Mai-Ngan; Groessl, Erik J.; Ho, Samuel B.] Univ Calif San Diego, San Diego, CA 92103 USA. [Asch, Steven] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chan, Kee; Hanchate, Amresh D.; Hernandez, Leilani; Clark, Jack; Gifford, Allen L.] VA Med Ctr, Boston, MA USA. [Wong, John B.] Tufts Univ, Boston, MA 02111 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 437A EP 438A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002158 ER PT J AU Bunchorntavakul, C Jones, LM Kikuchi, M Valiga, ME Nunes, F Aytaman, A Kaplan, DE Reddy, R Chang, KM AF Bunchorntavakul, Chalermrat Jones, Lisa M. Kikuchi, Masahiro Valiga, Mary E. Nunes, Frederick Aytaman, Ayse Kaplan, David E. Reddy, Rajender Chang, Kyong-Mi TI ACUTE HEPATITIS C: PRESENTATION AND CLINICAL COURSE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Bunchorntavakul, Chalermrat; Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Nunes, Frederick; Kaplan, David E.; Reddy, Rajender; Chang, Kyong-Mi] Univ Penn, Dept Med, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nunes, Frederick] Penn Hosp, Philadelphia, PA 19107 USA. [Aytaman, Ayse] VA New York Harbor Healthcare Syst, Brooklyn, NY 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 581A EP 581A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002446 ER PT J AU Kanwal, F Hoang, T Kramer, JR Chrusciel, T El-Serag, H Dominitz, J Asch, S AF Kanwal, Fasiha Hoang, Tuyen Kramer, Jennifer R. Chrusciel, Timothy El-Serag, Hashem Dominitz, Jason Asch, Steven TI EVALUATING QUALITY OF CARE IN PATIENTS WITH HEPATITIS C VIRUS INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kanwal, Fasiha; Chrusciel, Timothy] St Louis VA Med Ctr, St Louis, MO USA. [Kanwal, Fasiha; Chrusciel, Timothy] St Louis Univ, St Louis, MO 63103 USA. [Hoang, Tuyen] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Kramer, Jennifer R.; El-Serag, Hashem] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kramer, Jennifer R.; El-Serag, Hashem] Baylor Coll Med, Houston, TX 77030 USA. [Dominitz, Jason] VA Puget Healthcare Syst, Seattle, WA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 591A EP 592A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002467 ER PT J AU Gifford, AL Asch, S Williams, SA Hanchate, AD AF Gifford, Allen L. Asch, Steven Williams, Sandra A. Hanchate, Amresh D. TI COST OF CARING FOR PATIENTS WITH HEPATITIS C (HCV) IN THE US DEPARTMENT OF VETERAN AFFAIRS (VA) HEALTHCARE SYSTEM SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gifford, Allen L.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem VA Hosp, HIV Hepatitis QUERI Program, Bedford, MA USA. [Williams, Sandra A.; Hanchate, Amresh D.] VA Boston Healthcare Syst, Boston, MA USA. [Hanchate, Amresh D.] Boston Univ, Gen Internal Med Sect, Boston, MA 02215 USA. [Asch, Steven] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 597A EP 597A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002479 ER PT J AU Liu, QL Rehman, H Krishnasamy, Y Haque, K Schnellmann, RG Lemasters, JJ Zhong, Z AF Liu, Qinlong Rehman, Hasibur Krishnasamy, Yasodha Haque, Khujista Schnellmann, Rick G. Lemasters, John J. Zhong, Zhi TI AMPHIREGULIN STIMULATES LIVER REGENERATION AFTER SMALL-FOR-SIZE LIVER TRANSPLANTATION IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Schnellmann, Rick G.; Lemasters, John J.; Zhong, Zhi] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 686A EP 686A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002670 ER PT J AU Berendsen, TA Izamis, ML Usta, OB Rosado, A Uygun, K Yarmush, ML AF Berendsen, Tim A. Izamis, Maria-Louisa Usta, O. Berk Rosado, Aaron Uygun, Korkut Yarmush, Martin L. TI SUCCESSFUL SUBZERO NONFREEZING STORAGE AND TRANSPLANTATION OF RAT LIVERS FOR 3 DAYS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Berendsen, Tim A.; Izamis, Maria-Louisa; Usta, O. Berk; Rosado, Aaron; Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. RI USTA, O. Berk/A-5818-2008 OI USTA, O. Berk/0000-0001-9328-568X 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 688A EP 688A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002675 ER PT J AU Izamis, ML Uygun, B Price, G Berendsen, TA Saeidi, N Uygun, K Yarmush, ML AF Izamis, Maria-Louisa Uygun, Basak Price, Gavrielle Berendsen, Tim A. Saeidi, Nima Uygun, Korkut Yarmush, Martin L. TI BETTER THAN FRESH: SIMPLE EX VIVO PERFUSION OPTIMIZES ISCHEMIC AND FRESH DONOR LIVERS FOR TRANSPLANTATION AND SIGNIFICANTLY ENHANCED HEPATOCYTE YIELDS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Izamis, Maria-Louisa; Uygun, Basak; Price, Gavrielle; Berendsen, Tim A.; Saeidi, Nima; Uygun, Korkut; Yarmush, Martin L.] 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 688A EP 688A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002674 ER PT J AU Delgado-Borrego, A Gonzalez-Peralta, RP Raza, R Negre, B Goodman, Z Jonas, MM Chung, RT AF Delgado-Borrego, Aymin Gonzalez-Peralta, Regino P. Raza, Roshan Negre, Betania Goodman, Zachary Jonas, Maureen M. Chung, Raymond T. TI LONGITUDINAL EVALUATION OF ADIPONECTIN LEVELS IN HEPATITIS C INFECTED CHILDREN UNDERGOING ANTIVIRAL THERAPY: RESULTS FROM THE PEDS-C TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Delgado-Borrego, Aymin; Negre, Betania] Univ Miami, Miami, FL USA. [Gonzalez-Peralta, Regino P.] Univ FL, Coll Med, Gainesville, FL USA. [Delgado-Borrego, Aymin; Raza, Roshan; Jonas, Maureen M.] Childrens Hosp, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodman, Zachary] Inova Fairfax Hosp, Falls Church, VA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 701A EP 702A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002704 ER PT J AU Lin, WY Kumthip, K Wu, GY Cheng, D Peng, LF Jilg, N Fusco, DN Schaefer, EA Chung, RT AF Lin, Wenyu Kumthip, Kattareeya Wu, Guoyang Cheng, Du Peng, Lee F. Jilg, Nikolaus Fusco, Dahlene N. Schaefer, Esperance A. Chung, Raymond T. TI HIV AND HCV COOPERATIVELY INDUCE HEPATIC FIBROGENESIS IN HEPATOCYTE-HEPATIC STELLATE CELL COCULTURES MODEL SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Kumthip, Kattareeya; Wu, Guoyang; Cheng, Du; Peng, Lee F.; Jilg, Nikolaus; Fusco, Dahlene N.; Schaefer, Esperance A.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 753A EP 753A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003060 ER PT J AU Golden-Mason, L Bambha, K Cheng, LL Howell, CD Taylor, MW Clark, PJ Afdhal, NH Rosen, HR AF Golden-Mason, Lucy Bambha, Kiran Cheng, Linling Howell, Charles D. Taylor, Milton W. Clark, Paul J. Afdhal, Nezam H. Rosen, Hugo R. TI NK INHIBITORY RECEPTOR EXPRESSION ASSOCIATED WITH TREATMENT FAILURE AND IL-28B GENOTYPE IN PATIENTS WITH CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Golden-Mason, Lucy; Bambha, Kiran; Cheng, Linling; Rosen, Hugo R.] Univ Colorado Denver, GI Hepatol, Hepatitis Ctr C, Aurora, CO USA. [Golden-Mason, Lucy] Natl Jewish Hosp, Integrated Program Immunol, Denver, CO USA. [Howell, Charles D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Taylor, Milton W.] Indiana Univ, Dept Biol, Bloomington, IN USA. [Clark, Paul J.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Afdhal, Nezam H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RI Clark, Paul/A-1480-2012 OI Clark, Paul/0000-0002-1821-4969 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 807A EP 807A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003178 ER PT J AU Rodriguez-Diaz, E Baffy, G Pedrosa, MC Singh, SK AF Rodriguez-Diaz, Eladio Baffy, Gyorgy Pedrosa, Marcos C. Singh, Satish K. TI MICROVASCULAR ASSESSMENT OF PORTAL HYPERTENSION USING PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Rodriguez-Diaz, Eladio; Baffy, Gyorgy; Pedrosa, Marcos C.; Singh, Satish K.] VA Boston Healthcare Syst, Med Gastroenterol, Boston, MA USA. [Rodriguez-Diaz, Eladio; Pedrosa, Marcos C.; Singh, Satish K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Baffy, Gyorgy] 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 950A EP 950A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003472 ER PT J AU Schumacher, F Kroy, DC Hatting, M Gassler, N Boekschoten, MV Muller, M Streetz, KL Trautwein, C AF Schumacher, Fabienne Kroy, Daniela C. Hatting, Maximilian Gassler, Nikolaus Boekschoten, Mark V. Muller, Michael Streetz, Konrad L. Trautwein, Christian TI C-MET PROTECTS FROM NON-ALCOHOLIC-STEATOHEPATITIS (NASH) IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Schumacher, Fabienne; Kroy, Daniela C.; Hatting, Maximilian; Streetz, Konrad L.; Trautwein, Christian] Rhein Westfal TH Aachen, Dept Med 3, Aachen, Germany. [Gassler, Nikolaus] Rhein Westfal TH Aachen, Dept Pathol, Aachen, Germany. [Boekschoten, Mark V.; Muller, Michael] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, Wageningen, Netherlands. [Kroy, Daniela C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1172A EP 1172A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004181 ER PT J AU Fuchs, BC Hoshida, Y Fujii, T Yamada, S Lauwers, GY McGinn, CM Wei, L Kuroda, T Lanuti, M Gupta, S Crenshaw, A Onofrio, R Taylor, BR Winckler, W Golub, TR Tanabe, KK AF Fuchs, Bryan C. Hoshida, Yujin Fujii, Tsutomu Yamada, Suguru Lauwers, Gregory Y. McGinn, Christopher M. Wei, Lan Kuroda, Toshihiko Lanuti, Michael Gupta, Supriya Crenshaw, Andrew Onofrio, Robert Taylor, Bradley R. Winckler, Wendy Golub, Todd R. Tanabe, Kenneth K. TI EGFR INHIBITION PREVENTS CIRRHOSIS AND HEPATOCELLULAR CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Fuchs, Bryan C.; Fujii, Tsutomu; Yamada, Suguru; Lauwers, Gregory Y.; McGinn, Christopher M.; Wei, Lan; Kuroda, Toshihiko; Lanuti, Michael; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoshida, Yujin; Gupta, Supriya; Crenshaw, Andrew; Onofrio, Robert; Taylor, Bradley R.; Winckler, Wendy; Golub, Todd R.] Broad Inst, Cambridge, MA USA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1222A EP 1222A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004289 ER PT J AU Li, YH Carpenito, C June, C Kaplan, DE AF Li, Yonghai Carpenito, Carmine June, Carl Kaplan, David E. TI T-CELLS TRANSDUCED WITH HUMAN GLYPICAN-3 SPECIFIC CHIMERIC ANTIGEN RECEPTOR SPECIFICALLY LYSE HEPATOCELLULAR CARCINOMA CELL LINE IN VITRO SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Res Sect, Philadelphia, PA USA. [Li, Yonghai; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Carpenito, Carmine; June, Carl] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1279A EP 1279A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004411 ER PT J AU Goto, K Zhang, LL Shao, RX Lin, WY Jilg, N Schaefer, EA Zhao, H Fusco, DN Peng, LF Kato, N Chung, RT AF Goto, Kaku Zhang, Leiliang Shao, Run-Xuan Lin, Wenyu Jilg, Nikolaus Schaefer, Esperance A. Zhao, Hong Fusco, Dahlene N. Peng, Lee F. Kato, Naoya Chung, Raymond T. TI THE AMPK-RELATED KINASE SNARK REGULATES HCV THROUGH TGF-beta SIGNALING SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Goto, Kaku; Zhang, Leiliang; Shao, Run-Xuan; Lin, Wenyu; Jilg, Nikolaus; Schaefer, Esperance A.; Zhao, Hong; Fusco, Dahlene N.; Peng, Lee F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit, Boston, MA USA. [Goto, Kaku; Kato, Naoya] Univ Tokyo, Inst Med Sci, Unit Dis Control Genome Med, Tokyo, Japan. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1309A EP 1310A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004481 ER PT J AU Jilg, N Ng, A Lin, WY Goto, K Shao, RX Peng, LF Kumthip, K Fusco, DN Schaefer, EA Urban, TJ Goldstein, DB Chung, RT AF Jilg, Nikolaus Ng, Aylwin Lin, Wenyu Goto, Kaku Shao, Run-Xuan Peng, Lee F. Kumthip, Kattareeya Fusco, Dahlene N. Schaefer, Esperance A. Urban, Thomas J. Goldstein, David B. Chung, Raymond T. TI TRANSCRIPTOMIC ANALYSIS OF RESPONSES TO IFN-alpha AND IL28B IN PRIMARY HUMAN HEPATOCYTES REVEALS DIFFERENTIAL KINETIC INDUCTION OF KEY IFN STIMULATED GENES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Jilg, Nikolaus; Ng, Aylwin; Lin, Wenyu; Goto, Kaku; Shao, Run-Xuan; Peng, Lee F.; Kumthip, Kattareeya; Fusco, Dahlene N.; Schaefer, Esperance A.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. [Urban, Thomas J.; Goldstein, David B.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1311A EP 1311A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004484 ER PT J AU Rodgers, M Villareal, V Peng, LF Schaefer, EA Chung, RT Yang, PL AF Rodgers, Mary Villareal, Valerie Peng, Lee F. Schaefer, Esperance A. Chung, Raymond T. Yang, Priscilla L. TI HCV REPLICATION IS SENSITIVE TO CHANGES IN DESMOSTEROL HOMEOSTASIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Peng, Lee F.; Schaefer, Esperance A.; Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Rodgers, Mary; Villareal, Valerie; Yang, Priscilla L.] 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1314A EP 1315A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004492 ER PT J AU Berger, CT Kroy, DC Cheney, PC Tomlinson, M Kim, AY Lauer, GM Alter, G AF Berger, Christoph T. Kroy, Daniela C. Cheney, Patrick C. Tomlinson, Michelle Kim, Arthur Y. Lauer, Georg M. Alter, Galit TI DIFFERENTIAL DISTRIBUTION OF IMMUNE CELL SUBSETS AND CD160, CD161 AND KIR EXPRESSING NK CELLS BETWEEN LIVER AND PERIPHERAL BLOOD IN CHRONIC HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Berger, Christoph T.; Cheney, Patrick C.; Alter, Galit] MIT & Harvard, Ragon Inst MGH, Charlestown, MA USA. [Kroy, Daniela C.; Tomlinson, Michelle; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kroy, Daniela C.; Tomlinson, Michelle; Lauer, Georg 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1317A EP 1318A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004499 ER PT J AU Doi, H Kaplan, DE AF Doi, Hiroyoshi Kaplan, David E. TI HUMORAL FACTORS INDUCE B-CELL ACTIVATION IN HCV-RELATED CIRRHOSIS AND ARE ASSOCIATED WITH LOSS OF CD27+MEMORY B-CELLS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Sect, Philadelphia, PA USA. [Doi, Hiroyoshi; Kaplan, David E.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1321A EP 1321A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004506 ER PT J AU Cheng, D Lin, WY Llado, V Kumthip, K Jiig, N Schaefer, EA Fusco, DN Peng, LF Gong, GZ Mizoguchi, E Chung, RT AF Cheng, Du Lin, Wenyu Llado, Victoria Kumthip, Kattareeya Jiig, Nikolaus Schaefer, Esperance A. Fusco, Dahlene N. Peng, Lee F. Gong, Guozhong Mizoguchi, Emiko Chung, Raymond T. TI HCV STIMULATES HEPATIC FIBROGENESIS THROUGH INCREASING CHI3L1 EXPRESSION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Cheng, Du; Gong, Guozhong] Second Xiangya Hosp, Dept Infect Dis, Changsha, Hunan, Peoples R China. [Cheng, Du; Lin, Wenyu; Llado, Victoria; Kumthip, Kattareeya; Jiig, Nikolaus; Schaefer, Esperance A.; Fusco, Dahlene N.; Peng, Lee F.; Mizoguchi, Emiko; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1335A EP 1335A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004538 ER PT J AU Kuntzen, T Neumann-Haefelin, C Lennon, N Carlson, J Berical, AC Berlin, AM Timm, J Oniangue-Ndza, C Young, S Adams, S Kleyman, M Birch, CE Ledlie, T Roberts, AD Rosen, HR Bihl, FK Cerny, A Brander, C Spengler, U Galagan, J Marincola, FM Nusbaum, C Walker, BD Lake-Bakaar, G Daari, ES Jacobson, IM Gomperts, ED Edlin, BR Thimme, R Birren, BW Donfield, SM Chung, RT Kim, AY Lauer, GM Talal, A Marion, T Carrington, M Heckerman, D Henn, MR Allen, TM AF Kuntzen, Thomas Neumann-Haefelin, Christoph Lennon, Niall Carlson, Jonathan Berical, Andrew C. Berlin, Aaron M. Timm, Joerg Oniangue-Ndza, Cesar Young, Sarah Adams, Sharon Kleyman, Marianna Birch, Christopher E. Ledlie, Timothy Roberts, Andrew D. Rosen, Hugo R. Bihl, Florian K. Cerny, Andreas Brander, Christian Spengler, Ulrich Galagan, James Marincola, Francesco M. Nusbaum, Chad Walker, Bruce D. Lake-Bakaar, Gerond Daari, Eric S. Jacobson, Ira M. Gomperts, Edward D. Edlin, Brian R. Thimme, Robert Birren, Bruce W. Donfield, Sharyne M. Chung, Raymond T. Kim, Arthur Y. Lauer, Georg M. Talal, Andrew Marion, Tony Carrington, Mary Heckerman, David Henn, Matthew R. Allen, Todd M. TI PROTECTIVE HLA CLASS I ALLELES IN HCV INFECTION: IMMUNE CONTROL LINKED TO CLUSTERED CD8 ESCAPE MUTATIONS IN NS5B BY LARGE SCALE SEQUENCE ANALYSIS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kuntzen, Thomas] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Kuntzen, Thomas; Neumann-Haefelin, Christoph; Berical, Andrew C.; Oniangue-Ndza, Cesar; Kleyman, Marianna; Birch, Christopher E.; Walker, Bruce D.; Kim, Arthur Y.; Lauer, Georg M.; Carrington, Mary; Allen, Todd M.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Neumann-Haefelin, Christoph; Thimme, Robert] Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. [Lennon, Niall; Berlin, Aaron M.; Young, Sarah; Ledlie, Timothy; Roberts, Andrew D.; Galagan, James; Nusbaum, Chad; Birren, Bruce W.; Henn, Matthew R.] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA USA. [Carlson, Jonathan; Heckerman, David] Microsoft Res, Redmond, WA USA. [Timm, Joerg] Essen Univ Hosp, Dept Virol, Essen, Germany. [Adams, Sharon; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Adams, Sharon; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA. [Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Hlth Sci Ctr, Denver, CO USA. [Bihl, Florian K.] Osped San Giovanni Bellinzona, Serv Gastroenterol, Bellinzona, Switzerland. [Cerny, Andreas] Clin Moncucco, Lugano, Switzerland. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa HIVACAT, Barcelona, Spain. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain. [Spengler, Ulrich] Bonn Univ Hosp, Dept Internal Med 1, Bonn, Germany. [Marion, Tony] Univ Tennessee, Ctr Hlth Sci, Hepatitis Cooperat C, Memphis, TN 38163 USA. [Lake-Bakaar, Gerond; Jacobson, Ira M.; Edlin, Brian R.; Talal, Andrew] Weill Cornell Med Coll, Ctr Study Hepatitis C, New York, NY USA. [Daari, Eric S.] Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA 90095 USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Donfield, Sharyne M.] Rho Inc, Dept Biostat, Chapel Hill, NC USA. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Carrington, Mary] NCI, Expt Immunol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Neumann-Haefelin, Christoph/E-5550-2011 NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1341A EP 1342A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004552 ER PT J AU Schaefer, EA Jilg, N Kumthip, K Fusco, DN Cheng, D Shao, RX Lin, WY Chung, RT Peng, LF AF Schaefer, Esperance A. Jilg, Nikolaus Kumthip, Kattareeya Fusco, Dahlene N. Cheng, Du Shao, Run Xuan Lin, Wenyu Chung, Raymond T. Peng, Lee F. TI APOLIPOPROTEIN B-100 PROMOTES HCV REPLICATION AND PARTIALLY MEDIATES THE PROVIRAL EFFECTS OF MICRORNA122 SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Schaefer, Esperance A.; Jilg, Nikolaus; Kumthip, Kattareeya; Fusco, Dahlene N.; Cheng, Du; Shao, Run Xuan; Lin, Wenyu; Chung, Raymond T.; Peng, Lee F.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1341A EP 1341A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004551 ER PT J AU Wissniowski, TT Ocker, M Strobel, D Neureiter, D Schuppan, D AF Wissniowski, Thaddaeus T. Ocker, Matthias Strobel, Deike Neureiter, Daniel Schuppan, Detlef TI APONECROSIS - THE KEY TO MULTIMODAL IMMUNE THERAPY OF HCC? SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Wissniowski, Thaddaeus T.; Strobel, Deike] Univ Erlangen Nurnberg, Dept Med 1, Erlangen, Germany. [Schuppan, Detlef] BIDMC, Boston, MA USA. [Schuppan, Detlef] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Ocker, Matthias] Univ Marburg, Marburg, Germany. [Neureiter, Daniel] SALK, Salzburg, Austria. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1374A EP 1374A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004619 ER PT J AU Gordon, FD Chung, RT Curry, MP Schiano, TD Emre, S Babcock, GJ Broering, TJ Finberg, RW Szabo, G Zamore, PD Khettry, U Ambrosino, DM Leav, B Leney, M Smith, HL Molrine, DC AF Gordon, Fredric D. Chung, Raymond T. Curry, Michael P. Schiano, Thomas D. Emre, Sukru Babcock, Gregory J. Broering, Teresa J. Finberg, Robert W. Szabo, Gyongyi Zamore, Phillip D. Khettry, Urmila Ambrosino, Donna M. Leav, Brett Leney, Mark Smith, Heidi L. Molrine, Deborah C. TI MONOCLONAL ANTIBODY MBL-HCV1 SUPPRESSES RETURN OF HCV FOLLOWING LIVER TRANSPLANTATION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Gordon, Fredric D.; Khettry, Urmila] Lahey Clin Med Ctr, Burlington, MA 01803 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Curry, Michael P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schiano, Thomas D.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Emre, Sukru] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Babcock, Gregory J.; Broering, Teresa J.; Ambrosino, Donna M.; Leav, Brett; Leney, Mark; Smith, Heidi L.; Molrine, Deborah C.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Finberg, Robert W.; Szabo, Gyongyi; Zamore, Phillip D.] Univ Massachusetts, Sch Med, Worcester, MA USA. RI Zamore, Phillip/A-8941-2013 NR 0 TC 3 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1434A EP 1434A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004744 ER PT J AU Huang, J Schmeidler, J Beeri, MS West, RK Rosendorff, C Silverman, JM AF Huang, Jennifer Schmeidler, James Beeri, Michal S. West, Rebecca K. Rosendorff, Clive Silverman, Jeremy M. TI Fibrinogen and cognitive function in very old non-demented men SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Letter ID VASCULAR DEMENTIA; DISEASE C1 [Huang, Jennifer; Schmeidler, James; Beeri, Michal S.; West, Rebecca K.; Rosendorff, Clive; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY 10029 USA. [Rosendorff, Clive; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Huang, J (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. FU NIA NIH HHS [P01-AG02219, P50-AG05138, K01 AG023515] NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2011 VL 26 IS 10 BP 1099 EP 1100 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 825NZ UT WOS:000295287100013 PM 21905103 ER PT J AU Parekh, N Ribaudo, H Souda, S Chen, J Mmalane, M Powis, K Essex, M Makhema, J Shapiro, RL AF Parekh, Natasha Ribaudo, Heather Souda, Sajini Chen, Jennifer Mmalane, Mompati Powis, Kathleen Essex, Max Makhema, Joseph Shapiro, Roger L. TI Risk factors for very preterm delivery and delivery of very-small-for-gestational-age infants among HIV-exposed and HIV-unexposed infants in Botswana SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Botswana; Highly active antiretroviral therapy; Mother-to-child HIV transmission; Very preterm delivery; Very small for gestational age ID ACTIVE ANTIRETROVIRAL THERAPY; LOW-BIRTH-WEIGHT; INFECTED WOMEN; PREMATURE DELIVERY; PREGNANCY OUTCOMES; UNITED-STATES; PREECLAMPSIA; GROWTH AB Objective: To evaluate risk factors for very preterm delivery (VPTD) and very-small-for-gestational-age (VSGA) births in a country with a high HIV prevalence. Methods: Obstetric records at 6 hospitals across Botswana were reviewed at delivery; VPTD was defined as birth before 32 weeks of pregnancy and VSGA as birth weight below the 3rd percentile for Botswana-specific norms. Results: Of 16 219 live births born after 26 weeks of pregnancy, 701 (4.3%) were delivered very preterm and 607 (3.7%) were VSGA; 4347 (28.4%) were documented as HIV-exposed. In a multivariable analysis, HIV infection and hypertension during pregnancy were associated with a VPTD (adjusted odds ratio [AOR]: HIV 1.65, hypertension 1.75) and a VSGA birth (AOR: HIV infection 1.90, hypertension 3.44). Among HIV-infected women, the continuation of highly active antiretroviral therapy (HAART) from before conception was associated with a VSGA birth (AOR 1.75) but not with a VPTD (AOR 0.78). In a secondary analysis, HAART continuation was associated with hypertension during pregnancy (AOR 1.34). Conclusion: Hypertension and HIV infection were risk factors for a VPTD and a VSGA birth. Continuation of HAART from before conception was associated with a VSGA birth but not with a VPTD. (C) 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Parekh, Natasha] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Souda, Sajini; Mmalane, Mompati; Powis, Kathleen; Essex, Max; Makhema, Joseph; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Chen, Jennifer] Brigham & Womens Hosp, Boston, MA 02115 USA. [Powis, Kathleen; Essex, Max; Shapiro, Roger L.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA. EM rshapiro@hsph.harvard.edu FU Doris Duke Charitable Research Foundation in New York, NY, USA via Harvard Medical School, Boston, MA, USA; Centers for Disease Control and Prevention, Atlanta, GA, USA FX Funding for NP was provided from the Doris Duke Charitable Research Foundation in New York, NY, USA, through a Clinical Research Fellowship via Harvard Medical School, Boston, MA, USA. Funding for the study was provided by the Centers for Disease Control and Prevention, Atlanta, GA, USA. NR 25 TC 18 Z9 18 U1 0 U2 2 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 OCT PY 2011 VL 115 IS 1 BP 20 EP 25 DI 10.1016/j.ijgo.2011.04.008 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 833PG UT WOS:000295896800005 PM 21767835 ER PT J AU Choi, CJ Melki, SA AF Choi, Catherine J. Melki, Samir A. TI Maddox rod effect to confirm the visual significance of laser in situ keratomileusis flap striae SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID LASIK; MANAGEMENT AB Laser in situ keratomileusis (LASIK) flap striae can act as a Maddox rod, producing streaks of light perpendicular to the orientation of the striae. This phenomenon can be used in the diagnostic and surgical decision-making process after LASIK. We correlated persistent complaints of starburst by a patient to the presence of LASIK flap striae in both eyes. The more severe striae were subsequently treated with phototherapeutic keratectomy, with complete resolution of symptoms. The LASIK flap striae-induced Maddox rod effect can be used as a simple and useful method with high diagnostic and therapeutic value. C1 [Melki, Samir A.] Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. [Choi, Catherine J.; Melki, Samir A.] Harvard Univ, Sch Med, Boston, MA USA. [Melki, Samir A.] Boston Eye Grp, Boston, MA USA. RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 9 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2011 VL 37 IS 10 BP 1748 EP 1750 DI 10.1016/j.jcrs.2011.08.001 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 830MB UT WOS:000295660000003 PM 21930043 ER PT J AU Taneri, S Oehler, S Koch, J Azar, D AF Taneri, Suphi Oehler, Saskia Koch, Joerg Azar, Dimitri TI Effect of repositioning or discarding the epithelial flap in laser-assisted subepithelial keratectomy and epithelial laser in situ keratomileusis SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID EPI-LASIK; PHOTOREFRACTIVE KERATECTOMY; EXCIMER-LASER; CORNEAL HAZE; POSTOPERATIVE PAIN; ELECTRON-MICROSCOPY; CLINICAL-OUTCOMES; SURFACE ABLATION; MITOMYCIN-C; MYOPIA AB PURPOSE: To evaluate the influence of the epithelial flap after epithelial laser in situ keratomileusis (epi-LASIK) and laser-assisted subepithelial keratectomy (LASEK) to correct low to moderate ametropia on visual recovery, epithelial closure, pain, and haze formation. SETTING: Zentrum fur Refraktive Chirurgie, Augenabteilung am St. Franziskus Hospital, Munster, Germany. DESIGN: Comparative case series. METHODS: Patients having bilateral epi-LASIK or bilateral LASEK had 1 treatment with a repositioned epithelial flap and 1 treatment with a discarded flap. Patients were masked to the epithelial replacement. Primary outcomes were visual acuity (decimal scale), diameter of epithelial defect, pain score (subjective visual analog scale 0 to 10), and haze formation (Fantes scale). Postoperative visits were at 1, 2, and 4 days and after 3 months. RESULTS: Twenty patients had epi-LASIK and 20 patients had LASEK. The mean increase in uncorrected distance visual acuity from 1 day to 3 months was 0.32 to 0.99 (epi-LASIK flap-on), from 0.41 to 0.98 (epi-LASIK flap-off), from 0.26 to 0.96 (LASEK flap-on), and from 0.37 to 0.92 (LASEK flap-off), respectively. At 4 days, epithelial closure was complete in 79 of 80 eyes. Postoperative pain levels decreased comparably in all groups. Haze levels after 3 months were 0.45, 0.43, 0.35, and 0.35 (epi-LASIK flap-on, epi-LASIK flap-off, LASEK flap-on, LASEK flap-off, respectively). Efficacy indices after 3 months were 1.07, 1.09, 1.11, 1.07, respectively. CONCLUSION: No clinically significant differences in terms of visual recovery, epithelial closure time, pain perception, and haze formation between LASEK and epi-LASIK were detected regardless of epithelial flap retention. C1 [Taneri, Suphi; Oehler, Saskia; Koch, Joerg] Augenabt St Franziskus Hosp, Zentrum Refrakt Chirurg, D-48149 Munster, Germany. [Azar, Dimitri] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Taneri, S (reprint author), Augenabt St Franziskus Hosp, Zentrum Refrakt Chirurg, Hohenzollernring 57, D-48149 Munster, Germany. EM taneri@refraktives-zentrum.de OI Taneri, Suphi/0000-0003-0593-6847; Kiessler, Saskia/0000-0001-9527-8360 NR 70 TC 10 Z9 10 U1 0 U2 6 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 OCT PY 2011 VL 37 IS 10 BP 1832 EP 1846 DI 10.1016/j.jcrs.2011.05.026 PG 15 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 830MB UT WOS:000295660000016 PM 21930046 ER PT J AU Miller, KK AF Miller, K. K. TI Endocrine Dysregulation in Anorexia Nervosa Update SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; GROWTH-FACTOR-I; DOSE TRANSDERMAL TESTOSTERONE; TRABECULAR STRUCTURE-ANALYSIS; HORMONE SECRETORY PATTERN; POPULATION-BASED TWIN; MARROW STROMAL CELLS; ADOLESCENT GIRLS; EATING-DISORDERS; PEPTIDE-YY AB Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. (J Clin Endocrinol Metab 96: 2939-2949, 2011) C1 [Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. [Miller, K. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@partners.org FU National Institutes of Health [R01 DK052625, R01 MH083657] FX This work was supported in part by National Institutes of Health Grants R01 DK052625 and R01 MH083657. NR 114 TC 25 Z9 26 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 2939 EP 2949 DI 10.1210/jc.2011-1222 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600025 PM 21976742 ER PT J AU Klonoff, DC Buckingham, B Christiansen, JS Montori, VM Tamborlane, WV Vigersky, RA Wolpert, H AF Klonoff, David C. Buckingham, Bruce Christiansen, Jens S. Montori, Victor M. Tamborlane, William V. Vigersky, Robert A. Wolpert, Howard TI Continuous Glucose Monitoring: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; POINT-OF-CARE; RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE; PEDIATRIC-PATIENTS; PUMP THERAPY; FREESTYLE NAVIGATOR; METABOLIC-CONTROL; GLYCEMIC CONTROL AB Objective: The aim was to formulate practice guidelines for determining settings where patients are most likely to benefit from the use of continuous glucose monitoring (CGM). Participants: The Endocrine Society appointed a Task Force of experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, the Diabetes Technology Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Conclusions: The Task Force evaluated three potential uses of CGM: 1) real-time CGM in adult hospital settings; 2) real-time CGM in children and adolescent outpatients; and 3) real-time CGM in adult outpatients. The Task Force used the best available data to develop evidence-based recommendations about where CGM can be beneficial in maintaining target levels of glycemia and limiting the risk of hypoglycemia. Both strength of recommendations and quality of evidence were accounted for in the guidelines. (J Clin Endocrinol Metab 96: 2968-2979, 2011) C1 [Klonoff, David C.] Mills Peninsula Hlth Serv, San Mateo, CA 94401 USA. [Buckingham, Bruce] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Christiansen, Jens S.] Aarhus Univ Hosp, DK-8000 Aarhus C, Denmark. [Montori, Victor M.] Mayo Clin, Rochester, MN 55905 USA. [Tamborlane, William V.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Vigersky, Robert A.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA. [Wolpert, Howard] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Klonoff, DC (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo-society.org OI Montori, Victor/0000-0003-0595-2898 FU Diabetes Technology Society; European Society of Endocrinology FX Cosponsoring Associations: Diabetes Technology Society and European Society of Endocrinology. NR 78 TC 79 Z9 88 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 2968 EP 2979 DI 10.1210/jc.2010-2756 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600028 PM 21976745 ER PT J AU Ackerman, KE Nazem, T Chapko, D Russell, M Mendes, N Taylor, AP Bouxsein, ML Misra, M AF Ackerman, Kathryn E. Nazem, Taraneh Chapko, Dorota Russell, Melissa Mendes, Nara Taylor, Alexander P. Bouxsein, Mary L. Misra, Madhusmita TI Bone Microarchitecture Is Impaired in Adolescent Amenorrheic Athletes Compared with Eumenorrheic Athletes and Nonathletic Controls SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRABECULAR STRUCTURE-ANALYSIS; PANEL VOLUME CT; VIVO HR-PQCT; DISTAL RADIUS; POSTMENOPAUSAL WOMEN; ANOREXIA-NERVOSA; BODY-COMPOSITION; MINERAL DENSITY; YOUNG-WOMEN; COMPUTED-TOMOGRAPHY AB Context: Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. Objective: We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. Design and Setting: We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. Subjects and Outcome Measures: We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Results: Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. Conclusion: In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA. (J Clin Endocrinol Metab 96: 3123-3133, 2011) C1 [Ackerman, Kathryn E.; Nazem, Taraneh; Chapko, Dorota; Russell, Melissa; Mendes, Nara; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Childrens Hosp, Div Sports Med, Boston, MA 02116 USA. [Russell, Melissa; Misra, Madhusmita] Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Taylor, Alexander P.; Bouxsein, Mary L.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU National Institutes of Health [1 UL1 RR025758-01, 1 R01 HD060827-01A1] FX This work was supported by National Institutes of Health Grants 1 UL1 RR025758-01 and 1 R01 HD060827-01A1. NR 54 TC 31 Z9 32 U1 0 U2 9 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 OCT PY 2011 VL 96 IS 10 BP 3123 EP 3133 DI 10.1210/jc.2011-1614 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600048 PM 21816790 ER PT J AU Marsh, EE Shaw, ND Klingman, KM Tiamfook-Morgan, TO Yialamas, MA Sluss, PM Hall, JE AF Marsh, E. E. Shaw, N. D. Klingman, K. M. Tiamfook-Morgan, T. O. Yialamas, M. A. Sluss, P. M. Hall, J. E. TI Estrogen Levels Are Higher across the Menstrual Cycle in African-American Women Compared with Caucasian Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; POLYCYSTIC-OVARIAN-SYNDROME; RACIAL-DIFFERENCES; GRANULOSA-CELLS; AROMATASE-ACTIVITY; DIMERIC INHIBIN; GROWTH-FACTORS; SEX-HORMONE; SECRETION; CRITERIA AB Context: Previous studies have suggested that estrogen levels may be higher in African-American women (AAW) compared with Caucasian women (CW), but none have systematically examined estrogen secretion across the menstrual cycle or in relation to other reproductive hormones. Objective: The objective of the study was to compare estradiol (E2), progesterone (P), gonadotropins, androstenedione (a'dione), inhibins, and SHBG levels between AAW and CW across the menstrual cycle. Design, Setting, and Subjects: Daily blood samples were collected from regularly cycling AAW(n = 27) and CW (n = 27) for a full menstrual cycle, and serial ultrasounds were performed. Main Outcome Measures: Comparison of E2, P, LH, FSH, SHBG, inhibin A, inhibin B, and a'dione levels. Results: AAW and CW were of similar age (27.2 +/- 0.6 yr, mean +/- SEM) and body mass index (22.7 +/- 0.4 kg/m(2)). All subjects grew a single dominant follicle and had comparable cycle (25-35 d) and follicular phase (11-24 d) lengths. E2 levels were significantly higher in AAW compared with CW (P = 0.02) with the most pronounced differences in the late follicular phase (225.2 +/- 14.4 vs. 191.5 +/- 10.2 pg/ml; P = 0.02), midluteal phase (211.9 +/- 22.2 vs. 150.8 +/- 9.9, P < 0.001), and late luteal phase (144.4 +/- 13.2 vs. 103.5 +/- 8.5, P = 0.01). Although LH, FSH, inhibins A and B, P, a'dione, and SHBG were not different between the two groups, the a'dione to E2 ratio was lower in AAW(P < 0.001). Conclusions: Estradiol is higher in AAW compared with CW across the menstrual cycle. Higher estradiol in the face of similar androstenedione and FSH levels suggests enhanced aromatase activity in AAW. Such differences may contribute to racial disparities in bone mineral density, breast cancer, and uterine leiomyomas. (J Clin Endocrinol Metab 96: 3199-3206, 2011) C1 [Marsh, E. E.; Shaw, N. D.; Klingman, K. M.; Tiamfook-Morgan, T. O.; Yialamas, M. A.; Sluss, P. M.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Marsh, E. E.] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA. [Shaw, N. D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX 5,55 Fruit St, Boston, MA 02114 USA. EM jehall@partners.org RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Shaw, Natalie/0000-0002-0847-9170 FU National Institutes of Health [R01 HD 42708, M01RR01066, 5T32 HD007396]; The Harvard Clinical and Translational Science Center [UL1 RR 025758]; Harvard University FX This work was supported by National Institutes of Health Grants R01 HD 42708 and M01RR01066. N.D.S. received fellowship support from the National Institutes of Health (Grant 5T32 HD007396) and from the Scholars in Clinical Science program of Harvard Catalyst [The Harvard Clinical and Translational Science Center (Award #UL1 RR 025758) and financial contributions from Harvard University and its affiliated academic health care centers]. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. This study was initiated before 1997 and was therefore not registered with www.clinicaltrials.gov. NR 44 TC 24 Z9 24 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 3199 EP 3206 DI 10.1210/jc.2011-1314 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600057 PM 21849524 ER PT J AU Khan, AM Cheng, S Magnusson, M Larson, MG Newton-Cheh, C McCabe, EL Coviello, AD Florez, JC Fox, CS Levy, D Robins, SJ Arora, P Bhasin, S Lam, CSP Vasan, RS Melander, O Wang, TJ AF Khan, Abigail May Cheng, Susan Magnusson, Martin Larson, Martin G. Newton-Cheh, Christopher McCabe, Elizabeth L. Coviello, Andrea D. Florez, Jose C. Fox, Caroline S. Levy, Daniel Robins, Sander J. Arora, Pankaj Bhasin, Shalender Lam, Carolyn S. P. Vasan, Ramachandran S. Melander, Olle Wang, Thomas J. TI Cardiac Natriuretic Peptides, Obesity, and Insulin Resistance: Evidence from Two Community-Based Studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; INCIDENT CARDIOVASCULAR EVENTS; EMERGENCY-DEPARTMENT PRIDE; TERMINAL PRO-BNP; HEART-FAILURE; METABOLIC SYNDROME; NORMAL-WEIGHT; MICE LACKING; ANGIOTENSIN-II; ADIPOSE-TISSUE AB Background: The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown. Aim: The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction. Methods: We studied 7770 individuals from the Framingham Heart Study (n = 3833, 54% women) and the Malmo Diet and Cancer study (n = 3918, 60% women). We examined the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP) with obesity, insulin resistance, and various metabolic subtypes. Results: Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham, P = 0.001 in Malmo), whereas insulin resistance was associated with 10-30% lower levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were insulin sensitive had only modest reductions in N-BNP compared with nonobese, insulin-sensitive individuals. On the other hand, individuals who were nonobese but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower N-BNP in Malmo (P < 0.001), compared with nonobese and insulin-sensitive individuals. Adjustment for serum-free testosterone did not alter these associations. Conclusions: In both nonobese and obese individuals, insulin resistance is associated with lower natriuretic peptide levels. The relative natriuretic peptide deficiency seen in obesity could be partly attributable to insulin resistance, and could be one mechanism by which insulin resistance promotes hypertension. (J Clin Endocrinol Metab 96: 3242-3249, 2011) C1 [Khan, Abigail May; Cheng, Susan; Newton-Cheh, Christopher; McCabe, Elizabeth L.; Arora, Pankaj; Wang, Thomas J.] Harvard Univ, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Florez, Jose C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Harvard Univ, Sch Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Khan, Abigail May] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Cheng, Susan; Larson, Martin G.; Newton-Cheh, Christopher; McCabe, Elizabeth L.; Fox, Caroline S.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA. [Magnusson, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, SE-20041 Malmo, Sweden. Lund Univ, Dept Cardiol, Skanes Univ Hosp, SE-20502 Malmo, Sweden. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Newton-Cheh, Christopher; Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Fox, Caroline S.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20824 USA. [Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Prevent Med, Dept Med, Boston, MA 02118 USA. [Bhasin, Shalender] Boston Univ, Sch Med, Div Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Lam, Carolyn S. P.] Natl Univ Hlth Syst, Singapore 119228, Singapore. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org RI Arora, Pankaj/F-3437-2011; OI Arora, Pankaj/0000-0003-2420-3550; Larson, Martin/0000-0002-9631-1254; Magnusson, Martin/0000-0003-1710-5936; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, R01-HL-086875, R01-HL-094755]; Ellison Foundation FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Contract N01-HC-25195 and Grants R01-HL-086875 and R01-HL-094755. S.C. is supported by a grant from the Ellison Foundation. NR 62 TC 60 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP 3242 EP 3249 DI 10.1210/jc.2011-1182 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600062 PM 21849523 ER PT J AU Hatoum, IJ Greenawalt, DM Cotsapas, C Reitman, ML Daly, MJ Kaplan, LM AF Hatoum, Ida J. Greenawalt, Danielle M. Cotsapas, Chris Reitman, Marc L. Daly, Mark J. Kaplan, Lee M. TI Heritability of the Weight Loss Response to Gastric Bypass Surgery SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BARIATRIC SURGERY; RISK-FACTORS; OBESITY; ASSOCIATION; REGAIN; RATS AB Context: The use of Roux-en-Y gastric bypass (RYGB) surgery to treat severe obesity has grown dramatically. RYGB is highly effective, but the response in individual patients varies widely, and clinical predictors have been able to explain only a fraction of this variation. Objective: Our objective was to determine whether there is a significant genetic contribution to weight loss after RYGB. Methods: We genotyped 848 patients undergoing RYGB. Using identity-by-descent methods, we identified 13 pairs of first-degree relatives. We identified an additional 10 pairs of individuals who were living together but are not genetically related and randomly paired the remaining 794 individuals. We then compared weight loss within and across pairs. Results: First-degree relative pairs had a similar response to surgery, with a 9% mean difference in excess weight loss between members of each pair. This similarity was not seen with cohabitating individuals (26% mean difference; P = 0.005 vs. first-degree pairs) or unrelated individuals (25% mean difference; P = 0.001). Cohabitating individuals had within-pair differences in weight loss no more similar than randomly paired individuals (P = 0.60). The pair relationship explained a significant portion of the variation in weight loss in first-degree relatives [intraclass correlation coefficient (ICC) = 70.4%; P = 0.02] but not in random subjects (ICC = 0.9%; P = 0.48) or genetically unrelated cohabitating individuals (ICC = 14.3%; P = 0.67). Conclusions: Genetic factors strongly influence the effect of RYGB on body weight. Identification of the specific genes that mediate this effect will advance our understanding of the biological mechanisms of weight loss after RYGB and should help identify patients who will benefit the most from this intervention. (J Clin Endocrinol Metab 96: E1630-E1633, 2011) C1 [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Metab Lab, Charlestown, MA 02129 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Charlestown, MA 02129 USA. [Cotsapas, Chris; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA 02129 USA. [Hatoum, Ida J.; Cotsapas, Chris; Daly, Mark J.; Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Greenawalt, Danielle M.] Merck Res Labs, Dept Genet, Boston, MA 02115 USA. [Cotsapas, Chris; Daly, Mark J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Reitman, Marc L.] Merck Res Labs, Clin Pharmacol, Rahway, NJ 07065 USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Metab Lab, 149 13th St, Charlestown, MA 02129 USA. EM LMKaplan@partners.org RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU National Institutes of Health [DK088661, DK090956]; Merck Research Laboratories; Ethicon Endosurgery FX This work was supported by National Institutes of Health Grants DK088661 (to L. M. K.) and DK090956 (to L. M. K.), a research grant from Merck Research Laboratories (to L. M. K.), and a research grant from Ethicon Endosurgery (L. M. K.). NR 18 TC 22 Z9 22 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP E1630 EP E1633 DI 10.1210/jc.2011-1130 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600009 PM 21832118 ER PT J AU McCormack, SE McCarthy, MA Farilla, L Hrovat, MI Systrom, DM Grinspoon, SK Fleischman, A AF McCormack, Shana E. McCarthy, Meaghan A. Farilla, Loredana Hrovat, Mirko I. Systrom, David M. Grinspoon, Steven K. Fleischman, Amy TI Skeletal Muscle Mitochondrial Function Is Associated with Longitudinal Growth Velocity in Children and Adolescents SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; PHOSPHOCREATINE RECOVERY; INSULIN SENSITIVITY; ABNORMAL GROWTH; GLUCOSE; VARIABILITY; EXERCISE; HORMONE; DISEASE; ADULTS AB Context: Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth. Methods: Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using (31)P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr. Results: Data were complete for 23 subjects. Subjects were 11.3 +/- 1.9 (SD) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 +/- 1.5 cm/yr and for girls 6.5 +/- 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r(2) = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R(2) for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score. Conclusions: We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation. (J Clin Endocrinol Metab 96: E1612-E1618, 2011) C1 [McCormack, Shana E.; McCarthy, Meaghan A.; Farilla, Loredana; Grinspoon, Steven K.; Fleischman, Amy] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [McCormack, Shana E.; McCarthy, Meaghan A.; Farilla, Loredana; Grinspoon, Steven K.; Fleischman, Amy] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Hrovat, Mirko I.; Systrom, David M.] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Fleischman, Amy] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McCormack, Shana E.; Fleischman, Amy] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hrovat, Mirko I.] Mirtech Inc, Brockton, MA 02301 USA. RP Fleischman, A (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM afleischman@partners.org OI Systrom, David/0000-0002-9610-6330 FU National Institutes of Health [K23 DK080658, K24 DK064545]; National Center for Research Resources [1 UL1 RR025758-03, M01-RR-01066]; Lawson Wilkins Pediatric Endocrine Society; Children's Hospital Boston FX This work was supported by grants from the National Institutes of Health (K23 DK080658 to A. F. and K24 DK064545 to S. K. G.). The project described was supported by Grants 1 UL1 RR025758-03 and M01-RR-01066 to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources. (The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.) In addition, the study was supported by Genentech Clinical Scholars Award from the Lawson Wilkins Pediatric Endocrine Society (to A. F.) and the Career Development Award (to A. F.) from the Children's Hospital Boston. NR 23 TC 6 Z9 6 U1 1 U2 6 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 OCT PY 2011 VL 96 IS 10 BP E1612 EP E1618 DI 10.1210/jc.2011-1218 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600007 PM 21832105 ER PT J AU Keller, PA Harlam, B Loewenstein, G Volpp, KG AF Keller, Punam Anand Harlam, Bari Loewenstein, George Volpp, Kevin G. TI Enhanced active choice: A new method to motivate behavior change SO JOURNAL OF CONSUMER PSYCHOLOGY LA English DT Article DE Choice; Persuasion; Automatic enrollment; Social marketing ID ORGAN DONATION; OPTIMAL DEFAULTS; MANDATED CHOICE; SELF-CONTROL; DECISIONS; RESPONSIBILITY; REGRET; TIME; SATISFACTION; COMMITMENT AB High rates of medication non-adherence have significant public health and economic consequences. In other contexts such as savings behavior, opt-out policies, in which the alternative preferred by the policy maker is made the default, have gotten great traction but may not be feasible in health care settings. After reviewing previous applications, we present a series of studies, including two field experiments, that test the effectiveness of an alternative, 'active choice' policy in which there is no default, but decision makers are required to make a choice (Carroll, Choi, Laibson, Madrian, & Metrick, 2009; Spital, 1993, 1995). In addition, we propose and test a modified version of active choice, that we call 'enhanced active choice' that favors one alternative by highlighting losses incumbent in the in the non-preferred alternative. We recommend Enhanced Active Choice as a complement to automatic enrollment or when automatic enrollment is infeasible or unethical. (C) 2011 Society for Consumer Psychology. Published by Elsevier Inc. All rights reserved. C1 [Keller, Punam Anand] Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. [Harlam, Bari] CVS Caremark, Woonsocket, RI USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Philadelphia, PA USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Keller, PA (reprint author), Dartmouth Coll, Tuck Sch Business, Hanover, NH 03755 USA. EM punam.keller@dartmouth.edu NR 43 TC 25 Z9 25 U1 3 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1057-7408 J9 J CONSUM PSYCHOL JI J. Consum. Psychol. PD OCT PY 2011 VL 21 IS 4 SI SI BP 376 EP 383 DI 10.1016/j.jcps.2011.06.003 PG 8 WC Business; Psychology, Applied SC Business & Economics; Psychology GA 834XW UT WOS:000295998800002 ER PT J AU Denninger, JW van Nieuwenhuizen, AO Wisniewski, SR Luther, JF Trivedi, MH Rush, AJ Gollan, JK Pizzagalli, DA Fava, M AF Denninger, John W. van Nieuwenhuizen, Adrienne O. Wisniewski, Stephen R. Luther, James F. Trivedi, Madhukar H. Rush, A. John Gollan, Jackie K. Pizzagalli, Diego A. Fava, Maurizio TI Changes in Depressive Symptoms and Social Functioning in the Sequenced Treatment Alternatives to Relieve Depression Study SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Major depressive disorder; citalopram; social adjustment ID STAR-ASTERISK-D; QUALITY-OF-LIFE; IMPAIRMENT; SCALE AB Major depressive disorder (MDD) profoundly affects social functioning, including the ability to enjoy social activities with peers, friends, and family members. We sought to compare changes in social functioning and depressive symptoms in the first level of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated using flexible doses of citalopram for up to 14 weeks. We compared the change over the course of treatment in the social activities item of the Work and Social Adjustment Scale to the change in individual items of the Quick Inventory of Depressive Symptoms-Self-Rated (QIDS-SR). Improvement in social functioning was modestly positively correlated with improvement in sad mood, concentration/decision making, involvement, and energy/fatigability. Only 16% to 22% of the variance in the change in social functioning was accounted for by these symptoms, and only 32% was accounted for by the total QIDS-SR score. In this large real-world sample of outpatients treated using citalopram, changes in depressive symptoms do not entirely explain improvements in social functioning. C1 [Denninger, John W.; van Nieuwenhuizen, Adrienne O.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Rush, A. John] Duke Natl Univ Singapore, Off Clin Sci, Singapore, Singapore. [Gollan, Jackie K.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Denninger, JW (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 151 Merrimac St,Ste 400, Boston, MA 02114 USA. EM jdenninger@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH [N01 MH-90003]; National Institutes of Health; Centers for Disease Control; Kaplen Foundation; Massachusetts General Hospital; Massachusetts General Hospital Physicians Organization; AstraZeneca; Bristol-Meyers Squibb; Cephalon; Janssen; Lilly; Merck; Pfizer; Wyeth; Eli Lilly; Abbott; Alkermes; Aspect Medical Systems; Forest Laboratories; GlaxoSmithKline; Johnson Johnson; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon; Pamlab; Pharmavite; Roche; Sanofi-Synthelabo; Solvay; Cyberonic Inc; ImaRx Therapeutics, Inc; Bristol-Myers Squibb Company; Case-Western University; Singapore Clinical Research Institute; Agency for Healthcare Research and Quality (AHRQ); Corcept Therapeutics Inc; Cyberonics Inc; National Alliance for Research in Schizophrenia and Depression; NIMH; National Institute on Drug Abuse; Pharmacia Upjohn; Predix Pharmaceuticals (Epix); Solvay Pharmaceuticals Inc; Targacept; Best Practices; American Foundation of Suicide Prevention; ANT North America Inc (Advanced Neuro Technology); Abbott Laboratories; Alkermes Inc; BioResearch; BrainCells Inc; Cephalon Inc; Clinical Trials Solutions LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals Inc; Forest Pharmaceuticals Inc; Ganeden Biotech Inc; Johnson & Johnson Pharmaceutical Research Development; Novartis AG; Organon Pharmaceuticals; PamLab LLC; Pfizer Inc; Pharmavite LLC; RTC Logic LLC; Sanofi-Aventis US LLC; Shire; Synthelabo; Wyeth-Ayerst Laboratories; Affectis Pharmaceuticals AG; Amarin Pharma Inc; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management Inc; BioMarin Pharmaceuticals Inc; Biovail Corporation; CeNeRx Bio-Pharma; CNS Response Inc; Compellis Pharmaceuticals; Cypress Pharmaceutical Inc; Dov Pharmaceuticals Inc; Eisai Inc; EPIX Pharmaceuticals Inc; Euthymics Bioscience Inc; Fabre-Kramer Pharmaceuticals Inc; GenOmind LLC; Gruenthal GmbH; Janssen Pharmaceutica; Jazz Pharmaceuticals Inc; Johnson & Johnson Pharmaceutical Research & Development LLC.; Knoll Pharmaceuticals Corp.; Labopharm Inc; Lundbeck Inc; MedAvante In; Merck Co. Inc; Methylation Sciences; Neuronetics Inc; Nutrition 21; PharmaStar; Precision Human Biolaboratory; Prexa Pharmaceuticals Inc; PsychoGenics; Psylin Neurosciences Inc; Ridge Diagnostics Inc; RCT Logic LLC; Sanofi-Aventis US LLC.; Sepracor Inc; Schering-Plough Corporation; Somaxon Pharmaceuticals Inc; Somerset Pharmaceuticals Inc; Takeda Pharmaceutical Company Limited; Tetragenex Pharmaceuticals Inc; TransForm Pharmaceuticals Inc; Transcept Pharmaceuticals Inc; Vanda Pharmaceuticals Inc; Adamed Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Imedex LLC; MGH Psychiatry Reed/Primedia; MGH Psychiatry Academy/Reed Elsevier; United BioSource Corp FX The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was supported by the NIMH through the N01 MH-90003 contract. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government.; John Denninger has received or is receiving salary support from the National Institutes of Health, the Centers for Disease Control, the Kaplen Foundation, Massachusetts General Hospital, and the Massachusetts General Hospital Physicians Organization, as well as (through fellowships funded by unrestricted educational grants) from AstraZeneca, Bristol-Meyers Squibb, Cephalon, Janssen, Lilly, Merck, Pfizer, and Wyeth. Dr. Denninger has also received honoraria (through unrestricted educational grants) from AstraZeneca, Bristol-Meyers Squibb, Cephalon, Eli Lilly, Janssen, Pfizer, and Wyeth. Dr. Denninger and/or the Depression Clinical and Research Program of Massachusetts General Hospital have received or are receiving research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Synthelabo, Solvay, and Wyeth. Adrienne van Nieuwenhuizen reported no biomedical financial interests or potential conflicts of interest. Stephen Wisniewski reports having received consulting fees from Cyberonic Inc (2005-2009), ImaRx Therapeutics, Inc (2006), Bristol-Myers Squibb Company (2007-2008), Organon (2007), Case-Western University (2007), and the Singapore Clinical Research Institute (2009). James Luther reported no biomedical financial interests or potential conflicts of interest. Madhukar Trivedi is a consultant to or is on a speakers' bureau for Abbott Laboratories Inc, Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc), AstraZeneca, Bristol-Myers Squibb Company, Cephalon Inc, Cyberonics Inc, Eli Lilly & Company, Evotec, Fabre-Kramer Pharmaceuticals Inc, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Meade Johnson, Medtronic, Neuronetics, Otsuka Pharmaceuticals, Parke-Davis Pharmaceuticals Inc, Pfizer Inc, Sepracor, SHIRE Development, Solvay Pharmaceuticals, VantagePoint, and Wyeth-Ayerst Laboratories. He receives research support from the Agency for Healthcare Research and Quality (AHRQ), Corcept Therapeutics Inc, Cyberonics Inc, Merck, National Alliance for Research in Schizophrenia and Depression, NIMH, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Solvay Pharmaceuticals Inc, and Targacept. A. John Rush reports receiving royalties from UT Southwestern, speaking fees from Otsuka Pharamaceuticals, and consultant fees from Best Practices. Jackie Gollan has received research support from NIMH, National Alliance for Research in Schizophrenia and Depression, and American Foundation of Suicide Prevention. She has received royalties from American Psychological Association and Guilford Press. She has owned shares of Pfizer and Bristol-Myers Squibb stock. She has received a speaker honoria from AstraZeneca. She is a consultant for Prevail Inc. Diego Pizzagalli has received consulting fees from ANT North America Inc (Advanced Neuro Technology) and AstraZeneca and honoraria from AstraZeneca.; Maurizio Fava has received research support from Abbott Laboratories, Alkermes Inc, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells Inc, Bristol-Myers Squibb, Cephalon Inc, Clinical Trials Solutions LLC, Covidien, Eli Lilly and Company, EnVivo Pharmaceuticals Inc, Forest Pharmaceuticals Inc, Ganeden Biotech Inc, GlaxoSmithKline, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis AG, Orgaon Pharmaceuticals, PamLab LLC, Pfizer Inc, Pharmavite LLC, Roche, RTC Logic LLC, Sanofi-Aventis US LLC, Shire, Solvay Pharmaceuticals Inc, Synthelabo, and Wyeth-Ayerst Laboratories. Dr. Fava has received advisory/consulting fees from Abbott Laboratories, Affectis Pharmaceuticals AG, Amarin Pharma Inc, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management Inc, BioMarin Pharmaceuticals Inc, Biovail Corporation, BrainCells Inc, Bristol-Myers Squibb, CeNeRx Bio-Pharma, Cephalon Inc, Clinical Trials Solutions LLC, CNS Response Inc, Compellis Pharmaceuticals, Cypress Pharmaceutical Inc, Dov Pharmaceuticals Inc, Eisai Inc, Eli Lilly and Company, EPIX Pharmaceuticals Inc, Euthymics Bioscience Inc, Fabre-Kramer Pharmaceuticals Inc, Forest Pharmaceuticals Inc, GenOmind LLC, GlaxoSmithKline, Gruenthal GmbH, Janssen Pharmaceutica, Jazz Pharmaceuticals Inc, Johnson & Johnson Pharmaceutical Research & Development LLC., Knoll Pharmaceuticals Corp., Labopharm Inc, Lorex Pharmaceuticals, Lundbeck Inc, MedAvante Inc, Merck & Co. Inc, Methylation Sciences, Neuronetics Inc, Novartis AG, Nutrition 21, Organon Pharmaceuticals, PamLab LLC, Pfizer Inc, PharmaStar, Pharmavite LLC, Precision Human Biolaboratory, Prexa Pharmaceuticals Inc, PsychoGenics, Psylin Neurosciences Inc, Ridge Diagnostics Inc, Roche, RCT Logic LLC, Sanofi-Aventis US LLC., Sepracor Inc, Schering-Plough Corporation, Solvay Pharmaceuticals Inc, Somaxon Pharmaceuticals Inc, Somerset Pharmaceuticals Inc, Synthelabo, Takeda Pharmaceutical Company Limited, Tetragenex Pharmaceuticals Inc, TransForm Pharmaceuticals Inc, Transcept Pharmaceuticals Inc, Vanda Pharmaceuticals Inc, and Wyeth-Ayerst Laboratories. Dr. Fava also reports receiving speaking/publishing fees from Adamed Co, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cephalon Inc, Eli Lilly and Company, Forest Pharmaceuticals Inc, GlaxoSmithKline, Imedex LLC, MGH Psychiatry Reed/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon Pharmaceuticals, Pfizer Inc, PharmaStar, United BioSource Corp, and Wyeth-Ayerst Laboratories. Dr. Fava has equity holdings in Compellis, and receives royalty/patent or other income from the following: patent for the Sequential Parallel Comparison Design and patent application for a combination of azapirones and bupropion in MDD, copyright royalties for the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation Emergent Signs and Symptoms, and the State vs Trait, Assessability, Face Validity, Ecological Validity, and Rule of Three P's Criteria. NR 13 TC 12 Z9 12 U1 0 U2 2 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 OCT PY 2011 VL 199 IS 10 BP 807 EP 810 DI 10.1097/NMD.0b013e31822fcbe2 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 827BD UT WOS:000295399300014 PM 21964277 ER PT J AU Asada-Utsugi, M Uemura, K Noda, Y Kuzuya, A Maesako, M Ando, K Kubota, M Watanabe, K Takahashi, M Kihara, T Shimohama, S Takahashi, R Berezovska, O Kinoshita, A AF Asada-Utsugi, Megumi Uemura, Kengo Noda, Yasuha Kuzuya, Akira Maesako, Masato Ando, Koichi Kubota, Masakazu Watanabe, Kiwamu Takahashi, Makio Kihara, Takeshi Shimohama, Shun Takahashi, Ryosuke Berezovska, Oksana Kinoshita, Ayae TI N-cadherin enhances APP dimerization at the extracellular domain and modulates A beta production SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid precursor protein; amyloid beta; N-cadherin; synapse ID AMYLOID PRECURSOR PROTEIN; COPPER-BINDING DOMAIN; ALZHEIMERS-DISEASE; GXXXG MOTIFS; MUTATIONS; CONFORMATION; SECRETASE; CLEAVAGE; ADHESION; DIMER AB Sequential processing of amyloid precursor protein (APP) by beta- and gamma-secretase leads to the generation of amyloid-beta (A beta) peptides, which plays a central role in Alzheimer's disease pathogenesis. APP is capable of forming a homodimer through its extracellular domain as well as transmembrane GXXXG motifs. A number of reports have shown that dimerization of APP modulates A beta production. On the other hand, we have previously reported that N-cadherin-based synaptic contact is tightly linked to A beta production. In the present report, we investigated the effect of N-cadherin expression on APP dimerization and metabolism. Here, we demonstrate that N-cadherin expression facilitates cis-dimerization of APP. Moreover, N-cadherin expression led to increased production of A beta as well as soluble APP beta, indicating that beta-secretase-mediated cleavage of APP is enhanced. Interestingly, N-cadherin expression affected neither dimerization of C99 nor A beta production from C99, suggesting that the effect of N-cadherin on APP metabolism is mediated through APP extracellular domain. We confirmed that N-cadherin enhances APP dimerization by a novel luciferase-complementation assay, which could be a platform for drug screening on a high-throughput basis. Taken together, our results suggest that modulation of APP dimerization state could be one of mechanisms, which links synaptic contact and A beta production. C1 [Kinoshita, Ayae] Kyoto Univ, Grad Sch Med, Sch Hlth Sci, Sakyo Ku, Kyoto 6068507, Japan. [Asada-Utsugi, Megumi; Uemura, Kengo; Ando, Koichi; Watanabe, Kiwamu; Takahashi, Makio; Takahashi, Ryosuke] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto 6068507, Japan. [Shimohama, Shun] Sapporo Med Univ, Dept Neurol, Sapporo, Hokkaido, Japan. [Berezovska, Oksana] Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA USA. RP Kinoshita, A (reprint author), Kyoto Univ, Grad Sch Med, Sch Hlth Sci, Sakyo Ku, 53 Shogoin Kawaharacho, Kyoto 6068507, Japan. EM akinoshita@hs.med.kyoto-u.ac.jp FU KANAE Foundation for the promotion of medical science; NIH [AG15379]; Ministry of Education, Culture, Sports, Science and Technology [20300124] FX This work was supported by KANAE Foundation for the promotion of medical science (KU), NIH AG15379 (OB) and by Ministry of Education, Culture, Sports, Science and Technology (20300124, AK). We are grateful to Dr. S. Michnick, University of Montreal, Canada, who kindly provided pcDNA-hGLuc1 and pcDNA-hGLuc2 plasmid and Adherex Technologies (Durham, NC) for providing ADH-1. NR 40 TC 14 Z9 14 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2011 VL 119 IS 2 BP 354 EP 363 DI 10.1111/j.1471-4159.2011.07364.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 834PE UT WOS:000295973900011 PM 21699541 ER PT J AU Suh, J Lyckman, A Wang, LR Eckman, EA Guenette, SY AF Suh, Jaehong Lyckman, Alvin Wang, Lirong Eckman, Elizabeth A. Guenette, Suzanne Y. TI FE65 proteins regulate NMDA receptor activation-induced amyloid precursor protein processing SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE APLP2; APP; cortical neurons; FE65; FE65L1; NMDA ID C-TERMINAL FRAGMENT; APP MESSENGER-RNA; ALZHEIMERS-DISEASE; ALPHA-SECRETASE; BETA PRODUCTION; CELL-SURFACE; IN-VIVO; A-BETA; PROMOTES; EXPRESSION AB Amyloid precursor protein (APP) family members and their proteolytic products are implicated in normal nervous system function and Alzheimer's disease pathogenesis. APP processing and A beta secretion are regulated by neuronal activity. Various data suggest that NMDA receptor (NMDAR) activity plays a role in both non-amyloidogenic and amyloidogenic APP processing depending on whether synaptic or extrasynaptic NMDARs are activated, respectively. The APP-inter-acting FE65 proteins modulate APP trafficking and processing in cell lines, but little is known about their contribution to APP trafficking and processing in neurons, either in vivo or in vitro. In this study, we examined the contribution of the FE65 protein family to APP trafficking and processing in WT and FE65/FE65L1 double knockout neurons under basal conditions and following NMDAR activation. We report that FE65 proteins facilitate neuronal A beta secretion without affecting APP fast axonal transport to pre-synaptic terminals. In addition, FE65 proteins facilitate an NMDAR-dependent non-amyloidogenic APP processing pathway. Generation of high-molecular weight (HMW) species bearing an APP C-terminal epitope was also observed following NMDAR activation. These HMW species require proteasomal and calpain activities for their accumulation. Recovery of APP polypeptide fragments from electroeluted HMW species having molecular weights consistent with calpain I cleavage of APP suggests that HMW species are complexes formed from APP metabolic products. Our results indicate that the FE65 proteins contribute to physiological APP processing and accumulation of APP metabolic products resulting from NMDAR activation. C1 [Suh, Jaehong; Wang, Lirong; Guenette, Suzanne Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Genet & Aging Res, Charlestown, MA 02129 USA. [Lyckman, Alvin] Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Dept Neurol, Brighton, MA USA. [Eckman, Elizabeth A.] Mayo Clin Jacksonville, Jacksonville, FL USA. RP Guenette, SY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Genet & Aging Res, 114 16th St, Charlestown, MA 02129 USA. EM guenette@helix.mgh.harvard.edu FU NIH [AG15903]; Korea Research Foundation [KRF-2006-214-E00024] FX We thank Dr Nicolaos Robakis for providing R7 antibody; Dr W. Wasco for providing the APLP2 and APLP1 C-terminal antibodies and Dr D. M. Kovacs for providing the C66 APP C-terminal antibody. We also thank Drs Doo Yeon Kim, Henri Huttunen and Robert Moir for their scientific expertise. Sources of funding for this study include NIH AG15903 (SYG and JS) and the Korea Research Foundation fellowship (KRF-2006-214-E00024. JS). Authors report no conflict of interest. NR 54 TC 10 Z9 10 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2011 VL 119 IS 2 BP 377 EP 388 DI 10.1111/j.1471-4159.2011.07419.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 834PE UT WOS:000295973900013 PM 21824144 ER PT J AU Adams, JM AF Adams, Jeffrey M. TI Influencing the Future of Nursing An Interview With Sue Hassmiller SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Adams, JM (reprint author), Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, 275 Cambridge St,POB 4, Boston, MA 02114 USA. EM jadams9@partners.org NR 3 TC 2 Z9 2 U1 0 U2 1 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 OCT PY 2011 VL 41 IS 10 BP 394 EP 396 DI 10.1097/NNA.0b013e31822edb64 PG 3 WC Nursing SC Nursing GA 829YH UT WOS:000295622400003 ER PT J AU Glazer, G Erickson, JI Mylott, L Mulready-Shick, J Banister, G AF Glazer, Greer Erickson, Jeanette Ives Mylott, Laura Mulready-Shick, JoAnn Banister, Gaurdia TI Partnering and Leadership Core Requirements for Developing a Dedicated Education Unit SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID ACADEMIC-SERVICE PARTNERSHIPS AB Preparing new nurses to practice independently and provide safe and effective care has always been a priority for nurse leaders in academe and service but is becoming more of a challenge as patient acuity intensifies and care systems become more complex. Recent reports by the Carnegie Foundation 1 and by the Institute of Medicine and RWJF 2 call for nurse leaders to improve how nurses are prepared and educated by reducing the gap between classroom and clinical teaching and making better use of resources and partnerships available in the community. The development of a dedicated education unit is one strategy to address this gap. C1 [Glazer, Greer] Univ Massachusetts, Undergrad Nursing Program, Boston, MA 02125 USA. [Mulready-Shick, JoAnn] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Erickson, Jeanette Ives; Banister, Gaurdia] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Mylott, Laura] Brigham & Womens Hosp, Ctr Nursing Excellence, Dept Nursing, Boston, MA 02115 USA. RP Glazer, G (reprint author), Univ Massachusetts, Undergrad Nursing Program, 100 Morrissey Blvd, Boston, MA 02125 USA. EM greer.glazer@umb.edu NR 18 TC 10 Z9 10 U1 1 U2 9 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 OCT PY 2011 VL 41 IS 10 BP 401 EP 406 DI 10.1097/NNA.0b013e31822edd79 PG 6 WC Nursing SC Nursing GA 829YH UT WOS:000295622400005 PM 21934426 ER PT J AU Betancourt, JR Renfrew, MR AF Betancourt, Joseph R. Renfrew, Megan R. TI Unequal Treatment in the US: Lessons and Recommendations for Cancer Care Internationally SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE disparities; culture; cancer ID HEALTH-CARE; CARDIAC-CATHETERIZATION; RACIAL-DIFFERENCES; DECISION-MAKING; WHITE PATIENTS; MEDICAL-CARE; LUNG-CANCER; RACE; DISPARITIES; COMMUNICATION AB Despite interventions that have improved the overall health of the majority of Americans, racial and ethnic minorities have benefited less from these advances. Research has shown that multiple factors contribute to racial and ethnic disparities in health, health care, and cancer care. The Institute of Medicine Report, "Unequal Treatment" provides a detailed examination of racial/ethnic disparities in health care in the U. S., highlighting three clinical contributors-poor provider-patient communication, stereotyping in clinical decisionmaking, and patient mistrust. Although the findings and recommendations in "Unequal Treatment" are broad in scope, they provide a blueprint for how to address disparities in health care in general-as well as cancer care- and have direct implications for clinical practice, both nationally and internationally. We propose a patient-based approach to cross-cultural care as a model to improve communication with racial and ethnic minorities, and cross-cultural populations in general. We also highlight the importance of community based interventions, such as those that use health care navigators to promote cancer screening. If we hope to provide effective cancer care around the world, we must be attentive to the factors that impact minorities and vulnerable populations, and be prepared to address them. C1 [Betancourt, Joseph R.; Renfrew, Megan R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Dispar Solut Ctr, Boston, MA 02114 USA. RP Betancourt, JR (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Dispar Solut Ctr, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jbetancourt@partners.org NR 60 TC 2 Z9 2 U1 2 U2 3 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 OCT PY 2011 VL 33 SU 2 BP S149 EP S153 DI 10.1097/MPH.0b013e318230dfea PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 835ED UT WOS:000296016700016 PM 21952574 ER PT J AU Wozniak, J Petty, CR Schreck, M Moses, A Faraone, SV Biederman, J AF Wozniak, Janet Petty, Carter R. Schreck, Meghan Moses, Alana Faraone, Stephen V. Biederman, Joseph TI High level of persistence of pediatric bipolar-I disorder from childhood onto adolescent years: A four year prospective longitudinal follow-up study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Children; Adolescent; Course; Follow-up ID DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; PLACEBO-CONTROLLED TRIAL; SPECTRUM DISORDERS; NEURAL CIRCUITRY; NATURAL-HISTORY; DOUBLE-BLIND; CHILDREN; MANIA; PHENOTYPE AB Objective: To examine the longitudinal course of pediatric bipolar (BP)-I disorder in youth transitioning from childhood into adolescence. Methods: We conducted a four year prospective follow-up study of 78 youth with BP-I disorder 6-17 years old at ascertainment followed up into adolescent years (13.4 +/- 3.9 years). All subjects were comprehensively assessed with structured diagnostic interviews, neuropsychological testing, psychosocial, educational and treatment history assessments. BP disorder was considered persistent if subjects met full criteria for DSM-IV BP-I disorder at follow-up. Results: Of 78 BP-I participating youth subjects, 57 (73.1%), continued to meet full diagnostic criteria for BP-I Disorder. Of those with a non-persistent course, only 6.4% (n = 5) were euthymic (i.e., syndromatic and symptomatic remission) at the 4-year follow-up and were not receiving pharmacotherapy for the disorder. The other non-persistent cases either continued to have subthreshold BP-I disorder (n = 5, 6.4%), met full (n = 3, 3.8%) or subthreshold (n = 1, 1.3%) criteria for major depression, or were euthymic but were treated for the disorder (n = 7. 9.0%). Full persistence was associated with higher rates of major depression and disruptive behavior disorders at the follow-up assessment and higher use of stimulant medicines at the baseline assessment. Non-Peristent BP-I was also characterized by high levels of dysfunction and morbidity. Conclusions: This four year follow-up shows that the majority of BP-I disorder youth continue to experience persistent disorder into their mid and late adolescent years and its persistence is associated with high levels of morbidity and disability. Persistence of subsyndromal forms of bipolar disorder was also associated with dysfunction and morbidity. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Wozniak, Janet; Petty, Carter R.; Schreck, Meghan; Moses, Alana; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Wozniak, Janet; Biederman, Joseph] SUNY Upstate Med Univ, Harvard Univ, Sch Med, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jwozniak@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH [5R01MH66237-5]; McNeil; Shire; Janssen; Lilly; Boehringer-Ingelheim; GlaxoSmithKline; UCB (Schwarz) Pharma; Sepracor; National Institutes of Health; Novartis; Pfizer; Eli Lilly; Guilford Press; Elminda; Next Wave Pharmaceuticals; CME course; AstraZeneca; Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Forest; Glaxo; Gliatech; Merck; NARSAD; NIDA; New River; NICHD; Noven; Neurosearch; Organon; Otsuka; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.; Wyeth; Pediatric Psychopharmacology Council FX Dr. Wozniak is the author of the book, "Is Your Child Bipolar" published May 2008, Bantam Books. She has been a speaker for McNeil, Primedia/MGH Psychiatry Academy, on the Advisory Board for Pfizer and Shire and received research support from NIMH, McNeil, Shire, Janssen and Lilly. Her spouse John Winkelman MD, PhD has been on the Speakers Bureau for Boehringer-Ingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda, on the Advisory Board for Axon Labs, Boehringer-Ingelheim, Covance, GlaxoSmithKline, Impax, Luitpold Jazz Pharmaceuticals, Novartis, Neurogen, Novadel Pharma, Pfizer, UCB (Schwarz) Pharma, Sepracor, Takeda, Zeo and received research support from Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwarz) Pharma, Sepracor.; In the past year, Dr. Stephen Faraone has received consulting fees and has been on Advisory Boards for Shire Development and has received research support from Shire and the National Institutes of Health. In previous years, Dr. Faraone has received consulting fees or has been on Advisory Boards or has participated in continuing medical education programs sponsored by: Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. Dr. Faraone receives royalties from a book published by Guilford Press: Straight Talk about Your Child's Mental Health.; Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca: these royalties are paid to the Department of Psychiatry at MGH. In 2010, 12.; Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundacion Dr.Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.: the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, Dr. Joseph Biederman received a speaker's fee from the following sources: Fundacion Areces (Spain), Medice Pharmaceuticals (Germany) and the Spanish Child Psychiatry Association. In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, The Prechter Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc. and Wyeth.; This study was partially supported by NIMH 5R01MH66237-5 (to JW), The Prechter Foundation, and the Pediatric Psychopharmacology Council Fund. NR 56 TC 34 Z9 34 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1273 EP 1282 DI 10.1016/j.jpsychires.2010.10.006 PG 10 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500001 PM 21683960 ER PT J AU Mathis, KI Wynn, JK Breitmeyer, B Nuechterlein, KH Green, MF AF Mathis, Kristopher I. Wynn, Jonathan K. Breitmeyer, Bruno Nuechterlein, Keith H. Green, Michael F. TI The attentional blink in schizophrenia: Isolating the perception/attention interface SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Attentional blink; Attention; Perceptual impairment ID SERIAL VISUAL PRESENTATION; TEMPORAL ATTENTION; QUALITY-ASSURANCE; SELECTION; MECHANISM; DEFICITS; MASKING; MODEL AB Previous work has demonstrated that several aspects of visual processing are impaired in schizophrenia, including early perceptual processes and later higher-order processes. However, it remains unclear whether the stage of processing where early perception and later higher-order processes interact is impaired in schizophrenia. The current research examined this interface in schizophrenia using the attentional blink (AB) paradigm. We administered two rapid serial visual processing (RSVP) tasks to 143 patients with schizophrenia or schizoaffective disorder and 80 healthy controls: 1) a single target detection task, to measure basic visual perception; and 2) a dual target detection task, to measure the AB effect. In the dual target task, the two target stimuli (T1 and T2) were presented at varying positions or "lags" within a rapid sequential stream of distractor stimuli. Participants verbally identified the target stimuli. Both groups showed the expected AB effect, with T2 accuracy being poorest 200-500 ms after presentation of T1. However, patients showed an exaggerated AB effect compared to the healthy controls, with significantly reduced detection of T2, even after correcting for performance on the single target task. The reduction in accuracy was steeper and more pronounced in the patients during the AB lags, and it extended to lags before and after the typical AB. This performance pattern on the AB task suggests that patients with schizophrenia exhibit both deficits in visual processing at the interface of perceptual and attentional processing and a general attentional deficit. Published by Elsevier Ltd. C1 [Mathis, Kristopher I.; Wynn, Jonathan K.; Breitmeyer, Bruno; Nuechterlein, Keith H.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA 90073 USA. RP Mathis, KI (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, 11301 Wilshire Blvd,Bldg 210,Room 117, Los Angeles, CA 90073 USA. EM mathis@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIH [MH043292, MH065707] FX Funding for this study was provided by NIH Grants MH043292 and MH065707 (MFG); the NIH had no 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. NR 30 TC 11 Z9 12 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1346 EP 1351 DI 10.1016/j.jpsychires.2011.04.002 PG 6 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500010 PM 21550051 ER PT J AU Martin, LF Olincy, A Ross, RG Du, YP Singel, D Shatti, S Tregellas, JR AF Martin, Laura Frances Olincy, Ann Ross, Randy G. Du, Yiping P. Singel, Debra Shatti, Shireen Tregellas, Jason R. TI Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder (vol 45, pg 670, 2011) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Correction C1 [Martin, Laura Frances; Olincy, Ann; Ross, Randy G.; Du, Yiping P.; Singel, Debra; Shatti, Shireen; Tregellas, Jason R.] Univ Colorado Denver Sch Med, Aurora, CO 80045 USA. [Tregellas, Jason R.] Eastern Colorado Hlth Care Syst, Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80020 USA. RP Martin, LF (reprint author), Univ Colorado Denver Sch Med, Mail Stop F546,13001 E 17th Pl, Aurora, CO 80045 USA. EM laura.martin@ucdenver.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2011 VL 45 IS 10 BP 1410 EP 1410 DI 10.1016/j.jpsychires.2011.06.004 PG 1 WC Psychiatry SC Psychiatry GA 834XT UT WOS:000295998500020 ER PT J AU Malone, SK AF Malone, Susan Kohl TI Early to Bed, Early to Rise?: An Exploration of Adolescent Sleep Hygiene Practices SO JOURNAL OF SCHOOL NURSING LA English DT Review DE health/wellness; screening/risk identification; high school; integrative reviews ID SCHOOL START TIME; CHILDRENS SLEEP; STUDENTS; PATTERNS; BEHAVIOR; HEALTH; PREVALENCE; QUALITY; IMPACT; AGE AB Cognition, memory, safety, mental health, and weight are all affected by inadequate sleep. Biological studies indicate significant changes in sleep architecture during adolescence, such as changes in melatonin secretion, and a need for greater total sleep time. Yet, social contexts and cultural values impinge on these changing biological sleep needs making adolescents vulnerable to the dangers of insufficient sleep. Sleep hygiene practices are purported as potential mediating factors between biological sleep needs and the sociocultural context of sleep. The purpose of this literature review is to highlight biological and social factors contributing to insufficient sleep in adolescents, to explore the evidence of several recommended sleep hygiene practices, and to stimulate further research about how adolescents negotiate their shifting biological sleep needs amid increasing social demands. C1 Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. RP Malone, SK (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA. EM malones@nursing.upenn.edu NR 57 TC 10 Z9 11 U1 2 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1059-8405 J9 J SCH NURS JI J. Sch. Nurs. PD OCT PY 2011 VL 27 IS 5 BP 348 EP 354 DI 10.1177/1059840511410434 PG 7 WC Nursing SC Nursing GA 831MI UT WOS:000295734700010 PM 21606219 ER PT J AU Stepp, CE Merchant, GR Heaton, JT Hillman, RE AF Stepp, Cara E. Merchant, Gabrielle R. Heaton, James T. Hillman, Robert E. TI Effects of Voice Therapy on Relative Fundamental Frequency During Voicing Offset and Onset in Patients With Vocal Hyperfunction SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE vocal hyperfunction; muscle tension dysphonia; vocal nodules; fundamental frequency ID TENSION DYSPHONIA; PARKINSON-DISEASE; SURFACE EMG; MUSCLE; AERODYNAMICS; DISORDERS; BEHAVIOR; SPEAKERS AB Purpose: The purpose of this study was to determine whether the relative fundamental frequency (RFF) surrounding a voiceless consonant in patients with hyperfunctionally related voice disorders would normalize after a successful course of voice therapy. Method: Pre- and posttherapy measurements of RFF were compared in 16 subjects undergoing voice therapy for voice disorders associated with vocal hyperfunction. Results: A 2-way analysis of variance showed a statistically significant effect of both cycle of vibration near the consonant and therapy phase (pre- vs. post-), with p <. 001. A post hoc paired Student's t test showed that posttherapy RFF measurements were significantly higher (more typical; p <. 0001) than pretherapy measurements. Conclusions: Prior to therapy, participants exhibited lowered RFF values, similar to those found previously (Stepp, Hillman, & Heaton, 2010). After successful completion of voice therapy, RFF values increased toward patterns seen previously in individuals with healthy typical voice. The goal of voice therapy in these patients was to reduce laryngeal muscle tension; therefore, the increase of RFF toward more typical values may be indicative of decreased baseline laryngeal muscle tension resulting from therapy. Results are discussed further in terms of necessary research to incorporate RFF as a clinical measure of vocal hyperfunction. C1 [Stepp, Cara E.; Merchant, Gabrielle R.; Hillman, Robert E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Stepp, Cara E.; Merchant, Gabrielle R.; Heaton, James T.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Heaton, James T.; Hillman, Robert E.] Harvard Univ, Sch Med, Boston, MA USA. [Heaton, James T.; Hillman, Robert E.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Stepp, CE (reprint author), Boston Univ, Boston, MA 02215 USA. EM cstepp@bu.edu OI Merchant, Gabrielle/0000-0001-7251-1879 FU NIDCD NIH HHS [5T32DC000038-17, T32 DC000038] NR 30 TC 19 Z9 19 U1 0 U2 8 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT 1 PY 2011 VL 54 IS 5 BP 1260 EP 1266 DI 10.1044/1092-4388(2011/10-0274) PG 7 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 828XI UT WOS:000295537200002 PM 21498578 ER PT J AU Hammerness, PG Perrin, JM Shelley-Abrahamson, R Wilens, TE AF Hammerness, Paul G. Perrin, James M. Shelley-Abrahamson, Rachel Wilens, Timothy E. TI Cardiovascular Risk of Stimulant Treatment in Pediatric Attention-Deficit/Hyperactivity Disorder: Update and Clinical Recommendations SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE ADHD; cardiovascular; stimulant ID DEFICIT-HYPERACTIVITY DISORDER; SALTS EXTENDED-RELEASE; METHYLPHENIDATE TRANSDERMAL SYSTEM; AMERICAN-HEART-ASSOCIATION; SUDDEN CARDIAC DEATH; AMBULATORY BLOOD-PRESSURE; LONG-TERM TOLERABILITY; SCHOOL-AGED CHILDREN; AMPHETAMINE SALTS; LISDEXAMFETAMINE DIMESYLATE AB Objective: This review provides an update on the cardiovascular impact of therapeutic stimulant-class medication for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Relevant clinical literature was ascertained using PubMed searches limited to human studies and the English language as of May 2011. Current practice guidelines and consensus statements also were reviewed. Results: Stimulant-class medications for healthy children and adolescents with ADHD are associated with mean elevations in blood pressure (<= 5 mmHg) and heart rate (<= 10 beats/min) without changes in electrocardiographic parameters. A subset (5-15%) of children and adolescents treated may have a greater increase in heart rate or blood pressure at a given assessment or may report a cardiovascular-type complaint during stimulant treatment. It is extremely rare for a child or adolescent receiving stimulant medication to have a serious cardiovascular event during treatment, with the risk appearing similar to groups of children not receiving stimulant medication. Conclusions: Clinicians should adhere to current recommendations regarding the prescription of stimulant medications for youth with ADHD. Scientific inquiry is indicated to identify patients at heightened risk and to continue surveillance for the longer-term cardiovascular impact of these agents. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(10):978-990. C1 [Hammerness, Paul G.; Perrin, James M.; Shelley-Abrahamson, Rachel; Wilens, Timothy E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Massachusetts Gen Hosp Children, Div Gen Pediat, Boston, MA 02114 USA. [Hammerness, Paul G.; Shelley-Abrahamson, Rachel; Wilens, Timothy E.] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. RP Hammerness, PG (reprint author), 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Cephalon; Eli Lilly and Co.; GlaxoSmithKline; Johnson and Johnson; McNeil; Merck; New River; Novartis; Ortho-McNeil Janssen; Pfizer; Shire; Takeda; Elminda; Abbott; Nextwave; National Institutes of Health (NIH)/National Institute of Drug Abuse FX Dr. Hammerness has participated in continuing medical education (CME) activities, professional talks, and/or writing supported by Ortho-McNeil Janssen and Shire. He has served on the advisory board for Shire. He has participated in research studies funded by Cephalon, Eli Lilly and Co., GlaxoSmithKline, Johnson and Johnson, McNeil, Merck, New River, Novartis, Ortho-McNeil Janssen, Pfizer, Shire, Takeda, and Elminda. He has received honoraria from commercial entities supporting the Massachusetts General Hospital Psychiatry Academy. Dr. Perrin has served as a consultant for Pfizer. Dr. Wilens has received grant support from Abbott, McNeil, Eli Lilly and Co., Nextwave, the National Institutes of Health (NIH)/National Institute of Drug Abuse, Merck, and Shire. He has served on the speakers' bureau for Abbott, AstraZeneca, McNeil, Eli Lilly and Co., Nextwave, NIH, Novartis, Merck, and Shire. He receives royalties from Guilford Press, Ms. Shelley-Abrahamson reports no biomedical financial interests or potential conflicts of interest. NR 100 TC 39 Z9 40 U1 2 U2 9 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 OCT PY 2011 VL 50 IS 10 BP 978 EP 990 DI 10.1016/j.jaac.2011.07.018 PG 13 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 829EZ UT WOS:000295562700006 PM 21961773 ER PT J AU Atesok, KI Jupiter, JB Weiss, APC AF Atesok, Kivanc I. Jupiter, Jesse B. Weiss, Arnold-Peter C. TI Galeazzi Fracture SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID DISTAL RADIOULNAR JOINT; RADIAL SHAFT FRACTURES; BIOMECHANICAL EVALUATION; INTEROSSEOUS MEMBRANE; ANTERIOR DISLOCATION; FOREARM; ULNA; CHILDREN; PLATE; MONTEGGIA AB Galeazzi fracture is a fracture of the radial diaphysis with disruption at the distal radioulnar joint (DRUJ). Typically, the mechanism of injury is forceful axial loading and torsion of the forearm. Diagnosis is established on radiographic evaluation. Underdiagnosis is common because disruption of the ligamentous restraints of the DRUJ may be overlooked. Nonsurgical management with anatomic reduction and immobilization in a long-arm cast has been successful in children. In adults, nonsurgical treatment typically fails because of deforming forces acting on the distal radius and DRUJ. Open reduction and internal fixation is the preferred surgical option. Anatomic reduction and rigid fixation should be followed by intraoperative assessment of the DRUJ. Further intraoperative interventions are based on the reducibility and postreduction stability of the DRUJ. Misdiagnosis or inadequate management of Galeazzi fracture may result in disabling complications, such as DRUJ instability, malunion, limited forearm range of motion, chronic wrist pain, and osteoarthritis. C1 [Atesok, Kivanc I.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Weiss, Arnold-Peter C.] Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02912 USA. [Weiss, Arnold-Peter C.] Rhode Isl Hosp, Providence, RI USA. RP Atesok, KI (reprint author), Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. NR 44 TC 11 Z9 13 U1 0 U2 2 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD OCT PY 2011 VL 19 IS 10 BP 623 EP 633 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 831CU UT WOS:000295707100006 PM 21980027 ER PT J AU Forman, DE AF Forman, Daniel E. TI Nursing Homes and the Care of Heart Failure Residents: What Have We Learned? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material C1 [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, Div Cardiovasc Med, Boston VA Healthcare Syst, Boston, MA USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org NR 5 TC 1 Z9 1 U1 0 U2 2 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 OCT PY 2011 VL 12 IS 8 BP 544 EP 544 DI 10.1016/j.jamda.2010.07.015 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 834XP UT WOS:000295998100002 PM 21450200 ER PT J AU Kalva, SP Somarouthu, B Jaff, MR Wicky, S AF Kalva, Sanjeeva P. Somarouthu, Bhanusupriya Jaff, Michael R. Wicky, Stephan TI Segmental Arterial Mediolysis: Clinical and Imaging Features at Presentation and during Follow-up SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID FIBROMUSCULAR DYSPLASIA; VISCERAL ARTERIES; MESENTERIC-ARTERY; EMBOLIZATION; VASCULITIS; ANEURYSM; VARIANT AB Purpose: To review clinical and imaging features at presentation and during follow-up of patients with a suspected diagnosis of segmental arterial mediolysis (SAM). Materials and Methods: All cases of SAM diagnosed at a single institution from 2000 to 2010 were included. Diagnosis was based on characteristic radiologic features in the absence of other plausible diagnoses. Medical records were reviewed for demographics, presenting symptoms, and laboratory and imaging findings at presentation and during follow-up. Results: Fourteen patients (nine men; mean age, 53 y +/- 15) were diagnosed with SAM. Initial presentation included abdominal or flank pain (n = 8) and chest pain, headache, stroke, or suprapubic fullness (n = 1 each). Two patients were asymptomatic. Inflammatory markers were negative in all cases. Imaging at presentation revealed involvement of celiac (n = 7), common hepatic (n = 3), splenic (11 = 2), superior mesenteric (n = 5), renal (n = 5), and iliac (n = 2) arteries and the abdominal aorta (n = 1). Imaging demonstrated arterial dissections (n = 10), fusiform aneurysms (n = 6), arterial wall thickening (n = 2), and artery occlusion (n = 1). Clinical follow-up was available in 13 patients (median, 25 mo). Symptoms improved (n = 4), resolved (n = 3), or remained stable (n = 2), and four patients experienced new symptoms. Follow-up imaging, available in 10 patients at a median of 33 months, demonstrated new dissections, aneurysms, or arterial occlusions in five patients, including carotid artery dissection in three. Imaging findings remained stable (n = 3), improved (n = 1), or resolved (n = 1). Conclusions: SAM affects middle-aged and elderly patients. Visceral artery dissections and aneurysms are common. The disease progresses in nearly half the patients. Serial follow-up with computed tomographic angiography and/or magnetic resonance angiography may be necessary to monitor disease progression. C1 [Kalva, Sanjeeva P.; Somarouthu, Bhanusupriya; Wicky, Stephan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Dept Vasc Med, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB-832,55 Fruit St, Boston, MA 02114 USA. EM skalva@partners.org NR 25 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2011 VL 22 IS 10 BP 1380 EP 1387 DI 10.1016/j.jvir.2011.07.001 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 831DH UT WOS:000295708400006 PM 21840227 ER PT J AU Shaw, AT Yeap, BY Solomon, BJ Riely, GJ Gainor, J Engelman, JA Shapiro, GI Costa, DB Ou, SHI Butaney, M Salgia, R Maki, RG Varella-Garcia, M Doebele, RC Bang, YJ Kulig, K Selaru, P Tang, YY Wilner, KD Kwak, EL Clark, JW Iafrate, AJ Camidge, DR AF Shaw, Alice T. Yeap, Beow Y. Solomon, Benjamin J. Riely, Gregory J. Gainor, Justin Engelman, Jeffrey A. Shapiro, Geoffrey I. Costa, Daniel B. Ou, Sai-Hong I. Butaney, Mohit Salgia, Ravi Maki, Robert G. Varella-Garcia, Marileila Doebele, Robert C. Bang, Yung-Jue Kulig, Kimary Selaru, Paulina Tang, Yiyun Wilner, Keith D. Kwak, Eunice L. Clark, Jeffrey W. Iafrate, A. John Camidge, D. Ross TI Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis SO LANCET ONCOLOGY LA English DT Article ID EML4-ALK FUSION GENE; INFLAMMATORY MYOFIBROBLASTIC TUMOR; ANAPLASTIC LYMPHOMA KINASE; ACTIVATING MUTATIONS; PHASE-III; NEUROBLASTOMA; EXPRESSION; GEFITINIB; 2P23; EGFR AB Background ALK gene rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). In a recent phase 1 clinical trial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients with advanced, ALK-positive NSCLC. To assess whether crizotinib affects overall survival in these patients, we did a retrospective study comparing survival outcomes in crizotinib-treated patients in the trial and crizotinib-naive controls screened during the same time period. Methods We examined overall survival in patients with advanced, ALK-positive NSCLC who enrolled in the phase 1 clinical trial of crizotinib, focusing on the cohort of 82 patients who had enrolled through Feb 10, 2010. For comparators, we identified 36 ALK-positive patients from trial sites who were not given crizotinib (ALK-positive controls), 67 patients without ALK rearrangement but positive for EGFR mutation, and 253 wild-type patients lacking either ALK rearrangement or EGFR mutation. To assess differences in overall survival, we assessed subsets of clinically comparable ALK-positive and ALK-negative patients. Findings Among 82 ALK-positive patients who were given crizotinib, median overall survival from initiation of crizotinib has not been reached (95% CI 17 months to not reached); 1-year overall survival was 74% (95% CI 63-82), and 2-year overall survival was 54% (40-66). Overall survival did not differ based on age, sex, smoking history, or ethnic origin. Survival in 30 ALK-positive patients who were given crizotinib in the second-line or third-line setting was significantly longer than in 23 ALK-positive controls given any second-line therapy (median overall survival not reached [95% CI 14 months to not reached] vs 6 months [4-17], 1-year overall survival 70% [95% CI 50-83] vs 44% [23-64], and 2-year overall survival 55% [33-72] vs 12% [2-30]; hazard ratio 0.36, 95% CI 0.17-0.75; p=0.004). Survival in 56 crizotinib-treated, ALK-positive patients was similar to that in 63 ALK-negative, EGFR-positive patients given EGFR TKI therapy (median overall survival not reached [95% CI 17 months to not reached] vs 24 months [15-34], 1-year overall survival 71% [95% CI 58-81] vs 74% [61-83], and 2-year overall survival 57% [40-71] vs 52% [38-65]; p=0.786), whereas survival in 36 crizotinib-naive, ALK-positive controls was similar to that in 253 wild-type controls (median overall survival 20 months [95% CI 13-26] vs 15 months [13-17]; p=0.244). Interpretation In patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival compared with that of crizotinib-naive controls. ALK rearrangement is not a favourable prognostic factor in advanced NSCLC. Funding Pfizer Inc, V Foundation for Cancer Research. C1 [Shaw, Alice T.; Yeap, Beow Y.; Gainor, Justin; Engelman, Jeffrey A.; Kwak, Eunice L.; Clark, Jeffrey W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Riely, Gregory J.; Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shapiro, Geoffrey I.; Butaney, Mohit] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ou, Sai-Hong I.] Univ Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Varella-Garcia, Marileila; Doebele, Robert C.; Camidge, D. Ross] Univ Colorado, Ctr Canc, Aurora, CO USA. [Bang, Yung-Jue] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Kulig, Kimary; Selaru, Paulina; Tang, Yiyun; Wilner, Keith D.] Pfizer Inc, La Jolla, CA USA. [Kulig, Kimary; Selaru, Paulina; Tang, Yiyun; Wilner, Keith D.] Pfizer Inc, New York, NY USA. [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM ashaw1@partners.org RI Bang, Yung Jue/J-2759-2012; OI Costa, Daniel/0000-0002-0689-395X FU V Foundation for Cancer Research; Pfizer; Abbott Laboratories; ARIAD; Chugai; Merck; Boehringer-Ingelheim,; Tragara; Novartis; AstraZeneca; Pfizer Inc.; MGH Cancer Center; MGH Pathology Department; Sig Adler Cancer Research Fund; NCI Lung Cancer Spore [P50-CA090578]; American Cancer Society FX Pfizer Inc, V Foundation for Cancer Research.; ATS, BJS, DBC, RGM, Y-JB, ELK, and AJI received honoraria or consulting fees from Pfizer. RGM served as a paid expert witness for Pfizer. BJS, GJR, GIS, RGM, and Y-JB received research funding from Pfizer. KK, PS, YT, and KDW are employees and stockholders of Pfizer. AJI received honoraria or consulting fees from Abbott Laboratories. ATS, GJR, JAE, and JWC received honoraria or consulting fees from ARIAD. ATS and GJR received honoraria or consulting fees from Chugai. GJR received honoraria or consulting fees from Merck, Boehringer-Ingelheim, and Tragara. JAE received consulting fees and research funding from Novartis and AstraZeneca. All other authors declared no conflicts of interest.; We thank our patients and their families. We also thank members of the phase 1 study teams for their hard work, dedication, and support. The phase 1 trial of crizotinib was sponsored by Pfizer Inc. This study was supported by internal funds from the MGH Cancer Center and MGH Pathology Department. ATS is supported in part by the V Foundation for Cancer Research and by the Sig Adler Cancer Research Fund. BYY and DBC are supported by an NCI Lung Cancer Spore (P50-CA090578). DBC also receives funding from the American Cancer Society. Heather Saxton (Acumed; New York, NY, USA) assisted in collecting author statement forms, with funding from Pfizer. NR 33 TC 444 Z9 474 U1 5 U2 68 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 OCT PY 2011 VL 12 IS 11 BP 1004 EP 1012 DI 10.1016/S1470-2045(11)70232-7 PG 9 WC Oncology SC Oncology GA 833KW UT WOS:000295885200020 PM 21933749 ER PT J AU Mine, N Yamamoto, S Saito, N Yamazaki, S Suda, C Ishigaki, M Kufe, DW Von Hoff, DD Kawabe, T AF Mine, Naoki Yamamoto, Sayaka Saito, Naoya Yamazaki, Satoshi Suda, Chikako Ishigaki, Machiyo Kufe, Donald W. Von Hoff, Daniel D. Kawabe, Takumi TI CBP501-Calmodulin Binding Contributes to Sensitizing Tumor Cells to Cisplatin and Bleomycin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CALMODULIN INHIBITOR TRIFLUOPERAZINE; TARGET RECOGNITION; SIGNALING PATHWAYS; G(2) CHECKPOINT; PHOSPHORYLATION; DOXORUBICIN; ACTIVATION; RESISTANCE; PHENOTYPE; DISEASE AB CBP501 is an anticancer drug currently in randomized phase II clinical trials for patients with non-small cell lung cancer and malignant pleural mesothelioma. CBP501 was originally described as a unique G(2) checkpoint-directed agent that binds to 14-3-3, inhibiting the actions of Chk1, Chk2, mitogen-activated protein kinase-activated protein kinase 2, and C-Tak1. However, unlike a G(2) checkpoint inhibitor, CBP501 clearly enhances the accumulation of tumor cells at G(2)-M phase that is induced by cisplatin or bleomycin at low doses and short exposure. By contrast, CBP501 does not similarly affect the accumulation of tumor cells at G(2)-M that is induced by radiation, doxorubicin, or 5-fluorouracil treatment. Our recent findings point to an additional mechanism of action for CBP501. The enhanced accumulation of tumor cells at G(2)-M upon combined treatment with cisplatin and CBP501 results from an increase in intracellular platinum concentrations, which leads to increased binding of platinum to DNA. The observed CBP501-enhanced platinum accumulation is negated in the presence of excess Ca(2+). Some calmodulin inhibitors behave similarly to, although less potently than, CBP501. Furthermore, analysis by surface plasmon resonance reveals a direct, high-affinity molecular interaction between CBP501 and CaM (K(d) = 4.62 x 10(-8) mol/L) that is reversed by Ca(2+), whereas the K(d) for the complex between CBP501 and 14-3-3 is approximately 10-fold weaker and is Ca(2+) independent. We conclude that CaM inhibition contributes to CBP501's activity in sensitizing cancer cells to cisplatin or bleomycin. This article presents an additional mechanism of action which might explain the clinical activity of the CBP501-cisplatin combination. Mol Cancer Ther; 10(10); 1929-38. (C) 2011 AACR. C1 [Mine, Naoki; Yamamoto, Sayaka; Saito, Naoya; Yamazaki, Satoshi; Suda, Chikako; Ishigaki, Machiyo; Kawabe, Takumi] CanBas Co Ltd, Numazu 4100801, Japan. [Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Von Hoff, Daniel D.] Translat Genom Res Inst TGen, Phoenix, AZ USA. RP Kawabe, T (reprint author), CanBas Co Ltd, 2-2-1 Otemachi, Numazu 4100801, Japan. EM takumi@canbas.co.jp NR 29 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD OCT PY 2011 VL 10 IS 10 BP 1929 EP 1938 DI 10.1158/1535-7163.MCT-10-1139 PG 10 WC Oncology SC Oncology GA 834NK UT WOS:000295968200017 PM 21831962 ER PT J AU Sawyer, AM Canamucio, A Moriarty, H Weaver, TE Richards, KC Kuna, ST AF Sawyer, Amy M. Canamucio, Anne Moriarty, Helene Weaver, Terri E. Richards, Kathy C. Kuna, Samuel T. TI Do cognitive perceptions influence CPAP use? SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient compliance; Continuous positive airway pressure; Obstructive sleep apnea; Self efficacy ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; LONG-TERM COMPLIANCE; NASAL CPAP; ADHERENCE; THERAPY; HEALTH; HYPERTENSION; ASSOCIATION; ADULTS AB Objective: Nonadherence to CPAP increases health and functional risks of obstructive sleep apnea. The study purpose was to examine if disease and treatment cognitive perceptions influence short-term CPAP use. Methods: A prospective longitudinal study included 66, middle-aged (56.7 +/- 10.7 yr) subjects (34 [51.5%] Caucasians; 30 [45.4%] African Americans) with severe OSA (AHI 43.5 events/hr +/- 24.6). Following full-night diagnostic/CPAP polysomnograms, home CPAP use was objectively measured at 1 week and 1 month. The Self Efficacy Measure for Sleep Apnea (SEMSA) questionnaire, measuring risk perception, outcome expectancies, and self-efficacy, was collected at baseline, post-CPAP education, and after 1 week CPAP treatment. Regression models were used. Results: CPAP use at one week was 3.99 +/- 2.48 h/night and 3.06 +/- 2.43 h/night at one month. No baseline SEMSA domains influenced CPAP use. Post-education self-efficacy influenced one week CPAP use (1.52 +/- 0.53, p = 0.007). Self-efficacy measured post-education and after one week CPAP use also influenced one month CPAP (1.40 +/- 0.52, p = 0.009; 1.20 +/- 0.50, p = 0.02, respectively). Conclusion: Cognitive perceptions influence CPAP use, but only within the context of knowledge of CPAP treatment and treatment use. Practice implications: Patient education is important to OSA patients' formulation of accurate and realistic disease and treatment perceptions which influence CPAP adherence. Published by Elsevier Ireland Ltd. C1 [Sawyer, Amy M.] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadelphia, PA 19104 USA. [Canamucio, Anne] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ & Promot Res, Philadelphia, PA USA. [Sawyer, Amy M.; Kuna, Samuel T.] Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. [Weaver, Terri E.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Richards, Kathy C.] Univ Penn, Sch Nursing, Ctr Integrat Sci Aging, Philadelphia, PA 19104 USA. [Richards, Kathy C.] Univ Penn, Sch Nursing, Hartford Ctr Geriatr Nursing Excellence, Philadelphia, PA 19104 USA. [Sawyer, Amy M.] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. RP Sawyer, AM (reprint author), Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Claire M Fagin Hall,Rm 307B,418 Curie Blvd, Philadelphia, PA 19104 USA. EM asawyer@nursing.upenn.edu FU VA Stars & Stripes Healthcare Network Competitive Pilot Project Fund (Sawyer); NIH [K99NR011173]; Nursing/Patient Care Services Department at the Philadelphia VA Medical Center; Philips Respironics Sleep, Respironics Foundation; Cephalon FX Research support by VA Stars & Stripes Healthcare Network Competitive Pilot Project Fund (Sawyer) and NIH K99NR011173 (Sawyer). The authors would like to acknowledge the VISN 4 Eastern Regional Sleep Center staff and polysomnography technologists at the Philadelphia VA Medical Center for their diligence in caring for our research patients. We also would like to acknowledge the support of the Nursing/Patient Care Services Department at the Philadelphia VA Medical Center. The study was conducted at the Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania. The University of Pennsylvania IRB and the Philadelphia Veterans Affairs Medical Center IRB approved the study. Drs. Sawyer, Kuna, Moriarty and Richards and Ms Canamucio disclose the absence of financial conflicts of interest. Dr. Weaver has received research support from Philips Respironics Sleep, Respironics Foundation, and Cephalon; consults for Apnex Medical, Inc. and Cephalon, Inc.; receives royalties from Sanofi-Aventis Pharmaceutical, Merck & Co., Inc., Sleep Solutions, N.V. Organon, Apnex Medical, Inc., Ventus Medical, GlaxoSmithKline, Philips Respironics, Cephalon, Inc. NR 33 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2011 VL 85 IS 1 BP 85 EP 91 DI 10.1016/j.pec.2010.10.014 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 829GM UT WOS:000295566600014 PM 21071166 ER PT J AU Olfson, M Ascher-Svanum, H Faries, DE Marcus, SC AF Olfson, Mark Ascher-Svanum, Haya Faries, Douglas E. Marcus, Steven C. TI Predicting Psychiatric Hospital Admission Among Adults With Schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID PREVALENCE PSYCHOTIC DISORDERS; MODIFIABLE RISK-FACTORS; TARDIVE-DYSKINESIA; NEGATIVE SYMPTOMS; SUBSTANCE-ABUSE; INSIGHT; REHOSPITALIZATION; RELAPSE; SCALE; PSYCHOPATHOLOGY AB Objective: The authors identified patient characteristics that increased risk of hospital admission among adults with schizophrenia. Methods: A total of 1,460 participants in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) clinical trial were followed from the time they began a randomized trial of medication to first schizophrenia-related hospital admission. Results: In 869 person-years of follow-up, 203 patients were hospitalized. Increased risk of hospital admission was associated with early age (<= 17 years) of first antipsychotic treatment (adjusted hazard ratio [AHR]=2.16, 95% confidence interval [CI]=1.49-3.11), psychiatric hospitalization in past year (AHR=2.99, CI=2.23-4.00), having had DSM-IV alcohol (AHR=1.56, CI=1.16-2.10) or drug (AHR=1.50, CI=1.13-2.00) use disorders in the past five years, and baseline severe symptoms according to the Clinical Global Impressions Scale (AHR=1.54, CI=1.04-2.27), presence of tardive dyskinesia (AHR=1.55, CI=1.07-2.23), a high score on the positive symptoms subscale of the Positive and Negative Syndrome Scale (AHR=1.52, CI=1.07-2.15), and low social function (AHR=1.45, CI=1.03-2.04). As compared with olanzapine, the drugs quetiapine (AHR=2.14, CI=1.39-3.31), perphenazine (AHR=1.80, CI=1.11-2.94), and ziprasidone (AHR=2.70, CI=1.64-4.44) were associated with increased hospitalization risk. Risperidone was associated with a lower hospitalization risk than quetiapine (AHR=1.50, CI=1.01-2.22) and ziprasidone (AHR=1.89, CI=1.19-3.01). Conclusions: Efforts to lower hospital admission risk among individuals with schizophrenia should focus on history of early onset, recent inpatient admission, severe positive symptoms, poor social function, high global illness severity, and comorbid substance use disorders and on selection of an appropriate antipsychotic medication. (Psychiatric Services 62:1138-1145, 2011) C1 [Olfson, Mark] Columbia Univ, Dept Psychiat, New York, NY 10032 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Ascher-Svanum, Haya; Faries, Douglas E.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Univ Penn, Sch Social Practice & Policy, Philadelphia, PA 19104 USA. RP Olfson, M (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu FU Eli Lilly and Company; Bristol-Myers Squibb FX This project was supported by a research grant from Eli Lilly and Company to Columbia University, for which Dr. Olfson is principal investigator. In addition, Dr. Olfson has received a research grant to Columbia University from Bristol-Myers Squibb, and Dr. Marcus has served as a consultant to Bristol-Myers Squibb. NR 46 TC 24 Z9 24 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2011 VL 62 IS 10 BP 1138 EP 1145 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000006 PM 21969639 ER PT J AU Lesser, IM Zisook, S Gaynes, BN Wisniewski, SR Luther, JF Fava, M Khan, A McGrath, P Warden, D Rush, AJ Trivedi, M AF Lesser, Ira M. Zisook, Sidney Gaynes, Bradley N. Wisniewski, Stephen R. Luther, James F. Fava, Maurizio Khan, Ahsan McGrath, Patrick Warden, Diane Rush, A. John Trivedi, Madhukar TI Effects of Race and Ethnicity on Depression Treatment Outcomes: The CO-MED Trial SO PSYCHIATRIC SERVICES LA English DT Article ID STAR-ASTERISK-D; MEASUREMENT-BASED CARE; DIAGNOSTIC SCREENING QUESTIONNAIRE; REPORT QIDS-SR; UNITED-STATES; SELF-REPORT; MINORITY PATIENTS; QUICK INVENTORY; ANTIDEPRESSANT TREATMENT; PSYCHOMETRIC EVALUATION AB Objective: The investigators examined whether outcomes differ by race-ethnicity for patients with major depressive disorder in acute- (12 weeks) and continuation-phase (weeks 12-28) treatment with one of two antidepressant combinations or one selective serotonin reuptake inhibitor. Methods: This single-blind, seven-month prospective, randomized trial enrolled 352 non-Hispanic white (59%), 169 black (28%), and 79 white Hispanic (13%) participants from six primary and nine psychiatric care U.S. sites. Patients had nonpsychotic chronic or recurrent major depressive disorder (or both) of at least moderate severity. Escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine were delivered according to measurement-based care. The primary outcome was remission (last two consecutive 16-item Quick Inventory of Depressive Symptomatology-Self-Report ratings <8 and <6); secondary outcomes included side effects, adverse events, quality of life, function, and attrition. Results: Black participants had greater baseline psychiatric and medical comorbidity. Baseline depression severity did not significantly differ between groups. In both phases more blacks than those in other groups exited the trial early. There were only minor differences in side effects, no significant differences in remission rates, and no significant differences between groups in other outcomes for each treatment. Conclusions: Despite differences in sociodemographic characteristics and comorbidities, when measurement-based care was used, members of different minority groups had similar outcomes when treated with one antidepressant or a combination of two antidepressants. Black participants had the highest attrition rate, an important issue to address in clinical care. (Psychiatric Services 62:1167-1179, 2011) C1 [Lesser, Ira M.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Wisniewski, Stephen R.; Luther, James F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Khan, Ahsan] Univ Kansas, Sch Med, Dept Psychiat & Behav Sci, Wichita, KS 67214 USA. [McGrath, Patrick] Columbia Univ Coll Phys & Surg, Depress Evaluat Serv, New York, NY 10032 USA. [McGrath, Patrick] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Warden, Diane; Trivedi, Madhukar] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Trivedi, Madhukar] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, A. John] Duke Natl Univ Singapore, Off Clin Sci, Singapore, Singapore. RP Lesser, IM (reprint author), Harbor UCLA Med Ctr, Dept Psychiat, Box 8,1000 W Carson St,M-C 176847, Torrance, CA 90509 USA. EM ilesser@labiomed.org RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health (NIMH) [N01MH90003]; Pamlab, LLC; M-3 Corporation; Alkermes, Inc; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; CNS Response, Inc.; Covance; Covidien; Cypress Pharmaceutical, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; Icon Clinical Research; i3 Innovus/Ingenix; Janssen Pharmaceutica; Johnson Johnson PRD; Lundbeck Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; NextWave Pharmaceuticals; Novartis AG; Otsuka Pharmaceuticals; Pfizer Inc.; PharmoRx Therapeutics; Photothera; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Servier Laboratories; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Ltd; Tal Medical, Inc.; Vanda Pharmaceuticals, Inc.; patent for Sequential Parallel Comparison Design (SPCD); patent for research and licensing of SPCD with RCT Logic; Lippincott; Williams & Wilkins and World Scientific Publishing Co.; Guilford Press; CINP; Singapore College of Family Physicians; Targacept; Valient FX This project was funded by the National Institute of Mental Health (NIMH) under contract N01MH90003 to the University of Texas Southwestern Medical Center at Dallas. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of commercial products or organizations imply endorsement by the U.S. government. The NIMH had no role in the drafting or review of the manuscript, nor in the collection or analysis of the data. The authors appreciate the support of Forest Pharmaceuticals Inc., GlaxoSmithKline, Organon Inc., and Wyeth Pharmaceuticals in providing medications at no cost for this trial. The authors also acknowledge the editorial support of Jon Kilner, M.S., M.A.; Dr. Lesser reports no competing interests. Dr. Zisook has received research support from Pamlab, LLC. Dr. Gaynes has received grant support from M-3 Corporation. Dr. Wisniewski has been a consultant for Dey Pharmaceuticals and Venebio. Mr. Luther reports no competing interests. Dr. Fava has received research support from or been an advisor to the following: Alkermes, Inc.; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; CNS Response, Inc.; Covance; Covidien; Cypress Pharmaceutical, Inc.; Dinippon Sumitomo Pharma Co. Inc.; Eisai Inc.; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Eu-thymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; Icon Clinical Research; i3 Innovus/Ingenix; Janssen Pharmaceutica; Johnson & Johnson PRD; Lundbeck Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; NextWave Pharmaceuticals; Novartis AG; Otsuka Pharmaceuticals; Pamlab, LLC.; Pfizer Inc.; PharmoRx Therapeutics; Photothera; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Servier Laboratories; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Ltd; Tal Medical, Inc.; and Vanda Pharmaceuticals, Inc. He has equity holdings in Compellis. He has been a speaker for or published with the Belvoir Media Group; CME Institute/Physicians Postgraduate Press, Inc.; and the MGH Psychiatry Academy. In addition, Dr. Fava receives royalties or patent or other income as follows: patent for Sequential Parallel Comparison Design (SPCD); patent for research and licensing of SPCD with RCT Logic; patent application for a combination of azapirones and bupropion in major depressive disorder; copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, and SAFER; and royalties from Lippincott, Williams & Wilkins and World Scientific Publishing Co. Dr. Khan is on the speaker panel for Merck Schering-Plough. Dr. McGrath receives research and grant support from Roche Pharmaceuticals. Dr. Warden reports no competing interests. Dr. Rush has received royalty payments from Guilford Press, has been a consultant to Brain Resource, Inc., and has received a travel grant from CINP and a speaking fee from Singapore College of Family Physicians. Dr. Trivedi has been a speaker or received consultant honoraria from Abbott Laboratories, Inc.; Alkermes; AstraZeneca; Axon Advisors; Bristol-Myers Squibb; Cephalon, Inc.; CME Institute of Physicians; Eli Lilly and Company; Evotec; Forest Pharmaceuticals; GlaxoSmithKline; Johnson & Johnson PRD; Lundbeck, Inc.; MedAvante; Neuronetics; Otsuka Pharmaceuticals; Pamlab; Pfizer, Inc.; PgxHealth; Rexahn Pharmaceuticals; SHIRE Development; Takeda Pharmaceutical Company Ltd.; Tal Medical/Puretech Venture; and Transcept. Dr. Trivedi has also received research support from Naurex, Inc.; Targacept; and Valient. NR 65 TC 12 Z9 12 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2011 VL 62 IS 10 BP 1167 EP 1179 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000010 PM 21969643 ER PT J AU Kim, HM Chiang, C Kales, HC AF Kim, Hyungjin Myra Chiang, Claire Kales, Helen C. TI After the Black Box Warning: Predictors of Psychotropic Treatment Choices for Older Patients With Dementia SO PSYCHIATRIC SERVICES LA English DT Article ID ATYPICAL ANTIPSYCHOTIC MEDICATIONS; PLACEBO-CONTROLLED TRIALS; RISK; DEATH; DEMOGRAPHICS; METAANALYSIS; PREVALENCE; PSYCHOSIS; AMERICANS; MORTALITY AB Objectives: This study aimed to evaluate factors associated with the selection of pharmacological treatments often given as first-line treatments to elderly patients with neuropsychiatric symptoms associated with dementia. It also evaluated patterns of medication usage over time in the year preceding and three years after the U. S. Food and Drug Administration issued a black box warning for antipsychotic usage. Methods: A retrospective cohort consisted of 19,517 Veterans Affairs patients with diagnosed dementia and a new outpatient start with an antipsychotic agent (haloperidol, olanzapine, quetiapine, or risperidone) or valproic acid and its derivatives between May 1, 2004, and September 30, 2008. Patient and facility characteristics were examined for their association with the new starts of these medications. Results: Trends in the rate of fills for psychotropic medications varied, with yearly increases in the use of quetiapine, haloperidol, and valproic acid and decreasing use of olanzapine and risperidone. Predictors of haloperidol use included a new start in nonpsychiatric settings, prior benzodiazepine use, and any prior-year hospitalization. Anxiety disorder and major depression were predictive of not receiving haloperidol. Parkinson's disease was predictive of quetiapine use, whereas bipolar disorder was predictive of valproic acid use. Older age was predictive of use of antipsychotics rather than valproic acid. Urban facilities were less likely to use olanzapine, and significant regional variations were seen. Conclusions: Important patient and facility characteristics were associated with initiating different psychotropic agents among elderly dementia patients. In addition, the rate of use and the factors predictive of use varied across the study years. (Psychiatric Services 62:1207-1214, 2011) C1 [Kim, Hyungjin Myra; Chiang, Claire; Kales, Helen C.] US Dept Vet Affairs, Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. [Chiang, Claire; Kales, Helen C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. RP Kim, HM (reprint author), US Dept Vet Affairs, Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. EM myrakim@umich.edu FU National Institute of Mental Health [R01-MH078698-01] FX This research was supported by grant R01-MH078698-01 from the National Institute of Mental Health. Resources were also contributed by the Serious Mental Illness Treatment, Resource, and Evaluation Center in Ann Arbor. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The funding organizations had no role in any of the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 21 TC 9 Z9 9 U1 2 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2011 VL 62 IS 10 BP 1207 EP 1214 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000015 PM 21969648 ER PT J AU Lichtenthal, WG Nilsson, M Kissane, DW Breitbart, W Kacel, E Jones, EC Prigerson, HG AF Lichtenthal, Wendy G. Nilsson, Matthew Kissane, David W. Breitbart, William Kacel, Elizabeth Jones, Eric C. Prigerson, Holly G. TI Underutilization of Mental Health Services Among Bereaved Caregivers With Prolonged Grief Disorder SO PSYCHIATRIC SERVICES LA English DT Article ID COMPLICATED GRIEF; CONTROLLED-TRIAL; SYMPTOMS; ADULTS; CARE AB Objective: This study examined grief and mental health service use among 86 bereaved caregivers of advanced cancer patients. Methods: Caregivers were assessed before (median=3.1 months) and after (median=6.6 months) patients' deaths for prolonged grief disorder, axis I psychiatric disorders, mental health service use, suicidality, and health-related quality of life. Results: Sixteen percent of the bereaved sample met criteria for prolonged grief disorder, which was significantly associated with suicidality and poorer health-related quality of life, but not with mental health service use. The majority of bereaved caregivers with prolonged grief disorder did not access men-tal health services. In multivariable analyses, having discussed psychological concerns with a health care professional when the patient was ill was the only significant predictor of mental health service use during bereavement. Conclusions: Because bereaved caregivers with prolonged grief disorder underutilize mental health services, connecting them with services while the patient is still alive may be beneficial. (Psychiatric Services 62:1225-1229, 2011) C1 [Lichtenthal, Wendy G.; Kissane, David W.; Breitbart, William] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Lichtenthal, Wendy G.] Evelyn H Lauder Breast Ctr, New York, NY 10065 USA. [Nilsson, Matthew; Kacel, Elizabeth; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Psychooncol & Palliat Care Res, Boston, MA USA. [Nilsson, Matthew; Kacel, Elizabeth; Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jones, Eric C.] Univ N Carolina, Dept Anthropol, Greensboro, NC 27412 USA. RP Lichtenthal, WG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA. EM lichtenw@mskcc.org OI Jones, Eric/0000-0002-0999-2726; Lichtenthal, Wendy/0000-0003-3597-7826 FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA139944, CA156732]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute, Boston FX This research was supported in part by National Institute of Mental Health grant MH63892; National Cancer Institute grants CA106370, CA139944, and CA156732; and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute, Boston. NR 15 TC 35 Z9 36 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD OCT PY 2011 VL 62 IS 10 BP 1225 EP 1229 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 827WT UT WOS:000295461000019 PM 21969652 ER PT J AU Merle, JV Haas, V Burghardt, R Dohler, N Schneider, N Lehmkuhl, U Ehrlich, S AF Merle, J. V. Haas, V. Burghardt, R. Doehler, N. Schneider, N. Lehmkuhl, U. Ehrlich, S. TI Agouti-related protein in patients with acute and weight-restored anorexia nervosa SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Agouti-related protein; anorexia nervosa; leptin; neuroendocrinology; undernutrition ID BODY-MASS-INDEX; EATING-DISORDERS; MELANOCORTIN RECEPTORS; FEMALE ADOLESCENTS; BULIMIA-NERVOSA; FOOD-INTAKE; OBESE MEN; IN-VIVO; LEPTIN; GENE AB Background. An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain. Method. Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain. Results. In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients. Conclusions. Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits. C1 [Ehrlich, S.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch,Dept Ps, Charlestown, MA 02129 USA. [Merle, J. V.; Haas, V.; Burghardt, R.; Doehler, N.; Schneider, N.; Lehmkuhl, U.; Ehrlich, S.] Charite, CVK, Dept Child & Adolescent Psychiat, D-13353 Berlin, Germany. [Haas, V.] Charite, ECRC, Franz Volhard Clin Res Ctr, D-13353 Berlin, Germany. [Ehrlich, S.] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, D-8027 Dresden, Germany. RP Ehrlich, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Psychiat Neuroimaging Res Program,Med Sch,Dept Ps, CNY Bldg 120,Suite 100, Charlestown, MA 02129 USA. EM stefan@nmr.mgh.harvard.edu OI Ehrlich, Stefan/0000-0003-2132-4445 FU German Research Foundation; Charite Research Fund FX We thank Andrea Oskamp for help with the recruitment of the participants, Dirk Megow, Josef Priller and Ulrich Dirnagel for permission to use their ELISA reader and Alexandra Cheetham for help with the manuscript preparation. S.E. was supported by a fellowship of the German Research Foundation. The research was also supported by the Charite Research Fund. NR 47 TC 11 Z9 11 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2011 VL 41 IS 10 BP 2183 EP 2192 DI 10.1017/S0033291711000365 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 826BR UT WOS:000295326900017 PM 21426605 ER PT J AU Kambadakone, A Thabet, A Gervais, DA Mueller, PR Arellano, RS AF Kambadakone, Avinash Thabet, Ashraf Gervais, Debra A. Mueller, Peter R. Arellano, Ronald S. TI CT-guided Celiac Plexus Neurolysis: A Review of Anatomy, Indications, Technique, and Tips for Successful Treatment SO RADIOGRAPHICS LA English DT Article ID UNRESECTABLE PANCREATIC-CANCER; COMPUTED-TOMOGRAPHY; ANTERIOR APPROACH; PAIN MANAGEMENT; GANGLION BLOCK; ULTRASOUND; ALCOHOL; COMPLICATIONS; DISTORTIONS; EFFICACY AB The celiac plexus is the largest visceral plexus and is located deep in the retroperitoneum, over the anterolateral surface of the aorta and around the origin of the celiac trunk. It serves as a relay center for nociceptive impulses that originate from the upper abdominal viscera, from the stomach to the proximal transverse colon. Celiac plexus neurolysis, with agents such as ethanol, is an effective means of diminishing pain that arises from these structures. Percutaneous imaging-guided celiac plexus neurolysis has been established as an invaluable therapeutic option in the management of intractable abdominal pain in patients with upper abdominal malignancy. The use of multidetector computed tomography (CT) for imaging guidance has superseded other modalities and allows direct visualization of the spread of the neurolytic agent in the antecrural space. Accurate depiction of the retroperitoneal anatomy and the position of the needle tip helps avoid crucial anatomic structures such as the pancreas, aorta, celiac artery, and superior mesenteric artery. Proper patient education, meticulous preprocedure planning, use of optimal multidetector CT techniques, adjunctive CT maneuvers, and postprocedure care are integral to successful celiac plexus neurolysis. Celiac plexus neurolysis does not completely abolish pain; rather, it diminishes pain, helping to reduce opioid requirements and their related side effects and improving survival in patients with upper abdominal malignancy. (C) RSNA, 2011 . radiographics.rsna.org C1 [Kambadakone, Avinash; Thabet, Ashraf; Gervais, Debra A.; Mueller, Peter R.; Arellano, Ronald S.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM rarellano@partners.org NR 62 TC 18 Z9 23 U1 0 U2 6 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 OCT PY 2011 VL 31 IS 6 SI SI BP 1599 EP 1621 DI 10.1148/rg.316115526 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 834SU UT WOS:000295985200010 PM 21997984 ER PT J AU Steensma, DP AF Steensma, David P. TI Hematopoietic Growth Factors in Myelodysplastic Syndromes SO SEMINARS IN ONCOLOGY LA English DT Review ID COLONY-STIMULATING FACTOR; RECOMBINANT-HUMAN-ERYTHROPOIETIN; QUALITY-OF-LIFE; ACUTE MYELOBLASTIC-LEUKEMIA; INTERNATIONAL WORKING GROUP; TUMOR-NECROSIS-FACTOR; INTERNET-BASED SURVEY; TRANS-RETINOIC ACID; DARBEPOETIN-ALPHA; LOW-RISK AB Hematopoietic growth factors (HGFs) continue to be the most widely prescribed class of medications for patients with myelodysplastic syndromes (MDS), despite the advent of disease-modifying therapies for MDS (eg, azacitidine, decitabine, and lenalidomide) and the current absence of an MDS-specific US Food and Drug Administration (FDA)-approved indication for any of the HGFs. Erythropoiesis-stimulating agents (ESAs: epoetin alfa, darbepoetin alfa), myeloid growth factors (MGFs: filgrastim, pegfilgrastim, sargramostim), and the newest group of HGFs, thrombopoiesis-stimulating agents (TSAs: romiplostim, eltrombopag), can increase peripheral blood counts in some patients, and may ameliorate some of the signs and symptoms of MDS-associated bone marrow failure. Although HGFs are generally considered "supportive care" measures, recent data suggest that HGFs may alter the natural history of disease in MDS, either for better or worse. This review examines data on the safety and effectiveness of HGFs for patients with MDS. Semin Oncol 38:635-647 (C) 2011 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies,Leukemia Grp, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies,Leukemia Grp, 44 Binney St,Suite D1B30,Mayer 1B21, Boston, MA 02115 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 NR 103 TC 16 Z9 17 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2011 VL 38 IS 5 BP 635 EP 647 DI 10.1053/j.seminoncol.2011.04.014 PG 13 WC Oncology SC Oncology GA 833BT UT WOS:000295857500006 PM 21943670 ER PT J AU Kaur, P Fishman, JA Misdraji, J Varma, MC Kotton, CN AF Kaur, P. Fishman, J. A. Misdraji, J. Varma, M. C. Kotton, C. N. TI Disseminated Mycobacterium kansasii infection with hepatic abscesses in a renal transplant recipient SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE Mycobacterium kansasii; hepatic abscesses; renal transplant ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC STEM-CELL; NONTUBERCULOUS MYCOBACTERIA; DISEASE; PULMONARY; TUBERCULOSIS; DIAGNOSIS; FEATURES; PATIENT AB Mycobacterium kansasii is the second most frequent cause of non-tuberculous mycobacterial disease in the United States after Mycobacterium avium complex. While primarily it is a pulmonary disease, extrapulmonary manifestations are common. This case report describes a recent renal transplant recipient with disseminated M. kansasii infection presenting with hepatic abscesses, with discussion of clinical management issues and strategies, and a review of the literature. C1 [Kaur, P.; Fishman, J. A.; Kotton, C. N.] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Immunocompromised Host Pr, Boston, MA 02114 USA. [Misdraji, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Varma, M. C.] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Varma, M. C.] Harvard Univ, Sch Med, Boston, MA USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Immunocompromised Host Pr, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM ckotton@partners.org NR 29 TC 4 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD OCT PY 2011 VL 13 IS 5 BP 531 EP 535 DI 10.1111/j.1399-3062.2011.00633.x PG 5 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 832VR UT WOS:000295837900016 PM 21466641 ER PT J AU Melendez, V Pybus, B Sousa, J Li, Q Caridha, D Collazo, V Olmeda, R Riscoe, M Kelly, J AF Melendez, V. Pybus, B. Sousa, J. Li, Q. Caridha, D. Collazo, V. Olmeda, R. Riscoe, M. Kelly, J. TI Metabolism and disposition of novel liver stage-active acridone antimalarial drugs SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Melendez, V.; Pybus, B.; Sousa, J.; Li, Q.; Caridha, D.; Collazo, V.; Olmeda, R.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Riscoe, M.; Kelly, J.] Portland VA Med Ctr, Portland, OR USA. [Riscoe, M.; Kelly, J.] Portland State Univ, Portland, OR 97207 USA. RI Sousa, Jason/A-9177-2011 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 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2011 VL 16 SU 1 SI SI BP 145 EP 146 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 828RC UT WOS:000295519100419 ER PT J AU Zavadzkas, JA Mukherjee, R Rivers, WT Patel, RK Meyer, EC Black, LE McKinney, RA Oelsen, JM Stroud, RE Spinale, FG AF Zavadzkas, Juozas A. Mukherjee, Rupak Rivers, William T. Patel, Risha K. Meyer, Evan C. Black, Laurel E. McKinney, Richard A. Oelsen, J. Marshall Stroud, Robert E. Spinale, Francis G. TI Direct regulation of membrane type 1 matrix metalloproteinase following myocardial infarction causes changes in survival, cardiac function, and remodeling SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial infarction; matrix; myocardial remodeling; ventricular function ID GROWTH-FACTOR-BETA; TGF-BETA; EXTRACELLULAR-MATRIX; RESTRICTED OVEREXPRESSION; BINDING-PROTEINS; ANGIOGENESIS; PROTEOLYSIS; INHIBITION; ACTIVATION; ISCHEMIA AB Zavadzkas JA, Mukherjee R, Rivers WT, Patel RK, Meyer EC, Black LE, McKinney RA, Oelsen JM, Stroud RE, Spinale FG. Direct regulation of membrane type 1 matrix metalloproteinase following myocardial infarction causes changes in survival, cardiac function, and remodeling. Am J Physiol Heart Circ Physiol 301: H1656-H1666, 2011. First published June 10, 2011; doi:10.1152/ajpheart.00141.2011.-The membrane type 1 matrix metalloproteinase (MT1-MMP) is increased in left ventricular (LV) failure. However, the direct effects of altered MT1-MMP levels on survival, LV function, and geometry following myocardial infarction (MI) and the proteolytic substrates involved in this process remain unclear. MI was induced in mice with cardiac-restricted overexpression of MT1-MMP (MT1-MMPexp; full length human), reduced MT1-MMP expression (heterozygous; MT1-MMP(+/-)), and wild type. Post-MI survival was reduced with MT1-MMPexp and increased with MT1-MMP(+/-) compared with WT. LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT post-MI and was higher in the MT1-MMP(+/-) mice. In vivo localization of MT1-MMP using antibody-conjugated microbubbles revealed higher MT1-MMP levels post-MI, which were the highest in the MT1-MMPexp group and the lowest in the MT1-MMP(+/-) group. LV collagen content within the MI region was higher in the MT1-MMPexp vs. WT post-MI and reduced in the MT1-MMP(+/-) group. Furthermore, it was demonstrated that MT1-MMP proteolytically processed the profibrotic molecule, latency-associated transforming growth factor-1-binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by over fourfold in the post-MI MT1-MMPexp group and reduced in the MT1-MMP(+/-) group, which was directionally paralleled by phospho-Smad-3 levels, a critical signaling component of the profibrotic transforming growth factor pathway. We conclude that modulating myocardial MT1-MMP levels affected LV function and matrix structure, and a contributory mechanism for these effects is through processing of profibrotic signaling molecules. These findings underscore the diversity of biological effects of certain MMP types on the LV remodeling process. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vets Affairs Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Rm 625,770 MUSC Complex,114 Doughty St, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NIH [HL-057952, HL-059165, HL-095608]; Veterans' Affairs Health Administration FX This study was supported by NIH Grants HL-057952, HL-059165, and HL-095608 and by a Merit Award from the Veterans' Affairs Health Administration. NR 29 TC 14 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2011 VL 301 IS 4 BP H1656 EP H1666 DI 10.1152/ajpheart.00141.2011 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 826NE UT WOS:000295360100048 PM 21666120 ER PT J AU Carney, JK Schilling, LM Frank, SH Biddinger, PD Bertsch, TF Grace, CJ Finkelstein, JA AF Carney, Jan K. Schilling, Lisa M. Frank, Scott H. Biddinger, Paul D. Bertsch, Tania F. Grace, Christopher J. Finkelstein, Jonathan A. TI Planning and Incorporating Public Health Preparedness Into the Medical Curriculum SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PANDEMIC INFLUENZA PREPAREDNESS; DISASTER MEDICINE; EMERGENCY READINESS; TABLETOP EXERCISES; POPULATION HEALTH; EDUCATION; BIOTERRORISM; COMPETENCE; WORKFORCE; STUDENTS AB As part of a 2010 conference entitled "Patients and Populations: Public Health in Medical Education," faculty from four U.S. medical schools (Case Western Reserve University, Harvard Medical School, the University of Colorado School of Medicine, and the University of Vermont College of Medicine), collaborated on a workshop to help other medical educators develop scenariobased learning experiences as practical, engaging, and effective mechanisms for teaching public health principles to medical school students. This paper describes and compares four different medical schools' experiences using a similar pandemic exercise scenario, discusses lessons learned, and suggests a curricular framework for medical schools adding such exercises to their population health curriculum. Different strategies to create realistic scenarios and engage students, including use of professionals and stakeholders from the community, are described. (Am J Prev Med 2011;41(4S3):S193-S199) (C) 2011 American Journal of Preventive Medicine C1 [Carney, Jan K.; Bertsch, Tania F.; Grace, Christopher J.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Schilling, Lisa M.] Univ Colorado, Sch Med, Aurora, CO USA. [Frank, Scott H.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Frank, Scott H.] Case Western Reserve Univ, Dept Family Med, Cleveland, OH 44106 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Finkelstein, Jonathan A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Finkelstein, Jonathan A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Finkelstein, Jonathan A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Carney, JK (reprint author), Univ Vermont, Coll Med, Dept Med, N217,89 Beaumont Ave, Burlington, VT 05405 USA. EM jan.carney@uvm.edu FU CDC-AAMC (Association of American Medical Colleges) [5U36CD319276] FX Publication of this article was supported by the CDC-AAMC (Association of American Medical Colleges) Cooperative Agreement number 5U36CD319276. NR 55 TC 3 Z9 3 U1 1 U2 8 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 OCT PY 2011 VL 41 IS 4 SU 3 BP S193 EP S199 DI 10.1016/j.amepre.2011.05.026 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 832SK UT WOS:000295827300011 PM 21961664 ER PT J AU Cronin, J Livhits, M Mercado, C Chen, F Foster, N Chandler, C Gibbons, M Ko, CY Chen, DC AF Cronin, Jennifer Livhits, Masha Mercado, Cheryl Chen, Formosa Foster, Nova Chandler, Charles Gibbons, Melinda Ko, Clifford Y. Chen, David C. TI Quality Improvement Pilot Program for Vulnerable Elderly Surgical Patients SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 22nd Annual Scientific Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 21-23, 2011 CL Santa Barbara, CA SP Amer Coll Surg ID OLDER-ADULTS; SURGERY; INDICATORS; CARE AB The elderly are a growing surgical population with more comorbidities and less physiological reserve compared with nonelderly patients. The objective of our study was to implement a quality improvement pilot program targeting the specific needs of the elderly. We prospectively enrolled consecutive patients aged 65 years or older undergoing inpatient general or vascular surgery operations. Patients completed a preoperative assessment including the Vulnerable Elder Survey (VES) to determine baseline functional status and incidence of polypharmacy (five or more medications). They were interviewed postdischarge Day 2 and Day 30 for changes in functional status. An intervention was implemented consisting of an elderly-specific postoperative order set and preoperative risk reports sent to the surgical team with instructions to order physical therapy consults and home health nursing on discharge for VES 3 or greater and geriatrics consults for patients with polypharmacy. The elderly-specific order set was used for 71 per cent of the postintervention group. There were no differences in the percentage of participants receiving physical therapy, geriatric, or home health nursing consults between the two groups. The postintervention group had significantly better functional status on postdischarge Day 30 (P < 0.01). Our preliminary data suggest that individualizing care for elderly patients is feasible and may improve postoperative outcomes. C1 [Chen, David C.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 72 215, Dept Surg, Los Angeles, CA 90095 USA. [Foster, Nova; Chandler, Charles; Chen, David C.] Univ Calif Los Angeles, Dept Surg, Santa Monica, CA USA. [Gibbons, Melinda] Olive View UCLA, Dept Surg, Sylmar, CA USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Chen, DC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 72 215, Dept Surg, Box 956904, Los Angeles, CA 90095 USA. EM DCChen@mednet.ucla.edu NR 10 TC 6 Z9 6 U1 1 U2 6 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2011 VL 77 IS 10 BP 1305 EP 1308 PG 4 WC Surgery SC Surgery GA 829ED UT WOS:000295558600006 PM 22127075 ER PT J AU Coopey, SB Buckley, JM Smith, BL Hughes, KS Gadd, MA Specht, MC AF Coopey, Suzanne B. Buckley, Julliette M. Smith, Barbara L. Hughes, Kevin S. Gadd, Michele A. Specht, Michelle C. TI Lumpectomy Cavity Shaved Margins Do Not Impact Re-excision Rates in Breast Cancer Patients SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID 20-YEAR FOLLOW-UP; CONSERVING SURGERY; SURGICAL MARGINS; SYSTEMIC THERAPY; CONSERVATION; MASTECTOMY; RECURRENCE; RADIATION; SPECIMEN; TIME AB Background. The benefits of taking shaved cavity margins (SCM) at the time of lumpectomy are unclear. We sought to determine if taking SCM decreases re-excision rates by increasing the total breast tissue volume excised. Methods. We undertook a retrospective review of breast cancer patients who underwent lumpectomy from 2004 to 2006. Patients were divided into three groups. Group 1 had lumpectomy alone, group 2 had lumpectomy plus select (1-3) SCM, and group 3 had lumpectomy plus complete (>= 4) SCM. Pathologic findings and surgical outcomes were compared between groups. Results. 773 cancers treated by lumpectomy were included in this study; 197 were in group 1, 130 were in group 2, and 446 were in group 3. The mean total volume of breast tissue excised in group 1 (106.6 cm(3)) was significantly larger than the volume excised in groups 2 (79.3 cm(3)) and 3 (76.3 cm(3)). Rates of re-excision and successful breast-conservation therapy (BCT) were not significantly different between groups. Despite a lower total volume of breast tissue excised in groups 2 and 3, there was no significant increase in locoregional recurrence rates (LRR) at median follow-up of 54 months. Conclusions. Taking additional SCM during lumpectomy resulted in a significantly lower overall volume of breast tissue excised, with no increase in LRR. Contrary to prior studies, we found that SCM did not decrease re-excision rates or impact the success of BCT. Therefore, the main advantage of taking SCM appears to be that less breast tissue is excised, which could potentially improve cosmetic outcomes. C1 [Coopey, Suzanne B.; Buckley, Julliette M.; Smith, Barbara L.; Hughes, Kevin S.; Gadd, Michele A.; Specht, Michelle C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Coopey, SB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM scoopey@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 22 TC 17 Z9 17 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2011 VL 18 IS 11 BP 3036 EP 3040 DI 10.1245/s10434-011-1909-7 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 832XO UT WOS:000295844200004 PM 21947583 ER PT J AU Walsh, JE Young, MRI AF Walsh, Jarrett E. Young, M. Rita I. TI TGF-beta Regulation of Focal Adhesion Proteins and Motility of Premalignant Oral Lesions via Protein Phosphatase 1 SO ANTICANCER RESEARCH LA English DT Article DE Cytoskeleton; paxillin; phosphatase; PP-1; TGF-beta ID CELL MOTILITY; CANCER-CELLS; PANCREATIC-CANCER; PHOSPHORYLATION; MIGRATION; PAXILLIN; INVASION; SUPPRESSION; COMPLEXES; LINK AB Premalignant oral lesions have a high incidence of recurrence and progression to malignant disease and, although studies have shown the contribution of transforming growth factor beta (TGF-beta) to cancer progression, none have been conducted with premalignant oral lesion cells to determine the impact of TGF-beta in stimulating properties that are characteristic of more invasive cells. The present study focused on TGF-beta-modulation of paxillin and the serine/threonine protein phosphatase PP-I, and the impact on cellular motility. These studies show that TGF-beta stimulates premalignant lesion cell motility and up regulates expression of paxillin, as well as its co-localization with PP-I, while concurrently diminishing the level of paxillin serine phosphorylation. The TGF-beta-mediated up regulation of paxillin and co-localization with actin, as well as the TGF-beta-stimulated motility of premalignant lesion cells, were all blocked by inhibiting PP-I, indicating their dependence on PP-1 activity. These studies suggest interplay between TGF-beta and PP-1 in promoting a more malignant phenotype in premalignant oral lesion cells. C1 [Walsh, Jarrett E.; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Walsh, Jarrett E.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Walsh, JE (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Clinical Science and Biomedical Laboratory Research and Development Services of the Department of Veterans Affairs; National Institutes of Health [R01 DE018168, R01CA128837] FX This study is part of the doctoral dissertation of Jarrett Walsh. This study was supported by the Clinical Science and Biomedical Laboratory Research and Development Services of the Department of Veterans Affairs and by grants R01 DE018168 and R01CA128837 from the National Institutes of Health to MRIY. NR 22 TC 2 Z9 2 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD OCT PY 2011 VL 31 IS 10 BP 3159 EP 3164 PG 6 WC Oncology SC Oncology GA 830PA UT WOS:000295667700007 PM 21965722 ER PT J AU Shepardson, NE Shankar, GM Selkoe, DJ AF Shepardson, Nina E. Shankar, Ganesh M. Selkoe, Dennis J. TI Cholesterol Level and Statin Use in Alzheimer Disease I. Review of Epidemiological and Preclinical Studies SO ARCHIVES OF NEUROLOGY LA English DT Review ID AMYLOID PRECURSOR PROTEIN; MILD COGNITIVE IMPAIRMENT; E EPSILON-4 ALLELE; LATE-LIFE; RISK-FACTORS; PLASMA-LIPIDS; IN-VITRO; BETA; HYPERCHOLESTEROLEMIA; DEMENTIA C1 [Selkoe, Dennis J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol,Harvard Inst Med, Boston, MA 02115 USA. [Shankar, Ganesh M.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. RP Selkoe, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol,Harvard Inst Med, Room 730,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dselkoe@rics.bwh.harvard.edu FU National Institutes of Health [AG06173] FX This study was supported by grant AG06173 from the National Institutes of Health (Dr Selkoe). NR 35 TC 81 Z9 83 U1 1 U2 11 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 OCT PY 2011 VL 68 IS 10 BP 1239 EP 1244 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 830YV UT WOS:000295696700002 PM 21987540 ER PT J AU Lo, RY Hubbard, AE Shaw, LM Trojanowski, JQ Petersen, RC Aisen, PS Weiner, MW Jagust, WJ AF Lo, Raymond Y. Hubbard, Alan E. Shaw, Leslie M. Trojanowski, John Q. Petersen, Ronald C. Aisen, Paul S. Weiner, Michael W. Jagust, William J. CA Alzheimer's Dis Neuroimaging TI Longitudinal Change of Biomarkers in Cognitive Decline SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NEUROIMAGING INITIATIVE ADNI; VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; CSF BIOMARKERS; APOLIPOPROTEIN-E; FOLLOW-UP; HIPPOCAMPAL VOLUME; METABOLIC-CHANGES AB Objective: To delineate the trajectories of A beta 42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design: Cohort study. Setting: The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. Participants: A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures: Rates of change in level of A beta 42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results: Reductions in the level of A beta 42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of A beta 42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of A beta 42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion: Trajectories of A beta 42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. C1 [Lo, Raymond Y.; Hubbard, Alan E.; Jagust, William J.] Univ Calif Berkeley, Div Epidemiol, Berkeley, CA 94720 USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, 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.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Shaw, Leslie M.; Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. RP Lo, RY (reprint author), Univ Calif Berkeley, Div Epidemiol, 118 Barker Hall,MC3190, Berkeley, CA 94720 USA. EM rlo@berkeley.edu RI Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007 OI Preda, Adrian /0000-0003-3373-2438; Saykin, Andrew/0000-0002-1376-8532 FU Pfizer; National Institutes of Health (NIH) [AG024904, U01AG024904, P41 RR023953, R01 AG10897, P01AG19724, P50AG23501, R24 RR021992, R01 NS031966, P01AG012435, AG027859, AG027984, AG 024904, P30 AG010129, K01 AG030514]; National Institute of Neurological Disorders and Stroke [P01 AG 09215-20, P30 AG 10124-18, PO1 AG 17586-10, 1PO1 AG-19724-07, U01 AG 024904-05, P50 NS053488-02, UO1 AG029213-01, RC2NS069368, RC1AG035427, P30AG036468]; Marian S. Ware Alzheimer Program; NIH National Institute on Aging (NIA) [U01 AG 06786, P50 AG 16574, U01 AG 024904, R01 AG11378, U01-AG10483, U01-AG024904, R01-AG030048, R01-AG16381]; Baxter; Neuro-Hitech; Abbott; Martek; Nestle; Kenes International; Merck; Radiopharmaceuticals; US Department of Defense [DAMD17-01-1-0764]; Veterans Administration [MIRECC VISN 21]; State of California; Alzheimer's Association; ADNI NIH [U01 AG024904]; NIA; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation FX Dr Shaw has received funding for travel and speaker honoraria from Pfizer; serves on the editorial board of the journal Therapeutic Drug Monitoring; may potentially receive revenue for patent pending (application number 10/192,193): O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders, licensed by the University of Pennsylvania to Novartis; receives royalties from publication of Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring (Wolters Kluwer/Lippincott Williams & Wilkins, 2005); receives research support from the National Institutes of Health (NIH) (grantAG024904[coprincipal investigator {co-PI}, Biomarker Core Laboratory]); and receives board of directors' compensation and holds stock options in Saladax Biomedical. Dr Trojanowski has received funding for travel and honoraria from Takeda to attend numerous conferences not funded by industry; serves as an associate editor of the journal Alzheimer's & Dementia; may accrue revenue on patents regarding Modified Avidin-Biotin Technique, Method of Stabilizing Microtubules to Treat Alzheimer's Disease, Method of Detecting Abnormally Phosphorylated Tau, Method of Screening for Alzheimer's Disease or Disease Associated with the Accumulation of Paired Helical Filaments, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants, Rat Comprising Straight Filaments in Its Brain, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants to Treat Neurodegenerative Disorders and Brain and Spinal Cord Injuries, Diagnostic Methods for Alzheimer's Disease by Detection of Multiple MRNAs, Methods and Compositions for Determining Lipid Peroxidation Levels in Oxidant Stress Syndromes and Diseases, Compositions and Methods for Producing and Using Homogenous Neuronal Cell Transplants, Method of Identifying, Diagnosing and Treating alpha-synuclein Positive Neurodegenerative Disorders, Mutation-specific Functional Impairments in Distinct Tau Isoforms of Hereditary Frontotemporal Dementia and Parkinsonism Linked to Chromosome-17: Genotype Predicts Phenotype, Microtubule Stabilizing Therapies for Neurodegenerative Disorders, and Treatment of Alzheimer's and Related Diseases with an Antibody; and receives research support from the NIH National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke (grants P01 AG 09215-20 [PI], P30 AG 10124-18 [PI], PO1 AG 17586-10 [project 4 leader], 1PO1 AG-19724-07 [core C leader], U01 AG 024904-05 [coPI, Biomarker Core Laboratory], P50 NS053488-02 [PI], UO1 AG029213-01 [coinvestigator], RC2NS069368 [PI], RC1AG035427 [PI], and P30AG036468 [PI]) and from the Marian S. Ware Alzheimer Program. Dr Petersen serves on scientific advisory boards for Pfizer, Janssen Alzheimer Immunotherapy, Elan, and GE Healthcare; receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH/NIA (grants U01 AG 06786 [PI], P50 AG 16574 [PI], U01 AG 024904 [subcontract PI], and R01 AG11378 [coinvestigator]).; Dr Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan, Wyeth, Eisai, Neurochem, Schering-Plough, Bristol-Myers Squibb, Eli Lilly, NeuroPhage, Merck, Roche, Amgen, Genentech, Abbott, Pfizer, Novartis, and Medivation; receives research support from Pfizer, Baxter, Neuro-Hitech, Abbott, Martek, and the NIH/NIA (grants U01-AG10483 [PI], U01-AG024904 [coordinating center director], R01-AG030048 [PI], and R01-AG1381 [coinvestigator]); and has received stock options from Medivation and NeuroPhage. Dr Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly, CoMentis, Neurochem, Eisai, Avid, Aegis Therapies, Genentech, Allergan, Lippincott Williams&Wilkins, Bristol-Myers Squibb, Forest Laboratories, Pfizer, McKinsey & Company, Mitsubishi Tanabe Pharma Corporation, and Novartis; has received funding for travel from Nestle and Kenes International to attend conferences not funded by industry; serves on the editorial board of the journal Alzheimer's & Dementia; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan; receives research support from Merck, Radiopharmaceuticals, the NIH (grants U01AG024904 [PI], P41 RR023953 [PI], R01 AG10897 [PI], P01AG19724 [coinvestigator], P50AG23501 [coinvestigator], R24 RR021992 [coinvestigator], R01 NS031966 [coinvestigator], and P01AG012435 [coinvestigator]), the US Department of Defense (DAMD17-01-1-0764 [PI]), the Veterans Administration (MIRECC VISN 21 [core PI]), and the State of California; and holds stock in Synarc and Elan. Dr Jagust has served on a scientific advisory board for Genentech; has served as a consultant for Bayer Healthcare, GE Healthcare, Synarc, Janssen Alzheimer Immunotherapy, Genentech, TauRx, and Merck; and receives research support from the NIH (grants AG027859 [PI], AG027984 [PI], and AG 024904 [coinvestigator]) and the Alzheimer's Association.; Data collection and sharing for this project was funded by ADNI (NIH grant U01 AG024904), which is funded by the NIA and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca, Bayer Schering Pharma, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly, Medpace, Merck, Novartis, Pfizer, F. Hoffman-La Roche, Schering-Plough, Synarc, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (http: //www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and our study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 and the Dana Foundation. NR 40 TC 77 Z9 78 U1 3 U2 13 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 OCT PY 2011 VL 68 IS 10 BP 1257 EP 1266 DI 10.1001/archneurol.2011.123 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 830YV UT WOS:000295696700006 PM 21670386 ER PT J AU Blanquer, J Aspa, J Anzueto, A Ferrer, M Gallego, M Rajas, O Rello, J de Castro, FR Torres, A AF Blanquer, Jose Aspa, Javier Anzueto, Antonio Ferrer, Miguel Gallego, Miguel Rajas, Olga Rello, Jordi Rodriguez de Castro, Felipe Torres, Antonio TI SEPAR Guidelines for Nosocomial Pneumonia SO ARCHIVOS DE BRONCONEUMOLOGIA LA Spanish DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; HOSPITAL-ACQUIRED PNEUMONIA; INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; REQUIRING MECHANICAL VENTILATION; BRONCHOALVEOLAR LAVAGE FLUID; ANTIBIOTIC-THERAPY; CIRCUIT CHANGES; CRITICALLY-ILL C1 [Blanquer, Jose] Hosp Clin Univ, Unidad Cuidados Intensivos Resp, Valencia, Spain. [Aspa, Javier; Rajas, Olga] Univ Autonoma Madrid, Hosp Univ La Princesa, Madrid, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Ferrer, Miguel; Torres, Antonio] Hosp Clin Barcelona, Unidad Vigilancia Intensiva & Intermedia Resp, Serv Neumol, Inst Torax,IDIBAPS, Barcelona, Spain. [Gallego, Miguel] Corp Sanitaria Parc Tauli, Barcelona, Spain. [Rello, Jordi] VHIR Univ Autonoma Barcelona, UCI, Hosp Univ Vall dHebron, CibeRes, Barcelona, Spain. [Rodriguez de Castro, Felipe] Hosp Univ Gran Canaria Dr Negrin, Las Palmas Gran Canaria, Spain. RP Blanquer, J (reprint author), Hosp Clin Univ, Unidad Cuidados Intensivos Resp, Valencia, Spain. EM blanquer_jos@gva.es OI Rello, Jordi/0000-0003-0676-6210 NR 80 TC 4 Z9 5 U1 1 U2 2 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0300-2896 EI 1579-2129 J9 ARCH BRONCONEUMOL JI Arch. Bronconeumol. PD OCT PY 2011 VL 47 IS 10 BP 510 EP 520 DI 10.1016/j.arbres.2011.05.013 PG 11 WC Respiratory System SC Respiratory System GA 830OW UT WOS:000295667300006 PM 21908091 ER PT J AU Mathalon, DH AF Mathalon, Daniel H. TI Challenges Associated with Application of Clinical Staging Models to Psychotic Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID RESONANCE-IMAGING MORPHOMETRY; BRAIN; NEUROPLASTICITY; NEUROTOXICITY; SAFER C1 [Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv, 116D,4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Mathalon, Daniel/0000-0001-6090-4974 FU NIMH NIH HHS [U01 MH082022, R01 MH076989] NR 11 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2011 VL 70 IS 7 BP 600 EP 601 DI 10.1016/j.biopsych.2011.08.007 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 829PI UT WOS:000295595800001 PM 21924130 ER PT J AU Kelly, SK Shire, DB Chen, JH Doyle, P Gingerich, MD Cogan, SF Drohan, WA Theogarajan, LS Wyatt, JL Rizzo, JF AF Kelly, Shawn K. Shire, Douglas B. Chen, Jinghua Doyle, Patrick Gingerich, Marcus D. Cogan, Stuart F. Drohan, William A. Theogarajan, Luke S. Wyatt, John L. Rizzo, Joseph F. TI Communication and control system for a 15-channel hermetic retinal prosthesis SO BIOMEDICAL SIGNAL PROCESSING AND CONTROL LA English DT Article DE Retinal prosthesis; Retinal implant; Biomedical electrodes; Neuromuscular stimulation; Iridium oxide; Integrated circuit design; Telemetry; Medical devices ID ELECTRICAL-STIMULATION; IMPLANTATION; NEUROSTIMULATOR; DEGENERATION; RESPONSES AB A small, hermetic, wirelessly-controlled retinal prosthesis has been developed for pre-clinical studies in Yucatan minipigs. The device was attached conformally to the outside of the eye in the socket and received both power and data wirelessly from external sources. Based on the received image data, the prosthesis drove a subretinal thin-film polyimide array of sputtered iridium oxide stimulating electrodes. The implanted device included a hermetic titanium case containing a 15-channel stimulator and receiver chip and discrete circuit components. Feed throughs in the hermetic case connected the chip to secondary power- and data-receiving coils, which coupled to corresponding external power and data coils driven by power amplifiers. Power was delivered by a 125 kHz carrier, and data were delivered by amplitude shift keying of a 15.5 MHz carrier at 100 kbps. Stimulation pulse strength, duration and frequency were programmed wirelessly from an external computer system. The final assembly was tested in vitro in physiological saline and in vivo in two minipigs for up to five and a half months by measuring stimulus artifacts generated by the implant's current drivers. Published by Elsevier Ltd. C1 [Kelly, Shawn K.; Shire, Douglas B.; Doyle, Patrick; Gingerich, Marcus D.; Drohan, William A.; Rizzo, Joseph F.] Boston VA Healthcare Syst, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. [Kelly, Shawn K.; Doyle, Patrick; Drohan, William A.; Wyatt, John L.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Shire, Douglas B.; Gingerich, Marcus D.] Cornell Univ, Ithaca, NY 14853 USA. [Chen, Jinghua; Rizzo, Joseph F.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Cogan, Stuart F.] EIC Labs, Norwood, MA 02062 USA. [Theogarajan, Luke S.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. RP Kelly, SK (reprint author), 50 Vassar St,Room 36-576, Cambridge, MA 02139 USA. EM skkelly@mit.edu OI Kelly, Shawn/0000-0003-3533-5268 FU NEI NIH HHS [R01 EY016674-04A1, R01 EY016674] NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1746-8094 J9 BIOMED SIGNAL PROCES JI Biomed. Signal Process. Control PD OCT PY 2011 VL 6 IS 4 BP 356 EP 363 DI 10.1016/j.bspc.2011.05.007 PG 8 WC Engineering, Biomedical; Medical Laboratory Technology SC Engineering; Medical Laboratory Technology GA 828IS UT WOS:000295495300003 PM 21927618 ER PT J AU Wiren, KM Hashimoto, JG Semirale, AA Zhang, XW AF Wiren, Kristine M. Hashimoto, Joel G. Semirale, Anthony A. Zhang, Xiao-Wei TI Bone vs. fat: Embryonic origin of progenitors determines response to androgen in adipocytes and osteoblasts SO BONE LA English DT Article DE Androgen; Periosteum; Neural crest; Testosterone; Mesenchymal stem cell ID PARIETAL CALVARIAL BONES; SEX STEROIDS; STEM-CELLS; TESTOSTERONE LEVELS; NEURAL CREST; BODY-COMPOSITION; HYPOGONADAL MEN; CERVUS-ELAPHUS; YOUNG MEN; PERIOSTEUM AB Although androgen is considered an anabolic hormone, the consequences of androgen receptor (AR) overexpression in skeletally-targeted AR-transgenic lines highlight the detrimental effect of enhanced androgen sensitivity on cortical bone quality. A compartment-specific anabolic response is observed only in male and not in female AR3.6-transgenic (tg) mice, with increased periosteal bone formation and calvarial thickening. To identify anabolic signaling cascades that have the potential to increase bone formation, qPCR array analysis was employed to define expression differences between AR3.6-tg and wild-type (WT) periosteal tissue. Notably, categories that were significantly different between the two genotypes included axonal guidance, CNS development and negative regulation of Wnt signaling with a node centered on stem cell pathways. Further, fine mapping of AR3.6-tg calvaria revealed that anabolic thickening in vivo is not uniform across the calvaria, occurring only in frontal and in not parietal bones. Multipotent fraction 1 progenitor populations from both genotypes were cultured separately as frontal bone neural crest stem-like cells (fNCSC) and parietal bone mesenchymal stem-like cells (pMSC). Both osteoblastic and adipogenic differentiation in these progenitor populations was influenced by embryonic lineage and by genotype. Adipogenesis was enhanced in WT fNCSC compared to pMSC, but transgenic cultures showed strong suppression of lipid accumulation only in fNCSC cells. Osteoblastogenesis was significantly increased in transgenic fNCSC cultures compared to WT, with elevated alkaline phosphatase (ALP) activity and induction of mineralization and nodule formation assessed by alizarin red and von Kossa staining. Osteocalcin (OC) and ALP mRNA levels were also increased in fNCSC cultures from AR3.6-tg vs. WT, but in pMSC cultures ALP mRNA levels, mineralization and nodule formation were decreased in AR3.6-tg cells. Expression differences identified by array in long bone periosteal tissue from AR3.6-tg vs. WT were recapitulated in the fNCSC samples while pMSC profiles reflected cortical expression. These observations reveal the opposing effects of androgen signaling on lineage commitment and osteoblast differentiation that is enhanced in cells derived from a neural crest origin but inhibited in cells derived from a mesodermal origin, consistent with in vivo compartment-specific responses to androgen. Combined, these results highlight the complex action of androgen in the body that is dependent on the embryonic lineage and developmental origin of the cell. Further, these data these data suggest that the periosteum surrounding long bone is derived from neural crest. Published by Elsevier Inc. C1 [Wiren, Kristine M.; Hashimoto, Joel G.; Semirale, Anthony A.; Zhang, Xiao-Wei] Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Wiren, Kristine M.; Hashimoto, Joel G.; Semirale, Anthony A.; Zhang, Xiao-Wei] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Wiren, KM (reprint author), Portland VA Med Ctr P3 R&D39, 3710 SW Vet Hosp Rd, Portland, OR 97239 USA. EM wirenk@ohsu.edu OI Wiren, Kristine/0000-0002-6159-4450 FU United States Army Research Acquisition Activity Award [W81XWH-05-1-0086]; National Institute of Diabetes, Digestive Kidney Disease [R01 DK067541]; Veterans Affairs Merit Review Program FX This publication was made possible by grants from the United States Army Research Acquisition Activity Award No. W81XWH-05-1-0086 (KMW) and the National Institute of Diabetes, Digestive & Kidney Disease R01 DK067541 (KMW). KMW is a Research Career Scientist of the Department of Veterans Affairs and received support from the Veterans Affairs Merit Review Program. All work was performed in facilities provided by the Department of Veterans Affairs. The study sponsor(s) did not play a 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. The information contained in this publication does not necessarily reflect the position or the policy of the government, and no official endorsement should be inferred. NR 54 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2011 VL 49 IS 4 BP 662 EP 672 DI 10.1016/j.bone.2011.06.010 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZH UT WOS:000295240200009 PM 21704206 ER PT J AU Nimptsch, K Giovannucci, E Willett, WC Fuchs, CS Wei, EK Wu, KN AF Nimptsch, Katharina Giovannucci, Edward Willett, Walter C. Fuchs, Charles S. Wei, Esther K. Wu, Kana TI Body Fatness during Childhood and Adolescence, Adult Height, and Risk of Colorectal Adenoma in Women SO CANCER PREVENTION RESEARCH LA English DT Article ID GROWTH-FACTOR-I; MASS INDEX; CANCER-RISK; FOLLOW-UP; CARCINOMA SEQUENCE; PROSPECTIVE COHORT; PHYSICAL-ACTIVITY; YOUNG ADULTHOOD; ENERGY-BALANCE; RECTAL-CANCER AB The latest report by the World Cancer Research Fund/American Institute of Cancer Research concluded that there is convincing evidence that adult height and obesity are risk factors for colorectal cancer. However, studies relating body fatness during early life to the risk of colorectal cancer or adenoma are scarce. In the Nurses' Health Study II, participants recalled adult attained height and body shape at ages 5, 10, and 20 years (using a 9-level pictogram: 1 = most lean body shape, 9 = most overweight body shape) at baseline. Among 32,707 women who had at least one lower bowel endoscopy between 1991 and 2005, 2,327 colorectal adenomas were documented. Adult height was positively associated with risk of colorectal adenoma (multivariate OR per 2 inch increment 1.05, 95% CI: 1.01-1.09). Comparing women who were overweight (body shape level 6 or higher) to women who were most lean (body shape level 1), ORs (95% CI, P-trend) of colorectal adenoma for body shapes at ages 5, 10, and 20 years were 1.44 (1.04-1.99, 0.01), 1.21 (0.93-1.56, 0.05), and 1.03 (0.74-1.42, 0.58), respectively. Adjustment for adult body mass index did not change results substantially. The positive associations for body fatness at ages 5 and 10 years as well as adult height were restricted to distal adenoma, while not seen for proximal or rectal adenoma. Higher height and body fatness during childhood was associated with increased risk of distal adenoma later in life, independent of adult body weight. Cancer Prev Res; 4(10); 1710-8. (C)2011 AACR. C1 [Nimptsch, Katharina; Giovannucci, Edward; Willett, Walter C.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Willett, Walter C.; Fuchs, Charles S.; Wei, Esther K.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward; Willett, Walter C.; Fuchs, Charles S.; Wei, Esther K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Nimptsch, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,Room 304, Boston, MA 02115 USA. EM knimptsc@hsph.harvard.edu OI Nimptsch, Katharina/0000-0001-7877-205X FU American Institute for Cancer Research; National Cancer Institute [R01 CA50385]; Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (NCCRA); German Academic Exchange Service (DAAD) FX The work was supported by the American Institute for Cancer Research [Investigator initiated grant to K. Wu], National Cancer Institute (R01 CA50385 to W.C. Willett), and the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance (NCCRA to W.C. Willett). K. Nimptsch is the recipient of a scholarship within the Postdoc-Program of the German Academic Exchange Service (DAAD). NR 45 TC 13 Z9 14 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2011 VL 4 IS 10 BP 1710 EP 1718 DI 10.1158/1940-6207.CAPR-11-0272 PG 9 WC Oncology SC Oncology GA 829XP UT WOS:000295620000023 PM 21881026 ER PT J AU Theze, J Chakrabarti, LA Vingert, B Porichis, F Kaufmann, DE AF Theze, Jacques Chakrabarti, Lisa A. Vingert, Benoit Porichis, Filippos Kaufmann, Daniel E. TI HIV controllers: A multifactorial phenotype of spontaneous viral suppression SO CLINICAL IMMUNOLOGY LA English DT Review DE HIV; CD4 T cell; Pathogenesis; Controllers; Long-term non progressors; Protective immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; NATURAL-KILLER-CELLS; HIV-1-INFECTED ELITE CONTROLLERS; ACTIVE ANTIRETROVIRAL THERAPY; LONG-TERM NONPROGRESSORS; LOW-LEVEL VIREMIA; REPLICATION CAPACITY; DISEASE PROGRESSION; SIV INFECTION AB A small minority of HIV-infected individuals, known as HIV controllers, is able to exert long-term control over HIV replication in the absence of treatment. Increasing evidence suggests that the adaptive immune system plays a critical role in this control but also that a combination of several host and/or viral factors, rather than a single cause, leads to this rare phenotype. Here, we review recent advances in the study of these remarkable individuals. We summarize the epidemiology and clinical characteristics of HIV controllers, and subsequently describe contributing roles of host genetic factors, innate and adaptive immune responses, and viral factors to this phenotype. We emphasize distinctive characteristics of HIV-specific CD4 T cell responses and of CD4 T cell subpopulations that are frequently found in HIV controllers. We discuss major controversies in the field and the relevance of the study of HIV controllers for the development of novel therapeutic strategies and vaccines. (C) 2011 Elsevier Inc. All rights reserved. C1 [Theze, Jacques; Chakrabarti, Lisa A.; Vingert, Benoit] Inst Pasteur, Unite Immunogenet Cellulaire, F-75015 Paris, France. [Theze, Jacques] Inst Pasteur, Ctr Med Necker Pasteur, F-75015 Paris, France. [Porichis, Filippos; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Rayon Inst MGH & Harvard, Boston, MA 02114 USA. [Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kaufmann, Daniel E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Theze, J (reprint author), Inst Pasteur, Unite Immunogenet Cellulaire, 25-28 Rue Docteur Roux, F-75015 Paris, France. EM jtheze@pasteur.fr; dkaufmann@partners.org OI Chakrabarti, Lisa/0000-0002-1895-3630 FU Institut Pasteur; Agence Nationale de Recherche sur le Sida et les Hepatites (ANRS); NIH [RO1 HL 092565, P01AI-080192] FX J.T. and L. C. are supported by grants from Institut Pasteur and Agence Nationale de Recherche sur le Sida et les Hepatites (ANRS). All patients studied at Institut Pasteur are from ANRS Cohort 018 (Prof. Olivier Lambotte). D.E.K. is supported by grants from NIH (RO1 HL 092565 and P01AI-080192). NR 133 TC 20 Z9 21 U1 3 U2 13 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 OCT PY 2011 VL 141 IS 1 BP 15 EP 30 DI 10.1016/j.clim.2011.07.007 PG 16 WC Immunology SC Immunology GA 829EC UT WOS:000295558500003 PM 21865089 ER PT J AU Eisner, A Luoh, SW AF Eisner, Alvin Luoh, Shiuh-Wen TI Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease SO CURRENT EYE RESEARCH LA English DT Review DE Aromatase inhibitor; Dry eye; Estrogen; Retina; Short-wavelength-sensitive cones; Tamoxifen ID ADJUVANT ENDOCRINE THERAPY; ESTROGEN-RECEPTOR MODULATORS; OPEN-ANGLE GLAUCOMA; WAVELENGTH AUTOMATED PERIMETRY; POSTERIOR VITREOUS DETACHMENT; HORMONE REPLACEMENT THERAPY; LATERAL GENICULATE-NUCLEUS; IDIOPATHIC MACULAR HOLES; DUCT STENOSIS SECONDARY; RETINAL BLOOD-FLOW AB This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than similar to 50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response-sluggishness that becomes evident at similar to 2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis occasionally. We conclude by suggesting some avenues for future research into the visual and ocular effects of AIs, particularly as relates to assessment of cognitive function. C1 [Eisner, Alvin] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Womens Hlth Res Unit, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR USA. RP Eisner, A (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Womens Hlth Res Unit, Mail Code UHN70, Portland, OR 97239 USA. EM aeisnerphd@gmail.com FU NIH [EY014594] FX Portions of this work were supported by NIH grant EY014594 (to A. Eisner). We would like to thank Alison Conlin, MD, MPH, and David Sullivan, PhD, for critiquing the manuscript; and Linda Simmons, MLS, for help locating references. NR 302 TC 20 Z9 22 U1 1 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 2011 VL 36 IS 10 BP 867 EP 885 DI 10.3109/02713683.2011.594202 PG 19 WC Ophthalmology SC Ophthalmology GA 825MX UT WOS:000295283300001 PM 21819259 ER PT J AU Trzepacz, PT Spencer, TJ Zhang, SY Bangs, ME Witte, MM Desaiah, D AF Trzepacz, Paula T. Spencer, Thomas J. Zhang, Shuyu Bangs, Mark E. Witte, Michael M. Desaiah, Durisala TI Effect of atomoxetine on Tanner stage sexual development in children and adolescents with attention deficit/hyperactivity disorder: 18-month results from a double-blind, placebo-controlled trial SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE ADHD; Atomoxetine; Children and adolescents; Sexual development; Tanner stage ID DEFICIT HYPERACTIVITY DISORDER; PUBERTAL DEVELOPMENT; RACIAL-DIFFERENCES; PEDIATRIC-PATIENTS; STIMULANT DRUGS; GROWTH DEFICITS; MATURATION; HEALTH AB To determine the effects of long-term atomoxetine treatment on sexual development in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) as compared with placebo and with a national US survey in non-Hispanic white children and adolescents. This double-blind, placebo-controlled, relapse prevention, multicenter trial was conducted in pediatric patients (6-15 years) with DSM-IV diagnosed ADHD and lasting for similar to 18 months. All patients received 10 weeks of open-label atomoxetine treatment (0.5-1.8 mg/kg/day). Patients responding in the last 2 weeks of treatment were randomized to double-blind treatment with either placebo or atomoxetine for up to 9 months, after which atomoxetine patients were re-randomized to either continued atomoxetine treatment or to placebo for up to another 6 months. Patients randomized to placebo at first randomization remained on placebo. The Tanner stage was assessed by the investigator at baseline and at approximately 6, 12, and 18 months, and the rate of sexual development (change in the Tanner stage) was compared between treatment groups. No statistically significant differences were observed between treatment groups either in sexual development (mean time, in days, to the first Tanner stage change: atomoxetine, 464.3 +/- 23.0; placebo, 433.1 +/- 14.4; p == 0.33) or in the duration of treatment exposure (atomoxetine, 315.3 days; placebo, 315.1 days; p == 0.90). Similar proportions of patients had at least one Tanner stage increase (atomoxetine: 27.1%%; placebo: 31.9%%; p == 0.39). Proportions of patients in each baseline Tanner stage group moving to higher stages were not statistically significantly different (p == 0.88, p == 0.18, p > 0.99, p == 0.68 for baseline Tanner stages 1-4, respectively). The puberty onset age was similar across treatment groups and consistent with US normative data. Long-term atomoxetine treatment was not associated with any appreciable impact on or delay in sexual maturation in children with ADHD compared with US normative data. Study limitations include the relatively short duration of exposure to atomoxetine treatment, and the fact that half of the patients had been previously treated with stimulants. In addition, the Tanner stage data were collected as a secondary measure. Trial was completed prior to the requirement to post trials at initiation and therefore does not have a registration number. C1 [Trzepacz, Paula T.] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Spencer, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Trzepacz, PT (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM trzepacz_paula_t@lilly.com FU Eli Lilly and Company, Indianapolis, IN, USA FX This research was sponsored by Eli Lilly and Company, Indianapolis, IN, USA. This article was prepared by writing support from the sponsor. Drs Witte and Desaiah are medical writers and employees of Eli Lilly and Company. NR 27 TC 2 Z9 2 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD OCT PY 2011 VL 27 SU 2 SI SI BP 45 EP 52 DI 10.1185/03007995.2011.599372 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 829WL UT WOS:000295616100006 PM 21973230 ER PT J AU Wallace, M Lauwers, GY Chen, Y Dekker, E Fockens, P Sharma, P Meining, A AF Wallace, M. Lauwers, G. Y. Chen, Y. Dekker, E. Fockens, P. Sharma, P. Meining, A. TI Miami classification for probe-based confocal laser endomicroscopy SO ENDOSCOPY LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; CANCER IN-VIVO; ULCERATIVE-COLITIS; BARRETTS-ESOPHAGUS; NARROW-BAND; CELIAC-DISEASE; INTRAEPITHELIAL NEOPLASIA; CONVENTIONAL COLONOSCOPY; COLONIC-MUCOSA; BRUSH CYTOLOGY AB An essential element for any new advanced imaging technology is standardization of indications, terminology, categorization of images, and research priorities. In this review, we propose a state-of-the-art classification system for normal and pathological states in gastrointestinal disease using probe-based confocal laser endomicroscopy (pCLE). The Miami classification system is based on a consensus of pCLE users reached during a meeting held in Miami, Florida, in February 2009. C1 [Wallace, M.] Mayo Clin, Dept Gastroenterol, Jacksonville, FL 32224 USA. [Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Div Surg Pathol, Boston, MA 02114 USA. [Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Lauwers, G. Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y.] Univ Colorado, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. [Dekker, E.; Fockens, P.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Sharma, P.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Sharma, P.] Dept Vet Affairs Med Ctr, Kansas City, KS USA. [Meining, A.] Tech Univ Munich, Klinikum Rechts Isar, D-8000 Munich, Germany. RP Wallace, M (reprint author), Mayo Clin Jacksonville, 4500 San Pablo Rd S, Jacksonville, FL 32224 USA. EM wallace.michael@mayo.edu FU Mauna Kea Technologies; Barrx Inc.; Cook Medical; Olympus; Takeda; Boston Scientific; American BioOptics FX Dr Meining receives research funding from Mauna Kea Technologies and is co-patent holder of Cholangio-Flex probes. Dr Sharma receives funding from Barrx Inc., Cook Medical, Olympus, and Takeda. Dr Wallace receives research funding from Olympus, Cook Medical, Boston Scientific, Mauna Kea Technologies, and American BioOptics. Dr Dekker receives research funding from Olympus and has equipment on loan from Olympus and Mauna Kea Technologies. The other authors have nothing to declare. NR 44 TC 64 Z9 71 U1 0 U2 9 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2011 VL 43 IS 10 BP 882 EP 891 DI 10.1055/s-0030-1256632 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 829WX UT WOS:000295617700010 PM 21818734 ER PT J AU Donati, OF Stolzmann, P Desbiolles, L Leschka, S Kozerke, S Plass, A Wyss, C Falk, V Marincek, B Alkadhi, H Scheffel, H AF Donati, Olivio F. Stolzmann, Paul Desbiolles, Lotus Leschka, Sebastian Kozerke, Sebastian Plass, Andre Wyss, Christophe Falk, Volkmar Marincek, Borut Alkadhi, Hatem Scheffel, Hans TI Coronary artery disease: Which degree of coronary artery stenosis is indicative of ischemia? SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Coronary artery disease; Computed tomography; Magnetic resonance imaging; Ischemia; Coronary stenosis; Cardiac ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; ANGIOGRAPHY; ACCURACY AB Purpose: To prospectively determine the best cut-off value of stenosis degree for low-dose computed tomography coronary angiography (CTCA) to predict the hemodynamic significance of coronary artery stenoses compared to catheter angiography (CA) using a cardiac magnetic resonance based approach as standard of reference. Materials and methods: Fifty-two patients (mean age, 64 +/- 10 years) scheduled for CA underwent cardiac magnetic resonance (CMR) at 1.5-T and dual-source CTCA using prospective ECG-triggering the same day. Diagnostic performance of CTCA and CA to detect myocardial ischemia was evaluated with CMR as the standard of reference. The diagnostic performance and best cut-off values to predict the hemodynamic significance of coronary were determined from receiver operating characteristics analysis (ROC). Results: CA revealed >50% stenoses in 131/832 segments (15.7%) in 78/156 (50.0%) coronary arteries in 32/52 (62%) patients. CTCA revealed >50% stenoses in 148/807 (18.3%) segments, corresponding to 83/156 (53.2%) coronary arteries in 34/52 (65.4%) patients. CMR revealed ischemia in 118/832 (14.2%) myocardial segments corresponding to the territories of 60/156 (38.5%) coronary arteries in 29/52 (56%) patients. ROC analysis showed equal diagnostic performance for low-dose CTCA and CA with areas under the curve (AUC) of 0.82 and 0.83 (P = 0.64). The optimal cut-off value was determined at stenosis of >60% for the prediction of hemodynamically significant coronary stenosis by CTCA. Using this cut-off value, sensitivity, specificity, NPV and PPV to predict hemodynamic significance by CTCA were 100%, 83%, 100%, and 88% on a per-patient basis and 88%, 73%, 83% and 81% on a per-artery analysis, respectively. Conclusion: By considering coronary stenosis >60%, diagnostic performance for predicting the hemodynamic significance of coronary stenosis by CTCA is optimal and equals that of CA. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Stolzmann, Paul; Alkadhi, Hatem; Scheffel, Hans] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, Paul; Alkadhi, Hatem; Scheffel, Hans] Harvard Univ, Sch Med, Boston, MA USA. [Donati, Olivio F.; Stolzmann, Paul; Desbiolles, Lotus; Leschka, Sebastian; Marincek, Borut; Alkadhi, Hatem; Scheffel, Hans] Univ Zurich Hosp, Inst Diagnost Radiol, Zurich, Switzerland. [Kozerke, Sebastian] Univ & ETH Zurich, Inst Biomed Engn, Zurich, Switzerland. [Plass, Andre; Falk, Volkmar] Univ Zurich Hosp, Cardiovasc Surg Clin, Zurich, Switzerland. [Wyss, Christophe] Univ Zurich Hosp, Ctr Cardiovasc, Zurich, Switzerland. RP Scheffel, H (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza, Boston, MA 02114 USA. EM hans.scheffel@usz.ch RI Kozerke, Sebastian/J-3209-2015 OI Kozerke, Sebastian/0000-0003-3725-8884 NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD OCT PY 2011 VL 80 IS 1 BP 120 EP 126 DI 10.1016/j.ejrad.2010.07.010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 828XP UT WOS:000295538200018 PM 20708362 ER PT J AU Kimmelman, AC AF Kimmelman, Alec C. TI The dynamic nature of autophagy in cancer SO GENES & DEVELOPMENT LA English DT Review DE autophagy; cancer; tumor; metabolism; therapy ID PROTEIN-QUALITY CONTROL; TUMOR-SUPPRESSOR GENES; CELL-DEATH; TARGETING AUTOPHAGY; MAMMALIAN-CELLS; MAMMARY TUMORIGENESIS; RHEUMATOID-ARTHRITIS; MONITORING AUTOPHAGY; CARCINOMA-CELLS; HMGB1 RELEASE AB Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Kimmelman, AC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alec_kimmelman@dfci.harvard.edu FU Dana Farber Cancer Institute; National Cancer Institute [R01CA157490]; Kimmel Scholar Award; AACR-PanCAN FX I apologize for any omission of primary citations. I thank Dr. Alexei Protopopov for the SKY images and Drs. Jay Debnath, Nabeel Bardeesy, Brian Alexander, and Harvey Cantor for informative discussion and critical reading of the manuscript. I am supported by the Dana Farber Cancer Institute, National Cancer Institute Grant R01CA157490, Kimmel Scholar Award, and AACR-PanCAN Career Development Award. NR 110 TC 240 Z9 257 U1 7 U2 67 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT PY 2011 VL 25 IS 19 BP 1999 EP 2010 DI 10.1101/gad.17558811 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 832BO UT WOS:000295775600001 PM 21979913 ER PT J AU Hayes, GD Riedel, CG Ruvkun, G AF Hayes, Gabriel D. Riedel, Christian G. Ruvkun, Gary TI The Caenorhabditis elegans SOMI-1 zinc finger protein and SWI/SNF promote regulation of development by the mir-84 microRNA SO GENES & DEVELOPMENT LA English DT Article DE microRNAs; mir-84; let-7; SWI/SNF; chromatin; differentiation ID CHROMATIN-REMODELING COMPLEX; HETEROCHRONIC GENE LIN-14; ASYMMETRIC CELL-DIVISION; VULVA PRECURSOR CELLS; C-ELEGANS; TRANSCRIPTION FACTORS; NEURAL DEVELOPMENT; TARGET GENE; STEM-CELLS; LET-7 AB Hundreds of microRNAs (miRNAs) have been discovered in metazoans and plants, and understanding of their biogenesis has advanced dramatically; however, relatively little is known about the cofactors necessary for miRNA regulation of target gene expression. In Caenorhabditis elegans, the conserved miRNA let-7 and its paralogs, including mir-84, control the timing of stage-specific developmental events. To identify factors required for the activity of mir-84 and possibly other miRNAs, we screened for mutations that suppress the developmental defects caused by overexpression of mir-84. Mutations in the somi-1 gene prevent these defects without affecting the expression level of mir-84. Loss of somi-1 also causes phenotypes similar to deletion of mir-84, showing that somi-1 is necessary for the normal function of this miRNA. somi-1 encodes a zinc finger protein that localizes to nuclear foci and binds the promoters of let-60/RAS, lin-14, and lin-28, genes that may be targeted by mir-84 and similar miRNAs. Genetic evidence shows that somi-1 inhibits lin-14 and induction of the vulval precursors by the let-60/RAS pathway. Proteomic and genetic screens identified conserved chromatin-remodeling and homeodomain transcription factor complexes that work with somi-1 to regulate differentiation. Our results suggest that somi-1 coordinates a nuclear response that complements the activity of mir-84. C1 [Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu RI Hayes, Gabriel/B-9816-2012; OI Riedel, Christian/0000-0002-3689-8022 FU European Molecular Biology Organization; Human Frontier Science Program; NIH [GM44619] FX We thank members of the Ruvkun, Kaplan, and Ausubel laboratories for comments during this project and critical reading of the manuscript, in particular X. Wu, S. Curran, A. Frand, H. Gabel, J. Kim, W. Li, H.Y. Mak, J. Melo, D. Parry, and S. Russel. We thank John Asara of Beth Israel Deaconess Medical Center for mass spectrometry, J. Xu for microinjections, and the Caenorhabditis Genetics Center at the University of Minnesota for strains. Ann Rougvie provided strains and helpful comments. somi-1(tm562) was isolated by the Mitani laboratory of the Japanese National BioResources Project. C.G.R. was supported by long-term fellowships from the European Molecular Biology Organization and the Human Frontier Science Program. This work was funded by NIH grant GM44619 to G.R. NR 65 TC 10 Z9 12 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT PY 2011 VL 25 IS 19 BP 2079 EP 2092 DI 10.1101/gad.17153811 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 832BO UT WOS:000295775600008 PM 21979920 ER PT J AU Neumann-Haefelin, C Oniangue-Ndza, C Kuntzen, T Schmidt, J Nitschke, K Sidney, J Caillet-Saguy, C Binder, M Kersting, N Kemper, MW Power, KA Ingber, S Reyor, LL Hills-Evans, K Kim, AY Lauer, GM Lohmann, V Sette, A Henn, MR Bressanelli, S Thimme, R Allen, TM AF Neumann-Haefelin, Christoph Oniangue-Ndza, Cesar Kuntzen, Thomas Schmidt, Julia Nitschke, Katja Sidney, John Caillet-Saguy, Celia Binder, Marco Kersting, Nadine Kemper, Michael W. Power, Karen A. Ingber, Susan Reyor, Laura L. Hills-Evans, Kelsey Kim, Arthur Y. Lauer, Georg M. Lohmann, Volker Sette, Alessandro Henn, Matthew R. Bressanelli, Stephane Thimme, Robert Allen, Todd M. TI Human Leukocyte Antigen B27 Selects for Rare Escape Mutations That Significantly Impair Hepatitis C Virus Replication and Require Compensatory Mutations SO HEPATOLOGY LA English DT Article ID MHC-CLASS-I; INFECTION; POLYMERASE; EPITOPE; RNA; CLEARANCE; ALLELES; HLA-B27; FITNESS; CELLS AB Human leukocyte antigen B27 is associated with spontaneous viral clearance in hepatitis C virus (HCV) infection. Viral escape within the immunodominant, HLA-B27-restricted, HCV-specific, cluster of differentiation (CD)8(+) T-cell epitope, nonstructural protein (NS)5B(2841-2849) (ARMILMTHF), has been shown to be limited by viral fitness costs as well as broad T-cell cross-recognition, suggesting a potential mechanism of protection by HLA-B27. Here, we studied the subdominant HLA-B27-restricted epitope, NS5B(2936-2944) (GRAAICGKY), to further define the mechanisms of protection by HLA-B27. We identified a unique pattern of escape mutations within this epitope in a large cohort of HCV genotype 1a-infected patients. The predominant escape mutations represented conservative substitutions at the main HLA-B27 anchor residue or a T-cell receptor contact site, neither of which impaired viral replication capacity, as assessed in a subgenomic HCV replicon system. In contrast, however, in a subset of HLA-B27(+) subjects, rare escape mutations arose at the HLA-B27 anchor residue, R(2937), which nearly abolished viral replication. Notably, these rare mutations only occurred in conjunction with the selection of two equally rare, and structurally proximal, upstream mutations. Coexpression of these upstream mutations with the rare escape mutations dramatically restored viral replication capacity from <5% to >= 70% of wild-type levels. Conclusion: The selection of rare CTL escape mutations in this HLA-B27-restricted epitope dramatically impairs viral replicative fitness, unless properly compensated. These data support a role for the targeting of highly constrained regions by HLA-B27 in its ability to assert immune control of HCV and other highly variable pathogens. (HEPATOLOGY 2011;54:1157-1166) C1 [Neumann-Haefelin, Christoph; Oniangue-Ndza, Cesar; Kuntzen, Thomas; Kemper, Michael W.; Power, Karen A.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Neumann-Haefelin, Christoph; Schmidt, Julia; Nitschke, Katja; Kersting, Nadine; Thimme, Robert] Univ Freiburg, Dept Med 2, Freiburg, Germany. [Neumann-Haefelin, Christoph; Schmidt, Julia] Univ Freiburg, CCI, Freiburg, Germany. [Schmidt, Julia; Nitschke, Katja] Univ Freiburg, Fac Biol, Freiburg, Germany. [Kuntzen, Thomas] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Caillet-Saguy, Celia; Bressanelli, Stephane] Ctr Rech Gif, CNRS, Lab Virol Mol & Struct, UPR3296, Gif Sur Yvette, France. [Binder, Marco; Lohmann, Volker] Univ Heidelberg, Dept Infect Dis, Heidelberg, Germany. [Ingber, Susan; Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Reyor, Laura L.; Hills-Evans, Kelsey; Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Henn, Matthew R.] Broad Inst, Cambridge, MA USA. RP Allen, TM (reprint author), MGH E, CNY 6625,Bldg 149,13th St, Boston, MA 02129 USA. EM tallen2@partners.org RI Neumann-Haefelin, Christoph/E-5550-2011; Binder, Marco/E-9717-2011; Allen, Todd/F-5473-2011; OI Binder, Marco/0000-0002-5805-6109; Lohmann, Volker/0000-0001-8719-7608; Ingber, Susan/0000-0002-5290-8884; Bressanelli, Stephane/0000-0002-0921-6727 FU National Institute of Allergy and Infectious Disease (NIAID) [R01-AI067926, U19 AI082630]; Deutsche Forschungsgemeinschaft [NE 1567/1-1, KU 2250/1-1, FOR1202]; Bundesministerium fur Bildung und Forschung [BMBF 01EO0803]; French National Agency for Research on AIDS and Viral Hepatitis (ANRS) [AO 2010/CSS4]; Association pour la recherche sur le cancer (ARC) FX This project was funded, in part, with Federal funds from the National Institute of Allergy and Infectious Disease (NIAID) under grant R01-AI067926 (to T.M.A.) U19 AI082630 (to T.M.A. and G.M.L.), with funds from the Deutsche Forschungsgemeinschaft (Emmy Noether-Programm, NE 1567/1-1 to C.N.H.; KU 2250/1-1 to T.K.; and FOR1202 to V.L.), with funds from the Bundesministerium fur Bildung und Forschung (BMBF 01EO0803 to C.N.H.), with funds from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS; grant AO 2010/CSS4 to S.B.), and with funds from Association pour la recherche sur le cancer (ARC; postdoctoral fellowship to C.C.S.). NR 25 TC 19 Z9 19 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 IS 4 BP 1157 EP 1166 DI 10.1002/hep.24541 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KA UT WOS:000295577200008 PM 22006856 ER PT J AU Ripoll, LH Triebwasser, J Siever, LJ AF Ripoll, Luis H. Triebwasser, Joseph Siever, Larry J. TI Evidence-based pharmacotherapy for personality disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Avoidant personality disorder; borderline personality disorder; medication; psychopharmacology; schizotypal personality disorder ID SOCIAL ANXIETY DISORDER; PLACEBO-CONTROLLED-TRIAL; SELF-INJURIOUS-BEHAVIOR; POSITRON-EMISSION-TOMOGRAPHY; 18-MONTH FOLLOW-UP; POSTTRAUMATIC-STRESS-DISORDER; IMPULSIVE AGGRESSIVE-BEHAVIOR; RANDOMIZED CONTROLLED-TRIAL; VENLAFAXINE EXTENDED-RELEASE; FEMALE BORDERLINE-PATIENTS AB Patients with personality disorders are prescribed psychotropic medications with greater frequency than almost any other diagnostic group. Prescribing practices in these populations are often based on anecdotal evidence rather than rigorous data. Although evidence-based psychotherapy remains an integral part of treatment, Axis IT psychopathology is increasingly conceptualized according to neurobiological substrates that correspond to specific psychopharmacological strategies. We summarize the best available evidence regarding medication treatment of personality disordered patients and provide optimal strategies for evidence-based practice. Most available evidence is concentrated around borderline and schizotypal personality disorders, with some additional evidence concerning the treatment of avoidant and antisocial personality disorders. Although maladaptive personality symptoms respond to antidepressants, antipsychotics, mood stabilizers, and other medications, evidence-based pharmacotherapy is most useful in treating circumscribed symptom domains and induces only partial improvement. Most available evidence supports use of medication in reducing impulsivity and aggression, characteristic of borderline and antisocial psychopathology. Efforts have also begun to reduce psychotic-like symptoms and improve cognitive deficits characteristic of schizotypy. Indirect evidence is also provided for psychopharmacological reduction of social anxiety central to avoidant personality disorder. Evidence-based practice requires attention to domains of expected clinical improvement associated with a medication, relative to the potential risks. The development of future rational pharmacotherapy will require increased understanding of the neurobiological underpinnings of personality disorders and their component dimensions. Increasing efforts to translate personality theory and social cognitive neuroscience into increasingly specific neurobiological substrates may provide more effective targets for pharmacotherapy. C1 [Ripoll, Luis H.; Triebwasser, Joseph; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Ripoll, LH (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Luis.Ripoll@mssm.edu NR 185 TC 11 Z9 11 U1 8 U2 30 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD OCT PY 2011 VL 14 IS 9 BP 1257 EP 1288 DI 10.1017/51461145711000071 PG 32 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 827NG UT WOS:000295434600010 PM 21320390 ER PT J AU Delaney, RA Burns, A Emans, JB AF Delaney, R. A. Burns, A. Emans, J. B. TI Arteriovenous fistula formation after a closed proximal tibial fracture in a child SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID ARTERIAL INJURIES; ANEURYSM; FIBULA AB Arteriovenous fistula formation after a closed extremity fracture is rare. We present the case of an 11-year-old boy who developed an arteriovenous fistula between the anterior tibial artery and popliteal vein after closed fractures of the proximal tibia and fibula. The fractures were treated by closed reduction and casting. A fistula was diagnosed 12 weeks after the injury. It was treated by embolisation with coils. Subsequent angiography and ultrasonography confirmed patency of the popliteal vein and anterior and posterior tibial and peroneal arteries, with no residual shunting through the fistula. The fractures healed uneventfully and he returned to full unrestricted activities 21 weeks after his injury. C1 [Burns, A.; Emans, J. B.] Childrens Hosp Boston, Dept Orthopaed Surg, Boston, MA 02112 USA. RP Delaney, RA (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, 55 Fruit St,WHT 535, Boston, MA 02114 USA. EM radelaney@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD OCT PY 2011 VL 93B IS 10 BP 1424 EP 1426 DI 10.1302/0301-620X.93B10.27352 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 832DG UT WOS:000295781300024 PM 21969446 ER PT J AU Hobai, IA Gauran, C Chitilian, HV Ehrenfeld, JM Levinson, J Sandberg, WS AF Hobai, Ion A. Gauran, Cosmin Chitilian, Hovig V. Ehrenfeld, Jesse M. Levinson, John Sandberg, Warren S. TI The Management and Outcome of Documented Intraoperative Heart Rate-Related Electrocardiographic Changes SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE intraoperative complications; cardiac ischemia; myocardial infarction; mortality ID PERIPHERAL VASCULAR-SURGERY; SILENT MYOCARDIAL ISCHEMIA; ST-SEGMENT DEPRESSION; NONCARDIAC SURGERY; CARDIAC MORBIDITY; EVENTS; PATHOPHYSIOLOGY; ASSOCIATION; INFARCTION; MORTALITY AB Objectives: The authors analyzed surgical cases in which electrocardiographic (ECG) signs of cardiac ischemia were noted to be precipitated by increases in heart rate (ie, heart rate related ECG changes [REC]). The authors aimed to find REC incidence, specificity for coronary artery disease (CAD), and the outcome associated with different management strategies. Design: A retrospective review. Setting: A university hospital, tertiary care. Participants: Patients undergoing surgery under anesthesia. Interventions: A chart review. Measurements: The authors searched 158,252 anesthesia electronic records for comments noting REC (ie, ST-segment or T-wave changes). After excluding cases with potentially confounding conditions (eg, hypotension, hyperkalemia, and so on), 26 cases were analyzed. Results: REC commonly was precipitated by anesthesia-related events (ie, intubation, extubation, and treatment of bradycardia). In 24 cases, REC was managed by prompt heart rate reduction using beta-blocker agents, opioids, and/or cardioversion in the addition to the removal of stimulus. Only 1 case had a copy of the ECG printed. Two cases were aborted, 1 was shortened and 23 proceeded without change. Postoperative troponin T levels were checked, and cardiology consultation was obtained in selected cases and led to further cardiac evaluation in 6 cases. Postoperative myocardial infarction developed in only 1 patient in whom the ECG changes were allowed to persist throughout the case. Conclusions: This incidence of reported REC was much lower than the previously reported incidence of ischemia-related ECG changes, suggesting that the largest proportion of events go unnoticed. In many patients, subsequent cardiology workup did not confirm the existence of clinically significant CAD. (C) 2011 Elsevier Inc. All rights reserved. C1 [Hobai, Ion A.; Gauran, Cosmin; Chitilian, Hovig V.; Ehrenfeld, Jesse M.; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Levinson, John] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Hobai, IA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, GRB 444,55 Fruit St, Boston, MA 02114 USA. EM IHobai@Partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X NR 12 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2011 VL 25 IS 5 BP 791 EP 798 DI 10.1053/j.jvca.2011.03.174 PG 8 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 829FU UT WOS:000295564800008 PM 21724417 ER PT J AU Warraich, HJ Shahul, S Matyal, R Mahmood, F AF Warraich, Haider Javed Shahul, Sajid Matyal, Robina Mahmood, Feroze TI Bench to Bedside: Dynamic Mitral Valve Assessment SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Review DE 3-dimensional transesophageal echocardiography; mitral valve geometry; prosthetic mitral valve; mitral valve assessment software ID TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; ANNULAR GEOMETRY; REGURGITATION; REPAIR AB Purpose: The authors analyze a commercially available software package capable of geometrically reconstructing the mitral valve (MV) dynamically throughout systole. Description: Three-dimensional echocardiography has revolutionized the understanding of MV geometry. Advanced quantification software can be used to assess geometric changes in the MV, which have been shown to have important implications for MV surgery. Evaluation: The authors performed geometric analysis on 24 patients, with both anatomically normal and abnormal MVs to assess the feasibility of this new software. The application of this new software is briefly reviewed. Conclusion: This new software, despite its limitations, allows an improved perspective on MV geometry with implications for MV repair and surgical decision making. (C) 2011 Elsevier Inc. All rights reserved. C1 [Warraich, Haider Javed; Shahul, Sajid; Matyal, Robina; Mahmood, Feroze] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Warraich, HJ (reprint author), 1 Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, CC-454, Boston, MA 02215 USA. EM hwarraic@bidmc.harvard.edu RI Mahmood, Feroze/B-1383-2008 OI Mahmood, Feroze/0000-0002-7071-0476 NR 12 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD OCT PY 2011 VL 25 IS 5 BP 863 EP 866 DI 10.1053/j.jvca.2011.06.021 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 829FU UT WOS:000295564800022 PM 21962300 ER PT J AU Bjornerud, A Sorensen, AG Mouridsen, K Emblem, KE AF Bjornerud, Atle Sorensen, A. Gregory Mouridsen, Kim Emblem, Kyrre E. TI T-1- and T-2*-dominant extravasation correction in DSC-MRI: Part I-theoretical considerations and implications for assessment of tumor hemodynamic properties SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral hemodynamics; kinetic modeling; MRI; neurooncology; perfusion-weighted MRI ID CEREBRAL BLOOD-VOLUME; ARTERIAL INPUT FUNCTION; CONTRAST AGENT EXTRAVASATION; ENHANCED T-1-WEIGHTED MRI; BRAIN-TUMORS; PERFUSION; QUANTIFICATION; TRACER; ECHO; MAPS AB We present a novel contrast agent (CA) extravasation-correction method based on analysis of the tissue residue function for assessment of multiple hemodynamic parameters. The method enables semiquantitative determination of the transfer constant and can be used to distinguish between T-1- and T-2*-dominant extravasation effects, while being insensitive to variations in tissue mean transit time (MTT). Results in 101 patients with confirmed glioma suggest that leakage-corrected absolute cerebral blood volume (CBV) values obtained with the proposed method provide improved overall survival prediction compared with normalized CBV values combined with an established leakage-correction method. Using a standard gradient-echo echo-planar imaging sequence, similar to 60% and 10% of tumors with detectable CA extravasation mainly exhibited T-1- and T-2*-dominant leakage effects, respectively. The remaining 30% of leaky tumors had mixed T-1- and T-2*-dominant effects. Using an MTT-sensitive correction method, our results show that CBV is underestimated when tumor MTT is significantly longer than MTT in the reference tissue. Furthermore, results from our simulations suggest that the relative contribution of T-1-versus T-2*-dominant extravasation effects is strongly dependent on the effective transverse relaxivity in the extravascular space and may thus be a potential marker for cellular integrity and tissue structure. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2041-2053; doi:10.1038/jcbfm.2011.52; published online 20 April 2011 C1 [Bjornerud, Atle; Emblem, Kyrre E.] Oslo Univ Hosp, Intervent Ctr, Rikshosp, N-0027 Oslo, Norway. [Bjornerud, Atle] Oslo Univ Hosp, Dept Phys, N-0027 Oslo, Norway. [Sorensen, A. Gregory; Mouridsen, Kim; Emblem, Kyrre E.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sorensen, A. Gregory; Mouridsen, Kim; Emblem, Kyrre E.] Harvard Univ, Sch Med, Boston, MA USA. [Mouridsen, Kim] Univ Aarhus, Ctr Funct Integrat Neurosci, Aarhus, Denmark. RP Bjornerud, A (reprint author), Oslo Univ Hosp, Intervent Ctr, Rikshosp, N-0027 Oslo, Norway. EM atle.bjornerud@fys.uio.no RI Emblem, Kyrre/H-6691-2012 OI Emblem, Kyrre/0000-0002-6580-9519 FU Norwegian Research Council [191088/V50]; National Cancer Institute, National Institutes of Health FX AB Consultant/Advisory Boards; NordicNeuroLab AS, Bergen, Norway. KEE: Grant support; Norwegian Research Council; 191088/V50. AGS: Grant support; National Cancer Institute, National Institutes of Health. Consultant/Advisory boards; ACR-Image Metrix, BayerScheringPharma, Bristol Meyers Squibb, BiogenIdec, Merrimack Pharmaceuticals, Olea Medical, Mitsubishi Pharma, GE Healthcare, Regeneron, Novartis, Roche, Siemens Medical, Takeda, AstraZeneca, National Institutes of Health, Kit, Inc. KM: No potential conflicts of interest. NR 35 TC 33 Z9 33 U1 0 U2 10 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 OCT PY 2011 VL 31 IS 10 BP 2041 EP 2053 DI 10.1038/jcbfm.2011.52 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600009 PM 21505483 ER PT J AU Emblem, KE Bjornerud, A Mouridsen, K Borra, RJH Batchelor, TT Jain, RK Sorensen, AG AF Emblem, Kyrre E. Bjornerud, Atle Mouridsen, Kim Borra, Ronald J. H. Batchelor, Tracy T. Jain, Rakesh K. Sorensen, A. Gregory TI T-1- and T-2*-dominant extravasation correction in DSC-MRI: Part II-predicting patient outcome after a single dose of cediranib in recurrent glioblastoma patients SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anti-VEGF; DSC-MRI; glioblastoma; leakage correction; survival analysis ID CEREBRAL BLOOD-VOLUME; SUSCEPTIBILITY CONTRAST MRI; BRAIN-BARRIER PERMEABILITY; ENHANCED T-1-WEIGHTED MRI; HIGH-GRADE; MICROVASCULAR PERMEABILITY; AGENT EXTRAVASATION; GLIOMA GRADE; PERFUSION; TUMORS AB A 'vascular normalization index' (VNI) based on the changes in the magnetic resonance imaging (MRI) parameters K-trans and cerebral blood volume (CBV), combined with blood sampling, has been shown to correlate with patient outcome in recurrent glioblastoma after a single dose of antiangiogenic therapy. Here, by applying a novel contrast agent extravasation correction method insensitive to variations in tissue mean transit time, we show that a similar VNI parameter can be derived from a single dynamic susceptibility contrast MR acquisition rather than the three parameters shown previously. Our results show that this new VNI parameter, which combines changes in tumoral CBV and an apparent transfer constant from our leakage correction method, may provide prognostic information in an even simpler manner than prior efforts. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2054-2064; doi:10.1038/jcbfm.2011.39; published online 20 April 2011 C1 [Emblem, Kyrre E.; Mouridsen, Kim; Borra, Ronald J. H.; Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Emblem, Kyrre E.; Mouridsen, Kim; Borra, Ronald J. H.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA. [Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, Rikshosp, Oslo, Norway. [Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway. [Mouridsen, Kim] Univ Aarhus, Ctr Functionally Integrat Neurosci, Aarhus, Denmark. [Borra, Ronald J. H.] Turku Univ Hosp, Med Imaging Ctr SW Finland, FIN-20520 Turku, Finland. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Batchelor, Tracy T.] Harvard Univ, Sch Med, Boston, MA USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. RP Emblem, KE (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM kyrre@nmr.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012; OI Emblem, Kyrre/0000-0002-6580-9519; Borra, Ronald/0000-0001-8072-1243 FU Norwegian Research Council [191088/V50]; The Sigrid Juselius Foundation; Instrumentarium Research Foundation; Academy of Finland; Paulo Foundation; Finnish Medical Foundation; Takeda-Millennium; AstraZeneca; Pfizer; Dyax; MedImmune; National Cancer Institute; National Institutes of Health FX KEE received grant support from Norwegian Research Council, 191088/V50. AB is a consultant and on the advisory board of NordicNeuroLab AS, Bergen, Norway. RJHB received grant support from The Sigrid Juselius Foundation, the Instrumentarium Research Foundation, the Academy of Finland, the Paulo Foundation, and the Finnish Medical Foundation. TTB is a consultant and on the advisory boards of Vertex, Schering-Plough, Acceleron, Imclone, AstraZeneca, Roche/Genentech, and Amgen and received grant support from Takeda-Millennium, AstraZeneca, and Pfizer. RKJ received grant support from AstraZeneca, Dyax, and MedImmune and is a consultant and on the advisory boards of Astellas-Fibrogen, Dyax, Genzyme, Morphosys, AstraZeneca, Noxxon Pharma, Regeneron, and SynDevRx. AGS received grant support from National Cancer Institute and National Institutes of Health and is a consultant and on the advisory boards of ACR-Image Metrix, BayerScheringPharma, Bristol Meyers Squibb, BiogenIdec, Merrimack Pharmaceuticals, Olea Medical, Mitsubishi Pharma, GE Healthcare, Regeneron, Novartis, Roche, Siemens Medical, Takeda, AstraZeneca, National Institutes of Health, and Kit, Inc. NR 41 TC 13 Z9 14 U1 0 U2 7 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 OCT PY 2011 VL 31 IS 10 BP 2054 EP 2064 DI 10.1038/jcbfm.2011.39 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600010 PM 21505476 ER PT J AU Shen, Q Du, F Huang, SL Duong, TQ AF Shen, Qiang Du, Fang Huang, Shiliang Duong, Timothy Q. TI Spatiotemporal characteristics of postischemic hyperperfusion with respect to changes in T1, T2, diffusion, angiography, and blood-brain barrier permeability SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ADC; arterial spin labeling; CBF; cerebral ischemia; dynamic susceptibility-contrast; relaxation time ID CEREBRAL-ARTERY OCCLUSION; QUANTITATIVE DIFFUSION; ISCHEMIC STROKE; FOCAL ISCHEMIA; PERFUSION; TISSUE; REPERFUSION; RATS; MRI; FLOW AB The spatiotemporal dynamics of postischemic hyperperfusion (HP) remains incompletely understood. Diffusion, perfusion, T2, T1, angiographic, dynamic susceptibility-contrast magnetic resonance imaging (MRI) and magnetic resonance angiography were acquired longitudinally at multiple time points up to 7 days after stroke in rats subjected to 30-, 60-, and 90-minutes middle cerebral artery occlusion (MCAO). The spatiotemporal dynamics of postischemic HP was analyzed and compared with T1, T2 and blood-brain barrier (BBB) changes. No early HP within 3 hours after recanalization was observed. Late (>= 12 hours) HP was present in all animals of the 30-minute MCAO group (N = 20), half of the animals in the 60-minute MCAO group (N = 8), and absent in the 90-minute MCAO group (N = 9). Dynamic susceptibility-contrast MRI and magnetic resonance angiography corroborated HP. Hyperperfusion preceded T2 increase in some animals, but HP and T2 changes temporally coincided in others. T2 peaked first at 24 hours whereas HP peaked at 48 hours after occlusion, and HP resolved by day 7 in most animals at which point the arteries became tortuous. Pixel-by-pixel tracking analysis showed that tissue did not infarct (migrated from core or mismatch at 30 minutes to normal at 48 hours) showed normal cerebral blood flow (CBF), whereas infarct tissue (migrated from core or mismatch at 30 minutes to infarct at 48 hours) showed exaggerated CBF, indicating that HP was associated with poor outcome. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2076-2085; doi:10.1038/jcbfm.2011.64; published online 4 May 2011 C1 [Shen, Qiang; Du, Fang; Huang, Shiliang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Shen, Qiang/B-8784-2008; Huang, Shiliang/F-3143-2010 OI Shen, Qiang/0000-0002-4287-3403; FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, SDG-0430020N, SDG-0830293N] FX This work was supported by the NIH (R01-NS45879) and the American Heart Association (EIA 0940104N, SDG-0430020N, and SDG-0830293N). NR 40 TC 22 Z9 22 U1 0 U2 6 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 OCT PY 2011 VL 31 IS 10 BP 2076 EP 2085 DI 10.1038/jcbfm.2011.64 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 829YB UT WOS:000295621600012 PM 21540871 ER PT J AU Brun, R Staller, K Viner, S Kuo, B AF Brun, Rita Staller, Kyle Viner, Sofia Kuo, Braden TI Endoscopically Assisted Water Perfusion Esophageal Manometry With Minimal Sedation Technique, Indications, and Implication on the Clinical Management SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE esophageal manometry; endoscopy; motility; esophagus; conscious sedation ID INTRAVENOUS DIAZEPAM; MOTILITY; ANESTHESIA; SPHINCTER; FENTANYL; VOLUNTEERS; FREQUENCY; PRESSURES; MIDAZOLAM AB Goals: To demonstrate feasibility and clinical utility of endoscopically assisted manometry (EAM). Background: Esophageal manometry performed without sedation is the standard for assessment of esophageal motility. However, some patients cannot tolerate the procedure with intranasal intubation. We have accumulated experience performing EAM with minimal sedation on patients who cannot tolerate standard esophageal manometry. Study: We report our single center experience of EAM in adult patients. Patient records were analyzed retrospectively. Procedure protocol: Upper endoscopy is performed with minimal sedation to place a guide wire, over which a water perfusion manometry catheter is introduced and standard manometry protocol performed. Results: From 2007 to 2009, 51 patients underwent EAM, 41 (80.4%) for failed transnasal esophageal manometry and 10 (19.6%) for Zencker diverticulum, achalasia, or neurologic disease. Five patients could not tolerate the procedure despite sedation. No early or late complications were recorded and 100% of the completed procedures were diagnostic: 15 (32.6%) patients had a normal study, 13 (28.3%) were diagnosed with achalasia, 12 (26.1%) patients had low lower esophageal sphincter pressure, 10 (21.7%) patients showed ineffective esophageal motility, 3 (6.5%) patients had hypertensive lower esophageal sphincter, and 1 (2.2%) patient had nutcracker esophagus. Completed procedures resulted in treatment for achalasia (33.3%), medication changes (33.3%), completion of preoperative assessment for antireflux surgery (27.7%), or no impact clinical management (11.1%). EAM had a direct clinical impact on 89% of patients. Conclusions: EAM is a safe, reliable, and feasible technique providing objective diagnostic information that directly impacted clinical management in many problematic patients where the standard procedure failed. C1 [Brun, Rita; Staller, Kyle; Viner, Sofia; Kuo, Braden] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM bkuo@partners.org OI Staller, Kyle/0000-0003-4925-4290 FU International Foundation of Functional Gastrointestinal Disorders FX Work supported in part by a grant from the International Foundation of Functional Gastrointestinal Disorders. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2011 VL 45 IS 9 BP 759 EP 763 DI 10.1097/MCG.0b013e3182098bcd PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 821HZ UT WOS:000294967000007 PM 21602703 ER PT J AU Polyak, K AF Polyak, Kornelia TI Heterogeneity in breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID TUMOR EVOLUTION; MELANOMA-CELLS; IDENTIFICATION; REARRANGEMENT; LANDSCAPES; CARCINOMAS; PHENOTYPE; LEUKEMIA; FATE AB Breast cancer is a heterogeneous disease. There is a high degree of diversity between and within tumors as well as among cancer-bearing individuals, and all of these factors together determine the risk of disease progression and therapeutic resistance. Advances in technologies such as whole-genome sequencing and functional viability screens now allow us to analyze tumors at unprecedented depths. However, translating this increasing knowledge into clinical practice remains a challenge in part due to tumor evolution driven by the diversity of cancer cell populations and their microenvironment. The articles in this Review series discuss recent advances in our understanding of breast tumor heterogeneity, therapies tailored based on this knowledge, and future ways of assessing and treating heterogeneous tumors. C1 [Polyak, Kornelia] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02215 USA. [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA. RP Polyak, K (reprint author), Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, 450 Brookline Ave,D740C, Boston, MA 02215 USA. EM Kornelia_Polyak@dfci.harvard.edu FU National Cancer Institute; US Army Congressionally Directed Research; Avon Research Foundation; V Foundation; Breast Cancer Research Foundation; Novartis Pharmaceuticals Inc.; Susan G. Komen Foundation FX The author thanks Franziska Michor, Andriy Marusyk, and Ian Krop for their critical reading of this manuscript and useful discussions. K. Polyak is supported by the National Cancer Institute, US Army Congressionally Directed Research, the Avon Research Foundation, V Foundation, Breast Cancer Research Foundation, Novartis Pharmaceuticals Inc., and the Susan G. Komen Foundation. NR 34 TC 183 Z9 188 U1 9 U2 39 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 OCT PY 2011 VL 121 IS 10 BP 3786 EP 3788 DI 10.1172/JCI60534 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000004 PM 21965334 ER PT J AU Higgins, MJ Baselga, J AF Higgins, Michaele J. Baselga, Jose TI Targeted therapies for breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID PHASE-II; TRASTUZUMAB RESISTANCE; ADJUVANT CHEMOTHERAPY; RECEPTOR EXPRESSION; HORMONAL-THERAPY; PI3K INHIBITION; GROWTH; ACTIVATION; PIK3CA; TRIAL AB In recent years the description of well-defined molecular subtypes of breast cancer, together with the identification of the driving genetic alterations and signaling pathways, has led to the clinical development of a number of successful molecular targeted agents. This is best exemplified in the subset of HER2-amplified breast cancers, in which an increasing number of active agents are changing the natural history of this aggressive disease. Other targets are under exploration, and the clinical development of these agents will require a change from the current large, randomized trials in unselected patient populations to smaller trials in groups with a molecularly defined tumor type. In addition, combinatorial approaches that act on the secondary mutations and/or compensatory pathways in resistant tumors may markedly improve on the effects of targeted agents used alone. C1 [Higgins, Michaele J.; Baselga, Jose] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Baselga, J (reprint author), 55 Fruit St,YAW 9, Boston, MA 02114 USA. EM jbaselga@partners.org NR 90 TC 148 Z9 154 U1 4 U2 30 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2011 VL 121 IS 10 BP 3797 EP 3803 DI 10.1172/JCI57152 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000005 PM 21965336 ER PT J AU Russnes, HG Navin, N Hicks, J Borresen-Dale, AL AF Russnes, Hege G. Navin, Nicholas Hicks, James Borresen-Dale, Anne-Lise TI Insight into the heterogeneity of breast cancer through next-generation sequencing SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION PATTERNS; BONE-MARROW MICROMETASTASIS; DNA METHYLATION PATTERNS; TUMOR HETEROGENEITY; MOLECULAR SUBTYPES; SINGLE CELLS; ESOPHAGEAL ADENOCARCINOMA; KARYOTYPIC COMPARISONS; CLONAL HETEROGENEITY AB Rapid and sophisticated improvements in molecular analysis have allowed us to sequence whole human genomes as well as cancer genomes, and the findings suggest that we may be approaching the ability to individualize the diagnosis and treatment of cancer. This paradigmatic shift in approach will require clinicians and researchers to overcome several challenges including the huge spectrum of tumor types within a given cancer, as well as the cell-to-cell variations observed within tumors. This review discusses how next-generation sequencing of breast cancer genomes already reveals insight into tumor heterogeneity and how it can contribute to future breast cancer classification and management. C1 [Russnes, Hege G.; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Oslo, Norway. [Russnes, Hege G.] Oslo Univ Hosp, Div Pathol, Lab Mol Pathol, Oslo, Norway. [Russnes, Hege G.; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Oslo, Norway. [Russnes, Hege G.] Harvard Univ, Sch Med, Boston, MA USA. [Russnes, Hege G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Navin, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Navin, Nicholas] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Hicks, James] Cold Spring Harbor Labs, Cold Spring Harbor, NY USA. RP Russnes, HG (reprint author), Oslo Univ Hosp Radiumhosp, Dept Genet, Inst Canc Res, Posboks 4953 Nyadlen, N-0424 Oslo, Norway. EM heg@rr-research.no RI Russnes, Hege/N-6170-2015 OI Russnes, Hege/0000-0001-8724-1891 FU Norwegian Cancer Association; Radiumhospitalets legater; Norwegian Research Council; Raagholdt Foundation; Torsteds legat; Alice Kleberg Reynolds Foundation; Department of the Army [W81XWH04-1-0477]; Breast Cancer Research Foundation; Norwegian Research Council [155218/V40, 175240/S10]; Norwegian Cancer Society [D99061]; Health Region South East FX H.G. Russnes is funded by the Norwegian Cancer Association, Radiumhospitalets legater, the Norwegian Research Council, the Raagholdt Foundation, and Torsteds legat. N. Navin is funded by the Alice Kleberg Reynolds Foundation. J. Hicks and N. Navin were supported by grants from the Department of the Army (W81XWH04-1-0477) and the Breast Cancer Research Foundation. A.-L. Borresen-Dale's research was funded by the Norwegian Research Council (grants 155218/V40 and 175240/S10), the Norwegian Cancer Society (grant D99061), and the Health Region South East. NR 106 TC 96 Z9 102 U1 1 U2 16 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 OCT PY 2011 VL 121 IS 10 BP 3810 EP 3818 DI 10.1172/JCI57088 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000007 PM 21965338 ER PT J AU Wang, X Werneck, MBF Wilson, BG Kim, HJ Kluk, MJ Thom, CS Wischhusen, JW Evans, JA Jesneck, JL Nguyen, P Sansam, CG Cantor, H Roberts, CWM AF Wang, Xi Werneck, Miriam B. F. Wilson, Boris G. Kim, Hye-Jung Kluk, Michael J. Thom, Christopher S. Wischhusen, Jonathan W. Evans, Julia A. Jesneck, Jonathan L. Phuong Nguyen Sansam, Courtney G. Cantor, Harvey Roberts, Charles W. M. TI TCR-dependent transformation of mature memory phenotype T cells in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER STEM-CELLS; EMBRYONIC STEM; SELF-RENEWAL; ONCOGENIC TRANSFORMATION; FAMILIAL SCHWANNOMATOSIS; PROLYMPHOCYTIC LEUKEMIA; GERMLINE MUTATION AB A fundamental goal in cancer research is the identification of the cell types and signaling pathways capable of initiating and sustaining tumor growth, as this has the potential to reveal therapeutic targets. Stem and progenitor cells have been implicated in the genesis of select lymphoid malignancies. However, the identity of the cells in which mature lymphoid neoplasms are initiated remains unclear. Here, we investigate the origin of peripheral T cell lymphomas using mice in which Snf5, a chromatin remodelling-complex subunit with tumor suppressor activity, could be conditionally inactivated in developing T cells. In this model of mature peripheral T cell lymphomas, the cell of origin was a mature CD44(hi)CD122(lo)CD8(+) T cell that resembled a subset of memory cells that has capacity for self-renewal and robust expansion, features shared with stem cells. Further analysis showed that Snf5 loss led to activation of a Myc-driven signaling network and stem cell transcriptional program. Finally, lymphomagenesis and lymphoma proliferation depended upon TCR signaling, establishing what we believe to be a new paradigm for lymphoid malignancy growth. These findings suggest that the self-renewal and robust proliferative capacities of memory T cells are associated with vulnerability to oncogenic transformation. Our findings further suggest that agents that impinge upon TCR signaling may represent an effective therapeutic modality for this class of lethal human cancers. C1 [Wang, Xi; Wilson, Boris G.; Thom, Christopher S.; Wischhusen, Jonathan W.; Evans, Julia A.; Jesneck, Jonathan L.; Phuong Nguyen; Sansam, Courtney G.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wang, Xi; Wilson, Boris G.; Thom, Christopher S.; Wischhusen, Jonathan W.; Evans, Julia A.; Phuong Nguyen; Sansam, Courtney G.; Roberts, Charles W. M.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Wang, Xi; Wilson, Boris G.; Thom, Christopher S.; Wischhusen, Jonathan W.; Evans, Julia A.; Phuong Nguyen; Sansam, Courtney G.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Werneck, Miriam B. F.; Kim, Hye-Jung; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Werneck, Miriam B. F.; Kim, Hye-Jung; Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kluk, Michael J.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Jesneck, Jonathan L.] Broad Inst Harvard & Massachusetts Inst Technol, Canc Program, Boston, MA USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 657,44 Binney St, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu RI Werneck, Miriam/H-5802-2012 FU Garrett B. Smith Foundation; PHS [R01CA113794, U01-1156106, F32CA123776]; American Association of Cancer Research; Gherrin-Gelli Trust; Hope Street Kids foundation; National Cancer Institute [1 F32 CA130312-01A1] FX The authors thank Christopher Wilson for supplying the Lck-Cre and CD4-Cre strains, Anjana Rao for supplying the NFAT1 antibody, and Diana Alvarez Arias and Jonghwan Kim for technical assistance. The authors are also grateful to John Luckey, Nicholas Haining, and members of Cantor and Roberts laboratories for helpful discussion. C.W.M. Roberts was supported in part by the Garrett B. Smith Foundation, PHS awards R01CA113794 and U01-1156106, and a Stand Up to Cancer Innovative Research Grant from the American Association of Cancer Research. H. Cantor was supported in part by a gift from the Gherrin-Gelli Trust. C.G. Sansam was supported by PHS awards F32CA123776 and Hope Street Kids foundation. B.G. Wilson was supported by the Ruth L. Kirschstein National Research Service Award Fellowship 1 F32 CA130312-01A1 from the National Cancer Institute NR 71 TC 32 Z9 35 U1 0 U2 7 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 OCT PY 2011 VL 121 IS 10 BP 3834 EP 3845 DI 10.1172/JCI37210 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000013 PM 21926465 ER PT J AU Yaddanapudi, S Altintas, MM Kistler, AD Fernandez, I Moller, CC Wei, CL Peev, V Flesche, JB Forst, AL Li, J Patrakka, J Xiao, ZJ Grahammer, F Schiffer, M Lohmuller, T Reinheckel, T Gu, CK Huber, TB Ju, WJ Bitzer, M Rastaldi, MP Ruiz, P Tryggvason, K Shaw, AS Faul, C Sever, S Reiser, J AF Yaddanapudi, Suma Altintas, Mehmet M. Kistler, Andreas D. Fernandez, Isabel Moeller, Clemens C. Wei, Changli Peev, Vasil Flesche, Jan B. Forst, Anna-Lena Li, Jing Patrakka, Jaakko Xiao, Zhijie Grahammer, Florian Schiffer, Mario Lohmueller, Tobias Reinheckel, Thomas Gu, Changkyu Huber, Tobias B. Ju, Wenjun Bitzer, Markus Rastaldi, Maria P. Ruiz, Phillip Tryggvason, Karl Shaw, Andrey S. Faul, Christian Sever, Sanja Reiser, Jochen TI CD2AP in mouse and human podocytes controls a proteolytic program that regulates cytoskeletal structure and cellular survival SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; LACKING CD2-ASSOCIATED PROTEIN; NEPHROTIC-SYNDROME; CATHEPSIN-L; TGF-BETA; ACTIN CYTOSKELETON; KIDNEY PODOCYTES; SLIT DIAPHRAGM; RENAL-DISEASE; NEPHRIN AB Kidney podocytes are highly differentiated epithelial cells that form interdigitating foot processes with bridging slit diaphragms (SDs) that regulate renal ultrafiltration. Podocyte injury results in proteinuric kidney disease, and genetic deletion of SD-associated CD2-associated protein (CD2AP) leads to progressive renal failure in mice and humans. Here, we have shown that CD2AP regulates the TGF-beta 1-dependent translocation of dendrin from the SD to the nucleus. Nuclear dendrin acted as a transcription factor to promote expression of cytosolic cathepsin L (CatL). CatL proteolyzed the regulatory GTPase dynamin and the actin-associated adapter synaptopodin, leading to a reorganization of the podocyte microfilament system and consequent proteinuria. CD2AP itself was proteolyzed by CatL, promoting sustained expression of the protease during podocyte injury, and in turn increasing the apoptotic susceptibility of podocytes to TGF-beta 1. Our study identifies CD2AP as the gatekeeper of the podocyte TGF-beta response through its regulation of CatL expression and defines a molecular mechanism underlying proteinuric kidney disease. C1 [Yaddanapudi, Suma; Moeller, Clemens C.; Flesche, Jan B.; Gu, Changkyu; Sever, Sanja] Harvard Univ, Dept Med, Div Nephrol, Sch Med, Charlestown, MA USA. [Yaddanapudi, Suma; Moeller, Clemens C.; Flesche, Jan B.; Gu, Changkyu; Sever, Sanja] Massachusetts Gen Hosp, Charlestown, MA USA. [Altintas, Mehmet M.; Kistler, Andreas D.; Fernandez, Isabel; Wei, Changli; Peev, Vasil; Forst, Anna-Lena; Li, Jing; Faul, Christian; Reiser, Jochen] Univ Miami, Leonard Miller Sch Med, Div Nephrol & Hypertens, Miami, FL 33136 USA. [Xiao, Zhijie; Tryggvason, Karl] Karolinska Inst, Dept Med Biochem & Biophys, Div Matrix Biol, Stockholm, Sweden. [Patrakka, Jaakko] Karolinska Univ Hosp, Dept Renal Med, Stockholm, Sweden. [Grahammer, Florian; Huber, Tobias B.] Univ Hosp Freiburg, Div Renal, Freiburg, Germany. [Schiffer, Mario] Hannover Med Sch, Dept Med, Div Nephrol, D-3000 Hannover, Germany. [Lohmueller, Tobias; Reinheckel, Thomas] Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany. [Reinheckel, Thomas; Huber, Tobias B.] Univ Freiburg, Ctr Biol Signalling Studies Bioss, Freiburg, Germany. [Ju, Wenjun; Bitzer, Markus] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Rastaldi, Maria P.] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Renal Res Lab, Milan, Italy. [Rastaldi, Maria P.] Fdn DAmico Ric Malattie Renali, Milan, Italy. [Ruiz, Phillip] Univ Miami, Leonard Miller Sch Med, Dept Pathol & Surg, Miami, FL 33136 USA. [Shaw, Andrey S.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Sever, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, 149 13th St,8th Floor, Boston, MA 02129 USA. EM ssever@partners.org; jreiser@med.miami.edu RI Forst, Anna-Lena/K-1909-2015; OI Altintas, Mehmet/0000-0002-1871-6985; Schiffer, Mario/0000-0002-8414-1470 FU NIH [DK073495, DK089394, T32DK007540, DK087985]; German Academic Exchange Service; Swiss National Science Foundation [PBZHP3-128278]; Amgen-FROMO; NephCure foundation; Katz Family Fund FX We thank Kirk Campbell (Mount Sinai School of Medicine, New York, New York, USA) for helpful discussions; Livia S. Gandhi (Massachusetts General Hospital, Boston, Massachusetts, USA) for her help with cell culture; and Dayami Hernandez and Cristina Muresan (University of Miami, Miami, Florida, USA) for assistance with H&E staining and confocal microscopy, respectively. This work was supported by NIH grants DK073495 and DK089394 (to J. Reiser). C. Wei is the Halpin Scholar of the American Society of Nephrology. C.C. Moller was supported by a scholarship of the German Academic Exchange Service. A. Kistler is supported by grant PBZHP3-128278 from the Swiss National Science Foundation and an Amgen-FROMO fellowship. M.M. Altintas was supported by NIH training grant T32DK007540. S. Yaddanapudi was supported by NIH training grant T32DK007540. S. Sever was supported by NIH grant DK087985 as well as by the NephCure foundation. The authors also acknowledge the support of the Katz Family Fund. NR 54 TC 59 Z9 65 U1 0 U2 10 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 OCT PY 2011 VL 121 IS 10 BP 3965 EP 3980 DI 10.1172/JCI58552 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000025 PM 21911934 ER PT J AU Sadagurski, M Cheng, ZY Rozzo, A Palazzo, I Kelley, GR Dong, XC Krainc, D White, MF AF Sadagurski, Marianna Cheng, Zhiyong Rozzo, Aldo Palazzo, Isabella Kelley, Gregory R. Dong, Xiaocheng Krainc, Dimitri White, Morris F. TI IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-2; R6/2 TRANSGENIC MOUSE; EXPANDED CAG REPEAT; LIFE-SPAN EXTENSION; GROWTH-FACTOR-I; NUTRIENT HOMEOSTASIS; MUTANT HUNTINGTIN; INTRANUCLEAR INCLUSIONS; TRANSCRIPTION FACTOR; CALORIE RESTRICTION AB Aging is a major risk factor for the progression of neurodegenerative diseases, including Huntington disease (HD). Reduced neuronal IGF1 or Irs2 signaling have been shown to extend life span in mice. To determine whether Irs2 signaling modulates neurodegeneration in HD, we genetically modulated Irs2 concentrations in the R6/2 mouse model of HD. Increasing Irs2 levels in the brains of R6/2 mice significantly reduced life span and increased neuronal oxidative stress and mitochondrial dysfunction. In contrast, reducing Irs2 levels throughout the body (except in p cells, where Irs2 expression is needed to prevent diabetes onset; R6/2 center dot Irs2(+)/(-)center dot Irs2(beta tg) mice) improved motor performance and extended life span. The slower progression of HD-like symptoms was associated with increased nuclear localization of the transcription factor FoxO1 and increased expression of FoxO1-dependent genes that promote autophagy, mitochondrial function, and resistance to oxidative stress. Mitochondrial function improved and the number of autophagosomes increased in R6/2 center dot Irs2(+)/(-)center dot Irs2(beta tg) mice, whereas aggregate formation and oxidative stress decreased. Thus, our study suggests that Irs2 signaling can modulate HD progression. Since we found the expression of Irs2 to be normal in grade II HD patients, our results suggest that decreasing IRS2 signaling could be part of a therapeutic approach to slow the progression of HD. C1 [White, Morris F.] Harvard Univ, Sch Med, Childrens Hosp Boston,Div Endocrinol, Howard Hughes Med Inst,Karp Family Res Labs, Boston, MA 02115 USA. [Palazzo, Isabella; Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston,Div Endocrinol, Howard Hughes Med Inst,Karp Family Res Labs, Room 4210,300 Longwood Ave, Boston, MA 02115 USA. EM morris.white@childrens.harvard.edu FU NIH [DK38712, DK55326, R01NS051303]; Ellison foundation FX This project was supported by NIH grants DK38712, DK55326 (to M.F. White), and R01NS051303 (to D. Krainc) and by the Ellison foundation (to M.F. White and M. Sadagurski). NR 84 TC 49 Z9 50 U1 0 U2 6 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 OCT PY 2011 VL 121 IS 10 BP 4070 EP 4081 DI 10.1172/JCI46305 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000033 PM 21926467 ER PT J AU Akahoshi, M Song, CH Piliponsky, AM Metz, M Guzzetta, A Abrink, M Schlenner, SM Feyerabend, TB Rodewald, HR Pejler, G Tsai, M Galli, SJ AF Akahoshi, Mitsuteru Song, Chang Ho Piliponsky, Adrian M. Metz, Martin Guzzetta, Andrew Abrink, Magnus Schlenner, Susan M. Feyerabend, Thorsten B. Rodewald, Hans-Reimer Pejler, Gunnar Tsai, Mindy Galli, Stephen J. TI Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYCLASE ACTIVATING POLYPEPTIDE; COMMON STRIPED SCORPION; HELODERMA-SUSPECTUM; SNAKE-VENOM; BEE VENOM; BIOLOGICAL-PROPERTIES; HOST-DEFENSE; SUBSTANCE-P; PEPTIDE; MOUSE AB Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. C1 [Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Tsai, Mindy; Galli, Stephen J.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Song, Chang Ho] Chonbuk Natl Univ, Sch Med, Dept Anat, Jeonju, South Korea. [Piliponsky, Adrian M.] Univ Washington, Dept Pediat, Ctr Immun & lmmunotherapies, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Metz, Martin] Charite, Dept Dermatol & Allergy, Allergie Ctr Charite, D-13353 Berlin, Germany. [Abrink, Magnus] Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden. [Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer] Univ Ulm, Inst Immunol, Ulm, Germany. [Schlenner, Susan M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Feyerabend, Thorsten B.; Rodewald, Hans-Reimer] German Canc Res Ctr, Div Cellular Immunol, Heidelberg, Germany. [Pejler, Gunnar] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden. [Galli, Stephen J.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. RP Galli, SJ (reprint author), Stanford Univ, Sch Med, Dept Pathol, L-235,300 Pasteur Dr, Stanford, CA 94305 USA. EM sgalli@stanford.edu RI Metz, Martin/M-5237-2013; Metz, Martin/B-8799-2009 OI Metz, Martin/0000-0002-4070-9976; Metz, Martin/0000-0002-4070-9976 FU NIH [AI70813, AI23990, CA72074]; German Research Foundation (DFG) [Me 2668/2-1]; European Research Council [233074]; DFG [754-2-3] FX We thank C. Liu for excellent technical assistance and members of the Galli, Pejler, and Rodewald laboratories for discussions. This study was supported by grants from the NIH (AI70813, AI23990, and CA72074 to S.J. Galli), the German Research Foundation (DFG Me 2668/2-1 to M. Metz), and the European Research Council grant agreement (no. 233074 to H.R. Rodewald) and the DFG (754-2-3 to H.R. Rodewald). NR 78 TC 51 Z9 51 U1 1 U2 10 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 OCT PY 2011 VL 121 IS 10 BP 4180 EP 4191 DI 10.1172/JCI46139 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829RC UT WOS:000295601000043 PM 21926462 ER PT J AU Walsh, MP Seto, J Liu, EB Dehghan, S Hudson, NR Lukashev, AN Ivanova, O Chodosh, J Dyer, DW Jones, MS Seto, D AF Walsh, Michael P. Seto, Jason Liu, Elizabeth B. Dehghan, Shoaleh Hudson, Nolan R. Lukashev, Alexander N. Ivanova, Olga Chodosh, James Dyer, David W. Jones, Morris S. Seto, Donald TI Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACUTE RESPIRATORY-DISEASE; GENOME TYPE ANALYSIS; MOLECULAR-IDENTIFICATION; EPIDEMIC KERATOCONJUNCTIVITIS; INFECTION; PCR; RECOMBINATION; SEROTYPES; CHILDREN; SEQUENCE AB Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene delivery vectors for human gene therapy and in other biotechnological applications. Here, the full-genome analysis of the prototype HAdV-C6 and a recently identified virus provisionally termed HAdV-C57 are reported. Although the genomes of all species HAdV-C members are very similar to each other, the E3 region, hexon and fiber (ten proteins total) present a wide range of identity values at the amino acid level. Studies of these viruses in comparison to the other three HAdV-C prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and conservation within HAdV-C species. HAdV-C6 contains a recombination event within the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its loop 2 motif. C1 [Walsh, Michael P.; Seto, Jason; Liu, Elizabeth B.; Dehghan, Shoaleh; Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA 20110 USA. [Walsh, Michael P.; Seto, Jason; Liu, Elizabeth B.; Dehghan, Shoaleh; Seto, Donald] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. [Hudson, Nolan R.] David Grant USAF Med Ctr, Clin Invest Facil, Travis AFB, CA 94535 USA. [Lukashev, Alexander N.; Ivanova, Olga] Inst Poliomyelitis & Viral Encephalitides RAMS, Moscow, Russia. [Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Howe Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Jones, Morris S.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA. RP Seto, D (reprint author), George Mason Univ, Dept Bioinformat & Computat Biol, 10900 Univ Blvd,MSN 5B3, Manassas, VA 20110 USA. EM dseto@gmu.edu RI Lukashev, Alexander/G-2777-2013; OI Lukashev, Alexander/0000-0001-7365-0352; Ivanova, O.E./0000-0003-1784-4827 FU U.S. Public Health Service National Institutes of Health (NIH) [EY013124, P30EY014104]; U.S. Air Force Surgeon General [FDG20040024E]; Research to Prevent Blindness, Inc.; Department of Defense; EOS; HQ USAF Surgeon General Office, Directorate of Modernization (SGR); Defense Threat Reduction Agency (DTRA) FX This study was supported in part by U.S. Public Health Service National Institutes of Health (NIH) grants EY013124 (D.S., M.P.W., M.S.J. and J.C.) and P30EY014104 (J.C.). M.S.J. was also supported in part by the U.S. Air Force Surgeon General (Clinical Investigation no. FDG20040024E). J.C. was also funded by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, Inc. The sequencing of the genome from HAdV-C6 was undertaken with support from the Department of Defense in which one of the authors (D.S.; 2002 to 2004) was affiliated with the USAF Surgeon General Office, Directorate of Modernization (SGR), and the Epidemic Outbreak Surveillance (EOS) Program, Falls Church, VA. Portions from the HAdV-C6 work were funded specifically, during these time periods, by a grant from the U.S. Army Medical Research and Material Command (USAMRMC; DAMD17-03-2-0089), and additional support was provided through the EOS Project, funded by HQ USAF Surgeon General Office, Directorate of Modernization (SGR), and the Defense Threat Reduction Agency (DTRA). NR 42 TC 37 Z9 47 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2011 VL 49 IS 10 BP 3482 EP 3490 DI 10.1128/JCM.00156-11 PG 9 WC Microbiology SC Microbiology GA 826NK UT WOS:000295360700007 PM 21849694 ER PT J AU Vermehren, J Yu, ML Monto, A Yao, JD Anderson, C Bertuzis, R Schneider, G Sarrazin, C AF Vermehren, Johannes Yu, Ming-Lung Monto, Alexander Yao, Joseph D. Anderson, Christopher Bertuzis, Rasa Schneider, George Sarrazin, Christoph TI Multi-center evaluation of the Abbott RealTime HCV Assay for monitoring patients undergoing antiviral therapy for chronic hepatitis C SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE Chronic hepatitis C; Pegylated interferon; Ribavirin; RealTime HCV; bDNA; TMA; Rapid virologic response; Early virologic response; Response-guided therapy ID RAPID VIROLOGICAL RESPONSE; COBAS AMPLIPREP/COBAS TAQMAN; VIRUS-RNA QUANTIFICATION; ALPHA-2A PLUS RIBAVIRIN; TIME PCR ASSAYS; QUANTITATIVE DETECTION; GENOTYPE-1 PATIENTS; TREATMENT DURATION; MANAGEMENT; INFECTION AB Background: Hepatitis C virus (HCV) RNA monitoring during antiviral therapy is essential for early prediction of treatment success and failure to peginterferon alfa/ribavirin (PEG-IFN/RBV) therapy. Objectives: In this multi-center study we assessed the clinical utility of the Abbott RealTime HCV assay for monitoring patients undergoing antiviral therapy for chronic infection with HCV genotypes (GT) 1-3. Study design: We analyzed serum from 361 patients with chronic hepatitis C who had been treated with PEG-IFN/RBV. The predictive value of rapid virologic response (RVR), partial (>= 2log(10) decline) and complete (HCV-RNA undetectable) early virologic response (pEVR/cEVR) based on RealTime HCV for achieving sustained virologic response was evaluated. In addition, the utility of RealTime HCV to tailor treatment duration according to individual virologic responses was studied in a subset of 136 GT 1 patients and compared to the reference tests, Versant HCV Quantitative 3.0 (bDNA) and Qualitative (TMA) assay. Results: At week 4 of therapy, patients with RVR had a 100% and 93.5% probability to achieve an SVR in GT 1 and GT 2/3 patients, respectively. At week 12, patients who did not achieve a pEVR had a 97.2% and 100% probability of not achieving an SVR. In addition, assignment of GT 1 patients to abbreviated or extended treatment durations based on low baseline HCV-RNA (<800,000 IU/mL) and RVR or pEVR was highly concordant between RealTime HCV and bDNA/TMA assays (97.8% and 91.9%, respectively). Conclusions: The RealTime HCV assay is suitable for monitoring virologic response to PEG-INF/RBV therapy and tailoring treatment duration accordingly. (C) 2011 Elsevier B. V. All rights reserved. C1 [Vermehren, Johannes; Sarrazin, Christoph] Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. [Yu, Ming-Lung] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung Municipal Ta Tung Hosp, Dept Internal Med, Kaohsiung, Taiwan. [Monto, Alexander] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Yao, Joseph D.] Mayo Clin, Mayo Med Labs, Rochester, MN USA. [Anderson, Christopher; Bertuzis, Rasa; Schneider, George] Abbott Mol, Des Plaines, IL USA. RP Sarrazin, C (reprint author), Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. EM sarrazin@em.uni-frankfurt.de FU Abbott Molecular FX MLY, AM, JDY and CS have received research grants from Abbott Molecular. CA, RB and GS are employees of Abbott Molecular. NR 31 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD OCT PY 2011 VL 52 IS 2 BP 133 EP 137 DI 10.1016/j.jcv.2011.07.007 PG 5 WC Virology SC Virology GA 828WS UT WOS:000295535500014 PM 21803650 ER PT J AU Wu, HJ de Boer, JF Chen, TC AF Wu, Huijuan de Boer, Johannes F. Chen, Teresa C. TI Reproducibility of Retinal Nerve Fiber Layer Thickness Measurements Using Spectral Domain Optical Coherence Tomography SO JOURNAL OF GLAUCOMA LA English DT Article DE optical coherence tomography; retinal nerve fiber layer; reproducibility; glaucoma ID GLAUCOMATOUS EYES; STRATUS OCT; TIME-DOMAIN; MACULAR THICKNESS; HIGH-SPEED; PERFORMANCE AB Purpose: To evaluate the reproducibility of the peripapillary retinal nerve fiber layer (RNFL) thickness measurements obtained by Spectralis spectral domain optical coherence tomography (OCT) (Heidelberg Engineering, Heidelberg, Germany) in normal and glaucoma participants. Methods: Participants were recruited from a university-based clinic. Peripapillary RNFL thickness measurements were repeated 3 times during the same visit using the follow-up function. One eye of each participant was randomly selected for statistical analysis. Reproducibility was evaluated using within-subject standard deviation (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Spearman rank correlation coefficient analyses were used to assess the correlation of the standard deviation of the 3 measurements for each participant with the RNFL thickness value. Results: Forty-five normal participants and 33 glaucoma patients were included in the study. The CVs ranged from 1.45% [overall global (G)] to 2.59% [temporal quadrant (T)] in normal eyes and from 1.74% (G) to 3.22% (T) in the glaucomatous eyes. ICCs ranged from 0.977 (T) to 0.990 (G and inferior-nasal sector) in normal eyes and from 0.983 (T) to 0.997 (inferior quadrant) in glaucomatous eyes. Sw were from 1.34 mu m (G) to 2.39 mu m (superior-temporal and inferior-temporal sectors) in normal eyes and from 1.14 mu m (G) to 2.25 mu m (superior-nasal sector) in the glaucomatous eyes. There were no significant correlations between RNFL thickness values and the measurement variability for each participant. Conclusions: Spectralis OCT shows excellent reproducibility for measuring the peripapillary RNFL thickness values in both healthy and glaucoma participants. C1 [Wu, Huijuan; Chen, Teresa C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. [Wu, Huijuan] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. [de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, Amsterdam, Netherlands. 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 [R01 EY14975-01] FX Supported in part by the National Institutes of Health (R01 EY14975-01). NR 34 TC 52 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT-NOV PY 2011 VL 20 IS 8 BP 470 EP 476 DI 10.1097/IJG.0b013e3181f3eb64 PG 7 WC Ophthalmology SC Ophthalmology GA 829YI UT WOS:000295622500002 PM 20852437 ER PT J AU Fusco, DN Chung, RT AF Fusco, Dahlene N. Chung, Raymond T. TI New protease inhibitors for HCV - Help is on the way (vol 54, pg 1087, 2011) SO JOURNAL OF HEPATOLOGY LA English DT Correction C1 [Fusco, Dahlene N.; Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, 55 Fruit St,Warren 1007, Boston, MA 02114 USA. EM rtchung@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 0168-8278 J9 J HEPATOL JI J. Hepatol. PD OCT PY 2011 VL 55 IS 4 BP 952 EP 952 DI 10.1016/j.jhep.2010.12.016 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829WV UT WOS:000295617500039 ER PT J AU Koruth, JS Heist, EK Danik, S Barrett, CD Kabra, R Blendea, D Ruskin, J Mansour, M AF Koruth, Jacob S. Heist, E. Kevin Danik, Stephan Barrett, Conor D. Kabra, Rajesh Blendea, Dan Ruskin, Jeremy Mansour, Moussa TI Accuracy of left atrial anatomical maps acquired with a multielectrode catheter during catheter ablation for atrial fibrillation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Atrial fibrillation; Catheter ablation; Electrophysiology mapping; Imaging; Pulmonary vein isolation ID IMAGE INTEGRATION; PULMONARY; IMPACT AB Left atrial geometry provided by preprocedural MRI/CT imaging studies is often used to guide pulmonary vein isolation. Rapid 3D reconstruction of the left atrium (LA) can be obtained using multielectrode catheters in conjunction with electro-anatomical mapping (EAM) and can also be used to guide ablation. The objective of this study is to assess the accuracy of electro-anatomical left atrial maps acquired with the multispine catheter by comparing them to CT and MRI images. Forty patients undergoing ablation for atrial fibrillation were studied. All patients underwent preprocedural CT/MRI imaging. 3D reconstructions of the LA were obtained using a multispine catheter with the Ensite/NavX mapping system. The operator was blinded to the results of the preprocedural imaging studies while acquiring the LA maps. Mean map acquisition time was 10.3 +/- 3.0 min. There was a strong correlation between maximum pulmonary vein (PV) ostial length and intervein distances measured on the electro-anatomical maps and on the CT/MRI images. Moreover, 11 patients had right middle PVs which were detected during map acquisition. Six out of nine (67%) early branches of the right inferior PV and three out of three (100%) early branches of right superior PV were also identified. In two patients, one branch of the left superior PV and one branch of the left inferior PV were not detected during mapping. Left atrial anatomical maps acquired using multielectrode catheters in conjunction with EAM are accurate and provide information regarding pulmonary vein dimensions and geometry which is similar to that obtained with CT/MR imaging. C1 [Koruth, Jacob S.; Heist, E. Kevin; Danik, Stephan; Barrett, Conor D.; Kabra, Rajesh; Blendea, Dan; Ruskin, Jeremy; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 109, Boston, MA 02114 USA. EM mmansour@partners.org FU MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; St Jude FX Supported in part by the MGH Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Disclosures Jeremy Ruskin: Fellowship support: St Jude Moussa Mansour: Research Grant and Consultant: St Jude Others: None NR 15 TC 10 Z9 10 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD OCT PY 2011 VL 32 IS 1 BP 45 EP 51 DI 10.1007/s10840-011-9573-1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 828QZ UT WOS:000295518800006 PM 21503729 ER PT J AU Carter, EA Bonab, AA Paul, K Yerxa, J Tompkins, RG Fischman, AJ AF Carter, Edward A. Bonab, Ali A. Paul, Kasie Yerxa, John Tompkins, Ronald G. Fischman, Alan J. TI Association of Heat Production with F-18-FDG Accumulation in Murine Brown Adipose Tissue After Stress SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE animal imaging; molecular imaging; PET ID INSULIN-RESISTANCE; ADULT HUMANS; FAT AB Previous studies have demonstrated that cold stress results in increased accumulation of F-18-FDG in brown adipose tissue (BAT). Although it has been assumed that this effect is associated with increased thermogenesis by BAT, direct measurements of this phenomenon have not been reported. In the current investigation, we evaluated the relationship between stimulation of F-18-FDG accumulation in BAT by 3 stressors and heat production measured in vivo by thermal imaging. Male SKH-1 hairless mice were subjected to full-thickness thermal injury (30% of total body surface area), cold stress (4 degrees C for 24 h), or cutaneous wounds. Groups of 6 animals with each treatment were kept fasting overnight and injected with F-18-FDG. Sixty minutes after injection, the mice were sacrificed, and biodistribution was measured. Other groups of 6 animals subjected to the 3 stressors were studied by thermal imaging, and the difference in temperature between BAT and adjacent tissue was recorded (Delta T). Additional groups of 6 animals were studied by both thermal imaging and F-18-FDG biodistribution in the same animals. Accumulation of F-18-FDG in BAT was significantly (P < 0.0001) increased by all 3 treatments (burn, similar to 5-fold; cold, similar to 15-fold; and cutaneous wound, similar to 15-fold), whereas accumulation by adjacent white adipose tissue was unchanged. Compared with sham control mice, in animals exposed to all 3 stressors, Delta Ts showed significant (P < 0.001) increases. The DT between stressor groups was not significant; however, there was a highly significant linear correlation (r(2) = 0.835, P < 0.0001) between the DT measured in BAT versus adjacent tissue and F-18-FDG accumulation. These results establish, for the first time to our knowledge, that changes in BAT temperature determined in vivo by thermal imaging parallel increases in F-18-FDG accumulation. C1 [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Carter, Edward A.; Bonab, Ali A.; Paul, Kasie; Yerxa, John; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA. [Carter, Edward A.; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. [Yerxa, John; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Fruit St, Boston, MA 02114 USA. EM carter.ea@gmail.com RI Yerxa, John/E-7252-2017 OI Yerxa, John/0000-0002-5283-3069 FU National Institutes of Health [2P50 GM 021700-27A]; Shriners Hospitals for Children [8470] FX This study was supported in part by grants from the National Institutes of Health (2P50 GM 021700-27A) and Shriners Hospitals for Children (grant 8470). No other potential conflict of interest relevant to this article was reported. NR 21 TC 10 Z9 11 U1 0 U2 5 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 OCT 1 PY 2011 VL 52 IS 10 BP 1616 EP 1620 DI 10.2967/jnumed.111.090175 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 828XM UT WOS:000295537800021 PM 21914754 ER PT J AU Kalemkerian, GP Akerley, W Bogner, P Borghaei, H Chow, L Downey, RJ Gandhi, L Ganti, AKP Govindan, R Grecula, JC Hayman, J Heist, RS Horn, L Jahan, TM Koczywas, M Moran, CA Niell, HB O'Malley, J Patel, JD Ready, N Rudin, CM Williams, CC AF Kalemkerian, Gregory P. Akerley, Wallace Bogner, Paul Borghaei, Hossein Chow, Laura Downey, Robert J. Gandhi, Leena Ganti, Apar Kishor P. Govindan, Ramaswamy Grecula, John C. Hayman, James Heist, Rebecca Suk Horn, Leora Jahan, Thierry M. Koczywas, Marianna Moran, Cesar A. Niell, Harvey B. O'Malley, Janis Patel, Jyoti D. Ready, Neal Rudin, Charles M. Williams, Charles C., Jr. TI Small Cell Lung Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; carcinoma; small cell; neuroendocrine tumors; chemotherapy; radiotherapy; surgical resection ID PHASE-III TRIAL; PROPHYLACTIC CRANIAL IRRADIATION; COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; CISPLATIN PLUS ETOPOSIDE; FORTHCOMING 7TH EDITION; POSITRON-EMISSION-TOMOGRAPHY; MULTICENTER RANDOMIZED-TRIAL; DAILY THORACIC RADIOTHERAPY; COMBINED-MODALITY TREATMENT C1 [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bogner, Paul] Roswell Pk Canc Inst, Buffalo, NY USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chow, Laura] Fred Hutchinson Canc Res Ctr Seattle Canc Ctr All, Seattle, WA USA. [Downey, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gandhi, Leena] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Ganti, Apar Kishor P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ Sch Med, Washington, DC USA. [Grecula, John C.] Ohio State Univ Comprehens Canc Ctr James Canc Ho, Columbus, OH USA. [Grecula, John C.] Solove Res Inst, Columbus, OH USA. [Heist, Rebecca Suk] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Koczywas, Marianna] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Moran, Cesar A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Niell, Harvey B.] St Jude Childrens Res Hosp Univ Tennessee Canc In, Knoxville, TN USA. [O'Malley, Janis] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Rudin, Charles M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Williams, Charles C., Jr.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. RI Grecula, John/E-3149-2011 NR 177 TC 19 Z9 19 U1 2 U2 7 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 OCT PY 2011 VL 9 IS 10 BP 1086 EP 1113 PG 28 WC Oncology SC Oncology GA 831HZ UT WOS:000295721800002 PM 21975911 ER PT J AU Anderson, KC Alsina, M Bensinger, W Biermann, JS Chanan-Khan, A Cohen, AD Devine, S Djulbegovic, B Faber, EA Gasparetto, C Huff, CA Kassim, A Medeiros, BC Meredith, R Raje, N Schriber, J Singhal, S Somlo, G Stockerl-Goldstein, K Treon, SP Tricot, G Weber, DM Yahalom, J Yunus, F AF Anderson, Kenneth C. Alsina, Melissa Bensinger, William Biermann, J. Sybil Chanan-Khan, Asher Cohen, Adam D. Devine, Steven Djulbegovic, Benjamin Faber, Edward A., Jr. Gasparetto, Cristina Huff, Carol Ann Kassim, Adetola Medeiros, Bruno C. Meredith, Ruby Raje, Noopur Schriber, Jeffrey Singhal, Seema Somlo, George Stockerl-Goldstein, Keith Treon, Steven P. Tricot, Guido Weber, Donna M. Yahalom, Joachim Yunus, Furhan TI Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; multiple myeloma; Waldenstrom's monoclonal protein; C-reactive protein; combination chemotherapy; stem cell transplant; primary amyloidosis; cytogenetics; proteasome inhibitor; immunomodulatory drugs; bisphosphonates; supportive therapies; novel therapies ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; THALIDOMIDE PLUS DEXAMETHASONE; DONOR LYMPHOCYTE INFUSIONS; NEWLY-DIAGNOSED MYELOMA; RANDOMIZED CONTROLLED-TRIAL; PEGYLATED LIPOSOMAL DOXORUBICIN; POSITRON-EMISSION-TOMOGRAPHY; BONE-MARROW-TRANSPLANTATION; HIGH RESPONSE RATES C1 [Alsina, Melissa; Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Biermann, J. Sybil] Univ Michigan Comprehens Canc Ctr, Ann Arbor, MI USA. [Chanan-Khan, Asher] Roswell Pk Canc Inst, Buffalo, NY USA. [Cohen, Adam D.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Devine, Steven] Ohio State Univ Comprehens Canc Ctr James Canc Ho, Columbus, OH USA. [Devine, Steven] Solove Res Inst, Columbus, MS USA. [Faber, Edward A., Jr.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Gasparetto, Cristina] Duke Canc Inst, Durham, NC USA. [Huff, Carol Ann] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada. [Kassim, Adetola] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Medeiros, Bruno C.] Stanford Canc Inst, Stanford, CA USA. [Meredith, Ruby] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Raje, Noopur] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA. [Schriber, Jeffrey] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Singhal, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Stockerl-Goldstein, Keith] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Stockerl-Goldstein, Keith] Washington Univ Sch Med, Washington, DC USA. [Tricot, Guido] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Weber, Donna M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. RI Cohen, Adam/F-6729-2012; Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 199 TC 42 Z9 44 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2011 VL 9 IS 10 BP 1146 EP 1183 PG 38 WC Oncology SC Oncology GA 831HZ UT WOS:000295721800005 PM 21975914 ER PT J AU Laubach, JP Mitsiades, CS Mahindra, A Luskin, MR Rosenblatt, J Ghobrial, IM Schlossman, RL Avigan, D Raje, N Munshi, NC Anderson, KC Richardson, PG AF Laubach, Jacob P. Mitsiades, Constantine S. Mahindra, Anuj Luskin, Marlise R. Rosenblatt, Jacalyn Ghobrial, Irene M. Schlossman, Robert L. Avigan, David Raje, Noopur Munshi, Nikhil C. Anderson, Kenneth C. Richardson, Paul G. TI Management of Relapsed and Relapsed/Refractory Multiple Myeloma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article DE Multiple myeloma; lenalidomide; bortezomib; stem cell transplantation ID LENALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; LOW-DOSE THALIDOMIDE; SALVAGE THERAPY; BONE-MARROW; PHASE-III; CONSOLIDATION THERAPY; COMBINATION THERAPY; RENAL-FUNCTION; APEX TRIAL AB Despite significant progress in the treatment of multiple myeloma (MM) over the past decade, this disease remains incurable and almost all patients ultimately experience relapse and become refractory to treatment over time. However, the outlook for patients with relapsed MM has improved markedly with the use of the immunomodulatory drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib. Moreover, the development of new drug classes based on preclinical rationale and the introduction of next-generation agents is likely to further expand treatment options and improve outcomes for relapsed MM. (JNCCN 2011;9:1209-1216) C1 [Laubach, Jacob P.; Mitsiades, Constantine S.; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Mahindra, Anuj; Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Luskin, Marlise R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rosenblatt, Jacalyn; Avigan, David] Beth Israel Hosp, Boston, MA USA. RP Laubach, JP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1B25, Boston, MA 02215 USA. NR 80 TC 14 Z9 15 U1 0 U2 2 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 OCT PY 2011 VL 9 IS 10 BP 1209 EP 1216 PG 8 WC Oncology SC Oncology GA 831HZ UT WOS:000295721800008 PM 21975917 ER PT J AU Patel, VI Lancaster, RT Conrad, MF LaMuraglia, GM Kwolek, CJ Brewster, DC Cambria, RP AF Patel, Virendra I. Lancaster, Robert T. Conrad, Mark F. LaMuraglia, Glenn M. Kwolek, Christopher J. Brewster, David C. Cambria, Richard P. TI Comparable mortality with open repair of complex and infrarenal aortic aneurysm SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 23-26, 2010 CL Rockport, ME SP New England Soc Vasc Surg ID AFFAIRS SURGICAL RISK; OUTCOMES; QUALITY; ADJUSTMENT; EXPERIENCE; TRIAL; CARE; ERA; GRAFT AB Background: A consequence of endovascular aneurysm repair (EVAR) of anatomically straightforward infrarenal abdominal aortic aneurysm repair cohort (AAA) is that open aneurysm repair is more commonly performed for complex anatomy. Complex aneurysm repair with visceral vessel involvement (CAA) or combined aneurysm repair and visceral vessel reconstruction (VVR) has traditionally been considered to increase morbidity and mortality compared with repair of infrarenal AAA. This study evaluated contemporary outcomes of open abdominal aneurysm surgery, including AAA, CAA, and VVR using the National Surgical Quality Improvement Program (NSQIP) database. Methods: The NSQIP Participant Use File was queried by CPT code to identify patients undergoing AAA, CAA, and VVR (2005-2008). Comparative analysis of clinical features, technical details and 30-day outcomes was performed using univariate methods. Logistic regression analysis was used to identify predictors of morbidity and mortality. Results: A total of 2820 patients underwent AAA and 592 CAA. Renal insufficiency (ie, creatinine >1.4 mg/dL) rates were similar in AAA and CAA patients, however, more frequent in patients with VVR (51% vs 31% [no bypass]; P < .01). CAA was less likely to be performed urgently (6.3% vs 9.1%; P < .05) and was associated with increased operative time (254 +/- 100 vs 224 +/- 93; P < .01) compared with AAA. Univariate analysis showed that CAA did not increase mortality (5.7% vs 5.1%; P = .5). CAA slightly increased overall complications (32% vs 27%; P = .01) compared with AAA. 73 (2.5%) AAA and 84 (12%) CAA patients had simultaneous VVR and these patients exhibited a trend toward increased mortality (8.9% vs 5.2%; P = .07). VVR increased complications (43% (VVR) vs 26% [no bypass]; P < .01), including ventilation >48 hours (21% [VVR] vs 12% [no bypass]; P < .01), renal failure (7.6% [VVR] vs 4.1% [no bypass]; P = .04), and sepsis (13% [VVR] vs 6.3% ([no bypass]; P < .01). Multivariate analysis demonstrated that CAA (odds ratio [OR], 1.3 [95% confidence interval (CI), 1.1-1.6]; P = .01) and VVR (OR, 2.2 [95% CI, 1.8-3.6]; P < .01) increased the odds of any complication. Independent predictors of mortality included dependent functional status (OR, 3.6 [95% CI, 2.3-5.4]; P < .01), elevated pre-op creatinine (OR, 2.9 [95% CI, 2.2-4.0]; P < .01), type II diabetes (OR, 1.6 [95% CI, 1.05-2.4]; P = .03), and age (OR, 1.06 [95% CI, 1.03-1.08]; P < .01). Neither CAA (OR, 1.2 [95% CI, 0.84-1.8]; P = .3) nor VVR (OR, 1.6 [95% CI, 0.89-2.9]; P = .11) were associated with increased mortality compared with AAA. Conclusion: In contemporary practice the migration of open repair to increasingly complex cases has been achieved with 30-day mortality essentially equivalent to open repair of infrarenal AAA. Patients who require VVR do sustain increased complications, in particular renal failure. These data also emphasize the importance of baseline renal insufficiency in clinical decision making. CAA and VVR are associated with increased morbidity in comparison to AAA repair; however, both procedures can be safely performed in patients without increased risk of operative mortality. (J Vase Surg 2011;54: 952-9.) C1 [Patel, Virendra I.; Lancaster, Robert T.; Conrad, Mark F.; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Brewster, David C.; Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Patel, VI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org NR 39 TC 11 Z9 12 U1 0 U2 0 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 OCT PY 2011 VL 54 IS 4 BP 952 EP 959 DI 10.1016/j.jvs.2011.03.231 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 829FA UT WOS:000295562800004 PM 21723071 ER PT J AU Nguyen, BN Conrad, MF Guest, JM Hackney, L Patel, VI Kwolek, CJ Cambria, RP AF Bao-Ngoc Nguyen Conrad, Mark F. Guest, Julie M. Hackney, Lauren Patel, Viendra I. Kwolek, Christopher J. Cambria, Richard P. TI Late outcomes of balloon angioplasty and angioplasty with selective stenting for superficial femoral-popliteal disease are equivalent SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 23-26, 2010 CL Rockport, ME SP New England Soc Vasc Surg ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; CRITICAL LIMB ISCHEMIA; LEG BASIL TRIAL; FEMOROPOPLITEAL OCCLUSIVE DISEASE; REVASCULARIZATION STRATEGY; ENDOVASCULAR INTERVENTIONS; COST-EFFECTIVENESS; ARTERIAL-DISEASE; BYPASS-SURGERY; TASC-II AB Objective: Several trials have reported early superior patency of stenting over isolated angioplasty (plain old balloon angioplasty [POBA]) for infra-inguinal occlusive disease, yet long-term data are sparse. The purpose of this study was to contrast long-term clinical outcomes and costs of angioplasty alone vs angioplasty with selective stenting in the treatment of femoropopliteal occlusive disease. Methods: Patients undergoing primary endovascular treatments of the native femoropopliteal arteries from 2002 to 2009 were divided into two groups, POBA alone or stenting based on final treatment received at their index procedure. Study end points included actuarial 5-year primary patency (using strict criteria of any hemodynamic deterioration or return of symptoms), 5-year limb salvage, and 5-year survival and hospital costs. Results: Eight hundred twenty-four primary procedures were performed during the study interval; 517(63%) were POBA and 307 (37%) were stenting. The mean follow-up duration was 33 months (range, 0-98 months). The indication for intervention in the stenting group was claudication in 71% of the patients, whereas the remaining 29% had critical limb ischemia (CLI). In the POBA cohort, the indication for treatment was claudication in 59% of the patients and CLI in the remaining 41%. A higher percentage of POBA lesions were TransAtlantic Inter-Society Consensus (TASC) II A & B when compared to stenting (91% POBA vs 73% stenting; P < .001). There was no difference in overall 5-year primary patency (POBA 36% +/- 3%; stenting 41% +/- 4%; P = .31), nor was there a difference in patients with claudication (POBA 42% +/- 4%; stenting 45% +/- 4%; P = .8). In patients with CLI, the 4-year primary patency was 27% +/- 5% (POBA) vs 36% +/- 8% (stenting), P = .22; the 4-year limb salvage was 80% +/- 4% (POBA) vs 90% +/- 5% (stenting), P = .18. There was no difference in survival between the two groups (claudication: 83% +/- 3% POBA vs 84% +/- 4% stenting at 5 years (P = .65), CLI: 44% +/- 4% POBA vs 49% +/- 6% stenting at 4 years (P = .40). Subgroup analysis by lesion anatomy showed similar primary patency between POBA and stenting for TASC II A & B lesions, while the primary patency was significantly higher at 5 years after stenting of TASC II C & D lesions (34% +/- 6% vs 12% +/- 9%; P < .05). Stenting increased the procedural cost by 57% when compared to POBA (P < .001) regardless of treatment indication. In addition, stenting added 45% (P < .001) to the overall hospital cost of patients treated for claudication. Conclusion: Stenting resulted in equivalent long-term outcomes compared to POBA when stratified by indications. However, stenting yielded statistically better primary patency in patients with TASC II C & D lesions. The lack of improved clinical outcomes and significantly higher cost of stenting supports a posture of selective use of stents (especially in TASC II A & B) in the endovascular treatment of femoropopliteal occlusive disease. (J Vasc Surg 2011;54:1051-7.) C1 [Bao-Ngoc Nguyen] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, BN (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM bhnguyen@partners.org OI Goldman, Lauren/0000-0002-8469-2416 NR 32 TC 10 Z9 14 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 OCT PY 2011 VL 54 IS 4 BP 1051 EP 1057 DI 10.1016/j.jvs.2011.03.283 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 829FA UT WOS:000295562800017 PM 21636240 ER PT J AU Moreno, K Murray-Wijelath, J Yagi, M Kohler, T Hatsukami, T Clowes, A Sobel, M AF Moreno, Katherine Murray-Wijelath, Jacqui Yagi, Mayumi Kohler, Ted Hatsukami, Thomas Clowes, Alexander Sobel, Michael TI Circulating inflammatory cells are associated with vein graft stenosis SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; GLYCOPROTEIN IB-ALPHA; SURFACE P-SELECTIN; BYPASS-SURGERY; PLATELET ACTIVATION; NEOINTIMA FORMATION; NATURAL-HISTORY; VASCULAR INJURY; INTEGRIN MAC-1; RESTENOSIS AB Objective: Infrainguinal autogenous vein grafts are especially prone to narrowing and failure, and both inflammatory and thrombotic pathways are implicated. Platelets and monocytes are the key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. We therefore hypothesized that elevated levels of platelet-monocyte aggregates (PMA) might be associated with stenosis, and could possibly discriminate between patients with or without vein graft stenosis. Methods: Thirty-six vascular surgery patients were studied, in a stable quiescent period after infrainguinal autogenous vein graft bypasses for occlusive disease. Eighteen patients had hemodynainically significant graft stenoses confirmed by imaging, and 18 were free from stenosis. The level of PMA in whole blood was quantified after blood draw using two-color flow cytometry. Three measurements were made per sample: the basal, in-vivo level of aggregates (baseline PMA); the predisposition to spontaneously generate PMA (spontaneous PMA); and PMA generation by the addition of exogenous thrombin receptor-activating peptide (stimulated PMA). The baseline, in-vivo level of PMA was estimated by immediate flow analysis. The predisposition to spontaneously generate PMA was measured after in vitro incubation. Responsiveness to thrombin stimulation of the blood was quantified by the in vitro dose response to an exogenous thrombin receptor-activating peptide (sfllrn). Results: Baseline PMA levels were similar in patients with vein graft stenosis vs nonstenosis (14.8% +/- 3.2 vs 10.1% +/- 1.5, respectively, mean +/- SEM). However, patients with stenosis showed higher spontaneous PMA levels (58.5% +/- 4.5 vs 28.3% +/- 4.3; P < .001) and higher stimulated PMA levels (P < .001; analysis of variance). Covariables of smoking, diabetes, statin, or antithrombotic therapy could not account for these differences. Conclusions: Platelet-monocyte reactivity may play a role in the development of vein graft stenoses. Those with/without stenosis differed primarily in their threshold, or predisposition to form aggregates (spontaneous PMA), while their basal circulating levels of PMA (baseline PMA) were similar. These measurements may unmask pathologic differences in thrombo-inflammatory responsiveness that are not apparent in basal measurements. Understanding the causes and mechanisms leading to abnormal platelet-monocyte responses may improve approaches to predicting or preventing vein graft stenosis. (J Vase Surg 2011;54:1124-30.) Clinical Relevance: Infrainguinal autogenous vein grafts are especially prone to narrowing and failure with both inflammatory and thrombotic pathways implicated. Platelets and monocytes are key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. Excessive platelet-monocyte interactions are associated with myocardial infarction, unstable coronary syndrome, and cerebral vascular accidents. This article bridges clinical and basic science. It has a potentially large clinical impact in that it could lead to development of methods that identify patients who have increased risk of graft failure and provide clues that help with the design of drugs that limit thrombo-inflammatory processes that lead to graft failure. C1 VA Puget Sound Hlth Care Syst, Div Vasc Surg, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Moreno, K (reprint author), 1660 S Columbian Way,Bldg 1,Room 605, Seattle, WA 98108 USA. EM morenok@u.washington.edu FU US Department of Veterans Affairs, Office of Research and Development, Merit Review Agency; National Heart, Lung, and Blood Institute [T32 HL007828] FX Supported by a grant from the US Department of Veterans Affairs, Office of Research and Development, Merit Review Agency (M.S., T.K., T.H.), and National Heart, Lung, and Blood Institute, T32 HL007828 (K.M.). NR 44 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2011 VL 54 IS 4 BP 1124 EP 1130 DI 10.1016/j.jvs.2011.04.039 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 829FA UT WOS:000295562800027 PM 21906902 ER PT J AU Sedaghat, AR Cunningham, MJ AF Sedaghat, Ahmad R. Cunningham, Michael J. TI Does Balloon Catheter Sinuplasty Have a Role in the Surgical Management of Pediatric Sinus Disease? SO LARYNGOSCOPE LA English DT Editorial Material ID CHRONIC RHINOSINUSITIS; CHILDREN; ADENOIDECTOMY C1 [Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Cunningham, Michael J.] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Sedaghat, Ahmad R.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 5 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2011 VL 121 IS 10 BP 2053 EP 2054 DI 10.1002/lary.21929 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 824UX UT WOS:000295228800002 PM 21952904 ER PT J AU Reck, M Hermes, A Tan, EH Felip, E Klughammer, B Baselga, J AF Reck, Martin Hermes, Andreas Tan, Eng-Huat Felip, Enriqueta Klughammer, Barbara Baselga, Jose TI Tissue sampling in lung cancer: A review in light of the MERIT experience SO LUNG CANCER LA English DT Review DE Non-small-cell lung cancer; Tumour sampling; Bronchoscopy; Pathology; Biomarkers; Molecular analyses; EGFR inhibitors ID GROWTH-FACTOR RECEPTOR; FLEXIBLE FIBEROPTIC BRONCHOSCOPY; PHASE-III TRIAL; ADVANCED NSCLC; ERLOTINIB; CHEMOTHERAPY; BIOMARKERS; MUTATIONS; GEFITINIB; DOCETAXEL AB Lung cancer continues to present an enormous global burden of morbidity and mortality, despite an increasing therapeutic armamentarium of chemotherapy and targeted agents. Recent research efforts have been directed towards identifying predictors of response to treatment, in order to facilitate the selection of patients likely to obtain the greatest benefit from specific therapeutic interventions, with the ultimate goal of providing customized therapy. A strong scientific basis exists for the use of markers to identify patients who are most likely to respond to biological and targeted therapies, based on characteristics such as tumour genotype and histology. Biomarkers have the potential to aid in patient stratification (risk assessment), treatment-response identification (surrogate markers), or differential diagnosis (identifying individuals who are likely to respond well to specific therapies). Numerous trials have demonstrated correlations between molecular biomarkers and the outcome of treatment with targeted therapies such as epidermal growth factor inhibitor tyrosine-kinase inhibitors in patients with non-small-cell lung cancer (NSCLC). The recently completed MarkER Identification Trial (MERIT) found some evidence of a link between the molecular profile of a tumour and the clinical response to erlotinib in patients with relapsed NSCLC. However, MERIT also highlighted the difficulties in obtaining adequate samples for the various procedures involved in genetic analyses in clinical trials. Routine clinical practice brings its own challenges relating to biopsy techniques and tissue availability and this has implications for the application of molecular analyses in treatment -decision-making. Applying the lessons learned from tissue sampling and molecular testing in MERIT and other major NSCLC trials will be essential in paving the way for the routine use of biomarker analyses in clinical practice. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Reck, Martin; Hermes, Andreas] Grosshansdorf Hosp, D-22927 Grosshansdorf, Germany. [Tan, Eng-Huat] Natl Canc Ctr, Dept Med Oncol, Singapore 169610, Singapore. [Felip, Enriqueta] Vall dHebron Univ Hosp, Barcelona 08035, Spain. [Klughammer, Barbara] F Hoffmann La Roche Ltd, CH-4070 Basel, Switzerland. [Baselga, Jose] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reck, M (reprint author), Grosshansdorf Hosp, Wohrendamm 80, D-22927 Grosshansdorf, Germany. EM dr.martin.reck@web.de FU F. Hoffmann-La Roche; F. Hoffmann-La Roche Ltd.; Lilly; Pfizer; BMS; Merck; AstraZeneca FX Martin Reck has received payment for consultancy on advisory boards from F. Hoffmann-La Roche Ltd., Lilly, Pfizer, BMS, Merck and AstraZeneca, as well as honoraria for lectures from F. Hoffmann-La Roche Ltd., Lilly, Merck and AstraZeneca. Barbara Klughammer is an employee and stock holder of F. Hoffmann-La Roche Ltd.; This trial was funded by F. Hoffmann-La Roche. NR 34 TC 18 Z9 18 U1 0 U2 3 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 OCT PY 2011 VL 74 IS 1 BP 1 EP 6 DI 10.1016/j.lungcan.2011.05.002 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 830OE UT WOS:000295665500001 PM 21658788 ER PT J AU Creaney, J Yeoman, D Musk, AW de Klerk, N Skates, SJ Robinson, BWS AF Creaney, Jenette Yeoman, Deborah Musk, Arthur William de Klerk, Nicholas Skates, Steven J. Robinson, Bruce W. S. TI Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma-Which is best? SO LUNG CANCER LA English DT Article DE Mesothelioma; Tumor markers; Wittenoom; Mesothelin; SMRP; Osteopontin ID LUNG-CANCER; PLEURAL MESOTHELIOMA; POTENTIATING FACTOR; BREAST-CANCER; TUMOR-CELLS; DIAGNOSIS; BIOMARKERS; PROTEINS; MARKERS; FAMILY AB Background: Blood-based markers for malignant mesothelioma (MM), particularly soluble mesothelin and osteopontin, are currently of great clinical interest. As there is some concern about the sensitivity of osteopontin in serum versus plasma, we compared them in the same patient population to mesothelin. Methods: Soluble mesothelin and osteopontin concentrations were determined by commercial assays in blood samples from 66 patients with pleural MM, 47 patients with non-malignant asbestos-related lung or pleural disease, 42 patients with other benign pleural and lung diseases and 21 patients with lung cancer. Results: Soluble mesothelin and osteopontin in serum and plasma were significantly elevated in MM patients compared to patients with benign lung and pleural disease. At a level of specificity of 95% relative to patients with benign disease, the sensitivity of mesothelin in serum and plasma at presentation with symptoms was 67%, and for osteopontin in the plasma was 40% and in the serum was 20% for MM patients. Combining the serum mesothelin and plasma osteopontin markers using a logistic regression model did not significantly increase the area under the receiver operator curve. Conclusion: Plasma osteopontin has a superior diagnostic accuracy to serum. As the choice of blood sample type has limit effect on soluble mesothelin sensitivity, plasma should be collected for biomarker evaluation in patients suspected of having mesothelioma. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved. C1 [Creaney, Jenette; Yeoman, Deborah; Musk, Arthur William; de Klerk, Nicholas; Skates, Steven J.; Robinson, Bruce W. S.] Univ Western Australia, Natl Res Ctr Asbestos Related Dis, Sch Med & Pharmacol, Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Creaney, Jenette; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Australian Mesothelioma Tissue Bank, Nedlands, WA 6009, Australia. [Musk, Arthur William; Robinson, Bruce W. S.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Musk, Arthur William] Univ Western Australia, Dept Populat Hlth, Nedlands, WA 6009, Australia. [de Klerk, Nicholas] Telethon Inst Child Hlth Res, Biostat & Epidemiol Unit, Subiaco, WA 6008, Australia. [Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Creaney, J (reprint author), Univ Western Australia, Natl Res Ctr Asbestos Related Dis, Sch Med & Pharmacol, Sir Charles Gairdner Hosp, 4th Floor,G Block,Verdun St, Nedlands, WA 6009, Australia. EM creaneyj@cyllene.uwa.edu.au RI Robinson, Bruce/N-1900-2014; de Klerk, Nicholas/D-8388-2016 OI de Klerk, Nicholas/0000-0001-9223-0767 FU Fujirecbio Diagnostics Incorporated (FDI); National Health and Medical Research Council of Australia; Insurance Commission of Western Australia FX BR has previously received grant support from Fujirecbio Diagnostics Incorporated (FDI) (2004-2006). BR and JC have previously received honoraria from FDI (2006). The other authors have no conflicts to declare.; We would like to thank the staff of PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Hollywood Hospital and St John of God Pathology for their assistance with this study. This work was supported in part by the National Health and Medical Research Council of Australia and the Insurance Commission of Western Australia; these bodies had no role in the study design, implementation or manuscript preparation. NR 35 TC 21 Z9 22 U1 1 U2 5 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 OCT PY 2011 VL 74 IS 1 BP 55 EP 60 DI 10.1016/j.lungcan.2011.02.007 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 830OE UT WOS:000295665500009 PM 21397972 ER PT J AU Meadows, TA Bhatt, DL Cannon, CP Gersh, BJ Rother, J Goto, S Liau, CS Wilson, PWF Salette, G Smith, SC Steg, PG AF Meadows, Telly A. Bhatt, Deepak L. Cannon, Christopher P. Gersh, Bernard J. Roether, Joachim Goto, Shinya Liau, Chiau-Suong Wilson, Peter W. F. Salette, Genevieve Smith, Sidney C. Steg, Ph. Gabriel CA REACH Registry Investigators TI Ethnic Differences in Cardiovascular Risks and Mortality in Atherothrombotic Disease: Insights From the REduction of Atherothrombosis for Continued Health (REACH) Registry SO MAYO CLINIC PROCEEDINGS LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; CAROTID-ENDARTERECTOMY; DISPARITIES; OUTCOMES; POPULATION; OUTPATIENTS; PREVALENCE; MANAGEMENT; WHITES; ASIANS AB OBJECTIVE: To determine whether ethnic-specific differences in the prevalence of cardiovascular risk factors and outcomes exist worldwide among individuals with stable arterial disease. PATIENTS AND METHODS: From December 1, 2003, to June 30, 2004, the prospective, observational REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled 49,602 outpatients with coronary artery disease, cerebrovascular disease, and/or peripheral arterial disease from 7 predefined ethnic/racial groups: white, Hispanic, East Asian, South Asian, Other Asian, black, and Other (comprising any race distinct from those specified). The baseline demographic and risk factor profiles, medication use, and 2-year cardiovascular outcomes were assessed among these groups. RESULTS: The prevalence of traditional atherothrombotic risk factors varied significantly among the ethnic/racial groups. The use of medical therapies to reduce risk was comparable among all groups. At 2-year follow-up, the rate of cardiovascular death was significantly higher in blacks (6.1%) compared with all other ethnic/racial groups (3.9%; P=.01). Cardiovascular death rates were significantly lower in all 3 Asian ethnic/racial groups (overall, 2.1%) compared with the other groups (4.5%; P <.001). CONCLUSION: The REACH Registry, a large international study of individuals with atherothrombotic disease, documents the important ethnic-specific differences In cardiovascular risk factors and variations in cardiovascular mortality that currently exist worldwide. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Meadows, Telly A.] Mid Carolina Cardiol, Charlotte, NC USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Gersh, Bernard J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Roether, Joachim] Johannes Wesling Klinikum Minden, Dept Neurol, Minden, Germany. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Kanagawa 2591100, Japan. [Liau, Chiau-Suong] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Liau, Chiau-Suong] Sch Med, Taipei, Taiwan. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. [Salette, Genevieve] Sanofi Aventis, Paris, France. [Smith, Sidney C.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Steg, Ph. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, Ph. Gabriel] AP HP, Paris, France. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu FU AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; sanofi-aventis; Medicines Company; Lundbeck; Boehringer Ingelheim; Astellas; Bayer; Daiichi-Sankyo; GlaxoSmithKline; Kowa; Novartis; Otsuka; Schering-Plough; Takeda; Ono; Pfizer FX Dr Bhatt has received institutional research support from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, and The Medicines Company. Dr Gersh is a member (< 3 years) of the advisory boards of Bristol-Myers Squibb, Boston Scientific, Amorcyte Inc, Merck, Cardiovascular Therapeutics, and AstraZeneca. Dr Rather has received honoraria and consulting fees from sanofi-aventis, Bristol-Myers Squibb, Lundbeck, and Boehringer Ingelheim. Dr Goto has received honoraria and consulting fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Kowa, Novartis, Otsuka, sanofi-aventis, Schering-Plough, and Takeda, and he has received research grants from Eisai, Ono, sanofi-aventis, AstraZeneca, Kowa, and Pfizer. Dr Wilson has received grant support from sanofi-aventis. Dr Selette is an employee of sanofi-aventis. Dr Steg has received research grants from sanofi-aventis and has been either a speaker or a consultant for Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Endotis, GlaxoSmithKline, Medtronic, MSD, Nycomed, sanofi-aventis, Servier, and The Medicines Company. NR 20 TC 22 Z9 24 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2011 VL 86 IS 10 BP 960 EP 967 DI 10.4065/mcp.2011.0010 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 830NS UT WOS:000295664300006 PM 21964173 ER PT J AU Resnik, L Reiber, G Evans, R Steager, P Barnabe, K AF Resnik, Linda Reiber, Gayle Evans, Rachel Steager, Pam Barnabe, Kate TI New Guidebook to Facilitate VA/DoD Collaboration in Health Care Research SO MILITARY MEDICINE LA English DT Editorial Material C1 [Resnik, Linda; Steager, Pam; Barnabe, Kate] Providence VA Med Ctr, Providence, RI 02908 USA. [Resnik, Linda] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Reiber, Gayle] US Dept Vet Affairs, VA Puget Sound Healthcare Syst, Washington, DC 20420 USA. [Reiber, Gayle] Univ Washington, Seattle, WA 98195 USA. [Evans, Rachel] Brooke Army Med Ctr, Ctr Intrepid, Ft Sam Houston, TX 78234 USA. RP Resnik, L (reprint author), Providence VA Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD OCT PY 2011 VL 176 IS 10 BP 1085 EP 1087 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 831EK UT WOS:000295711300001 PM 22128638 ER PT J AU Young, RH Louis, DN AF Young, Robert H. Louis, David N. TI The Warrens and other pioneering clinician pathologists of the Massachusetts General Hospital during its early years: an appreciation on the 200th anniversary of the hospital founding SO MODERN PATHOLOGY LA English DT Article DE John Collins Warren; JBS Jackson; Oliver Wendell Holmes; John Bacon; Calvin Ellis; Reginald Heber Fitz; J Collins Warren; William Fiske Whitney AB To celebrate the bicentennial of the 1811 charter to establish the Massachusetts General Hospital, we tell the stories of the physicians and surgeons of the hospital who practiced pathology until the discipline was more firmly established with the recruitment of James Homer Wright who became the first full-time pathologist at the hospital in 1896. One of the two co-founders of the hospital, John Collins Warren (famed primarily for being the surgeon at the first public demonstration of ether anesthesia) had a major interest in pathology; he published a book focused on gross pathology (1837) and began the important specimen collection subsequently known as the Warren Anatomical Museum at Harvard Medical School (HMS). An early physician, John Barnard Swett Jackson, became the first professor of pathology in the United States (1847) and was a noted collector whose specimens were added to the Warren Museum. Dr Jackson showed no interest in microscopy when it became available, but microscopy was promoted from circa the late 1840s at Harvard and likely at the hospital by Oliver Wendell Holmes, the famed essayist who was on the staff of the hospital and faculty at the medical school. Microscopy was probably first used at the Hospital with any frequency on examination of fluids by the first officially designated 'Microscopist,' John Bacon Jr, in 1851, and after the mid-1850s by Calvin Ellis on anatomic specimens; Ellis went on to pioneering reform of the HMS curriculum. Reginald Heber Fitz succeeded Ellis in 1871 and was the first to be officially designated as 'Pathologist' at the hospital. Fitz is remembered for two major contributions: his paper showing the nature of, and potential surgical cure for, the disease that he termed 'appendicitis'; and his description of acute pancreatitis. With the microscope now firmly entrenched and with the increase in surgery after Fitz's work on appendicitis, surgical pathology grew quickly. J Collins Warren, the grandson of the co-founder, had a major interest in pathology and in 1895 published an impressive volume entitled 'Surgical Pathology and Therapeutics.' Dr Warren had a major interest in breast disease and was a pioneer of needle biopsy in the evaluation of breast masses. In 1888, William Fiske Whitney joined the staff of the hospital and spent his nearly 30-year career practicing primarily as a surgical pathologist, making particular innovations in intraoperative consultation. The contributions of these individuals brought the field from a gross pathology-oriented discipline mostly oriented around teaching to a microscopy-dependent practice integral to patient care, and hence set the stage for the formal founding of the Pathology department in 1896. Modern Pathology (2011) 24, 1285-1294; doi:10.1038/modpathol.2011.132; published online 16 September 2011 C1 [Young, Robert H.; Louis, David N.] Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Sch Med, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 30 TC 2 Z9 2 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2011 VL 24 IS 10 BP 1285 EP 1294 DI 10.1038/modpathol.2011.132 PG 10 WC Pathology SC Pathology GA 828DU UT WOS:000295482200001 PM 21926958 ER PT J AU Zhang, HJ Abraham, N Khan, LA Hall, DH Fleming, JT Gobel, V AF Zhang, Hongjie Abraham, Nessy Khan, Liakot A. Hall, David H. Fleming, John T. Goebel, Verena TI Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis SO NATURE CELL BIOLOGY LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; EPITHELIAL-CELLS; C-ELEGANS; BRANCHED-CHAIN; FATTY-ACID; ENDOPLASMIC-RETICULUM; GOLGI-COMPLEX; POLARITY; SPHINGOLIPIDS; TRAFFICKING AB Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into multiple ectopic lumens. We show that multiple-lumen formation is caused by apicobasal polarity conversion, and demonstrate that in situ modulation of lipid biosynthesis is sufficient to reversibly switch apical domain identities on growing membranes of single post-mitotic cells, shifting lumen positions. Follow-on targeted lipid-biosynthesis pathway screens and functional genetic assays were designed to identify a putative single causative lipid species. They demonstrate that fatty-acid biosynthesis affects polarity through sphingolipid synthesis, and reveal ceramide glucosyltransferases (CGTs) as end-point biosynthetic enzymes in this pathway. Our findings identify glycosphingolipids, CGT products and obligate membrane lipids, as critical determinants of in vivo polarity and indicate that they sort new components to the expanding apical membrane. C1 [Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A.; Fleming, John T.; Goebel, Verena] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A.; Fleming, John T.; Goebel, Verena] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hall, David H.] Albert Einstein Coll Med, Dept Neurosci, Ctr Elegans Anat C, Bronx, NY 10461 USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. EM gobel@helix.mgh.harvard.edu FU IBD [DK43351]; BA DE [DK57521]; NIH [HD044589, GM078653]; Mattina R. Proctor Award FX Strains and plasmids were provided by D. Bail lie (Fraser University, Burnaby, British Columbia, Canada), A. Croce (IFOM Istituto FIRC di Oncologia Molecolare, Milan, Italy), B. Grant (Rutgers University, Piscataway, New Jersey, USA), K. Kemphues (Cornell University, Ithaca, New York, USA), K. Nehrke (University of Rochester Medical Center, Rochester New York, USA), G. Ruvkun (Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA), K. Strange (Vanderbilt University Medical Center, Salisbury Cove Maine, USA), J. Simske (Case Western Reserve University School of Medicine, Cleveland, Ohio, USA), S. Mitani (National Bioresource Project Japan) and the Caenorhabditis Genetics Center (NIH Center for Research Resources). We thank G. Ruvkun for the lethal RNAi library, and J. Moore (Avanti Polar Lipids); Mary McKee (MGH Microscopy Core/partially funded by the IBD grant DK43351 and BA DE award DK57521) and K. Nygen; Christopher Crocker; and Edward Membreno for contributions to LC/MS; TEM; illustrations and C. elegans maintenance, respectively. We thank F. Solomon and B. Winckler for critical reading of the manuscript and H. Weinstein and A. Walker for ongoing support. This work was supported by NIH grants HD044589 and GM078653 and a Mattina R. Proctor Award to V.G. NR 70 TC 43 Z9 62 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2011 VL 13 IS 10 BP 1189 EP U68 DI 10.1038/ncb2328 PG 24 WC Cell Biology SC Cell Biology GA 829WY UT WOS:000295617900009 PM 21926990 ER PT J AU Kuo, TC Chen, CT Baron, D Onder, TT Loewer, S Almeida, S Weismann, CM Xu, P Houghton, JM Gao, FB Daley, GQ Doxsey, S AF Kuo, Tse-Chun Chen, Chun-Ting Baron, Desiree Onder, Tamer T. Loewer, Sabine Almeida, Sandra Weismann, Cara M. Xu, Ping Houghton, Jean-Marie Gao, Fen-Biao Daley, George Q. Doxsey, Stephen TI Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity SO NATURE CELL BIOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; NEURAL PROGENITORS; ASYMMETRIC INHERITANCE; MEDIATED ABSCISSION; MARKER PROMININ-1; HIGHER EUKARYOTES; PROTEIN-TURNOVER; SELF-RENEWAL; IN-VIVO AB The midbody is a singular organelle formed between daughter cells during cytokinesis and required for their final separation. Midbodies persist in cells long after division as midbody derivatives (MB(d)s), but their fate is unclear. Here we show that MB(d)s are inherited asymmetrically by the daughter cell with the older centrosome. They selectively accumulate in stem cells, induced pluripotent stem cells and potential cancer 'stem cells' in vivo and in vitro. MB(d) loss accompanies stem-cell differentiation, and involves autophagic degradation mediated by binding of the autophagic receptor NBR1 to the midbody protein CEP55. Differentiating cells and normal dividing cells do not accumulate MB(d)s and possess high autophagic activity. Stem cells and cancer cells accumulate MB(d)s by evading autophagosome encapsulation and exhibit low autophagic activity. MB(d) enrichment enhances reprogramming to induced pluripotent stem cells and increases the in vitro tumorigenicity of cancer cells. These results indicate unexpected roles for MB(d)s in stem cells and cancer 'stem cells'. C1 [Kuo, Tse-Chun; Chen, Chun-Ting; Baron, Desiree; Weismann, Cara M.; Xu, Ping; Doxsey, Stephen] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Onder, Tamer T.; Loewer, Sabine; Daley, George Q.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Onder, Tamer T.; Loewer, Sabine; Daley, George Q.] Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Onder, Tamer T.; Loewer, Sabine; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Onder, Tamer T.; Loewer, Sabine; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Onder, Tamer T.; Loewer, Sabine; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Almeida, Sandra; Weismann, Cara M.; Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Houghton, Jean-Marie] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Doxsey, S (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. EM stephen.doxsey@umassmed.edu RI Onder, Tamer /H-3330-2013 OI Onder, Tamer /0000-0002-2372-9158 FU National Institute of Child Health and Human Development; National Institutes of Health [GM051994, F32 GM084660-02]; W.M. Keck Foundation; Ellison Foundation [AG-SS-1918-07]; Department of Defense [W81XWH-08-1-0457, W81XWH-06-1-0140]; Diabetes and Endocrine Resource Center [5P30DK3252025]; Diabetes Endocrinology Research Center [DK32520] FX We thank E. Baehrecke for critical reading of the manuscript, T. Schlaeger and colleagues for assistance with H1-OGN and associated cell lines, the University of Massachusetts Medical School (UMMS) Flow Facility for assistance with MBd enrichment, P. Furcinitti of UMMS Digital Light Microscopy Core Facility for assistance with imaging, the UMMS DERC Morphology Core for assistance with immunohistochemitry, D. Guertin and C. Sparks for assistance with SMP preparation, S. Lyle and C. Powers for sample preparation and H-L. Liu for assistance with clone construction. We thank N. Mizushima for GFP-LC3-expressing Atg5-/- and matched wild-type MEFs, M. Komatsu and T. Ishii for p62-/- and matched wild-type MEFs, S. Jones for ex vivo C57BL/6 MEFs, B. Lewis for mouse hepatocellular cancer lines, S. Pino for in vitro activated T cells, W. Jiang for MKLP1-GFP plasmid, K. Khanna for CEP55-eGFP plasmid, J. Lippincott Schwartz and G. Gaietta for plasmids for FPP assay, B. Levine (UT Southwestern) for Flag-tagged BECN1-expressing plasmid, A. Khodjakov for CETN1-GFP-expressing plasmids, K. Lee for hCenexin1 antibody and the Progeria Society for cell lines. The alpha 6F antibody to Na/K-ATPase developed by D. M. Fambrough and the H4B4 antibody to LAMP2 developed by J.T. August and J. E. K. Hildreth were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by The University of Iowa, Department of Biology. This work was supported by funding from the National Institutes of Health (GM051994 to S.D. and F32 GM084660-02 to D.B.), the W.M. Keck Foundation to S.D., the Ellison Foundation (AG-SS-1918-07) to S.D., the Department of Defense (W81XWH-08-1-0457 to S.D. and W81XWH-06-1-0140 to C-T.C.) and the Diabetes and Endocrine Resource Center (5P30DK3252025). Core resources supported by the Diabetes Endocrinology Research Center grant DK32520 were also used. NR 70 TC 87 Z9 90 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2011 VL 13 IS 10 BP 1214 EP U110 DI 10.1038/ncb2332 PG 19 WC Cell Biology SC Cell Biology GA 829WY UT WOS:000295617900011 PM 21909099 ER PT J AU Walcott, BP Coumans, JVCE Kahle, KT AF Walcott, Brian P. Coumans, Jean-Valery C. E. Kahle, Kristopher T. TI Diagnostic pitfalls in spine surgery: masqueraders of surgical spine disease SO NEUROSURGICAL FOCUS LA English DT Article DE differential diagnosis; medical error; nerve compression syndrome; nutrition disorder; vascular malformations; autoimmune diseases of the nervous system; infectious disease; vasculitis ID QUADRILATERAL SPACE SYNDROME; THORACIC OUTLET SYNDROME; SUPRASCAPULAR NERVE ENTRAPMENT; SUBACUTE COMBINED DEGENERATION; LOW-BACK-PAIN; COPPER DEFICIENCY MYELOPATHY; PERIPHERAL ARTERIAL-DISEASE; OUTCOMES RESEARCH TRIAL; OF-THE-LITERATURE; MULTIPLE-SCLEROSIS AB Disorders of the spine are common in clinical medicine, and spine surgery is being performed with increasing frequency in the US. Although many patients with an established diagnosis of a true surgically treatable lesion are referred to a neurosurgeon, the evaluation of patients with spinal disorders can be complex and fraught with diagnostic pitfalls. While "common conditions are common," astute clinical acumen and vigilance are necessary to identify lesions that masquerade as surgically treatable spine disease that can lead to erroneous diagnosis and treatment. In this review, the authors discuss musculoskeletal, peripheral nerve, metabolic, infectious, inflammatory, and vascular conditions that mimic the syndromes produced by surgical lesions. It is possible that nonsurgical and surgical conditions coexist at times, complicating treatment plans and natural histories. Awareness of these diagnoses can help reduce diagnostic error, thereby avoiding the morbidity and expense associated with an unnecessary operation. (DOI: 10.3171/2011.7.FOCUS11114) C1 [Walcott, Brian P.; Coumans, Jean-Valery C. E.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Coumans, Jean-Valery C. E.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 77 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD OCT PY 2011 VL 31 IS 4 AR E1 DI 10.3171/2011.7.FOCUS11114 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 827DE UT WOS:000295406500002 PM 21961853 ER PT J AU Sarrar, L Ehrlich, S Merle, JV Pfeiffer, E Lehmkuhl, U Schneider, N AF Sarrar, Lea Ehrlich, Stefan Merle, Julia Valeska Pfeiffer, Ernst Lehmkuhl, Ulrike Schneider, Nora TI Cognitive flexibility and Agouti-related protein in adolescent patients with anorexia nervosa SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Anorexia nervosa; Cognitive functions; Cognitive flexibility; Adolescents; Weight gain; Agouti-related protein ID BODY-MASS-INDEX; BULIMIA-NERVOSA; EATING-DISORDERS; WEIGHT-GAIN; CLINICAL-IMPLICATIONS; LEPTIN; BRAIN; ASSOCIATION; ANTAGONIST; DEPRESSION AB Introduction: Cognitive flexibility and the flexible learning and relearning of stimulus-reward-associations are important for decision-making and goal-directed behavior. Studies on patients with anorexia nervosa (AN) have shown difficulties in cognitive functions associated with malnutrition and extreme underweight. However, to date we find a tack of neuropsychological studies on cognitive flexibility among adolescent patients with AN. Furthermore, the underlying biological mechanisms remain unclear. Therefore, we aim to examine cognitive functions, especially reward association learning, as a measure of cognitive flexibility in adolescent patients with AN and investigate the relationship between Agouti-related protein (AGRP) and cognitive functions. Methods: The study population consists of 30 patients with AN (M-age = 16.2 +/- 1.2) and a healthy control group (CG) of 28 female adolescents (M-age = 16.3 +/- 1.3). All subjects completed a neuropsychological test battery including the probabilistic Object Reversal Task, the Digit Symbol Test and the Trail Making Test. Patients with AN were explored before and after weight gain, the CG initially and after 3 months. Results: Subtle deficits in cognitive flexibility were found in patients with AN compared to the CG. After weight gain, the AN group improved relative to their baseline values in most of the variables but did not reach CG values. They still showed slight impairments. Moreover the study revealed a clear association between AGRP levels and cognitive flexibility. Discussion: Cognitive flexibility plays an important role in AN and may be modulated by abnormal levels of the appetite-regulating peptide AGRP. Even subtle impairments in cognitive flexibility can be relevant for the ability to fully engage in therapy and therefore may hinder a prosperous treatment. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Sarrar, Lea; Merle, Julia Valeska; Pfeiffer, Ernst; Lehmkuhl, Ulrike; Schneider, Nora] Charite, Dept Child & Adolescent Psychiat Psychosomat & Ps, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Ehrlich, Stefan] Harvard Univ, Psychiat Neuroimaging Res Program, Dept Psychiat, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. RP Sarrar, L (reprint author), Charite, Dept Child & Adolescent Psychiat Psychosomat & Ps, Campus Virchow Klinikum, D-13353 Berlin, Germany. EM lea.sarrar@charite.de OI Ehrlich, Stefan/0000-0003-2132-4445 NR 57 TC 28 Z9 28 U1 3 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD OCT PY 2011 VL 36 IS 9 BP 1396 EP 1406 DI 10.1016/j.psyneuen.2011.03.014 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 829TZ UT WOS:000295608500014 PM 21531082 ER PT J AU Blackwell, T Yaffe, K Ancoli-Israel, S Redline, S Ensrud, KE Stefanick, ML Laffan, A Stone, KL AF Blackwell, Terri Yaffe, Kristine Ancoli-Israel, Sonia Redline, Susan Ensrud, Kristine E. Stefanick, Marcia L. Laffan, Alison Stone, Katie L. CA Osteoporotic Fractures Men MrOS St TI Association of Sleep Characteristics and Cognition in Older Community-Dwelling Men: the MrOS Sleep Study SO SLEEP LA English DT Article DE Sleep fragmentation; total sleep time; cognitive function; aging ID OSTEOPOROTIC FRACTURES; DAYTIME SLEEPINESS; APNEA SYNDROME; PERFORMANCE; QUALITY; ADULTS; SCALE; IMPAIRMENT; ACTIGRAPHY; INSOMNIA AB Study Objectives: To examine the association of objectively and subjectively measured sleep characteristics with cognition in older men. Design: A population-based cross-sectional study. Setting: 6 centers in the United States. Participants: 3,132 community-dwelling older men (mean age 76.4 +/- 5.6 years). Interventions: None. Measurements and Results: Objectively measured sleep predictors from wrist actigraphy were total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Subjective sleep predictors were self-reported poor sleep (Pittsburgh Sleep Quality Index [PSQI] > 5), excessive daytime sleepiness (EDS, Epworth Sleepiness Scale Score > 10), and TST. Cognitive outcomes were measured with the Modified Mini-Mental State examination (3MS), the Trails B test, and the Digit Vigilance Test (DVT). After adjustment for multiple potential confounders, WASO was modestly related to poorer cognition. Compared to those with WASO < 90 min, men with WASO >= 90 min took 6.1 sec longer to complete the Trails B test and had a 0.9-point worse 3MS score, on average (P < 0.05). Actigraphically measured long sleepers had a slightly worse 3MS score compared to those with 7-8 h of sleep, but had similar Trails B and DVT completion times. Compared to those who self-reported sleeping 7-8 h, long sleepers (> 8 h) on average took 8.6 sec more to complete the Trails B test, had a 0.6-point worse 3MS score, and took 46 sec longer to complete the DVT (P < 0.05). PSQI and ED S were not independently related to cognitive outcomes. Conclusions: There were modest cross-sectional associations of WASO and self-reported long sleep with cognition among older community-dwelling men. ED S and PSQI were not related to cognition. C1 [Blackwell, Terri; Laffan, Alison; Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 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 USA. [Stefanick, Marcia L.] Stanford Univ, Dept Med, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Blackwell, T (reprint author), San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM tblackwell@sfcc-cpmc.net FU Sepracor; Litebook; Dymedix, Inc. FX This was not an industry supported study. Dr. Ancoli-Israel has consulted for or is on the advisory boards of Ferring Pharmaceuticals, GlaxoSmithKline, Merck, NeuroVigil, Pfizer, Philips Respironics, Sanofi-Aventis, Sepracor, Scherling-Plough, and Perdue and has received research support from Sepracor and Litebook. Dr. Redline is the incumbent of an endowed chair professorship donated to Harvard Medical School by Dr. Peter Farrell, the founder and board chairman of ResMed, Inc, has received research support from Dymedix, Inc, and has received equipment for use in research from Philips Respironics. The other authors have indicated no financial conflicts of interest. NR 45 TC 53 Z9 54 U1 1 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD OCT 1 PY 2011 VL 34 IS 10 BP 1347 EP 1356 DI 10.5665/SLEEP.1276 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 829ZC UT WOS:000295624800011 PM 21966066 ER PT J AU Li, STT Paterniti, DA Tancredi, DJ Co, JPT West, DC AF Li, Su-Ting T. Paterniti, Debora A. Tancredi, Daniel J. Co, John Patrick T. West, Daniel C. TI Is Residents' Progress on Individualized Learning Plans Related to the Type of Learning Goal Set? SO ACADEMIC MEDICINE LA English DT Article ID MEDICAL PROFESSIONALISM; PHYSICIAN CHARTER; MILLENNIUM AB Purpose To determine the types of learning goals residents select for their individualized learning plans (ILPs) and the relationship between goal type and progress toward achieving that goal. Method Pediatric and combined pediatric residents at 46 U. S. training programs completed a Web-based survey on ILPs in 2008-2009, describing their most important learning goal and the goals on which they made the most and least progress. Using iterative inductive review, responses were categorized into seven types (six corresponding with the Accreditation Council for Graduate Medical Education general competencies). Descriptive statistics and regression models were used to assess the relationship between goal type and progress made. Results Of 1,739 eligible residents, 992 (57%) completed the survey; 668 (38%) had previously completed an ILP and described their learning goals. Residents were more likely to report medical knowledge (MK) (53.7%) and patient care (PC) (25.9%) goals as most important and less likely to report professionalism (1.5%) and systems-based practice (SBP) (1.0%) goals as most important. Compared with progress on MK goals, residents reported significantly greater progress on PC (odds ratio [OR]: 2.20; 95% confidence interval [CI]: 1.57-3.09) and practice-based learning and improvement teaching (OR: 2.99; 95% CI: 1.59-5.63) goals and less progress on SBP goals (OR: 0.16; 95% CI: 0.05-0.56). Conclusions Residents most commonly identified MK and PC learning goals as the most important. Residents made more progress on goals related to everyday tasks, such as PC and teaching, compared with goals less integrated in everyday training, such as SBP. C1 [Li, Su-Ting T.] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. [Paterniti, Debora A.] Univ Calif Davis, Sch Med, Dept Internal Med, Sacramento, CA 95817 USA. [Paterniti, Debora A.] Univ Calif Davis, Sch Med, Dept Sociol, Sacramento, CA 95817 USA. [Paterniti, Debora A.; Tancredi, Daniel J.] Univ Calif Davis, Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA 95817 USA. [Tancredi, Daniel J.] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. [Co, John Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. [Co, John Patrick T.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Off Grad Med Educ, Boston, MA 02115 USA. [West, Daniel C.] Univ Calif San Francisco, Sch Med, Dept Pediat, Pediat Program, San Francisco, CA 94143 USA. RP Li, STT (reprint author), 2516 Stockton Blvd, Sacramento, CA USA. EM su-ting.li@ucdmc.ucdavis.edu RI liu, jing/D-9482-2012; Tancredi, Daniel/O-3381-2013; OI Tancredi, Daniel/0000-0002-3884-7907; Li, Su-Ting/0000-0002-9104-912X FU Association of Pediatric Program Directors FX Funding for this study was provided in part by a special projects grant from the Association of Pediatric Program Directors. The funders had no role in the concept and design, analysis, interpretation of data, or drafting or revising of the manuscript. NR 21 TC 7 Z9 7 U1 0 U2 4 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 OCT PY 2011 VL 86 IS 10 BP 1293 EP 1299 DI 10.1097/ACM.0b013e31822be22b PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 826MA UT WOS:000295357000030 PM 21869666 ER PT J AU Ripp, J Babyatsky, M Fallar, R Bazari, H Bellini, L Kapadia, C Katz, JT Pecker, M Korenstein, D AF Ripp, Jonathan Babyatsky, Mark Fallar, Robert Bazari, Hasan Bellini, Lisa Kapadia, Cyrus Katz, Joel T. Pecker, Mark Korenstein, Deborah TI The Incidence and Predictors of Job Burnout in First-Year Internal Medicine Residents: A Five-Institution Study SO ACADEMIC MEDICINE LA English DT Article ID PATIENT-CARE; PERSONALITY; ASSOCIATION; WELLNESS; DISTRESS; PROGRAM; EMPATHY; EVENTS; STRESS; ERRORS AB Purpose Job burnout is prevalent among U. S. internal medicine (IM) residents and may lead to depression, suboptimal patient care, and medical errors. This study sought to identify factors predicting new burnout to better identify at-risk residents. Method The authors administered surveys to first-year IM residents at five institutions twice between June 2008 and June 2009, linking individual pre- and postresponses. Surveys measured job burnout, sleepiness, personality traits, and other characteristics. Burnout was defined using the most commonly identified definition and another stricter definition. Results Of 263 eligible residents, 185 (70%) completed both surveys. Among 114 residents who began free of burnout and completed both surveys, 86 (75%) developed burnout, with no differences across institutions. They were significantly more likely to report a disorganized personality style (9 versus 0; 11% versus 0%; P = .019) and less likely to report receiving regular performance feedback (34 versus 13; 63% versus 87%; P = .057). Using a stricter definition, 50% (78/156) of residents developed burnout. They were less likely to plan to pursue subspecialty training (49 versus 63; 78% versus 93%; P = .016) or have a calm personality style (59 versus 70; 77% versus 90%; P = .029). There were no significant associations between burnout incidence and duty hours, clinical rotation, demographics, social supports, loan debt, or psychiatric history. Conclusions This study identified a high burnout incidence. The associations observed between burnout incidence and personality style, lack of feedback, and career choice uncertainty may inform interventions to prevent burnout and associated hazards. C1 [Korenstein, Deborah] Mt Sinai Sch Med, Dept Med, Internal Med Residency Program, New York, NY USA. [Fallar, Robert] Mt Sinai Hosp, Survey Ctr, New York, NY 10029 USA. [Bazari, Hasan] Massachusetts Gen Hosp, Internal Med Residency Training Program, Boston, MA 02114 USA. [Bellini, Lisa] Univ Penn, Sch Med, Internal Med Residency Training Program, Philadelphia, PA 19104 USA. [Kapadia, Cyrus] Yale Univ, Sch Med, Internal Med Residency Training Program, New Haven, CT USA. [Katz, Joel T.] Brigham & Womens Hosp, Internal Med Residency Training Program, Boston, MA 02115 USA. [Pecker, Mark] Weill Cornell Med Coll, New York, NY USA. RP Ripp, J (reprint author), 1 Gustave L Levy Pl,Box 1216, New York, NY 10029 USA. EM Jonathan.Ripp@mountsinai.org OI Fallar, Robert/0000-0002-2968-7630; Pecker, Mark/0000-0002-1542-1954 NR 34 TC 21 Z9 23 U1 1 U2 14 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 OCT PY 2011 VL 86 IS 10 BP 1304 EP 1310 DI 10.1097/ACM.0b013e31822c1236 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 826MA UT WOS:000295357000032 PM 21869661 ER PT J AU Maust, DT Mavandadi, S Eakin, A Streim, JE DiFillipo, S Snedden, T Oslin, DW AF Maust, Donovan T. Mavandadi, Shahrzad Eakin, April Streim, Joel E. DiFillipo, Suzanne Snedden, Thomas Oslin, David W. TI Telephone-Based Behavioral Health Assessment for Older Adults Starting a New Psychiatric Medication SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; LATE-LIFE DEPRESSION; PRIMARY-CARE; ANTIDEPRESSANT PHARMACOTHERAPY; PSYCHOTROPIC MEDICATIONS; ANXIETY DISORDERS; OFFICE VISITS; UNITED-STATES; DSM-IV AB Objectives: The purpose of this study is to explore behavioral health symptoms and characteristics of noninstitutionalized older adults newly started on an antidepressant, anxiolytic, or antipsychotic agent by nonpsychiatrist physicians. Design: Naturalistic cohort study of older adults participating in the Pharmaceutical Assistance Contract for the Elderly (PACE) of the state of Pennsylvania. Setting/Participants: Noninstitutionalized adults in Pennsylvania. Measurements: Standardized scales including the Blessed Orientation-Memory-Concentration (BOMC) test, Mini International Neuropsychiatric Interview (including Psychosis, Mania, Generalized Anxiety Disorder [GAD], Panic Disorder, and Alcohol Abuse/Dependence modules), Patient Health Questionnaire-9 (PHQ-9), Paykel Scale for suicide ideation, and Medical Outcomes Survey (SF-12). Results: Participants were mostly women (83.7%) with a mean age of 79.2 years (SD 7.1). The average PHQ-9 score for those on antidepressants was 5.8 (5.2), with no statistically significant difference between medication groups (F-[2,F-409] = 1.48, p = 0.23); just seven (4.9%) of those receiving anxiolytics met criteria for an anxiety disorder, which was not significantly different than other medication classes (chi(2) (2) = 0.83, p = 0.66). Overall, 197 (47.8%) of the sample did not meet criteria for a mental health disorder. Just 69 (28.8%) of those on antidepressants reported depression as the self-reported reason for taking the medication, while 91 (22.8%) of the total reported poor sleep or stressful life events as the reason. Conclusions: In this sample, many older persons received psychotropic medications despite low symptomatology, increasing the costs of care and possible exposure to unnecessary side effects. It is important to understand perceived benefit to both patient and provider of such prescribing patterns and work towards minimizing unnecessary use. (Am J Geriatr Psychiatry 2011; 19: 851-858) C1 [Maust, Donovan T.; Mavandadi, Shahrzad; Eakin, April; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Mavandadi, Shahrzad; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Mavandadi, Shahrzad; Streim, Joel E.; DiFillipo, Suzanne; Oslin, David W.] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA. [Snedden, Thomas] Penn Dept Aging, PACE Program, Harrisburg, PA USA. RP Maust, DT (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,2nd Floor, Philadelphia, PA 19104 USA. EM Donovan.Maust@uphs.upenn.edu FU Pennsylvania Department of Aging; NIMH; Department of Psychiatry, University of Pennsylvania FX This work was funded by the PACE Program of the Pennsylvania Department of Aging. DTM is supported by the NIMH-funded Clinical Research Scholars Program of the Department of Psychiatry, University of Pennsylvania. NR 37 TC 12 Z9 12 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD OCT PY 2011 VL 19 IS 10 BP 851 EP 858 DI 10.1097/JGP.0b013e318202c1dc PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 823XN UT WOS:000295161400003 PM 21946801 ER PT J AU Fett, NM Toporcer, MB Dalmau, J Shinohara, MM Vogl, DT AF Fett, Nicole M. Toporcer, Mary B. Dalmau, Josep Shinohara, Michi M. Vogl, Dan T. TI Scleromyxedema and dermato-neuro syndrome in a patient with multiple myeloma effectively treated with dexamethasone and bortezomib SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID PAPULAR MUCINOSIS; THALIDOMIDE; THERAPY C1 [Fett, Nicole M.] Univ Penn, Perelman Ctr Adv Med, Dept Dermatol, Sch Med, Philadelphia, PA 19104 USA. [Fett, Nicole M.] Philadelphia VA Med Ctr, Dept Med, Div Dermatol, Philadelphia, PA USA. [Toporcer, Mary B.] Doylestown Dermatol, Doylestown, PA USA. [Dalmau, Josep] Univ Penn, Dept Neurol, Sch Med, Philadelphia, PA 19104 USA. [Shinohara, Michi M.] Univ Penn, Dept Dermatopathol, Sch Med, Philadelphia, PA 19104 USA. [Vogl, Dan T.] Univ Penn, Div Hematol & Oncol, Dept Med, Sch Med, Philadelphia, PA 19104 USA. RP Fett, NM (reprint author), Univ Penn, Perelman Ctr Adv Med, Dept Dermatol, Sch Med, Suite 1 330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu OI Vogl, Dan/0000-0002-2935-2566; Dalmau, Josep/0000-0001-5856-2813 NR 19 TC 12 Z9 12 U1 0 U2 5 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 OCT PY 2011 VL 86 IS 10 BP 893 EP 896 DI 10.1002/ajh.22131 PG 4 WC Hematology SC Hematology GA 824WB UT WOS:000295231800022 PM 22026006 ER PT J AU Sparks, MA O'Seaghdha, CM Sethi, SK Jhaveri, KD AF Sparks, Matthew A. O'Seaghdha, Conall M. Sethi, Sidharth Kumar Jhaveri, Kenar D. TI Embracing the Internet as a Means of Enhancing Medical Education in Nephrology SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Internet; e-learning; nephrology; education; blogs ID PROFESSIONALISM AB This review discusses how the internet currently is being used to provide medical education in the nephrology community and addresses some of the issues and dilemmas unique to using this media. It focuses on how blogs, wikis, podcasts/YouTube, social bookmarking/media, and mobile devices are used to deliver e-learning in nephrology. Am J Kidney Dis. 58(4): 512-518. (C) 2011 by the National Kidney Foundation, Inc. C1 [O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Brigham & Womens Hosp, Boston, MA 02114 USA. [O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Boston, MA USA. [Sethi, Sidharth Kumar] Ram Manohar Lohia Hosp, New Delhi, India. [Sethi, Sidharth Kumar] Postgrad Inst Med Educ & Res, Dept Pediat, New Delhi, India. [Jhaveri, Kenar D.] Hofstra N Shore Long Isl Jewish Sch Med, Div Kidney Dis & Hypertens, Great Neck, NY USA. [Sparks, Matthew A.] Duke Univ, Div Nephrol, Dept Med, Med Ctr,MSRBII, Durham, NC 27707 USA. RP Sparks, MA (reprint author), Duke Univ, Div Nephrol, Dept Med, Med Ctr,MSRBII, 2 Genome Ct,Rm 2018,Bay 17, Durham, NC 27707 USA. EM matthew.sparks@duke.edu OI Sparks, Matthew/0000-0003-2075-2691 NR 13 TC 15 Z9 15 U1 0 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2011 VL 58 IS 4 BP 512 EP 518 DI 10.1053/j.ajkd.2011.06.009 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 826UE UT WOS:000295379600006 PM 21840099 ER PT J AU Skotko, BG Levine, SP Goldstein, R AF Skotko, Brian G. Levine, Susan P. Goldstein, Richard TI Having a Son or Daughter With Down Syndrome: Perspectives From Mothers and Fathers SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Down syndrome; prenatal diagnosis; parent; attitudes; trisomy 21 ID INTELLECTUAL DISABILITY; EXCEPTIONAL-CHILDREN; POSTNATAL DIAGNOSIS; BEHAVIORAL-PROBLEMS; MENTAL-RETARDATION; SYNDROME ADVANTAGE; AUTISTIC-CHILDREN; MATERNAL STRESS; YOUNG-CHILDREN; FAMILIES AB This study asks parents who have children with Down syndrome (DS) how they feel about their lives so that such information could be shared with expectant couples during prenatal counseling sessions. A valid and reliable survey instrument was mailed to 4,924 households on the mailing lists of six non-profit DS organizations. Of the 2,044 respondents, 99% reported that they love their son or daughter; 97% were proud of them; 79% felt their outlook on life was more positive because of them; 5% felt embarrassed by them; and 4% regretted having them. The parents report that 95% of their sons or daughters without DS have good relationships with their siblings with DS. The overwhelming majority of parents surveyed report that they are happy with their decision to have their child with DS and indicate that their sons and daughters are great sources of love and pride. (C) 2011 Wiley-Liss, Inc. C1 [Skotko, Brian G.] Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Levine, Susan P.] Family Resource Associates Inc, Shrewsbury, NJ USA. [Goldstein, Richard] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Skotko, BG (reprint author), Childrens Hosp, Dept Med, Div Genet, 300 Longwood Ave,Hunnewell 5, Boston, MA 02115 USA. EM brian.skotko@childrens.harvard.edu RI Skotko, Brian/D-1375-2013 OI Skotko, Brian/0000-0002-5232-9882 FU Tim White Foundation; Fred Lovejoy House-Staff Research and Education Fund; Joel and Barbara Alpert Endowment for the Children of the City FX Grant sponsor: Tim White Foundation; Grant sponsor: Fred Lovejoy House-Staff Research and Education Fund; Grant sponsor: Joel and Barbara Alpert Endowment for the Children of the City. NR 83 TC 35 Z9 35 U1 4 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2011 VL 155A IS 10 BP 2335 EP 2347 DI 10.1002/ajmg.a.34293 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 826BL UT WOS:000295326300004 PM 21915989 ER PT J AU Skotko, BG Levine, SP Goldstein, R AF Skotko, Brian G. Levine, Susan P. Goldstein, Richard TI Having a Brother or Sister With Down Syndrome: Perspectives From Siblings SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Down syndrome; trisomy 21; siblings; brother; sister; prenatal diagnosis; attitudes ID CHILDREN; AUTISM; ADJUSTMENT; QUESTIONNAIRES; DISABILITIES; INDIVIDUALS; FATHERS; MOTHERS; SCALE AB This study asks brothers and sisters about their feelings and perceptions toward their sibling with Down syndrome (DS). We analyzed valid and reliable surveys from 822 brothers and sisters whose families were on the mailing lists of six non-profit DS organizations around the country. More than 96% of brothers/sisters that responded to the survey indicated that they had affection toward their sibling with DS; and 94% of older siblings expressed feelings of pride. Less than 10% felt embarrassed, and less than 5% expressed a desire to trade their sibling in for another brother or sister without DS. Among older siblings, 88% felt that they were better people because of their siblings with DS, and more than 90% plan to remain involved in their sibling's lives as they become adults. The vast majority of brothers and sisters describe their relationship with their sibling with DS as positive and enhancing. (C) 2011 Wiley-Liss, Inc. C1 [Skotko, Brian G.] Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Levine, Susan P.] Family Resource Associates Inc, Shrewsbury, NJ USA. [Goldstein, Richard] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Skotko, BG (reprint author), Childrens Hosp, Dept Med, Div Genet, 300 Longwood Ave,Hunnewell 5, Boston, MA 02115 USA. EM brian.skotko@childrens.harvard.edu RI Skotko, Brian/D-1375-2013 OI Skotko, Brian/0000-0002-5232-9882 FU Tim White Foundation; Fred Lovejoy House-staff Research and Education Fund; Joel and Barbara Alpert Endowment for the Children of the City FX Grant sponsor: Tim White Foundation; Grant sponsor: Fred Lovejoy House-staff Research and Education Fund; Grant sponsor: Joel and Barbara Alpert Endowment for the Children of the City. NR 27 TC 18 Z9 18 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2011 VL 155A IS 10 BP 2348 EP 2359 DI 10.1002/ajmg.a.34228 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 826BL UT WOS:000295326300005 PM 21910244 ER PT J AU Skotko, BG Levine, SP Goldstein, R AF Skotko, Brian G. Levine, Susan P. Goldstein, Richard TI Self-Perceptions From People With Down Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Down syndrome; prenatal diagnosis; attitudes; self-esteem; trisomy 21 ID QUESTIONNAIRES; MOTHERS AB This study asks people with Down syndrome (DS), ages 12 and older, about their self-perception so that their information could be shared with new and expectant parents of children with DS. We analyzed valid and reliable survey instruments from 284 people with DS on the mailing lists of 6 non-profit DS organizations around the country. Among those surveyed, nearly 99% of people with DS indicated that they were happy with their lives, 97% liked who they are, and 96% liked how they look. Nearly 99% people with DS expressed love for their families, and 97% liked their brothers and sisters. While 86% of people with DS felt they could make friends easily, those with difficulties mostly had isolating living situations. A small percentage expressed sadness about their life. In our qualitative analysis, people with DS encouraged parents to love their babies with DS, mentioning that their own lives were good. They further encouraged health-care professionals to value them, emphasizing that they share similar hopes and dreams as people without DS. Overall, the overwhelming majority of people with DS surveyed indicate they live happy and fulfilling lives. (C) 2011 Wiley-Liss, Inc. C1 [Skotko, Brian G.] Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Levine, Susan P.] Family Resource Associates Inc, Shrewsbury, NJ USA. [Goldstein, Richard] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Skotko, BG (reprint author), Childrens Hosp, Dept Med, Div Genet, 300 Longwood Ave,Hunnewell 5, Boston, MA 02115 USA. EM brian.skotko@childrens.harvard.edu RI Skotko, Brian/D-1375-2013 OI Skotko, Brian/0000-0002-5232-9882 FU Tim White Foundation; Fred Lovejoy House-Staff Research and Education Fund; Joel and Barbara Alpert Endowment for the Children of the City FX Grant sponsor: Tim White Foundation; Grant sponsor: Fred Lovejoy House-Staff Research and Education Fund; Grant sponsor: Joel and Barbara Alpert Endowment for the Children of the City. NR 30 TC 22 Z9 22 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2011 VL 155A IS 10 BP 2360 EP 2369 DI 10.1002/ajmg.a.34235 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 826BL UT WOS:000295326300006 PM 21910246 ER PT J AU Mantzoros, CS Magkos, F Brinkoetter, M Sienkiewicz, E Dardeno, TA Kim, SY Hamnvik, OPR Koniaris, A AF Mantzoros, Christos S. Magkos, Faidon Brinkoetter, Mary Sienkiewicz, Elizabeth Dardeno, Tina A. Kim, Sang-Yong Hamnvik, Ole-Petter R. Koniaris, Anastasia TI Leptin in human physiology and pathophysiology SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE adipokines; adipose tissue; leptin resistance; leptin deficiency; hypoleptinemia ID RECOMBINANT HUMAN LEPTIN; METHIONYL HUMAN LEPTIN; ACTIVE ANTIRETROVIRAL THERAPY; DIET-INDUCED OBESITY; REVERSES INSULIN-RESISTANCE; PROTHYROTROPIN-RELEASING HORMONE; EMERGING CLINICAL-APPLICATIONS; ISOLATED RAT ADIPOCYTES; DEFICIENT OB/OB MICE; BLOOD-BRAIN-BARRIER AB Mantzoros CS, Magkos F, Brinkoetter M, Sienkiewicz E, Dardeno TA, Kim SY, Hamnvik OP, Koniaris A. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301: E567-E584, 2011. First published July 26, 2011; doi: 10.1152/ajpendo.00315.2011.-Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics. C1 [Mantzoros, Christos S.; Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A.; Kim, Sang-Yong; Koniaris, Anastasia] Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Mantzoros, Christos S.; Hamnvik, Ole-Petter R.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Hamnvik, Ole-Petter R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Kim, Sang-Yong] Chosun Univ, Div Endocrinol, Kwangju, South Korea. [Magkos, Faidon] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. RP Mantzoros, CS (reprint author), Harvard Univ, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Sch Med, FD 875 330 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-58785, DK-079929, DK-081913]; VA Merit Review Award FX The Mantzoros group is supported by Grants DK-58785, DK-079929, and DK-081913 from the National Institute of Diabetes and Digestive and Kidney Diseases and a VA Merit Review Award. NR 289 TC 157 Z9 161 U1 5 U2 61 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2011 VL 301 IS 4 BP E567 EP E584 DI 10.1152/ajpendo.00315.2011 PG 18 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 829JU UT WOS:000295576300001 PM 21791620 ER PT J AU Irita, J Okura, T Jotoku, M Nagao, T Enomoto, D Kurata, M Desilva, VR Miyoshi, K Matsui, Y Uede, T Denhardt, DT Rittiling, SR Higaki, J AF Irita, Jun Okura, Takafumi Jotoku, Masanori Nagao, Tomoaki Enomoto, Daijiro Kurata, Mie Desilva, Veena Rasika Miyoshi, Ken-ichi Matsui, Yutaka Uede, Toshimitsu Denhardt, David T. Rittiling, Susan R. Higaki, Jitsuo TI Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE inflammation; eplerenone; macrophage; fibroblast; epithelial-mesenchymal transition; podocyte injury ID MICE LACKING OSTEOPONTIN; SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; RENAL INJURY; TRANSCRIPTIONAL REGULATION; CAROTID ATHEROSCLEROSIS; MACROPHAGE INFILTRATION; ESSENTIAL-HYPERTENSION; CARDIAC-HYPERTROPHY; MESANGIAL CELLS AB Irita J, Okura T, Jotoku M, Nagao T, Enomoto D, Kurata M, Desilva VR, Miyoshi K, Matsui Y, Uede T, Denhardt DT, Rittiling SR, Higaki J. Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney. Am J Physiol Renal Physiol 301: F833-F844, 2011. First published July 6, 2011; doi:10.1152/ajprenal.00557.2010.-Osteopontin (OPN) has been implicated in the pathology of several renal conditions. Recently, we demonstrated in vitro that aldosterone has important roles in collagen synthesis by inducing OPN (Irita J, Okura T, Kurata M, Miyoshi K, Fukuoka T, Higaki J. Hypertension 51: 507-513, 2008). The aim of the present study was to clarify the roles of OPN in aldosterone-mediated renal fibrosis by infusing aldosterone into either wild-type (WT) or OPN knockout mice (OPN(-/-)). We used uninephrectomized mice treated with aldosterone and high salt to exacerbate renal fibrosis. After 4 wk of treatment with aldosterone, we showed similar increases in systolic blood pressure in both strains of mice. Urine albumin excretion was greater in aldosterone-infused WT mice than in aldosterone-infused OPN(-/-) mice. Immunohistochemical analysis showed high levels of OPN expression in aldosterone-infused WT mice. Interstitial fibrosis and inflammatory infiltrations were increased in aldosterone-infused WT mice compared with either vehicle-infused WT or aldosterone-infused OPN(-/-) mice. These changes were ameliorated markedly by eplerenone treatment in aldosterone-infused WT mice. Aldosterone-infused WT mice also had increased expression of NADPH oxidase subunits compared with aldosterone-infused OPN(-/-) mice. We observed a marked increase in oxidative stress markers in aldosterone-infused WT mice compared with aldosterone-infused OPN(-/-) mice. These results indicate that OPN is a promoter of aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney and suggest that inhibition of OPN may be a potential therapeutic target for prevention of renal injury. C1 [Irita, Jun; Okura, Takafumi; Jotoku, Masanori; Nagao, Tomoaki; Enomoto, Daijiro; Kurata, Mie; Desilva, Veena Rasika; Miyoshi, Ken-ichi; Higaki, Jitsuo] Ehime Univ, Grad Sch Med, Dept Integrated Med & Informat, Toon, Ehime, Japan. [Matsui, Yutaka] Hokkaido Univ, Inst Med Genet, Dept Matrix Med, Sapporo, Hokkaido, Japan. [Uede, Toshimitsu] Hokkaido Univ, Inst Med Genet, Div Mol Immunol, Sapporo, Hokkaido, Japan. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. [Rittiling, Susan R.] Forsyth Inst, Boston, MA USA. RP Okura, T (reprint author), Ehime Univ, Grad Sch Med, Dept Integrated Med & Informat, Toon, Ehime, Japan. EM okura@m.ehime-u.ac.jp RI uede, toshimitsu/A-4273-2012 FU Japan Society for the Promotion of Science [20790595, 22590912] FX This work was supported by a Grant-in-Aid for Young Scientists (B) awarded to J. Irita by the Japan Society for the Promotion of Science (20790595) and by a Grant-in-Aid Scientific Research (C) awarded to T. Okura by the Japan Society for the Promotion of Science (22590912). NR 41 TC 22 Z9 22 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2011 VL 301 IS 4 BP F833 EP F844 DI 10.1152/ajprenal.00557.2010 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 826RB UT WOS:000295370500018 PM 21734100 ER PT J AU Lieu, TA Au, D Krishnan, JA Moss, M Selker, H Harabin, A Taggart, V Connors, A AF Lieu, Tracy A. Au, David Krishnan, Jerry A. Moss, Marc Selker, Harry Harabin, Andrea Taggart, Virginia Connors, Alfred CA Comparative Effectiveness Res Lung TI Comparative Effectiveness Research in Lung Diseases and Sleep Disorders Recommendations from the National Heart, Lung, and Blood Institute Workshop SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE randomized controlled trials; observational studies; implementation; study designs; methodology ID UNITED-STATES; TIME-SERIES; CARE; SAFETY; NETWORK; ASTHMA; TRIAL AB The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. C1 [Harabin, Andrea; Taggart, Virginia] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Connors, Alfred] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Au, David] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Au, David] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Au, David] Dept Vet Affairs, Seattle, WA USA. [Krishnan, Jerry A.] Univ Chicago, Dept Med, Asthma & COPD Ctr, Chicago, IL 60637 USA. [Krishnan, Jerry A.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Moss, Marc] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Selker, Harry] Tufts Univ, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Clin & Translat Sci Inst, Boston, MA 02111 USA. RP Taggart, V (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM taggartv@nih.gov FU Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health; HSR&D, VA Puget Sound Health Care System FX Supported by the Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health.; D.A. was funded by HSR&D, VA Puget Sound Health Care System. The views expressed in this manuscript are those of the authors and do not necessarily represent the opinions of the Department of Veterans Affairs. NR 42 TC 23 Z9 24 U1 1 U2 4 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 OCT 1 PY 2011 VL 184 IS 7 BP 848 EP 856 DI 10.1164/rccm.201104-0634WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 827DM UT WOS:000295407300020 PM 21965016 ER PT J AU Kumar, D Blumberg, EA Danziger-Isakov, L Kotton, CN Halasa, NB Ison, MG Avery, RK Green, M Allen, UD Edwards, KM Miller, G Michaels, MG AF Kumar, D. Blumberg, E. A. Danziger-Isakov, L. Kotton, C. N. Halasa, N. B. Ison, M. G. Avery, R. K. Green, M. Allen, U. D. Edwards, K. M. Miller, G. Michaels, M. G. CA AST Infect Dis Community Practice TI Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE Consensus; immunogenicity; respiratory virus ID BRONCHIOLITIS OBLITERANS SYNDROME; RESPIRATORY VIRAL-INFECTIONS; HUMORAL IMMUNE-RESPONSE; LIVER-TRANSPLANT; ANTIBODY-RESPONSE; VIRUS-INFECTIONS; IMMUNIZATION; IMMUNOGENICITY; AZATHIOPRINE; SAFETY AB Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients. C1 [Kumar, D.] Univ Alberta, Edmonton, AB, Canada. [Blumberg, E. A.] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Danziger-Isakov, L.] Cleveland Clin, Inst Pediat, Cleveland, OH 44106 USA. [Kotton, C. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, G.] Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. [Ison, M. G.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Ison, M. G.] Northwestern Univ, Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA. [Avery, R. K.] Cleveland Clin, Inst Med, Dept Infect Dis, Cleveland, OH 44106 USA. [Green, M.; Michaels, M. G.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Allen, U. D.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Kumar, D (reprint author), Univ Alberta, Edmonton, AB, Canada. EM deepali.kumar@ualberta.ca NR 72 TC 60 Z9 60 U1 2 U2 5 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 OCT PY 2011 VL 11 IS 10 BP 2020 EP 2030 DI 10.1111/j.1600-6143.2011.03753.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 826SO UT WOS:000295375000008 PM 21957936 ER PT J AU Czuczman, AD Thomas, LE Boulanger, AB Brown, DF Marill, KA AF Czuczman, A. D. Thomas, L. E. Boulanger, A. B. Brown, D. F. Marill, K. A. TI Interpreting Red Blood Cells in Lumbar Puncture: Distinguishing True Subarachnoid Hemorrhage From Traumatic Tap SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 [Czuczman, A. D.; Thomas, L. E.; Boulanger, A. B.; Brown, D. F.; Marill, K. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S314 EP S315 PG 2 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300399 ER PT J AU Dutta, S Long, W Reisner, AT AF Dutta, S. Long, W. Reisner, A. T. TI An Electronic Tool for Improved Communication of Radiographic Incidental Findings to Discharged Emergency Department Patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S309 EP S310 PG 2 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300385 ER PT J AU Hasegawa, K Hagiwara, Y Chiba, T Watase, H Brown, CA Walls, RM Brown, DF AF Hasegawa, K. Hagiwara, Y. Chiba, T. Watase, H. Brown, I. I. I. C. A. Walls, R. M. Brown, D. F. TI Emergency Airway Management in Japan: Interim Analysis of a Multi-Center Prospective Observational Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Kawaguchi Municipal Med Ctr, Kawaguchi, Saitama, Japan. Obama Municipal Hosp, Obama, Fukui, Japan. Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S306 EP S306 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300378 ER PT J AU Horton, C Capp, R Odewole, M Marill, K AF Horton, C. Capp, R. Odewole, M. Marill, K. TI Are Patients Admitted to the Hospital From the Emergency Department With Sepsis Due to Health Care-Associated Infections More Likely to Have Severe Sepsis or Septic Shock in the Initial 4 Hours of Emergency Department Arrival? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Harvard Affiliated Emergency Med Residency Brigh, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S291 EP S291 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300335 ER PT J AU Hsia, RY Asch, SM Weiss, RE Zingmond, D Liang, L Han, W McCreath, H Sun, BC AF Hsia, R. Y. Asch, S. M. Weiss, R. E. Zingmond, D. Liang, L. Han, W. McCreath, H. Sun, B. C. TI Is Ambulance Diversion Associated With Increased Mortality for Emergency Department Patients Who Are Admitted? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S181 EP S181 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300012 ER PT J AU Jesus, JE Allen, MB Donnino, MW Grossman, SA Hale, CC Breu, AC Bracey, A O'Connor, JL Fisher, J AF Jesus, J. E. Allen, M. B. Donnino, M. W. Grossman, S. A. Hale, C. C. Breu, A. C. Bracey, A. O'Connor, J. L. Fisher, J. TI Code Status During Medical Emergencies: Are We Getting It Wrong? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 [Jesus, J. E.; Allen, M. B.; Donnino, M. W.; Grossman, S. A.; Hale, C. C.; Breu, A. C.; Bracey, A.; O'Connor, J. L.; Fisher, J.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S264 EP S265 PG 2 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300259 ER PT J AU Peacock, W Diercks, D Hollander, J Singer, A Birkhahn, R Shapiro, N Arnold, W Noland, B Nagumey, J AF Peacock, W. Diercks, D. Hollander, J. Singer, A. Birkhahn, R. Shapiro, N. Arnold, W. Noland, B. Nagumey, J. TI Can Point of Care Be as Good as the Central Lab? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Penn, Philadelphia, PA 19104 USA. Stony Brook Univ & Med Ctr, Stony Brook, NY USA. New York Methodist Hosp, Brooklyn, NY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Alere Inc, Waltham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Shapiro, Nathan/F-1718-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S239 EP S239 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300184 ER PT J AU Penn, J Borczuk, P Peak, D AF Penn, J. Borczuk, P. Peak, D. TI Identification of Patients With Traumatic Intracranial Hemorrhage Who Are at Low Risk for Deterioration or Neurosurgical Intervention SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S287 EP S287 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300324 ER PT J AU Siegelman, JN Marill, KA Adler, JN AF Siegelman, J. N. Marill, K. A. Adler, J. N. TI Tachydysrhythmia Treatment and Adverse Events in Patients With Wolff-Parkinson-White Syndrome SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 [Siegelman, J. N.; Marill, K. A.; Adler, J. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S236 EP S237 PG 2 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300177 ER PT J AU Wen, LS Geduld, HI Nagumey, JT Wallis, LA AF Wen, L. S. Geduld, H., I Nagumey, J. T. Wallis, L. A. TI Perceptions of Graduates From Africa's First Emergency Medicine Training Program at the University of Cape Town/Stellenbosch University SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 Brigham & Womens & Massachusetts Gen Hosp, Boston, MA USA. Univ Stellenbosch, Univ Cape Town, Cape Town, South Africa. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S193 EP S193 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300047 ER PT J AU White, BA Biddinger, PD Yuchiao, C Greene, B Carignan, S Brown, DF AF White, B. A. Biddinger, P. D. Yuchiao, C. Greene, B. Carignan, S. Brown, D. F. TI Boarding Inpatients in the Emergency Department Increases Discharged Patient Length of Stay SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Annual Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2011 CL San Francisco, CA SP Amer Coll Emergency Phys C1 [White, B. A.; Biddinger, P. D.; Yuchiao, C.; Greene, B.; Carignan, S.; Brown, D. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2011 VL 58 IS 4 SU S BP S187 EP S187 PG 1 WC Emergency Medicine SC Emergency Medicine GA 827ID UT WOS:000295421300030 ER PT J AU Sugarman, J Taylor, H Jaff, MR Sullivan, TM AF Sugarman, Jeremy Taylor, Holly Jaff, Michael R. Sullivan, Timothy M. TI Live Case Demonstrations: Attitudes and Ethical Implications for Practice SO ANNALS OF VASCULAR SURGERY LA English DT Article ID TRANSMISSIONS AB Background: Live case demonstrations (LCDs) are now prevalent in medical education courses despite ethical concerns including that they may expose patients to undue risk. However, there are limited data regarding many aspects of LCDs to help inform policies and guidelines regarding them. Methods: We conducted an Internet-based survey of clinicians who have served as faculty or attended the 2009 and 2010 professional meetings sponsored by VIVA (Vascular Interventional Advances). Results: There were 106 VIVA 2009 respondents and 165 VIVA 2010 respondents. Observing an LCD was more valuable than watching a prerecorded video for most (70% in 2009; 82% in 2010) respondents. About one-third of respondents thought that LCD patients are exposed to more risk than non-LCD patients. Respondents who had been operators were more likely to agree that LCD patients are exposed to more risk (p = 0.001 in 2009; p = 0.022 in 2010). Approximately one-third of respondents in 2009 and one-half in 2010 thought that patients experience direct medical benefit in an LCD. The majority (71% in 2009; 76% in 2010) indicated that they would support the decision of a family member or friend to be an LCD patient, few (44% in 2009; 58% in 2010) indicated that they personally would agree to be an LCD patient. Conclusions: This survey provides new insights into the value and risk of LCDs. Obtaining the perspective of patients would be extremely valuable in helping to ensure that the ethical aspects of LCDs are addressed properly and thoroughly. C1 [Sugarman, Jeremy; Taylor, Holly] Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD 21205 USA. [Sugarman, Jeremy] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Sugarman, Jeremy; Taylor, Holly] Johns Hopkins Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Dept Med, Boston, MA 02114 USA. [Jaff, Michael R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sullivan, Timothy M.] Abbott NW Hosp, Minneapolis Heart Inst, Minneapolis, MN 55407 USA. RP Sugarman, J (reprint author), Johns Hopkins Univ, Johns Hopkins Berman Inst Bioeth, 1809 Ashland Ave,Room 203, Baltimore, MD 21205 USA. EM jsugarman@jhu.edu FU VIVA Physicians FX VIVA Physicians, a not-for-profit 501 (c) (3) organization, provided funding for this project. NR 11 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD OCT PY 2011 VL 25 IS 7 BP 867 EP 872 DI 10.1016/j.avsg.2011.03.014 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 825TN UT WOS:000295305100001 PM 21680147 ER PT J AU Ruggiero, NJ Jaff, MR AF Ruggiero, Nicholas J., II Jaff, Michael R. TI The Current Management of Aortic, Common Iliac, and External Iliac Artery Disease: Basic Data Underlying Clinical Decision Making SO ANNALS OF VASCULAR SURGERY LA English DT Article ID AORTOILIAC OCCLUSIVE DISEASE; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; TERM-FOLLOW-UP; ENDOVASCULAR ANEURYSM REPAIR; LOWER-EXTREMITY ISCHEMIA; KISSING STENTS TECHNIQUE; POOR DISTAL RUNOFF; HIGH-RISK PATIENTS; END-TO-SIDE; AXILLOFEMORAL BYPASS AB The management of aortoiliac occlusive disease is a rapidly evolving field in vascular medicine and surgery. There are multiple approaches that must be considered, ranging from medical management to endovascular and open surgical procedures. The introduction of percutaneous endovascular techniques has significantly changed the landscape of the field forever. We will compare and contrast different treatment strategies and critically review the available literature to allow for evidence-based clinical decisions to be made about the surgical and endovascular management of aortoiliac occlusive disease. C1 [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA 02114 USA. [Ruggiero, Nicholas J., II] Thomas Jefferson Univ, Jefferson Med Coll, Div Cardiol, Philadelphia, PA 19107 USA. RP Jaff, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM mjaff@partners.org NR 159 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD OCT PY 2011 VL 25 IS 7 BP 990 EP 1003 DI 10.1016/j.avsg.2011.05.003 PG 14 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 825TN UT WOS:000295305100018 PM 21784611 ER PT J AU Singh, JA Houston, TK Ponce, BA Maddox, G Bishop, MJ Richman, J Campagna, EJ Henderson, WG Hawn, MT AF Singh, Jasvinder A. Houston, Thomas K. Ponce, Brent A. Maddox, Grady Bishop, Michael J. Richman, Joshua Campagna, Elizabeth J. Henderson, William G. Hawn, Mary T. TI Smoking As a Risk Factor for Short-Term Outcomes Following Primary Total Hip and Total Knee Replacement in Veterans SO ARTHRITIS CARE & RESEARCH LA English DT Article ID POSTOPERATIVE PULMONARY COMPLICATIONS; QUALITY IMPROVEMENT PROGRAM; SURGEON PROCEDURE VOLUME; BODY-MASS INDEX; CIGARETTE-SMOKE; UNITED-STATES; GENERAL-ANESTHESIA; ABDOMINAL-SURGERY; WOUND-INFECTION; SURGICAL CARE AB Objective. To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR). Methods. We used data from the national Veterans Affairs Surgical Quality Improvement Program to examine the association of smoking status at surgery with 30-day postoperative complication rates (including surgical site and other infections, pneumonia, stroke, myocardial infarction, mortality, and other complications) in veterans undergoing primary elective THR or TKR. Multilevel multivariable-adjusted logistic regression models, adjusted for age, race/ethnicity, work relative value units, American Society of Anesthesiology classification, and year of surgery, with additional adjustment for wound classification for surgical site infections, were used. Results. A total of 33,336 patients, 95% men and 80% white with a mean age of 64 years, underwent elective primary THR/TKR between October 2001 and September 2008. Fifty-seven percent never smoked, 19% were prior smokers, and 24% were current smokers. Current smokers undergoing THR/TKR were significantly more likely than never smokers to have surgical site infections (odds ratio [OR] 1.41, 95% CI 1.16-1.72), pneumonia (OR 1.53, 95% CI 1.10-2.14), stroke (OR 2.61, 95% CI 1.26-5.41), and 1-year mortality (OR 1.63, 95% CI 1.31-2.02). Prior smokers were significantly more likely than nonsmokers to have pneumonia, (OR 1.34, 95% CI 1.00-1.80), stroke (OR 2.14, 95% CI 1.12-4.10), and urinary tract infection (OR 1.26, 95% CI 1.02-1.55). Conclusion. Current smoking at the time of elective THR or TKR is associated with increased postarthroplasty complications, especially surgical site infections and pneumonia. Preoperative smoking cessation programs should be considered in patients undergoing elective THR or TKR. C1 [Singh, Jasvinder A.; Ponce, Brent A.; Maddox, Grady; Richman, Joshua; Hawn, Mary T.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ponce, Brent A.; Maddox, Grady; Richman, Joshua; Hawn, Mary T.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Rochester, MN USA. [Houston, Thomas K.] Bedford VA Med Ctr, Bedford, MA USA. [Bishop, Michael J.] VA Cent Off, Washington, DC USA. [Bishop, Michael J.] VA Puget Sound, Seattle, WA USA. [Bishop, Michael J.] Univ Washington, Sch Med, Seattle, WA USA. [Campagna, Elizabeth J.; Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Denver VA Med Ctr, Aurora, CO USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com RI Houston, Thomas/F-2469-2013; OI singh, jasvinder/0000-0003-3485-0006 FU VA [IIR IAB 06-038-2]; Allergan; Takeda; Savient; Wyeth; Amgen FX Supported by the VA (grant IIR IAB 06-038-2) and the use and resources of facilities at the Department of VA Medical Centers at Bedford, Massachusetts, Birmingham, Alabama, and Puget Sound, Washington.; Mr. Singh has received consultant fees, speaking fees, and/or honoraria (less than $ 10,000 each) from Savient, Novartis, Takeda, URL Pharmaceuticals, and Abbott, and has received research and travel grants from Allergan, Takeda, Savient, Wyeth, and Amgen. Dr. Ponce has received consultant fees, speaking fees, and/or honoraria (less than $ 10,000) from Arinex and (more than $ 10,000) from Tornier. NR 54 TC 29 Z9 29 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2011 VL 63 IS 10 BP 1365 EP 1374 DI 10.1002/acr.20555 PG 10 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200002 PM 21770042 ER PT J AU Stefanik, JJ Guermazi, A Zhu, YY Zumwalt, AC Gross, KD Clancy, M Lynch, JA Segal, NA Lewis, CE Roemer, FW Powers, CM Felson, DT AF Stefanik, Joshua J. Guermazi, Ali Zhu, Yanyan Zumwalt, Ann C. Gross, K. Douglas Clancy, Margaret Lynch, John A. Segal, Neil A. Lewis, Cora E. Roemer, Frank W. Powers, Christopher M. Felson, David T. TI Quadriceps Weakness, Patella Alta, and Structural Features of Patellofemoral Osteoarthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID KNEE OSTEOARTHRITIS; WEIGHT-BEARING; JOINT SPACE; PAIN; ASSOCIATION; STRENGTH; KINEMATICS; COHORT; RISK AB Objective. To determine the relationship between quadriceps weakness and cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and if this relationship is modified by patella alta. Methods. The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk of knee osteoarthritis. Concentric knee extensor strength was measured using an isokinetic dynamometer. Patella alta was measured using the Insall-Salvati ratio (ISR) on the lateral radiograph, and cartilage damage and BMLs were graded on magnetic resonance imaging in the PFJ. We determined the association between quadriceps weakness with cartilage damage and BMLs in the PFJ among knees with (ISR >= 1.2) and without (ISR < 1.2) patella alta using multiple binomial regression. Results. A total of 807 knees were studied (mean age 62 years, body mass index 30 kg/m(2), ISR 1.10) and 64% were from women. Compared with the knees in the highest strength tertile, those in the lowest had 10.2% (95% confidence interval [95% CI] 3, 18), 9.1% (95% CI 2, 16), and 7.1% (95% CI 1, 13) higher prevalence of lateral PFJ cartilage damage, medial PFJ cartilage damage, and lateral PFJ BMLs, respectively. The association between quadriceps weakness with cartilage damage and BMLs was not different between knees with and without patella alta in the lateral PFJ. Conclusion. Quadriceps weakness was associated with PFJ cartilage damage and BMLs. While both patella alta and quadriceps weakness were associated with PFJ damage, the combination of the two was not associated with more damage than either of these factors alone. C1 [Stefanik, Joshua J.; Guermazi, Ali; Zhu, Yanyan; Zumwalt, Ann C.; Gross, K. Douglas; Clancy, Margaret; Roemer, Frank W.; Felson, David T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gross, K. Douglas] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Lynch, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Segal, Neil A.] Univ Iowa, Iowa City, IA USA. [Lewis, Cora E.] Univ Alabama, Birmingham, AL USA. [Roemer, Frank W.] Klinikum Augsburg, Augsburg, Germany. [Powers, Christopher M.] Univ So Calif, Los Angeles, CA USA. RP Stefanik, JJ (reprint author), Boston Univ, Sch Med, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM stefanik@bu.edu RI Lynch, John/F-8209-2012; Powers, Christopher/J-2662-2014; OI Felson, David/0000-0002-2668-2447 FU NIH [U01-AG18820, U01-AG18832, U01-AG18947, U01-AG19069, AR-47785, T32AR007598]; Arthritis Foundation; Facet Solutions; Genzyme; Merck Serono; Novartis; Stryker; GE Healthcare FX The Multicenter Osteoarthritis Study is supported by the NIH (grants U01-AG18820, U01-AG18832, U01-AG18947, U01-AG19069, and AR-47785). Dr. Stefanik's work was supported by a doctoral dissertation award from the Arthritis Foundation and the NIH (T32AR007598).; Dr. Guermazi has received consultancies, speaking fees, and/or honoraria (less than $10,000 each) from Facet Solutions, Genzyme, and Merck Serono and (more than $10,000 each) from Novartis and Stryker. Dr. Guermazi is a shareholder and President of Boston Imaging Core Labs and has received a grant from GE Healthcare. Dr. Roemer is a shareholder and Vice President of Boston Imaging Core Labs. NR 22 TC 26 Z9 28 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2011 VL 63 IS 10 BP 1391 EP 1397 DI 10.1002/acr.20528 PG 7 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200005 PM 21702087 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Association of Peptic Ulcer Disease and Pulmonary Disease With Risk of Periprosthetic Fracture After Primary Total Knee Arthroplasty SO ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; SUPRACONDYLAR FRACTURES; FEMORAL FRACTURES; FEMUR; MORTALITY; REPLACEMENT; MORBIDITY AB Objective. To assess the association of specific comorbidities with periprosthetic fractures after primary total knee replacement (TKR). Methods. We used the prospectively collected data in the Mayo Clinic total joint registry from 1989-2008 on all patients who had undergone primary TKR. The outcome of interest was postoperative periprosthetic fractures during followup. The main predictors of interest were comorbidities grouped from the validated Deyo-Charlson index. Multivariable-adjusted Cox regression analyses were adjusted for sex, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, operative diagnosis, and implant fixation. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. Results. We included 17,633 primary TKRs with a mean followup of 6.3 years. The mean age was 68 years, 55% were women, and the mean BMI was 31 kg/m(2). There were 188 postoperative periprosthetic fractures on postoperative day 1 or later; 162 fractures (86%) occurred on postoperative day 90 or later. In multivariable analyses that simultaneously adjusted for all comorbidities and other variables (age, sex, BMI, ASA, operative diagnosis, and cement status), the following 2 conditions were significantly associated with an increased hazard of postoperative periprosthetic fractures: peptic ulcer disease (HR 1.87, 95% CI 1.28-2.75; P = 0.0014) and chronic obstructive pulmonary disease (HR 1.62, 95% CI 1.10-2.40; P = 0.02). Conclusion. Peptic ulcer disease and chronic obstructive pulmonary disease are associated with a higher risk of periprosthetic fractures after primary TKR. This may be related to the disease or its treatments, which need further study. Identification of specific risk factors may allow for implementation of intervention strategies to reduce this risk. C1 [Singh, Jasvinder A.] Univ Alabama, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU NIH [1-KL2-RR024151-01]; Abbott; Novartis; Savient; Takeda; URL Pharmaceuticals; Amgen; Wyeth; Zimmer; DePuy; Stryker; Osteotech FX Supported by an NIH Clinical Translational Science Award (grant 1-KL2-RR024151-01, Mayo Clinic Center for Clinical and Translational Research).; Dr. Singh has received consultant fees and/or honoraria (less than $10,000 each) from Abbott, Novartis, Savient, Takeda, and URL Pharmaceuticals, and has received research and travel grants from Amgen, Savient, Takeda, and Wyeth. Dr. Lewallen has received consultant fees and/or speaking fees (less than $10,000) from Zimmer; has received institutional research funds from DePuy, Stryker, and Zimmer; and has received royalties from Osteotech and Zimmer. NR 29 TC 6 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2011 VL 63 IS 10 BP 1471 EP 1476 DI 10.1002/acr.20548 PG 6 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200015 PM 21748860 ER PT J AU Sathirapongsasuti, JF Lee, H Horst, BAJ Brunner, G Cochran, AJ Binder, S Quackenbush, J Nelson, SF AF Sathirapongsasuti, Jarupon Fah Lee, Hane Horst, Basil A. J. Brunner, Georg Cochran, Alistair J. Binder, Scott Quackenbush, John Nelson, Stanley F. TI Exome sequencing-based copy-number variation and loss of heterozygosity detection: ExomeCNV SO BIOINFORMATICS LA English DT Article ID CIRCULAR BINARY SEGMENTATION; GENOME-WIDE ASSOCIATION; FREQUENCY-DISTRIBUTION; GENE; CAPTURE; POPULATION; ENRICHMENT; MUTATIONS; VARIABLES; QUOTIENT AB Motivation: The ability to detect copy-number variation (CNV) and loss of heterozygosity (LOH) from exome sequencing data extends the utility of this powerful approach that has mainly been used for point or small insertion/deletion detection. Results: We present ExomeCNV, a statistical method to detect CNV and LOH using depth-of-coverage and B-allele frequencies, from mapped short sequence reads, and we assess both the method's power and the effects of confounding variables. We apply our method to a cancer exome resequencing dataset. As expected, accuracy and resolution are dependent on depth-of-coverage and capture probe design. C1 [Sathirapongsasuti, Jarupon Fah; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sathirapongsasuti, Jarupon Fah; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sathirapongsasuti, Jarupon Fah; Lee, Hane; Nelson, Stanley F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Lee, Hane; Horst, Basil A. J.; Cochran, Alistair J.; Binder, Scott; Nelson, Stanley F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Horst, Basil A. J.] Columbia Univ, Med Ctr, Dept Dermatol, New York, NY 10032 USA. [Horst, Basil A. J.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Brunner, Georg] Skin Canc Ctr Hornheide, Dept Canc Res, Munster, Germany. RP Sathirapongsasuti, JF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RI Nelson, Stanley/D-4771-2009 FU National Heart, Lung, Blood Institute of the US National Institutes of Health [1RC2 HL101715]; National Institute for Mental Health [R01 MH071852]; National Institute of Arthritis, Musculoskeletal and Skin Disorders [P30 AR057230]; National Cancer Institute [P30 CA16042] FX Funding: National Heart, Lung, Blood Institute of the US National Institutes of Health grant (1RC2 HL101715, to J.Q.); National Institute for Mental Health (R01 MH071852); National Institute of Arthritis, Musculoskeletal and Skin Disorders (P30 AR057230); National Cancer Institute (P30 CA16042). NR 34 TC 165 Z9 167 U1 4 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2011 VL 27 IS 19 BP 2648 EP 2654 DI 10.1093/bioinformatics/btr462 PG 7 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 827FC UT WOS:000295412200005 PM 21828086 ER PT J AU Rossin, E Lin, TI Ho, HJ Mentzer, SJ Pyne, S AF Rossin, Elizabeth Lin, Tsung-I Ho, Hsiu J. Mentzer, Steven J. Pyne, Saumyadipta TI A framework for analytical characterization of monoclonal antibodies based on reactivity profiles in different tissues SO BIOINFORMATICS LA English DT Article ID FLOW-CYTOMETRIC DATA; SKEW T-DISTRIBUTION; DISTRIBUTIONS; ANTIGENS; CLUSTERS; MODELS AB Motivation: Monoclonal antibodies (mAbs) are among the most powerful and important tools in biology and medicine. MAb development is of great significance to many research and clinical applications. Therefore, objective mAb classification is essential for categorizing and comparing mAb panels based on their reactivity patterns in different cellular species. However, typical flow cytometric mAb profiles present unique modeling challenges with their non-Gaussian features and intersample variations. It makes accurate mAb classification difficult to do with the currently used kernel-based or hierarchical clustering techniques. Results: To address these challenges, in the present study we developed a formal two-step framework called mAbprofiler for systematic, parametric characterization of mAb profiles. Further, we measured the reactivity of hundreds of new antibodies in diverse tissues using flow cytometry, which we successfully classified using mAbprofiler. First, mAbprofiler fits a mAb's flow cytometric histogram with a finite mixture model of skew t distributions that is robust against non-Gaussian features, and constructs a precise, smooth and mathematically rigorous profile. Then it performs novel curve clustering of the fitted mAb profiles using a skew t mixture of non-linear regression model that can handle intersample variation. Thus, mAbprofiler provides a new framework for identifying robust mAb classes, all well defined by distinct parametric templates, which can be used for classifying new mAb samples. We validated our classification results both computationally and empirically using mAb profiles of known classification. C1 [Rossin, Elizabeth; Pyne, Saumyadipta] MIT, Broad Inst, Cambridge, MA 02142 USA. [Rossin, Elizabeth; Pyne, Saumyadipta] Harvard Univ, Cambridge, MA 02142 USA. [Pyne, Saumyadipta] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rossin, Elizabeth; Pyne, Saumyadipta] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lin, Tsung-I] Natl Chung Hsing Univ, Inst Stat, Taichung 40227, Taiwan. [Lin, Tsung-I] Natl Chung Hsing Univ, Dept Appl Math, Taichung 40227, Taiwan. [Ho, Hsiu J.] Tunghai Univ, Dept Stat, Taichung 40704, Taiwan. [Lin, Tsung-I] China Med Univ, Dept Publ Hlth, Taichung, Taiwan. [Mentzer, Steven J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Adapt & Regenerat Biol, Boston, MA 02115 USA. RP Pyne, S (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. FU National Science Council of Taiwan [NSC99-2118-M-005-001-MY2] FX Funding: TL thanks the National Science Council of Taiwan (NSC99-2118-M-005-001-MY2) for financial support. NR 37 TC 7 Z9 7 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2011 VL 27 IS 19 BP 2746 EP 2753 DI 10.1093/bioinformatics/btr468 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 827FC UT WOS:000295412200018 PM 21846734 ER PT J AU Bitler, BG Nicodemus, JP Li, H Cai, Q Wu, H Hua, X Li, TY Birrer, MJ Godwin, AK Cairns, P Zhang, RG AF Bitler, Benjamin G. Nicodemus, Jasmine P. Li, Hua Cai, Qi Wu, Hong Hua, Xiang Li, Tianyu Birrer, Michael J. Godwin, Andrew K. Cairns, Paul Zhang, Rugang TI Wnt5a Suppresses Epithelial Ovarian Cancer by Promoting Cellular Senescence SO CANCER RESEARCH LA English DT Article ID BETA-CATENIN; HETEROCHROMATIN FOCI; IN-VIVO; PREMATURE SENESCENCE; ONCOGENIC RAS; TARGET GENES; HUMAN-CELLS; TUMOR; P53; PML AB Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. Thus, there is an urgent need to develop novel therapeutics for this disease. Cellular senescence is an important tumor suppression mechanism that has recently been suggested as a novel mechanism to target for developing cancer therapeutics. Wnt5a is a noncanonical Wnt ligand that plays a context-dependent role in human cancers. Here, we investigate the role of Wnt5a in regulating senescence of EOC cells. We show that Wnt5a is expressed at significantly lower levels in human EOC cell lines and in primary human EOCs (n = 130) compared with either normal ovarian surface epithelium (n = 31; P = 0.039) or fallopian tube epithelium (n = 28; P < 0.001). Notably, a lower level of Wnt5a expression correlates with tumor stage (P = 0.003) and predicts shorter overall survival in EOC patients (P = 0.003). Significantly, restoration of Wnt5a expression inhibits the proliferation of human EOC cells both in vitro and in vivo in an orthotopic EOC mouse model. Mechanistically, Wnt5a antagonizes canonical Wnt/beta-catenin signaling and induces cellular senescence by activating the histone repressor A/promyelocytic leukemia senescence pathway. In summary, we show that loss of Wnt5a predicts poor outcome in EOC patients and Wnt5a suppresses the growth of EOC cells by triggering cellular senescence. We suggest that strategies to drive senescence in EOC cells by reconstituting Wnt5a signaling may offer an effective new strategy for EOC therapy. Cancer Res; 71(19); 6184-94. (C)2011 AACR. C1 [Bitler, Benjamin G.; Nicodemus, Jasmine P.; Li, Hua; Zhang, Rugang] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Cai, Qi] Fox Chase Canc Ctr, Biosample Repository Facil, Philadelphia, PA 19111 USA. [Wu, Hong] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Hua, Xiang] Fox Chase Canc Ctr, Transgen Facil, Philadelphia, PA 19111 USA. [Li, Tianyu] Fox Chase Canc Ctr, Dept Bioinformat & Biostat, Philadelphia, PA 19111 USA. [Cairns, Paul] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Zhang, RG (reprint author), Fox Chase Canc Ctr, Womens Canc Program, W446,333 Cottman Ave, Philadelphia, PA 19111 USA. EM rugang.zhang@fccc.edu FU NCI FCCC-UPenn ovarian cancer SPORE [P50 CA083638]; SPORE career development award; DOD [OC093420]; OCRF program; NCI [CA-009035-35] FX R. Zhang is an Ovarian Cancer Research Fund (OCRF) Liz Tilberis Scholar. This work was supported in part by a NCI FCCC-UPenn ovarian cancer SPORE (P50 CA083638) pilot project and SPORE career development award (to R. Zhang), a DOD ovarian cancer academy award (OC093420 to R Zhang), an OCRF program project (to R. Zhang, M.J. Birrer, and A. K. Godwin), and a generous gift from Catherine and Peter Getchell. B. G. Bitler is supported by a NCI postdoctoral training grant (CA-009035-35). NR 50 TC 37 Z9 39 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2011 VL 71 IS 19 BP 6184 EP 6194 DI 10.1158/0008-5472.CAN-11-1341 PG 11 WC Oncology SC Oncology GA 827AQ UT WOS:000295397700012 PM 21816908 ER PT J AU Stevens, KN Vachon, CM Lee, AM Slager, S Lesnick, T Olswold, C Fasching, PA Miron, P Eccles, D Carpenter, JE Godwin, AK Ambrosone, C Winqvist, R Brauch, H Schmidt, MK Cox, A Cross, SS Sawyer, E Hartmann, A Beckmann, MW Schulz-Wendtland, R Ekici, AB Tapper, WJ Gerty, SM Durcan, L Graham, N Hein, R Nickels, S Flesch-Janys, D Heinz, J Sinn, HP Konstantopoulou, I Fostira, F Pectasides, D Dimopoulos, AM Fountzilas, G Clarke, CL Balleine, R Olson, JE Fredericksen, Z Diasio, RB Pathak, H Ross, E Weaver, J Rudiger, T Forsti, A Dunnebier, T Ademuyiwa, F Kulkarni, S Pylkas, K Jukkola-Vuorinen, A Ko, YD Van Limbergen, E Janssen, H Peto, J Fletcher, O Giles, GG Baglietto, L Verhoef, S Tomlinson, I Kosma, VM Beesley, J Greco, D Blomqvist, C Irwanto, A Liu, J Blows, FM Dawson, SJ Margolin, S Mannermaa, A Martin, NG Montgomery, GW Lambrechts, D Silva, ID Severi, G Hamann, U Pharoah, P Easton, DF Chang-Claude, J Yannoukakos, D Nevanlinna, H Wang, XS Couch, FJ AF Stevens, Kristen N. Vachon, Celine M. Lee, Adam M. Slager, Susan Lesnick, Timothy Olswold, Curtis Fasching, Peter A. Miron, Penelope Eccles, Diana Carpenter, Jane E. Godwin, Andrew K. Ambrosone, Christine Winqvist, Robert Brauch, Hiltrud Schmidt, Marjanka K. Cox, Angela Cross, Simon S. Sawyer, Elinor Hartmann, Arndt Beckmann, Matthias W. Schulz-Wendtland, Ruediger Ekici, Arif B. Tapper, William J. Gerty, Susan M. Durcan, Lorraine Graham, Nikki Hein, Rebecca Nickels, Stephan Flesch-Janys, Dieter Heinz, Judith Sinn, Hans-Peter Konstantopoulou, Irene Fostira, Florentia Pectasides, Dimitrios Dimopoulos, Athanasios M. Fountzilas, George Clarke, Christine L. Balleine, Rosemary Olson, Janet E. Fredericksen, Zachary Diasio, Robert B. Pathak, Harsh Ross, Eric Weaver, JoEllen Ruediger, Thomas Forsti, Asta Duennebier, Thomas Ademuyiwa, Foluso Kulkarni, Swati Pylkaes, Katri Jukkola-Vuorinen, Arja Ko, Yon-Dschun Van Limbergen, Erik Janssen, Hilde Peto, Julian Fletcher, Olivia Giles, Graham G. Baglietto, Laura Verhoef, Senno Tomlinson, Ian Kosma, Veli-Matti Beesley, Jonathan Greco, Dario Blomqvist, Carl Irwanto, Astrid Liu, Jianjun Blows, Fiona M. Dawson, Sarah-Jane Margolin, Sara Mannermaa, Arto Martin, Nicholas G. Montgomery, Grant W. Lambrechts, Diether Silva, Isabel dos Santos Severi, Gianluca Hamann, Ute Pharoah, Paul Easton, Douglas F. Chang-Claude, Jenny Yannoukakos, Drakoulis Nevanlinna, Heli Wang, Xianshu Couch, Fergus J. CA GENICA Consortium TI Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; CONFER SUSCEPTIBILITY; RISK-FACTORS; ALLELES; POPULATION; VARIANTS; COMPLEX; CONSORTIUM; PROTEINS AB Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240-9. (C)2011 AACR. C1 [Stevens, Kristen N.; Vachon, Celine M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Lee, Adam M.; Diasio, Robert B.] Mayo Clin, Dept Pharmacol, Rochester, MN 55905 USA. [Wang, Xianshu; Couch, Fergus J.] Mayo Clin, Lab Med & Pathol, Rochester, MN 55905 USA. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Miron, Penelope] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eccles, Diana; Tapper, William J.; Gerty, Susan M.; Durcan, Lorraine; Graham, Nikki] Univ Southampton, Fac Med, Southampton Univ Hosp, NHS Trust, Southampton SO9 5NH, Hants, England. [Carpenter, Jane E.; Clarke, Christine L.] Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol, Lawrence, KS 66045 USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Lab Med, Lawrence, KS 66045 USA. [Ambrosone, Christine] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Winqvist, Robert; Ademuyiwa, Foluso] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Kulkarni, Swati] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Pylkaes, Katri] Univ Oulu, Oulu Univ Hosp, Canc Genet Lab, Dept Clin Genet & Bioctr Oulu, Oulu, Finland. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Gene Environm Interact & Breast Canc Germany GENI, D-7000 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Brauch, Hiltrud] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, Bonn, Germany. [Brauch, Hiltrud] Univ Bonn, Inst Pathol, Fac Med, D-5300 Bonn, Germany. [Brauch, Hiltrud] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany. [Brauch, Hiltrud] Deutsch Krebsforschungszentrum, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. [Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Expt Therapy & Mol Pathol, Amsterdam, Netherlands. [Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Epidemiol MKS, Amsterdam, Netherlands. [Verhoef, Senno] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin SV, Amsterdam, Netherlands. [Cox, Angela] Univ Sheffield, Fac Med Dent & Hlth, Dept Oncol, Inst Canc Studies, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Fac Med Dent & Hlth, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England. [Sawyer, Elinor] Guys & St Thomas NHS Fdn Trust, Natl Inst Hlth Res Comprehens, Biomed Res Ctr, London, England. [Peto, Julian; Silva, Isabel dos Santos] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. [Fletcher, Olivia] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Hartmann, Arndt] Univ Erlangen Nurnberg, Inst Pathol, Univ Hosp Erlangen, D-8520 Erlangen, Germany. [Schulz-Wendtland, Ruediger] Univ Erlangen Nurnberg, Inst Diagnost Radiol, Univ Hosp Erlangen, D-8520 Erlangen, Germany. [Ekici, Arif B.; Chang-Claude, Jenny] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, Germany. [Beckmann, Matthias W.] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Breast Ctr Franconia, D-8520 Erlangen, Germany. [Hein, Rebecca; Nickels, Stephan] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Sinn, Hans-Peter; Yannoukakos, Drakoulis] Univ Hosp Heidelberg, Dept Pathol, Heidelberg, Germany. [Flesch-Janys, Dieter; Heinz, Judith] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Konstantopoulou, Irene; Fostira, Florentia] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab IRRP, Athens, Greece. [Pectasides, Dimitrios] Hippokrateion Hosp, Oncol Sect, Dept Internal Med, Athens, Greece. [Dimopoulos, Athanasios M.] Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut, GR-11527 Athens, Greece. [Fountzilas, George] Aristotle Univ Thessaloniki, Dept Med Oncol, Papageorgiou Hosp, Thessaloniki, Greece. [Balleine, Rosemary] Westmead Hosp, Dept Translat Oncol, Western Sydney Local Hlth Network, Westmead, NSW 2145, Australia. [Pathak, Harsh; Weaver, JoEllen] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Ross, Eric] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany. [Forsti, Asta; Hamann, Ute] Deutsch Krebsforschungszentrum, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. [Forsti, Asta; Hamann, Ute] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. [Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, Bonn, Germany. [Van Limbergen, Erik; Janssen, Hilde] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Louvain, Belgium. [Lambrechts, Diether] Katholieke Univ Leuven, Vesalius Res Ctr, Louvain, Belgium. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia. [Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Tomlinson, Ian] Univ Oxford, Oxford Comprehens Biomed Res Ctr, Oxford, England. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Dept Pathol, Inst Clin Med, Kuopio, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Bioctr Kuopio, SF-70210 Kuopio, Finland. [Beesley, Jonathan] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, QIMR GWAS Collect, Brisbane, Qld 4006, Australia. [Greco, Dario; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00290 Helsinki, Finland. [Irwanto, Astrid; Liu, Jianjun] Genome Inst Singapore, Div Human Genet, Singapore, Singapore. [Blows, Fiona M.; Dawson, Sarah-Jane; Pharoah, Paul] Univ Cambridge, Dept Oncol, Cambridge, England. [Blows, Fiona M.; Dawson, Sarah-Jane; Pharoah, Paul] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Easton, Douglas F.] Strangeways Res Lab, Dept Genet Epidemiol, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 4RN, England. [Margolin, Sara] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. RP Vachon, CM (reprint author), Mayo Clin, Dept Hlth Sci Res, Charlton 6-239,200 1st St SW, Rochester, MN 55905 USA. EM vachon.celine@mayo.edu RI Verdrengh, Evelien/H-4571-2012; Ekici, Arif/C-3971-2013; Montgomery, Grant/B-7148-2008; OI Martin, Nicholas/0000-0003-4069-8020; Greco, Dario/0000-0001-9195-9003; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510; ADEMUYIWA, FOLUSO/0000-0002-6766-2258; Giles, Graham/0000-0003-4946-9099; Montgomery, Grant/0000-0002-4140-8139; Cross, Simon/0000-0003-2044-1754; Dawson, Sarah-Jane/0000-0002-8276-0374; Konstantopoulou, Irene/0000-0002-0470-0309 FU Deutsche Krebshilfe e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research Center (DKFZ); Federal Ministry of Education and Research (BMBF) Germany [01KH0402, 01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation of Medical Research, Stuttgart; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart; University Tubingen, Germany; Molecular Genetics of Breast Cancer; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Institute of Pathology, Medical Faculty of the University of Bonn, Germany; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany; Australian NHMRC [209057, 251553, 504711]; Breast Cancer Campaign [2004Nov49]; Yorkshire Cancer Research; Hellenic Cooperative Oncology Group [HR R_BG/04]; Greek General Secretary for Research and Technology (GSRT); European Union [LSHC-CT-2003-503297]; Dr. Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V.; Cancer Research UK [C1287/A7497, C490/A11021, C1287/A10118, C1287/A5260]; Breakthrough Breast Cancer and acknowledges NHS; "Stichting tegen Kanker" [232-2008]; Finnish Cancer Foundation; Sigrid Juselius Foundation; Academy of Finland [132473]; University of Finland; Oulu University Hospital; Helsinki University Central Hospital Research Fund; Finnish Cancer Society; SPORE [P-50CA83638, U01CA69631, 5U01CA113916]; Eileen Stein Jacoby Fund; Cancer Center Support Grant Shared Resource [P30 CA016056-32]; Deutsches Krebsforschungszentrum; National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation Trust; King's College London; King's College Hospital NHS Foundation Trust; National Health and Medical Research Council of Australia; Cancer Institute NSW; National Breast Cancer Foundation; Dutch Cancer Society [2009-4363] FX The MARIE study was supported by the Deutsche Krebshilfe e.V. grant 70-2892-BR I, the Hamburg Cancer Society, the German Cancer Research Center (DKFZ), and the DNA extraction and genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany grant 01KH0402.; The GENICA Network was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation of Medical Research, Stuttgart, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University Tubingen, Germany (H. Brauch, Christina Justenhoven); Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany (U. Hamann); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Y.-D. Ko, Christian Baisch); Institute of Pathology, Medical Faculty of the University of Bonn, Germany (Hans-Peter Fischer); and Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany (Thomas Bruning, Beate Pesch, Volker Harth, and Sylvia Rabstein).; The MCCS was supported by Australian NHMRC grants 209057, 251553, and 504711 and infrastructure provided by the Cancer Council Victoria.; The SBCS was supported by the Breast Cancer Campaign (grant 2004Nov49 to A. Cox) and by Yorkshire Cancer Research core funding.; This work was supported by the Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, funded at 75% by the European Union.; P. A. Fasching was partly funded by the Dr. Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V.; The BBC NCRN study is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre and the National Cancer Research Network (NCRN).; LMBC is supported by European Union Framework Programme 6 Project LSHC-CT-2003-503297 (the Cancerdegradome) and by the "Stichting tegen Kanker" (232-2008).; OBCS was supported by grants and other funding from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Finland, and Oulu University Hospital.; SEARCH was supported by Cancer Research UK grants C1287/A7497, C490/A11021, C1287/A10118, and C1287/A5260.; The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.; A.K. Godwin was funded by SPORE P-50CA83638, U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund.; Data and samples were obtained from the RPCI Data Bank and BioRepository (DBBR; ref. 40), a Cancer Center Support Grant Shared Resource (P30 CA016056-32).; The SKKDKFZS study was supported by the Deutsches Krebsforschungszentrum.; E. Sawyer is funded by the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.; The ABCTB is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW, and the National Breast Cancer Foundation.; M.K. Schmidt was funded by the Dutch Cancer Society grant 2009-4363. NR 40 TC 59 Z9 60 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2011 VL 71 IS 19 BP 6240 EP 6249 DI 10.1158/0008-5472.CAN-11-1266 PG 10 WC Oncology SC Oncology GA 827AQ UT WOS:000295397700017 PM 21844186 ER PT J AU Wang, M Morsbach, F Sander, D Gheorghiu, L Nanda, A Benes, C Kriegs, M Krause, M Dikomey, E Baumann, M Dahm-Daphi, J Settleman, J Willers, H AF Wang, Meng Morsbach, Fabian Sander, David Gheorghiu, Liliana Nanda, Akash Benes, Cyril Kriegs, Malte Krause, Mechthild Dikomey, Ekkehard Baumann, Michael Dahm-Daphi, Jochen Settleman, Jeffrey Willers, Henning TI EGF Receptor Inhibition Radiosensitizes NSCLC Cells by Inducing Senescence in Cells Sustaining DNA Double-Strand Breaks SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; WILD-TYPE P53; LUNG-CANCER; CELLULAR SENESCENCE; DIFFERENTIAL SENSITIVITY; IONIZING-RADIATION; ANTICANCER AGENTS; NUCLEAR IMPORT; ZD1839 IRESSA AB The mechanisms by which inhibition of the epidermal growth factor receptor (EGFR) sensitizes non-small cell lung cancer (NSCLC) cells to ionizing radiation remain poorly understood. We set out to characterize the radiosensitizing effects of the tyrosine kinase inhibitor erlotinib and the monoclonal antibody cetuximab in NSCLC cells that contain wild-type p53. Unexpectedly, EGFR inhibition led to pronounced cellular senescence but not apoptosis of irradiated cells, both in vitro and in vivo. Senescence was completely dependent on wild-type p53 and associated with a reduction in cell number as well as impaired clonogenic radiation survival. Study of ten additional NSCLC cell lines revealed that senescence is a prominent mechanism of radiosensitization in 45% of cell lines and occurs not only in cells with wild-type p53 but also in cells with mutant p53, where it is associated with an induction of p16. Interestingly, senescence and radiosensitization were linked to an increase in residual radiation-induced DNA double-strand breaks irrespective of p53/p16 status. This effect of EGFR inhibition was at least partially mediated by disruption of the MEK-ERK pathway. Thus, our data indicate a common mechanism of radiosensitization by erlotinib or cetuximab across diverse genetic backgrounds. Our findings also suggest that assays that are able to capture the initial proliferative delay that is associated with senescence should be useful for screening large cell line panels to identify genomic biomarkers of EGFR inhibitor-mediated radiosensitization. Cancer Res; 71(19); 6261-9. (C)2011 AACR. C1 [Wang, Meng; Morsbach, Fabian; Sander, David; Gheorghiu, Liliana; Nanda, Akash; Willers, Henning] Massachusetts Gen Hosp, Ctr Canc, Lab Cellular & Mol Radiat Oncol, Charlestown, MA USA. [Benes, Cyril; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. [Morsbach, Fabian; Sander, David; Kriegs, Malte; Dikomey, Ekkehard; Dahm-Daphi, Jochen] Univ Hamburg, Dept Radiat Oncol, Hamburg, Germany. [Nanda, Akash] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Krause, Mechthild; Baumann, Michael] Univ Hosp Carl Gustav Carus, Dept Radiat Oncol, Dresden, Germany. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3,55 Fruit St, Boston, MA 02114 USA. EM hwillers@partners.org FU Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer; NCI [RO1 CA115830, P50 CA090578]; Radiological Society of North America (RSNA); Deutsche Forschungsgemeinschaft DFG [PAK 190, DI 457/8-1]; Roentgen Resident Research Award FX This work was in part supported by the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, NCI P50 CA090578 (J. Settleman, H. Willers), NCI RO1 CA115830 (J. Settleman), a Radiological Society of North America (RSNA) Roentgen Resident Research Award (A. Nanda), and the Deutsche Forschungsgemeinschaft DFG PAK 190, DI 457/8-1 (J. Dahm-Daphi, E. Dikomey, M. Krause, M. Baumann). NR 52 TC 55 Z9 58 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2011 VL 71 IS 19 BP 6261 EP 6269 DI 10.1158/0008-5472.CAN-11-0213 PG 9 WC Oncology SC Oncology GA 827AQ UT WOS:000295397700019 PM 21852385 ER PT J AU Yu, XG Lichterfeld, M AF Yu, Xu G. Lichterfeld, Mathias TI Elite control of HIV p21 (waf-1/cip-1) at its best SO CELL CYCLE LA English DT Editorial Material ID ACTIVATED/MEMORY T-CELLS; KINASE; RESPONSES; PROTEINS C1 [Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Yu, Xu G.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mlichterfeld@partners.org FU NIAID NIH HHS [R01 AI078799, R21 AI093203-01A1, R21 AI093203] NR 11 TC 4 Z9 4 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2011 VL 10 IS 19 BP 3213 EP 3214 DI 10.4161/cc.10.19.17051 PG 2 WC Cell Biology SC Cell Biology GA 827FB UT WOS:000295412100002 PM 21926474 ER PT J AU Visus, C Wang, YY Lozano-Leon, A Ferris, RL Silver, S Szczepanski, MJ Brand, RE Ferrone, CR Whiteside, TL Ferrone, S DeLeo, AB Wang, XH AF Visus, Carmen Wang, Yangyang Lozano-Leon, Antonio Ferris, Robert L. Silver, Susan Szczepanski, Miroslaw J. Brand, Randall E. Ferrone, Cristina R. Whiteside, Theresa L. Ferrone, Soldano DeLeo, Albert B. Wang, Xinhui TI Targeting ALDH(bright) Human Carcinoma-Initiating Cells with ALDH1A1-Specific CD8(+) T Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER STEM-CELLS; ALDEHYDE DEHYDROGENASE 1; MONOCLONAL-ANTIBODIES; CLASS-I; HISTOCOMPATIBILITY ANTIGENS; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; HEAVY-CHAINS; HISTONE H3; NECK AB Purpose: Cancer-initiating cells (CIC) are considered to represent the subpopulation of tumor cells that is resistant to conventional cancer treatments, highly tumorigenic in immunodeficient mice, and responsible for tumor recurrence and metastasis. Based on an elevated aldehyde dehydrogenase (ALDH) activity attributable to ALDH1/3 isoforms, ALDH(bright) cells have been identified and isolated from tumors and shown to have characteristics of CIC. The ALDH1A1 isoform was previously identified as a tumor antigen recognized by CD8(+) T cells. This study examines the ability of ALDH1A1-specific CD8(+) T cells to eliminate ALDH(bright) cells and control tumor growth and metastases. Experimental Design: ALDH(bright) cells were isolated by flow cytometry using ALDEFLUOR from HLA-A2(+) human head and neck, breast, and pancreas carcinoma cell lines and tested for their tumorigenicity in immunodeficient mice. ALDH1A1-specific CD8(+) T cells were generated in vitro and tested for their ability to eliminate CICs in vitro and in vivo by adoptive transfer to immunodeficient mice bearing human tumor xenografts. Results: ALDH(bright) cells isolated by flow cytometry from HLA-A2(+) breast, head and neck, and pancreas carcinoma cell lines at low numbers (500 cells) were tumorigenic in immunodeficientmice. ALDH(bright) cells present in these cell lines, xenografts, or surgically removed lesions were recognized by ALDH1A1-specific CD8(+) T cells in vitro. Adoptive therapy with ALDH1A1-specific CD8(+) T cells eliminated ALDH(bright) cells, inhibited tumor growth and metastases, or prolonged survival of xenograft-bearing immunodeficient mice. Conclusions: The results of this translational study strongly support the potential of ALDH1A1-based immunotherapy to selectively target CICs in human cancer. Clin Cancer Res; 17(19); 6174-84. (C) 2011 AACR. C1 [Visus, Carmen; Wang, Yangyang; Lozano-Leon, Antonio; Ferris, Robert L.; Szczepanski, Miroslaw J.; Whiteside, Theresa L.; Ferrone, Soldano; DeLeo, Albert B.; Wang, Xinhui] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Basic Res Div, Pittsburgh, PA 15213 USA. [Visus, Carmen; Szczepanski, Miroslaw J.; Whiteside, Theresa L.; Ferrone, Soldano; DeLeo, Albert B.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Wang, Yangyang; Ferrone, Soldano] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. [Lozano-Leon, Antonio; Brand, Randall E.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Ferris, Robert L.; Whiteside, Theresa L.; Ferrone, Soldano; Wang, Xinhui] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15213 USA. [Ferris, Robert L.; Whiteside, Theresa L.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. [Silver, Susan] Consult Serv, Pittsburgh, PA USA. [Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ferrone, Cristina R.] Harvard Univ, Sch Med, Boston, MA USA. RP DeLeo, AB (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Basic Res Div, Res Pavil,Suite 2-26C, Pittsburgh, PA 15213 USA. EM deleo@pitt.edu RI Wang, Yangyang/E-1549-2013 FU National Cancer Institute at NIH [DE12321, CA109688, P50 CA097190, CA138188]; Hillman Foundation; Hirshberg Foundation for Pancreatic Cancer Research; DOD Concept Award [BC085485]; Elsa U. Pardee Foundation; Pennsylvania Department of Health; [RO3 CA141086] FX This work was supported by National Cancer Institute at the NIH grants DE12321 and CA109688 (to C. Visus, A. B. DeLeo, and T. L. Whiteside), P50 CA097190 (to C. Visus, A. B. DeLeo, and R. L. Ferris), and CA138188 (to Y. Wang and S. Ferrone), the Hillman Foundation (to A. B. DeLeo), Hirshberg Foundation for Pancreatic Cancer Research (to C. Visus), DOD Concept Award BC085485 (to C. Visus, X. Wang, and A. B. DeLeo), the Elsa U. Pardee Foundation (to X. Wang), RO3 CA141086 (to C. R. Ferrone and X. Wang), and the Pennsylvania Department of Health (to A. B. DeLeo and S. Ferrone), which specifically disclaims responsibility for any analyses, interpretations, or conclusions detailed in this report. NR 41 TC 59 Z9 62 U1 0 U2 9 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 OCT 1 PY 2011 VL 17 IS 19 BP 6174 EP 6184 DI 10.1158/1078-0432.CCR-11-1111 PG 11 WC Oncology SC Oncology GA 827VR UT WOS:000295457900009 PM 21856769 ER PT J AU Atzori, F Tabernero, J Cervantes, A Prudkin, L Andreu, J Rodriguez-Braun, E Domingo, A Guijarro, J Gamez, C Rodon, J Di Cosimo, S Brown, H Clark, J Hardwick, JS Beckman, RA Hanley, WD Hsu, K Calvo, E Rosello, S Langdon, RB Baselga, J AF Atzori, Francesco Tabernero, Josep Cervantes, Andres Prudkin, Ludmila Andreu, Jordi Rodriguez-Braun, Edith Domingo, Amparo Guijarro, Jorge Gamez, Cristina Rodon, Jordi Di Cosimo, Serena Brown, Holly Clark, Jason Hardwick, James S. Beckman, Robert A. Hanley, William D. Hsu, Karl Calvo, Emiliano Rosello, Susana Langdon, Ronald B. Baselga, Jose TI A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID INHIBITOR FIGITUMUMAB CP-751,871; METASTATIC COLORECTAL-CANCER; IGF-1 RECEPTOR; ANTITUMOR-ACTIVITY; COMBINATION; ONCOLOGY; THERAPY; H7C10; RISK; CARBOPLATIN AB Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose. Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis. Paired baseline and on-treatment skin and tumor biopsy samples were collected for PD analyses. Results: Eighty patients with chemotherapy-refractory solid tumors were enrolled. One dose-limiting toxicity was noted, but a maximum-tolerated dose was not identified. Grade 1 to 3 hyperglycemia, responsive to metformin, occurred in 15 (19%) patients. At dose levels or more than 5 mg/kg, dalotuzumab mean terminal half-life was 95 hours or more, mean C-min was more than 25 mu g/mL, clearance was constant, and serum exposures were approximately dose proportional. Decreases in tumor IGF-1R, downstream receptor signaling, and Ki67 expression were observed. F-18-Fluorodeoxy-glucose positron emission tomography metabolic responses occurred in three patients. One patient with Ewing's sarcoma showed a mixed radiologic response. The recommended phase II doses were 10, 20, and 30 mg/kg for the weekly, every other week, and every third week schedules, respectively. Conclusions: Dalotuzumab was generally well-tolerated, exhibited dose-proportional PK, inhibited IGF-1R pathway signaling and cell proliferation in treated tumors, and showed clinical activity. The low clearance rate and long terminal half-life support more extended dosing intervals. Clin Cancer Res; 17(19); 6304-12. (C) 2011 AACR. C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Atzori, Francesco; Tabernero, Josep; Prudkin, Ludmila; Andreu, Jordi; Rodon, Jordi; Di Cosimo, Serena; Calvo, Emiliano; Baselga, Jose] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, E-08193 Barcelona, Spain. [Gamez, Cristina] Bellvitge Hosp, Barcelona, Spain. [Cervantes, Andres; Rodriguez-Braun, Edith; Domingo, Amparo; Guijarro, Jorge; Rosello, Susana] Univ Valencia, Hosp Clin, Valencia, Spain. [Brown, Holly; Clark, Jason; Hardwick, James S.; Beckman, Robert A.; Hanley, William D.; Hsu, Karl; Langdon, Ronald B.] Merck, Whitehouse Stn, NJ 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 Rosello Keranen, Susana/E-7734-2015; Serena, Di Cosimo/E-9418-2017 OI Rosello Keranen, Susana/0000-0003-3915-4130; Serena, Di Cosimo/0000-0002-4666-8052 FU Merck Co., Inc. FX This study was funded by Merck & Co., Inc., manufacturer of dalotuzumab. NR 33 TC 59 Z9 60 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2011 VL 17 IS 19 BP 6304 EP 6312 DI 10.1158/1078-0432.CCR-10-3336 PG 9 WC Oncology SC Oncology GA 827VR UT WOS:000295457900021 PM 21810918 ER PT J AU Oxnard, GR Janjigian, YY Arcila, ME Sima, CS Kass, SL Riely, GJ Pao, W Kris, MG Ladanyi, M Azzoli, CG Miller, VA AF Oxnard, Geoffrey R. Janjigian, Yelena Y. Arcila, Maria E. Sima, Camelia S. Kass, Samantha L. Riely, Gregory J. Pao, William Kris, Mark G. Ladanyi, Marc Azzoli, Christopher G. Miller, Vincent A. TI Maintained Sensitivity to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer Recurring after Adjuvant Erlotinib or Gefitinib SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-III TRIAL; MUTATIONS; CHEMOTHERAPY; ADENOCARCINOMA; METASTASIS; RESISTANCE; PLACEBO; TUMOR; GENE AB Purpose: Given the unprecedented efficacy of EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutant lung cancer, adjuvant TKI therapy is an appealing strategy. However, there are conflicting findings regarding the potential benefit of adjuvant EGFR-TKI in patients with lung cancer harboring EGFR mutations. To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI. Experimental Design: Patients with recurrent EGFR-mutant lung cancer following adjuvant TKI were identified using an Institutional Review Board-approved mechanism. Recurrent cancer specimens were tested for resistance mutations. Sensitivity to retreatment with EGFR-TKI was evaluated. Results: Twenty-two patients with cancers harboring an EGFR sensitizing mutation received adjuvant erlotinib or gefitinib for a median of 17 months (range 1-37 months). T790M was more common in cancers which recurred while receiving TKI than in those which recurred after stopping TKI (67% vs. 0%, P = 0.011). Fourteen patients who developed recurrence after stopping EGFR-TKI were retreated, with a median time to progression of 10 months and radiographic response seen in 8 of 11 patients with evaluable disease (73%). Conclusions: Recurrence of EGFR-mutant lung cancer after stopping adjuvant TKI should not preclude a trial of TKI retreatment; a phase II trial of erlotinib in this setting is underway. Studies of adjuvant EGFR-TKI will underestimate the potential survival benefit of adjuvant TKI for patients with EGFR-mutant lung cancers if retreatment at recurrence is not given. Clin Cancer Res; 17(19); 6322-8. (C) 2011 AACR. C1 [Oxnard, Geoffrey R.; Janjigian, Yelena Y.; Kass, Samantha L.; Riely, Gregory J.; Pao, William; Kris, Mark G.; Azzoli, Christopher G.; Miller, Vincent A.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv,Div Solid Tumor Oncol, New York, NY USA. [Arcila, Maria E.; Ladanyi, Marc] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Mol Diagnost Serv, Dept Pathol, New York, NY USA. [Sima, Camelia S.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY USA. [Pao, William; Ladanyi, Marc] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM goxnard@partners.org OI Kris, Mark/0000-0002-7317-5341 FU Boehringer-Ingelheim; AstraZeneca; Enzon; Xcovery; ASCO; National Cancer Institute [R21-CA115051, P01-CA129243] FX Y.Y. Janjigian: commercial research grant, Boehringer-Ingelheim. G.J. Riely: consultant/advisory board, AstraZeneca, Boehringer-Ingelheim, Ariad, Chugai, and Tragara. W. Pao: commercial research grant, AstraZeneca, Enzon, and Xcovery; ownership interest, Molecular MD; consultant/advisory board, Molecular MD, AstraZeneca, Bristol-Myers Squibb, and Symphony Evolution. M. G. Kris: consultant/advisory board, Boehringer-Ingelheim and Pfizer. V. A. Miller: consultant/advisory board, Boehringer-Ingelheim Pharmaceuticals, OSI Pharmaceuticals, and Genentech. The other authors disclosed no potential conflicts of interest.; This work was supported by an ASCO Young Investigator Award and National Cancer Institute grants R21-CA115051 and P01-CA129243. NR 35 TC 23 Z9 25 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2011 VL 17 IS 19 BP 6322 EP 6328 DI 10.1158/1078-0432.CCR-11-1080 PG 7 WC Oncology SC Oncology GA 827VR UT WOS:000295457900023 PM 21831955 ER PT J AU Pitsillides, CM Runnels, JM Spencer, JA Zhi, L Wu, MX Lin, CP AF Pitsillides, Costas M. Runnels, Judith M. Spencer, Joel A. Zhi, Liang Wu, Mei X. Lin, Charles P. TI Cell Labeling Approaches for Fluorescence-Based In Vivo Flow Cytometry SO CYTOMETRY PART A LA English DT Review DE in vivo flow cytometry; cell tracking; circulating tumor cells; circulating immune cells ID CIRCULATING TUMOR-CELLS; MULTIPLE-MYELOMA; CANCER-CELLS; POPULATIONS; ANTIBODIES; BLOOD AB We provide an overview of the methods used to label circulating cells for fluorescence detection by in vivo flow cytometry. These methods are useful for cell tracking in small animals without the need to draw blood samples and are particularly useful for the detection of circulating cancer cells and quantification of circulating immune cells. (C) 2011 International Society for Advancement of Cytometry C1 [Pitsillides, Costas M.; Runnels, Judith M.; Spencer, Joel A.; Zhi, Liang; Wu, Mei X.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Pitsillides, Costas M.; Runnels, Judith M.; Spencer, Joel A.; Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Lin, CP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu RI Zhou, Feng/E-9510-2011; Spencer, Joel/A-4590-2013 FU NIH [P01 CA111519, R01 CA125690, R21 HL098750, R01 HL0095722] FX Grant sponsor: NIH; Grant number: P01 CA111519; Grant number: R01 CA125690; Grant number: R21 HL098750; Grant number: R01 HL0095722 NR 32 TC 15 Z9 15 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD OCT PY 2011 VL 79A IS 10 SI SI BP 758 EP 765 DI 10.1002/cyto.a.21125 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 825XS UT WOS:000295316100003 PM 21905206 ER PT J AU Darland, DC Cain, JT Berosik, MA Saint-Geniez, M Odens, PW Schaubhut, GJ Frisch, S Stemmer-Rachamimov, A Darland, T D'Amore, PA AF Darland, Diane C. Cain, Jacob T. Berosik, Matthew A. Saint-Geniez, Magali Odens, Patrick W. Schaubhut, Geoffrey J. Frisch, Sarah Stemmer-Rachamimov, Anat Darland, Tristan D'Amore, Patricia A. TI Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Neural development; Forebrain; Neurogenesis; VEGF isoforms; Telencephalon ID STIMULATES AXONAL OUTGROWTH; LARGE GENE LISTS; NERVOUS-SYSTEM; RADIAL GLIA; TRANSCRIPTION FACTORS; BRAIN ANGIOGENESIS; MOUSE DEVELOPMENT; CEREBRAL-CORTEX; CELL-SURVIVAL; ID PROTEINS AB This work was designed to determine the role of the vascular endothelial growth factor A (VEGF) isoforms during early neuroepithelial development in the mammalian central nervous system (CNS), specifically in the forebrain. An emerging model of interdependence between neural and vascular systems includes VEGF, with its dual roles as a potent angiogenesis factor and neural regulator. Although a number of studies have implicated VEGF in CNS development, little is known about the role that the different VEGF isoforms play in early neurogenesis. We used a mouse model of disrupted VEGF isoform expression that eliminates the predominant brain isoform, VEGF164, and expresses only the diffusible form, VEGF120. We tested the hypothesis that VEGF164 plays a key role in controlling neural precursor populations in developing cortex. We used microarray analysis to compare gene expression differences between wild type and VEGF120 mice at E9.5, the primitive stem cell stage of the neuroepithelium. We quantified changes in PHH3-positive nuclei, neural stem cell markers (Pax6 and nestin) and the Tbr2-positive intermediate progenitors at E11.5 when the neural precursor population is expanding rapidly. Absence of VEGF164 (and VEGF188) leads to reduced proliferation without an apparent effect on the number of Tbr2-positive cells. There is a corresponding reduction in the number of mitotic spindles that are oriented parallel to the ventricular surface relative to those with a vertical or oblique angle. These results support a role for the VEGF isoforms in supporting the neural precursor population of the early neuroepithelium. (C) 2011 Elsevier inc. All rights reserved. C1 [Darland, Diane C.; Cain, Jacob T.; Berosik, Matthew A.; Odens, Patrick W.; Schaubhut, Geoffrey J.; Frisch, Sarah; Darland, Tristan] Univ N Dakota, Dept Biol, Grand Forks, ND 58202 USA. [Saint-Geniez, Magali; D'Amore, Patricia A.] Schepens Eye Res Inst, Boston, MA USA. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. [Darland, Tristan] Turtle Mt Community Coll, Belcourt, ND USA. RP Darland, DC (reprint author), Univ N Dakota, Dept Biol, Grand Forks, ND 58202 USA. EM diane.darland@email.und.edu FU University of North Dakota Biology Department; College of Arts and Sciences; North Dakota EPSCoR; National Institutes of Health [NIH-NINDS R15 NS057807-01/-02, 3R15NS057807-01S1, EY05318, EY015435]; American Heart Association [AHA0715542Z] FX The authors thank Dr. Andras Nagy for the use of the VEGF-lacZ mouse line. The authors thank Ken Drees of the UND Biology Department for his technical support with sequencing. The authors wish to acknowledge the help of the faculty startup funds from the University of North Dakota Biology Department, College of Arts and Sciences and the North Dakota EPSCoR program. These studies were supported by National Institutes of Health grants NIH-NINDS R15 NS057807-01/-02 and 3R15NS057807-01S1 (DCD), EY05318 and EY015435 (PAD) with additional support from a predoctoral award from the American Heart Association (AHA0715542Z, JTC). NR 84 TC 11 Z9 13 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2011 VL 358 IS 1 BP 9 EP 22 DI 10.1016/j.ydbio.2011.06.045 PG 14 WC Developmental Biology SC Developmental Biology GA 824JP UT WOS:000295198500002 PM 21803034 ER PT J AU Attridge, RT Frei, CR Restrepo, MI Lawson, KA Ryan, L Pugh, MJV Anzueto, A Mortensen, EM AF Attridge, R. T. Frei, C. R. Restrepo, M. I. Lawson, K. A. Ryan, L. Pugh, M. J. V. Anzueto, A. Mortensen, E. M. TI Guideline-concordant therapy and outcomes in healthcare-associated pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Drug resistance; guidelines for management of pneumonia; health outcomes; pneumonia ID COMMUNITY-ACQUIRED PNEUMONIA; SINGLE-CENTER EXPERIENCE; HOSPITALIZED-PATIENTS; ADMINISTRATIVE DATA; RESISTANT BACTERIA; UNITED-STATES; EPIDEMIOLOGY; MORTALITY; VALIDATION; PREDICTION AB Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy. We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model. A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12-2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86-2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82-2.48) in the propensity score analysis. In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy. C1 [Attridge, R. T.; Frei, C. R.; Ryan, L.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, San Antonio, TX 78229 USA. [Attridge, R. T.] Univ Incarnate Word, Feik Sch Pharm, San Antonio, TX USA. [Restrepo, M. I.; Pugh, M. J. V.; Anzueto, A.; Mortensen, E. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Restrepo, M. I.; Mortensen, E. M.] S Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX USA. [Restrepo, M. I.; Pugh, M. J. V.; Anzueto, A.; Mortensen, E. M.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Attridge, R. T.; Frei, C. R.; Lawson, K. A.; Ryan, L.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, 7703 Floyd Curl Dr,MC 6220, San Antonio, TX 78229 USA. EM freic@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; OI Mortensen, Eric/0000-0002-3880-5563 FU National Institute of Nursing Research (Bethesda, MD, USA) [R01NR010828]; South Texas Veterans Health Care System (San Antonio, TX, USA); The University of Texas at Austin; National Institutes of Health [KL2 RR025766, K23HL096054]; The University of Texas at Austin College of Pharmacy; Ortho-McNeil Janssen (Titusville, NJ, USA); South Texas Veterans Health Care System Audie L. Murphy Division; The University of Texas Health Science Center at San Antonio FX This project was supported by a grant from the National Institute of Nursing Research (Bethesda, MD, USA; grant R01NR010828). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. This material is the result of work supported with resources and the use of facilities at the South Texas Veterans Health Care System (San Antonio, TX, USA) and The University of Texas at Austin. E. M. Mortensen, the principal investigator, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. C. R. Frei is supported by a National Institutes of Health Grant KL2 RR025766, salary support from The University of Texas at Austin College of Pharmacy, and research support from Ortho-McNeil Janssen (Titusville, NJ, USA). M. I. Restrepo is supported by a National Institutes of Health Grant K23HL096054, salary support by the South Texas Veterans Health Care System Audie L. Murphy Division and The University of Texas Health Science Center at San Antonio. The funding agencies had no role in conducting the study, or role in the preparation, review or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Dept of Veterans Affairs (Washington, DC, USA). NR 29 TC 54 Z9 55 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 2011 VL 38 IS 4 BP 878 EP 887 DI 10.1183/09031936.00141110 PG 10 WC Respiratory System SC Respiratory System GA 827EK UT WOS:000295410200019 PM 21436359 ER PT J AU Wang, FM Galson, DL Roodman, GD Ouyang, HJ AF Wang, Feng-Ming Galson, Deborah L. Roodman, G. David Ouyang, Hongjiao TI Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses pro-survival XBP1 signaling in human multiple myeloma cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; FACTOR-KAPPA-B; TRANSCRIPTION FACTOR; MESSENGER-RNA; ER STRESS; DIFFERENTIATION; ACTIVATION; IRE1; PROLIFERATION; PATHOGENESIS AB Objective. Resveratrol, trans-3, 4', 5,-trihydroxystilbene, suppresses multiple myeloma (MM). The endoplasmic reticulum (ER) stress response component inositol-requiring enzyme 1 alpha (IRE1 alpha)/X-box binding protein 1 (XBP1) axis is essential for MM pathogenesis. We investigated the molecular action of resveratrol on IRE1 alpha/XBP1 axis in human MM cells. Materials and Methods. Human MM cell lines ANBL-6, OPM2, and MM.1S were utilized to determine the molecular signaling events following treatment with resveratrol. The stimulation of IRE1 alpha/XBP1 axis was analyzed by Western blot and reverse transcription polymerase chain reaction. The effect of resveratrol on the transcriptional activity of spliced XBP1 was assessed by luciferase assays. Chromatin immunoprecipitation was performed to determine the effects of resveratrol on the DNA binding activity of XBP1 in MM cells. Results. Resveratrol activated IRE1 alpha as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1 alpha and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter. Conclusions. Resveratrol exerts its chemotherapeutic effect on human MM cells through mechanisms involving the impairment of the pro-survival XBP1 signaling and the activation of pro-apoptotic ER stress response. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Wang, Feng-Ming; Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Ctr Bone Biol UPMC, Pittsburgh, PA USA. [Wang, Feng-Ming] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610064, Peoples R China. [Wang, Feng-Ming; Galson, Deborah L.; Roodman, G. David; Ouyang, Hongjiao] Univ Pittsburgh, Sch Med, Dept Med Hematol Oncol, Pittsburgh, PA USA. [Ouyang, Hongjiao] Univ Pittsburgh, Sch Dent Med, Dept Comprehens Care Restorat Dent & Endodont, Pittsburgh, PA USA. RP Ouyang, HJ (reprint author), VA Pittsburgh Healthcare Syst, R&D151-U,2W 143,Univ Dr C, Pittsburgh, PA 15240 USA. EM hoo1@pitt.edu RI Wang, Fengming/H-6450-2011; Galson, Deborah/E-9370-2010 OI Wang, Fengming/0000-0001-5340-228X; Galson, Deborah/0000-0002-2045-8807 FU National Institutes of Health, Bethesda, MD, USA [DE017439]; Multiple Myeloma Research Foundation; VA Merit Review Fund; National Natural Science Foundation, P. R. China [30901677] FX This work was supported by grants from the National Institutes of Health, Bethesda, MD, USA (grant number DE017439 to H.-J.O.), the Multiple Myeloma Research Foundation (to H.-J.O.), and the VA Merit Review Fund (to G.D.R.). F.M.W is in part supported by the National Natural Science Foundation, P. R. China (grant number 30901677). We acknowledge the Veterans Administration Pittsburgh Healthcare System Research and Development for the use of their facilities. NR 33 TC 33 Z9 34 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 2011 VL 39 IS 10 BP 999 EP 1006 DI 10.1016/j.exphem.2011.06.007 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 827KL UT WOS:000295427300005 PM 21723843 ER PT J AU Carlson, KF Gravely, AA Noorbaloochi, S Simon, AB Bangerter, AK Sayer, NA AF Carlson, Kathleen F. Gravely, Amy A. Noorbaloochi, Siamak Simon, Alisha Baines Bangerter, Ann K. Sayer, Nina A. TI Post-deployment injury among new combat veterans enrolled in Veterans Affairs (VA) healthcare SO INJURY PREVENTION LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MORTALITY; IRAQ AB The purpose of this study was to examine prevalence and potential risk factors for post-deployment injury among Iraq and Afghanistan combat veterans enrolled in Veterans Affairs (VA) healthcare. A national, stratified sample of Iraq/Afghanistan combat Veteran VA users was surveyed in 2008. Mental and physical health, including medically-treated injuries sustained since deployment, were self-reported. Injury risk was estimated using survey logistic regression. Stratified ORs and 95% CIs were adjusted for potential confounders and non-response bias and weighted to represent the target population. Nearly half the population reported post-deployment injuries. In multivariate models, veterans with probable post-traumatic stress disorder (OR=2.1; 95% CI 1.3 to 3.5), self-reported diagnosed depression (OR=3.6; 95% CI 1.8 to 7.0) and anger problems (OR=2.4; 95% CI 1.4 to 4.2) had greater odds of post-deployment injury. Deployment-related injuries were also strongly associated with odds of post-deployment injury. Results suggest that mental health disorders increase the odds of post-deployment injury among combat veteran VA users. Longitudinal research examining these associations is warranted. C1 [Carlson, Kathleen F.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Gravely, Amy A.; Noorbaloochi, Siamak; Simon, Alisha Baines; Bangerter, Ann K.; Sayer, Nina A.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Noorbaloochi, Siamak; Sayer, Nina A.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Sayer, Nina A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. RP Carlson, KF (reprint author), Portland VA Med Ctr R&D 66, Portland Ctr Study Chron Comorbid Mental & Phys D, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kathleen.carlson@va.gov RI Schueter, nicos/A-3625-2014; Sayer, Nina/E-3249-2016 FU US Department of Veterans Affairs (VA), Veterans Health Administration, Health Services Research and Development Service [RRP 07-315, TPP 67-005, CDA 08-025] FX This research was supported by the US Department of Veterans Affairs (VA), Veterans Health Administration, Health Services Research and Development Service grants (RRP 07-315; TPP 67-005; CDA 08-025). The findings and conclusions of this manuscript are those of the authors and do not necessarily represent those of the VA. NR 20 TC 4 Z9 4 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD OCT PY 2011 VL 17 IS 5 BP 343 EP 347 DI 10.1136/ip.2010.030213 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 823MB UT WOS:000295125300012 PM 21546526 ER PT J AU Ronan, L Pienaar, R Williams, G Bullmore, ET Crow, TJ Roberts, N Jones, PB Suckling, J Fletcher, PC AF Ronan, Lisa Pienaar, Rudolph Williams, Guy Bullmore, Edward T. Crow, Tim J. Roberts, Neil Jones, Peter B. Suckling, John Fletcher, Paul C. TI INTRINSIC CURVATURE: A MARKER OF MILLIMETER-SCALE TANGENTIAL CORTICO-CORTICAL CONNECTIVITY? SO INTERNATIONAL JOURNAL OF NEURAL SYSTEMS LA English DT Article DE Intrinsic curvature; cortical connectivity; surface morphology ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; PREFRONTAL CORTEX; VISUAL-CORTEX; WHITE-MATTER; BRAIN SIZE; NETWORKS; SYSTEM; SCHIZOPHRENIA; COMMUNICATION AB In this paper, we draw a link between cortical intrinsic curvature and the distributions of tangential connection lengths. We suggest that differential rates of surface expansion not only lead to intrinsic curvature of the cortical sheet, but also to differential inter-neuronal spacing. We propose that there follows a consequential change in the profile of neuronal connections: specifically an enhancement of the tendency towards proportionately more short connections. Thus, the degree of cortical intrinsic curvature may have implications for short-range connectivity. C1 [Ronan, Lisa; Bullmore, Edward T.; Fletcher, Paul C.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England. [Pienaar, Rudolph] Massachusetts Gen Hosp, Childrens Hosp Boston, Boston, MA 02114 USA. [Williams, Guy] Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge, England. [Crow, Tim J.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Roberts, Neil] Univ Edinburgh, Queens Med Res Inst, Clin Res Imaging Ctr, Edinburgh, Midlothian, Scotland. [Jones, Peter B.] Univ Cambridge, Dept Expt Psychol, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. RP Ronan, L (reprint author), Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England. EM lr344@cam.ac.uk; pcf22@cam.ac.uk RI Bullmore, Edward/C-1706-2012; OI Bullmore, Edward/0000-0002-8955-8283; Jones, Peter/0000-0002-0387-880X FU Wellcome Trust; Bernard Wolfe Health Neuroscience Fund; Wellcome/MRC FX This work was supported by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund, and carried out at the Wellcome/MRC funded Behavioural and Clinical Neurosciences Institute, University of Cambridge. We would also like to thank L. Parr and D. Ginsburg. NR 47 TC 28 Z9 28 U1 0 U2 8 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0129-0657 EI 1793-6462 J9 INT J NEURAL SYST JI Int. J. Neural Syst. PD OCT PY 2011 VL 21 IS 5 BP 351 EP 366 DI 10.1142/S0129065711002948 PG 16 WC Computer Science, Artificial Intelligence SC Computer Science GA 825LX UT WOS:000295279000001 PM 21956929 ER PT J AU Pedraza-Alva, G Merida, LB del Rio, R Fierro, NA Cruz-Munoz, ME Olivares, N Melchy, E Igras, V Hollander, GA Burakoff, SJ Rosenstein, Y AF Pedraza-Alva, Gustavo Merida, Lilia B. del Rio, Roxana Fierro, Nora A. Cruz-Munoz, Mario E. Olivares, Norma Melchy, Erika Igras, Vivian Hollaender, Georg A. Burakoff, Steven J. Rosenstein, Yvonne TI CD43 Regulates the Threshold for T Cell Activation by Targeting Cbl Functions SO IUBMB LIFE LA English DT Article DE T cell activation; CD43; Cbl; PKC theta ID WISKOTT-ALDRICH SYNDROME; E3 UBIQUITIN LIGASE; LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; PROTEIN-KINASE-C; NEGATIVE REGULATION; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAY; MOUSE LEUKOSIALIN; ANTIGEN RECEPTOR; CUTTING EDGE AB T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesired activation of T cells by regulating TCR signals. In this report, we show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement inhibits TCR-dependent c-Cbl tyrosine phosphorylation, c-Cbl interaction with the adapter molecule Crk-L and promotes Cbl-b degradation in a PKC theta-dependent manner. Consequently, the prolonged tyrosine phosphorylation and delayed degradation of ZAP-70 and of the zeta chain lead to enhanced mitogen-activated protein kinase activation and robust TC response. These data indicates that CD43-mediated signals lower the threshold for TC activation by restricting the c-Cbl and Cbl-b inhibitory effects on TCR signaling. In addition to the strength and duration of intracellular signals, our data underscore temporality with which certain molecules are engaged as yet another mechanism to fine tune TC signal quality, and ultimately immune function. (C) 2011 IUBMB IUBMB Life, 63(10): 940-948, 2011 C1 [Pedraza-Alva, Gustavo; Merida, Lilia B.; del Rio, Roxana; Fierro, Nora A.; Cruz-Munoz, Mario E.; Olivares, Norma; Melchy, Erika; Rosenstein, Yvonne] Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Cuernavaca 62210, Mor, Mexico. [Igras, Vivian; Rosenstein, Yvonne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hollaender, Georg A.] Univ Basel, Childrens Hosp, Basel, Switzerland. [Hollaender, Georg A.] Univ Basel, Dept Res & Clin Biol Sci, Basel, Switzerland. [Burakoff, Steven J.] Mt Sinai Med Ctr, Tish Canc Inst, New York, NY USA. RP Rosenstein, Y (reprint author), Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Av Univ 2001, Cuernavaca 62210, Mor, Mexico. EM yvonne@ibt.unam.mx FU Consejo Nacional de Ciencia y Tecnologia (CONACyT); Direccion General de Apoyo al Personal Academico (DGAPA)/UNAM, Mexico FX The authors thank Dr. Leonor Perez Martinez for critical reading of the manuscript and O. Lopez for technical help. The authors also thank the blood bank of the Hospital Regional del IMSS in Cuernavaca for leukocyte concentrates. This work was partially funded by grants from the Consejo Nacional de Ciencia y Tecnologia (CONACyT), and the Direccion General de Apoyo al Personal Academico (DGAPA)/UNAM, Mexico. NR 45 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD OCT PY 2011 VL 63 IS 10 SI SI BP 940 EP 948 DI 10.1002/iub.554 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 826SV UT WOS:000295375800022 PM 21905200 ER PT J AU Bilezikian, JP Khan, A Potts, JT Brandi, ML Clarke, BL Shoback, D Juppner, H D'Amour, P Fox, J Rejnmark, L Mosekilde, L Rubin, MR Dempster, D Gafni, R Collins, MT Sliney, J Sanders, J AF Bilezikian, John P. Khan, Aliya Potts, John T., Jr. Brandi, Maria Luisa Clarke, Bart L. Shoback, Dolores Jueppner, Harald D'Amour, Pierre Fox, John Rejnmark, Lars Mosekilde, Leif Rubin, Mishaela R. Dempster, David Gafni, Rachel Collins, Michael T. Sliney, Jim Sanders, James TI Hypoparathyroidism in the Adult: Epidemiology, Diagnosis, Pathophysiology, Target-Organ Involvement, Treatment, and Challenges for Future Research SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HYPOPARATHYROIDISM; CALCIUM; EPIDEMIOLOGY; GENETICS; PARATHYROID HORMONE; HYPOCALCEMIA ID CALCIUM-SENSING RECEPTOR; FAMILIAL ISOLATED HYPOPARATHYROIDISM; PARATHYROID-HORMONE PTH; CANDIDIASIS-ECTODERMAL DYSTROPHY; BONE-MINERAL DENSITY; LONG-TERM TREATMENT; AUTOSOMAL RECESSIVE HYPOPARATHYROIDISM; HYPOCALCEMIA FOLLOWING THYROIDECTOMY; POLYENDOCRINE SYNDROME TYPE-1; 3RD INTERNATIONAL WORKSHOP AB Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease. (C) 2011 American Society for Bone and Mineral Research. C1 [Bilezikian, John P.; Rubin, Mishaela R.; Sliney, Jim] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Khan, Aliya] McMaster Univ, Div Endocrinol, Hamilton, ON, Canada. [Khan, Aliya] McMaster Univ, Div Geriatr, Hamilton, ON, Canada. [Potts, John T., Jr.; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Potts, John T., Jr.; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Brandi, Maria Luisa] Univ Florence, Sch Med, Dept Internal Med, Unit Bone & Mineral Metab, Florence, Italy. [Clarke, Bart L.] Mayo Clin, Dept Med, Rochester, MN USA. [Shoback, Dolores] Univ Calif San Francisco, San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [D'Amour, Pierre] Hop St Luc, CHUM, Ctr Rech, Montreal, PQ H2X 1P1, Canada. [D'Amour, Pierre] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Fox, John] NPS Pharmaceut, Bedminster, NJ USA. [Rejnmark, Lars; Mosekilde, Leif] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark. [Dempster, David] Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. [Dempster, David] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. [Gafni, Rachel; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Sanders, James] Hypoparathyroidism Assoc, Idaho Falls, ID USA. RP Bilezikian, JP (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. EM jpb2@columbia.edu OI Rejnmark, Lars/0000-0002-2152-4247 FU NPS Pharmaceuticals; NIH [RO1, R37 DK46718, DK 069350]; Research Service of the Department of Veterans Affairs; F.I.R.M.O. Fondazione Raffaella Becagli; FDA [FD 002525]; Division of Intramural Research, NIDCR, NIH FX JPB, MR, JS, LR, and LM receive investigator-initiated research support from NPS Pharmaceuticals. DS receives funding from NIH RO1 and the Research Service of the Department of Veterans Affairs; MLB acknowledges support from F.I.R.M.O. Fondazione Raffaella Becagli; HJ acknowledges funding from NIH R37 DK46718; JB, MR, and DD acknowledge support from NIH (DK 069350) and the FDA (FD 002525); and MC and RG acknowledge support by the Division of Intramural Research, NIDCR, NIH, and state that this article represents the opinions of the authors and not of the NIH or the US federal government. NR 143 TC 113 Z9 118 U1 0 U2 12 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2011 VL 26 IS 10 BP 2317 EP 2337 DI 10.1002/jbmr.483 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZQ UT WOS:000295241100001 PM 21812031 ER PT J AU Misra, M Katzman, D Miller, KK Mendes, N Snelgrove, D Russell, M Goldstein, MA Ebrahimi, S Clauss, L Weigel, T Mickley, D Schoenfeld, DA Herzog, DB Klibanski, A AF Misra, Madhusmita Katzman, Debra Miller, Karen K. Mendes, Nara Snelgrove, Deirdre Russell, Melissa Goldstein, Mark A. Ebrahimi, Seda Clauss, Laura Weigel, Thomas Mickley, Diane Schoenfeld, David A. Herzog, David B. Klibanski, Anne TI Physiologic Estrogen Replacement Increases Bone Density in Adolescent Girls With Anorexia Nervosa SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ANOREXIA NERVOSA; ADOLESCENTS; BONE DENSITY; BONE TURNOVER; BONE METABOLISM; ESTROGEN; TRANSDERMAL; IGF-1 ID LOW-DOSE ESTROGEN; GROWTH-FACTOR-I; MINERAL DENSITY; SECRETORY DYNAMICS; TURNER-SYNDROME; DOUBLE-BLIND; HORMONE; WOMEN; METABOLISM; THERAPY AB Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low BMD in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiologic estrogen doses that mimic puberty on BMD has not been examined. We enrolled 110 girls with AN and 40 normal-weight controls 12 to 18 years of age of similar maturity. Subjects were studied for 18 months. Mature girls with AN (bone age [BA] >= 15 years, n = 96) were randomized to 100 mu g of 17 beta-estradiol (with cyclic progesterone) or placebo transdermally for 18 months. Immature girls with AN (BA < 15 years, n = 14) were randomized to incremental low-dose oral ethinyl-estradiol (3.75 mu g daily from 0 to 6 months, 7.5 mu g from 6 to 12 months, 11.25 mu g from 12 to 18 months) to mimic pubertal estrogen increases or placebo for 18 months. All BMD measures assessed by dual-energy X-ray absorptiometry (DXA) were lower in girls with AN than in control girls. At baseline, girls with AN randomized to estrogen (AN E+) did not differ from those randomized to placebo (AN E-) for age, maturity, height, BMI, amenorrhea duration, and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with the AN E- group, even after controlling for baseline age and weight. It is concluded that physiologic estradiol replacement increases spine and hip BMD in girls with AN. (C) 2011 American Society for Bone and Mineral Research. C1 [Misra, Madhusmita; Miller, Karen K.; Mendes, Nara; Russell, Melissa; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita; Miller, Karen K.; Mendes, Nara; Russell, Melissa; Goldstein, Mark A.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Misra, Madhusmita; Russell, Melissa] MassGen Children Hosp, Pediat Endocrine Unit, Boston, MA USA. [Katzman, Debra; Snelgrove, Deirdre] Hosp Sick Children, Div Adolescent Med, Toronto, ON M5G 1X8, Canada. [Goldstein, Mark A.] MassGen Children Hosp, Div Adolescent Med, Boston, MA USA. [Ebrahimi, Seda] Cambridge Eating Disorders Ctr, Cambridge, MA USA. [Clauss, Laura] Ctr Eating Disorders Management, Bedford, NH USA. [Weigel, Thomas] McLean Hosp, Klarman Ctr, Belmont, MA 02178 USA. [Weigel, Thomas] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Mickley, Diane] Wilkins Ctr Eating Disorders, Greenwich, CT USA. [Schoenfeld, David A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU National Institutes of Health [R01 DK 062249, K23 RR018851, M01-RR-01066, 1 UL1 RR025758-03] FX We thank the skilled nursing and bionutrition staff of the Clinical Research Center of Massachusetts General Hospital, Boston, MA, USA, and Clinical Investigation Center of the Hospital for Sick Children, Toronto, Ontario, Canada, for their help with carrying out this study. Finally, we thank our subjects, without whom this study would not have been possible. This work was supported by National Institutes of Health Grants R01 DK 062249, K23 RR018851, M01-RR-01066, and 1 UL1 RR025758-03. NR 34 TC 71 Z9 74 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2011 VL 26 IS 10 BP 2430 EP 2438 DI 10.1002/jbmr.447 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZQ UT WOS:000295241100011 PM 21698665 ER PT J AU Puzhko, S Goodyer, CG Kerachian, MA Canaff, L Misra, M Juppner, H Bastepe, M Hendy, GN AF Puzhko, Svetlana Goodyer, Cynthia Gates Kerachian, Mohammad Amin Canaff, Lucie Misra, Madhusmita Jueppner, Harald Bastepe, Murat Hendy, Geoffrey N. TI Parathyroid Hormone Signaling via G alpha s Is Selectively Inhibited by an NH2-Terminally Truncated G alpha s: Implications for Pseudohypoparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE PARATHYROID HORMONE; STIMULATORY G PROTEIN; CYCLIC AMP; PSEUDOHYPOPARATHYROIDISM; ALBRIGHT HEREDITARY OSTEODYSTROPHY ID STIMULATORY G-PROTEIN; ALBRIGHTS HEREDITARY OSTEODYSTROPHY; G-ALPHA(S) CARBOXYL-TERMINUS; ADENYLYL-CYCLASE; EPIGENETIC DEFECTS; GNAS LOCUS; RECEPTOR; GENE; SUBUNIT; ACTIVATION AB Pseudohypoparathyroid patients have resistance predominantly to parathyroid hormone (PTH), and here we have examined the ability of an alternative G alpha s-related protein to inhibit G alpha s activity in a hormone-selective manner. We tested whether the GNAS exon A/B-derived NH2-terminally truncated (Tr) alpha s protein alters stimulation of adenylate cyclase by the PTH receptor (PTHR1), the thyroid-stimulating hormone (TSH) receptor (TSHR), the beta(2)-adrenergic receptor (beta(2)AR), or the AVP receptor (V2R). HEK293 cells cotransfected with receptor and full-length (FL) G alpha s +/- Tr alpha s protein expression vectors were stimulated with agonists (PTH [10(-7) to 10(-9)M], TSH [1 to 100 mU], isoproterenol [10(-6) to 10(-8)M], or AVP [10(-6) to 10(-8)M]). Following PTH stimulation, HEK293 cells cotransfected with PTHR1 + FL G alpha s + Tr alpha s had a significantly lower cAMP response than those transfected with only PTHR1 + FL G alpha s. Tr alpha s also exerted an inhibitory effect on the cAMP levels stimulated by TSH via the TSHR but had little or no effect on isoproterenol or AVP acting via beta(2)AR or V2R, respectively. These differences mimic the spectrum of hormone resistance in pseudohypoparathyroidism type 1a (PHP-1a) and type 1b (PHP-1b) patients. In opossum kidney (OK) cells, endogenously expressing the PTHR1 and beta(2)AR, the exogenous expression of Tr alpha s at a level similar to endogenous FL G alpha s resulted in blunting of the cAMP response to PTH, whereas that to isoproterenol was unaltered. A pseudopseudohypoparathyroid patient with Albright hereditary osteodystrophy harbored a de novo paternally inherited M1I G alpha s mutation. Similar maternally inherited mutations at the initiation codon have been identified previously in PHP-1a patients. The M1I alpha s mutant (lacking the first 59 amino acids of G alpha s) blunted the increase in cAMP levels stimulated via the PTHR1 in both HEK293 and OK cells similar to the Tr alpha s protein. Thus NH2-terminally truncated forms of G alpha s may contribute to the pathogenesis of pseudohypoparathyroidism by inhibiting the activity of G alpha s itself in a GPCR selective manner. (C) 2011 American Society for Bone and Mineral Research. C1 [Puzhko, Svetlana; Goodyer, Cynthia Gates] McGill Univ, Endocrine Res Lab, Montreal, PQ H3Z 2Z3, Canada. [Goodyer, Cynthia Gates] McGill Univ, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada. [Goodyer, Cynthia Gates; Hendy, Geoffrey N.] McGill Univ, Dept Med, Montreal, PQ H3Z 2Z3, Canada. [Kerachian, Mohammad Amin; Canaff, Lucie; Hendy, Geoffrey N.] Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. [Kerachian, Mohammad Amin; Hendy, Geoffrey N.] McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada. [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita; Jueppner, Harald; Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA USA. [Misra, Madhusmita] MassGen Children, Pediat Endocrine Unit, Boston, MA USA. [Jueppner, Harald] MassGen Children, Pediat Nephrol Unit, Boston, MA USA. [Jueppner, Harald; Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Hendy, Geoffrey N.] McGill Univ, Dept Physiol, Montreal, PQ H3Z 2Z3, Canada. [Hendy, Geoffrey N.] Royal Victoria Hosp, Hormones & Canc Res Unit, Montreal, PQ H3A 1A1, Canada. RP Goodyer, CG (reprint author), McGill Univ, Montreal Childrens Hosp, Res Inst, Endocrine Res Lab, Room 415-1,4060 Ste Catherine St W, Montreal, PQ H3Z 2Z3, Canada. EM cindy.goodyer@muhc.mcgill.ca; geoffrey.hendy@mcgill.ca FU Canadian Institutes of Health Research; National Institute of Diabetes and Digestive and Kidney Diseases [R37 DK46718, RO1 DK073911]; Kidney Foundation of Canada; Research Institute of the McGill University Health Centre FX This work was supported by operating grants from the Canadian Institutes of Health Research (to CGG and GNH) and by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK46718 to HJ and RO1 DK073911 to MB). L.C. was supported by Fellowships from the Kidney Foundation of Canada and the Research Institute of the McGill University Health Centre. NR 46 TC 12 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2011 VL 26 IS 10 BP 2473 EP 2485 DI 10.1002/jbmr.461 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZQ UT WOS:000295241100015 PM 21713996 ER PT J AU Clines, GA Mohammad, KS Grunda, JM Clines, KL Niewolna, M McKenna, CR McKibbin, CR Yanagisawa, M Suva, LJ Chirgwin, JM Guise, TA AF Clines, Gregory A. Mohammad, Khalid S. Grunda, Jessica M. Clines, Katrina L. Niewolna, Maria McKenna, C. Ryan McKibbin, Christopher R. Yanagisawa, Masashi Suva, Larry J. Chirgwin, John M. Guise, Theresa A. TI Regulation of Postnatal Trabecular Bone Formation by the Osteoblast Endothelin A Receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ENDOTHELIN A RECEPTOR; ENDOTHELIN-1; OSTEOBLAST; BONE; SEX STEROIDS ID ANDROGEN DEPRIVATION THERAPY; PULMONARY ARTERIAL-HYPERTENSION; RECOMBINANT CONGENIC MICE; SITE-SPECIFIC REGULATION; QUANTITATIVE TRAIT LOCI; PROSTATE-CANCER; OSTEOCLAST FORMATION; GROWTH; PATHWAY; CELLS AB Endothelin-1 (ET-1) is a potent vasoconstrictor that also stimulates cells in the osteoblast lineage by binding to the endothelin A receptor (ETAR). ET-1 ligand is widely secreted, particularly by the vasculature. However, the contributions of ETAR signaling to adult bone homeostasis have not been defined. ETAR was inactivated in osteoblasts by crossing ETAR-floxed and osteocalcin-Cre mice. Histomorphometric analyses were performed on 4-, 8-, and 12-week-old osteoblast-targeted ETAR knockout (KO) and wild-type (WT) male and female mice. Tibial trabecular bone volume was significantly lower from 12 weeks in KO versus WT mice in both males and females. Bone-formation rate, osteoblast density, and in vitro osteoblast differentiation were reduced by targeted inactivation of ETAR. A separate longitudinal analysis was performed between 8 and 64 weeks to examine the effect of aging and castration on bone metabolism in ETAR KO mice. Hypogonadism did not change the rate of bone accrual in WT or KO females. However, eugonadal KO males had a significantly larger increase in tibial and femoral bone acquisition than WT mice. Male mice castrated at: 8 weeks of age showed the reverse: KO mice had reduced rates of tibial and femoral BMD acquisition compared with WT mice. In vitro, ET-1 increased osteoblast proliferation, survival, and differentiation. Dihydrotestosterone also increased osteoblast differentiation using a mechanism distinct from the actions of ET-1. These results demonstrate that endothelin signaling in osteoblasts is an important regulator of postnatal trabecular bone remodeling and a modulator of androgen effects on bone. (C) 2011 American Society for Bone and Mineral Research. C1 [Clines, Gregory A.] Univ Alabama, Dept Med, Birmingham VA Med Ctr, Div Endocrinol Diabet & Metab,Endocrinol Sect, Birmingham, AL 35294 USA. [Clines, Gregory A.] Vet Affairs Med Ctr, Birmingham, AL USA. [Clines, Gregory A.; Mohammad, Khalid S.; Clines, Katrina L.; Niewolna, Maria; McKenna, C. Ryan; McKibbin, Christopher R.; Chirgwin, John M.; Guise, Theresa A.] Univ Virginia, Dept Med, Div Endocrinol & Metab, Charlottesville, VA USA. [Yanagisawa, Masashi] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. [Yanagisawa, Masashi] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA. [Suva, Larry J.] Univ Arkansas Med Sci, Ctr Orthopaed Res, Dept Orthopaed Surg, Little Rock, AR 72205 USA. RP Clines, GA (reprint author), Univ Alabama, Dept Med, Birmingham VA Med Ctr, Div Endocrinol Diabet & Metab,Endocrinol Sect, 1808 7th Ave S,BDB 730, Birmingham, AL 35294 USA. EM clines@uab.edu FU NIH [R01 DK067333, F32 AR52295, K08 118428]; Gerald D Aurbach Endowment; Carl L Nelson Chair in Orthopaedic Creativity; Mellon Institute and Cancer Center of the University of Virginia; Endocrine Fellows Foundation FX This work was supported by NIH Grants R01 DK067333, F32 AR52295, and K08 118428; the Gerald D Aurbach Endowment, the Carl L Nelson Chair in Orthopaedic Creativity; the Mellon Institute and Cancer Center of the University of Virginia; and the Endocrine Fellows Foundation. We would like to thank Dr Thomas Clemens for providing osteocalcin-Cre mice and helpful discussions, the UAB Center for Metabolic Bone Disease Bone Histomorphometry Core, and the UAB Center for AIDS Research Flow Cytometry Core. NR 47 TC 12 Z9 12 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2011 VL 26 IS 10 BP 2523 EP 2536 DI 10.1002/jbmr.450 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824ZQ UT WOS:000295241100019 PM 21698666 ER PT J AU Shiraishi, H Ahlfors, SP Stufflebeam, SM Knake, S Larsson, PG Hamalainen, MS Takano, K Okajima, M Hatanaka, K Saitoh, S Dale, AM Halgren, E AF Shiraishi, Hideaki Ahlfors, Seppo P. Stufflebeam, Steven M. Knake, Susanne Larsson, Pal G. Haemaelaeinen, Matti S. Takano, Kyoko Okajima, Maki Hatanaka, Keisaku Saitoh, Shinji Dale, Anders M. Halgren, Eric TI Comparison of Three Methods for Localizing Interictal Epileptiform Discharges With Magnetoencephalography SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MEG; epilepsy; dynamic statistical parametric mapping; minimum current estimate; minimum norm estimate; equivalent current dipole ID TEMPORAL-LOBE EPILEPSY; EVOKED MAGNETIC-FIELDS; HUMAN-BRAIN; SOURCE LOCALIZATION; CORTICAL SURFACE; PRESURGICAL EVALUATION; PARTIALIS CONTINUA; NEURONAL-ACTIVITY; WAVE DISCHARGES; EEG AB Purpose: To compare three methods of localizing the source of epilepti-form activity recorded with magnetoencephalography: equivalent current dipole, minimum current estimate, and dynamic statistical parametric mapping (dSPM), and to evaluate the solutions by comparison with clinical symptoms and other electrophysiological and neuroradiological findings. Methods: Fourteen children of 3 to 15 years were studied. Magnetoencephalography was collected with a whole-head 204-channel helmetshaped sensor array. We calculated equivalent current dipoles and made minimum current estimate and dSPM movies to estimate the cortical distribution of interictal epileptiform discharges in these patients. Results: The results for four patients with localization-related epilepsy and one patient with Landau-Kleffner Syndrome were consistent among all the three analysis methods. In the rest of the patients, minimum current estimate and dSPM suggested multifocal or widespread activity; in these patients, the equivalent current dipole results were so scattered that interpretation of the results was not possible. For 9 patients with localization-related epilepsy and generalized epilepsy, the epileptiform discharges were wide spread or only slow waves, but dSPM suggested a possible propagation path of the interictal epileptiform discharges. Conclusion: Minimum current estimate and dSPM could identify the propagation of epileptiform activity with high temporal resolution. The results of dSPM were more stable because the solutions were less sensitive to background brain activity. C1 [Shiraishi, Hideaki] Hokkaido Univ, Dept Pediat, Grad Sch Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan. [Shiraishi, Hideaki; Ahlfors, Seppo P.; Stufflebeam, Steven M.; Knake, Susanne; Haemaelaeinen, Matti S.; Dale, Anders M.; Halgren, Eric] Harvard Univ, Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Charlestown, MA USA. [Ahlfors, Seppo P.; Stufflebeam, Steven M.; Haemaelaeinen, Matti S.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Knake, Susanne] Univ Marburg, Epilepsy Ctr Marburg, Dept Neurol, Marburg, Germany. [Larsson, Pal G.] Oslo Univ Hosp, Dept Neurosurg, Oslo, Norway. [Hatanaka, Keisaku] Okayama Univ Sci, Dept Appl Phys, Okayama 700, Japan. [Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Shiraishi, H (reprint author), Hokkaido Univ, Dept Pediat, Grad Sch Med, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM siraisi@nmr.mgh.harvard.edu RI Shiraishi, Hideaki/A-8427-2012; Hamalainen, Matti/C-8507-2013; Ahlfors, Seppo/P-3644-2016; OI Saitoh, Shinji/0000-0001-6911-3351 FU National Institutes of Health [NS18741]; MIND Institute (DOE) [DE-FG03-99ER62764]; National Center for Research Resources [P41RR14075] FX This study was supported by the National Institutes of Health (NS18741), the MIND Institute (DOE grant DE-FG03-99ER62764), and the National Center for Research Resources (P41RR14075). NR 78 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD OCT PY 2011 VL 28 IS 5 BP 431 EP 440 DI 10.1097/WNP.0b013e318231c86f PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 827DZ UT WOS:000295409100001 PM 21946369 ER PT J AU Bhatt, AB Brenner, RP Van Cott, AC AF Bhatt, Amar B. Brenner, Richard P. Van Cott, Anne C. TI Generalized Paroxysmal Fast Activity and Tonic Seizures in Older Adults SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Tonic movements; Generalized epilepsy; Adult epilepsy; Lennox-Gastaut syndrome ID ABSENCE SEIZURES AB Generalized paroxysmal fast activity is an uncommon ictal EEG pattern usually associated with tonic seizures. Patients with generalized paroxysmal fast activity typically have multiple seizure types beginning in childhood and are refractory to antiepileptic drug therapy. We describe 3 hospitalized adult patients (age, older than 55 years) with new-onset tonic movements, noted during an acute illness, associated with generalized paroxysmal fast activity on EEG. These seizures were characterized by subtle stiffening of the arms, trunk, and face for up to 3 seconds. All patients had multiple medical problems and polypharmacy. None had a history of static encephalopathy, other epileptiform abnormalities on EEG, other seizure types, or significant neuroimaging abnormalities. In contrast to previously described reports in children, all three adults responded to antiepileptic drug monotherapy. EEG played a critical role in differentiating tonic seizures from nonepileptic movements in these three cases. C1 [Bhatt, Amar B.; Brenner, Richard P.; Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Med Ctr, Pittsburgh, PA 15260 USA. [Van Cott, Anne C.] Vet Affairs Pittsburgh Hlth Care Syst, Div Neurol, Pittsburgh, PA USA. RP Bhatt, AB (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 1161 21st Ave S,A-0118 Med Ctr N, Nashville, TN 37232 USA. EM biga898@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD OCT PY 2011 VL 28 IS 5 BP 474 EP 477 DI 10.1097/WNP.0b013e318231c8dd PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 827DZ UT WOS:000295409100006 PM 21946373 ER PT J AU Tung, N Silver, DP AF Tung, Nadine Silver, Daniel P. TI Chek2 DNA Damage Response Pathway and Inherited Breast Cancer Risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHK2 PROTEIN-KINASE; 1100DELC MUTATION; BRCA2 MUTATIONS; CHECKPOINT PATHWAY; IONIZING-RADIATION; OVARIAN-CANCER; STRAND BREAKS; PHOSPHORYLATION; CHEK2-ASTERISK-1100DELC; ACTIVATION C1 [Tung, Nadine] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Silver, Daniel P.] Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. RP Tung, N (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 49 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2011 VL 29 IS 28 BP 3813 EP 3815 DI 10.1200/JCO.2011.37.1476 PG 3 WC Oncology SC Oncology GA 826RI UT WOS:000295371300019 PM 21876079 ER PT J AU Moy, B Polite, BN Halpern, MT Stranne, SK Winer, EP Wollins, DS Newman, LA AF Moy, Beverly Polite, Blase N. Halpern, Michael T. Stranne, Steven K. Winer, Eric P. Wollins, Dana S. Newman, Lisa A. TI American Society of Clinical Oncology Policy Statement: Opportunities in the Patient Protection and Affordable Care Act to Reduce Cancer Care Disparities SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH-INSURANCE; OUTCOMES; RACE AB Patients in specific vulnerable population groups suffer disproportionately from cancer. The elimination of cancer disparities is critically important for lessening the burden of cancer. The Patient Protection and Affordable Care Act provides both opportunities and challenges for addressing cancer care disparities and access to care. The American Society of Clinical Oncology (ASCO) advocates for policies that ensure access to cancer care for the underserved. Such policies include insurance reform and the reduction of economic barriers to quality health care. Building on ASCO's prior statement on disparities in cancer care (2009), this article summarizes elements of the health care law that are relevant to cancer disparities and provides recommendations for addressing major provisions in the law. It outlines specific strategies to address insurance reform, access to care, quality of care, prevention and wellness, research on health care disparities, and diversity in the health care workforce. ASCO is committed to leading efforts toward the improvement of cancer care among the most vulnerable patients. J Clin Oncol 29: 3816-3824. (C) 2011 by American Society of Clinical Oncology C1 [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Polite, Blase N.] Univ Chicago, Chicago, IL 60637 USA. [Halpern, Michael T.] Res Triangle Inst Int, Res Triangle Pk, NC USA. [Stranne, Steven K.] Polsinelli Shughart PC, Washington, DC USA. [Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA. [Newman, Lisa A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,LRH-308, Boston, MA 02114 USA. EM bmoy@partners.org NR 27 TC 49 Z9 49 U1 0 U2 7 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 OCT 1 PY 2011 VL 29 IS 28 BP 3816 EP 3824 DI 10.1200/JCO.2011.35.8903 PG 9 WC Oncology SC Oncology GA 826RI UT WOS:000295371300020 PM 21810680 ER PT J AU Ng, AK LaCasce, A Travis, LB AF Ng, Andrea K. LaCasce, Ann Travis, Lois B. TI Risk of Second Malignant Neoplasm Among Patients With Lymphoma Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID B-CELL LYMPHOMA; ADVANCED FOLLICULAR LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; NON-HODGKINS-LYMPHOMA; STUDY-GROUP GLSG; PHASE-III; ELDERLY-PATIENTS; R-CHOP; CYCLOPHOSPHAMIDE; MITOXANTRONE C1 [Ng, Andrea K.; LaCasce, Ann] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Travis, Lois B.] Rubin Ctr Canc Survivorship, Rochester, NY USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 18 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 OCT 1 PY 2011 VL 29 IS 28 BP 3834 EP 3835 DI 10.1200/JCO.2011.38.1152 PG 4 WC Oncology SC Oncology GA 826RI UT WOS:000295371300024 ER PT J AU Ghoshhajra, BB Techasith, T Choy, G Rojas, CA Pomerantz, SR AF Ghoshhajra, Brian B. Techasith, Tust Choy, Garry Rojas, Carlos A. Pomerantz, Stuart R. TI Using Keynote to Present Radiology Images SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Computers in medicine; Radiology Information Systems (RIS); Radiology teaching file; Image processing; Image display; Productivity; Keynote ID STACK MODE; POWERPOINT; DISPLAY AB Numerous articles have offered instructions for working with advanced radiology images in Microsoft PowerPoint (Redmond, WA); however, no articles have detailed instructions to do the same on alternative presentation software. Apple Macintosh (Cupertino, CA) computers are gaining popularity with many radiologists, due in part to the availability of a powerful, free, open-source Digital Imaging and Communications in Medicine (DICOM) viewing and manipulating software OsiriX (http://www.osirix-viewer.com). Apple's own presentation software, Keynote, is particularly effective in dealing with medical images and cine clips. This article demonstrates how to use Apple's Keynote software to present radiology images and scrollable image stacks, without third-party add-on software. The article also illustrates how to compress media files and protect patient information in Keynote presentations. Lastly, it addresses the steps to converting between PowerPoint and Keynote file formats. Apple's Keynote software enables quick and efficient addition of multiple static images or scrollable image stacks, compression of media files, and removal of patient information. These functions can be accomplished by inexperienced users with no software modifications. C1 [Ghoshhajra, Brian B.; Techasith, Tust; Rojas, Carlos A.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Techasith, Tust; Rojas, Carlos A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Ghoshhajra, BB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM bghoshhajra@partners.org RI Ghoshhajra, Brian/J-2114-2016 OI Ghoshhajra, Brian/0000-0002-3865-3432 NR 6 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD OCT PY 2011 VL 24 IS 5 BP 844 EP 847 DI 10.1007/s10278-010-9345-y PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 825KU UT WOS:000295274000014 PM 20978920 ER PT J AU Axon, RN Tice, JA Egede, LE AF Axon, R. Neal Tice, Jeffrey A. Egede, Leonard E. TI Vitamin D as a Mediator of Racial Differences in Blood Pressure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; HYPERTENSION; HEALTH; TRENDS; RISK; SUPPLEMENTATION; PREVALENCE; AWARENESS; DISEASE; ADULTS C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Axon, R. Neal; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Axon, R. Neal; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Tice, Jeffrey A.] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1088 EP 1089 DI 10.1007/s11606-011-1791-9 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600004 PM 21748433 ER PT J AU Lyles, CR Karter, AJ Young, BA Spigner, C Grembowski, D Schillinger, D Adler, N AF Lyles, Courtney R. Karter, Andrew J. Young, Bessie A. Spigner, Clarence Grembowski, David Schillinger, Dean Adler, Nancy TI Patient-Reported Racial/Ethnic Healthcare Provider Discrimination and Medication Intensification in the Diabetes Study of Northern California (DISTANCE) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes; healthcare disparities; managed care; race/ethnicity; quality; discrimination ID QUALITY-OF-CARE; PERCEIVED DISCRIMINATION; HYPERTENSION MANAGEMENT; RACIAL-DISCRIMINATION; TECHNICAL QUALITY; CLINICAL-PRACTICE; BLOOD-PRESSURE; UNITED-STATES; ADHERENCE; DISEASE AB BACKGROUND: Racial/ethnic minority patients are more likely to report experiences with discrimination in the healthcare setting, potentially leading to reduced access to appropriate care; however, few studies evaluate reports of discrimination with objectively measured quality of care indicators. OBJECTIVE: To evaluate whether patient-reported racial/ethnic discrimination by healthcare providers was associated with evidence of poorer quality care measured by medication intensification. RESEARCH DESIGN AND PARTICIPANTS: Baseline data from the Diabetes Study of Northern California (DISTANCE), a random, race-stratified sample from the Kaiser Permanente Diabetes Registry from 2005-2006, including both survey and medical record data. MAIN MEASURES: Self-reported healthcare provider discrimination (from survey data) and medication intensification (from electronic prescription records) for poorly controlled diabetes patients (A1c >= 9.0%; systolic BP >= 140 mmHg or diastolic BP >= 90 mmHg; low-density lipoprotein (LDL) >= 130 mg/dl). KEY RESULTS: Of 10,409 eligible patients, 21% had hyperglycemia, 14% had hyperlipidemia, and 32% had hypertension. Of those with hyperglycemia, 59% had their medications intensified, along with 40% with hyperlipidemia, 33% with hypertension, and 47% in poor control of any risk factor. In adjusted log-binomial GEE models, discrimination was not associated with medication intensification [RR = 0.96 (95% CI: 0.74, 1.24) for hyperglycemia, RR = 1.23 (95% CI: 0.93, 1.63) for hyperlipidemia, RR = 1.06 (95% CI: 0.69, 1.61) for hypertension, and RR = 1.08 (95% CI: 0.88, 1.33) for the composite cohort]. CONCLUSIONS: We found no evidence that patient-reported healthcare discrimination was associated with less medication intensification. While not associated with this technical aspect of care, discrimination could still be associated with other aspects of care (e.g., patient-centeredness, communication). C1 [Lyles, Courtney R.; Spigner, Clarence; Grembowski, David] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Karter, Andrew J.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Young, Bessie A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Adler, Nancy] UCSF, Ctr Hlth & Community, San Francisco, CA USA. [Schillinger, Dean] UCSF, San Francisco Gen Hosp, Ctr Vulnerable Populat, San Francisco, CA USA. RP Lyles, CR (reprint author), Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Box 359455, Seattle, WA 98195 USA. EM crees@u.washington.edu FU National Research Service; AHRQ [HS013853]; NIDDK [R01 DK65664, R01 DK080726]; NICHD [R01 HD46113] FX This project was supported by a National Research Service Award, grant number HS013853 from AHRQ, and funds were provided by NIDDK R01 DK65664, NICHD R01 HD46113, and NIDDK R01 DK080726. None of the authors had conflicts of interest, and the funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. All authors contributed to the conception and design, and drafting and critical revision of the manuscript, including final approval of the version to be published. NR 43 TC 5 Z9 5 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1138 EP 1144 DI 10.1007/s11606-011-1729-2 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600014 PM 21547610 ER PT J AU Ahluwalia, SC Gross, CP Chaudhry, SI Leo-Summers, L Van Ness, PH Fried, TR AF Ahluwalia, Sangeeta C. Gross, Cary P. Chaudhry, Sarwat I. Leo-Summers, Linda Van Ness, Peter H. Fried, Terri R. TI Change in Comorbidity Prevalence with Advancing Age Among Persons with Heart Failure SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE heart failure; comorbidity; prevalence; age groups ID OBSTRUCTIVE PULMONARY-DISEASE; MULTIPLE CHRONIC CONDITIONS; CHRONIC KIDNEY-DISEASE; ELDERLY POPULATION; DIASTOLIC FUNCTION; OLDER PATIENTS; IMPACT; MORTALITY; ENALAPRIL; SURVIVAL AB BACKGROUND: Comorbidity-a condition that co-exists with a primary illness-is common among older persons with heart failure and can complicate the overall management of this population. OBJECTIVES: To determine the relationship between advancing age and the prevalence and patterns of comorbidity among older persons with heart failure. DESIGN: Retrospective longitudinal cohort study PARTICIPANTS: A total of 201,130 Medicare beneficiaries with heart failure stratified into three age strata in 2001: 66-75, 76-85, and 86+ years, and followed over 5 years. MEASUREMENTS: (1) Prevalence of 19 conditions as identified by the Chronic Conditions Warehouse from Medicare claims data, characterized as concordant (related to heart failure) or discordant (unrelated to heart failure), and (2) overall comorbidity burden, defined as count of conditions. RESULTS: The median number of comorbidities rose from four (IQR: 2-5) to five (IQR: 4-7) among the young-old, and from 4 (IQR: 3-6) to 6 (IQR: 5-8) among the middle-old and oldest-old between 2001 and 2006. In 2001, the majority of concordant conditions were more prevalent among the youngest than oldest beneficiaries (e.g., diabetes 46.2% vs 26.9%; kidney disease 21.8% vs 18.4%), while the majority of discordant conditions were more prevalent among the oldest-old than youngest-old beneficiaries (e.g., dementia 39.6% vs 9.9%; hip fracture 9.5% vs 1.9%). Discordant conditions increased in prevalence faster among the oldest than youngest beneficiaries (e.g., dementia 13% points versus 9% points). CONCLUSION: Among older Medicare beneficiaries with heart failure, there is a higher overall burden of comorbidity and greater prevalence of discordant comorbidity among the oldest old. Comorbidity prevalence increases over time, with discordant comorbidity increasing at the fastest rate among the oldest old. This comorbidity burden highlights the challenge of effectively treating heart failure while simultaneously managing co-existing and unrelated conditions. C1 [Ahluwalia, Sangeeta C.] VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Gross, Cary P.; Chaudhry, Sarwat I.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Leo-Summers, Linda; Van Ness, Peter H.] Yale Univ, Sch Med, Program Aging, New Haven, CT 06510 USA. [Van Ness, Peter H.; Fried, Terri R.] Yale Univ, Sch Med, Dept Internal Med, Sect Geriatr, New Haven, CT 06510 USA. [Fried, Terri R.] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Ahluwalia, SC (reprint author), VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90064 USA. EM sangeeta.ahluwalia@va.gov FU National Institute on Aging [T32AG1934, K24 AG028443, K23AG030986]; Office of Academic Affiliation at the VA Greater Los Angeles HSR&D Center of Excellence; Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine [2P30AG021342-06 NIH/NIA] FX Dr. Ahluwalia was supported by a training grant from the National Institute on Aging (T32AG1934) and is currently supported by an Office of Academic Affiliation's VA Associated Health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. Dr. Fried is a recipient of a Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging (K24 AG028443). Dr. Chaudhry is the recipient of a Paul Beeson/K23 Career Development Award (K23AG030986) from the National Institute on Aging. Supported by the Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (#2P30AG021342-06 NIH/NIA). NR 41 TC 23 Z9 23 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1145 EP 1151 DI 10.1007/s11606-011-1725-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600015 PM 21573881 ER PT J AU Steinman, MA Harlow, JB Massie, BM Kaboli, PJ Fung, KZ Heidenreich, PA AF Steinman, Michael A. Harlow, John B. Massie, Barry M. Kaboli, Peter J. Fung, Kathy Z. Heidenreich, Paul A. TI Age and Receipt of Guideline-Recommended Medications for Heart Failure: A Nationwide Study of Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE guideline adherence; heart failure; aging; health services research; quality of care ID QUALITY-OF-CARE; BETA-BLOCKER THERAPY; CONVERTING ENZYME-INHIBITORS; OLDER PATIENTS; DIABETES-MELLITUS; CLINICAL-PRACTICE; MANAGED MEDICARE; ELDERLY-PATIENTS; NORTH-CAROLINA; TRIAL AB BACKGROUND: Older patients often receive less guideline-concordant care for heart failure than younger patients. OBJECTIVE: To determine whether age differences in heart failure care are explained by patient, provider, and health system characteristics and/or by chart-documented reasons for non-adherence to guidelines. DESIGN AND PATIENTS: Retrospective cohort study of 2,772 ambulatory veterans with heart failure and left ventricular ejection fraction < 40% from a 2004 nationwide medical record review program (the VA External Peer Review Program). MAIN MEASURES: Ambulatory use of ACE inhibitors, angiotensin receptor blockers (ARBs), and beta blockers. RESULTS: Among 2,772 patients, mean age was 73 +/- 10 years, 87% received an ACE inhibitor or ARB, and 82% received a beta blocker. When patients with explicit chart-documented reasons for not receiving these drugs were excluded, 95% received an ACE inhibitor or ARB and 89% received a beta blocker. In multivariable analyses controlling for a variety of patient and health system characteristics, the adjusted odds ratio for ACE-inhibitor and ARB use was 0.43 (95% CI 0.24-0.78) for patients age 80 and over vs. those age 50-64 years, and the adjusted odds ratio for beta blocker use was 0.66 (95% CI 0.48-0.93) between the two age groups. The magnitude of these associations was similar but not statistically significant after excluding patients with chart-documented reasons for not prescribing ACE inhibitors or ARBs and beta blockers. CONCLUSIONS: A high proportion of veterans receive guideline-recommended medications for heart failure. Older veterans are consistently less likely to receive these drugs, although these differences were no longer significant when accounting for patients with chart-documented reasons for not prescribing these drugs. Closely evaluating reasons for non-prescribing in older adults is essential to assessing whether non-treatment represents good clinical judgment or missed opportunities to improve care. C1 [Steinman, Michael A.] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, San Francisco, CA 94121 USA. [Steinman, Michael A.; Harlow, John B.; Fung, Kathy Z.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.; Harlow, John B.; Massie, Barry M.; Fung, Kathy Z.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [Massie, Barry M.; Heidenreich, Paul A.] Vet Hlth Adm Congest Heart Failure Qual Enhanceme, Washington, DC USA. [Kaboli, Peter J.] Iowa City VA Healthcare Syst, Comprehens Access & Delivery Res & Evaluat CADR, Iowa City, IA USA. [Kaboli, Peter J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Div Gen Internal Med, Iowa City, IA USA. [Heidenreich, Paul A.] Palo Alto VA Hlth Care Syst, Div Cardiol, Palo Alto, CA USA. [Heidenreich, Paul A.] Stanford Univ, Palo Alto, CA 94304 USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program REAP, 4150 Clement St,VA Box 181 G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu OI Heidenreich, Paul/0000-0001-7730-8490 FU VA Health Services Research and Development Service [IIR 06-080-2]; National Institute on Aging; American Federation for Aging Research [K23-AG030999] FX This work was funded by the VA Health Services Research and Development Service (IIR 06-080-2, Dr. Steinman) and by the National Institute on Aging and American Federation for Aging Research (K23-AG030999, Dr. Steinman). The funding sources had no control over the analysis, writing, or decision to publish this manuscript. NR 44 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1152 EP 1159 DI 10.1007/s11606-011-1745-2 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600016 PM 21604076 ER PT J AU Seal, KH Cohen, G Bertenthal, D Cohen, BE Maguen, S Daley, A AF Seal, Karen H. Cohen, Greg Bertenthal, Daniel Cohen, Beth E. Maguen, Shira Daley, Aaron TI Reducing Barriers to Mental Health and Social Services for Iraq and Afghanistan Veterans: Outcomes of an Integrated Primary Care Clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veterans; mental health; health services utilization; primary care ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE CARE; WAR VETERANS; RISK-FACTORS; US-VETERANS; DEPRESSION; DIAGNOSES; COMBAT; ASSOCIATION AB BACKGROUND: Despite high rates of post-deployment psychosocial problems in Iraq and Afghanistan veterans, mental health and social services are under-utilized. OBJECTIVE: To evaluate whether a Department of Veterans Affairs (VA) integrated care (IC) clinic (established in April 2007), offering an initial three-part primary care, mental health and social services visit, improved psychosocial services utilization in Iraq and Afghanistan veterans compared to usual care (UC), a standard primary care visit with referral for psychosocial services as needed. DESIGN: Retrospective cohort study using VA administrative data. POPULATION: Five hundred and twenty-six Iraq and Afghanistan veterans initiating primary care at a VA medical center between April 1, 2005 and April 31, 2009. MAIN MEASURES: Multivariable models compared the independent effects of primary care clinic type (IC versus UC) on mental health and social services utilization outcomes. KEY RESULTS: After 2007, compared to UC, veterans presenting to the IC primary care clinic were significantly more likely to have had a within-30-day mental health evaluation (92% versus 59%, p < 0.001) and social services evaluation [77% (IC) versus 56% (UC), p < 0.001]. This exceeded background system-wide increases in mental health services utilization that occurred in the UC Clinic after 2007 compared to before 2007. In particular, female veterans, younger veterans, and those with positive mental health screens were independently more likely to have had mental health and social service evaluations if seen in the IC versus UC clinic. Among veterans who screened positive for a parts per thousand yenaEuro parts per thousand 1 mental health disorder(s), there was a median of 1 follow-up specialty mental health visit within the first year in both clinics. CONCLUSIONS: Among Iraq and Afghanistan veterans new to primary care, an integrated primary care visit further improved the likelihood of an initial mental health and social services evaluation over background increases, but did not improve retention in specialty mental health services. C1 [Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Seal, Karen H.; Cohen, Greg; Bertenthal, Daniel; Cohen, Beth E.; Maguen, Shira; Daley, Aaron] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Seal, KH (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,Box 111A 1, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov FU San Francisco VA HSR&D Research Enhancement Award Program; Department of Defense [W81XWH-08-2-0072, W81XWH-08-2-0106] FX We would like to thank Dr. Rina Shah and Dr. Dawn Lawhon for their leadership in the design and coordination of the SFVAMC Integrated Care Clinic. We acknowledge the support of the San Francisco VA HSR&D Research Enhancement Award Program. We would also like to thank Ms. Ann Chu for her assistance in data abstraction. Finally, we acknowledge and thank veterans of Iraq and Afghanistan for their service to our country.; This study was funded by Department of Defense awards W81XWH-08-2-0072 and W81XWH-08-2-0106. The funders had no role in the design, data analysis, writing or approval of the manuscript. NR 57 TC 20 Z9 20 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1160 EP 1167 DI 10.1007/s11606-011-1746-1 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600017 PM 21647750 ER PT J AU Grenard, JL Munjas, BA Adams, JL Suttorp, M Maglione, M McGlynn, EA Gellad, WF AF Grenard, Jerry L. Munjas, Brett A. Adams, John L. Suttorp, Marika Maglione, Margaret McGlynn, Elizabeth A. Gellad, Walid F. TI Depression and Medication Adherence in the Treatment of Chronic Diseases in the United States: A Meta-Analysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE depression; adherence; chronic disease; meta-analysis ID HYPERTENSIVE AFRICAN-AMERICANS; CORONARY-HEART-DISEASE; PATIENT-ADHERENCE; MATHEMATICAL CONTRIBUTIONS; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; META-ANALYSIS; NONADHERENCE; PREDICTORS; SYMPTOMS AB OBJECTIVE: To conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens. DATA SOURCES: We searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence. STUDY APPRAISAL AND SYNTHESIS METHODS: Data abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis. RESULTS: The estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures. LIMITATIONS: The meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used. CONCLUSIONS: This analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it. C1 [Grenard, Jerry L.] Claremont Grad Univ, Sch Community & Global Hlth, San Dimas, CA 91773 USA. [Munjas, Brett A.; Adams, John L.; Suttorp, Marika; Maglione, Margaret; Gellad, Walid F.] RAND Corp, Santa Monica, CA USA. [McGlynn, Elizabeth A.] Kaiser Permanente Ctr Effectiveness & Safety Res, Pasadena, CA USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gellad, Walid F.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Grenard, JL (reprint author), Claremont Grad Univ, Sch Community & Global Hlth, 180 E Via Verde St,Suite 100, San Dimas, CA 91773 USA. EM jerry.grenard@cgu.edu FU Agency for Healthcare Research and Quality (AHRQ) [T32 HS00046-14]; VA HSR&D Career Development Award [CDA 09-207]; Mehlman Vogel Castagnetti FX This research was supported by the Agency for Healthcare Research and Quality (AHRQ: T32 HS00046-14), a VA HSR&D Career Development Award to Dr. Gellad (CDA 09-207), and by Mehlman Vogel Castagnetti. NR 88 TC 103 Z9 107 U1 6 U2 36 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1175 EP 1182 DI 10.1007/s11606-011-1704-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600019 PM 21533823 ER PT J AU Erickson, B Dhaliwal, G Henderson, MC Amsterdam, E Rencic, J AF Erickson, Brandon Dhaliwal, Gurpreet Henderson, Mark C. Amsterdam, Ezra Rencic, Joseph TI Effusive Reasoning SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE pattern recognition; analytic reasoning; problem representation; clinical diagnostic reasoning ID PRIMARY SYSTEMIC AMYLOIDOSIS; RESTRICTIVE CARDIOMYOPATHY; CONSTRICTIVE PERICARDITIS; INVOLVEMENT; FEATURES C1 [Rencic, Joseph] Tufts Med Ctr, Dept Internal Med, Boston, MA 02111 USA. [Erickson, Brandon; Rencic, Joseph] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Henderson, Mark C.] Univ Calif Davis, Med Ctr, Dept Internal Med, Sacramento, CA 95817 USA. [Amsterdam, Ezra] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Dept Internal Med, Sacramento, CA 95817 USA. RP Rencic, J (reprint author), Tufts Med Ctr, Dept Internal Med, 750 Washington St,Box 398, Boston, MA 02111 USA. EM jrencic@tuftsmedicalcenter.org NR 15 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1204 EP 1208 DI 10.1007/s11606-011-1785-7 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600023 PM 21761239 ER PT J AU Erickson, B Dhaliwal, G Henderson, MC Amsterdam, E Rencic, J AF Erickson, Brandon Dhaliwal, Gurpreet Henderson, Mark C. Amsterdam, Ezra Rencic, Joseph TI Effusive Reasoning (vol 26, pg 1204, 2011) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Correction C1 [Erickson, Brandon; Rencic, Joseph] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Amsterdam, Ezra] Calif State Univ Sacramento, Dept Internal Med, Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA 95819 USA. [Rencic, Joseph] Tufts Med Ctr, Dept Internal Med, Boston, MA USA. RP Erickson, B (reprint author), Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2011 VL 26 IS 10 BP 1235 EP 1235 DI 10.1007/s11606-011-1846-y PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826CS UT WOS:000295329600030 ER PT J AU Massie, BM AF Massie, Barry M. TI Novel targets for the treatment of heart failure: Perspectives from a heart failure clinician and trialist SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID SURVIVAL; ENALAPRIL; MORTALITY C1 [Massie, Barry M.] Univ Calif San Francisco, Div Cardiol, San Francisco VAMC, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Massie, BM (reprint author), Univ Calif San Francisco, Div Cardiol, San Francisco VAMC, San Francisco, CA 94143 USA. EM barry.massie@va.gov NR 8 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD OCT PY 2011 VL 51 IS 4 BP 438 EP 440 DI 10.1016/j.yjmcc.2011.03.016 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 825SR UT WOS:000295302900002 PM 21549124 ER PT J AU Healy, B Chitnis, T Engler, D AF Healy, Brian Chitnis, Tanuja Engler, David TI Improving power to detect disease progression in multiple sclerosis through alternative analysis strategies SO JOURNAL OF NEUROLOGY LA English DT Article DE Clinical trials; Disease progression; Multiple sclerosis; Sample size calculations ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INTERFERON BETA-1A; CLINICAL-TRIALS; RELAPSE RATE; DISABILITY; MULTICENTER; NATALIZUMAB; MRI; MS AB In patients with multiple sclerosis, investigation of a treatment effect on disease progression in clinical trials and observational studies often uses sustained progression on the expanded disability status scale (EDSS) as an outcome. It is not clear whether this outcome is the most powerful to detect a treatment effect on clinical disease progression. Assessment of EDSS modeling choice on the detection of treatment effect was of interest. This assessment was separately conducted under three potential treatment effects: treatment reducing the chance of higher future EDSS, treatment increasing the chance of lower future EDSS, and treatment leading to both effects. To assess the effect of modeling choice, nine modeling strategies were applied to the data to determine the most powerful approach. EDSS measurements were simulated at 6 month intervals for 24 months. Each patient's initial EDSS value ranged between 0 and 3, and probabilities of transitioning from one EDSS state to another were based on the empirical probabilities of transition obtained from available clinical data. Modeling approaches based on sustained progression had less power than approaches which modeled the EDSS score directly, regardless of treatment effect. This difference was especially pronounced when the treatment effect corresponded to an increase in the probability of improvement. Sustained progression on the EDSS is a less powerful outcome measure for clinical progression than approaches based on the actual EDSS values. C1 [Healy, Brian; Chitnis, Tanuja] Brigham & Womens Hosp, Partners MS Ctr, Brookline, MA 02445 USA. [Healy, Brian] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Engler, David] 230 TMCB Brigham Young Univ, Dept Stat, Provo, UT 84602 USA. RP Healy, B (reprint author), Brigham & Womens Hosp, Partners MS Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM bchealy@partners.org FU EMD-Serono Inc. FX Drs. Healy and Chitnis would like to acknowledge EMD-Serono Inc. for research support during the completion of this manuscript. NR 28 TC 9 Z9 9 U1 1 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD OCT PY 2011 VL 258 IS 10 BP 1812 EP 1819 DI 10.1007/s00415-011-6021-1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 828WI UT WOS:000295534400009 PM 21472497 ER PT J AU Zhao, NH Wang, DD Huang, XB Karri, SK Wu, HY Zheng, MX AF Zhao, Ninghui Wang, Doris D. Huang, Xiaobin Karri, Surya K. Wu, Haiying Zheng, Mingxiu TI Spontaneous otogenic pneumocephalus presenting with occipital subcutaneous emphysema as primary symptom: could tension gas cause the destruction of cranial bones? Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE pneumocephalus; hyperpneumatization; emphysema; minimally invasive surgery ID OF-THE-LITERATURE; CT DEMONSTRATION; PNEUMATOCELE; HYPERPNEUMATIZATION; AIR AB The authors report, to the best of their knowledge, the first case of a spontaneous tension pneumocephalus with subcutaneous emphysema. Hyperpneumatization of the cranium and mechanical compression contributed jointly to the formation of a fistula, and air pressure caused a subsequent disruption of the suture and air leakage into the subcutaneous space. A minimally invasive otological procedure proved efficacious for resolution. (DOI: 10.3171/2011.6.JNS11104) C1 [Zhao, Ninghui; Huang, Xiaobin] Kunming Med Coll, Dept Neurosurg, Affiliated Hosp 2, Kunming 650101, Yunnan, Peoples R China. [Wu, Haiying; Zheng, Mingxiu] Kunming Med Coll, Dept Otorhinolaryngol, Affiliated Hosp 2, Kunming 650101, Yunnan, Peoples R China. [Zhao, Ninghui; Karri, Surya K.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. [Wang, Doris D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. RP Zhao, NH (reprint author), Kunming Med Coll, Dept Neurosurg, Affiliated Hosp 2, 1 Mayuan, Kunming 650101, Yunnan, Peoples R China. EM zhaoninghui@hotmail.com NR 25 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2011 VL 115 IS 4 BP 679 EP 683 DI 10.3171/2011.6.JNS11104 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 825SD UT WOS:000295301500004 PM 21740114 ER PT J AU Grisanzio, C Seeley, A Chang, M Collins, M Di Napoli, A Cheng, SC Percy, A Beroukhim, R Signoretti, S AF Grisanzio, Chiara Seeley, Apryle Chang, Michelle Collins, Michael Di Napoli, Arianna Cheng, Su-Chun Percy, Andrew Beroukhim, Rameen Signoretti, Sabina TI Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients SO JOURNAL OF PATHOLOGY LA English DT Article DE renal cell carcinoma; mouse model; orthotopic xenograft; sub-renal capsule implantation ID RENAL-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; CARBONIC-ANHYDRASE-IX; DIFFERENTIAL-DIAGNOSIS; DRUG ACTIVITY; CANCER; MODEL; THERAPY; IMMUNOTHERAPY; IMPLANTATION AB Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumour tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphological, phenotypic and genetic characteristics of the kidney tumour tissues before and after implantation. Twenty kidney tumours were transplanted into mice. Successful tumour growth was detected in 19 cases (95%). The histopathological and immunophenotypic features of the xenografts and those of the original tumours largely overlapped in all cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumours and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6/10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing and for deeper understanding of kidney carcinogenesis. The raw data of the SNP array analysis has been submitted to the GEO database (Accession No. GSE29062). Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Signoretti, Sabina] Harvard Univ, Dept Pathol, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Grisanzio, Chiara; Seeley, Apryle; Beroukhim, Rameen; Signoretti, Sabina] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Percy, Andrew] Harvard Univ, Sch Med, Div Hematol Oncol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Beroukhim, Rameen] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Signoretti, S (reprint author), Harvard Univ, Dept Pathol, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02215 USA. EM ssignoretti@partners.org FU Dana-Farber/Harvard Cancer Center; Istituto Dermopatico dell'Immacolata, Italy; American Italian Cancer Foundation; Achille Lattuca Foundation, Italy; NIH [K08CA122833]; Doris Duke Charitable Foundation FX We thank Victoria E. Brown and Brittany Bahamon for assistance with immunohistochemical stains. This work was supported by the Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE and by an Award from Istituto Dermopatico dell'Immacolata, Italy to SS. CG is the recipient of an American Italian Cancer Foundation's International Postdoctoral Research Fellowship. ADN is the recipient of a Fellowship Award from the Achille Lattuca Foundation, Italy. RB is the recipient of awards from the NIH (K08CA122833) and the Doris Duke Charitable Foundation. NR 61 TC 13 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2011 VL 225 IS 2 BP 212 EP 221 DI 10.1002/path.2929 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 826ZF UT WOS:000295393400009 PM 21710693 ER PT J AU Mishra, RK Devereux, RB Cohen, BE Whooley, MA Schiller, NB AF Mishra, Rakesh K. Devereux, Richard B. Cohen, Beth E. Whooley, Mary A. Schiller, Nelson B. TI Prediction of Heart Failure and Adverse Cardiovascular Events in Outpatients with Coronary Artery Disease Using Mitral E/A Ratio in Conjunction with E-Wave Deceleration Time: The Heart and Soul Study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Echocardiography; Diastolic function; Mitral deceleration time; Mitral E-to-A ratio; Heart failure; Adverse cardiovascular events ID VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; DIASTOLIC FUNCTION; VELOCITY; ECHOCARDIOGRAPHY; RECOMMENDATIONS; MORTALITY; PRESSURE; LIFE AB Background: Deceleration time (DT) of early mitral inflow (E) is a marker of diastolic left ventricular (LV) chamber stiffness that is routinely measured during the quantitation of LV diastolic function with Doppler echocardiography. Shortened DT after myocardial infarction predicts worse cardiovascular outcome. Recent studies have shown that indexing DT to peak E-wave velocity (pE) augments its prognostic power in a population with a high prevalence of coronary risk factors and in patients with hypertension during antihypertensive treatment. However, in ambulatory subjects with stable coronary artery disease (CAD), it is not known whether DT predicts cardiovascular events and whether DT/pE improves its prognostic power. Methods: The ability of DT and DT/pE to predict heart failure (HF) hospitalizations and other major adverse cardiovascular events (MACEs) was studied prospectively in 926 ambulatory patients with stable CAD enrolled in the Heart and Soul Study. Unadjusted and multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for HF and other MACEs. Results: During a mean of 6.3 +/- 2.0 years, there were 124 hospitalizations for HF and 198 other MACEs. Relative to participants with mitral E/A ratios in the normal range (0.75 < E/A < 1.5; n = 604), those with E/A ratios >= 1.5 (n = 107) had an increased risk for HF (HR, 2.54; 95% CI, 1.52-4.25, P < .001) but not for other MACEs (HR, 1.00; 95% CI, 0.60-1.68; P = 1.00), while those with E/A ratios <= 0.75 (n = 215) were not at increased risk for either outcome. Among patients with normal E/A ratios, lower DT/pE predicted HF (HR, 0.47; 95% CI, 0.23-0.97, P = .04 per point increase in ln{msec/[cm/sec]}), while DT alone did not. However, in this group with normal E/A ratios, neither DT/pE nor DT alone was predictive of other MACEs. In patients with E/A ratios <= 0.75 (n = 215) and those with E/A ratios >= 1.5 (n = 107), neither DT nor DT/pE predicted either end point. Conclusions: In ambulatory patients with stable CAD, restrictive filling (E/A ratio >= 1.5) is a powerful predictor of HF. Among those with normal mitral E/A ratios (0.75-1.5), only DT/pE predicts HF, while neither DT nor DT/pE predicts other MACEs. This suggests that mitral E/A ratio has significant prognostic value in patients with CAD, and in those with normal mitral E/A ratios, the normalization of DT to pE augments its prognostic power. (J Am Soc Echocardiogr 2011;24:1134-40.) C1 [Mishra, Rakesh K.; Cohen, Beth E.; Whooley, Mary A.] Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Mishra, Rakesh K.; Cohen, Beth E.; Whooley, Mary A.; Schiller, Nelson B.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Devereux, Richard B.] Weill Cornell Med Coll, Greenberg Div Cardiol, Dept Med, New York, NY USA. RP Mishra, RK (reprint author), San Francisco VA Med Ctr, Div Cardiol 111C, 4150 Clement St, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu NR 17 TC 7 Z9 7 U1 1 U2 1 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 OCT PY 2011 VL 24 IS 10 BP 1134 EP 1140 DI 10.1016/j.echo.2011.06.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 827WE UT WOS:000295459200010 PM 21764551 ER PT J AU Moreno, PR Astudillo, L Elmariah, S Purushothaman, KR Purushothaman, M Lento, PA Sharma, SK Fuster, V Adams, DH AF Moreno, Pedro R. Astudillo, Luis Elmariah, Sammy Purushothaman, K. Raman Purushothaman, Meeranani Lento, Patrick A. Sharma, Samin K. Fuster, Valentin Adams, David H. TI Increased macrophage infiltration and neovascularization in congenital bicuspid aortic valve stenosis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID PLAQUE VULNERABILITY; ANGIOGENESIS; DISEASE; CALCIFICATION; INFLAMMATION; PROGRESSION; MUTATIONS; CELLS AB Objectives: Patients with congenital bicuspid aortic valves have aortic valve stenosis at a relatively young age compared with patients with tricuspid aortic valves. We hypothesize that aortic valve stenosis evolves from a more aggressive inflammatory process, with increased macrophage/T-cell and neovessel content in congenital bicuspid aortic valveswhen compared with that seen in tricuspid valves. Methods: Fifty-one severely stenotic aortic valves were obtained at the time of aortic valve replacement. A total of 17 bicuspid and 34 tricuspid aortic valves were evaluated. Macrophage/T-cell infiltration (CD68 plus CD3) and neovessel density (CD34) were evaluated with immunohistochemical staining. Leaflet calcification and ossification were also quantified. Real-time polymerase chain reaction was used to assess expression of chondromodulin 1 and vascular endothelial growth factor. Results: The density of macrophages/T cells was greater in congenital bicuspid aortic valves than in tricuspid valves (51 +/- 31 vs 23 +/- 13 cells/mm(2), P = .002). Neovascularization was more frequently noted in congenital bicuspid aortic valves when compared with tricuspid valves (31 +/- 10 vs 21 +/- 9 vessels/mm(2), P = .0005), and calcification was more severe (P = .03). Expression of chondromodulin 1 demonstrated a 6-fold downregulation (P = .0003) and expression of vascular endothelial growth factor demonstrated a 2-fold increase (P = .02) in congenital bicuspid aortic valves compared with that seen in tricuspid valves. Multivariable analyses demonstrated significant associations between bicuspid aortic valve anatomy and increased inflammatory cell infiltration (beta = 25.8, P = .0007) and neovascularization (beta = 9.4, P = .001), despite adjusting for measured covariates. Conclusions: The pathogenesis of aortic valve stenosis in bicuspid aortic valves is associated with a more aggressive inflammatory process with increased macrophage infiltration and neovascularization when compared with that seen in tricuspid valves. (J Thorac Cardiovasc Surg 2011; 142:895-901) C1 [Moreno, Pedro R.; Astudillo, Luis; Elmariah, Sammy; Purushothaman, K. Raman; Purushothaman, Meeranani; Sharma, Samin K.; Fuster, Valentin] Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, New York, NY 10029 USA. [Lento, Patrick A.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. [Adams, David H.] Mt Sinai Sch Med, Dept Cardiothorac Surg, New York, NY 10029 USA. [Elmariah, Sammy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fuster, Valentin] CNIC, Madrid, Spain. RP Moreno, PR (reprint author), Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. EM pedro.moreno@msnyuhealth.org RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Sharma, Sanjeev Kumar/0000-0002-3273-0708 FU Glorney-Raisbeck Fellowship Program; Corlette Glorney Foundation; New York Academy of Medicine; GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease; National Heart, Lung, and Blood Institute [T32 HL007824] FX Dr. Elmariah was supported by the Glorney-Raisbeck Fellowship Program, the Corlette Glorney Foundation, and the New York Academy of Medicine; by the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease; and by a grant from the National Heart, Lung, and Blood Institute (T32 HL007824). NR 25 TC 13 Z9 14 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2011 VL 142 IS 4 BP 895 EP 901 DI 10.1016/j.jtcvs.2011.03.002 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 825FF UT WOS:000295255700025 PM 21481422 ER PT J AU Baid-Agrawal, S Farris, AB Pascual, M Mauiyyedi, S Farrell, ML Tolkoff-Rubin, N Collins, AB Frei, U Colvin, RB AF Baid-Agrawal, Seema Farris, Alton B., III Pascual, Manuel Mauiyyedi, Shamila Farrell, Mary Lin Tolkoff-Rubin, Nina Collins, A. Bernard Frei, Ulrich Colvin, Robert B. TI Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy SO KIDNEY INTERNATIONAL LA English DT Article DE antibody-mediated rejection; hepatitis; kidney transplantation ID ANTIBODY-MEDIATED REJECTION; RENAL-ALLOGRAFT REJECTION; DONOR-SPECIFIC ANTIBODY; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; VIRUS-INFECTION; C4D DEPOSITS; PERITUBULAR CAPILLARIES; PRODUCT C4D; KIDNEY; BIOPSIES AB Transplant glomerulopathy (TG) has received much attention in recent years as a symptom of chronic humoral rejection; however, many cases lack C4d deposition and/or circulating donor-specific antibodies (DSAs). To determine the contribution of other causes, we studied 209 consecutive renal allograft indication biopsies for chronic allograft dysfunction, of which 25 met the pathological criteria of TG. Three partially overlapping etiologies accounted for 21 (84%) cases: C4d-positive (48%), hepatitis C-positive (36%), and thrombotic microangiopathy (TMA)-positive (32%) TG. The majority of patients with confirmed TMA were also hepatitis C positive, and the majority of hepatitis C-positive patients had TMA. DSAs were significantly associated with C4d-positive but not with hepatitis C-positive TG. The prevalence of hepatitis C was significantly higher in the TG group than in 29 control patients. Within the TG cohort, those who were hepatitis C-positive developed allograft failure significantly earlier than hepatitis C-negative patients. Thus, TG is not a specific diagnosis but a pattern of pathological injury involving three major overlapping pathways. It is important to distinguish these mechanisms, as they may have different prognostic and therapeutic implications. Kidney International (2011) 80, 879-885; doi:10.1038/ki.2011.194; published online 22 June 2011 C1 [Baid-Agrawal, Seema; Frei, Ulrich] Charite, Dept Nephrol & Med Intens Care, Campus Virchow Clin, D-13353 Berlin, Germany. [Farris, Alton B., III] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Pascual, Manuel] Univ Hosp Lausanne CHUV, Transplantat Ctr, Dept Med, Lausanne, Switzerland. [Mauiyyedi, Shamila] Univ Texas Hlth Sci Ctr Houston, Dept Pathol & Lab Med, Houston, TX USA. [Farrell, Mary Lin; Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. [Farrell, Mary Lin; Tolkoff-Rubin, Nina; Collins, A. Bernard; Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA USA. [Collins, A. Bernard; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Farrell, Mary Lin; Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. [Pascual, Manuel] Univ Hosp Lausanne CHUV, Dept Surg, Lausanne, Switzerland. RP Baid-Agrawal, S (reprint author), Charite, Dept Nephrol & Med Intens Care, Campus Virchow Clin, Augustenburger Pl 1, D-13353 Berlin, Germany. EM seema.baid-agrawal@charite.de NR 52 TC 54 Z9 56 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2011 VL 80 IS 8 BP 879 EP 885 DI 10.1038/ki.2011.194 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 827DF UT WOS:000295406600013 PM 21697808 ER PT J AU Ng, AK Hodgson, DC AF Ng, Andrea K. Hodgson, David C. TI Is there a role for consolidative radiation therapy for aggressive B-cell lymphoma in the rituximab era? SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID CHOP PLUS RADIOTHERAPY; NON-HODGKINS-LYMPHOMA; BREAST-CANCER; CHEMOTHERAPY; SURVIVAL C1 [Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. [Hodgson, David C.] Univ Toronto, Dept Radiat Oncol, Toronto, ON, Canada. [Hodgson, David C.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. RP Ng, AK (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. EM Ang@lroc.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2011 VL 52 IS 10 BP 1821 EP 1822 DI 10.3109/10428194.2011.594193 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 824CA UT WOS:000295176800001 PM 21942327 ER PT J AU Gera, J Lichtenstein, A AF Gera, Joseph Lichtenstein, Alan TI The mammalian target of rapamycin pathway as a therapeutic target in multiple myeloma SO LEUKEMIA & LYMPHOMA LA English DT Review DE Multiple myeloma; mTOR; rapalogs ID PHASE-II TRIAL; RENAL-CELL CARCINOMA; PROTEIN-KINASE; WALDENSTROM MACROGLOBULINEMIA; ENHANCED SENSITIVITY; SYNERGISTIC ACTIVITY; INHIBITOR RAPAMYCIN; MTOR INHIBITION; AKT ACTIVITY; TUMOR-CELLS AB The mammalian target of rapamycin (mTOR) is centrally located, linking proximal oncogenic cascades to critical downstream pathways that drive tumor growth. mTOR regulates such diverse functions as protein translation, proliferation, viability, autophagy, metabolism homeostasis, monitoring of energy reserves, and induction of angiogenesis. Given its fundamental role in tumorigenesis, it is not surprising that a huge effort is being made to develop mTOR inhibitors. The existence of feedback pathways that become activated subsequent to mTOR inhibition has complicated these efforts. However, the fact that mTOR exists in two separate complexes, TORC1 and TORC2, and rapalogs primarily inhibit only TORC1 and TORC2 is actually a key activator of AKT, has injected new energy into the quest to find inhibitors that can inhibit both complexes. In myeloma models, preclinical studies confirm the activity of rapalogs as well as newer TORC1/TORC2 inhibitors, and early phase clinical trials have begun. In addition, the recent finding of up-regulated myeloma cell expression of DEPTOR, an mTOR binding protein that restricts mTOR activity, suggests an additional future therapeutic target specific to the myeloma tumor model. C1 UCLA Sch Med, Greater Los Angeles VA Healthcare Ctr, Div Hematol Oncol, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. RP Lichtenstein, A (reprint author), VA W LA Hosp, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov NR 67 TC 17 Z9 19 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2011 VL 52 IS 10 BP 1857 EP 1866 DI 10.3109/10428194.2011.580478 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 824CA UT WOS:000295176800009 PM 21599581 ER PT J AU Yung, KT Zheng, WL Zhao, CG Martinez-Ramon, M van der Kouwe, A Posse, S AF Yung, Kaung-Ti Zheng, Weili Zhao, Chenguang Martinez-Ramon, Manel van der Kouwe, Andre Posse, Stefan TI Atlas-Based Automated Positioning of Outer Volume Suppression Slices in Short-Echo Time 3D MR Spectroscopic Imaging of the Human Brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR spectroscopic imaging; lipid suppression; outer volume suppression; affine transformation; brain atlas ID PROJECTION PRESATURATION; INTENSITY NONUNIFORMITY; LOCALIZATION; OPTIMIZATION; REGISTRATION; REGIONS; IMAGES; ROBUST; N3 AB Spatial suppression of peripheral lipid-containing regions in volumetric MR spectroscopic imaging of the human brain requires placing large numbers of outer volume suppression (OVS) slices, which is time-consuming, prone to operator error and may introduce subject-dependent variability in volume coverage. We developed a novel, computationally efficient atlas-based approach for automated positioning of up to 16 OVS slices and the MR spectroscopic imaging slab. Standardized positions in Montreal Neurological Institute atlas space were established offline using a recently developed iterative optimization procedure. During the scanning session, positions in subject space were computed using affine transformation of standardized positions in Montreal Neurological Institute space. Offline analysis using magnetization prepared rapid gradient echo scans from 11 subjects demonstrated reliable OVS placement, comparable with but faster than iterative placement in subject space. This atlas-based method was further validated in 14 subjects using 3D short-echo time proton-echo-planar-spectroscopic-imaging at 3 T. Comparison of manual and automatic placement using 8 OVS slices demonstrated consistent MR spectroscopic imaging volume selection and comparable spectral quality with similar degree of lipid suppression and number of usable voxels. Automated positioning of 16 OVS slices enabled larger volume coverage, while maintaining similar spectral quality and lipid suppression. Atlas-based automatic prescription of short echo time MR spectroscopic imaging is expected to be advantageous for longitudinal and cross-sectional studies. Magn Reson Med 66: 911-922, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Yung, Kaung-Ti; Zheng, Weili; Zhao, Chenguang; Posse, Stefan] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. [Martinez-Ramon, Manel] Univ Carlos III Madrid, Dept Signal Theory & Commun, Madrid, Spain. [van der Kouwe, Andre] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Posse, Stefan] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Posse, Stefan] Univ New Mexico, Dept Phys & Astron, Albuquerque, NM 87131 USA. RP Posse, S (reprint author), Univ New Mexico, Sch Med, Dept Neurol, 1 Univ New Mexico,MSC 105620, Albuquerque, NM 87131 USA. EM sposse@unm.edu RI Martinez-Ramon, Manel/C-2304-2008 FU MIND Research Network (DOE) [DE-FG02-99ER62764]; University of New Mexico School of Medicine; MICINN (Spanish Government) [TEC2008-0243] FX Grant sponsor: MIND Research Network (DOE); Grant number: DE-FG02-99ER62764; Grant sponsor: University of New Mexico School of Medicine Brain and Behavioral Illness Signature Program; Grant sponsor: Grant Sponsor: MICINN (Spanish Government); Grant number: TEC2008-0243. NR 31 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2011 VL 66 IS 4 BP 911 EP 922 DI 10.1002/mrm.22887 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500001 PM 21469184 ER PT J AU Bogner, W Chmelik, M Andronesi, OC Sorensen, AG Trattnig, S Gruber, S AF Bogner, W. Chmelik, M. Andronesi, O. C. Sorensen, A. G. Trattnig, S. Gruber, S. TI In Vivo (31)P Spectroscopy by Fully Adiabatic Extended Image Selected In Vivo Spectroscopy: A Comparison Between 3 T and 7 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE phosphorus; spectroscopy; extended ISIS; single voxel; 7 T; high field ID MAGNETIC-RESONANCE-SPECTROSCOPY; INVERSION FOCI PULSES; NMR-SPECTROSCOPY; INVIVO SPECTROSCOPY; HUMAN BRAIN; METABOLITE CONCENTRATIONS; ABSOLUTE QUANTIFICATION; INITIAL-EXPERIENCE; HIGH-FIELD; MR SYSTEM AB An improved image selected in vivo spectroscopy (ISIS) sequence for localized (31)P magnetic resonance spectroscopy at 7 T was developed. To reduce errors in localization accuracy, adiabatic excitation, gradient offset independent adiabatic inversion pulses, and a special extended ISIS ordering scheme were used. The localization accuracy of extended ISIS was investigated in phantoms. The possible spectral quality and reproducibility in vivo was explored in a volunteer (brain, muscle, and liver). A comparison between 3 T and 7 T was performed in five volunteers. Adiabatic extended ISIS provided high spectral quality and accurate localization. The contamination in phantom experiments was only similar to 5%, even if a pulse repetition time similar to 1.2.T(1) was chosen to maximize the signal-to-noise ratio per unit time. High reproducibility was found in the calf muscle for 2.5 cm isotropic voxels at 7 T. When compared with 3 T, localized (31)P magnetic resonance spectroscopy in the human calf muscle at 7 T provided similar to 3.2 times higher signal-to-noise ratio (as judged from phosphocreatine peak amplitude in frequency domain after matched filtering). At 7 T, extended ISIS allowed the performance of high-quality localized (31)P magnetic resonance spectroscopy in a short measurement time (similar to 3 to 4 min) and isotropic voxel sizes of similar to 2.5 to 3 cm. With such short measurement times, localized (31)P magnetic resonance spectroscopy has the potential to be applied not only for clinical research but also for routine clinical practice. Magn Reson Med 66: 923-930, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Bogner, W.; Chmelik, M.; Trattnig, S.; Gruber, S.] Med Univ Vienna, MR Ctr Excellence, Dept Radiol, A-1090 Vienna, Austria. [Andronesi, O. C.; Sorensen, A. G.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Trattnig, S (reprint author), Med Univ Vienna, MR Ctr Excellence, Dept Radiol, Lazarettgasse 14, A-1090 Vienna, Austria. EM siegfried.trattnig@meduniwien.ac.at OI Bogner, Wolfgang/0000-0002-0130-3463 FU OeNB Jubilaeumsfond [13629, 13834]; Vienna Spots of Excellence des Wiener Wissenschafts-und Technologie-Fonds (WWTF)-Vienna Advanced Imaging Center (VIACLIC) FX Grant sponsor: OeNB Jubilaeumsfond; Grant numbers: 13629, 13834; Grant sponsor: Vienna Spots of Excellence des Wiener Wissenschafts-und Technologie-Fonds (WWTF)-Vienna Advanced Imaging Center (VIACLIC). NR 36 TC 20 Z9 21 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2011 VL 66 IS 4 BP 923 EP 930 DI 10.1002/mrm.22897 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500002 PM 21446033 ER PT J AU Sun, PZ Wang, EF Cheung, JS Zhang, XA Benner, T Sorensen, AG AF Sun, Phillip Zhe Wang, Enfeng Cheung, Jerry S. Zhang, Xiaoan Benner, Thomas Sorensen, A. Gregory TI Simulation and Optimization of Pulsed Radio Frequency Irradiation Scheme for Chemical Exchange Saturation Transfer (CEST) MRI-Demonstration of pH-Weighted Pulsed-Amide Proton CEST MRI in an Animal Model of Acute Cerebral Ischemia SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT Gordon Research Conference of In-Vivo-MR-Proctor-Academy CY JUL, 2010 CL Andover, NH SP In Vivo MR Proctor Acad DE amide proton transfer; chemical exchange saturation transfer; pH; radio frequency; stroke ID MAGNETIZATION-TRANSFER; PARACEST AGENTS; CONTRAST AGENTS; RF IRRADIATION; IN-VIVO; 3 TESLA; PENUMBRA; LACTATE; POWER; TIME AB Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is capable of measuring dilute labile protons and microenvironmental properties. However, the CEST contrast is dependent upon experimental conditions-particularly, the radiofrequency (RF) irradiation scheme. Although continuous-wave RF irradiation has been used conventionally, the limited RF pulse duration or duty cycle of most clinical systems requires the use of pulsed RF irradiation. Here, the conventional numerical simulation is extended to describe pulsed-CEST MRI contrast as a function of RF pulse parameters (i.e., RF pulse duration and flip angle) and labile proton properties (i.e., exchange rate and chemical shift). For diamagnetic CEST agents undergoing slow or intermediate chemical exchange, simulation shows a linear regression relationship between the optimal mean RF power of pulsed-CEST MRI and continuous-wave-CEST MRI. The optimized pulsed-CEST contrast is approximately equal to that of continuous-wave-CEST MRI for exchange rates less than 50 s(-1), as confirmed experimentally using a multicompartment pH phantom. In the acute stroke animals, we showed that pulsed-and continuous-wave-amide proton CEST MRI demonstrated similar contrast. In summary, our study elucidated the RF irradiation dependence of pulsed-CEST MRI contrast, providing useful insights to guide its experimental optimization and quantification. Magn Reson Med 66: 1042-1048, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S.; Benner, Thomas; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S.; Benner, Thomas; Sorensen, A. Gregory] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wang, Enfeng; Zhang, Xiaoan] Zhengzhou Univ, Affiliated Hosp 3, Dept Radiol, Zhengzhou, Henan Province, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIBIB NIH HHS [K01 EB009771-02, K01 EB009771-01, K01 EB009771-03, K01 EB009771, 1K01EB009771]; NINDS NIH HHS [R21 NS061119, R21 NS061119-01A1, R21NS061119] NR 33 TC 26 Z9 27 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2011 VL 66 IS 4 BP 1042 EP 1048 DI 10.1002/mrm.22894 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500015 PM 21437977 ER PT J AU Dash, R Chung, JH Chan, T Yamada, M Barral, J Nishimura, D Yang, PC Simpson, PC AF Dash, Rajesh Chung, Jaehoon Chan, Trevor Yamada, Mayumi Barral, Joelle Nishimura, Dwight Yang, Phillip C. Simpson, Paul C. TI A Molecular MRI Probe to Detect Treatment of Cardiac Apoptosis In Vivo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac MRI; apoptosis; doxorubicin; annexin-V; SPIO; alpha-1-adrenergic agonist ID MESENCHYMAL STEM-CELLS; MAGNETIC-RESONANCE; ANNEXIN-V; 1.5 T; CARDIOMYOPATHY; NANOPARTICLES; SURVIVAL; MYOCYTES; AGENT; DEATH AB Cell death by apoptosis is critical in myocardial diseases, and noninvasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69 nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, nonischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible. Magn Reson Med 66:1152-1162, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Dash, Rajesh; Chan, Trevor; Simpson, Paul C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Dash, Rajesh; Chan, Trevor; Simpson, Paul C.] San Francisco VA Med Ctr, Res Serv, San Francisco, CA USA. [Dash, Rajesh; Simpson, Paul C.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Dash, Rajesh; Simpson, Paul C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Dash, Rajesh; Chung, Jaehoon; Chan, Trevor; Yamada, Mayumi; Yang, Phillip C.] Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Barral, Joelle; Nishimura, Dwight] Stanford Univ, Med Ctr, Dept Elect Engn, Stanford, CA 94305 USA. RP Simpson, PC (reprint author), VA Med Ctr, 111-C-8,4150 Clement St, San Francisco, CA 94121 USA. EM paul.simpson@ucsf.edu FU VA; NIH; American Heart Association, Western States Affiliate; Sarnoff Cardiovascular Research Foundation FX Grant sponsors: VA and NIH; American Heart Association, Western States Affiliate; Sarnoff Cardiovascular Research Foundation. NR 28 TC 28 Z9 31 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2011 VL 66 IS 4 BP 1152 EP 1162 DI 10.1002/mrm.22876 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500027 PM 21360750 ER PT J AU Cohen-Adad, J Mareyam, A Keil, B Polimeni, JR Wald, LL AF Cohen-Adad, J. Mareyam, A. Keil, B. Polimeni, J. R. Wald, L. L. TI 32-Channel RF Coil Optimized for Brain and Cervical Spinal Cord at 3 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE RF coil; phased-array; brain; spinal cord ID PHASED-ARRAY; PHYSIOLOGICAL NOISE; HEAD COIL; IN-VIVO; MRI; TESLA; UNCERTAINTY; ECHO; FMRI AB Diffusion and functional magnetic resonance imaging of the spinal cord remain challenging due to the small cross-sectional size of the cord and susceptibility-related distortions. Although partially addressable through parallel imaging, few highly parallel array coils have been implemented for the cervical cord. Here, we developed a 32-channel coil that fully covers the brain and c-spine and characterized its performance in comparison with a commercially available head/neck/spine array. Image and temporal signal-to-noise ratio were, respectively, increased by 2x and 1.8x in the cervical cord. Averaged g-factors at 4x acceleration were lowered by 22% in the brain and by 39% in the spinal cord, enabling 1-mm isotropic R = 4 multi-echo magnetization prepared gradient echo of the full brain and c-spine in 3:20 min. Diffusion imaging of the cord at 0.6 x 0.6 x 5 mm(3) resolution and tractography of the full brain and c-spine at 1.7-mm isotropic resolution were feasible without noticeable distortion. Improvements of this nature potentially enhance numerous basic and clinical research studies focused on spinal and supraspinal regions. Magn Reson Med 66:1198-1208, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Cohen-Adad, J.; Mareyam, A.; Keil, B.; Polimeni, J. R.; Wald, L. L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Cohen-Adad, J.; Keil, B.; Polimeni, J. R.; Wald, L. L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, L. L.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Cohen-Adad, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM jcohen@nmr.mgh.harvard.edu RI Keil, Boris/P-1411-2014; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU National Institute of Health [P41RR14075, U01MH093765]; French MS Society (ARSEP) FX Grant sponsor: National Institute of Health; Grant number: P41RR14075, U01MH093765; Grant sponsor: French MS Society (ARSEP) NR 43 TC 17 Z9 17 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2011 VL 66 IS 4 BP 1198 EP 1208 DI 10.1002/mrm.22906 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 826LV UT WOS:000295356500032 PM 21433068 ER PT J AU Baur, DM Klotsche, J Hamnvik, OPR Sievers, C Pieper, L Wittchen, HU Stalla, GK Schmid, RM Kales, SN Mantzoros, CS AF Baur, Dorothee M. Klotsche, Jens Hamnvik, Ole-Petter R. Sievers, Caroline Pieper, Lars Wittchen, Hans-Ulrich Stalla, Guenter K. Schmid, Roland M. Kales, Stefanos N. Mantzoros, Christos S. TI Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INSULIN THERAPY; METFORMIN; DISEASE; PREVALENCE; DETECT AB There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk. We examined the association between diabetes, cancer, and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality. Participants in the Diabetes Cardiovascular Risk and Evaluation: Targets and Essential Data for Commitment of Treatment study, a nationwide cross-sectional and prospective epidemiological study, were recruited from German primary care practices. In the cross-sectional study, subjects with type 2 diabetes mellitus had a higher prevalence of malignancies (66/1308, 5.1%) compared to nondiabetic subjects (185/6211, 3.0%) (odds ratio, 1.64; 95% confidence interval, 1.12-2.41) before and after adjustment for age, sex, hemoglobin A(1c), smoking status, and body mass index. Patients on metformin had a lower prevalence of malignancies, comparable with that among nondiabetic patients, whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders; inclusion of metformin in these regimens decreased the prevalence of malignancies. In the prospective analyses, diabetic patients in general and diabetic patients treated with insulin (either as monotherapy or in combination with other treatments) had a 2- and 4-fold, respectively, higher mortality rate than nondiabetic patients, even after adjustment for potential confounders (incidence of cancer deaths in patients with type 2 diabetes mellitus [2.6%] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [1.2%]). Our results suggest that diabetes and medications for diabetes, with the exception of the insulin sensitizer metformin, increase cancer risk and mortality. (C) 2011 Elsevier Inc. All rights reserved. C1 [Baur, Dorothee M.; Kales, Stefanos N.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med & Epide, Boston, MA 02115 USA. [Baur, Dorothee M.; Kales, Stefanos N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Baur, Dorothee M.; Schmid, Roland M.] Tech Univ Munich, Dept Med 2, Klinikum Rechts Isar, D-8000 Munich, Germany. [Klotsche, Jens; Pieper, Lars; Wittchen, Hans-Ulrich] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. [Hamnvik, Ole-Petter R.] Harvard Univ, Med Sch Boston, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. [Hamnvik, Ole-Petter R.] Harvard Univ, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med,Sch Med, Boston, MA 02115 USA. [Sievers, Caroline; Stalla, Guenter K.] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. RP Baur, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Environm & Occupat Med & Epide, 665 Huntington Ave, Boston, MA 02115 USA. EM dbaur@hsph.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011; Wittchen, Hans-Ulrich/A-8507-2014; OI Wittchen, Hans-Ulrich/0000-0002-6311-7711 FU Pfizer, Karlsruhe, Germany; Assistance to Firefighters [EMW-2006-FP-01493, EMW-FP-00835] FX Diabetes Cardiovascular Risk and Evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) is a cross-sectional and prospective, longitudinal, nationwide clinical epidemiological study. DETECT is supported by an unrestricted educational grant from Pfizer, Karlsruhe, Germany. Members of the DETECT Study Group are as follows: (principal investigator) Prof Dr H-U Wittchen; (staff members) Dipl.-Psych. L Pieper, Dipl.-Math. J Klotsche, Dr T Eichler, Dr H Glaesmer, E Katze. Steering Committee: Prof Dr H Lehnert (Lubeck), Prof Dr GK Stalla (Munchen), Prof Dr AM Zeiher (Frankfurt); Advisory Board: Prof Dr W Marz (Heidelberg/Graz), Prof Dr S Silber (Munchen), Prof Dr U Koch (Hamburg), Priv.-Doz. Dr D Pittrow (Munchen/Dresden), Prof Dr M Wehling (Mannheim), Dr D Leistner (Frankfurt), Priv.-Doz. Dr H J Schneider (Munchen), Dr C Sievers (Munchen).; DMB and SNK were supported by the Assistance to Firefighters grants program managed by the Federal Emergency Management Agency in the Department of Homeland Security EMW-2006-FP-01493 and EMW-FP-00835. NR 21 TC 41 Z9 44 U1 0 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2011 VL 60 IS 10 BP 1363 EP 1371 DI 10.1016/j.metabol.2010.09.012 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826IN UT WOS:000295347900003 PM 21081242 ER PT J AU Tanwar, PS Zhang, LH Teixeira, JM AF Tanwar, Pradeep S. Zhang, LiHua Teixeira, Jose M. TI Adenomatous Polyposis Coli (APC) Is Essential for Maintaining the Integrity of the Seminiferous Epithelium SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MULLERIAN-INHIBITING SUBSTANCE; BETA-CATENIN EXPRESSION; TUMOR-SUPPRESSOR; SERTOLI-CELLS; WNT/BETA-CATENIN; LEYDIG-CELLS; SEXUAL-DIFFERENTIATION; ENDOMETRIAL CANCER; ADHERENS JUNCTIONS; DUCT REGRESSION AB Sertoli cells provide the microenvironment necessary for germ cell development and spermatogenesis; disruption of Sertoli cell morphology or function can lead to germ cell aplasia, which is observed in testicular dysgenesis syndrome. Mutation of the adenomatous polyposis coli (APC) gene has been associated with various human cancers, including testicular cancer, but its involvement in nonmalignant testicular pathologies has not been reported. We have developed a mouse model (APC(cko)) that expresses a truncated form of APC in Sertoli cells. Despite normal embryonic and early postnatal testicular development in APC(cko) mice, premature germ cell loss and Sertoli cell-only seminiferous tubules were observed in mutant testes without affecting Sertoli cell quiescence, apoptosis, or differentiation, which were confirmed by the absence of both proliferating cell nuclear antigen, DNA strand breaks, and anti-Mullerian hormone, respectively. We show that mutant Sertoli cells lose their apical extensions, which would normally enclose germ cells during various stages of spermatogenesis, and were unable to maintain the blood-testis barrier because of disrupted expression of junctional proteins. We also observed an up-regulation of Snail and Slug, markers suggestive of epithelial-mesenchymal transition in the Sertoli cells, but tumorigenesis was not observed. No comparable phenotype was observed with Sertoli cell-specific loss-of-function mutations in beta-catenin, leading us to speculate that truncation of APC in Sertoli cells results in progressive degeneration of the seminiferous tubules by a mechanism that disrupts the integrity of Sertoli cell junctions independently of APC-regulated beta-catenin activities and leads to development of a Sertoli cell-only phenotype. (Molecular Endocrinology 25: 1725-1739, 2011) C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Thier 913, 55 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NICHD [HD052701]; Vincent Memorial Research Funds FX This work was supported in part by the NICHD Grant HD052701 (to J.M.T.) and by Vincent Memorial Research Funds. NR 65 TC 19 Z9 20 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2011 VL 25 IS 10 BP 1725 EP 1739 DI 10.1210/me.2011-0057 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826AC UT WOS:000295322700005 PM 21816903 ER PT J AU Cornely, OA Herbrecht, R Viscoli, C Greene, R Ruhnke, M Vitek, A Vydra, J van Amsterdam, RG Meems, L AF Cornely, O. A. Herbrecht, R. Viscoli, C. Greene, R. Ruhnke, M. Vitek, A. Vydra, J. van Amsterdam, R. G. Meems, L. TI Efficacy and safety of micafungin salvage monotherapy vs. active control intravenous monotherapy in patients with invasive aspergillosis SO MYCOSES LA English DT Meeting Abstract C1 [Cornely, O. A.] Univ Hosp Cologne, Cologne, Germany. [Herbrecht, R.] Hosp Hautepierre, Strasbourg, France. [Viscoli, C.] Univ Genoa, San Martino Hosp, Genoa, Italy. [Greene, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruhnke, M.] Charite, Berlin, Germany. RI Herbrecht, Raoul/D-3471-2013 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 0933-7407 J9 MYCOSES JI Mycoses PD OCT PY 2011 VL 54 SU 2 SI SI BP 93 EP 94 PG 2 WC Dermatology; Mycology SC Dermatology; Mycology GA 826FB UT WOS:000295336100206 ER PT J AU Adli, M Bernstein, BE AF Adli, Mazhar Bernstein, Bradley E. TI Whole-genome chromatin profiling from limited numbers of cells using nano-ChIP-seq SO NATURE PROTOCOLS LA English DT Article ID EPIGENETIC CHARACTERIZATION; IMMUNOPRECIPITATION ASSAY; MAPS AB Chromatin immunoprecipitation (ChIP) combined with high-throughput sequencing (ChIP-seq) has become the gold standard for whole-genome mapping of protein-DNA interactions. However, conventional ChIP protocols necessitate the use of large numbers of cells, and library preparation steps associated with current high-throughput sequencing platforms require substantial amounts of DNA; both of these factors preclude the application of ChIP-seq technology to many biologically important but rare cell types. Here we describe a nano-ChIP-seq protocol that combines a high-sensitivity small-scale ChIP assay and a tailored procedure for generating high-throughput sequencing libraries from scarce amounts of ChIP DNA. In terms of the numbers of cells required, the method provides two to three orders of magnitude of improvement over the conventional ChIP-seq method and the entire procedure can be completed within 4 d. C1 [Adli, Mazhar; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Adli, Mazhar; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Adli, Mazhar; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Adli, M (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM madli@mgh.harvard.edu; bernstein.bradley@mgh.harvard.edu FU Starr Cancer Consortium; Charles E. Culpeper Scholarship; US National Human Genome Research Institute; National Institutes of Health Roadmap for Epigenomics; National Heart, Lung and Blood Institute FX We acknowledge all the members of the Bernstein Lab for constructive discussions during the method development. We thank M. Coyne, S. Furuyama, S. Gillespie and N.A. Okan for their critical reading of the manuscript and J. Zhu, N. Shoresh and T. Mikkelsen for computational assistance. This research was supported by funds from the Starr Cancer Consortium, a Charles E. Culpeper Scholarship, the US National Human Genome Research Institute, the National Institutes of Health Roadmap for Epigenomics and the National Heart, Lung and Blood Institute. NR 10 TC 80 Z9 81 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD OCT PY 2011 VL 6 IS 10 BP 1656 EP 1668 DI 10.1038/nprot.2011.402 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 826OS UT WOS:000295364100012 PM 21959244 ER PT J AU Olson, EM Lin, NU Krop, IE Winer, EP AF Olson, Erin M. Lin, Nancy U. Krop, Ian E. Winer, Eric P. TI The ethical use of mandatory research biopsies SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; CLINICAL-TRIAL DESIGNS; CELL LUNG-CANCER; INFORMED-CONSENT; ANTICANCER AGENTS; CHEMOTHERAPY PLUS; TUMOR-BIOPSIES; PARTICIPATION; ONCOLOGISTS; PREDICTORS AB Increasingly, clinical trials incorporate translational research questions aimed at identifying biomarkers of response or resistance to agents under investigation. Biomarker assays can require tissue samples to be collected through a research biopsy before therapy, during treatment, or at the time of tumor progression. Such biopsy samples will generally not provide a direct benefit to the patient and, given the risks associated with any surgical procedure, ethical concerns have been raised when the participant's enrollment on a clinical trial depends on their consent to undergo a research biopsy. In this Perspectives article, we present the rationale for mandatory research biopsies and offer suggestions for standardization to ensure that high-quality, patient-centered, clinical trials continue to be designed with scientific and ethical rigor. Olson, E. M. et al. Nat. Rev. Clin. Oncol. 8, 620-625 (2011); published online 2 August 2011; doi:10.1038/nrclinonc.2011.114 C1 [Olson, Erin M.; Lin, Nancy U.; Krop, Ian E.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Winer, EP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ewiner@partners.org FU NCI NIH HHS [K12 CA133250] NR 40 TC 26 Z9 26 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2011 VL 8 IS 10 BP 620 EP U1539 DI 10.1038/nrclinonc.2011.114 PG 6 WC Oncology SC Oncology GA 827CJ UT WOS:000295403400009 PM 21808265 ER PT J AU Yaffe, K Lindquist, K Schwartz, AV Vitartas, C Vittinghoff, E Satterfield, S Simonsick, EM Launer, L Rosano, C Cauley, JA Harris, T AF Yaffe, K. Lindquist, K. Schwartz, A. V. Vitartas, C. Vittinghoff, E. Satterfield, S. Simonsick, E. M. Launer, L. Rosano, C. Cauley, J. A. Harris, T. TI Advanced glycation end product level, diabetes, and accelerated cognitive aging SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; OXIDATIVE STRESS; PENTOSIDINE; ACCUMULATION; DEMENTIA; DECLINE; ELDERS; HEALTH; SERUM AB Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of > 1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p = 0.05) but not different 3MS score (p = 0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall < 0.001; DSST 5.9, 7.4, and 4.5 point decline, p = 0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio = 1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio = 1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes. Neurology (R) 2011;77:1351-1356 C1 [Yaffe, K.; Vitartas, C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, K.; Schwartz, A. V.; Vittinghoff, E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Lindquist, K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Yaffe, K.; Vitartas, C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Satterfield, S.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Launer, L.; Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA. [Rosano, C.; Cauley, J. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Cauley, Jane A/0000-0003-0752-4408 FU NIH, National Institute of Aging; American Health Assistance Foundation [A201-0029]; Amgen; Merck Serono; GlaxoSmithKline; Anonymous Foundation; Alzheimer Association; NIH (NIA, NIDDK, NIMH); Department of Defense; NIH (NIDDK, NIA); Medtronic, Inc.; Zoll Medical Corporation; NIH (NIA, NIDDK, NHLBI, NIAID, NIMH); NIH/NIA; Novartis; NIH; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX NIA contract nos. N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Aging, and by a grant from the American Health Assistance Foundation, grant no. A201-0029.; Dr. Yaffe has served on data safety monitoring boards for Pfizer Inc, Medivation, Inc. and the NIH (NIMH and NIA trials); and has received research support from the NIH (NIA, NIDDK, NIMH), the Department of Defense, American Health Assistance Foundation, Anonymous Foundation, and the Alzheimer Association. K. Lindquist reports no disclosures. Dr. Schwartz serves on a scientific advisory board for GlaxoSmithKline; has received speaker honoraria from Amgen and Merck Serono; has received funding for travel from Amgen; and receives research support from Merck Serono, GlaxoSmithKline, the NIH (NIDDK, NIA). C. Vitartas reports no disclosures. Dr. Vittinghoff receives publishing royalties for Regression Methods in Biostatistics: Linear, Logistic, Survival and Repeated Measures Models (Springer Verlag, 2005); and receives research support from Medtronic, Inc., Zoll Medical Corporation, Amgen, and the NIH (NIA, NIDDK, NHLBI, NIAID, NIMH). Dr. Satterfield receives research support from the NIH/NIA. Dr. Simonsick serves as an Associate Editor for the Journal of Gerontology Medical Sciences and on the editorial board of the Journal of Aging and Health. Dr. Launer receives research support from the NIH/NIA Intramural Research Program. Dr. Rosano reports no disclosures. Dr. Cauley receives research support from Novartis. Dr. Harris receives research support from the NIH. NR 31 TC 48 Z9 48 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2011 VL 77 IS 14 BP 1351 EP 1356 DI 10.1212/WNL.0b013e3182315a56 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 828XV UT WOS:000295539000010 PM 21900628 ER PT J AU Brown, ML Bonomi, L Ungerleider, N Zina, J Kimura, F Mukherjee, A Sidis, Y Schneyer, A AF Brown, Melissa L. Bonomi, Lara Ungerleider, Nathan Zina, Jessica Kimura, Fuminori Mukherjee, Abir Sidis, Yisrael Schneyer, Alan TI Follistatin and Follistatin Like-3 Differentially Regulate Adiposity and Glucose Homeostasis SO OBESITY LA English DT Article ID TGF-BETA FAMILY; INSULIN-RESISTANCE; PANCREATIC-ISLETS; MUSCLE MASS; MYOSTATIN; ACTIVIN; MICE; BINDING; CELL; ADIPOGENESIS AB Transforming growth factor-beta superfamily ligands, including activin and myostatin, modulate body composition, islet function, and glucose homeostasis. Their bioactivity is controlled by the antagonists follistatin (FST) and FST like-3 (FSTL3). The hypothesis tested was that FST and FSTL3 have distinct roles in regulating body composition, glucose homeostasis, and islet function through regulation of activin and myostatin bioactivity. Three genetic mutant mouse lines were created. FSTL3 knockout (FSTL3 KO), a mouse line producing only the FST288 isoform (FST288-only) and a double mutant (2xM) in which the lines were crossed. FST288-only males were lighter that wild-type (WT) littermates while FSTL3 KO and 2xM males had reduced perigonadal fat pad weights. However, only 2xM mice had increased whole body fat mass and decreased lean mass by quantitative nuclear magnetic resonance (qNMR). Fasting glucose levels in FSTL3 WT and KO mice were lower than FST mice in younger animals but were higher in older mice. Serum insulin and pancreatic insulin content in 2xM mice was significantly elevated over other genotypes. Nevertheless, 2xM mice were relatively insulin resistant and glucose intolerant compared to FST288-only and WT mice. Fractional islet area and proportion of beta-cells/islet were increased in FSTL3 KO and 2xM, but not FST288-only mice. Despite their larger size, islets from FSTL3 KO and 2xM mice were not functionally enhanced compared to WT mice. These results demonstrate that body composition and glucose homeostasis are differentially regulated by FST and FSTL3 and that their combined loss is associated with increased fat mass and insulin resistance despite elevated insulin production. C1 [Brown, Melissa L.; Bonomi, Lara; Ungerleider, Nathan; Zina, Jessica; Kimura, Fuminori; Schneyer, Alan] Univ Massachusetts Amherst, Pioneer Valley Life Sci Inst, Springfield, MA USA. [Mukherjee, Abir; Sidis, Yisrael] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Univ Massachusetts Amherst, Pioneer Valley Life Sci Inst, Springfield, MA USA. EM Alan.schneyer@bhs.org FU National Institutes of Health/NIDDK [5 R01 DK075058]; Center for Excellence in Apoptosis Research at UMass/PVLSI FX The authors are grateful for the critical contributions of Melissa Thomas (Massachusetts General Hospital, Boston, MA) and Susan Bonner-Weir (Joslin Diabetes Center, Boston, MA). We also appreciate the extensive technical assistance with histological experiments from Brooke Bentley (Pioneer Valley Life Sciences Institute (PVLSI), Springfield, MA). This work was supported by a National Institutes of Health/NIDDK grant 5 R01 DK075058 and the Center for Excellence in Apoptosis Research at UMass/PVLSI. NR 26 TC 16 Z9 16 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 1940 EP 1949 DI 10.1038/oby.2011.97 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700004 PM 21546932 ER PT J AU Wadden, TA Neiberg, RH Wing, RR Clark, JM Delahanty, LM Hill, JO Krakoff, J Otto, A Ryan, DH Vitolins, MZ AF Wadden, Thomas A. Neiberg, Rebecca H. Wing, Rena R. Clark, Jeanne M. Delahanty, Linda M. Hill, James O. Krakoff, Jonathan Otto, Amy Ryan, Donna H. Vitolins, Mara Z. CA Look AHEAD Res Grp TI Four-Year Weight Losses in the Look AHEAD Study: Factors Associated With Long-Term Success SO OBESITY LA English DT Article ID LIFE-STYLE INTERVENTION; DIABETES-PREVENTION-PROGRAM; LOSS MAINTENANCE; CARDIOVASCULAR-DISEASE; BEHAVIORAL TREATMENT; PHYSICAL-ACTIVITY; OBESE-PATIENTS; ACTIVITY GOALS; RISK-FACTORS; MANAGEMENT AB This report provides a further analysis of the year 4 weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with long-term success. A total of 5,145 overweight/obese men and women with type 2 diabetes were randomly assigned to an intensive lifestyle intervention (ILI) or a usual care group, referred to as Diabetes Support and Education (DSE). ILI participants were provided approximately weekly group or individual treatment in year 1; continued but less frequent contact was provided in years 2-4. DSE participants received three group educational sessions in all years. As reported previously, at year 4, ILI participants lost an average of 4.7% of initial weight, compared with 1.1% for DSE (P < 0.0001). More ILI than DSE participants lost >= 5% (46% vs. 25%, P < 0.0001) and >= 10% (23% vs. 10%, P < 0.0001) of initial weight. Within the ILI, achievement of both the 5% and 10% categorical weight losses at year 4 was strongly related to meeting these goals at year 1. A total of 887 participants in ILI lost >= 10% at year 1, of whom 374 (42.2%) achieved this loss at year 4. Participants who maintained the loss, compared with those who did not, attended more treatment sessions and reported more favorable physical activity and food intake at year 4. These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., >= 5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years. C1 [Wadden, Thomas A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Neiberg, Rebecca H.] Wake Forest Univ, Dept Biostatist Sci, Winston Salem, NC 27109 USA. [Wing, Rena R.] Miriam Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI USA. [Clark, Jeanne M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Delahanty, Linda M.] Harvard Univ, Sch Med, Boston, MA USA. [Delahanty, Linda M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hill, James O.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Krakoff, Jonathan] NIDDK, NIH, Phoenix, AZ USA. [Otto, Amy] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Dept Clin Res, Baton Rouge, LA USA. [Vitolins, Mara Z.] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. RP Wadden, TA (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM Wadden@mail.med.upenn.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; Centers for Disease Control and Prevention; Department of Health and Human Services; National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Department of Veterans Affairs FX Federal sponsors; National Institute of Diabetes and Digestive and Kidney Diseases. Mary Evans, PhD; Barbara Harrison, MS; Van S. Hubbard, MD, PhD; Susan Z. Yanovski, MD; Robert Kuczmarski, PhD; National Heart, Lung, and Blood Institute. Lawton S. Cooper, MD, MPH; Peter Kaufman, PhD, FABMR; Centers for Disease Control and Prevention. Edward W. Gregg, PhD; David F. Williamson, PhD; Ping Zhang, PhD; This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; the Centers for Disease Control and Prevention; and the Department of Veterans Affairs. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. NR 53 TC 149 Z9 154 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 1987 EP 1998 DI 10.1038/oby.2011.230 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700010 PM 21779086 ER PT J AU de Miguel-Yanes, JM Manning, AK Shrader, P McAteer, JB Goel, A Hamsten, A Fox, CS Florez, JC Dupuis, J Meigs, JB AF de Miguel-Yanes, Jose M. Manning, Alisa K. Shrader, Peter McAteer, Jarred B. Goel, Anuj Hamsten, Anders Fox, Caroline S. Florez, Jose C. Dupuis, Josee Meigs, James B. CA Behalf PROCARDIS TI Variants at the Endocannabinoid Receptor CB1 Gene (CNR1) and Insulin Sensitivity, Type 2 Diabetes, and Coronary Heart Disease SO OBESITY LA English DT Article ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; CANNABINOID RECEPTORS; ARTERY-DISEASE; CELL FUNCTION; RISK-FACTORS; FOOD-INTAKE; OBESITY; GLUCOSE; LOCI AB Inhibition of the endocannabinoid receptor CB1 improves insulin sensitivity, lowers glycemia, and slows atherosclerosis. We analyzed whether common variants in the gene encoding CB1, CNR1, are associated with insulin resistance, risk of type 2 diabetes (T2D) or coronary heart disease (CHD). We studied 2,411 participants of the Framingham Offspring Study (mean age 60 years, 52% women) for quantitative traits and CHD, and the Framingham SHARe database for T2D risk. We genotyped 19 single-nucleotide polymorphisms (SNPs) that tagged 85% (at r(2) = 0.8) of common (>5%) CNR1 SNPs. Fasting blood glucose and insulin at the 7th (1999-2001) exam were collected. We used age-, sex-, BMI-adjusted models to test additive associations of genotype with homeostasis model assessment of insulin resistance (HOMA(IR)) (linear mixed-effect models), T2D, or CHD. To account for multiple tests of SNPs, we generated empirical P values. The C allele at SNP rs806365 (frequency, 57.4%), similar to 4.1 kb 3' from CNR1, was associated with increased HOMA(IR) (n = 2,261, beta = 0.05 per C, empirical P = 0.01), risk of T2D (674 cases, odds ratio = 1.19 per C, nominal P = 0.01) and CHD (237 cases, hazard ratio = 1.23 per C, nominal P = 0.04). The association of rs806365 with HOMA(IR) was replicated in a meta-analysis of two independent cohorts (National Health and Nutrition Examination Survey III genetic cohort (NHANES-III) plus Partners Case-Control Diabetes Study; 2,540 white individuals, beta = 0.037, nominal P = 0.007), but not in the large Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Consortium (n = 29,248, nominal P = 0.74). The association of rs806365 was not replicated either with T2D in Diabetes Genetics Replication and Meta-analysis (DIAGRAM) (n = 10,128, nominal P = 0.31), or with CHD in PROCARDIS (n = 13,614, nominal P = 0.37). Although supported by initial results, we found no reproducible statistical association of common variation at CNR1 with insulin resistance, T2D, or CHD. C1 [de Miguel-Yanes, Jose M.; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [de Miguel-Yanes, Jose M.; Fox, Caroline S.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [de Miguel-Yanes, Jose M.] Univ Gregorio Maranon, Gen Hosp, Dept Med Interna, Madrid, Spain. [Manning, Alisa K.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Boston, MA USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Goel, Anuj] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Goel, Anuj] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Hamsten, Anders] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden. [Fox, Caroline S.; Dupuis, Josee] Natl Heart & Lung Inst, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Dupuis, Josee/0000-0003-2871-3603 FU sanofi-aventis; National Heart, Lung, and Blood Institute [N01-HC-25195]; American Diabetes Association; Boston University; NIH-NCRR [1S10RR163736-01A1]; European Community [LSHMCT-2007-037273]; AstraZeneca; Knut, and Alice Wallenberg Foundation; British Heart Foundation; Wellcome Trust [076113]; "Instituto de Salud Carlos III", Madrid, Spain [2009/90071]; NIDDK [K24 DK080140]; NIH [K23 DK65978-04]; GlaxoSmithKline FX This study was supported by: an investigator-initiated research grant from sanofi-aventis (J.B.M.), the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), an American Diabetes Association Career Development Award (J.B.M.), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH-NCRR Shared Instrumentation grant (1S10RR163736-01A1). PROCARDIS was supported by the European Community Sixth Framework Program (LSHMCT-2007-037273), AstraZeneca, the Knut, and Alice Wallenberg Foundation and the British Heart Foundation. PROCARDIS also made use of data generated by the WTCCC. A full list of the investigators who contributed to the generation of the WTCCC data, funding for which was provided by the Wellcome Trust under award 076113, is available from www.wtccc.org.uk. J.M.de.M.-Y. is supported by a "Bolsa de Ampliacion de Estudios" from the "Instituto de Salud Carlos III", Madrid, Spain (2009/90071). J.B.M. is also supported by NIDDK K24 DK080140. J.C.F. is supported by a NIH Research Career Award K23 DK65978-04.; J.B.M. currently has research grants from GlaxoSmithKline, and serves on a consultancy board for Interleukin Genetics. NR 48 TC 5 Z9 5 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2011 VL 19 IS 10 BP 2031 EP 2037 DI 10.1038/oby.2011.135 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 825IX UT WOS:000295266700016 PM 21633404 ER PT J AU Levy, DE Winickoff, JP Rigotti, NA AF Levy, Douglas E. Winickoff, Jonathan P. Rigotti, Nancy A. TI School Absenteeism Among Children Living With Smokers SO PEDIATRICS LA English DT Article DE secondhand smoke; school-aged children; caregivers; economic burden ID ENVIRONMENTAL TOBACCO-SMOKE; RESPIRATORY ILLNESS; ECONOMIC-EVALUATION; PARENTAL SMOKING; UNITED-STATES; ASTHMA; EXPOSURE; HEALTH; PERFORMANCE; CHILDHOOD AB OBJECTIVE: Involuntary tobacco smoke exposure causes substantial morbidity in children. We hypothesized that children exposed to tobacco smoke in the home would have increased school absenteeism with associated costs due to lost caregiver wages/time. METHODS: We analyzed data on health and absenteeism among schoolchildren aged 6 to 11 years identified in the 2005 National Health Interview Survey (NHIS). We used multivariate models to assess the relationships between adult-reported household smoking and child health and school absenteeism. Analyses were adjusted for children's and parents' demographic and socioeconomic characteristics. The value of lost caregiver time was estimated by using self-reported employment and earnings data in the NHIS and publicly available time-use data. RESULTS: Children living with 1 or >= 2 adults who smoked in the home had 1.06 (95% confidence interval [CI]: 0.54-1.55) and 1.54 (95% CI: 0.95-2.12) more days absent from school per year, respectively, than children living with 0 smokers in the home. Living with >= 2 adults who smoked in the home was associated with increased reports of having >= 3 ear infections in the previous 12 months (adjusted odds ratio [aOR]: 2.65 [95% CI: 1.36-5.16]) and having a chest cold in the 2 weeks before interview (aOR: 1.77 [95% CI: 1.03-3.03]) but not with having vomiting/diarrhea in the previous 2 weeks (aOR: 0.93 [95% CI: 0.45-1.89]). Caregivers' time tending children absent from school was valued at $227 million per year. CONCLUSIONS: Tobacco smoke exposure has significant consequences for children and families above and beyond child morbidity, including academic disadvantage and financial burden. Pediatrics 2011;128:650-656 C1 [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Winickoff, Jonathan P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Winickoff, Jonathan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Winickoff, Jonathan P.] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Div Gen Pediat, Boston, MA USA. [Winickoff, Jonathan P.] Amer Acad Pediat, Julius B Richmond Ctr, Elk Grove Village, IL USA. RP Levy, DE (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM dlevy3@partners.org FU Flight Attendant Medical Research Institute; Julius B. Richmond Center of Excellence of the American Academy of Pediatrics through Flight Attendant Medical Research Institute; National Heart Lung and Blood Institute [K24-HL0440] FX Dr Levy was funded by the Flight Attendant Medical Research Institute. Dr Winickoff was supported by the Julius B. Richmond Center of Excellence of the American Academy of Pediatrics through a grant from the Flight Attendant Medical Research Institute. Dr Rigotti was supported by National Heart Lung and Blood Institute grant K24-HL0440. NR 36 TC 18 Z9 18 U1 0 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2011 VL 128 IS 4 BP 650 EP 656 DI 10.1542/peds.2011-1067 PG 7 WC Pediatrics SC Pediatrics GA 827DH UT WOS:000295406800039 PM 21890826 ER PT J AU Anspacher, M Frintner, MP Denno, D Pak-Gorstein, S Olness, K Spector, J O'Callahan, C AF Anspacher, Melanie Frintner, Mary Pat Denno, Donna Pak-Gorstein, Suzinne Olness, Karen Spector, Jonathan O'Callahan, Cliff TI Global Health Education for Pediatric Residents: A National Survey SO PEDIATRICS LA English DT Article DE global health; international health; resident training; medical education ID INTERNATIONAL HEALTH; CHILD HEALTH; MEDICAL-STUDENTS; EXPERIENCE; OPPORTUNITIES; PROGRAM; ELECTIVES; SURGERY AB OBJECTIVE: To assess exposure to global health (GH) training, future plans to work or volunteer abroad, and the importance of GH training in program selection among graduating pediatric residents. METHODS: A national, random sample of graduating pediatric residents was surveyed in the 2008 American Academy of Pediatrics' Annual Graduating Residents Survey. Questions specific to GH training were included. RESULTS: The adjusted survey response rate was 59% (546 of 927); 534 residents from 170 programs responded to at least 1 GH question. GH training was an essential/very important factor in selecting a residency program for 22% of the respondents, and 21% reported participating in GH training during residency. In multivariate analyses, participation in GH training was associated with being single (adjusted odds ratio [aOR]: 1.90 [95% confidence interval (CI): 1.10-3.27]), graduating from a US medical school (aOR: 2.45 [95% CI: 1.14-5.28]), lower educational debt (aOR: 2.63 [95% CI: 1.54-4.49]), and training at a larger program (aOR: 2.73 [95% CI: 1.47-5.06]). One-third of respondents reported definite/very likely plans to work/volunteer in a developing country after residency; these respondents were more likely to be single (aOR: 1.82 [95% CI: 1.14-2.92]) and international medical school graduates (aOR: 2.10 [95% CI: 1.19-3.73]). Fewer than 50% of respondents received education in the majority of topics considered essential to GH training. CONCLUSIONS: GH-training opportunities are important to pediatric residents when selecting a program, and many are graduating with intentions to volunteer/work in a developing country after residency. The low exposure to GH topics among a broad cross-section of pediatric residents suggests that additional work is needed to adequately prepare pediatricians for work in GH after residency. Pediatrics 2011; 128:e959-e965 C1 [Anspacher, Melanie] Childrens Natl Med Ctr, Pediat Hosp Div, Washington, DC 20010 USA. [Frintner, Mary Pat] Amer Acad Pediat, Elk Grove Village, IL USA. [Denno, Donna; Pak-Gorstein, Suzinne] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Olness, Karen] Case Western Reserve Univ, Dept Global Child Hlth, Cleveland, OH 44106 USA. [Spector, Jonathan] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [O'Callahan, Cliff] Middlesex Hosp Family Med Residency, Dept Pediat, Middletown, CT USA. RP Anspacher, M (reprint author), Childrens Natl Med Ctr, Pediat Hosp Div, 111 Michigan Ave NW, Washington, DC 20010 USA. EM manspach@cnmc.org RI yan, liu/A-1822-2015 OI yan, liu/0000-0001-8517-1084 FU AAP FX This research was supported by the AAP. NR 30 TC 22 Z9 22 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2011 VL 128 IS 4 BP E959 EP E965 DI 10.1542/peds.2011-0129 PG 7 WC Pediatrics SC Pediatrics GA 827DH UT WOS:000295406800023 PM 21911354 ER PT J AU Oujiri, J Hakeem, A Pack, Q Holland, R Meyers, D Hildebrand, C Bridges, A Roach, MA Vogelman, B AF Oujiri, James Hakeem, Abdul Pack, Quinn Holland, Robert Meyers, David Hildebrand, Christopher Bridges, Alan Roach, Mary A. Vogelman, Bennett TI Republished original article: Resident-initiated interventions to improve inpatient heart-failure management SO POSTGRADUATE MEDICAL JOURNAL LA English DT Article ID ELECTRONIC HEALTH RECORD; ACUTE MYOCARDIAL-INFARCTION; CLINICAL DECISION-SUPPORT; QUALITY-OF-CARE; IMPLEMENTATION; PERFORMANCE; INDICATORS; MORTALITY; SYSTEMS; SAFETY AB Background: Third-year internal medicine residents participating in a quality improvement rotation identified gaps between the Joint Commission's ORYX quality guidelines and clinical practices for the inpatient management of heart failure (HF) at the William S. Middleton Memorial Veterans Hospital. Residents focused on the performance metrics associated with tobacco-cessation counselling documentation, ejection fraction assessment and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescriptions. Methods: After analysing data collected by the External Peer Review Program, residents reviewed the institution's admissions and discharge processes with the aim of improving quality and compliance. In redesigning these processes, residents created an admissions template and a discharge face sheet, and compared specific ORYX measure compliance rates before and after institution-wide implementation. Results: Following implementation of the tobacco-cessation admissions template, 100% of HF patients who used tobacco received documented cessation counselling, compared with 59% prior to intervention (p<0.01, n=32). Following implementation of the mandatory discharge face sheet, 97% of HF patients (compared with 92% preintervention, p>0.05) received comprehensive discharge instruction; LV function assessment went from 98% to 100% (p>0.05); and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription for left ventricular systolic dysfunction at discharge (or documentation of a contra-indication) went from 82% to 100% (p<0.01, n=48). Discussion: By implementing a standardised admissions template and a mandatory discharge face sheet, the hospital improved its processes of documentation and increased adherence to quality-performance measures. By strengthening residents' learning and commitment to quality improvement, the hospital created a foundation for future changes in the systems that affect patient care. C1 [Oujiri, James; Roach, Mary A.; Vogelman, Bennett] Univ Wisconsin Madison Sch Med & Publ Hlth, Madison, WI USA. [Oujiri, James; Holland, Robert; Meyers, David; Hildebrand, Christopher; Bridges, Alan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Hakeem, Abdul] Univ Cincinnati Coll Med, Div Cardiovasc Dis, Cincinnati, OH USA. [Pack, Quinn] Henry Ford Hlth Syst K 14, Div Cardiovasc Dis, Detroit, MI USA. RP Vogelman, B (reprint author), Educ Program Off, Internal Med Residency Program, Suite 5000,1685 Highland Ave, Madison, WI 53705 USA. EM bsv@medicine.wisc.edu FU Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health; Residency Review Committee for Internal Medicine; William S Middleton Memorial Veterans Administration Hospital; University of Wisconsin Institute for Clinical and Translational Research; NIH [1 UL1RR025011] FX Completion of this paper was made possible by a grant from the Medical Education and Research Committee (MERC) of the University of Wisconsin-Madison School of Medicine and Public Health as well as by the support of the Education Innovation Project of the Residency Review Committee for Internal Medicine, of which we are a participating residency. These QI projects received widespread support from the William S Middleton Memorial Veterans Administration Hospital, especially the director, D Thompson, and personnel in the Information Technology, Pharmacy, Nursing, and Organisation Improvement departments. Results of these projects were shared at the Association of Program Directors in Internal Medicine (APDIM) meeting in April, 2009. We also wish to acknowledge the support of the University of Wisconsin Institute for Clinical and Translational Research, funded through an NIH Clinical and Translational Science Award (CTSA), grant no 1 UL1RR025011. NR 18 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0032-5473 J9 POSTGRAD MED J JI Postgrad. Med. J. PD OCT PY 2011 VL 87 IS 1032 BP 700 EP 705 DI 10.1136/pgmj.2009.39339rep PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825GO UT WOS:000295259400009 PM 21954033 ER PT J AU Skinner, HD Hong, TS Krishnan, S AF Skinner, Heath D. Hong, Theodore S. Krishnan, Sunil TI Charged-Particle Therapy for Hepatocellular Carcinoma SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PROTON-BEAM THERAPY; ACTIVE BREATHING CONTROL; RADIATION-THERAPY; LIVER-CANCER; COMPUTED-TOMOGRAPHY; PHASE-II; RADIOTHERAPY; MALIGNANCIES; EXPERIENCE; TUMORS C1 [Skinner, Heath D.; Krishnan, Sunil] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Unit 097, Houston, TX 77030 USA. [Hong, Theodore S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Krishnan, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Unit 097, B2-4829,1515 Holcombe Blvd, Houston, TX 77030 USA. EM skrishnan@mdanderson.org RI Skinner, Heath/A-1669-2012 OI Skinner, Heath/0000-0003-1836-151X FU National Institutes of Health (NIH) [CA021239] FX Supported in part by a program project grant from the National Institutes of Health (NIH CA021239) to TSH. NR 42 TC 17 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2011 VL 21 IS 4 BP 278 EP 286 DI 10.1016/j.semradonc.2011.05.007 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 826IM UT WOS:000295347800006 PM 21939857 ER PT J AU Woo, M Isganaitis, E Cerletti, M Fitzpatrick, C Wagers, AJ Jimenez-Chillaron, J Patti, ME AF Woo, Melissa Isganaitis, Elvira Cerletti, Massimiliano Fitzpatrick, Connor Wagers, Amy J. Jimenez-Chillaron, Jose Patti, Mary Elizabeth TI Early Life Nutrition Modulates Muscle Stem Cell Number: Implications for Muscle Mass and Repair SO STEM CELLS AND DEVELOPMENT LA English DT Article ID LOW-BIRTH-WEIGHT; MYOGENIC SATELLITE CELLS; SKELETAL-MUSCLE; GLUCOSE-INTOLERANCE; INSULIN-RESISTANCE; FIBER COMPOSITION; ADULT MYOGENESIS; SELF-RENEWAL; IN-UTERO; REGENERATION AB Suboptimal nutrition during prenatal and early postnatal development is associated with increased risk for type 2 diabetes during adult life. A hallmark of such diabetes risk is altered body composition, including reduced lean mass and increased adiposity. Since stem cell number and activity are important determinants of muscle mass, modulation of perinatal nutrition could alter stem cell number/function, potentially mediating developmentally programmed reductions in muscle mass. Skeletal muscle precursors (SMP) were purified from muscle of mice subjected to prenatal undernutrition and/or early postnatal high-fat diet (HFD)-experimental models that are both associated with obesity and diabetes risk. SMP number was determined by flow cytometry, proliferative capacity measured in vitro, and regenerative capacity of these cells determined in vivo after muscle freeze injury. Prenatally undernutrition (UN) mice showed significantly reduced SMP frequencies [Control (C) 4.8%+/- 0.3% (% live cells) vs. UN 3.2%+/- 0.4%, P=0.015] at 6 weeks; proliferative capacity was unaltered. Reduced SMP in UN was associated with 32% decrease in regeneration after injury (C 16%+/- 3% of injured area vs. UN 11%+/- 2%; P<0.0001). SMP frequency was also reduced in HFD-fed mice (chow 6.4%+/- 0.6% vs. HFD 4.7%+/- 0.4%, P=0.03), and associated with 44% decreased regeneration (chow 16%+/- 2.7% vs. HFD 9%+/- 2.2%; P<0.0001). Prenatal undernutrition was additive with postnatal HFD. Thus, both prenatal undernutrition and postnatal overnutrition reduce myogenic stem cell frequency and function, indicating that developmentally established differences in muscle-resident stem cell populations may provoke reductions in muscle mass and repair and contribute to diabetes risk. C1 [Woo, Melissa; Isganaitis, Elvira; Cerletti, Massimiliano; Fitzpatrick, Connor; Wagers, Amy J.; Jimenez-Chillaron, Jose; Patti, Mary Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Woo, Melissa; Isganaitis, Elvira] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Cerletti, Massimiliano; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. [Patti, Mary Elizabeth] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU American Diabetes Association; Graetz Foundation; NRSA; Lawson-Wilkins Pediatric Endocrine Society; Burroughs Wellcome Fund; Harvard Stem Cell Institute; NIH [1RO1 AG033053]; Joslin Diabetes Center Flow Cytometry Core; Joslin DERC [5P30 DK036836-23]; Boston Area Claude D. Pepper Muscle Progenitor Core [P30 AG031679-02] FX We gratefully acknowledge research grant support from the American Diabetes Association (research grant and mentored postdoctoral fellowship awards to M.E.P.), the Graetz Foundation (to M.E.P.), individual NRSA (to M.W.), the Lawson-Wilkins Pediatric Endocrine Society (to E.I.), and a Burroughs Wellcome Fund Career Award, Harvard Stem Cell Institute Program Grant, and NIH grant 1RO1 AG033053 (to A.J.W.). This work was supported in part by the Joslin Diabetes Center Flow Cytometry Core, supported by the Harvard Stem Cell Institute and Joslin DERC (5P30 DK036836-23), and the Boston Area Claude D. Pepper Muscle Progenitor Core (P30 AG031679-02). NR 43 TC 29 Z9 29 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD OCT PY 2011 VL 20 IS 10 BP 1763 EP 1769 DI 10.1089/scd.2010.0349 PG 7 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 826AX UT WOS:000295324900012 PM 21247245 ER PT J AU Bis, JC Kavousi, M Franceschini, N Isaacs, A Abecasis, GR Schminke, U Post, WS Smith, AV Cupples, LA Markus, HS Schmidt, R Huffman, JE Lehtimaki, T Baumert, J Munzel, T Heckbert, SR Dehghan, A North, K Oostra, B Bevan, S Stoegerer, EM Hayward, C Raitakari, O Meisinger, C Schillert, A Sanna, S Volzke, H Cheng, YC Thorsson, B Fox, CS Rice, K Rivadeneira, F Nambi, V Halperin, E Petrovic, KE Peltonen, L Wichmann, HE Schnabel, RB Dorr, M Parsa, A Aspelund, T Demissie, S Kathiresan, S Reilly, MP Taylor, K Uitterlinden, A Couper, DJ Sitzer, M Kahonen, M Illig, T Wild, PS Orru, M Ludemann, J Shuldiner, AR Eiriksdottir, G White, CC Rotter, JI Hofman, A Seissler, J Zeller, T Usala, G Ernst, F Launer, LJ D'Agostino, RB O'Leary, DH Ballantyne, C Thiery, J Ziegler, A Lakatta, EG Chilukoti, RK Harris, TB Wolf, PA Psaty, BM Polak, JF Li, X Rathmann, W Uda, M Boerwinkle, E Klopp, N Schmidt, H Wilson, JF Viikari, J Koenig, W Blankenberg, S Newman, AB Witteman, J Heiss, G van Duijn, C Scuteri, A Homuth, G Mitchell, BD Gudnason, V O'Donnell, CJ AF Bis, Joshua C. Kavousi, Maryam Franceschini, Nora Isaacs, Aaron Abecasis, Goncalo R. Schminke, Ulf Post, Wendy S. Smith, Albert V. Cupples, L. Adrienne Markus, Hugh S. Schmidt, Reinhold Huffman, Jennifer E. Lehtimaki, Terho Baumert, Jens Muenzel, Thomas Heckbert, Susan R. Dehghan, Abbas North, Kari Oostra, Ben Bevan, Steve Stoegerer, Eva-Maria Hayward, Caroline Raitakari, Olli Meisinger, Christa Schillert, Arne Sanna, Serena Voelzke, Henry Cheng, Yu-Ching Thorsson, Bolli Fox, Caroline S. Rice, Kenneth Rivadeneira, Fernando Nambi, Vijay Halperin, Eran Petrovic, Katja E. Peltonen, Leena Wichmann, H. Erich Schnabel, Renate B. Doerr, Marcus Parsa, Afshin Aspelund, Thor Demissie, Serkalem Kathiresan, Sekar Reilly, Muredach P. Taylor, Kent Uitterlinden, Andre Couper, David J. Sitzer, Matthias Kahonen, Mika Illig, Thomas Wild, Philipp S. Orru, Marco Luedemann, Jan Shuldiner, Alan R. Eiriksdottir, Gudny White, Charles C. Rotter, Jerome I. Hofman, Albert Seissler, Jochen Zeller, Tanja Usala, Gianluca Ernst, Florian Launer, Lenore J. D'Agostino, Ralph B., Sr. O'Leary, Daniel H. Ballantyne, Christie Thiery, Joachim Ziegler, Andreas Lakatta, Edward G. Chilukoti, Ravi Kumar Harris, Tamara B. Wolf, Philip A. Psaty, Bruce M. Polak, Joseph F. Li, Xia Rathmann, Wolfgang Uda, Manuela Boerwinkle, Eric Klopp, Norman Schmidt, Helena Wilson, James F. Viikari, Jorma Koenig, Wolfgang Blankenberg, Stefan Newman, Anne B. Witteman, Jacqueline Heiss, Gerardo van Duijn, Cornelia Scuteri, Angelo Homuth, Georg Mitchell, Braxton D. Gudnason, Vilmundur O'Donnell, Christopher J. CA CARDIoGRAM Consortium TI Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque SO NATURE GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; URIC-ACID LEVELS; HEART-DISEASE; MYOCARDIAL-INFARCTION; GENETIC-LOCI; LIPID-LEVELS; ATHEROSCLEROSIS; RISK; POPULATION AB Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 x 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events. C1 [Bis, Joshua C.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Kavousi, Maryam; Dehghan, Abbas; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Kavousi, Maryam; Dehghan, Abbas; Rivadeneira, Fernando; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline; van Duijn, Cornelia] Sponsored Netherlands Consortium Healthy Aging NC, NGI, Rotterdam, Netherlands. [Franceschini, Nora; Li, Xia; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Isaacs, Aaron; van Duijn, Cornelia] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Isaacs, Aaron; Oostra, Ben; van Duijn, Cornelia] Ctr Med Syst Biol, Leiden, Netherlands. [Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Schminke, Ulf] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, Greifswald, Germany. [Post, Wendy S.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Smith, Albert V.; Thorsson, Bolli; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Cupples, L. Adrienne; Demissie, Serkalem; White, Charles C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, L. Adrienne; Fox, Caroline S.; Wolf, Philip A.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Markus, Hugh S.; Bevan, Steve] St Georges Univ London, Ctr Clin Neurosci, London, England. [Schmidt, Reinhold; Stoegerer, Eva-Maria] Med Univ Graz, Dept Neurol, Graz, Austria. [Huffman, Jennifer E.; Hayward, Caroline] Western Gen Hosp, Human Genet Unit, Inst Genet & Mol Med, MRC, Edinburgh EH4 2XU, Midlothian, Scotland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland. [Baumert, Jens; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Muenzel, Thomas; Schnabel, Renate B.; Wild, Philipp S.; Zeller, Tanja; Blankenberg, Stefan] Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [North, Kari] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Schillert, Arne; Ziegler, Andreas] Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. [Sanna, Serena; Orru, Marco; Usala, Gianluca; Uda, Manuela] CNR, IRGB, Cagliari, Italy. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Cheng, Yu-Ching] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rivadeneira, Fernando; Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Nambi, Vijay; Ballantyne, Christie] Baylor Coll Med, Houston, TX 77030 USA. [Nambi, Vijay] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Prevent, Houston, TX USA. [Nambi, Vijay] Ben Taub Gen Hosp, Houston, TX 77030 USA. [Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Petrovic, Katja E.] Med Univ Graz, Graz, Austria. [Petrovic, Katja E.] Gen Hosp, Dept Neurol, Graz, Austria. [Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Peltonen, Leena] Univ Helsinki, Biomedicum, Inst Mol Med Finland, Helsinki, Finland. [Peltonen, Leena] Natl Inst Hlth & Welf, Helsinki, Finland. [Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Parsa, Afshin; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Taylor, Kent; Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Sitzer, Matthias] Klinikum Herford, Dept Neurol, Herford, Germany. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Illig, Thomas; Klopp, Norman] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Muenchen, Neuherberg, Germany. [Illig, Thomas] Hannover Med Sch, Biobank Hannover Med Sch, D-3000 Hannover, Germany. [Orru, Marco] Santa Barbara Hosp, Div Med, Cardiol Operating Unit, Santa Barbara, CA, Italy. [Luedemann, Jan] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Seissler, Jochen] Univ Munich, Med Clin Innenstadt, Ctr Diabet, Munich, Germany. [Ernst, Florian; Chilukoti, Ravi Kumar; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [O'Leary, Daniel H.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Boston, MA 02111 USA. [Thiery, Joachim] Univ Hosp Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany. [Thiery, Joachim] Univ Leipzig, Fac Med, Leipzig Res Ctr Civilizat Dis, Leipzig, Germany. [Lakatta, Edward G.; Scuteri, Angelo] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Boston, MA 02111 USA. [Rathmann, Wolfgang] Univ Dusseldorf, Inst Biometr & Epidemiol, German Diabet Ctr, Leibniz Ctr Diabet Res, Dusseldorf, Germany. [Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. RP Bis, JC (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM joshbis@uw.edu; odonnellc@nhlbi.nih.gov RI Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Hayward, Caroline/M-8818-2016; Aspelund, Thor/C-5983-2008; Abecasis, Goncalo/B-7840-2010; Rice, Kenneth/A-4150-2013; Newman, Anne/C-6408-2013; Meisinger, Christine/B-5358-2014; Schnabel, Renate/F-6527-2014; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; OI Meisinger, Christa/0000-0002-9026-6544; sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825; Ziegler, Andreas/0000-0002-8386-5397; Bevan, Steve/0000-0003-0490-6830; Mitchell, Braxton/0000-0003-4920-4744; Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Hayward, Caroline/0000-0002-9405-9550; Cupples, L. Adrienne/0000-0003-0273-7965; Aspelund, Thor/0000-0002-7998-5433; Rice, Kenneth/0000-0001-5779-4495; Newman, Anne/0000-0002-0106-1150; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Dehghan, Abbas/0000-0001-6403-016X FU US National Institutes of Health (NIH) [N01-AG-12100]; National Institute on Aging (NIA) Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); NIH [R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06]; University of Maryland General Clinical Research Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center; Paul Beeson Physician Faculty Scholars in Aging Program; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; US National Institutes of Health [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research; Netherlands Organisation for Scientific Research; Erasmus Medical Center; Centre for Medical Systems Biology (CMSB); National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute of Aging [AG-023629, AG-15928, AG-20098, AG-027058, AG08122, AG16495, AG033193]; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; National Institute of Neurological Disorders and Stroke [NS17950]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Netherlands Organisation of Scientific Research (NWO, De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; NWO [918-76-619]; Erasmus Medical Center and Erasmus University; Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Bundesministeriumfuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; National Institute on Aging, NIH; National Institute on Aging [NO1-AG-1-2109]; National Institute on Aging to the University of Michigan [263-MA-410953]; National Institutes of Health [HG005581, HL084729]; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; Austrian Science Fond (FWF) [P20545-P05, P13180]; Medical University of Graz; European Community [201668]; government of Rheinland-Pfalz ('Stiftung Rheinland Pfalzfur Innovation') [AZ 961-386261/733]; Wissenschafft Zukunft; 'Schwerpunkt Vaskulare Pravention' of the Johannes Gutenberg-University of Mainz; BoehringerIngelheim; Philips Medical Systems; Gutenberg Heart Study; National Genome Network 'NGFNplus' [A3 01GS0833]; Federal Ministry of Education and Research, Germany; Helmholtz Zentrum Munchen; German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research (BMBF); German National Genome Research Network (NGFNplus) [01GS0834]; University of Ulm; Munich Center of Health Sciences (MC Health); Karl-Wilder Foundation; German Diabetes Center; German Federal Ministry of Health; Ministry of Innovation, Science, Research and Technology of the State of North Rhine Westphalia; Office of the Scottish Government; Royal Society; European Union [LSHG-CT-2006-018947]; Academy of Finland [117797, 121584, 126925]; Social Insurance Institution of Finland; University Hospital Medical funds to Tampere; Turku University Hospitals; Finnish Foundation of Cardiovascular Research FX The Age, Gene/Environment Susceptibility (AGES) Reykjavik Study was funded by US National Institutes of Health (NIH) contract N01-AG-12100, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).; The Old Order Amish Studies were supported by grants and contracts from the NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification Study), U01 GM074518-04 (The Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study) and U01 HL072515-06 (the Heredity and Phenotype Intervention (HAPI) heart study), the University of Maryland General Clinical Research Center grant M01 RR 16500, the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center and the Paul Beeson Physician Faculty Scholars in Aging Program. We thank our Amish research volunteers for their long-standing partnership in research and the research staff at the Amish Research Clinic for their hard work and dedication.; The Atherosclerosis Risk in Communities Study (ARIC) was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and US National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Study infrastructure was partly supported by grant number UL1RR025005, a component of the US National Institutes of Health and NIH Roadmap for Medical Research.; The Erasmus Rucphen Family Study was supported by grants from The Netherlands Organisation for Scientific Research, Erasmus Medical Center and the Centre for Medical Systems Biology (CMSB). We are grateful to all study participants and their relatives, the general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work and P. Snijders for his help in data collection.; The Cardiovascular Health Study research reported in this article was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants HL080295, HL075366, HL087652, HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098 and AG-027058 from the National Institute of Aging. See also http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00069 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the US National Institutes of Health and Boston University School of Medicine was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278) and by grants from the National Institute of Neurological Disorders and Stroke (NS17950, P. A. W.) and the National Institute of Aging (AG08122, AG16495, P. A. W. and AG033193, S. S.). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project.; Rotterdam Study I and II (RS I and RS II): The Rotterdam GWAS was funded by the Netherlands Organisation of Scientific Research (NWO, De Nederlandse Organisatie voor Wetenschappelijk Onderzoek) Investments (number 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project number 050-060-810. This study was further supported by an NWO grant (vici, 918-76-619). The Rotterdam Study was funded by the Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the participants and staff from the Rotterdam Study, the participating general practioners and the pharmacists. We thank P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk and S. Bervoets for their help in creating the GWAS database. We would like to thank T. A. Knoch, L. V. de Zeeuw, A. Abuseiris and R. de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the National German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministeriumfuer Forschung und Technology under grants #01 AK 803 A-H and #01 IG 07015 G, for access to their grid resources.; The SardiNIA Study: This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. The SardiNIA ('Progenia') team was supported by Contract NO1-AG-1-2109 from the National Institute on Aging. The efforts of G. R. A. were supported in part by contract 263-MA-410953 from the National Institute on Aging to the University of Michigan and by research grants HG005581 and HL084729 from the National Institutes of Health (to G.R.A.).; The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants number 01ZZ9603, 01ZZ0103 and 01ZZ0403), and the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. The SHIP authors are grateful to the contribution of A. Teumer, A. Hoffmann and A. Petersmann in generating the SNP data. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG.; The Austrian Stroke Prevention Study (ASPS): The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS.; The Coronary Artery Progression Study: Research leading these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 201668; AtheroRemo.; The Gutenberg Heart Study was funded through the government of Rheinland-Pfalz ('Stiftung Rheinland Pfalzfur Innovation', contract number AZ 961-386261/733), the research programs 'Wissenschafft Zukunft' and 'Schwerpunkt Vaskulare Pravention' of the Johannes Gutenberg-University of Mainz and its contract with BoehringerIngelheim and Philips Medical Systems, including an unrestricted grant for the Gutenberg Heart Study. Specifically, the research reported in this article was supported by the National Genome Network 'NGFNplus' (contract number project A3 01GS0833) by the Federal Ministry of Education and Research, Germany.; Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFNplus, project number 01GS0834) and through additional funds from the University of Ulm. Furthermore, the research was supported within the Munich Center of Health Sciences (MC Health) as part of Ludwig-Maximilians-Universitat Munich (LMU) innovative. IMT measurement of the KORA cohort was funded by a grant of the Karl-Wilder Foundation. Finally, part of this work was financed by the German Diabetes Center, which is funded by the German Federal Ministry of Health and the Ministry of Innovation, Science, Research and Technology of the State of North Rhine Westphalia.; The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government, the Royal Society and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of L. Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney.; The Cardiovascular Risk in Young Finns Study was supported by the Academy of Finland (grant numbers 117797, 121584 and 126925), the Social Insurance Institution of Finland, University Hospital Medical funds to Tampere, and Turku University Hospitals, the Finnish Foundation of Cardiovascular Research. NR 37 TC 92 Z9 92 U1 0 U2 11 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 OCT PY 2011 VL 43 IS 10 BP 940 EP U40 DI 10.1038/ng.920 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200007 PM 21909108 ER PT J AU Bass, AJ Lawrence, MS Brace, LE Ramos, AH Drier, Y Cibulskis, K Sougnez, C Voet, D Saksena, G Sivachenko, A Jing, R Parkin, M Pugh, T Verhaak, RG Stransky, N Boutin, AT Barretina, J Solit, DB Vakiani, E Shao, WL Mishina, Y Warmuth, M Jimenez, J Chiang, DY Signoretti, S Kaelin, WG Spardy, N Hahn, WC Hoshida, Y Ogino, S DePinho, RA Chin, L Garraway, LA Fuchs, CS Baselga, J Tabernero, J Gabriel, S Lander, ES Getz, G Meyerson, M AF Bass, Adam J. Lawrence, Michael S. Brace, Lear E. Ramos, Alex H. Drier, Yotam Cibulskis, Kristian Sougnez, Carrie Voet, Douglas Saksena, Gordon Sivachenko, Andrey Jing, Rui Parkin, Melissa Pugh, Trevor Verhaak, Roel G. Stransky, Nicolas Boutin, Adam T. Barretina, Jordi Solit, David B. Vakiani, Evi Shao, Wenlin Mishina, Yuji Warmuth, Markus Jimenez, Jose Chiang, Derek Y. Signoretti, Sabina Kaelin, William G., Jr. Spardy, Nicole Hahn, William C. Hoshida, Yujin Ogino, Shuji DePinho, Ronald A. Chin, Lynda Garraway, Levi A. Fuchs, Charles S. Baselga, Jose Tabernero, Josep Gabriel, Stacey Lander, Eric S. Getz, Gad Meyerson, Matthew TI Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion SO NATURE GENETICS LA English DT Article ID HUMAN BREAST; TUMOR-SUPPRESSOR; PROSTATE-CANCER; LUNG-CANCER; GENES; COMPLEX; RISK; CHROMOSOME-5Q21; TUMORIGENESIS; REARRANGEMENT AB Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma(1) and have surveyed exons of protein-coding genes for mutations in 11 affected individuals(2,3). Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7x and 31.9x coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted inframe fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with beta-catenin(4) in colorectal carcinogenesis(5,6), the fusion lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. C1 [Bass, Adam J.; Lawrence, Michael S.; Ramos, Alex H.; Cibulskis, Kristian; Sougnez, Carrie; Voet, Douglas; Saksena, Gordon; Sivachenko, Andrey; Jing, Rui; Parkin, Melissa; Pugh, Trevor; Verhaak, Roel G.; Stransky, Nicolas; Barretina, Jordi; Hahn, William C.; Hoshida, Yujin; Chin, Lynda; Garraway, Levi A.; Gabriel, Stacey; Lander, Eric S.; Getz, Gad; Meyerson, Matthew] Broad Inst, Cambridge, MA USA. [Bass, Adam J.; Brace, Lear E.; Ramos, Alex H.; Pugh, Trevor; Verhaak, Roel G.; Boutin, Adam T.; Kaelin, William G., Jr.; Spardy, Nicole; Hahn, William C.; Ogino, Shuji; DePinho, Ronald A.; Chin, Lynda; Garraway, Levi A.; Fuchs, Charles S.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Kaelin, William G., Jr.; Hahn, William C.; DePinho, Ronald A.; Garraway, Levi A.; Fuchs, Charles S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bass, Adam J.; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. [Solit, David B.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Vakiani, Evi] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Shao, Wenlin; Mishina, Yuji; Warmuth, Markus] Novartis Inst Biomed Res, Cambridge, MA USA. [Jimenez, Jose; Baselga, Jose; Tabernero, Josep] Hosp Valle De Hebron, Dept Med Oncol, Barcelona, Spain. [Chiang, Derek Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Signoretti, Sabina; Ogino, Shuji; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Signoretti, Sabina; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Lander, Eric S.] MIT, Cambridge, MA 02139 USA. [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Getz, G (reprint author), Broad Inst, Cambridge, MA USA. EM gadgetz@broadinstitute.org; matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Drier, Yotam/K-5208-2012 OI Drier, Yotam/0000-0003-1725-2995 FU US National Institutes of Health [K08CA134931]; GI SPORE Developmental Project Award [P50CA127003]; National Human Genome Research Institute FX We thank all members of the Biological Samples Platform and DNA Sequencing Platforms of the Broad Institute, without whose work this sequencing project could not have occurred, and R. Shivdasani and M. Freedman for helpful discussion. This work was supported by US National Institutes of Health grant K08CA134931 (A.J.B.), a GI SPORE Developmental Project Award (P50CA127003; M. M.) and the National Human Genome Research Institute (E.S.L.). NR 39 TC 152 Z9 157 U1 4 U2 14 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 OCT PY 2011 VL 43 IS 10 BP 964 EP U67 DI 10.1038/ng.936 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200010 PM 21892161 ER PT J AU Ripke, S Sanders, AR Kendler, KS Levinson, DF Sklar, P Holmans, PA Lin, DY Duan, J Ophoff, RA Andreassen, OA Scolnick, E Cichon, S Clair, DS Corvin, A Gurling, H Werge, T Rujescu, D Blackwood, DHR Pato, CN Malhotra, AK Purcell, S Dudbridge, F Neale, BM Rossin, L Visscher, PM Posthuma, D Ruderfer, DM Fanous, A Stefansson, H Steinberg, S Mowry, BJ Golimbet, V De Hert, M Jonsson, EG Bitter, I Pietilainen, OPH Collier, DA Tosato, S Agartz, I Albus, M Alexander, M Amdur, RL Amin, F Bass, N Bergen, SE Black, DW Borglum, AD Brown, MA Bruggeman, R Buccola, NG Byerley, WF Cahn, W Cantor, RM Carr, VJ Catts, SV Choudhury, K Cloninger, CR Cormican, P Craddock, N Danoy, PA Datta, S De Haan, L Demontis, D Dikeos, D Djurovic, S Donnelly, P Donohoe, G Duong, L Dwyer, S Fink-Jensen, A Freedman, R Freimer, NB Friedl, M Georgieva, L Giegling, I Gill, M Glenthoj, B Godard, S Hamshere, M Hansen, M Hansen, T Hartmann, AM Henskens, FA Hougaard, DM Hultman, CM Ingason, A Jablensky, AV Jakobsen, KD Jay, M Jurgens, G Kahn, R Keller, MC Kenis, G Kenny, E Kim, Y Kirov, GK Konnerth, H Konte, B Krabbendam, L Krasucki, R Lasseter, VK Laurent, C Lawrence, J Lencz, T Lerer, FB Liang, KY Lichtenstein, P Lieberman, JA Linszen, DH Lonnqvist, J Loughland, CM Maclean, AW Maher, BS Maier, W Mallet, J Malloy, P Mattheisen, M Mattingsdal, M McGhee, KA McGrath, JJ McIntosh, A McLean, DE McQuillin, A Melle, I Michie, PT Milanova, V Morris, DW Mors, O Mortensen, PB Moskvina, V Muglia, P Myin-Germeys, I Nertney, DA Nestadt, G Nielsen, J Nikolov, I Nordentoft, M Norton, N Nothen, MM O'Dushlaine, CT Olincy, A Olsen, L O'Neill, FA Orntoft, TF Owen, MJ Pantelis, C Papadimitriou, G Pato, MT Peltonen, L Petursson, H Pickard, B Pimm, J Pulver, AE Puri, V Quested, D Quinn, EM Rasmussen, HB Rethelyi, JM Ribble, R Rietschel, M Riley, BP Ruggeri, M Schall, U Schulze, TG Schwab, SG Scott, RJ Shi, JX Sigurdsson, E Silverman, JM Spencer, CCA Stefansson, K Strange, A Strengman, E Stroup, TS Suvisaari, J Terenius, L Thirumalai, S Thygesen, JH Timm, S Toncheva, D van den Oord, E van Os, J van Winkel, R Veldink, J Walsh, D Wang, AG Wiersma, D Wildenauer, DB Williams, HJ Williams, NM Wormley, B Zammit, S Sullivan, PF O'Donovan, MC Daly, MJ Gejman, PV AF Ripke, Stephan Sanders, Alan R. Kendler, Kenneth S. Levinson, Douglas F. Sklar, Pamela Holmans, Peter A. Lin, Dan-Yu Duan, Jubao Ophoff, Roel A. Andreassen, Ole A. Scolnick, Edward Cichon, Sven Clair, David St. Corvin, Aiden Gurling, Hugh Werge, Thomas Rujescu, Dan Blackwood, Douglas H. R. Pato, Carlos N. Malhotra, Anil K. Purcell, Shaun Dudbridge, Frank Neale, Benjamin M. Rossin, Lizzy Visscher, Peter M. Posthuma, Danielle Ruderfer, Douglas M. Fanous, Ayman Stefansson, Hreinn Steinberg, Stacy Mowry, Bryan J. Golimbet, Vera De Hert, Marc Jonsson, Erik G. Bitter, Istvan Pietilainen, Olli P. H. Collier, David A. Tosato, Sarah Agartz, Ingrid Albus, Margot Alexander, Madeline Amdur, Richard L. Amin, Farooq Bass, Nicholas Bergen, Sarah E. Black, Donald W. Borglum, Anders D. Brown, Matthew A. Bruggeman, Richard Buccola, Nancy G. Byerley, William F. Cahn, Wiepke Cantor, Rita M. Carr, Vaughan J. Catts, Stanley V. Choudhury, Khalid Cloninger, C. Robert Cormican, Paul Craddock, Nicholas Danoy, Patrick A. Datta, Susmita De Haan, Lieuwe Demontis, Ditte Dikeos, Dimitris Djurovic, Srdjan Donnelly, Peter Donohoe, Gary Duong, Linh Dwyer, Sarah Fink-Jensen, Anders Freedman, Robert Freimer, Nelson B. Friedl, Marion Georgieva, Lyudmila Giegling, Ina Gill, Michael Glenthoj, Birte Godard, Stephanie Hamshere, Marian Hansen, Mark Hansen, Thomas Hartmann, Annette M. Henskens, Frans A. Hougaard, David M. Hultman, Christina M. Ingason, Andres Jablensky, Assen V. Jakobsen, Klaus D. Jay, Maurice Juergens, Gesche Kahn, Renes Keller, Matthew C. Kenis, Gunter Kenny, Elaine Kim, Yunjung Kirov, George K. Konnerth, Heike Konte, Bettina Krabbendam, Lydia Krasucki, Robert Lasseter, Virginia K. Laurent, Claudine Lawrence, Jacob Lencz, Todd Lerer, F. Bernard Liang, Kung-Yee Lichtenstein, Paul Lieberman, Jeffrey A. Linszen, Don H. Lonnqvist, Jouko Loughland, Carmel M. Maclean, Alan W. Maher, Brion S. Maier, Wolfgang Mallet, Jacques Malloy, Pat Mattheisen, Manuel Mattingsdal, Morten McGhee, Kevin A. McGrath, John J. McIntosh, Andrew McLean, Duncan E. McQuillin, Andrew Melle, Ingrid Michie, Patricia T. Milanova, Vihra Morris, Derek W. Mors, Ole Mortensen, Preben B. Moskvina, Valentina Muglia, Pierandrea Myin-Germeys, Inez Nertney, Deborah A. Nestadt, Gerald Nielsen, Jimmi Nikolov, Ivan Nordentoft, Merete Norton, Nadine Noethen, Markus M. O'Dushlaine, Colm T. Olincy, Ann Olsen, Line O'Neill, F. Anthony Orntoft, Torben F. Owen, Michael J. Pantelis, Christos Papadimitriou, George Pato, Michele T. Peltonen, Leena Petursson, Hannes Pickard, Ben Pimm, Jonathan Pulver, Ann E. Puri, Vinay Quested, Digby Quinn, Emma M. Rasmussen, Henrik B. Rethelyi, Janos M. Ribble, Robert Rietschel, Marcella Riley, Brien P. Ruggeri, Mirella Schall, Ulrich Schulze, Thomas G. Schwab, Sibylle G. Scott, Rodney J. Shi, Jianxin Sigurdsson, Engilbert Silverman, Jeremy M. Spencer, Chris C. A. Stefansson, Kari Strange, Amy Strengman, Eric Stroup, T. Scott Suvisaari, Jaana Terenius, Lars Thirumalai, Srinivasa Thygesen, Johan H. Timm, Sally Toncheva, Draga van den Oord, Edwin van Os, Jim van Winkel, Ruud Veldink, Jan Walsh, Dermot Wang, August G. Wiersma, Durk Wildenauer, Dieter B. Williams, Hywel J. Williams, Nigel M. Wormley, Brandon Zammit, Stan Sullivan, Patrick F. O'Donovan, Michael C. Daly, Mark J. Gejman, Pablo V. CA Schizophrenia Psychiat Genome-Wide TI Genome-wide association study identifies five new schizophrenia loci SO NATURE GENETICS LA English DT Article ID COMMON SNPS EXPLAIN; BIPOLAR DISORDER; HUMAN HEIGHT; LARGE PROPORTION; MICRORNA; VARIANTS; SUSCEPTIBILITY; HERITABILITY; INDIVIDUALS; ANCESTRY AB We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)). 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EM pgejman@gmail.com RI Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lencz, Todd/J-3418-2014; McQuillin, Andrew/C-1623-2008; Stroup, Thomas/F-9188-2014; Demontis, Ditte/M-4515-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Sigurdsson, Engilbert/D-2486-2014; Myin-Germeys, Inez /L-5106-2014; Jablensky, Assen/H-5116-2014; Pickard, Benjamin/K-3923-2014; Hansen, Thomas/O-5965-2014; Holmans, Peter/F-4518-2015; Mortensen, Preben/D-2358-2015; SCHALL, ULRICH/G-7452-2013; Mattheisen, Manuel/B-4949-2012; Pantelis, Christos/H-7722-2014; Nielsen, Jimmi /G-2990-2010; Liang, Kung-Yee/F-8299-2011; Cahn , Wiepke /B-5743-2013; Catts, Stanley/G-6917-2013; Tosato, Sarah /E-6045-2010; Cloninger, Claude/F-5357-2012; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Maher, Brion/F-9185-2010; Ingason, Andres/G-6817-2012; Bergen, Sarah/I-8313-2012; McIntosh, Andrew/B-9379-2008; McGrath, John/G-5493-2010 OI Andreassen, Ole A./0000-0002-4461-3568; Henskens, Frans/0000-0003-2358-5630; Visscher, Peter/0000-0002-2143-8760; Suvisaari, Jaana/0000-0001-7167-0990; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; Stefansson, Hreinn/0000-0002-9331-6666; Escott-Price, Valentina/0000-0003-1784-5483; Golimbet, Vera/0000-0002-9960-7114; Agartz, Ingrid/0000-0002-9839-5391; Jonsson, Erik/0000-0001-8368-6332; Nothen, Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Morris, Derek/0000-0002-3413-570X; Rethelyi, Janos/0000-0002-3641-012X; Myin-Germeys, Inez/0000-0002-3731-4930; KELLER, MATTHEW/0000-0002-6075-9882; Gill, Michael/0000-0003-0206-5337; Buccola, Nancy/0000-0003-1378-4636; lichtenstein, paul/0000-0003-3037-5287; Thygesen, Johan H/0000-0002-7479-3459; Melle, Ingrid /0000-0002-9783-548X; Ruderfer, Douglas/0000-0002-2365-386X; Lencz, Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Zammit, Stanley/0000-0002-2647-9211; Stroup, Thomas/0000-0002-3123-0672; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Sigurdsson, Engilbert/0000-0001-9404-7982; Pickard, Benjamin/0000-0002-2374-6329; Hansen, Thomas/0000-0001-6703-7762; Holmans, Peter/0000-0003-0870-9412; Mortensen, Preben/0000-0002-5230-9865; Mattheisen, Manuel/0000-0002-8442-493X; Pantelis, Christos/0000-0002-9565-0238; Cloninger, Claude/0000-0003-3096-4807; McIntosh, Andrew/0000-0002-0198-4588; McGrath, John/0000-0002-4792-6068 FU US National Institutes of Health FX We thank the study participants and the research staff at the many study sites. Over 40 US National Institutes of Health grants and similar numbers of government grants from other countries, along with substantial private and foundation support, enabled this work. We greatly appreciate the sustained efforts of T. Lehner (National Institute of Mental Health) on behalf of the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC). Detailed acknowledgments, including grant support, are listed in the Supplementary Note. NR 32 TC 535 Z9 547 U1 11 U2 154 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 OCT PY 2011 VL 43 IS 10 BP 969 EP U77 DI 10.1038/ng.940 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200011 ER PT J AU Sklar, P Ripke, S Scott, LJ Andreassen, OA Cichon, S Craddock, N Edenberg, HJ Nurnberger, JI Rietschel, M Blackwood, D Corvin, A Flickinger, M Guan, WH Mattingsdal, M McQuillin, A Kwan, P Wienker, TF Daly, M Dudbridge, F Holmans, PA Lin, DY Burmeister, M Greenwood, TA Hamshere, ML Muglia, P Smith, EN Zandi, PP Nievergelt, CM McKinney, R Shilling, PD Schork, NJ Bloss, CS Foroud, T Koller, DL Gershon, ES Liu, CY Badner, JA Scheftner, WA Lawson, WB Nwulia, EA Hipolito, M Coryell, W Rice, J Byerley, W McMahon, FJ Schulze, TG Berrettini, W Lohoff, FW Potash, JB Mahon, PB McInnis, MG Zollner, S Zhang, P Craig, DW Szelinger, S Barrett, TB Breuer, R Meier, S Strohmaier, J Witt, SH Tozzi, F Farmer, A McGuffin, P Strauss, J Xu, W Kennedy, JL Vincent, JB Matthews, K Day, R Ferreira, MA O'Dushlaine, C Perlis, R Raychaudhuri, S Ruderfer, D Hyoun, PL Smoller, JW Li, J Absher, D Thompson, RC Meng, FG Schatzberg, AF Bunney, WE Barchas, JD Jones, EG Watson, SJ Myers, RM Akil, H Boehnke, M Chambert, K Moran, J Scolnick, E Djurovic, S Melle, I Morken, G Gill, M Morris, D Quinn, E Muhleisen, TW Degenhardt, FA Mattheisen, M Schumacher, J Maier, W Steffens, M Propping, P Nothen, MM Anjorin, A Bass, N Gurling, H Kandaswamy, R Lawrence, J McGhee, K McIntosh, A McLean, AW Muir, WJ Pickard, BS Breen, G St Clair, D Caesar, S Gordon-Smith, K Jones, L Fraser, C Green, EK Grozeva, D Jones, IR Kirov, G Moskvina, V Nikolov, I O'Donovan, MC Owen, MJ Collier, DA Elkin, A Williamson, R Young, AH Ferrier, IN Stefansson, K Stefansson, H Porgeirsson, P Steinberg, S Gustafsson, O Bergen, SE Nimgaonkar, V Hultman, C Landen, M Lichtenstein, P Sullivan, P Schalling, M Osby, U Backlund, L Frisen, L Langstrom, N Jamain, S Leboyer, M Etain, B Bellivier, F Petursson, H Sigurosson, E Muller-Mysok, B Lucae, S Schwarz, M Schofield, PR Martin, N Montgomery, GW Lathrop, M Oskarsson, H Bauer, M Wright, A Mitchell, PB Hautzinger, M Reif, A Kelsoe, JR Purcell, SM AF Sklar, Pamela Ripke, Stephan Scott, Laura J. Andreassen, Ole A. Cichon, Sven Craddock, Nick Edenberg, Howard J. Nurnberger, John I., Jr. Rietschel, Marcella Blackwood, Douglas Corvin, Aiden Flickinger, Matthew Guan, Weihua Mattingsdal, Morten McQuillin, Andrew Kwan, Phoenix Wienker, Thomas F. Daly, Mark Dudbridge, Frank Holmans, Peter A. Lin, Danyu Burmeister, Margit Greenwood, Tiffany A. Hamshere, Marian L. Muglia, Pierandrea Smith, Erin N. Zandi, Peter P. Nievergelt, Caroline M. McKinney, Rebecca Shilling, Paul D. Schork, Nicholas J. Bloss, Cinnamon S. Foroud, Tatiana Koller, Daniel L. Gershon, Elliot S. Liu, Chunyu Badner, Judith A. Scheftner, William A. Lawson, William B. Nwulia, Evaristus A. Hipolito, Maria Coryell, William Rice, John Byerley, William McMahon, Francis J. Schulze, Thomas G. Berrettini, Wade Lohoff, Falk W. Potash, James B. Mahon, Pamela B. McInnis, Melvin G. Zoellner, Sebastian Zhang, Peng Craig, David W. Szelinger, Szabocls Barrett, Thomas B. Breuer, Rene Meier, Sandra Strohmaier, Jana Witt, Stephanie H. Tozzi, Federica Farmer, Anne McGuffin, Peter Strauss, John Xu, Wei Kennedy, James L. Vincent, John B. Matthews, Keith Day, Richard Ferreira, Manuel A. O'Dushlaine, Colm Perlis, Roy Raychaudhuri, Soumya Ruderfer, Douglas Hyoun, Phil L. Smoller, Jordan W. Li, Jun Absher, Devin Thompson, Robert C. Meng, Fan Guo Schatzberg, Alan F. Bunney, William E. Barchas, Jack D. Jones, Edward G. Watson, Stanley J. Myers, Richard M. Akil, Huda Boehnke, Michael Chambert, Kim Moran, Jennifer Scolnick, Ed Djurovic, Srdjan Melle, Ingrid Morken, Gunnar Gill, Michael Morris, Derek Quinn, Emma Muehleisen, Thomas W. Degenhardt, Franziska A. Mattheisen, Manuel Schumacher, Johannes Maier, Wolfgang Steffens, Michael Propping, Peter Noethen, Markus M. Anjorin, Adebayo Bass, Nick Gurling, Hugh Kandaswamy, Radhika Lawrence, Jacob McGhee, Kevin McIntosh, Andrew McLean, Alan W. Muir, Walter J. Pickard, Benjamin S. Breen, Gerome St Clair, David Caesar, Sian Gordon-Smith, Katherine Jones, Lisa Fraser, Christine Green, Elaine K. Grozeva, Detelina Jones, Ian R. Kirov, George Moskvina, Valentina Nikolov, Ivan O'Donovan, Michael C. Owen, Michael J. Collier, David A. Elkin, Amanda Williamson, Richard Young, Allan H. Ferrier, I. Nicol Stefansson, Kari Stefansson, Hreinn Porgeirsson, Porgeir Steinberg, Stacy Gustafsson, Omar Bergen, Sarah E. Nimgaonkar, Vishwajit Hultman, Christina Landen, Mikael Lichtenstein, Paul Sullivan, Patrick Schalling, Martin Osby, Urban Backlund, Lena Frisen, Louise Langstrom, Niklas Jamain, Stephane Leboyer, Marion Etain, Bruno Bellivier, Frank Petursson, Hannes Sigurosson, Engilbert Mueller-Mysok, Bertram Lucae, Susanne Schwarz, Markus Schofield, Peter R. Martin, Nick Montgomery, Grant W. Lathrop, Mark Oskarsson, Hogni Bauer, Michael Wright, Adam Mitchell, Philip B. Hautzinger, Martin Reif, Andreas Kelsoe, John R. Purcell, Shaun M. CA Psychiat GWAS Consortium Bipolar D TI Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 SO NATURE GENETICS LA English DT Article ID PSYCHIATRIC-DISORDERS; CACNA1C; SCHIZOPHRENIA; INDIVIDUALS; RISK; PSYCHOSIS; GENETICS; ANK3 AB We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 x 10(-7)). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci. C1 [Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Sklar, Pamela; Ripke, Stephan; Daly, Mark; Ferreira, Manuel A.; O'Dushlaine, Colm; Perlis, Roy; Raychaudhuri, Soumya; Ruderfer, Douglas; Hyoun, Phil L.; Smoller, Jordan W.; Bergen, Sarah E.; Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sklar, Pamela; Ripke, Stephan; Daly, Mark; Ferreira, Manuel A.; O'Dushlaine, Colm; Perlis, Roy; Raychaudhuri, Soumya; Ruderfer, Douglas; Hyoun, Phil L.; Smoller, Jordan W.; Bergen, Sarah E.; Purcell, Shaun M.] Harvard Univ, Sch Med, Boston, MA USA. [Ripke, Stephan; Daly, Mark; Ferreira, Manuel A.; O'Dushlaine, Colm; Perlis, Roy; Raychaudhuri, Soumya; Ruderfer, Douglas; Smoller, Jordan W.; Chambert, Kim; Moran, Jennifer; Scolnick, Ed; Bergen, Sarah E.; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Scott, Laura J.; Flickinger, Matthew; Guan, Weihua; Kwan, Phoenix; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Scott, Laura J.; Flickinger, Matthew; Guan, Weihua; Kwan, Phoenix; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Andreassen, Ole A.; Mattingsdal, Morten; Djurovic, Srdjan; Melle, Ingrid] Univ Oslo, Inst Clin Med, European Network Bipolar Res Expert Ctr ENBREC Gr, Oslo, Norway. [Andreassen, Ole A.; Melle, Ingrid] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Cichon, Sven; Muehleisen, Thomas W.; Degenhardt, Franziska A.; Mattheisen, Manuel; Schumacher, Johannes; Propping, Peter; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.; Degenhardt, Franziska A.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Craddock, Nick; Holmans, Peter A.; Hamshere, Marian L.; Gordon-Smith, Katherine; Fraser, Christine; Green, Elaine K.; Grozeva, Detelina; Jones, Ian R.; Kirov, George; Moskvina, Valentina; Nikolov, Ivan; O'Donovan, Michael C.; Owen, Michael J.] Cardiff Univ, Sch Med, Med Res Council MRC Ctr Neuropsychiat Genet & Gen, Cardiff, S Glam, Wales. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Dept Med & Mol Genet, Indianapolis, IN USA. [Nurnberger, John I., Jr.; Foroud, Tatiana; Koller, Daniel L.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA. [Rietschel, Marcella; Schulze, Thomas G.; Breuer, Rene; Meier, Sandra; Strohmaier, Jana; Witt, Stephanie H.] Univ Heidelberg, Dept Genet Epidemiol Psychiat, Cent Inst Mental Hlth Mannheim, D-6800 Mannheim, Germany. [Blackwood, Douglas; McGhee, Kevin; McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [Blackwood, Douglas; McGhee, Kevin; McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Med Genet Sect, Edinburgh, Midlothian, Scotland. [Corvin, Aiden; Gill, Michael; Morris, Derek; Quinn, Emma] Trinity Coll Dublin, Neuropsychiat Genet Res Grp, Dept Psychiat, Dublin, Ireland. [Corvin, Aiden; Gill, Michael; Morris, Derek; Quinn, Emma] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland. [Mattingsdal, Morten] Sorlandet Hosp HF, Kristiansand, Norway. [McQuillin, Andrew; Anjorin, Adebayo; Bass, Nick; Gurling, Hugh; Kandaswamy, Radhika; Lawrence, Jacob] UCL, Mol Psychiat Lab, Res Dept Mental Hlth Sci, London, England. [Wienker, Thomas F.; Mattheisen, Manuel; Steffens, Michael] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany. [Dudbridge, Frank] Univ London, London Sch Hyg & Trop Med, London, England. [Holmans, Peter A.] Cardiff Univ, Sch Med, Biostat & Bioinformat Unit, Cardiff, S Glam, Wales. [Lin, Danyu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Burmeister, Margit; Li, Jun] Univ Michigan, Dept Psychiat, Dept Human Genet, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Greenwood, Tiffany A.; Nievergelt, Caroline M.; McKinney, Rebecca; Shilling, Paul D.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Hamshere, Marian L.; Muglia, Pierandrea; Tozzi, Federica; Moskvina, Valentina] GlaxoSmithKline Res & Dev Ltd, Neurosci Ctr Excellence Drug Discovery, Verona, Italy. [Smith, Erin N.; Schork, Nicholas J.; Bloss, Cinnamon S.] Scripps Translat Sci Inst, La Jolla, CA USA. [Smith, Erin N.; Schork, Nicholas J.; Bloss, Cinnamon S.] Scripps Hlth, La Jolla, CA USA. [Zandi, Peter P.; Potash, James B.; Mahon, Pamela B.] Johns Hopkins Univ & Hosp, Dept Mental Hlth, Baltimore, MD USA. [Gershon, Elliot S.; Liu, Chunyu; Badner, Judith A.; Reif, Andreas] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Scheftner, William A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Lawson, William B.; Nwulia, Evaristus A.; Hipolito, Maria] Howard Univ, Coll Med, Dept Psychiat & Behav Sci, Washington, DC USA. [Coryell, William] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Rice, John] Washington Univ, Sch Med, St Louis, MO USA. [Byerley, William] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [McMahon, Francis J.; Schulze, Thomas G.] NIMH, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat, Gottingen, Germany. [Berrettini, Wade; Lohoff, Falk W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Craig, David W.; Szelinger, Szabocls] Translat Genom Res Inst, Phoenix, AZ USA. [Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA. [Farmer, Anne; McGuffin, Peter; Breen, Gerome; Collier, David A.; Elkin, Amanda; Williamson, Richard] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat SGDP Ctr, London WC2R 2LS, England. [Strauss, John; Vincent, John B.] Ctr Addict & Mental Hlth, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada. [Xu, Wei] Princess Margaret Hosp, Dept Biostat, Toronto, ON M4X 1K9, Canada. [Kennedy, James L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Sect, Toronto, ON, Canada. [Matthews, Keith; Young, Allan H.; Ferrier, I. Nicol] Univ Dundee, Sch Med, Dundee, Scotland. [Day, Richard] Royal Victoria Infirm, Sch Neurol Neurobiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Ferreira, Manuel A.; Martin, Nick; Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Thompson, Robert C.; Bunney, William E.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Meng, Fan Guo; Barchas, Jack D.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. [Schatzberg, Alan F.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Jones, Edward G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Ctr Neurosci, Davis, CA 95616 USA. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Morken, Gunnar] St Olavs Hosp, Dept Psychiat, Trondheim, Norway. [Morken, Gunnar] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Maier, Wolfgang] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. [Breen, Gerome; St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa] Univ Birmingham, Dept Psychiat, Sch Clin & Expt Med, Birmingham, W Midlands, England. [Young, Allan H.] Univ British Columbia, Inst Mental Hlth, Vancouver, BC V5Z 1M9, Canada. [Stefansson, Kari; Stefansson, Hreinn; Porgeirsson, Porgeir; Steinberg, Stacy; Gustafsson, Omar] deCODE Genet, Reykjavik, Iceland. [Nimgaonkar, Vishwajit] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Hultman, Christina; Landen, Mikael; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Landen, Mikael; Langstrom, Niklas] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Sullivan, Patrick] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Schalling, Martin; Osby, Urban; Frisen, Louise] Karolinska Inst, Dept Mol Med, Stockholm, Sweden. [Backlund, Lena] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Jamain, Stephane; Leboyer, Marion; Etain, Bruno; Bellivier, Frank] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. [Jamain, Stephane; Leboyer, Marion; Etain, Bruno; Bellivier, Frank] Univ Paris Est, Fac Med, Creteil, France. [Jamain, Stephane; Leboyer, Marion; Etain, Bruno; Bellivier, Frank] Hop H Mondor A Chenevier, AP HP, Dept Psychiat, Creteil, France. [Jamain, Stephane; Leboyer, Marion; Etain, Bruno; Bellivier, Frank] Fdn Fondamental, ENBREC Grp, Creteil, France. [Petursson, Hannes; Sigurosson, Engilbert] Univ Iceland, Div Psychiat, Landspitali Univ Hosp, Reykjavik, Iceland. [Mueller-Mysok, Bertram; Lucae, Susanne] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Schwarz, Markus] Psychiat Ctr Nordbaden, Wiesloch, Germany. [Schofield, Peter R.] Prince Wales Med Inst, Sydney, NSW, Australia. [Wright, Adam; Mitchell, Philip B.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Lathrop, Mark] Ctr Natl Genotypage, Evry, France. [Bauer, Michael] Univ Hosp Carl Gustav Carus, ENBREC Grp, Dept Psychiat & Psychotherapy, Dresden, Germany. [Wright, Adam; Mitchell, Philip B.] Black Dog Inst, Sydney, NSW, Australia. [Hautzinger, Martin] Univ Tubingen, Dept Clin & Dev Psychol, Inst Psychol, Tubingen, Germany. [Reif, Andreas] Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany. [Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, STEP, Dept Psychiat, San Diego, CA USA. RP Sklar, P (reprint author), Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. EM pamela.sklar@mssm.edu RI Pickard, Benjamin/K-3923-2014; Breen, Gerome/A-5540-2010; Schalling, Martin/F-1518-2015; Holmans, Peter/F-4518-2015; Montgomery, Grant/B-7148-2008; Mattheisen, Manuel/B-4949-2012; Melle, Ingrid /B-4858-2011; Schumacher, Johannes/F-4970-2015; Ruderfer, Douglas/M-5795-2016; Lohoff, Falk/M-7951-2016; BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Ferreira, Manuel/D-3609-2013; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Smith, Erin/E-5933-2011; Liu, Chunyu/G-7561-2012; McInnis, Melvin/F-6963-2012; Bergen, Sarah/I-8313-2012; McIntosh, Andrew/B-9379-2008; Burmeister, Margit/A-3157-2013; McGuffin, Peter/A-1565-2012; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Zhang, Peng/N-2920-2014 OI McMahon, Francis/0000-0002-9469-305X; Escott-Price, Valentina/0000-0003-1784-5483; Nothen, Markus/0000-0002-8770-2464; Andreassen, Ole A./0000-0002-4461-3568; Etain, Bruno/0000-0002-5377-1488; Edenberg, Howard/0000-0003-0344-9690; Steffens, Michael/0000-0002-6445-8593; Greenwood, Tiffany/0000-0002-6080-6503; Nurnberger, John/0000-0002-7674-1767; Gill, Michael/0000-0003-0206-5337; Schofield, Peter/0000-0003-2967-9662; lichtenstein, paul/0000-0003-3037-5287; Moran, Jennifer/0000-0002-5664-4716; Mitchell, Philip/0000-0002-7954-5235; Stefansson, Hreinn/0000-0002-9331-6666; Jamain, Stephane/0000-0002-4321-4100; Matthews, Keith/0000-0002-4478-5888; Nievergelt, Caroline/0000-0001-5766-8923; Lawson, William/0000-0002-9324-7090; Corvin, Aiden/0000-0001-6717-4089; O'Donovan, Michael/0000-0001-7073-2379; Backlund, Lena/0000-0001-9399-5024; Morris, Derek/0000-0002-3413-570X; Tozzi, Federica/0000-0002-3536-2920; Pickard, Benjamin/0000-0002-2374-6329; Breen, Gerome/0000-0003-2053-1792; Schalling, Martin/0000-0001-5011-2922; Holmans, Peter/0000-0003-0870-9412; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Melle, Ingrid /0000-0002-9783-548X; Schumacher, Johannes/0000-0001-9217-6457; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Liu, Chunyu/0000-0002-5986-4415; McInnis, Melvin/0000-0002-0375-6247; McIntosh, Andrew/0000-0002-0198-4588; Burmeister, Margit/0000-0002-1914-2434; McGuffin, Peter/0000-0002-9888-2907; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Zhang, Peng/0000-0003-1182-1392 FU US National Institutes of Health (NIH) [MH078151, MH081804, MH059567, MH59553, MH080372, 1U54RR025204]; Genetic Association Information Network (GAIN); NIMH Intramural Research Program; Tzedakah Foundation; American Philosophical Society; Stardust foundation; National Library of Medicine; Stanley Foundation for Medical Research; Wellcome Trust; Pritzker Neuropsychiatric Disorders Research Fund L.L.C.; GlaxoSmithKline; Research Council of Norway [167153/V50, 163070/V50, 175345/V50]; South-East Norway Health Authority [123-2004]; EU (ENBREC) FX We would like to recognize the contribution of thousands of subjects without whom this work would not be possible. T. Lehner (National Institute of Mental Health (NIMH)) was instrumental in initiating and planning the overall project. D. Posthuma and the Dutch Genetic Cluster Computer provided invaluable computational resources. We also thank the PGC schizophrenia group for allowing us to perform the combined analyses of six loci before publication. This work was supported by many grants from the US National Institutes of Health (NIH) (MH078151, MH081804, MH059567 supplement, MH59553, MH080372 and 1U54RR025204). Other sources of support include: the Genetic Association Information Network (GAIN), the NIMH Intramural Research Program, the Tzedakah Foundation, the American Philosophical Society, the Stardust foundation, the National Library of Medicine, the Stanley Foundation for Medical Research and the Wellcome Trust, the Pritzker Neuropsychiatric Disorders Research Fund L.L.C., GlaxoSmithKline, as well as grants for individual studies (see the Supplemental Note for a full list of Acknowledgements). The TOP Study was supported by grants from the Research Council of Norway (167153/V50, 163070/V50 and 175345/V50), the South-East Norway Health Authority (123-2004) and the EU (ENBREC). Additional acknowledgments can be found in the Supplementary Note. NR 31 TC 248 Z9 252 U1 6 U2 55 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 OCT PY 2011 VL 43 IS 10 BP 977 EP U162 DI 10.1038/ng.943 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200012 ER PT J AU Wain, LV Verwoert, GC O'Reilly, PF Shi, G Johnson, T Johnson, AD Bochud, M Rice, KM Henneman, P Smith, AV Ehret, GB Amin, N Larson, MG Mooser, V Hadley, D Dorr, M Bis, JC Aspelund, T Esko, T Janssens, ACJW Zhao, JH Heath, S Laan, M Fu, JY Pistis, G Luan, JA Arora, P Lucas, G Pirastu, N Pichler, I Jackson, AU Webster, RJ Zhang, F Peden, JF Schmidt, H Tanaka, T Campbell, H Igl, W Milaneschi, Y Hottenga, JJ Vitart, V Chasman, DI Trompet, S Bragg-Gresham, JL Alizadeh, BZ Chambers, JC Guo, XQ Lehtimaki, T Kuhnel, B Lopez, LM Polasek, O Boban, M Nelson, CP Morrison, AC Pihur, V Ganesh, SK Hofman, A Kundu, S Mattace-Raso, FUS Rivadeneira, F Sijbrands, EJG Uitterlinden, AG Hwang, SJ Vasan, RS Wang, TJ Bergmann, S Vollenweider, P Waeber, G Laitinen, J Pouta, A Zitting, P McArdle, WL Kroemer, HK Volker, U Volzke, H Glazer, NL Taylor, KD Harris, TB Alavere, H Haller, T Keis, A Tammesoo, ML Aulchenko, Y Barroso, I Khaw, KT Galan, P Hercberg, S Lathrop, M Eyheramendy, S Org, E Sober, S Lu, XW Nolte, IM Penninx, BW Corre, T Masciullo, C Sala, C Groop, L Voight, BF Melander, O O'Donnell, CJ Salomaa, V d'Adamo, AP Fabretto, A Faletra, F Ulivi, S Del Greco, MF Facheris, M Collins, FS Bergman, RN Beilby, JP Hung, J Musk, AW Mangino, M Shin, SY Soranzo, N Watkins, H Goel, A Hamsten, A Gider, P Loitfelder, M Zeginigg, M Hernandez, D Najjar, SS Navarro, P Wild, SH Corsi, AM Singleton, A de Geus, EJC Willemsen, G Parker, AN Rose, LM Buckley, B Stott, D Orru, M Uda, M van der Klauw, MM Zhang, WH Li, XZ Scott, J Chen, YDI Burke, GL Kahonen, M Viikari, J Doring, A Meitinger, T Davies, G Starr, JM Emilsson, V Plump, A Lindeman, JH 't Hoen, PAC Konig, IR Felix, JF Clarke, R Hopewell, JC Ongen, H Breteler, M Debette, S DeStefano, AL Fornage, M Mitchell, GF Smith, NL Holm, H Stefansson, K Thorleifsson, G Thorsteinsdottir, U Samani, NJ Preuss, M Rudan, I Hayward, C Deary, IJ Wichmann, HE Raitakari, OT Palmas, W Kooner, JS Stolk, RP Jukema, JW Wright, AF Boomsma, DI Bandinelli, S Gyllensten, UB Wilson, JF Ferrucci, L Schmidt, R Farrall, M Spector, TD Palmer, LJ Tuomilehto, J Pfeufer, A Gasparini, P Siscovick, D Altshuler, D Loos, RJF Toniolo, D Snieder, H Gieger, C Meneton, P Wareham, NJ Oostra, BA Metspalu, A Launer, L Rettig, R Strachan, DP Beckmann, JS Witteman, JCM Erdmann, J van Dijk, KW Boerwinkle, E Boehnke, M Ridker, PM Jarvelin, MR Chakravarti, A Abecasis, GR Gudnason, V Newton-Cheh, C Levy, D Munroe, PB Psaty, BM Caulfield, MJ Rao, DC Tobin, MD Elliott, P van Duijn, CM AF Wain, Louise V. Verwoert, Germaine C. O'Reilly, Paul F. Shi, Gang Johnson, Toby Johnson, Andrew D. Bochud, Murielle Rice, Kenneth M. Henneman, Peter Smith, Albert V. Ehret, Georg B. Amin, Najaf Larson, Martin G. Mooser, Vincent Hadley, David Doerr, Marcus Bis, Joshua C. Aspelund, Thor Esko, Tonu Janssens, A. Cecile J. W. Zhao, Jing Hua Heath, Simon Laan, Maris Fu, Jingyuan Pistis, Giorgio Luan, Jian'an Arora, Pankaj Lucas, Gavin Pirastu, Nicola Pichler, Irene Jackson, Anne U. Webster, Rebecca J. Zhang, Feng Peden, John F. Schmidt, Helena Tanaka, Toshiko Campbell, Harry Igl, Wilmar Milaneschi, Yuri Hottenga, Jouke-Jan Vitart, Veronique Chasman, Daniel I. Trompet, Stella Bragg-Gresham, Jennifer L. Alizadeh, Behrooz Z. Chambers, John C. Guo, Xiuqing Lehtimaki, Terho Kuehnel, Brigitte Lopez, Lorna M. Polasek, Ozren Boban, Mladen Nelson, Christopher P. Morrison, Alanna C. Pihur, Vasyl Ganesh, Santhi K. Hofman, Albert Kundu, Suman Mattace-Raso, Francesco U. S. Rivadeneira, Fernando Sijbrands, Eric J. G. Uitterlinden, Andre G. Hwang, Shih-Jen Vasan, Ramachandran S. Wang, Thomas J. Bergmann, Sven Vollenweider, Peter Waeber, Gerard Laitinen, Jaana Pouta, Anneli Zitting, Paavo McArdle, Wendy L. Kroemer, Heyo K. Voelker, Uwe Voelzke, Henry Glazer, Nicole L. Taylor, Kent D. Harris, Tamara B. Alavere, Helene Haller, Toomas Keis, Aime Tammesoo, Mari-Liis Aulchenko, Yurii Barroso, Ines Khaw, Kay-Tee Galan, Pilar Hercberg, Serge Lathrop, Mark Eyheramendy, Susana Org, Elin Sober, Siim Lu, Xiaowen Nolte, Ilja M. Penninx, Brenda W. Corre, Tanguy Masciullo, Corrado Sala, Cinzia Groop, Leif Voight, Benjamin F. Melander, Olle O'Donnell, Christopher J. Salomaa, Veikko d'Adamo, Adamo Pio Fabretto, Antonella Faletra, Flavio Ulivi, Sheila Del Greco, Fabiola M. Facheris, Maurizio Collins, Francis S. Bergman, Richard N. Beilby, John P. Hung, Joseph Musk, A. William Mangino, Massimo Shin, So-Youn Soranzo, Nicole Watkins, Hugh Goel, Anuj Hamsten, Anders Gider, Pierre Loitfelder, Marisa Zeginigg, Marion Hernandez, Dena Najjar, Samer S. Navarro, Pau Wild, Sarah H. Corsi, Anna Maria Singleton, Andrew de Geus, Eco J. C. Willemsen, Gonneke Parker, Alex N. Rose, Lynda M. Buckley, Brendan Stott, David Orru, Marco Uda, Manuela van der Klauw, Melanie M. Zhang, Weihua Li, Xinzhong Scott, James Chen, Yii-Der Ida Burke, Gregory L. Kahonen, Mika Viikari, Jorma Doering, Angela Meitinger, Thomas Davies, Gail Starr, John M. Emilsson, Valur Plump, Andrew Lindeman, Jan H. 't Hoen, Peter A. C. Koenig, Inke R. Felix, Janine F. Clarke, Robert Hopewell, Jemma C. Ongen, Halit Breteler, Monique Debette, Stephanie DeStefano, Anita L. Fornage, Myriam Mitchell, Gary F. Smith, Nicholas L. Holm, Hilma Stefansson, Kari Thorleifsson, Gudmar Thorsteinsdottir, Unnur Samani, Nilesh J. Preuss, Michael Rudan, Igor Hayward, Caroline Deary, Ian J. Wichmann, H-Erich Raitakari, Olli T. Palmas, Walter Kooner, Jaspal S. Stolk, Ronald P. Jukema, J. Wouter Wright, Alan F. Boomsma, Dorret I. Bandinelli, Stefania Gyllensten, Ulf B. Wilson, James F. Ferrucci, Luigi Schmidt, Reinhold Farrall, Martin Spector, Tim D. Palmer, Lyle J. Tuomilehto, Jaakko Pfeufer, Arne Gasparini, Paolo Siscovick, David Altshuler, David Loos, Ruth J. F. Toniolo, Daniela Snieder, Harold Gieger, Christian Meneton, Pierre Wareham, Nicholas J. Oostra, Ben A. Metspalu, Andres Launer, Lenore Rettig, Rainer Strachan, David P. Beckmann, Jacques S. Witteman, Jacqueline C. M. Erdmann, Jeanette van Dijk, Ko Willems Boerwinkle, Eric Boehnke, Michael Ridker, Paul M. Jarvelin, Marjo-Riitta Chakravarti, Aravinda Abecasis, Goncalo R. Gudnason, Vilmundur Newton-Cheh, Christopher Levy, Daniel Munroe, Patricia B. Psaty, Bruce M. Caulfield, Mark J. Rao, Dabeeru C. Tobin, Martin D. Elliott, Paul van Duijn, Cornelia M. CA LifeLines Cohort Study EchoGen Consortium AortaGen Consortium CHARGE Consortium Heart Failure KidneyGen Consortium CKDGen Consortium Cardiogenics Consortium CardioGram TI Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure SO NATURE GENETICS LA English DT Article ID ADRENERGIC-RECEPTOR TRAFFICKING; CARDIOVASCULAR-DISEASE RISK; BLOOD-PRESSURE; HEART-FAILURE; HYPERTENSION; METAANALYSIS; MORTALITY; GENE; MICE; RELEVANCE AB Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP. C1 [O'Reilly, Paul F.; Chambers, John C.; Zhang, Weihua; Li, Xinzhong; Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. 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[Doering, Angela] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Meitinger, Thomas; Pfeufer, Arne] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh, Midlothian, Scotland. [Plump, Andrew] Merck Res Lab, Rahway, NJ USA. [Lindeman, Jan H.] Leiden Univ Med Ctr, Dept Vasc Surg, Leiden, Netherlands. ['t Hoen, Peter A. C.] Leiden Univ Med Ctr, Leiden Genome Technol Ctr, Leiden, Netherlands. [Koenig, Inke R.; Preuss, Michael] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany. [Felix, Janine F.] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-6900 Heidelberg, Germany. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Debette, Stephanie] Boston Univ Sch Med, Dept Neurol, Boston, MA USA. [DeStefano, Anita L.] Boston Univ Sch Publ Hlth, Boston, MA USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Smith, Nicholas L.; Siscovick, David; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Ctr Dept Vet Affairs Off Res & Dev, Seattle, WA USA. [Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur] deCODE Genet Inc, Reykjavik, Iceland. [Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Samani, Nilesh J.] Glenfield Hosp, Leicester Natl Inst Hlth Res NIHR Biomed Res Unit, Leicester, Leics, England. [Preuss, Michael; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, Lubeck, Germany. [Rudan, Igor] Univ Split Med Sch, Croatian Ctr Global Hlth, Split, Croatia. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Palmas, Walter] Columbia Univ, New York, NY USA. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Palmer, Lyle J.] Ontario Canc Inst Res, Toronto, ON, Canada. [Palmer, Lyle J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. [Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Meneton, Pierre] Ctr Rech Cordeliers, INSERM, U872, Paris, France. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, Lausanne, Switzerland. [van Dijk, Ko Willems] Leiden Univ Med Ctr, Dept Internal Med, Leiden, Netherlands. [Boerwinkle, Eric] Ctr Human Genet, Houston, TX USA. [Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr, Oulu, Finland. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rao, Dabeeru C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Rao, Dabeeru C.] Washington Univ, Dept Math, Sch Med, St Louis, MO 63130 USA. [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, London, England. [van Duijn, Cornelia M.] Erasmus MC, Ctr Med Syst Biol, Rotterdam, Netherlands. RP Elliott, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. EM mt47@leicester.ac.uk; p.elliott@imperial.ac.uk; c.vanduijn@erasmusmc.nl RI Erdmann, Jeanette/P-7513-2014; Hernandez-Fuentes, Maria/B-5011-2010; Abecasis, Goncalo/B-7840-2010; Rudan, Igor/I-1467-2012; Willems van Dijk, Ko/A-1798-2008; Singleton, Andrew/C-3010-2009; Pirastu, Nicola/G-4358-2011; Arora, Pankaj/F-3437-2011; Laan, Maris/A-4100-2011; Beckmann, Jacques S /A-9772-2008; 't Hoen, Peter/A-4857-2012; Aspelund, Thor/C-5983-2008; EHRET, Georg/A-9532-2009; Lucas, Gavin/D-4346-2012; Deary, Ian/C-6297-2009; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Boban, Mladen/E-2777-2017; Feitosa, Mary/K-8044-2012; Gudnason, Vilmundur/K-6885-2015; Mattace- Raso, Francesco/L-2541-2015; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Shi, Gang/D-3301-2016; Hypponen, Elina/B-2596-2014; Smith, Albert/K-5150-2015; Bochud, Murielle/A-3981-2010; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Aulchenko, Yurii/M-8270-2013; Altshuler, David/A-4476-2009; van der Klauw, Melanie/A-2138-2014; d'Adamo, Adamo Pio/G-4064-2011; Palmer, Lyle/K-3196-2014; Kronenberg, Florian/B-1736-2008; Schalling, Martin/F-1518-2015; Eggermann, Thomas/F-3807-2014; Breteler, Monique /J-5058-2014; Bakker, Stephan/J-4023-2015; Maxwell, Patrick/C-5557-2008; Lopez, Lorna/F-7265-2010; Hadley, David/I-6902-2012; Heath, Simon/J-4138-2012; Rice, Kenneth/A-4150-2013; Stolk, Ronald/B-2341-2013; Pfeufer, Arne/B-6634-2013; Giallauria, Francesco/B-5681-2013; Newman, Anne/C-6408-2013; Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Gale, Daniel/D-5594-2013; Colaus, PsyColaus/K-6607-2013 OI Kleber, Marcus/0000-0003-0663-7275; Wain, Louise/0000-0003-4951-1867; Gillebert, Thierry/0000-0002-3832-919X; Janssens, A Cecile/0000-0002-6153-4976; Forouhi, Nita/0000-0002-5041-248X; Ziad Alizadeh, Behrooz/0000-0002-1415-8007; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Wallace, Chris/0000-0001-9755-1703; Ouwehand, Willem/0000-0002-7744-1790; Lawlor, Debbie A/0000-0002-6793-2262; Bergmann, Sven/0000-0002-6785-9034; Ramachandran, Vasan/0000-0001-7357-5970; Erdmann, Jeanette/0000-0002-4486-6231; Kundu, Suman/0000-0002-6305-2559; Hernandez-Fuentes, Maria/0000-0002-7558-9441; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397; Sijbrands, Eric/0000-0001-8857-7389; Magi, Reedik/0000-0002-2964-6011; Fuchsberger, Christian/0000-0002-5918-8947; Johnson, Toby/0000-0002-5998-3270; Org, Elin/0000-0003-1451-9375; Abecasis, Goncalo/0000-0003-1509-1825; Zgaga, Lina/0000-0003-4089-9703; Rudan, Igor/0000-0001-6993-6884; Willems van Dijk, Ko/0000-0002-2172-7394; Arora, Pankaj/0000-0003-2420-3550; Laan, Maris/0000-0002-8519-243X; Beckmann, Jacques S /0000-0002-9741-1900; Aspelund, Thor/0000-0002-7998-5433; EHRET, Georg/0000-0002-5730-0675; Feitosa, Mary/0000-0002-0933-2410; Pirastu, Nicola/0000-0002-5363-3886; Faletra, Flavio/0000-0003-1483-3612; Esko, Tonu/0000-0003-1982-6569; Larson, Martin/0000-0002-9631-1254; Felix, Janine/0000-0002-9801-5774; Pichler, Irene/0000-0001-8251-0757; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; de Geus, Eco/0000-0001-6022-2666; Rivadeneira, Fernando/0000-0001-9435-9441; Hypponen, Elina/0000-0003-3670-9399; Smith, Albert/0000-0003-1942-5845; Bochud, Murielle/0000-0002-5727-0218; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Aulchenko, Yurii/0000-0002-7899-1575; Altshuler, David/0000-0002-7250-4107; van der Klauw, Melanie/0000-0001-7178-009X; d'Adamo, Adamo Pio/0000-0001-9367-4909; Palmer, Lyle/0000-0002-1628-3055; Kronenberg, Florian/0000-0003-2229-1120; Schalling, Martin/0000-0001-5011-2922; Bakker, Stephan/0000-0003-3356-6791; Maxwell, Patrick/0000-0002-0338-2679; Rice, Kenneth/0000-0001-5779-4495; Stolk, Ronald/0000-0002-0518-1205; Giallauria, Francesco/0000-0003-4119-9397; Newman, Anne/0000-0002-0106-1150; Ulivi, Sheila/0000-0003-3606-835X; Gale, Daniel/0000-0002-9170-1579; FU US National Institutes of Health; National Heart, Lung, and Blood Institute, European FX A number of the participating studies and authors are members of the CHARGE and Global BPgen consortia. Many funding mechanisms by the US National Institutes of Health and National Heart, Lung, and Blood Institute, European and private funding agencies contributed to this work, and a full list of acknowledgements is provided in the Supplementary Note. NR 33 TC 169 Z9 171 U1 4 U2 53 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 OCT PY 2011 VL 43 IS 10 BP 1005 EP U122 DI 10.1038/ng.922 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 825XT UT WOS:000295316200017 PM 21909110 ER PT J AU Aomatsu, T Imaeda, H Matsumoto, K Kimura, E Yoden, A Tamai, H Fujiyama, Y Mizoguchi, E Andoh, A AF Aomatsu, T. Imaeda, H. Matsumoto, K. Kimura, E. Yoden, A. Tamai, H. Fujiyama, Y. Mizoguchi, E. Andoh, A. TI Faecal chitinase 3-like-1: a novel biomarker of disease activity in paediatric inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID COLONIC EPITHELIAL-CELLS; CROHNS-DISEASE; INTESTINAL INFLAMMATION; ULCERATIVE-COLITIS; ENDOSCOPIC ACTIVITY; CALPROTECTIN LEVELS; BACTERIAL ADHESION; ACTIVITY INDEX; SERUM YKL-40; VALIDATION AB Background Chitinase 3-like-1 (CHI3L1) is up-regulated in the inflamed mucosa of inflammatory bowel disease (IBD). Aim To evaluate the usefulness of a faecal CHI3L1 assay, as a reliable marker for predicting the severity of paediatric IBD. Methods Faecal samples were obtained from ulcerative colitis (UC, n = 94), Crohn's disease (CD, n = 87), and healthy individuals (n = 56). The faecal CHI3L1 and calprotectin levels were determined by ELISA. For endoscopic evaluation, the sum of the Matts' score for UC and the simple endoscopic score for CD (SES-CD) were used. Ileal lesions were evaluated by ultrasonography. Results Faecal CHI3L1 levels were significantly elevated in active UC (median 366.6 ng/g, n = 44) and active CD (median 632.7 ng/g, n = 48) patients, as compared with healthy individuals (median 2.2 ng/g, n = 56). In UC patients, the faecal CHI3L1 levels were positively correlated with the sum of the Matts' score (r = 0.73, P < 0.01, n = 42). In CD patients, there was a significant correlation between faecal CHI3L1 levels and endoscopic activity as determined by the SES-CD scoring system (r = 0.61, P < 0.01, n = 25). The faecal CHI3L1 levels of patients with wall thickening of their small intestine were significantly higher than those of healthy controls or patients without wall thickening. The cutoff value of 13.7 ng/g for fecal CHI3L1(the 95th percentile of the control value) predicted active lesions in IBD patients with a sensitivity of 84.7% and a specificity of 88.9%. Conclusion Faecal CHI3L1 assays may be useful for predicting the severity and activity of mucosal inflammation in IBD. Aliment Pharmacol Ther 2011; 34: 941-948 C1 [Andoh, A.] Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, Japan. [Aomatsu, T.; Imaeda, H.; Fujiyama, Y.] Shiga Univ Med Sci, Dept Med, Otsu, Shiga 5202192, Japan. [Aomatsu, T.; Yoden, A.; Tamai, H.] Osaka Med Coll, Dept Pediat, Takatsuki, Osaka 569, Japan. [Matsumoto, K.; Kimura, E.] Mikuri Immunol Lab Co, Yao, Japan. [Mizoguchi, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA. [Mizoguchi, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. RP Andoh, A (reprint author), Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 5202192, Japan. EM andoh@belle.shiga-med.ac.jp OI Imaeda, Hirotsugu/0000-0002-5516-8527 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [21590809]; Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan; National Institutes of Health [R01 DK80070]; Eli and Edythe Broad Medical Foundation FX This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21590809), and a grant from the Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan. Emiko Mizoguchi has been supported by grants from the National Institutes of Health (R01 DK80070) and Eli and Edythe Broad Medical Foundation. NR 42 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD OCT PY 2011 VL 34 IS 8 BP 941 EP 948 DI 10.1111/j.1365-2036.2011.04805.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 822WU UT WOS:000295082000013 PM 21848856 ER PT J AU Caballero, AE AF Caballero, A. Enrique TI Understanding the Hispanic/Latino Patient SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Culture; Hispanic; Latino; Treatment barriers; Type 2 diabetes mellitus ID MEXICAN-AMERICAN MEN; PHYSICAL-ACTIVITY; SELF-MANAGEMENT; SAN-ANTONIO; MINORITY POPULATIONS; INSULIN-RESISTANCE; METABOLIC SYNDROME; HEALTH BELIEFS; R230C VARIANT; LEISURE-TIME AB The Hispanic/Latino population is the largest minority group in the United States, representing approximately 16% of the population in 2010. The US Census Bureau defines Hispanic/Latino origin as ethnicity, which tends to be associated with culture and is distinct from race. Based on the US Census Bureau classifications, Hispanics/Latinos have at least 3 main racial backgrounds (white, black, and Native Indian), with the combination and proportion differing among Hispanic/Latino subgroups. The reflection of these racial differences in genetic ancestry partly explains why biological characteristics differ among Hispanic/Latino subgroups. Partly as a result of variations in biological characteristics, the risk of type 2 diabetes mellitus varies among Hispanic/Latino subgroups. According to data from the 1982 to 1984 Hispanic Health and Nutrition Examination Survey (HHANES), the prevalence of diagnosed and undiagnosed type 2 diabetes among adults aged 45 to 74 years was higher in Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%). In addition to genetics, there are multiple social and cultural factors that affect the prevalence and course of type 2 diabetes in Hispanic/Latino individuals. Although certain aspects of Hispanic/Latino culture may become barriers in the management of type 2 diabetes in this population, these cultural characteristics may also represent an opportunity for prevention and/or improvement of care. It is important for healthcare providers to have an understanding and appreciation of Hispanic/Latino culture in order to provide their Hispanic/Latino patients with healthcare that is culturally and socially appropriate. Only by considering genetic, social, and cultural factors can type 2 diabetes be successfully prevented, treated, and managed in Hispanic/Latino patients. (C) 2011 Published by Elsevier Inc. The American Journal of Medicine (2011) 124, S10-S15 C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Caballero, AE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM enrique.caballero@joslin.harvard.edu FU Daiichi Sankyo, Inc. FX Medical writing services and editorial assistance provided by Karen Stauffer, PhD, and Lucy Whitehouse, of inScience Communications, a Wolters Kluwer business, were funded by Daiichi Sankyo, Inc. NR 45 TC 23 Z9 24 U1 6 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2011 VL 124 IS 10 SU 1 BP S10 EP S15 DI 10.1016/j.amjmed.2011.07.018 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825GD UT WOS:000295258300003 PM 21939793 ER PT J AU Cersosimo, E Musi, N AF Cersosimo, Eugenio Musi, Nicolas TI Improving Treatment in Hispanic/Latino Patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cultural competence; Hispanic; Latino; Treatment barriers; Type 2 diabetes mellitus ID DIABETES SELF-MANAGEMENT; LIMITED ENGLISH PROFICIENCY; BLOOD-PRESSURE CONTROL; BODY-MASS INDEX; MEXICAN-AMERICANS; UNITED-STATES; HEALTH-CARE; SAN-ANTONIO; RACIAL/ETHNIC DIFFERENCES; PHYSICAL-ACTIVITY AB The prevalence of type 2 diabetes mellitus is higher in Hispanic/Latino individuals living in the United States compared with their non-Hispanic white counterparts. Many factors contribute to the increased prevalence of type 2 diabetes, including biological characteristics, socioeconomic conditions, and cultural aspects. The contribution of genetics to the risk of type 2 diabetes in Hispanic/Latino patients is becoming increasingly clear, but this inherent risk factor cannot be modified. However, certain socioeconomic and cultural factors, such as reduced access to healthcare, language barriers, cultural beliefs, and lack of cultural competence by the healthcare provider, are modifiable and should be overcome in order to improve the management of type 2 diabetes in Hispanic/Latino patients. At the healthcare system level, policies should be put into place to reduce disparities between Hispanics/Latinos and non-Hispanic whites regarding health insurance coverage and access to healthcare. At the healthcare provider and patient level, cultural beliefs should be taken into consideration when selecting adequate treatment. Overall, type 2 diabetes management should be individualized by identifying the preferred language and level of acculturation for each patient. These considerations are necessary to further improve communication through culturally appropriate educational materials and programs. These strategies may help to overcome the barriers in the treatment of type 2 diabetes in Hispanic/Latino patients. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, S16-S21 C1 [Cersosimo, Eugenio; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Texas Diabet Inst, San Antonio, TX 78229 USA. [Musi, Nicolas] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Cersosimo, E (reprint author), 701 S Zarzamora,MS 10-5, San Antonio, TX 78284 USA. EM Eugenio.Cersosimo@uhs-sa.com FU Daiichi Sankyo, Inc. FX Medical writing services and editorial assistance provided by Karen Stauffer, PhD, and Lucy Whitehouse, of inScience Communications, a Wolters Kluwer business, were funded by Daiichi Sankyo, Inc. NR 46 TC 6 Z9 6 U1 2 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2011 VL 124 IS 10 SU 1 BP S16 EP S21 DI 10.1016/j.amjmed.2011.07.019 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 825GD UT WOS:000295258300004 PM 21939794 ER PT J AU Gervais, DA Arellano, RS AF Gervais, Debra A. Arellano, Ronald S. TI Percutaneous Tumor Ablation for Hepatocellular Carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE hepatocellular carcinoma (HCC); liver; microwave ablation; percutaneous ethanol instillation; radiofrequency ablation; tumor ablation ID RADIOFREQUENCY TISSUE ABLATION; MICROWAVE COAGULATION THERAPY; PROSPECTIVE RANDOMIZED-TRIAL; PRIMARY LIVER-CANCER; ETHANOL INJECTION; IRREVERSIBLE ELECTROPORATION; PROGNOSTIC-FACTORS; HEPATIC-TUMORS; US GUIDANCE; CIRRHOSIS AB OBJECTIVE. This report reviews the current clinical status of percutaneous ablation of hepatocellular carcinoma (HCC). CONCLUSION. HCC is increasing in incidence. Multiple percutaneous ablation methods are now available for primary treatment or for bridging to transplantation. Percutaneous ethanol instillation and radiofrequency ablation are the most extensively evaluated percutaneous treatments for HCC. Newer technologies are being evaluated and may change future practice patterns. C1 [Gervais, Debra A.; Arellano, Ronald S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, Boston, MA 02214 USA. RP Gervais, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent,Dept Radiol, White 270,55 Fruit St, Boston, MA 02214 USA. EM dgervais@partners.org NR 55 TC 31 Z9 34 U1 0 U2 9 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2011 VL 197 IS 4 BP 789 EP 794 DI 10.2214/AJR.11.7656 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000048 PM 21940565 ER PT J AU Stolzmann, P Goetti, RP Maurovich-Horvat, P Hoffmann, U Flohr, TG Leschka, S Alkadhi, H AF Stolzmann, Paul Goetti, Robert P. Maurovich-Horvat, Pal Hoffmann, Udo Flohr, Thomas G. Leschka, Sebastian Alkadhi, Hatem TI Predictors of Image Quality in High-Pitch Coronary CT Angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE coronary angiography; CT; radiation dosage ID DUAL-SOURCE CT; HEART-RATE-VARIABILITY; COMPUTED-TOMOGRAPHY AB OBJECTIVE. High-pitch coronary CT angiography (CTA) shows an alternative coronary CTA protocol to retrospectively ECG-gated imaging that is associated with a significantly lower radiation exposure. Yet, the diagnostic quality of high-pitch coronary CTA cannot be sufficiently predicted on the basis of heart rate (HR) alone. Thus, we sought to prospectively identify the predictors of diagnostic high-pitch coronary CTA. SUBJECTS AND METHODS. One hundred consecutive patients (16 women, 84 men; mean age, 67 +/- 10 years) without restrictions in HR frequency or variability underwent prospectively ECG-gated high-pitch coronary artery calcification (CAC) scoring and coronary CTA using dual-source 128-MDCT. High-pitch CAC was graded on the basis of motion artifacts; high-pitch coronary CTA was graded on the basis of image quality by each of two independent and blinded readers. Predictors of coronary CTA image quality were assessed by multivariate logistic regression, including body mass index, risk of coronary artery disease, Agatston score, HR frequency and variability, and motion artifacts on CAC. If high-pitch coronary CTA was nondiagnostic, the examination was repeated using a retrospectively ECG-gated coronary CTA protocol. RESULTS. HR frequency (66 +/- 20 beats per minute [bpm]) and variability (12 +/- 10 bpm) during high-pitch coronary CTA was not significantly different from that during high-pitch CAC. Interobserver agreement for image quality reading was good (k = 0.79) for CAC and excellent (k = 0.88) for coronary CTA. High-pitch CAC showed no motion artifacts in 1304 of 1396 segments (93.4%) in 78 of 100 patients. Diagnostic image quality of high-pitch coronary CTA was found in 1413 of 1457 segments (97%) in 82 of 100 patients. Multivariate logistic regression revealed HR frequency (odds ratio, 1.04; p < 0.05) and motion artifacts on preceding high-pitch CAC (odds ratio, 94.55; p < 0.001) as significant independent predictors of image quality of high-pitch coronary CTA. The mean effective radiation doses of high-pitch CAC and coronary CTA were 0.4 +/- 0.1 mSv (0.3-0.5 mSv) and 1.0 +/- 0.2 mSv (0.8-1.2 mSv; p < 0.001), respectively. CONCLUSION. HR frequency and motion artifacts on preceding high-pitch CAC represent significant independent predictors of image quality in high-pitch coronary CTA. C1 [Stolzmann, Paul; Maurovich-Horvat, Pal; Hoffmann, Udo; Alkadhi, Hatem] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, Paul; Goetti, Robert P.; Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland. [Flohr, Thomas G.] CT CTE PA, Siemens Healthcare, Forchheim, Germany. [Leschka, Sebastian] Gen Hosp, Inst Radiol, St Gallen, Switzerland. RP Stolzmann, P (reprint author), Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland. EM pstolzmann@partners.org RI Goetti, Robert/I-8961-2012; OI Maurovich-Horvat, Pal/0000-0003-0885-736X NR 18 TC 13 Z9 13 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 OCT PY 2011 VL 197 IS 4 BP 851 EP 858 DI 10.2214/AJR.10.6072 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000055 PM 21940572 ER PT J AU Hamilton, BE Nesbit, GM Dosa, E Gahramanov, S Rooney, B Nesbit, EG Raines, J Neuwelt, EA AF Hamilton, Bronwyn E. Nesbit, Gary M. Dosa, Edit Gahramanov, Seymur Rooney, Bill Nesbit, Eric G. Raines, Joshua Neuwelt, Edward A. TI Comparative Analysis of Ferumoxytol and Gadoteridol Enhancement Using T1-and T2-Weighted MRI in Neuroimaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE contrast agents; glial neoplasms; iron oxide nanoparticles; nephrogenic systemic fibrosis; ultrasmall superparamagnetic iron oxides ID CENTRAL-NERVOUS-SYSTEM; CONTRAST AGENT; BRAIN-TUMORS; FERUMOXTRAN-10; NANOPARTICLES; FERUMOXIDES AB OBJECTIVE. Ferumoxytol, an ultrasmall superparamagnetic iron oxide particle, has been suggested as a potential alternative MRI contrast agent in patients with renal failure. We compared ferumoxytol to gadoteridol enhancement on T1- and T2-weighted MRI in CNS disorders to explore its diagnostic utility. SUBJECTS AND METHODS. Data were collected from three protocols in 70 adults who underwent alternate-day gadoteridol-and ferumoxytol-enhanced MRI using identical parameters. Two neuroradiologists measured lesion-enhancing size and intensity on contrast-enhanced T1-weighted images in consensus. T2-weighted images were evaluated for the presence of contrast-enhanced hypointensity. Mixed model repeated measures analysis of variance determined differences between T1-weighted enhancement size and intensity for individual protocols and group. RESULTS. After exclusions, 49 MRI studies in 29 men and 20 women (mean age, 51 years) were assessed. T1-weighted estimated enhancing sizes were different between agents (p = 0.0456) as a group; however, no differences were observed with untreated gliomas (n = 17) in two protocols (p = 1.0 and p = 0.99, respectively). Differences in T1-weighted enhancement intensity between agents were significant for the group overall (p = 0.0006); however, three-way interactions were not significant (p = 0.1233). T2-weighted images were assessed for contrast-enhanced hypointensity, observed in 26 of 49 (53%) ferumoxytol and zero of 49 (0%) gadoteridol scans. CONCLUSION. Ferumoxytol may be a useful MRI contrast agent in patients who are unable to receive gadolinium-based contrast agents. Greater experience with a wider variety of disorders is necessary to understand differences in enhancement with ferumoxytol compared with gadolinium-based contrast agents, given their different mechanisms of action. C1 [Hamilton, Bronwyn E.; Nesbit, Gary M.; Nesbit, Eric G.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Dosa, Edit; Gahramanov, Seymur; Raines, Joshua; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Rooney, Bill] Oregon Hlth & Sci Univ, Adv Imaging Res Lab, Portland, OR 97239 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA. [Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR USA. RP Hamilton, BE (reprint author), Oregon Hlth & Sci Univ, Dept Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code CR 135, Portland, OR 97239 USA. EM hamiltob@ohsu.edu FU National Institutes of Health [NS44687, NS53468, CA137488]; Department of Veterans Affairs FX This research was funded in part by the National Institutes of Health (grants NS44687, NS53468, and CA137488) and by a Veterans Affairs Merit Review grant from the Department of Veterans Affairs to E. A. Neuwelt. NR 19 TC 32 Z9 32 U1 1 U2 11 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 OCT PY 2011 VL 197 IS 4 BP 981 EP 988 DI 10.2214/AJR.10.5992 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000072 PM 21940589 ER PT J AU Abbara, S AF Abbara, Suhny TI Diverticula Kissing Vessel Sign Reply SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Abbara, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 2 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 OCT PY 2011 VL 197 IS 4 BP W790 EP W790 DI 10.2214/AJR.11.6722 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000040 ER PT J AU Sneag, DB Krajewski, K Giardino, A O'Regan, KN Shinagare, AB Jagannathan, JP Ramaiya, N AF Sneag, Darryl B. Krajewski, Katherine Giardino, Angela O'Regan, Kevin N. Shinagare, Atul B. Jagannathan, Jyothi P. Ramaiya, Nikhil TI Extrahepatic Spread of Hepatocellular Carcinoma: Spectrum of Imaging Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE extrahepatic; hepatocellular carcinoma (HCC); metastases; vascular invasion ID PRIMARY LIVER-CANCER; METASTASES; THROMBOSIS; CIRRHOSIS; WORLDWIDE; FEATURES; AUTOPSY; TRENDS AB OBJECTIVE. The purpose of this article is to describe the imaging findings of extrahepatic spread of hepatocellular carcinoma (HCC). CONCLUSION. Detecting extrahepatic metastases in HCC is critical in determining the optimal treatment plan for patients. Identifying the presence of extrahepatic metastases in patients with advanced disease may eliminate unnecessary surgery, such as liver transplantation or partial hepatic resection, and help direct the appropriate therapy. C1 [Sneag, Darryl B.; Krajewski, Katherine; Giardino, Angela; O'Regan, Kevin N.; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, Boston, MA 02215 USA. [Sneag, Darryl B.; Krajewski, Katherine; Giardino, Angela; O'Regan, Kevin N.; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Imaging,Dana Farber Canc Inst,Mellins Lib, Boston, MA 02215 USA. RP Sneag, DB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Mellins Lib, 75 Francis St, Boston, MA 02215 USA. EM darrylsneag@gmail.com NR 17 TC 5 Z9 5 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 OCT PY 2011 VL 197 IS 4 BP W658 EP W664 DI 10.2214/AJR.10.6402 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822WL UT WOS:000295081000014 PM 21940537 ER PT J AU Kondratiev, S Duraisamy, S Unitt, CL Green, MR Pinkus, GS Shipp, MA Kutok, JL Drapkin, RI Rodig, SJ AF Kondratiev, Svetlana Duraisamy, Sekhar Unitt, Christine L. Green, Michael R. Pinkus, Geraldine S. Shipp, Margaret A. Kutok, Jeffery L. Drapkin, Ronny I. Rodig, Scott J. TI Aberrant Expression of the Dendritic Cell Marker TNFAIP2 by the Malignant Cells of Hodgkin Lymphoma and Primary Mediastinal Large B-Cell Lymphoma Distinguishes These Tumor Types From Morphologically and Phenotypically Similar Lymphomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE TNFAIP2; Hodgkin Lymphoma; primary mediastinal (thymic) large B-cell lymphoma; immunohistochemistry ID NECROSIS-FACTOR-ALPHA; PRIMARY RESPONSE GENE; CLASSICAL HODGKIN; CD23 EXPRESSION; STERNBERG CELLS; FEATURES; GALECTIN-1; ACTIVATION; TRAF1; REED AB Tumor necrosis factor-alpha-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor alpha (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity = 87%) and specific (specificity = 96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice. C1 [Kondratiev, Svetlana; Unitt, Christine L.; Pinkus, Geraldine S.; Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Duraisamy, Sekhar; Drapkin, Ronny I.] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Green, Michael R.; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, 3rd Floor,75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org RI Green, Michael/F-3482-2013; Drapkin, Ronny/E-9944-2016 OI Green, Michael/0000-0001-6309-9472; Drapkin, Ronny/0000-0002-6912-6977 FU Lymphoma Targeting and Testing Center (LTTC) of the Dana-Farber Cancer Institute FX The authors gratefully acknowledge the technical assistance provided by Donna Skinner, Teri Bowman, and Janice Williams. This study was partially funded by the Lymphoma Targeting and Testing Center (LTTC) of the Dana-Farber Cancer Institute. NR 26 TC 11 Z9 11 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2011 VL 35 IS 10 BP 1531 EP 1539 DI 10.1097/PAS.0b013e31822bd476 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 822WK UT WOS:000295080800012 PM 21921781 ER PT J AU Baran, JL Duncan, LM AF Baran, Johanna L. Duncan, Lyn M. TI Combined Melanocytic Nevi: Histologic Variants and Melanoma Mimics SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE combined nevi; melanoma; clonal nevus; inverted type A; blue nevus ID EPITHELIOID CELL NEVI; BLUE NEVI; SPINDLE; DIFFERENTIATE; COMPONENTS; CHILDREN; LESIONS; ORIGIN; ADULTS; NAEVI AB Combined melanocytic nevi are composed of 2 or more distinct populations of nevomelanocytes. Most commonly used to describe the combination of blue nevi with common nevi, it may also be applied to other combinations of benign melanocytic proliferations, including Spitz nevi and nevi with deep dermal pigmented nevomelanocytes. We report the incidence and distribution of these tumors at the Massachusetts General Hospital over the past decade and review guidelines for diagnostic criteria and nomenclature. Between 2000 and 2010 we identified 511 cases of combined nevi, represented by 4 histologically distinct diagnostic categories: (1) blue nevus, (2) nevi with deep dermal pigmented nevomelanocytes (plexiform/deep penetrating, inverted type A/clonal), (3) Spitz or pigmented spindled cell nevus, combined with another type of nevus (usually common or dysplastic), and (4) other combinations including 2 or more nevus types. Nearly one fifth of these tumors displayed atypical features; atypia was observed more often in combined nevi with Spitz or deep pigmented elements (26 of 55, 47%, and 25 of 98, 26%, respectively) than in combined common and blue nevi (37 of 336, 11%). Clinical follow-up data were available for 83% of the patients with atypical combined nevi; none developed recurrence or metastasis with a mean follow-up of over 4 years. C1 [Duncan, Lyn M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit WRN 825, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit WRN 825, 55 Fruit St, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu NR 30 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2011 VL 35 IS 10 BP 1540 EP 1548 DI 10.1097/PAS.0b013e31822e9f5e PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 822WK UT WOS:000295080800013 PM 21881487 ER PT J AU Linskey, KR Dias-Santagata, D Nazarian, RM Le, LP Lam, Q Bellucci, KSW Robinson-Bostom, L Mihm, MC Hoang, MP AF Linskey, Katy R. Dias-Santagata, Dora Nazarian, Rosalynn M. Le, Long P. Lam, Quynh Bellucci, Kirsten S. W. Robinson-Bostom, Leslie Mihm, Martin C., Jr. Hoang, Mai P. TI Malignant Neurocristic Hamartoma: A Tumor Distinct From Conventional Melanoma and Malignant Blue Nevus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE malignant neurocristic hamartoma; mutational analyses; Ki-67; CD117 ID CONGENITAL MELANOCYTIC NEVI; MONOCLONAL-ANTIBODY; SPITZ NEVI; PROLIFERATIVE ACTIVITY; UVEAL MELANOMA; KIT EXPRESSION; CANCER; MUTATIONS; DISEASE; INVOLVEMENT AB Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials-the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. [Dias-Santagata, Dora; Nazarian, Rosalynn M.; Le, Long P.; Mihm, Martin C., Jr.; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. [Mihm, Martin C., Jr.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Bellucci, Kirsten S. W.] Hlth Network Labs, Dept Pathol, Allentown, PA USA. [Bellucci, Kirsten S. W.] LeHigh Valley Hosp Network, Allentown, PA USA. [Robinson-Bostom, Leslie] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 30 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2011 VL 35 IS 10 BP 1570 EP 1577 DI 10.1097/PAS.0b013e31822389b7 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 822WK UT WOS:000295080800016 PM 21934481 ER PT J AU Culley, DJ Boyd, JD Palanisamy, A Xie, ZC Kojima, K Vacanti, CA Tanzi, RE Crosby, G AF Culley, Deborah J. Boyd, Justin D. Palanisamy, Arvind Xie, Zhongcong Kojima, Koji Vacanti, Charles A. Tanzi, Rudolph E. Crosby, Gregory TI Isoflurane Decreases Self-renewal Capacity of Rat Cultured Neural Stem Cells SO ANESTHESIOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; ADULT NEUROGENESIS; EARLY EXPOSURE; ANESTHESIA; MEMORY; GABA; BRAIN; 60-DAY-OLD; PERSISTENT; 7-DAY-OLD AB Background: In models, isoflurane produces neural and behavioral deficits in vitro and in vivo. This study tested the hypothesis that neural stem cells are adversely affected by isoflurane such that it inhibits proliferation and kills these cells. Methods: Sprague-Dawley rat embryonic neural stem cells were plated onto 96-well plates and treated with isoflurane, 0.7, 1.4, or 2.8%, in 21% oxygen for 6 h and fixed either at the end of treatment or 6 or 24 h later. Control plates received 21% oxygen under identical conditions. Cell proliferation was assessed immunocytochemically using 5-ethynyl-2'-deoxyuridine incorporation and death by propidium iodide staining, lactate dehydrogenase release, and nuclear expression of cleaved caspase 3. Data were analyzed at each concentration using an ANOVA; P < 0.05 was considered significant. Results: Isoflurane did not kill neural stem cells by any measure at any time. Isoflurane, 1.4 and 2.8%, reduced cell proliferation based upon 5-ethynyl-2'-deoxyuridine incorporation, whereas isoflurane, 0.7%, had no effect. At 24 h after treatment, the net effect was a 20-30% decrease in the number of cells in culture. Conclusions: Isoflurane does not kill neural stem cells in vitro. At concentrations at and above the minimum alveolar concentrations required for general anesthesia (1.4 and 2.8%), isoflurane inhibits proliferation of these cells but has no such effect at a subminimum alveolar concentration (0.7%). These data imply that dosages of isoflurane at and above minimum alveolar concentrations may reduce the pool of neural stem cells in vivo but that lower dosages may be devoid of such effects. C1 [Culley, Deborah J.; Palanisamy, Arvind; Kojima, Koji; Vacanti, Charles A.; Crosby, Gregory] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Boyd, Justin D.] Harvard Univ, Brigham & Womens Hosp, Harvard NeuroDiscovery Ctr, Sch Med,Lab Drug Discovery Neurodegenerat, Boston, MA 02115 USA. [Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. [Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA USA. RP Culley, DJ (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Lab Aging Neurosci, 75 Francis St, Boston, MA 02115 USA. EM dculley@zeus.bwh.harvard.edu FU Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts; National Institutes of Health, Bethesda, Maryland [RO1 AG20253, RO1 GM088817, K08NS048140, R21AG029856, R01 GM088801, KO8 GM077057]; FAER FX Received from the Department of Anesthesia, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts. Submitted for publication April 13, 2010. Accepted for publication April 21, 2011. Supported by the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and grants RO1 AG20253 and RO1 GM088817 (to Dr. Crosby), K08NS048140, R21AG029856, and R01 GM088801 (to Dr. Xie), and KO8 GM077057 (to Dr. Culley) from the National Institutes of Health, Bethesda, Maryland.; One or more authors of this peer-reviewed article have been supported by FAER. In conjunction with the FAER 25th anniversary, articles and editorials in ANESTHESIOLOGY October 2011 issue celebrate the accomplishments of FAER. For additional information visit www.FAER.org. NR 27 TC 33 Z9 36 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2011 VL 115 IS 4 BP 754 EP 763 DI 10.1097/ALN.0b013e318223b78b PG 10 WC Anesthesiology SC Anesthesiology GA 822VX UT WOS:000295079500017 PM 21666433 ER PT J AU Cotten, JF Le Ge, R Banacos, N Pejo, E Husain, SS Williams, JH Raines, DE AF Cotten, Joseph F. Le Ge, Ri Banacos, Natalie Pejo, Ervin Husain, S. Shaukat Williams, James H. Raines, Douglas E. TI Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats A Comparative Study of Dosing and the Impact on Adrenocortical Function SO ANESTHESIOLOGY LA English DT Article ID CRITICALLY-ILL PATIENTS; LOW-DOSE ETOMIDATE; CUSHINGS-SYNDROME; REMIFENTANIL GI87084B; ANESTHESIA; INDUCTION; PHARMACOKINETICS; RESPONSES; HYPERCORTISOLEMIA; SUPPRESSION AB Background: Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods: A closed-loop system using the electroencephalo-graphic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min. Results: The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomidate > carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions: Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative-hypnotic maintenance agents when hemodynamic stability is desirable. C1 [Cotten, Joseph F.; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.] Harvard Univ, Sch Med, Boston, MA USA. [Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 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; FAER FX Received from the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication November 23, 2010. Accepted for publication February 4, 2011. 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, carboetomidate, and related analogs (application numbers PCT/US10/41379 [July 8, 2010] and PCT/US09/38872 [March 31, 2009]). Three authors (Drs. Raines, Cotten, and Husain) and their respective laboratories, departments, and institutions could receive compensation related to the development or sale of these drugs. Dr. Raines has an equity interest in Annovation BioPharma, Inc., which has an option to license the etomidate analogs evaluated in this study.; One or more authors of this peer-reviewed article have been supported by FAER. In conjunction with the FAER 25th anniversary, articles and editorials in ANESTHESIOLOGY October 2011 issue celebrate the accomplishments of FAER. For additional information visit www.FAER.org. NR 37 TC 24 Z9 25 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2011 VL 115 IS 4 BP 764 EP 773 DI 10.1097/ALN.0b013e31821950de PG 10 WC Anesthesiology SC Anesthesiology GA 822VX UT WOS:000295079500018 PM 21572317 ER PT J AU Solt, K Cotten, JF Cimenser, A Wong, KFK Chemali, JJ Brown, EN AF Solt, Ken Cotten, Joseph F. Cimenser, Aylin Wong, Kin F. K. Chemali, Jessica J. Brown, Emery N. TI Methylphenidate Actively Induces Emergence from General Anesthesia SO ANESTHESIOLOGY LA English DT Article ID STEADY-STATE RESPONSE; ISOFLURANE ANESTHESIA; PREFRONTAL CORTEX; BISPECTRAL INDEX; SLEEP; PHYSOSTIGMINE; MODULATION; NARCOLEPSY; RECEPTORS; AROUSAL AB Background: Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia. Methods: Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions. Results: Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155-331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4-8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions: Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery. C1 [Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F. K.; Chemali, Jessica J.; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Solt, Ken; Cotten, Joseph F.; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Solt, Ken; Brown, Emery N.] 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 RI Wong, Kin Foon Kevin/C-7896-2014; OI Solt, Ken/0000-0001-5328-2062 FU National Institutes of Health, Bethesda, Maryland [DP1-OD003646, K08-GM094394, K08-GM083216]; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; FAER FX Received from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. Submitted for publication February 16, 2011. Accepted for publication June 28, 2011. Supported by grants DP1-OD003646, K08-GM094394, and K08-GM083216 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. This work has been presented, in part, at annual meetings of the Association of University Anesthesiologists (Denver, Colorado, April 10, 2010) and the Society for Neuroscience (San Diego, California, November 14, 2010).; One or more authors of this peer-reviewed article have been supported by FAER. In conjunction with the FAER 25th anniversary, articles and editorials in the ANESTHESIOLOGY October 2011 issue celebrate the accomplishments of FAER. For additional information visit www.FAER.org. NR 49 TC 52 Z9 55 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2011 VL 115 IS 4 BP 791 EP 803 DI 10.1097/ALN.0b013e31822e92e5 PG 13 WC Anesthesiology SC Anesthesiology GA 822VX UT WOS:000295079500021 PM 21934407 ER PT J AU Petersen, B Austen, KF Bloch, KD Hotta, Y Ichinose, F Kanaoka, Y Zapol, WM AF Petersen, Bodil Austen, K. Frank Bloch, Kenneth D. Hotta, Yukako Ichinose, Fumito Kanaoka, Yoshihide Zapol, Warren M. TI Cysteinyl Leukotrienes Impair Hypoxic Pulmonary Vasoconstriction in Endotoxemic Mice SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; VASCULAR-PERMEABILITY; C-4 SYNTHASE; MAST-CELLS; RECEPTOR; PROTEIN; 5-LIPOXYGENASE; RATS; B-4; PURIFICATION AB Background: Sepsis impairs hypoxic pulmonary vasoconstriction (HPV) in patients and animal models, contributing to systemic hypoxemia. Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl leukotrienes to the impairment of HPV is unknown. Methods: Wild-type mice, mice deficient in leukotriene C-4 synthase, the enzyme responsible for cysteinyl leukotriene synthesis, and mice deficient in cysteinyl leukotriene receptor 1 were studied 18 h after challenge with either saline or endotoxin. HPV was measured by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion. Concentrations of cysteinyl leukotrienes were determined in the bronchoalveolar lavage fluid. Results: In the bronchoalveolar lavage fluid of all three strains, cysteinyl leukotrienes were not detectable after saline challenge; whereas endotoxin challenge increased cysteinyl leukotriene concentrations in wild-type mice and mice deficient in cysteinyl leukotriene receptor 1, but not in mice deficient in leukotriene C-4 synthase. HPV did not differ among the three mouse strains after saline challenge (120 +/- 26, 114 +/- 16, and 115 +/- 24%, respectively; mean +/- SD). Endotoxin challenge markedly impaired HPV in wild-type mice (41 +/- 20%) but only marginally in mice deficient in leukotriene C-4 synthase (96 +/- 16%, P < 0.05 vs. wild-type mice), thereby preserving systemic oxygenation. Although endotoxin modestly decreased HPV in mice deficient in cysteinyl leukotriene receptor 1 (80 +/- 29%, P < 0.05 vs. saline challenge), the magnitude of impairment was markedly less than in endotoxin-challenged wild-type mice. Conclusion: Cysteinyl leukotrienes importantly contribute to endotoxin-induced impairment of HPV in part via a cysteinyl leukotriene receptor 1-dependent mechanism. C1 [Petersen, Bodil; Bloch, Kenneth D.; Hotta, Yukako; Ichinose, Fumito; Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Austen, K. Frank; Kanaoka, Yoshihide] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Austen, K. Frank; Kanaoka, Yoshihide] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org FU National Institutes of Health, Bethesda, Maryland [P01HL36110, R01HL74352, R01GM79360, R01HL090630, R01HL42397] FX Received from the Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and the Department of Medicine and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School. Submitted for publication December 14, 2010. Accepted for publication July 1, 2011. Supported by the grants P01HL36110 (to Dr. Austen), R01HL74352 (to Dr. Bloch), R01GM79360 (to Dr. Ichinose), R01HL090630 (to Dr. Kanaoka), and R01HL42397 (to Dr. Zapol) from the National Institutes of Health, Bethesda, Maryland. NR 47 TC 4 Z9 4 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 OCT PY 2011 VL 115 IS 4 BP 804 EP 811 DI 10.1097/ALN.0b013e31822e94bd PG 8 WC Anesthesiology SC Anesthesiology GA 822VX UT WOS:000295079500022 PM 21934409 ER PT J AU Baker, K AF Baker, Keith TI Determining Resident Clinical Performance Getting Beyond the Noise SO ANESTHESIOLOGY LA English DT Article ID QUALITY-OF-CARE; COGNITIVE-ABILITY; MEDICAL-EDUCATION; CERTIFICATION EXAMINATION; STANDARDIZED PATIENTS; EXAMINATION SCORES; PATIENT SIMULATOR; THINKING BIASES; ABOVE-AVERAGE; LAKE WOBEGON AB Background: Valid and reliable (dependable) assessment of resident clinical skills is essential for learning, promotion, and remediation. Competency is defined as what a physician can do, whereas performance is what a physician does in everyday practice. There is an ongoing need for valid and reliable measures of resident clinical performance. Methods: Anesthesia residents were evaluated confidentially on a weekly basis by faculty members who supervised them. The electronic evaluation form had five sections, including a rating section for absolute and relative-to-peers performance under each of the six Accreditation Council for Graduate Medical Education core competencies, clinical competency committee questions, rater confidence in having the resident perform cases of increasing difficulty, and comment sections. Residents and their faculty mentors were provided with the resident's formative comments on a biweekly basis. Results: From July 2008 to June 2010, 140 faculty members returned 14,469 evaluations on 108 residents. Faculty scores were pervasively positively biased and affected by idiosyncratic score range usage. These effects were eliminated by normalizing each performance score to the unique scoring characteristics of each faculty member (Z-scores). Individual Z-scores had low amounts of performance information, but signal averaging allowed determination of reliable performance scores. Average Z-scores were stable over time, related to external measures of medical knowledge, identified residents referred to the clinical competency committee, and increased when performance improved because of an intervention. Conclusions: This study demonstrates a reliable and valid clinical performance assessment system for residents at all levels of training. C1 Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM khbaker@partners.org NR 56 TC 19 Z9 19 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 OCT PY 2011 VL 115 IS 4 BP 862 EP 878 DI 10.1097/ALN.0b013e318229a27d PG 17 WC Anesthesiology SC Anesthesiology GA 822VX UT WOS:000295079500030 PM 21795965 ER PT J AU Viale, G Regan, MM Dell'Orto, P Mastropasqua, MG Maiorano, E Rasmussen, BB MacGrogan, G Forbes, JF Paridaens, RJ Colleoni, M Lang, I Thurlimann, B Mouridsen, H Mauriac, L Gelber, RD Price, KN Goldhirsch, A Gusterson, BA Coates, AS AF Viale, G. Regan, M. M. Dell'Orto, P. Mastropasqua, M. G. Maiorano, E. Rasmussen, B. B. MacGrogan, G. Forbes, J. F. Paridaens, R. J. Colleoni, M. Lang, I. Thuerlimann, B. Mouridsen, H. Mauriac, L. Gelber, R. D. Price, K. N. Goldhirsch, A. Gusterson, B. A. Coates, A. S. CA BIG 1-98 Collaborative & Int Breas TI Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial SO ANNALS OF ONCOLOGY LA English DT Article DE aromatase inhibitor; breast cancer; prognostic factor; tamoxifen ID EARLY BREAST-CANCER; INTERNATIONAL EXPERT CONSENSUS; POSTMENOPAUSAL WOMEN; COMPARING LETROZOLE; PREDICTIVE-VALUE; PRIMARY THERAPY; TAMOXIFEN; EXPRESSION; HIGHLIGHTS; BIOMARKERS AB Background: On average, aromatase inhibitors are better than tamoxifen when used as initial or sequential therapy for postmenopausal women with endocrine-responsive early breast cancer. Because there may be contraindications to their use based on side-effects or cost, we investigated subgroups in which aromatase inhibitors may be more or less important. Patients and methods: Breast International Group 1-98 trial randomized 6182 women among four groups comparing letrozole and tamoxifen with sequences of each agent; 5177 (84%) had centrally confirmed estrogen receptor (ER) positivity. We assessed whether centrally determined ER, progesterone receptor (PgR), human epidermal growth factor receptor 2, and Ki-67 labeling index, alone or in combination with other prognostic features, predicted the magnitude of letrozole effectiveness compared with either sequence or tamoxifen monotherapy. Results: Individually, none of the markers significantly predicted differential treatment effects. Subpopulation treatment effect pattern plot analysis of a composite measure of prognostic risk revealed three patterns. Estimated 5-year disease-free survival for letrozole monotherapy, letrozole -> tamoxifen, tamoxifen -> letrozole, and tamoxifen monotherapy were 96%, 94%, 93%, and 94%, respectively, for patients at lowest risk; 90%, 91%, 93%, and 86%, respectively, for patients at intermediate risk; and 80%, 76%, 74%, and 69%, respectively, for patients at highest risk. Conclusion: A composite measure of risk informs treatment selection better than individual biomarkers and supports the choice of 5 years of letrozole for patients at highest risk for recurrence. C1 [Viale, G.; Dell'Orto, P.; Mastropasqua, M. G.] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Int Breast Canc Study Grp Cent Pathol Off, I-20141 Milan, Italy. [Regan, M. M.; Gelber, R. D.; Price, K. N.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr,Frontier Sci &, Boston, MA 02115 USA. [Maiorano, E.] Univ Bari Aldo Moro, Dept Pathol Anat, Int Breast Canc Study Grp Cent Pathol Off, Bari, Italy. [Rasmussen, B. B.] Herlev Hosp, Dept Pathol, DK-2730 Herlev, Denmark. [MacGrogan, G.] Inst Bergonie, Dept Pathol, Bordeaux, France. [Forbes, J. F.] Univ Newcastle, Calvary Mater Newcastle, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. [Paridaens, R. J.] Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Med Oncol, Louvain, Belgium. [Colleoni, M.; Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Lang, I.] Natl Inst Oncol, Budapest, Hungary. [Thuerlimann, B.] Kantonsspital, Breast Ctr, Swiss Grp Clin Canc Res, St Gallen, Switzerland. [Mouridsen, H.] Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark. [Goldhirsch, A.] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Gusterson, B. A.] Univ Glasgow, Inst Canc Sci, Int Breast Canc Study Grp Cent Pathol Review Off, Glasgow, Lanark, Scotland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. RP Viale, G (reprint author), Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Int Breast Canc Study Grp Cent Pathol Off, Via Ripamonti 435, I-20141 Milan, Italy. EM giuseppe.viale@ieo.it RI Maiorano, Eugenio/F-1382-2015; OI Maiorano, Eugenio/0000-0002-0472-5338 FU Novartis [KG080081]; National Cancer Institute at National Institutes of Health [CA075362]; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; Foundation for Clinical Cancer Research of Eastern Switzerland FX Susan G. Komen for the Cure (Promise Grant KG080081); Novartis; National Cancer Institute at National Institutes of Health (CA075362); IBCSG (funded by Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; Foundation for Clinical Cancer Research of Eastern Switzerland). NR 20 TC 44 Z9 45 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2011 VL 22 IS 10 BP 2201 EP 2207 DI 10.1093/annonc/mdq738 PG 7 WC Oncology SC Oncology GA 823ZR UT WOS:000295168500006 PM 21335417 ER PT J AU Karlsson, P Sun, Z Braun, D Price, KN Castiglione-Gertsch, M Rabaglio, M Gelber, RD Crivellari, D Collins, J Murray, E Zaman, K Colleoni, M Gusterson, BA Viale, G Regan, MM Coates, AS Goldhirsch, A AF Karlsson, P. Sun, Z. Braun, D. Price, K. N. Castiglione-Gertsch, M. Rabaglio, M. Gelber, R. D. Crivellari, D. Collins, J. Murray, E. Zaman, K. Colleoni, M. Gusterson, B. A. Viale, G. Regan, M. M. Coates, A. S. Goldhirsch, A. TI Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE amenorrhea; breast cancer; chemotherapy; goserelin; hormonal therapy; node negative ID 2 RANDOMIZED-TRIALS; CHEMOENDOCRINE THERAPY; PREDICTIVE-VALUE; RECEPTOR STATUS; EXPRESSION; AMENORRHEA; MODALITY; ESTROGEN; SURVIVAL; WOMEN AB Background: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. Patients and methods: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF -> goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. Results: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF -> goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). Conclusions: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea. C1 [Karlsson, P.] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Oncol, Inst Clin Sci,Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Sun, Z.; Braun, D.; Regan, M. M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr,Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sun, Z.; Braun, D.; Regan, M. M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Price, K. N.] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA USA. [Castiglione-Gertsch, M.] Univ Geneva, Unite Oncogynecol, Dept Med, Med Hop, CH-1211 Geneva 4, Switzerland. [Rabaglio, M.] Univ Bern, Inselspital, IBCSG Coordinating Ctr, CH-3010 Bern, Switzerland. [Rabaglio, M.] Univ Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Gelber, R. D.] Harvard Univ, Sch Med, Sch Publ Hlth,Dana Farber Canc Inst, IBCSG Stat Ctr,Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gelber, R. D.] Harvard Univ, Sch Med, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA. [Crivellari, D.] Ctr Riferimento Oncol, Dept Med Oncol, I-33081 Aviano, Italy. [Collins, J.] Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. [Murray, E.] Univ Cape Town, Groote Shuur Hosp, Dept Radiat Oncol, ZA-7925 Cape Town, South Africa. [Zaman, K.] CHU Vaudois, Dept Med Oncol, Ctr Canc Lausanne, Lausanne & Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Colleoni, M.] European Inst Oncol, Res Unit Med Senol, Dept Med, Milan, Italy. [Gusterson, B. A.] Univ Glasgow, Inst Canc Sci, IBCSG Pathol Review Off, Glasgow, Lanark, Scotland. [Viale, G.] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, IBCSG Pathol Off, Milan, Italy. [Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Goldhirsch, A.] Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Karlsson, P (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Oncol, Inst Clin Sci,Sahlgrenska Acad, S-41345 Gothenburg, Sweden. EM per.karlsson@oncology.gu.se FU Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK); Swedish Society for Cancer Research (Cancerfonden) FX We acknowledge the initial support provided by the Ludwig Institute for Cancer Research and the Cancer League of Ticino and the continuing support for central coordination, data management, and statistics provided by the Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (NHMRC 890028, 920876, 950328, 980379, 141711); the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research (SAKK); the Swiss Cancer League; and the United States National Institutes of Health (CA-75362). We also acknowledge support for the Cape Town participants from the Cancer Association of South Africa; for the St Gallen participants from the Foundation for Clinical Research of Eastern Switzerland (OSKK); and for the Gothenburg participants from the Swedish Society for Cancer Research (Cancerfonden). Astra-Zeneca provided the Zoladex (R) free of charge. NR 21 TC 21 Z9 22 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2011 VL 22 IS 10 BP 2216 EP 2226 DI 10.1093/annonc/mdq735 PG 11 WC Oncology SC Oncology GA 823ZR UT WOS:000295168500008 PM 21325445 ER PT J AU Josephs, D Hutson, TE Cowey, CL Pickering, LM Larkin, JM Gore, ME Van Hemelrijck, M McDermott, DF Powles, T Chowdhury, P Karapetis, C Harper, PG Choueiri, TK Chowdhury, S AF Josephs, Debra Hutson, Thomas E. Cowey, Charles L. Pickering, Lisa M. Larkin, James M. Gore, Martin E. Van Hemelrijck, Mieke McDermott, David F. Powles, Thomas Chowdhury, Paramit Karapetis, Chris Harper, Peter G. Choueiri, Toni K. Chowdhury, Simon TI Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis SO BJU INTERNATIONAL LA English DT Article DE renal cell carcinoma; haemodialysis; sunitinib; chronic kidney disease ID CANCER; KIDNEY; SAFETY; PHARMACOKINETICS; DISEASE AB OBJECTIVE To further investigate the effect of sunitinib, which is currently a standard of care for the treatment of metastatic renal cell carcinoma (mRCC), in patients with severe renal impairment or those undergoing dialysis. PATIENTS AND METHODS Clinical databases were used to identify all patients with mRCC treated with sunitinib in seven institutions internationally. Databases were searched to identify only those patients with an estimated glomerular filtration rate of <30 mL/min/1.73 m(2) or those who had end-stage renal disease requiring dialysis. Baseline characteristics, adverse event data, response and progression-free survival were recorded. RESULTS Nineteen patients met the inclusion criteria, 10 of whom were undergoing haemodialysis. Of the nine non-dialysis-dependent patients at drug initiation, the median estimated glomerular filtration rate was 27 mL/min/1.73 m(2) (range 23-29). Baseline characteristics included a median age of 61 years (range 44-77); 17 patients had a Karnofsky performance status of >80; eight patients had more than two metastatic sites and 17 had undergone prior nephrectomy. The estimated median progression-free survival of this cohort was 43 weeks (range 7 to 158+) and progression has not yet been reached in six patients. Partial response or stable disease was observed as best response in 15 patients. The most common treatment-related adverse events included fatigue, diarrhoea, hand-foot skin reaction (HFSR), nausea and vomiting and rash. Grade three treatment-related adverse events including fatigue (seven patients), HFSR (two patients), diarrhoea (one patient), rash (one patient) and stomatitis (one patient) occurred in a total of 12 patients. Only one patient experienced a grade four adverse event (HFSR). Only diarrhoea (P = 0.0002), HFSR (P < 0.0001) and neutropenia (P = 0.001) were more common in patients undergoing haemodialysis compared with non-dialysis-dependent patients. Four of the non-dialysis dependent patients started at a dose of 50 mg compared with three of the patients undergoing haemodialysis. However five and two of the patients undergoing haemodialysis started at doses of 37.5 mg and 25 mg daily, respectively, compared with four and one of the non-dialysis-dependent patients. All patients took sunitinib for 4 out of every 6 weeks. Dose reductions during treatment were performed in eight patients but only one patient required discontinuation of treatment. CONCLUSION These data suggest that patients with severe renal impairment or end-stage renal disease on haemodialysis can be safely treated with sunitinib at doses of 25-50 mg daily for 4 weeks followed by a 2-week break. The observed efficacy of therapy is similar to that reported in patients with normal renal function. These preliminary results warrant confirmation in a larger cohort of patients. C1 [Josephs, Debra; Chowdhury, Paramit; Harper, Peter G.; Chowdhury, Simon] Guys Hosp, Guys & St Thomas Hosp, London SE1 9RT, England. [Pickering, Lisa M.; Larkin, James M.; Gore, Martin E.] Royal Marsden Hosp, London SW3 6JJ, England. [Pickering, Lisa M.; Larkin, James M.; Gore, Martin E.] Kings Coll London, London WC2R 2LS, England. [Powles, Thomas] Barts & London Hosp, London, England. [Hutson, Thomas E.; Cowey, Charles L.] Baylor Sammons Canc Ctr, Dallas, TX USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karapetis, Chris] Flinders Med Ctr, Bedford Pk, SA, Australia. RP Chowdhury, S (reprint author), Guys Hosp, Guys & St Thomas Hosp, 9th Floor Tower Wing, London SE1 9RT, England. EM Simon.Chowdhury@gstt.nhs.uk FU Pfizer; Glaxosmithkline FX Martin E. Gore and Thomas E. Hutson are on the advisory board and are members of the speaker's bureau for Sunitinib and Pfizer; James M. Larkin and Lisa M. Pickering have received travel grants, research funding and are members of the advisory board for Pfizer; Simon Chowdhury is on the advisory board for Novartis, GlaxoSmithkline and Sanofi Aventis; Toni K. Choueiri is on the advisory board for Bayer/Onyx Pharmaceuticals, Novartis, GlaxoSmithkline, Abbot, Genentech and Agennix, and is a consultant for Bayer/Onyx Pharmaceuticals, Novartis, GlaxoSmithkline and Pfizer; Thomas Powles has received research grants from Pfizer and Glaxosmithkline. NR 19 TC 25 Z9 25 U1 0 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 OCT PY 2011 VL 108 IS 8 BP 1279 EP 1283 DI 10.1111/j.1464-410X.2010.09990 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 827AL UT WOS:000295397000011 PM 21244613 ER PT J AU Goff, BA Matthews, B Andrilla, CHA Miller, JW Trivers, KF Berry, D Lishner, DM Baldwin, LM AF Goff, Barbara A. Matthews, Barbara Andrilla, C. Holly A. Miller, Jacqueline W. Trivers, Katrina F. Berry, Donna Lishner, Denise M. Baldwin, Laura-Mae TI How Are Symptoms of Ovarian Cancer Managed? A Study of Primary Care Physicians SO CANCER LA English DT Article DE primary care physicians; screening; symptoms; ovarian cancer; CA125; transvaginal ultrasound ID UNITED-STATES; DIAGNOSIS; WOMEN; POPULATION; INDEX; EARLIER; RISK AB BACKGROUND: A study was undertaken to identify the diagnostic approaches that primary care physicians and gynecologists undertake in women with symptoms associated with ovarian cancer. METHODS: A vignette-based survey was mailed to 3200 primary care physicians from the American Medical Association Physician Masterfile. The vignette described a 55-year-old woman with symptoms associated with ovarian cancer, although ovarian cancer was never mentioned. The authors evaluated patient, physician, and practice characteristics associated with a workup that could detect ovarian cancer. RESULTS: The survey response rate was 61.7%. After exclusions, 1532 physicians were included. Overall, 89.5% of physicians reported that they would recommend testing that can detect ovarian cancer ( 71.2% ultrasound; 25.4% pelvic computed tomography; 26.5% CA125). In adjusted analysis, the only patient factor associated with ovarian cancer testing was symptom type, genitourinary versus gastrointestinal ( risk ratio, 1.07; 95% confidence interval, 1.03-1.11). Physician and practice characteristics associated with recommending of ovarian cancer testing included specialty ( gynecologists > family physicians and internists); type of practice ( group > solo); clinical teaching ( yes > no); and within Census division, location of practice, with all Central ( East, West, North, and South) and Atlantic ( Middle and South) areas having a lower likelihood than New England. CONCLUSIONS: On the basis of a vignette in which a woman reported symptoms associated with ovarian cancer, the majority of primary care physicians and gynecologists would not recommend CA125, but would recommend imaging of the pelvis. Gynecologists, physicians involved with clinical teaching, and those in group practices were significantly more likely to recommend testing that could lead to an ovarian cancer diagnosis. Cancer 2011; 117: 4414-23. (C) 2011 American Cancer Society. C1 [Goff, Barbara A.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Matthews, Barbara; Andrilla, C. Holly A.; Lishner, Denise M.; Baldwin, Laura-Mae] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Miller, Jacqueline W.; Trivers, Katrina F.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Berry, Donna] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. RP Goff, BA (reprint author), Univ Washington, Sch Med, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. EM bgoff@uw.edu FU Centers for Disease Control and Prevention (CDC) through the University of Washington Health Promotion Research Centers [U48DP001911]; Centers for Disease Control and Prevention (CDC) through the Alliance for Reducing Cancer, Northwest; CDC [U48DP001911]; National Cancer Institute FX This project was funded by the Centers for Disease Control and Prevention (CDC) through the University of Washington Health Promotion Research Centers Cooperative Agreement U48DP001911, and through the Alliance for Reducing Cancer, Northwest, funded by both the CDC (grant U48DP001911, V. Taylor, principal investigator) and the National Cancer Institute. The findings and conclusions in this journal article are those of the authors and do not necessarily represent the official position of the CDC. NR 36 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2011 VL 117 IS 19 BP 4414 EP 4423 DI 10.1002/cncr.26035 PG 10 WC Oncology SC Oncology GA 824TN UT WOS:000295225200013 PM 21413001 ER PT J AU Ciernik, IF Niemierko, A Harmon, DC Kobayashi, W Chen, YL Yock, TI Ebb, DH Choy, E Raskin, KA Liebsch, N Hornicek, FJ DeLaney, TF AF Ciernik, I. Frank Niemierko, Andrzej Harmon, David C. Kobayashi, Wendy Chen, Yen-Lin Yock, Torunn I. Ebb, David H. Choy, Edwin Raskin, Kevin A. Liebsch, Norbert Hornicek, Francis J. DeLaney, Thomas F. TI Proton-Based Radiotherapy for Unresectable or Incompletely Resected Osteosarcoma SO CANCER LA English DT Article DE osteosarcoma; sarcoma; radiotherapy; proton therapy; particle therapy; combined modality ID CARBON-ION RADIOTHERAPY; LOCAL-CONTROL; THERAPY; EXPERIENCE; SARCOMA; CHEMOTHERAPY; IRRADIATION; RADIATION; CANCER; TUMORS AB BACKGROUND: A study was undertaken to assess clinical outcome and the role of proton therapy for local control of osteosarcoma (OSA). METHODS: All patients who received proton therapy or mixed photon-proton radiotherapy from 1983 to 2009 at the Massachusetts General Hospital were reviewed. Criteria for proton therapy were the need for high dose in the context of highly conformal radiotherapy of unresected or partially resected OSA, positive postoperative margins, postoperative imaging studies with macroscopic disease, or incomplete resection as defined by the surgeon. The primary endpoint was local control of the site treated; secondary endpoints were disease-free survival (DFS), overall survival (OS), long-term toxicity, and prognostic factors associated with clinical outcome. RESULTS: Fifty-five patients with a median age of 29 years (range, 2-76 years) were offered proton therapy. The mean dose was 68.4 gray (Gy; standard deviation, 5.4 Gy). Of the total dose, 58.2% (range, 11%-100%) was delivered with protons. Local control after 3 and 5 years was 82% and 72%, respectively. The distant failure rate was 26% after 3 and 5 years. The 5-year DFS was 65%, and the 5-year OS was 67%. The extent of surgical resection did not correlate with outcome. Risk factors for local failure were >= 2 grade disease (P < .0001) and total treatment length (P = .008). Grade 3 to 4 late toxicity was seen in 30.1 % of patients. One patient died from treatment-associated acute lymphocytic leukemia, and 1 from secondary carcinoma of the maxilla. CONCLUSIONS: Proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected OSA. Cancer 2011; 117: 4522-30. (C) 2011 American Cancer Society. C1 [DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Ciernik, I. Frank] Univ Zurich Hosp, Clin Res Ctr, CH-8091 Zurich, Switzerland. [Niemierko, Andrzej; Harmon, David C.; Chen, Yen-Lin; Yock, Torunn I.; Ebb, David H.; Choy, Edwin; Raskin, Kevin A.; Liebsch, Norbert; Hornicek, Francis J.; DeLaney, Thomas F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Harmon, David C.; Choy, Edwin] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Ebb, David H.] Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02114 USA. [Raskin, Kevin A.; Hornicek, Francis J.] Massachusetts Gen Hosp, Div Orthoped Oncol, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org OI Choy, Edwin/0000-0001-9896-8084 FU National Cancer Institute [PO1CA021239]; Zurich Cancer League, Switzerland FX Supported in part by grant PO1CA021239 from the National Cancer Institute and in part by the Zurich Cancer League, Switzerland. NR 26 TC 32 Z9 35 U1 3 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2011 VL 117 IS 19 BP 4522 EP 4530 DI 10.1002/cncr.26037 PG 9 WC Oncology SC Oncology GA 824TN UT WOS:000295225200025 PM 21448934 ER PT J AU Peterson, CL Kautz, SA Neptune, RR AF Peterson, Carrie L. Kautz, Steven A. Neptune, Richard R. TI Muscle work is increased in pre-swing during hemiparetic walking SO CLINICAL BIOMECHANICS LA English DT Article DE Post-stroke; Mechanical work; Simulation; Three-dimensional; Biomechanics ID MECHANICAL WORK; ENERGY-COST; LOWER-EXTREMITY; MOTOR CONTROL; STROKE; GAIT; SPEED; MODEL; DETERMINANTS; PROPULSION AB Background: Muscle mechanical work is likely affected by gait abnormalities in hemiparetic walking during the paretic pre-swing phase (i.e., double support phase preceding paretic toe-off). Previous experimental studies suggest that muscle work may be decreased in the paretic leg, but paretic work may have been underestimated since experimental approaches based on net joint moments do not account for co-contraction of antagonist muscles. Also, whether the non-paretic leg does more work compared to control subjects at matched speeds and how work generation may differ between hemiparetic subjects walking with different self-selected speeds remains unknown. Methods: Three-dimensional forward dynamics simulations of two representative hemiparetic subjects walking with different self-selected speeds (i.e.. limited community = 0.45 m/s and community walkers = 0.9 m/s) and a speed and age-matched control subject were generated to quantify musculotendon (fiber and in-series tendon) work during paretic pre-swing. Findings: Total paretic and non-paretic fiber work were increased in both the limited community and community hemiparetic walkers compared to the control. Increased fiber work in the limited community walker was primarily related to decreased fiber and tendon work by the paretic plantar flexors requiring compensatory work by other muscles. Increased fiber work in the community walker was primarily related to increased work by the hip abductors and adductors. Interpretation: The hemiparetic walkers would expend more metabolic energy during pre-swing if the hemiparetic and control subjects were to perform work with the same mechanical efficiency. These results may partly explain the increased metabolic cost of hemiparetic walkers compared to nondisabled walkers at matched speeds. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Peterson, Carrie L.; Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Div Phys Therapy, Charleston, SC 29425 USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Peterson, Carrie/C-6007-2016; OI Peterson, Carrie/0000-0002-7169-2089; Kautz, Steven/0000-0003-3151-8235 FU NIH [RO1 HD46820]; Rehabilitation Research & Development Service of the VA; NSF FX This work was funded by NIH grant RO1 HD46820, the Rehabilitation Research & Development Service of the VA and a NSF Graduate Research Fellowship. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD, VA or United States Government. NR 38 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD OCT PY 2011 VL 26 IS 8 BP 859 EP 866 DI 10.1016/j.clinbiomech.2011.04.010 PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 822TR UT WOS:000295073000011 PM 21605927 ER PT J AU Russell, M Breggia, A Mendes, N Klibanski, A Misra, M AF Russell, Melissa Breggia, Anne Mendes, Nara Klibanski, Anne Misra, Madhusmita TI Growth hormone is positively associated with surrogate markers of bone turnover during puberty SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ORAL GLUCOSE-LOAD; HEALTHY-CHILDREN; SERUM MARKERS; CARBOXYTERMINAL PROPEPTIDE; ADOLESCENT GIRLS; BOYS; METABOLISM; GHRELIN; AXIS; AGE AB Background Puberty is characterized by increases in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) and the pubertal growth spurt. Bone formation and resorption also increase, consistent with increased bone metabolism. Objective To determine the relationship between pubertal bone metabolism, GH and IGF-1. We hypothesized that bone turnover peaks at the time of greatest pubertal GH secretion. Design and Subjects Subjects included 86 girls and boys, 917 years-old (BMI 10th-90th percentiles). Because higher endogenous GH secretion is associated with a higher nadir following oral glucose, we used the GH nadir following a 2-h OGTT as indicative of GH status. Fasting serum IGF-1, aminoterminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX) were obtained. Subjects were grouped per expected timing of peak growth. Group 1: Tanner 1 girls and Tanner 1-2 boys (period preceding peak growth), Group 2: Tanner 2-3 girls and Tanner 3-4 boys (period of peak growth) and Group 3: Tanner 4-5 girls and Tanner 5 boys (period following peak growth). Results GH peaked at mid-puberty (Group 2) and IGF-1 in late puberty (Group 3). P1NP and CTX were highest in mid-puberty compared with early and late puberty (P = 0.0009 and 0.006 in girls and P = 0.005 and 0.04 in boys). GH, but not IGF-1, correlated with P1NP (r = 0.46 in both genders, P <= 0.008) and CTX (r = 0.37 and 0.38, P = 0.04 and 0.02 in girls and boys, respectively). Similarly, on regression modelling, GH (but not IGF-1) predicted both bone turnover markers in both genders. Conclusion GH is strongly associated with pubertal bone metabolism, independent of systemic IGF-1 in girls and boys. C1 [Russell, Melissa; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Russell, Melissa; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA. [Russell, Melissa; Misra, Madhusmita] Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. [Breggia, Anne] Maine Med Lab, Portland, ME USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015 FU Harvard Clinical and Translational Science Center, from the National Center for Research Resources [1 UL1 RR025758-03, M01-RR-01066] FX We thank the research nurses and bionutritionists at the Clinical Research Center at Massachusetts General Hospital and our subjects, without whom this study would not have been possible. The project described was supported by Grant Numbers 1 UL1 RR025758-03 and M01-RR-01066, Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 28 TC 7 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2011 VL 75 IS 4 BP 482 EP 488 DI 10.1111/j.1365-2265.2011.04088.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822LO UT WOS:000295048600012 PM 21535073 ER PT J AU Kawamori, D Akiyama, M Hu, J Hambro, B Kulkarni, RN AF Kawamori, D. Akiyama, M. Hu, J. Hambro, B. Kulkarni, R. N. TI Growth factor signalling in the regulation of alpha-cell fate SO DIABETES OBESITY & METABOLISM LA English DT Review DE cell growth; GLP-1; glucagon; insulin signalling; secretion ID GLUCAGON-LIKE PEPTIDE-1; TYPE-2 DIABETES-MELLITUS; SWITCH-OFF HYPOTHESIS; BETA-CELL; RECEPTOR EXPRESSION; ENDOCRINE PANCREAS; INSULIN-RECEPTOR; KNOCKOUT MICE; A-CELL; SECRETION AB Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic alpha-cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring beta-cells are emerging as central modulator(s) of alpha-cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the alpha-cell-specific insulin receptor knockout (alpha IRKO) mouse manifests hypersecretion of glucagon in the postprandial stage and exhibits defective secretion in fasting-induced hypoglycaemia, together mimicking the alpha-cell defects observed in type 2 diabetes. Interestingly, alpha IRK0 mice display a progressive increase in beta-cell mass and a concomitant decrease in alpha-cells. Lineage trace analyses reveal that the new beta-cells originate, in part, from the insulin receptor-deficient alpha-cells indicating a critical role for alpha-cell insulin signalling in determining beta-cell origin. Our studies also reveal that glucagon-like peptide-1 (GLP-1) treatment of alpha IRK mice suppresses glucagon secretion despite absence of functional insulin receptors precluding a role for insulin in GLP-1 action on alpha-cells in this model. These findings highlight the significance of insulin signalling in the regulation of alpha-cell biology. C1 [Kawamori, D.; Akiyama, M.; Hu, J.; Hambro, B.; Kulkarni, R. N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Kawamori, D.; Akiyama, M.; Hu, J.; Hambro, B.; Kulkarni, R. N.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kawamori, D.] Osaka Univ, Grad Sch Med, Med Educ Ctr, Osaka, Japan. [Kawamori, D.] Osaka Univ, Grad Sch Med, Dept Metab Med, Osaka, Japan. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, 1 Joslin Pl, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU Manpei Suzuki Diabetes Foundation, Japan; JDRF; American Diabetes Association; National Institutes of Health FX D. K. is the recipient of a Research Fellowship (Manpei Suzuki Diabetes Foundation, Japan) and a JDRF Postdoctoral Fellowship. The authors acknowledge support from the American Diabetes Association (R. N. K.) and the National Institutes of Health (R. N. K.). NR 61 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2011 VL 13 SU 1 BP 21 EP 30 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826HE UT WOS:000295344400005 PM 21824253 ER PT J AU Patel, SG Ahnen, DJ AF Patel, Swati G. Ahnen, Dennis J. TI Isn't It Time to Stop Talking About Colonoscopy Quality and Start Doing Something About It? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID COLORECTAL-CANCER; NEGATIVE COLONOSCOPY; ENDOSCOPIST; PREVENTION; RISK C1 [Patel, Swati G.; Ahnen, Dennis J.] Denver VA Med Ctr, Div Gastroenterol, Dept Med, Denver, CO 80220 USA. [Patel, Swati G.; Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver, CO USA. RP Ahnen, DJ (reprint author), Denver VA Med Ctr, Div Gastroenterol, Dept Med, Denver, CO 80220 USA. EM dennis.ahnen@ucdenver.edu NR 18 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2011 VL 56 IS 10 BP 2776 EP 2779 DI 10.1007/s10620-011-1860-2 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823YP UT WOS:000295164600019 PM 21863330 ER PT J AU Kuo, B Maneerattanaporn, M Lee, AA Baker, JR Wiener, SM Chey, WD Wilding, GE Hasler, WL AF Kuo, Braden Maneerattanaporn, Monthira Lee, Allen A. Baker, Jason R. Wiener, Stephen M. Chey, William D. Wilding, Gregory E. Hasler, William L. TI Generalized Transit Delay on Wireless Motility Capsule Testing in Patients with Clinical Suspicion of Gastroparesis, Small Intestinal Dysmotility, or Slow Transit Constipation SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Gastric emptying; Colonic transit; Nausea and vomiting; Constipation; Intestinal pseudoobstruction ID SEGMENTAL COLONIC TRANSIT; REGIONAL GUT TRANSIT; SMALL-BOWEL TRANSIT; IDIOPATHIC CONSTIPATION; ANTRODUODENAL MANOMETRY; SUBTOTAL COLECTOMY; SCINTIGRAPHY; DIAGNOSIS; SYMPTOMS; HEALTHY AB The prevalence of generalized transit delay and relation to symptoms in suspected gastroparesis, intestinal dysmotility, or slow transit constipation are unknown. The aims of this study were (1) to define prevalence of generalized dysmotility using wireless motility capsules (WMC), (2) to relate to symptoms in suspected regional delay, (3) to compare results of WMC testing to conventional transit studies to quantify new diagnoses, and (4) to assess the impact of results of WMC testing on clinical decisions. WMC transits were analyzed in 83 patients with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Isolated regional delays were observed in 32% (9% stomach, 5% small bowel, 18% colon). Transits were normal in 32% and showed generalized delays in 35%. Symptom profiles were similar with normal transit, isolated delayed gastric, small intestinal, and colonic transit, and generalized delay (P = NS). Compared to conventional tests, WMC showed discordance in 38% and provided new diagnoses in 53%. WMC testing influenced management in 67% (new medications 60%; modified nutritional regimens 14%; surgical referrals 6%) and eliminated needs for testing not already done including gastric scintigraphy (17%), small bowel barium transit (54%), and radioopaque colon marker tests (68%). WMC testing defines localized and generalized transit delays with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Symptoms do not predict the results of WMC testing. WMC findings provide new diagnoses in > 50%, may be discordant with conventional tests, and can influence management by changing treatments and eliminating needs for other tests. These findings suggest potential benefits of this method in suspected dysmotility syndromes and mandate prospective investigation to further define its clinical role. C1 [Maneerattanaporn, Monthira; Baker, Jason R.; Chey, William D.; Hasler, William L.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Kuo, Braden] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Lee, Allen A.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA. [Wiener, Stephen M.] Pentucket Med, Ctr Digest Care, Haverhill, MA USA. [Wilding, Gregory E.] SUNY Buffalo, Dept Stat, Buffalo, NY 14260 USA. RP Hasler, WL (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, 3912 Taubman Ctr,5362, Ann Arbor, MI 48109 USA. EM whasler@umich.edu FU SmartPill Corp. FX Dr. Kuo has received research funding and is on the Advisory Board for SmartPill Corp. Dr. Chey is on the Advisory Board for SmartPill Corp. Dr. Wilding has served as a consultant for SmartPill Corp. Dr. Hasler has served as a consultant and has received research funding from SmartPill Corp. NR 36 TC 23 Z9 25 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2011 VL 56 IS 10 BP 2928 EP 2938 DI 10.1007/s10620-011-1751-6 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823YP UT WOS:000295164600040 PM 21625964 ER PT J AU Solomon, M Bonafede, M Pan, K Wilson, K Beam, C Chakravarti, P Spiegel, B AF Solomon, M. Bonafede, M. Pan, K. Wilson, K. Beam, C. Chakravarti, P. Spiegel, B. TI Direct Medical Care Costs Among Pegylated Interferon Plus Ribavirin-Treated and Untreated Chronic Hepatitis C Patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis C; Pegylated interferon; Burden of illness; Administrative claims database analysis ID QUALITY-OF-LIFE; BURDEN; MANAGEMENT; INFECTION; ILLNESS; DISEASE AB Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG-RBV), is costly and has a significant adverse event profile. To quantify the direct economic burden of HCV infection and PEG-RBV treatment for HCV. Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG-RBV treatment on direct medical expenditure. The matched analysis included 20,002 patients. PEG-RBV-treated patients had higher total direct medical costs ($28,547 vs. $21,752; P < 0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P < 0.001), and outpatient physician visit costs ($894 vs. $787; P < 0.001), but lower inpatient costs ($3,942 vs. $9,543; P < 0.001) and emergency room costs ($366 vs. $505; P < 0.001). After multivariate adjustment, PEG-RBV use was associated with an additional $9,423 in total direct medical costs and an additional $12,244 in HCV-related total medical costs. Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients. C1 [Spiegel, B.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Chakravarti, P.] Novartis Pharmaceut, E Hanover, NJ USA. [Beam, C.] Human Genome Sci Inc, Rockville, MD USA. [Bonafede, M.; Pan, K.; Wilson, K.] Thomson Reuters Healthcare, Cambridge, MA USA. [Solomon, M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Spiegel, B (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Human Genome Sciences; Novartis Pharmaceuticals Corporation; Thomson Reuters FX This study was funded in full by Human Genome Sciences and Novartis Pharmaceuticals Corporation, which employs Cynthia Beam and Paula Chakravarti, respectively. Thomson Reuters was awarded a contract to conduct the study and is the employer of Machaon Bonafede, Katy Pan, and Kathleen Wilson. Brennan Spiegel and Matthew Solomon received funding from Human Genome Sciences to serve as consultants in support of the study. NR 24 TC 10 Z9 10 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 OCT PY 2011 VL 56 IS 10 BP 3024 EP 3031 DI 10.1007/s10620-011-1802-z PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823YP UT WOS:000295164600051 PM 21717127 ER PT J AU Michaelis, KA Knox, AJ Xu, M Kiseljak-Vassiliades, K Edwards, MG Geraci, M Kleinschmidt-DeMasters, BK Lillehei, KO Wierman, ME AF Michaelis, Katherine A. Knox, Aaron J. Xu, Mei Kiseljak-Vassiliades, Katja Edwards, Michael G. Geraci, Mark Kleinschmidt-DeMasters, B. K. Lillehei, Kevin O. Wierman, Margaret E. TI Identification of Growth Arrest and DNA-Damage-Inducible Gene beta (GADD45 beta) as a Novel Tumor Suppressor in Pituitary Gonadotrope Tumors SO ENDOCRINOLOGY LA English DT Article ID INHIBITORY GENE; P53 PROTEIN; ADENOMAS; EXPRESSION; PROLIFERATION; TUMORIGENESIS; GADD45-GAMMA; INVASION; CANCER; CARCINOMAS AB Gonadotrope and null cell pituitary tumors cause significant morbidity, often presenting with signs of hypogonadism together with visual disturbances due to mass effects. Surgery and radiation are the only therapeutic options to date. To identify dysregulated genes and pathways that may play a role in tumorigenesis and/or progression, molecular profiling was performed on 14 gonadotrope tumors, with nine normal human pituitaries obtained at autopsy serving as controls. Bioinformatic analysis identified putative downstream effectors of tumor protein 53 (p53) that were consistently repressed in gonadotrope pituitary tumors, including RPRM, P21, and PMAIP1, with concomitant inhibition of the upstream p53 regulator, PLAGL1(Zac1). Further analysis of the growth arrest and DNA damage-inducible (GADD45) family revealed no change in the p53 target, GADD45 alpha, but identified repression of GADD45 beta in pituitary tumors in addition to the previously reported inhibition of GADD45 gamma. Overexpression of GADD45 beta in L beta T2 mouse gonadotrope cells blocked tumor cell proliferation and increased rates of apoptosis in response to growth factor withdrawal. Stable gonadotrope cell transfectants expressing increased GADD45 beta showed decreased colony formation in soft agar, confirming its normal role as a tumor suppressor. Unlike previous studies of GADD45 gamma in pituitary tumors and alpha and beta in other tumors, bisulfite sequencing showed no evidence of hypermethylation of the GADD45 beta promoter in human pituitary tumor samples to explain the repression of its expression. Thus, GADD45 beta is a novel pituitary tumor suppressor whose reexpression blocks proliferation, survival, and tumorigenesis. Together these studies identify new targets and mechanisms to explore in pituitary tumor initiation and progression. (Endocrinology 152: 3603-3613, 2011) C1 [Michaelis, Katherine A.; Knox, Aaron J.; Xu, Mei; Kiseljak-Vassiliades, Katja; Edwards, Michael G.; Geraci, Mark; Wierman, Margaret E.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA. [Kleinschmidt-DeMasters, B. K.] Univ Colorado Denver, Dept Pathol, Aurora, CO 80045 USA. [Lillehei, Kevin O.] Univ Colorado Denver, Dept Neurosurg, Aurora, CO 80045 USA. [Xu, Mei; Kiseljak-Vassiliades, Katja; Wierman, Margaret E.] Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. RP Wierman, ME (reprint author), Univ Colorado, Sch Med, Vet Affairs Med Ctr Endo 111H, 1055 Clermont St, Denver, CO 80220 USA. EM Margaret.Wierman@ucdenver.edu FU Veterans Affairs Merit Review FX This work was supported by Veterans Affairs Merit Review to M.E.W. NR 42 TC 40 Z9 43 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2011 VL 152 IS 10 BP 3603 EP 3613 DI 10.1210/en.2011-0109 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822WN UT WOS:000295081200005 PM 21810943 ER PT J AU Cypess, AM Zhang, HB Schulz, TJ Huang, TL Espinoza, DO Kristiansen, K Unterman, TG Tseng, YH AF Cypess, Aaron M. Zhang, Hongbin Schulz, Tim J. Huang, Tian Lian Espinoza, Daniel O. Kristiansen, Karsten Unterman, Terry G. Tseng, Yu-Hua TI Insulin/IGF-I Regulation of Necdin and Brown Adipocyte Differentiation Via CREB- and FoxO1-Associated Pathways SO ENDOCRINOLOGY LA English DT Article ID PRADER-WILLI-SYNDROME; PROTEIN-KINASE B; GROWTH-FACTOR-I; ADIPOSE-TISSUE; GENE-EXPRESSION; RECOMBINANT ADENOVIRUSES; TRANSCRIPTIONAL CONTROL; RETINOBLASTOMA PROTEIN; GLUCOSE-TRANSPORT; CORE PROMOTER AB Brown adipose tissue plays an important role in obesity, insulin resistance, and diabetes. We have previously shown that the transition from brown preadipocytes to mature adipocytes is mediated in part by insulin receptor substrate (IRS)-1 and the cell cycle regulator protein necdin. In this study, we used pharmacological inhibitors and adenoviral dominant negative constructs to demonstrate that this transition involves IRS-1 activation of Ras and ERK1/2, resulting in phosphorylation of cAMP response element-binding protein (CREB) and suppression of necdin expression. This signaling did not include an elevation of intracellular calcium. A constitutively active form of CREB expressed in IRS-1 knockout cells decreased necdin promoter activity, necdin mRNA, and necdin protein levels, leading to a partial restoration of differentiation. By contrast, forkhead box protein (Fox)O1, which is regulated by the phosphoinositide 3 kinase-Akt pathway, increased necdin promoter activity. Based on reporter gene assays using truncations of the necdin promoter and chromatin immunoprecipitation studies, we demonstrated that CREB and FoxO1 are recruited to the necdin promoter, likely interacting with specific consensus sequences in the proximal region. Based on these results, we propose that insulin/IGF-I act through IRS-1 phosphorylation to stimulate differentiation of brown preadipocytes via two complementary pathways: 1) the Ras-ERK1/2 pathway to activate CREB and 2) the phosphoinositide 3 kinase-Akt pathway to deactivate FoxO1. These two pathways combine to decrease necdin levels and permit the clonal expansion and coordinated gene expression necessary to complete brown adipocyte differentiation. (Endocrinology 152: 3680-3689, 2011) C1 [Cypess, Aaron M.; Zhang, Hongbin; Schulz, Tim J.; Huang, Tian Lian; Espinoza, Daniel O.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. [Zhang, Hongbin; Kristiansen, Karsten] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. [Unterman, Terry G.] Univ Illinois, Coll Med, Dept Med & Physiol & Biophys, Chicago, IL 60612 USA. Jesse Brown Vet Affairs Med Ctr, Chicago, IL 60612 USA. RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM aaron.cypess@joslin.harvard.edu; yu-hua.tseng@joslin.harvard.edu RI Schulz, Tim/F-4842-2013; Kristiansen, Karsten/J-5148-2014 OI Schulz, Tim/0000-0002-8413-3972; Kristiansen, Karsten/0000-0002-6024-0917 FU Eli Lilly Foundation; National Institutes of Health [DK070722, DK077097, P30 DK46200, P30 DK040561, DK33201, DK046200, DK081604, DK087317, RR025757, DK41430]; Harvard Medical School; Beth Israel Deaconess Medical Center-Harvard/Massachusetts Institute of Technology Health Sciences and Technology; Department of Veterans Affairs; Pfizer, Inc.; Merck Co. FX This work was supported by the Eli Lilly Foundation and National Institutes of Health Grants DK070722, DK077097, P30 DK46200, and P30 DK040561 (to Y.-H.T.), DK33201, DK046200, DK081604, DK087317, and RR025757 (to A.M.C.), and DK41430(to T.G.U.), the Eleanor and Miles Shore 50th Anniversary Fellowship Program from Harvard Medical School (Y.-H.T.), the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center-Harvard/Massachusetts Institute of Technology Health Sciences and Technology, in collaboration with Pfizer, Inc. and Merck & Co. (A.M.C.), and the Department of Veterans Affairs Merit Review Program (T.G.U.). NR 57 TC 20 Z9 21 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2011 VL 152 IS 10 BP 3680 EP 3689 DI 10.1210/en.2011-1229 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822WN UT WOS:000295081200013 PM 21862615 ER PT J AU Chen, S Webber, MJ Vilardaga, JP Khatri, A Brown, D Ausiello, DA Lin, HY Bouley, R AF Chen, Sylvia Webber, Matthew J. Vilardaga, Jean-Pierre Khatri, Ashok Brown, Dennis Ausiello, Dennis A. Lin, Herbert Y. Bouley, Richard TI Visualizing Microtubule-Dependent Vasopressin Type 2 Receptor Trafficking Using a New High-Affinity Fluorescent Vasopressin Ligand SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; NEPHROGENIC DIABETES-INSIPIDUS; HUMAN OXYTOCIN RECEPTOR; RENAL EPITHELIAL-CELLS; COLLECTING DUCT CELLS; MEDIATED ENDOCYTOSIS; MOLECULAR-CLONING; EARLY ENDOSOMES; ANGIOTENSIN-II; WATER CHANNEL AB The vasopressin receptor type 2 (V2R) is the major target of vasopressin (VP) in renal epithelial cells. Although it is known that VP induces V2R internalization, accumulation in the perinuclear area, and degradation, the V2R intracellular trafficking pathways remain elusive. We visualized this process by developing a new fluorescent VP analog tagged by tetramethylrhodamine (TMR)-[Lys-( PEG)(2)-Suc-TMR8] VP or (VPTMR). This ligand is fully functional as revealed by its high binding affinity toward V2R [(K-d) = 157 +/- 52 nM] and ability to increase intracellular cAMP 32-fold. VPTMR induced V2R internalization in LLC-PK1 cells expressing either a FLAG-tagged receptor (FLAG-V2R) or V2R C-terminally tagged with green fluorescent protein (GFP) (V2R-GFP). After internalization, VPTMR and V2R-GFP colocalized in the perinuclear area, suggesting that the hormone and receptor traffic along the same pathway. VPTMR and V2R colocalized initially with the early endosome markers EEA1 and Rab5, and later with the recycling and late endosome markers Rab11 and Rab25. Epi-fluorescence microscopy of LLC-PK1 cells expressing GFP-tagged microtubules (MT) showed that VPTMR-containing vesicles travel along the MT network, and even remain attached to MT during the metaphase and anaphase of mitosis. Colchicine, a MT-depolymerizing agent, abolished perinuclear accumulation of VPTMR, and Western blot analysis showed that VP-induced V2R-GFP degradation is markedly retarded, but not abolished, by colchicine (10 mu M). We conclude that the new VPTMR ligand is suitable for dissecting V2R and VP internalization and trafficking in cells, and that V2R trafficking and down-regulation is an MT-dependent mechanism. (Endocrinology 152: 3893-3904, 2011) C1 [Bouley, Richard] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Webber, Matthew J.; Vilardaga, Jean-Pierre; Brown, Dennis; Ausiello, Dennis A.; Lin, Herbert Y.; Bouley, Richard] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. [Chen, Sylvia; Khatri, Ashok] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Univ Pittsburgh, Lab GPCR Biol, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15261 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Room 8218,185 Cambridge St, Boston, MA 02114 USA. EM Bouley.Richard@mgh.harvard.edu OI Webber, Matthew/0000-0003-1092-4410 FU National Institutes of Health [PO1DK38452, DK11794, R01DK087688]; National Kidney Foundation; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Center for the Study of Inflammatory Bowel Disease [DK43351] FX This work was supported by National Institutes of Health grants PO1DK38452 (to D.B. and D.A.A.), DK11794 (to S.C. and A.K.), and R01DK087688 (to J.-P.V.). R. Bouley received an investigator award from the National Kidney Foundation. The Microscopy Core facility of the Massachusetts General Hospital Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43351). NR 66 TC 5 Z9 5 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2011 VL 152 IS 10 BP 3893 EP 3904 DI 10.1210/en.2011-1049 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822WN UT WOS:000295081200034 PM 21828182 ER PT J AU Clarkson, AN Talbot, CL Wang, PY MacLaughlin, DT Donahoe, PK McLennan, IS AF Clarkson, Andrew N. Talbot, Caroline L. Wang, Pei-Yu MacLaughlin, David T. Donahoe, Patricia K. McLennan, Ian S. TI Mullerian inhibiting substance is anterogradely transported and does not attenuate avulsion-induced death of hypoglossal motor neurons SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Axonal transport; Avulsion; MISRII; ALK3 ID NERVE INJURY; IN-VITRO; NEUROTROPHIC FACTOR; AXONAL-TRANSPORT; MOTONEURONS; MECHANISMS; HORMONE; GROWTH; RECEPTOR; HUMANS AB Mullerian Inhibiting Substance (MIS. Anti-Miillerian hormone) is a gonadal hormone that contributes to the subtle sex-biases in the nervous system. Mature neurons of both sexes also produce MIS, suggesting that MIS may be a paracrine regulator of adult neural networks. We report here that murine hypoglossal motor neurons produce MIS and its receptors, MISRII and bone morphogenetic protein receptor 1A (BMPR1A, ALK3), but differentially transport them, with only MIS being detectable in axons. The production of MIS and its receptors were rapidly down regulated after axonal damage, which is a characteristic of genes involved in mature neuronal function. MIS is a survival factor for embryonic spinal motor neurons, but the rate of cell loss after hypoglossal nerve avulsion was normal in Mis(-/-) mice and was not attenuated by intraventricular administration of MIS. These observations suggest that MIS may be involved in anterograde rather than autocrine or retrograde regulation of neurons. (C) 2010 Elsevier Inc. All rights reserved. C1 [McLennan, Ian S.] Univ Otago, MIS Neurobiol Grp, Dept Anat & Struct Biol, Dunedin 9054, New Zealand. [Wang, Pei-Yu] Natl Chengchi Univ, Inst Neurosci, Taipei 116, Taiwan. [Wang, Pei-Yu] Natl Chengchi Univ, Res Ctr Mind Brain & Learning, Taipei 116, Taiwan. [MacLaughlin, David T.; Donahoe, Patricia K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA USA. RP McLennan, IS (reprint author), Univ Otago, MIS Neurobiol Grp, Dept Anat & Struct Biol, POB 913, Dunedin 9054, New Zealand. EM ian.mclennan@anatomy.otago.ac.nz OI WANG, PEI-YU/0000-0002-1792-8935 FU Otago Innovation Limited; NERF (Foundation for Science Research and Technology); Maurice and Phyllis Paykel Trust; Neurological Foundation of New Zealand FX This work was supported by Otago Innovation Limited (ISM), NERF (Foundation for Science Research and Technology) (ISM), Maurice and Phyllis Paykel Trust and AFJ Mickle Scholarship (CLT) and Postdoctoral Fellowship from the Neurological Foundation of New Zealand (ANC). The authors thank N. Batchelor for production and care of the mice. NR 28 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2011 VL 231 IS 2 BP 304 EP 308 DI 10.1016/j.expneurol.2010.12.019 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 823FV UT WOS:000295108800013 PM 21195071 ER PT J AU Todani, A Ciolino, JB Ament, JD Colby, KA Pineda, R Belin, MW Aquavella, JV Chodosh, J Dohlman, CH AF Todani, Amit Ciolino, Joseph B. Ament, Jared D. Colby, Kathryn A. Pineda, Roberto Belin, Michael W. Aquavella, James V. Chodosh, James Dohlman, Claes H. TI Titanium back plate for a PMMA keratoprosthesis: clinical outcomes SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE Boston Keratoprosthesis; Keratoprosthesis; KPro; BKPro; Retroprosthetic membrane; RPM; PMMA; Titanium AB To compare the rate of retroprosthetic membrane (RPM) formation in Boston Keratoprosthesis (BKPro) with polymethyl methacrylate (PMMA) versus titanium backplates. Retrospective comparative chart review. Multicenter study population: a total of 78 eyes with keratoprosthesis implants with either PMMA or titanium backplates were included in the study. To be included in the study, all subjects had to have completed a minimum of 6-month follow-up period. Incidence of RPM development at 6-month postoperative period was noted across the study population. PMMA and titanium backplates were then compared by their rate of association with subsequent RPM. Twenty-three out of 55 eyes (41.8%) with PMMA backplates and three out of 23 eyes (13.0%) with titanium backplates had developed an RPM at 6 months after implantation. The titanium backplates were associated with significantly less RPM formation than PMMA backplates (p = 0.014, Chi-square test). Titanium seems to be associated with less RPM formation than PMMA when used as a material for the BKPro back plate. C1 [Todani, Amit; Ciolino, Joseph B.; Ament, Jared D.; Colby, Kathryn A.; Pineda, Roberto; Chodosh, James; Dohlman, Claes H.] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. [Belin, Michael W.] Univ Arizona, Dept Ophthalmol & Vis Sci, Marana, AZ 85658 USA. [Aquavella, James V.] Univ Rochester, Inst Eye, Rochester, NY 14642 USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM claes_dohlman@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary FX Study was supported by the Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary. NR 12 TC 35 Z9 35 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD OCT PY 2011 VL 249 IS 10 BP 1515 EP 1518 DI 10.1007/s00417-011-1684-y PG 4 WC Ophthalmology SC Ophthalmology GA 823NL UT WOS:000295129000011 PM 21519940 ER PT J AU Karst, AM Levanon, K Duraisamy, S Liu, JF Hirsch, MS Hecht, JL Drapkin, R AF Karst, Alison M. Levanon, Keren Duraisamy, Sekhar Liu, Joyce F. Hirsch, Michelle S. Hecht, Jonathan L. Drapkin, Ronny TI Stathmin 1, a marker of PI3K pathway activation and regulator of microtubule dynamics, is expressed in early pelvic serous carcinomas SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Fallopian tube; Pelvic serous carcinoma; TP53; Stathmin 1; p27 ID FALLOPIAN-TUBE EPITHELIUM; CELL-CYCLE; OVARIAN-CANCER; GENE-EXPRESSION; CARCINOGENESIS; P27(KIP1); BENIGN; P53; PATHOGENESIS; POOR AB Background. Most high-grade pelvic serous carcinomas (HGPSCs) arise from fallopian tube epithelium (FTE). To date, few markers have been shown to characterize FTE transformation. Stathmin 1 (STMN1) is a candidate oncogene whose activity is influenced by p53, p27Kip1 (p27), and PI3K/Akt pathway activation. As a microtubule destabilizing protein, STMN1 regulates cytoskeletal dynamics, cell cycle progression, mitosis, and cell migration. This study examines the expression of STMN1 and its negative regulator p27 along the morphologic continuum from normal EVE to invasive carcinoma. Methods. STMN1 and p27 expression were examined by immunohistochemistry (IHC) in benign (n =12) and malignant (n = 13) fallopian tubes containing normal epithelium, morphologically benign putative precursor lesions ("p53 signatures"), potential transitional precursor lesions ("proliferative p53 signatures"), tubal intraepithelial carcinoma (TIC), and/or invasive serous carcinoma. STMN1 expression was further assessed in 131 late-stage HGPSCs diagnosed as primary ovarian and in 6 ovarian cancer cell lines by IHC and Western blot, respectively. Results. STMN1 expression was absent in benign FTE and infrequently detected in p53 signatures. However, it was weakly expressed in proliferative p53 signatures and robustly induced upon progression to TIC and invasive carcinoma, typically accompanied by decreased p27 levels. STMN1 was expressed in >80% of high-grade serous ovarian carcinomas and cell lines. Conclusions. STMN1 is a novel marker of early serous carcinoma that may play a role in FTE tumor initiation. Our data are consistent with a model by which STMN1 overexpression, resulting from loss of p27-mediated regulation, may potentiate aberrant cell proliferation, migration, and/or loss of polarity during early tumorigenesis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Karst, Alison M.; Levanon, Keren; Duraisamy, Sekhar; Liu, Joyce F.; Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hirsch, Michelle S.; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Hecht, Jonathan L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Drapkin, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, JFB-215D,450 Brookline Ave, Boston, MA 02215 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU Canadian Institutes of Health Research; Marsha Rivkin Foundation; AACR; Claire and Emmanuel G. Rosenblatt Foundation; ASCO; Prevent Cancer Foundation; Pallotta Investigator Fund; NIH [K12 CA08772307]; Novartis Pharmaceuticals; Ovarian Cancer Research Fund; Robert and Debra First Fund; Randi and Joel Cutler Ovarian Cancer Research Fund; The Mary Kay Foundation; SPORE [P50 CA105009] FX Special thanks to the faculty and staff of the BWH Department of Pathology for allocation of tissues. This work was supported by a Canadian Institutes of Health Research Fellowship (AMK), Marsha Rivkin Foundation Scientific Scholar Award (KL), AACR-George and Patricia Sehl Fellowship for Cancer Genetics Research (KL), American Physicians Fellowship for Medicine in Israel - Claire and Emmanuel G. Rosenblatt Foundation Grant (KL); ASCO Young Investigator Award and Prevent Cancer Foundation (JFL), Pallotta Investigator Fund (JFL), NIH - K12 CA08772307 (JFL) and P50 CA105009 (SPORE), Novartis Pharmaceuticals (RD), Ovarian Cancer Research Fund (RD): Robert and Debra First Fund (RD), Randi and Joel Cutler Ovarian Cancer Research Fund (RD), and The Mary Kay Foundation (RD). NR 42 TC 46 Z9 49 U1 1 U2 8 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 OCT PY 2011 VL 123 IS 1 BP 5 EP 12 DI 10.1016/j.ygyno.2011.05.021 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 824NL UT WOS:000295208500002 PM 21683992 ER PT J AU Saginaw, MA Gong, WS Haburcakova, C Merfeld, DM AF Saginaw, Michael A. Gong, Wangsong Haburcakova, Csilla Merfeld, Daniel M. TI Attenuation of Eye Movements Evoked by a Vestibular Implant at the Frequency of the Baseline Pulse Rate SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Biomedical engineering; prosthetics; translational medicine; vestibuloocular reflex (VOR) ID SEMICIRCULAR CANAL PROSTHESIS; ELECTRICAL-STIMULATION; VESTIBULOOCULAR REFLEX; SQUIRREL-MONKEY; RESPONSES AB We are developing a vestibular implant to electrically stimulate vestibular neurons in the semicircular canals in order to alleviate vertigo, which is a commonly occurring problem. However, since electrical stimulation causes synchronous (phase-locked) neural responses, such electrical stimulation might also cause inappropriate vestibuloocular eye movements, which might, in turn, cause visual blurring. We investigated the eye movements evoked in the guinea pig using electric stimulation with a constant rate of 250 pulses per second (pps), and measured 0.010 degrees peak-to-peak eye movements on an average at 250 Hz, with an average peak velocity amplitude of 8.1 degrees/s, which might cause visual blurring. However, after half an hour of stimulation, that component reduced to 1.6 degrees/s (0.0020 degrees peak-to-peak). The average time constant for this reduction was 5.0 min. After one week of constant stimulation, the 250-Hz response component was only slightly smaller, at 1.2 degrees/s (0.0015 degrees peak-to-peak). We conclude that although an electrical prosthesis with a resting rate of 250 pps may cause some visual blurring when first turned on, such blurring is very likely to attenuate and be imperceptible within several minutes. C1 [Saginaw, Michael A.] MathWorks Inc, Natick, MA 01760 USA. [Gong, Wangsong; Haburcakova, Csilla; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Gong, Wangsong; Haburcakova, Csilla; Merfeld, Daniel M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Saginaw, MA (reprint author), MathWorks Inc, Natick, MA 01760 USA. EM MSaginaw@alum.mit.edu; wangsong_gong@meei.harvard.edu; Csilla_Haburcakova@meei.harvard.edu; dan_merfeld@meei.harvard.edu FU U.S. Department of Health and Human Services under National Institutes of Health (NIH) [F31 DC006202]; NIH [R01 DC03066, R01 DC008167]; European Commission [225929] FX Manuscript received March 23, 2010; revised August 11, 2010; accepted October 25, 2010. Date of publication December 3, 2010; date of current version September 21, 2011. This work was supported in part by the U.S. Department of Health and Human Services under National Institutes of Health (NIH) Fellowship F31 DC006202, NIH Grant R01 DC03066, and Grant R01 DC008167, and in part by the European Commission under Project 225929. Asterisk indicates corresponding author. NR 33 TC 9 Z9 9 U1 0 U2 3 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 OCT PY 2011 VL 58 IS 10 BP 2732 EP 2739 DI 10.1109/TBME.2010.2095850 PN 1 PG 8 WC Engineering, Biomedical SC Engineering GA 823JR UT WOS:000295119000004 PM 21134812 ER PT J AU Lee, J Boas, DA Kim, SJ AF Lee, Jonghwan Boas, David A. Kim, Sung June TI Multiphysics Neuron Model for Cellular Volume Dynamics SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Biological cells; biological system modeling; cellular biophysics; physiology ID ACTION-POTENTIAL PROPAGATION; INTRINSIC OPTICAL SIGNALS; STRUCTURAL-CHANGES; SLICES; STATES AB Even though cellular volume dynamics has been linked to cell apoptosis and intrinsic optical signals, there is no quantitative model for describing neuronal volume dynamics on the millisecond time scale. This study introduces a multiphysics neuron model, where the cell volume is a time-varying variable and multiple physical principles are combined to build governing equations. Using this model, we analyzed neuronal volume responses during excitation, which elucidated the variety of optical signals observed experimentally across the literature. Several physiological conditions were examined to investigate their effect on the pattern of volume response. In addition, we analyzed volume responses on a longer time scale with repetitive stimulation to study the characteristics of slow cell swelling. This multiscale analysis of the multiphysics model will provide not only a novel quantitative elucidation of physiologically important issues related with cellular volume dynamics but also a chance for further studies, such as the interesting possibility of inferring the balance of ion flux from plateau volume changes. C1 [Lee, Jonghwan; Boas, David A.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Kim, Sung June] Seoul Natl Univ, Sch Elect Engn & Comp Sci, Seoul 151742, South Korea. [Kim, Sung June] Seoul Natl Univ, Interuniv Semicond Res Ctr, Seoul 151742, South Korea. RP Lee, J (reprint author), Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM jonghwan@nmr.mgh.harvard.edu; dboas@nmr.mgh.harvard.edu; kimsj@snu.ac.kr FU U.S. National Institutes of Health [R01NS057476]; Ministry of Education, Science and Technology of Korea [20110001662]; Korea Health 21 RD Project [A084359] FX Manuscript received March 31, 2011; revised May 20, 2011; accepted June 1, 2011. Date of publication June 9, 2011; date of current version September 21, 2011. This work was supported in part by the U.S. National Institutes of Health under Grant R01NS057476, by the Ministry of Education, Science and Technology of Korea under the Pioneer Project 20110001662, and by the Korea Health 21 R&D Project under Grant A084359. Asterisk indicates corresponding author. NR 17 TC 2 Z9 3 U1 1 U2 9 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 OCT PY 2011 VL 58 IS 10 BP 3000 EP 3003 DI 10.1109/TBME.2011.2159217 PN 2 PG 4 WC Engineering, Biomedical SC Engineering GA 823DN UT WOS:000295102600016 PM 21659016 ER PT J AU Etzel, JP Larson, MF Anawalt, BD Collins, J Dominitz, JA AF Etzel, Jason P. Larson, Meaghan F. Anawalt, Bradley D. Collins, Judith Dominitz, Jason A. TI Assessment and Management of Low Bone Density in Inflammatory Bowel Disease and Performance of Professional Society Guidelines SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; osteoporosis; guideline; hypogonadism ID POPULATION-BASED COHORT; MINERAL DENSITY; CROHNS-DISEASE; ULCERATIVE-COLITIS; FRACTURE RISK; FRAGILITY FRACTURE; CORTICOSTEROID USE; OLMSTED COUNTY; OSTEOPOROSIS; DIAGNOSIS AB Background: Inflammatory bowel disease (IBD) patients have increased prevalence of osteoporosis, leading to guideline recommendations for bone mineral density (BMD) testing. The study aim was to identify predictors of BMD testing and treatment and assess guideline effectiveness to identify IBD patients with osteoporosis. Methods: Records of all IBD patients at seven medical facilities were reviewed for clinical data and BMD testing from January 1996 through October 2006. Results: A total of 2035 patients had 317 bone density tests performed. Osteopenia was found in 48% of patients, osteoporosis in 26%. Among patients meeting guideline criteria for BMD testing and >= 1 year of follow-up, 23.3% underwent testing. The strongest predictors of testing were menopause (adjusted hazard ratio [AHR] 3.02) and receiving care at a tertiary center (AHR 2.56). Testing rates were low in patients with age >= 60 years, ulcerative colitis, and a history of inpatient IBD treatment. Osteoporotic patients received calcium/vitamin D and bisphosphonates in 59% and 75% of cases, respectively. Osteoporotic males had a 37% rate of hypogonadism. Guideline criteria do not distinguish patients with osteoporosis. The criteria had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 23%, 27%, and 81% for osteoporosis in the tested population, respectively. Conclusions: Osteoporosis is highly prevalent in the IBD population, but BMD testing and osteoporosis treatments are underutilized. Male hypogonadism is common in osteoporotic IBD patients. Guidelines do not identify IBD patients with osteoporosis. C1 [Etzel, Jason P.; Collins, Judith] Oregon Hlth & Sci Univ, Dept Med, Div Gastroenterol, Portland, OR 97201 USA. [Larson, Meaghan F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Anawalt, Bradley D.] Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), VAPSHCS S 111 GI, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Jason.Dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU VA Puget Sound Health Care System, Seattle, Washington FX There was no funding for this study. This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. The views and opinions of the authors expressed herein do not necessarily state or reflect those of the United States Government or the Department of Veterans Affairs. The authors have no conflicts of interest to disclose. NR 38 TC 24 Z9 26 U1 0 U2 3 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 OCT PY 2011 VL 17 IS 10 BP 2122 EP 2129 DI 10.1002/ibd.21601 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823RF UT WOS:000295140800017 PM 21910174 ER PT J AU Long, MD Crandall, WV Leibowitz, IH Duffy, L del Rosario, F Kim, SC Integlia, MJ Berman, J Grunow, J Colletti, RB Schoen, BT Patel, AS Baron, H Israel, E Russell, G Ali, S Herfarth, HH Martin, C Kappelman, MD AF Long, Millie D. Crandall, Wallace V. Leibowitz, Ian H. Duffy, Lynn del Rosario, Fernando Kim, Sandra C. Integlia, Mark J. Berman, James Grunow, John Colletti, Richard B. Schoen, Bess T. Patel, Ashish S. Baron, Howard Israel, Esther Russell, George Ali, Sabina Herfarth, Hans H. Martin, Christopher Kappelman, Michael D. CA ImproveCareNow Collaborative TI Prevalence and Epidemiology of Overweight and Obesity in Children with Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE obesity; overweight; children; IBD ID BODY-MASS INDEX; US CHILDREN; CHILDHOOD; ADIPONECTIN; ADOLESCENTS; LEPTIN AB Background: Obesity is a significant public health threat to children in the United States. The aims were to: 1) Determine the prevalence of obesity in a multicenter cohort of children with inflammatory bowel disease (IBD); 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. Methods: We used data from the ImproveCareNow Collaborative for pediatric IBD, a multicenter registry of children with IBD, collected between April 2007 and December 2009. Children ages 2-18 years were classified into body mass index (BMI) percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI >85%) and obese (BMI >95%) status. Results: The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohn's disease [CD] and 30.1% for ulcerative colitis [UC] and indeterminate colitis [IC]). African American race (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.10-2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19-2.34) were positively associated with overweight/obese status. Prior IBD-related surgery (OR 1.73, 95% CI 1.07-2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. Conclusions: Approximately one in five children with CD and one in three with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population. C1 [Long, Millie D.; Herfarth, Hans H.; Martin, Christopher] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC 27599 USA. [Long, Millie D.; Kim, Sandra C.; Herfarth, Hans H.; Martin, Christopher; Kappelman, Michael D.] Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA. [Crandall, Wallace V.] Nationwide Childrens Hosp, Div Gastroenterol, Columbus, OH USA. [Leibowitz, Ian H.; Duffy, Lynn] Inova Pediat Digest Dis Ctr, Fairfax, VA USA. [del Rosario, Fernando] Nemours Childrens Clin, Orlando, FL USA. [del Rosario, Fernando] Nemours Childrens Clin, Orlando, FL USA. [Kim, Sandra C.; Kappelman, Michael D.] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Pediat, Chapel Hill, NC 27599 USA. [Integlia, Mark J.; Berman, James] Barbara Bush Childrens Hosp, Portland, ME USA. Loyola Univ, Dept Pediat, Chicago, IL 60611 USA. [Grunow, John] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Colletti, Richard B.] Univ Vermont, Dept Pediat, Burlington, VT USA. [Schoen, Bess T.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Patel, Ashish S.] UT SW Med Ctr, Div Pediat Gastroenterol, Dallas, TX USA. [Patel, Ashish S.] Childrens Med Ctr, Dallas, TX 75235 USA. [Baron, Howard] Pediat Gastroenterol & Nutr Associates, Las Vegas, NV USA. [Israel, Esther; Russell, George] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Ali, Sabina] Childrens Hosp & Res Ctr, Div Gastroenterol, Oakland, CA USA. RP Long, MD (reprint author), Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, CB 7080, Chapel Hill, NC 27599 USA. EM millie_long@med.unc.edu RI Crandall, Wallace/E-2928-2011 FU NIH [T32 DK007634, 5-KL2-RR025746-02, P30 DK034987]; Crohn's and Colitis Foundation of America FX Supported, in part, by grants from the NIH (T32 DK007634, 5-KL2-RR025746- 02, P30 DK034987), and a junior faculty career development award from the Crohn's and Colitis Foundation of America. NR 16 TC 59 Z9 63 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 OCT PY 2011 VL 17 IS 10 BP 2162 EP 2168 DI 10.1002/ibd.21585 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823RF UT WOS:000295140800022 PM 21910178 ER PT J AU Baugh, CW Reisner, AT AF Baugh, Christopher William Reisner, Andrew Tomas TI QTc pseudoprolongation SO INTERNAL AND EMERGENCY MEDICINE LA English DT Letter ID HYPOKALEMIA C1 [Baugh, Christopher William] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Reisner, Andrew Tomas] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Baugh, CW (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House 2nd Floor, Boston, MA 02115 USA. EM cbaugh@partners.org NR 4 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1828-0447 J9 INTERN EMERG MED JI Intern. Emerg. Med. PD OCT PY 2011 VL 6 IS 5 BP 473 EP 475 DI 10.1007/s11739-010-0498-y PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 822YT UT WOS:000295087200017 PM 21161436 ER PT J AU Chua, SL Maurer, T Chren, MM AF Chua, Ser Ling Maurer, Toby Chren, Mary-Margaret TI Adaptation of a Runyankore version of Skindex-16 for oral administration in Mbarara, Uganda SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; SKIN DISEASES; CULTURAL-ADAPTATION; RELIABILITY; VALIDITY; ALPHA AB Background Health-related quality of life instruments are typically developed and validated for use in developed countries by patients who can read and write. Little is known about the feasibility of using adaptations of validated instruments in situations where literacy rates are low. Objective We aimed to translate, culturally adapt, and test an oral version of Skindex-16 in Runyankore, the predominant language in Mbarara, Uganda, for use in dermatologic research. Methods Skindex-16 was forward-and back-translated to Runyankore. The Runyankore version was administered orally to 47 dermatology patients and 47 random hospital visitors. Additional questions regarding duration, dyspigmentation, concealment status of the skin problem, and overall quality of life effect were also asked. Results Oral delivery was feasible; <= 10 minutes per subject. High Cronbach alpha values (0.86, 0.88, and 0.85 for symptoms, emotions, and functioning subscales, respectively) demonstrated internal consistency reliability. As hypothesized, subjects with reported skin problems, dyspigmentation, and difficulty in concealment had higher mean Skindex scores. A total of 72.4% of responses to the open-ended question were addressed in Skindex-16, indicating content validity. Conclusion The orally delivered Runyankore version of Skindex-16 is reliable, with construct and content validity, and feasible for use in dermatology research in Mbarara, Uganda. Orally administered quality of life instruments have potential for use in low literacy groups worldwide. C1 [Chua, Ser Ling; Maurer, Toby; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94110 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Chua, Ser Ling] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Dermatol, San Francisco, CA 94110 USA. RP Chua, SL (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Dermatol, 1001 Potrero Ave, San Francisco, CA 94110 USA. EM schua@doctors.org.uk FU British Association of Dermatologists; National Institute of Health [K24 AR052667] FX We would like to thank the investigators and staff of the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort, a collaboration between University of California, San Francisco, Harvard and Mbarara University of Science and Technology in Uganda, for making this study possible. SLC was supported by the Roger Harman African Travelling Fellowship from the British Association of Dermatologists. MMC was supported by a grant from the National Institute of Health (K24 AR052667). NR 17 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 2011 VL 50 IS 10 BP 1249 EP 1254 DI 10.1111/j.1365-4632.2011.04894.x PG 6 WC Dermatology SC Dermatology GA 824BY UT WOS:000295176300009 PM 21950290 ER PT J AU Dennehy, EB Marangell, LB Allen, MH Chessick, C Wisniewski, SR Thase, ME AF Dennehy, Ellen B. Marangell, Lauren B. Allen, Michael H. Chessick, Cheryl Wisniewski, Stephen R. Thase, Michael E. TI Suicide and suicide attempts in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar disorder; Suicide; Suicide attempt ID MOOD DISORDERS; RISK-FACTORS; COMPLETED SUICIDE; FOLLOW-UP; COMORBIDITY; MORTALITY; PREDICTORS; BEHAVIOR AB Background: The current report describes individuals with bipolar disorder who attempted or completed suicide while participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Methods: Baseline and course features of individuals with suicide events are described. Results: Among the 4360 people with bipolar disorder enrolled, 182 individuals made 270 prospectively observed suicidal acts, including 8 completed suicides. This represents a suicide rate of .014 per 100 person years in STEP-BD. which included frequent clinical visits, evidence based care, and standardized assessment at each patient contact. Approximately 1/3 of those who attempted suicide had more than one attempt during study participation. Those who completed suicide tended to do so early in study participation, and half of them did so on their first attempt. Limitations: While this study is limited to description of individuals and precipitants of completed suicides and attempts in STEP-BD, further analyses are planned to explore risk factors and potential interventions for prevention of suicidal acts in persons with bipolar disorder. Conclusions: Persons with bipolar disorder are at high risk for suicide. Overall rates of suicide events in STEP-BD were lower than expected, suggesting that the combination of frequent clinical visits (i.e.. access to care), standardized assessment, and evidence-based treatment were helpful in this population. (C) 2011 Elsevier B.V. All rights reserved. C1 [Dennehy, Ellen B.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. [Marangell, Lauren B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Marangell, Lauren B.] Baylor Coll Med, Mood Disorders Ctr, Menninger Dept Psychiat, Houston, TX 77030 USA. [Marangell, Lauren B.] US Dept Vet Affairs, Houston, TX USA. [Allen, Michael H.; Chessick, Cheryl] Univ Colorado, Denver Depress Ctr, Denver, CO 80202 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Dennehy, EB (reprint author), Purdue Univ, Dept Psychol Sci, 703 3rd St, W Lafayette, IN 47907 USA. EM edennehy@purdue.edu RI Allen, Michael/A-8776-2011; OI Wisniewski, Stephen/0000-0002-3877-9860 FU National Institute of Mental Health (NIMH), National Institutes of Health [N01MH80001] FX The STEP-BD study was conducted with federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under Contract N01MH80001. NIMH had no role in study design. An NIMH staff member was a member of the committee that reviewed all reported suicide events; decisions whether deaths were coded as a suicide were determined in some cases by a death certificate, and in some cases by the presence of a clear suicide note or other evidence in support of clear suicidal intention. Ruling of whether events were coded as a suicide attempts were based on patient self report, evidence of self-harm and/or evidence of clear intent for self-harm, and were based on consensus of the committee members. Other than that, NIMH staff had no involvement 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 31 TC 26 Z9 27 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2011 VL 133 IS 3 BP 423 EP 427 DI 10.1016/j.jad.2011.04.036 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 823HB UT WOS:000295112000008 PM 21601286 ER PT J AU Bobo, WV Chen, H Trivedi, MH Stewart, JW Nierenberg, AA Fava, M Kurian, BT Warden, D Morris, DW Luther, JF Husain, MM Cook, IA Lesser, IM Kornstein, SG Wisniewski, SR Rush, AJ Shelton, RC AF Bobo, William V. Chen, Helen Trivedi, Madhukar H. Stewart, Jonathan W. Nierenberg, Andrew A. Fava, Maurizio Kurian, Benji T. Warden, Diane Morris, David W. Luther, James F. Husain, Mustafa M. Cook, Ian A. Lesser, Ira M. Kornstein, Susan G. Wisniewski, Stephen R. Rush, A. John Shelton, Richard C. TI Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: A CO-MED report SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Escitalopram; Venlafaxine; Bupropion; Mirtazapine; Major depressive disorder; Melancholic features ID STAR-ASTERISK-D; MEASUREMENT-BASED CARE; PSYCHIATRIC-DISORDERS; CLINICAL-PRACTICE; TERM OUTCOMES; SELF-REPORT; VENLAFAXINE; SYMPTOMATOLOGY; OUTPATIENTS; MEDICATIONS AB Background: The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown. Methods: Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram + placebo (the MONO condition), bupropion-sustained release + escitalopram, or venlafaxine-extended release + mirtazapine (the COMB conditions) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial. Secondary data analyses were conducted to compare demographic and clinical characteristics, and contrast clinical responses according to drug treatment, in patients with MDD-MF (n = 124) and non-melancholic MDD (n =481). Results: While numerically lower, remission rates in MDD-MF did not differ significantly from those with non-melancholic MDD either at 12 (33.1% vs. 41.0%, aOR 1.16, p = 0.58) or 28 (39.5% vs. 46.8%, aOR = 1.02, p= 0.93) weeks of treatment. Remission rates did not differ significantly between combination and monotherapy groups in either MDD-MF or non-melancholic MDD patients at either time point. Similar conclusions were reached for response rates, premature study discontinuation, and self-rated depression symptom severity. Limitations: This is a secondary analysis of data from the CO-MED trial, which was not designed to address differential treatment response in melancholic and non-melancholic MDD. Conclusions: We found no evidence of differential remission or response rates to antidepressant combination or monotherapy between melancholic/non-melancholic MDD patients, or according to antidepressant treatment group, after 12 and 28 weeks. Melancholic features may not be a valid predictor of more favorable response to antidepressant combination therapy as initial treatment. (C) 2011 Elsevier B.V. All rights reserved. C1 [Bobo, William V.; Shelton, Richard C.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Chen, Helen] KK Womens & Childrens Hosp, Mental Wellness Serv, Singapore, Singapore. [Trivedi, Madhukar H.; Kurian, Benji T.; Warden, Diane; Morris, David W.; Husain, Mustafa M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Morris, David W.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Morris, David W.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Luther, James F.; Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Cook, Ian A.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Depress Res & Clin Program, Los Angeles, CA USA. [Lesser, Ira M.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Lesser, Ira M.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Kornstein, Susan G.] Virginia Commonwealth Univ, Inst Womens Hlth, Richmond, VA USA. [Rush, A. John] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. RP Bobo, WV (reprint author), 1500 21st Ave S,Suite 2200, Nashville, TN 37212 USA. EM william.v.bobo@vanderbilt.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health [N01MH90003]; Lundbeck; GlaxoSmithKline; Advanced Neuromodulation Systems; Best Practice Project Management; Bristol-Myers Squibb/Otsuka; Cyberonics; Forest Pharmaceuticals; Gerson Lehrman Group, GlaxoSmithKline; Jazz Pharmaceuticals; Magellan Health Services; Merck Company; Neuronetics; Novartis Pharmaceuticals; Ono Pharmaceuticals; Organon; Otsuka Pharmaceuticals; Pamlab, Pfizer; Transcept Pharmaceuticals; Urban Institute; Wyeth Ayerst; Cyberonics Inc.; Forest Laboratories; Otsuka; Guilford Publications; Healthcare Technology Systems; National Institutes of Mental Health; Stanley Medical Research Institute; Targacept, Inc.; Pfizer, Inc.; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Pharmaceutica; Pamlab; Repligen, Inc.; St. Jude Medical; Aspect Medical System/Covidian; Boehringer-Ingelheim FX This project was funded by the National Institute of Mental Health under Contract N01MH90003 to UT Southwestern Medical Center at Dallas (Pls A.J. Rush, M.H. Trivedi). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. The NIMH had no role in the drafting or review of the manuscript, nor in the collection or analysis of the data.; Helen Chen, MD, has received research support from Lundbeck, and speaker fees from A. John Rush, MD, has received consultant fees from Advanced Neuromodulation Systems, AstraZeneca, Best Practice Project Management, Bristol-Myers Squibb/Otsuka, Cyberonics, Forest Pharmaceuticals, Gerson Lehrman Group, GlaxoSmithKline, Jazz Pharmaceuticals, Magellan Health Services, Merck & Company, Neuronetics, Novartis Pharmaceuticals, Ono Pharmaceuticals, Organon, Otsuka Pharmaceuticals, Pamlab, Pfizer, Transcept Pharmaceuticals, Urban Institute and Wyeth Ayerst; speaking fees from Cyberonics Inc., Forest Laboratories, GlaxoSmithKline and Otsuka; royalties from Guilford Publications, and Healthcare Technology Systems; and research support from National Institutes of Mental Health and the Stanley Medical Research Institute. He has owned stock in Pfizer.; Benji T. Kurian, MD, has received research support from Targacept, Inc., and Pfizer, Inc.; Diane Warden, PhD, MBA, has previously owned stock in Pfizer, Inc., and Bristol-Myers Squibb.; Richard C. Shelton, MD, has served as a consultant for Eli Lilly and Company, Evotec AG, Forest Pharmaceuticals. Gideon Richter PLC, Janssen Pharmaceutica, Medronic, Inc., Otsuka Pharmaceuticals, Pamlab, Inc., Pfizer, Inc., Repligen, Inc., and Sierra Neuropharmaceuticals. He has received research support from Eli Lilly and Company, Forest Pharmaceuticals, Janssen Pharmaceutica, Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, Inc., Repligen, Inc., and St. Jude Medical.; Ira M. Lesser, MD, has received research support from the National Institute of Mental Health and Aspect Medical System/Covidian.; Susan G. Kornstein, MD, has served as a consultant for Bristol-Myers Squibb, Forest Laboratories, Eli Lilly and Company, Pfizer, Inc., Rexahn, Dey Pharma, PGxhealth, Takeda, and Wyeth. She has received research support from the National Institute of Mental Health, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Forest Laboratories, Wyeth, Novartis, Pfizer, Inc., Otsuka, and Takeda. She has received book royalties from Guildord Press. NR 50 TC 17 Z9 17 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2011 VL 133 IS 3 BP 467 EP 476 DI 10.1016/j.jad.2011.04.032 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 823HB UT WOS:000295112000014 PM 21601287 ER PT J AU Walcott, BP Cvetanovich, GL Barnard, ZR Nahed, BV Kahle, KT Curry, WT AF Walcott, Brian P. Cvetanovich, Gregory L. Barnard, Zachary R. Nahed, Brian V. Kahle, Kristopher T. Curry, William T. TI Surgical treatment and outcomes of metastatic breast cancer to the spine SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Breast neoplasms; Neoplasm metastasis; Spine; Surgery ID SINGLE-FRACTION RADIOSURGERY; CORD; COMPRESSION; SURGERY; DISEASE; TRIAL AB Metastatic vertebral body and spinal epidural lesions cause significant pain and neurological morbidity and negatively impact quality of life and survival. In instances of metastatic epidural spinal cord compression, treatment typically involves surgery and radiotherapy. The incidence of spinal metastases in breast cancer patients is high. In the light of recent improvements in survival among some patients with breast cancer, we reviewed the treatments and outcomes for patients with breast cancer who presented to our institution with metastatic epidural spinal cord compression. We identified all patients undergoing open surgery for the treatment of breast cancer metastases to the spine at our center from 1 January 2001 to 31 December 2009. We retrospectively reviewed records for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. The Death Master File from the United States Social Security Administration was queried to identify the date of death where the medical record was incomplete. Outcomes were assessed by overall survival as well as preoperative and postoperative ambulatory status, bladder function, and the American Spinal Injury Association impairment classification system (ASIA). A total of 15 female patients were identified as having surgical intervention directly related to breast cancer metastasis to the spine. Most lesions (12/15) were located in the anterior vertebral column (vertebral body and/or pedicle). Two patients required re-operation, one for epidural fluid collection and one for infection. Roughly half of the patients (8/15) had well-controlled systemic disease at the time of surgery. Five patients had non-contiguous metastatic lesions elsewhere in the spine. Median survival following surgery was 1025 days; control of systemic disease did not predict duration of postoperative survival. Seven patients had documented improvement in their ability to ambulate in the first 30 days following surgery. Bladder function was preserved in all. No patient deteriorated; and five patients had postoperative improvement of their ASIA impairment scale grade. We concluded that aggressive therapy, including surgery, is warranted for patients with symptomatic metastatic epidural spinal cord compression from breast cancer, including in the setting of advanced and progressive systemic disease. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Barnard, Zachary R.; Nahed, Brian V.; Kahle, Kristopher T.; Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Cvetanovich, Gregory L.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM Walcott.brian@mgh.harvard.edu NR 22 TC 5 Z9 6 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD OCT PY 2011 VL 18 IS 10 BP 1336 EP 1339 DI 10.1016/j.jocn.2011.02.020 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 824FX UT WOS:000295188900011 PM 21782449 ER PT J AU Leung, F Leung, J Siao-Salera, R Mann, S Ramirez, F Friedland, S Amato, A Radaelli, F Hsieh, YH AF Leung, F. Leung, J. Siao-Salera, R. Mann, S. Ramirez, F. Friedland, S. Amato, A. Radaelli, F. Hsieh, Y-H TI Removal of infused water predominantly during insertion (water exchange) is consistently associated with a greater reduction of pain score - review of data in RCTs of water method colonoscopy SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 [Leung, F.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Sacramento, CA USA. [Leung, F.] David Geffen Sch Med Ucla, Sacramento, CA USA. [Leung, J.; Mann, S.] Uc Davis Med Ctr, Vanchcs, Sacramento Vamc, Sacramento, CA USA. [Siao-Salera, R.] Vanchcs, Sacramento Vamc, Mather, CA USA. [Ramirez, F.] Mayo Clin, Scottsdale, AZ USA. [Friedland, S.] Stanford Univ, Palo Alto Vamc, Palo Alto, CA 94304 USA. [Amato, A.] Valduce Hosp, Como, Italy. [Radaelli, F.; Hsieh, Y-H] Buddhist Dalin Tzu Chi Gen Hosp, Chiayi, Taiwan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2011 VL 26 SU 5 SI SI BP 128 EP 129 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823CG UT WOS:000295099200346 ER PT J AU Lillemoe, KD AF Lillemoe, Keith D. TI What Are The Complex Operations and Why? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Complex surgical procedures; Surgical training ID SURGERY AB Introduction Surgeons are often judged by their ability to perform complex surgical procedures. Discussion Data show the number of these procedures as defined by the number of procedures performed during surgical training may be significantly more common than would be expected by their program directors. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lillemoe, KD (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM Klillemoe@partners.org NR 4 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2011 VL 15 IS 10 BP 1722 EP 1723 DI 10.1007/s11605-011-1569-8 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 824CF UT WOS:000295177600009 PM 21796464 ER PT J AU Ratai, EM Pilkenton, S He, J Fell, R Bombardier, JP Joo, CG Lentz, MR Kim, WK Burdo, TH Autissier, P Annamalai, L Curran, E O'Neil, SP Westmoreland, SV Williams, KC Masliah, E Gonzalez, RG AF Ratai, E. -M. Pilkenton, S. He, J. Fell, R. Bombardier, J. P. Joo, C. -G. Lentz, M. R. Kim, W. -K. Burdo, T. H. Autissier, P. Annamalai, L. Curran, E. O'Neil, S. P. Westmoreland, S. V. Williams, K. C. Masliah, E. Gonzalez, R. Gilberto TI CD8(+) lymphocyte depletion without SIV infection does not produce metabolic changes or pathological abnormalities in the rhesus macaque brain SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE accelerated SIV macaque model; Magnetic resonance spectroscopy; NeuroAIDS ID SIMIAN IMMUNODEFICIENCY VIRUS; CENTRAL-NERVOUS-SYSTEM; RESONANCE-SPECTROSCOPY REVEALS; IN-VIVO; MAGNETIC-RESONANCE; N-ACETYLASPARTATE; NEURONAL INJURY; PRIMATE MODEL; AIDS DEMENTIA; HIV DEMENTIA AB Background Simian immunodeficiency virus (SIV) infection and persistent CD8(+) lymphocyte depletion rapidly leads to encephalitis and neuronal injury. The objective of this study is to confirm that CD8 depletion alone does not induce brain lesions in the absence of SIV infection. Methods Four rhesus macaques were monitored by proton magnetic resonance spectroscopy (H-1-MRS) before and biweekly after anti-CD8 antibody treatment for 8 weeks and compared with four SIV-infected animals. Post-mortem immunohistochemistry was performed on these eight animals and compared with six uninfected, non-CD8-depleted controls. Results CD8-depleted animals showed stable metabolite levels and revealed no neuronal injury, astrogliosis or microglial activation in contrast to SIV-infected animals. Conclusions Alterations observed in MRS and lesions in this accelerated model of neuroAIDS result from unrestricted viral expansion in the setting of immunodeficiency rather than from CD8(+) lymphocyte depletion alone. C1 [Ratai, E. -M.; Pilkenton, S.; He, J.; Fell, R.; Bombardier, J. P.; Joo, C. -G.; Lentz, M. R.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA USA. [Ratai, E. -M.; Pilkenton, S.; He, J.; Joo, C. -G.; Lentz, M. R.; Kim, W. -K.; Annamalai, L.; Curran, E.; O'Neil, S. P.; Westmoreland, S. V.; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA USA. [Ratai, E. -M.; Pilkenton, S.; He, J.; Fell, R.; Bombardier, J. P.; Joo, C. -G.; Lentz, M. R.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Kim, W. -K.; Burdo, T. H.; Autissier, P.; Williams, K. C.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Burdo, T. H.; Autissier, P.; Williams, K. C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Annamalai, L.; Curran, E.; O'Neil, S. P.; Westmoreland, S. V.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Masliah, E.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org RI ANNAMALAI, LAKSHMANAN/F-4220-2011 FU NIH [R21NS059331, R01NS050041, R01NS040237, R01NS-37654, R01MH62962, HNRC MH59754, HNRC MH62512, NIH-NS051129, RR00168]; National Center for Research Resources [P41RR14075] FX Supported by NIH grants R21NS059331 (EMR), R01NS050041 (RGG), R01NS040237 (KW), R01NS-37654 (KW), R01MH62962 (EM), HNRC MH59754 (EM), HNRC MH62512 (EM), NIH-NS051129 (MRL), and RR00168 (NEPRC Base Grant). The Massachusetts General Hospital Athinoula A. Martinos Center for Biomedical Imaging is also supported by the National Center for Research Resources grant number P41RR14075. NR 37 TC 11 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 2011 VL 40 IS 5 BP 300 EP 309 DI 10.1111/j.1600-0684.2011.00475.x PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 823PR UT WOS:000295135600003 PM 21463330 ER PT J AU Fernandez, CV Li, N Mullen, EA Grundy, PE Perman, EJ Shamberger, RC Ehrlich, PF Dome, JS AF Fernandez, Conrad V. Li, Ning Mullen, Elizabeth A. Grundy, Paul E. Perman, Elizabeth J. Shamberger, Robert C. Ehrlich, Peter F. Dome, Jeffrey S. TI Barriers to the Enrollment of Children in the Children's Oncology Group Study of Very Low Risk Wilms Tumor: A Report from the Children's Oncology Group SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE attitudes; very low risk; Wilms ID CHEST COMPUTED-TOMOGRAPHY; CANCER-STUDY-GROUP; STAGE-I; DIAGNOSIS; SURGERY AB Very low risk Wilms tumor is defined by favorable histology, age below 2 years, tumor weight less than 550 g, and stage I. The Children's Oncology Group is currently studying a nephrectomy-only strategy for these patients but the accrual rate is slightly below expected. Twenty-five of 31 institutions responded with reasons by physicians and/or parents for electing not to participate. Parents were primarily concerned with the experimental nature of the study, whereas physicians were concerned about accurate staging, with some overlap. We point out the necessity of assessing these concerns in predicting feasibility of and accrual to a therapy reduction study. C1 [Fernandez, Conrad V.] Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, Halifax, NS B3K 6R8, Canada. [Grundy, Paul E.] Stollery Childrens Hosp, Dept Pediat, Edmonton, AB, Canada. [Li, Ning] Epidemiol & Biostat Coll Publ Hlth & Profess, Childrens Oncol Data Ctr, Dept Epidemiol & Biostat, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Mullen, Elizabeth A.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA USA. [Shamberger, Robert C.] Harvard Univ, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. [Perman, Elizabeth J.] Childrens Mem Med Ctr, Dept Pathol & Lab Med, Chicago, IL USA. [Ehrlich, Peter F.] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat Surg, Ann Arbor, MI 48109 USA. [Dome, Jeffrey S.] Childrens Natl Med Ctr, Dept Oncol, Washington, DC 20010 USA. RP Fernandez, CV (reprint author), Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM Conrad.fernandez@iwk.nshealth.ca FU National Cancer Institute, National Institutes of Health, Bethesda, MD [U10 CA98543]; NCCF [U10 CA98543-02]; USPHS; [CA-42326] FX Research is supported by the Chair's Grant U10 CA98543 of the Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD.; This study is supported by NCCF U10 CA98543-02 and USPHS; CA-42326. NR 14 TC 3 Z9 3 U1 0 U2 1 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 OCT PY 2011 VL 33 IS 7 BP 521 EP 523 DI 10.1097/MPH.0b013e31821b8dd5 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 823WM UT WOS:000295157900024 PM 21941145 ER PT J AU Jacobson, CC Kumar, S Kimball, AB AF Jacobson, Christine C. Kumar, Sandeep Kimball, Alexa B. TI Latitude and psoriasis prevalence SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jacobson, Christine C.] Sutter Hlth, Dept Dermatol, Greenbrae, CA USA. [Kumar, Sandeep] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, 50 Stanybrd St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 3 TC 20 Z9 20 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2011 VL 65 IS 4 BP 870 EP 873 DI 10.1016/j.jaad.2009.05.047 PG 4 WC Dermatology SC Dermatology GA 824GB UT WOS:000295189300025 PM 21920244 ER PT J AU Feldman, AS McDougal, WS AF Feldman, Adam S. McDougal, W. Scott TI Long-Term Outcome of Excisional Organ Sparing Surgery for Carcinoma of the Penis SO JOURNAL OF UROLOGY LA English DT Article DE penis; penile neoplasms; neoplasm recurrence, local; carcinoma, squamous cell; urogenital surgical procedures ID SQUAMOUS-CELL CARCINOMA; RECURRENCE; T1 AB Purpose: We present our experience with penile sparing surgery for localized carcinoma in situ and T1 penile squamous cell carcinoma. We report outcomes and recommendations for a penile sparing approach. Materials and Methods: A total of 60 patients underwent penile sparing surgery for penile squamous cell carcinoma since 1995. Four patients without recurrence had less than 6 months of followup and were excluded from study. Data included disease stage, cellular differentiation, tumor site, penile sparing surgery type and recurrence information. Results: Followup was adequate in 28 patients with carcinoma in situ and in 28 with T1 disease. The overall recurrence rate was 21.4% with equal recurrences of carcinoma in situ and T1 tumors (each 21.4%). Mean +/- SD time to recurrence was 4.28 +/- 2.81 years (range 0.5 to 11). More than 25% of recurrences developed after 5 years. Mean followup in censored patients was 5.47 +/- 3.88 years (maximum 16). There was no difference in time to recurrence after carcinoma in situ and T1 tumors (p = 0.738). T1 tumors on the glans carried a slightly higher risk of recurrence (p = 0.049). At 5 years 13.8% of patients at risk had late recurrence with a mean time to recurrence of 7.25 +/- 2.62 years. No patients with carcinoma in situ showed invasion or metastasis. Two patients with T1 disease presented with metastasis and 3 had late metastasis. Conclusions: Penile sparing surgery is a safe option for local control for appropriate carcinoma in situ and T1 squamous cell carcinoma of the penis. Carcinoma in situ recurrence may be re-treated with penile sparing surgery. T1 tumors that recur require more aggressive resection. Our data show significant late recurrences in patients and the need for long-term followup. C1 [McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM wmcdougal@partners.org RI yang, xu/G-1624-2011 NR 8 TC 23 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2011 VL 186 IS 4 BP 1303 EP 1307 DI 10.1016/j.juro.2011.05.084 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 827BE UT WOS:000295399500034 PM 21862071 ER PT J AU Spencer, RJ Young, RH Goodman, A AF Spencer, Ryan J. Young, Robert H. Goodman, Annekathryn TI The risk of squamous cell carcinoma in persistent vulvar ulcers SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Vulva; Ulcer; Squamous cell carcinoma ID PUNCH BIOPSY; DIAGNOSIS; LYMPHADENECTOMY AB Objective: The standard evaluation for vulvar ulcers includes an office biopsy. There are limited data regarding the false-negative rate of a punch biopsy in detecting squamous cell carcinoma of the vulva. This study reports on pathologic discrepancies between office biopsy and subsequent wide local excision for nonhealing vulvar ulcers. Methods: A retrospective review of the surgical records of 118 consecutive vulvar procedures was performed. Eleven women with persistent vulvar ulcers in the absence of a mass or pigmented lesion were identified. Patient demographics, physical examination, office evaluation, and surgical and pathology reports for these 11 women were reviewed. Results: A persistent vulvar ulcer was the presenting complaint in 11 (13.8%) of 80 women with squamous cell disease. Most women were postmenopausal, with a median age of 72 years. Nine of the 11 women had an office biopsy performed before consultation with a gynecologic oncologist. Five (55%) of these specimens had benign findings on office biopsy but revealed invasive squamous cell carcinoma after subsequent excision. Three of four women with prior diagnosis of lichen sclerosis had ulcers harboring invasive carcinoma. Conclusions: Vulvar ulceration may be the only presenting symptom in women with vulvar squamous cell carcinoma especially in postmenopausal women. Prompt office biopsy should remain part of the standard diagnostic evaluation; however, cancer should be suspected even with a negative biopsy result if ulcerations persist. More extensive tissue sampling in the operating room should be considered for these women. C1 [Spencer, Ryan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Yawkey Ctr, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Goodman, Annekathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Spencer, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Yawkey Ctr, 32 Fruit St,Suite 4F, Boston, MA 02114 USA. EM rjspencer@partners.org NR 27 TC 2 Z9 2 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 OCT PY 2011 VL 18 IS 10 BP 1067 EP 1071 DI 10.1097/gme.0b013e3182175a68 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 823XE UT WOS:000295160300008 PM 21670713 ER PT J AU Vaughan, S Coward, JI Bast, RC Berchuck, A Berek, JS Brenton, JD Coukos, G Crum, CC Drapkin, R Etemadmoghadam, D Friedlander, M Gabra, H Kaye, SB Lord, CJ Lengyel, E Levine, DA McNeish, IA Menon, U Mills, GB Nephew, KP Oza, AM Sood, AK Stronach, EA Walczak, H Bowtell, DD Balkwill, FR AF Vaughan, Sebastian Coward, Jermaine I. Bast, Robert C., Jr. Berchuck, Andy Berek, Jonathan S. Brenton, James D. Coukos, George Crum, Christopher C. Drapkin, Ronny Etemadmoghadam, Dariush Friedlander, Michael Gabra, Hani Kaye, Stan B. Lord, Chris J. Lengyel, Ernst Levine, Douglas A. McNeish, Iain A. Menon, Usha Mills, Gordon B. Nephew, Kenneth P. Oza, Amit M. Sood, Anil K. Stronach, Euan A. Walczak, Henning Bowtell, David D. Balkwill, Frances R. TI Rethinking ovarian cancer: recommendations for improving outcomes SO NATURE REVIEWS CANCER LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; CLEAR-CELL CARCINOMA; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; BRCA2 MUTATION CARRIERS; GRADE SEROUS CARCINOMA; REGULATORY T-CELLS; FALLOPIAN-TUBE; PANCREATIC-CANCER; ANTIBODY BLOCKADE; GENOMIC ANALYSIS AB There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article. C1 [Bowtell, David D.] Univ Melbourne, Canc Genom & Genet Program, Melbourne, Vic 8006, Australia. [Bowtell, David D.] Univ Melbourne, Australian Ovarian Canc Study, Peter MacCallum Canc Ctr, Dept Biochem, Melbourne, Vic 8006, Australia. [Vaughan, Sebastian; Gabra, Hani; Stronach, Euan A.] Ovarian Canc Act Res Ctr, London W12 0NN, England. [Coward, Jermaine I.] Royal Marsden Hosp, London SW3 6JJ, England. [Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Ovarian Canc Res Lab, Houston, TX 77030 USA. [Berchuck, Andy] Duke Univ, Med Ctr, Div Gynecol Oncol, Durham, NC 27710 USA. [Berek, Jonathan S.] Stanford Univ, Stanford Womens Canc Ctr, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Brenton, James D.] Canc Res UK, Li Ka Shing Ctr, Cambridge CB2 0RE, England. [Balkwill, Frances R.] Queen Mary Univ London, Ctr Canc & Inflammat, Barts & London Med Sch, London EC1M 6BQ, England. [Walczak, Henning] Univ London Imperial Coll Sci Technol & Med, Div Immunol & Inflammat, London SW7 2AZ, England. [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77230 USA. [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77230 USA. [Oza, Amit M.] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Nephew, Kenneth P.] Indiana Univ Sch Med, Bloomington, IN 47405 USA. [Menon, Usha] UCL, Elizabeth Garrett Inst Womens Hlth, London NW1 2BU, England. [McNeish, Iain A.] Queen Mary Univ London, Barts Canc Inst, London EC1M 6BQ, England. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lengyel, Ernst] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Lord, Chris J.] Inst Canc Res, Breakthrough Toby Robins Breast Canc Res Inst, London SW3 6JB, England. [Kaye, Stan B.] Royal Marsden Hosp, Inst Canc Res, Med Sect, Sutton SM2 5PT, Surrey, England. [Friedlander, Michael] Prince Wales Canc Ctr, Dept Med Oncol, Randwick, NSW 2031, Australia. [Etemadmoghadam, Dariush] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. [Drapkin, Ronny] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Coukos, George] Univ Penn, Ctr Res Womens Hlth, Philadelphia, PA 19104 USA. [Crum, Christopher C.] Brigham & Womens Hosp, Boston, MA 02445 USA. RP Bowtell, DD (reprint author), Univ Melbourne, Canc Genom & Genet Program, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia. EM d.bowtell@petermac.org RI Lord, Christopher/B-3295-2012; Coward, Jermaine/C-1779-2012; Bast, Robert/E-6585-2011; friedlander, michael/G-3490-2013; Lengyel, Ernst/D-9220-2014; Drapkin, Ronny/E-9944-2016; Coward, Jermaine/F-2903-2016; Bowtell, David/H-1007-2016; OI McNeish, Iain/0000-0002-9387-7586; Balkwill, Frances/0000-0002-5587-9759; Lord, Christopher/0000-0002-3226-0515; Bast, Robert/0000-0003-4621-8462; friedlander, michael/0000-0002-6488-0604; Lengyel, Ernst/0000-0001-8624-1507; Drapkin, Ronny/0000-0002-6912-6977; Coward, Jermaine/0000-0002-2309-9379; Bowtell, David/0000-0001-9089-7525; Brenton, James/0000-0002-5738-6683 FU Cancer Research UK; Medical Research Council [, G0501974, G0601891]; NCI NIH HHS [CA109298, CA85289, P30 CA016672, P50 CA083639, P50 CA098258, P50 CA105009, P50 CA83639, R01 CA085289, R01 CA111882, U01 CA151461, U01 CA152990, U54 CA151668]; NIGMS NIH HHS [RC2GM092599] NR 86 TC 399 Z9 409 U1 7 U2 71 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD OCT PY 2011 VL 11 IS 10 BP 719 EP 725 DI 10.1038/nrc3144 PG 7 WC Oncology SC Oncology GA 823VU UT WOS:000295155600011 PM 21941283 ER PT J AU Wang, LD Wagers, AJ AF Wang, Leo D. Wagers, Amy J. TI Dynamic niches in the origination and differentiation of haematopoietic stem cells SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID BONE-MARROW MICROENVIRONMENT; PROGENITOR CELLS; SELF-RENEWAL; IN-VIVO; AORTIC ENDOTHELIUM; STEM/PROGENITOR CELLS; OSTEOBLAST LINEAGE; DROSOPHILA OVARY; ENDOSTEAL NICHE; SKELETAL-MUSCLE AB Haematopoietic stem cells (HSCs) are multipotent, self-renewing progenitors that generate all mature blood cells. HSC function is tightly controlled to maintain haematopoietic homeostasis, and this regulation relies on specialized cells and factors that constitute the haematopoietic 'niche', or microenvironment. Recent discoveries, aided in part by technological advances in in vivo imaging, have engendered a new appreciation for the dynamic nature of the niche, identifying novel cellular and acellular niche components and uncovering fluctuations in the relative importance of these components over time. These new insights significantly improve our understanding of haematopoiesis and raise fundamental questions about what truly constitutes a stem cell niche. C1 [Wang, Leo D.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Wang, Leo D.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wang, Leo D.] Dana Farber Childrens Hosp, Ctr Canc, Boston, MA 02215 USA. [Wagers, Amy J.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Wang, LD (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA. EM Leo.Wang@childrens.harvard.edu; amy.wagers@joslin.harvard.edu FU US National Institutes of Health (NIH) [HL088582, HL100402, T32CA136432]; Keck Foundation FX We thank L. Silberstein and T. Reya for provision of unpublished data and C. Dall'Osso, A. Hartigan and T. Nageswara Rao for helpful comments on the manuscript. This work was funded, in part, by grants from the US National Institutes of Health (NIH) (HL088582 and HL100402 to A.J.W.) and the Keck Foundation. L.D.W. is supported by an NIH T32 Training Grant (T32CA136432). Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. NR 149 TC 126 Z9 129 U1 4 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD OCT PY 2011 VL 12 IS 10 BP 643 EP 655 DI 10.1038/nrm3184 PG 13 WC Cell Biology SC Cell Biology GA 823XD UT WOS:000295160200013 PM 21886187 ER PT J AU Mizukami, K Ishikawa, M Akatsu, H Abrahamson, EE Ikonomovic, MD Asada, T AF Mizukami, Katsuyoshi Ishikawa, Masanori Akatsu, Hiroyasu Abrahamson, Eric E. Ikonomovic, Milos D. Asada, Takashi TI An immunohistochemical study of the serotonin 1A receptor in the hippocampus of subjects with Alzheimer's disease SO NEUROPATHOLOGY LA English DT Article DE Alzheimer's disease; hippocampus; immunohistochemistry; neurofibrillary tangle; serotonin 1A receptor ID MILD COGNITIVE IMPAIRMENT; 5-HT1A RECEPTORS; RAT-BRAIN; DEMENTIA; NEURONS; BINDING; 5-HYDROXYTRYPTAMINE(1A); ACETYLCHOLINE; LOCALIZATION; GLUTAMATE AB Alzheimer's disease (AD) is associated with neuronal degeneration, synaptic loss and deficits in multiple neurotransmitter systems. Alterations in the serotonin 1A (5-HT1A) receptor can contribute to impaired cognitive function in AD, and both in vitro binding and Positron emission tomography (PET) imaging studies have demonstrated that 5-HT1A receptors in the hippocampus/medial temporal cortex are affected early in AD. This neuropathological study examined the localization and immunoreaction intensity of 5-HT1A receptor protein in AD hippocampus with the goal to determine whether neuronal receptor levels are influenced by the severity of NFT severity defined by Braaks' pathological staging and to provide immunohistochemical confirmation of the binding assays and PET imaging studies. Subjects included AD patients and non-AD controls (NC) stratified into three Braaks' stages (Braak 0-II, NC; Braak III/IV and V/VI, AD). In the Braak 0-II group, 5-HT1A-immunoreactivity (ir) was prominent in the neuropil of the CA1 and subiculum, moderate in the dentate gyrus molecular layer (DGml), and low in the CA3 and CA4. No changes in 5-HT1A-ir were observed in the hippocampus of AD subjects in the Braak III/IV group. Hippocampal 5-HT1A-ir intensity was markedly decreased in the CA1 region in 6/11 (54.5%) subjects in the Braak V/VI group. Across all three groups combined, there was a statistically significant association between reduced 5HT1A-ir and neuronal loss in the CA1, but not in the CA3. The present data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until the end-stage of NFT progression in AD. Thus, the utility of PET imaging using a 5-HT1A-specific radiolabeled probe as a marker of hippocampal neuronal loss may be limited to the CA1 field in advanced stage AD cases. C1 [Mizukami, Katsuyoshi; Ishikawa, Masanori; Asada, Takashi] Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 3058575, Japan. [Akatsu, Hiroyasu] Fukushimura Hosp, Choju Med Inst, Aichi, Japan. [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15260 USA. RP Mizukami, K (reprint author), Univ Tsukuba, Inst Clin Med, Dept Psychiat, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM mizukami@md.tsukuba.ac.jp FU NIH [NIA AG05133, AG14449]; Snee-Reinhardt Charitable Foundation; Japanese Ministry of Education, Culture, Sports, Science and Technology; ADRC at the University of Pittsburgh FX We are indebted to the support of the participants in the ADRC at the University of Pittsburgh. This study was supported by NIH grants NIA AG05133 (University of Pittsburgh ADRC), and AG14449 (MDI), The Snee-Reinhardt Charitable Foundation (MDI), and by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KM). Ms. Suganya Srinivasan, Ms. Natsuko Kato and Ms. Megumi Mitani provided expert technical assistance. NR 31 TC 6 Z9 6 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0919-6544 J9 NEUROPATHOLOGY JI Neuropathology PD OCT PY 2011 VL 31 IS 5 BP 503 EP 509 DI 10.1111/j.1440-1789.2010.01193.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 823SK UT WOS:000295145500006 PM 21269332 ER PT J AU Witsell, DL Rauch, SD Tucci, DL Telian, SA Roland, PS Nguyen-Huynh, AT Schulz, K AF Witsell, David L. Rauch, Steven D. Tucci, Debara L. Telian, Steven A. Roland, Peter S. Nguyen-Huynh, Anh T. Schulz, Kristine TI The Otology Data Collection Project: Report from the CHEER Network SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE practice-based research network; tinnitus; dizziness ID HANDICAP INVENTORY; DIZZINESS; TINNITUS; VERTIGO AB Objective. To describe and communicate data collected in the CHEER (Creating Healthcare Excellence through Education and Research) infrastructure proof-of-concept study to facilitate understanding of the potential capabilities of practice-based research networks and to present pilot data for development of future research initiatives. Study Design. Prospective observational study of CHEER infrastructure operational capacity using a convenience sample of all patients presenting to the practices with tinnitus, dizziness, or a combination of these symptoms. Setting. The CHEER network of community and academic practice sites. Subjects and Methods. The data collection exercise collected demographic, clinical, treatment, and health-related quality-of- life surveys on tinnitus, dizziness, and migraine disorders. Descriptive analysis of the data is presented. Results. Of the sites in the CHEER network, 73% (16/22) successfully enrolled subjects; a total of 1532 patients were enrolled in 8 months. Tinnitus alone, dizziness alone, and both occurred in 28%, 34%, and 29%, respectively. Patients complaining of tinnitus and dizziness had lower quality of life than those sufferers with 1 disorder. Migraine was associated with 27% of patients. The most frequent diagnoses for patients with tinnitus and dizziness were Meniere disease (34%), vertiginous migraine (18%), and benign paroxysmal positional vertigo (16%). Conclusion. Descriptive data on patients with common disorders can be rapidly collected within the framework of a practice-based research network. The data in this study provide valuable pilot information on the targeted disorders, providing a baseline for development of future epidemiological data and clinical trials. C1 [Witsell, David L.; Tucci, Debara L.; Schulz, Kristine] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Rauch, Steven D.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Telian, Steven A.] Univ Michigan, Dept Otolaryngol, Ann Arbor, MI 48109 USA. [Roland, Peter S.] Univ Texas SW, Dept Otolaryngol, Dallas, TX USA. [Nguyen-Huynh, Anh T.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. RP Witsell, DL (reprint author), Duke Univ, Med Ctr, Box 3805, Durham, NC 27710 USA. EM david.witsell@duke.edu OI Nguyen-Huynh, Anh/0000-0002-9628-580X; Roland, Peter/0000-0003-4152-7346 FU Otonomy, Inc; NIH-IDCD; National Institute on Deafness and Other Communication Disorders (NIDCD); [5R33DC008632-04]; [NIDCD R21/R33] FX Steven Rauch is a consultant, medical case reviews, for BestDoctors, Inc, and a recipient of research funding from Otonomy, Inc, and NIH-IDCD. Debara L. Tucci is a consultant for Otonomy, Inc. Peter Roland is on the advisory board of Cochlear Corporation, MedEl Corporation, and Entopic Therapeutics; a consultant for Foresight Biotherapeutics, Inc; and a consultant and speaker for Alcon Labs.; National Institute on Deafness and Other Communication Disorders (NIDCD).; Grant number 5R33DC008632-04; NIDCD R21/R33 Phased Infrastructure Grant for Patient-Oriented Research. NR 11 TC 9 Z9 9 U1 0 U2 4 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 OCT PY 2011 VL 145 IS 4 BP 572 EP 580 DI 10.1177/0194599811416063 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 824VR UT WOS:000295230800010 PM 21771950 ER PT J AU Borsook, D Rosenthal, P AF Borsook, David Rosenthal, Perry TI Chronic (neuropathic) corneal pain and blepharospasm: Five case reports SO PAIN LA English DT Article DE Blepharospasm; Cornea; Neuropathic pain; Confocal ID VIVO CONFOCAL MICROSCOPY; BENIGN ESSENTIAL BLEPHAROSPASM; LIDOCAINE PATCH 5-PERCENT; FOCAL DYSTONIA; BASAL-GANGLIA; BLINK REFLEX; DRY EYE; GLOBUS-PALLIDUS; DIAGNOSTIC-TOOL; SKIN BIOPSY AB Pain and focal dystonias have been associated with chronic pain conditions such as complex regional pain syndrome. Corneal pain, frequently known as "dry eye'', may be a neuropathic pain condition with abnormalities of the nerve plexus. Here we present 5 case histories of patients with defined corneal pain (with associated neuropathic features) and objective measures of changes in the nerve plexus and associated blepharospasm. A putative relationship between pain and blepharospasm suggests potential involvement of the basal ganglia in both these conditions. (C) 2011 Published by Elsevier B. V. on behalf of International Association for the Study of Pain. C1 [Rosenthal, Perry] Boston Fdn Sight, Needham, MA USA. [Borsook, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Borsook, David] Massachusetts Gen Hosp, McLean Hosp, Ctr Pain & Brain, Boston, MA 02114 USA. RP Rosenthal, P (reprint author), Boston Fdn Sight, 464 Hillside Ave, Needham Hts, MA 02494 USA. EM prosenthal@bostonsight.org NR 67 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2011 VL 152 IS 10 BP 2427 EP 2431 DI 10.1016/j.pain.2011.06.006 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 824PF UT WOS:000295213700034 PM 21752546 ER PT J AU Selim, AJ Rogers, W Qian, SX Brazier, J Kazis, LE AF Selim, Alfredo J. Rogers, William Qian, Shirley X. Brazier, John Kazis, Lewis E. TI A preference-based measure of health: the VR-6D derived from the veterans RAND 12-Item Health Survey SO QUALITY OF LIFE RESEARCH LA English DT Article DE Utility measures; SF-6D; Cost-effectiveness analysis; Health-related quality of life ID NONPARAMETRIC BAYESIAN METHOD; COST-EFFECTIVENESS ANALYSIS; UTILITY-FUNCTIONS; SF-6D; EQ-5D; STANDARD; QUALITY; SCORES; SF-36; SF-12 AB The Veterans RAND 12-Item Health Survey (VR-12) is currently the major endpoint used in the Medicare managed care outcomes measure in the Healthcare Effectiveness Data and Information Set (HEDIS(A (R))), referred to as the Health Outcomes Survey (HOS). The purpose of this study is to adapt the Brazier SF-6D utility measure to the VR-12 to generate a single utility index. We used the HOS cohorts 2 and 3 for SF-36 data and 9 for VR-12 data. We calculated SF-6D scores from the SF-36 using the algorithms developed by Brazier and colleagues. The values of the Brazier SF-6D were used to estimate utility scores from the VR-12 using a mapping approach based on a 2-stage mapping procedure, named as VR-6D. The VR-6D derived from the VR-12 has similar distributional properties as the SF-6D. The change in VR-6D showed significant variations across disease groups with different levels of morbidity and mortality. This study produced a utility measure for the VR-12 that is comparable to the SF-6D and responsive to change. The VR-6D can be used in evaluations of health care plans and cost-effectiveness analysis to compare the health gains that health care interventions can achieve. C1 [Selim, Alfredo J.; Qian, Shirley X.; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, CAPP, Boston, MA 02118 USA. [Selim, Alfredo J.; Rogers, William; Qian, Shirley X.; Kazis, Lewis E.] VA Med Ctr, Hlth Serv Res & Dev Field Program, CHQOER, Bedford, MA USA. [Selim, Alfredo J.] Boston VA Hlth Care Syst, Sect Gen Internal Med & Emergency Serv, West Roxbury, MA USA. [Selim, Alfredo J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rogers, William] Tufts Univ New England Med Ctr, Hlth Inst, Boston, MA 02111 USA. [Brazier, John] Univ Sheffield, Sch Hlth & Related Res ScHARR, Sheffield, S Yorkshire, England. RP Kazis, LE (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, CAPP, 715 Albany St,T3 W, Boston, MA 02118 USA. EM lek@bu.edu OI Kazis, Lewis/0000-0003-1800-5849; Brazier, John/0000-0001-8645-4780 FU Center for Medicare; National Committee for Quality Assurance (NCQA) [HHSM-500-2009-00051C]; Center for the Assessment of Pharmaceutical Practices (CAPP) Boston University School of Public Health, Boston MA; Center for Health Quality, Outcomes and Economic Research (CHQOER), Veterans Administration Medical Center, Bedford MA; Center for Medicaid Services FX The research in this article was supported in part by the Centers for Medicare and Medicaid Services and the National Committee for Quality Assurance (NCQA) under contract number HHSM-500-2009-00051C; the Center for the Assessment of Pharmaceutical Practices (CAPP) Boston University School of Public Health, Boston MA and the Center for Health Quality, Outcomes and Economic Research (CHQOER), Veterans Administration Medical Center, Bedford MA. NR 38 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD OCT PY 2011 VL 20 IS 8 BP 1337 EP 1347 DI 10.1007/s11136-011-9866-y PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 823PY UT WOS:000295136500018 PM 21336657 ER PT J AU Fonarow, GC Smith, EE Saver, JL Reeves, MJ Hernandez, AF Peterson, ED Sacco, RL Schwamm, LH AF Fonarow, Gregg C. Smith, Eric E. Saver, Jeffrey L. Reeves, Mathew J. Hernandez, Adrian F. Peterson, Eric D. Sacco, Ralph L. Schwamm, Lee H. TI Improving Door-to-Needle Times in Acute Ischemic Stroke The Design and Rationale for the American Heart Association/American Stroke Association's Target: Stroke Initiative SO STROKE LA English DT Article DE acute stroke; thrombolytics; quality of care; quality improvement ID TISSUE-PLASMINOGEN ACTIVATOR; RT-PA STROKE; QUALITY IMPROVEMENT; POOLED ANALYSIS; CARE; SYSTEMS; DELAYS; THROMBOLYSIS; MANAGEMENT; ALTEPLASE AB Background and Purpose-The benefits of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke are time-dependent, and guidelines recommend a door-to-needle time of <= 60 minutes. However, fewer than one third of acute ischemic stroke patients who receive tPA are treated within guideline-recommended door-to-needle times. This article describes the design and rationale of Target: Stroke, a national initiative organized by the American Heart Association/American Stroke Association in partnership with other organizations to assist hospitals in increasing the proportion of tPA-treated patients who achieve guideline-recommended door-to-needle times. Methods-The initial program goal is to achieve a door-to-needle time <60 minutes for at least 50% of acute ischemic stroke patients. Key best practice strategies previously associated with achieving faster door-to-needle times in acute ischemic stroke were identified. Results-The 10 key strategies chosen by Target: Stroke include emergency medical service prenotification, activating the stroke team with a single call, rapid acquisition and interpretation of brain imaging, use of specific protocols and tools, premixing tPA, a team-based approach, and rapid data feedback. The program includes many approaches intended to promote hospital participation, implement effective strategies, share best practices, foster collaboration, and achieve stated goals. A detailed program evaluation is also included. In the first year, Target: Stroke has enrolled over 1200 United States hospitals. Conclusions-Target: Stroke, a multidimensional initiative to improve the timeliness of tPA administration, aims to elevate clinical performance in the care of acute ischemic stroke, facilitate the more rapid integration of evidence into clinical practice, and improve outcomes. (Stroke. 2011;42:2983-2989.) C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA. EM gfonarow@mednet.ucla.edu RI Hernandez, Adrian F./A-7818-2016; OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU National Institutes of Health; Michigan Stroke Registry; AHA [0675060N]; Johnson Johnson; Lilly; Bristol-Myers Squibb; Sanofi-Aventis; Merck-Schering Plough partnership FX G.C.F. serves a member of the GWTG Steering Committee, receives research support from the National Institutes of Health (significant), served as a consultant to Pfizer (modest); and is an employee of the University of California, which holds a patent on retriever devices for stroke (significant). E. E. S. serves as a member of the GWTG Steering Subcommittee and has served on an advisory board for Genentech (modest). J.L.S. serves as a member of the GWTG Science Subcommittee, as a scientific consultant regarding trial design and conduct to CoAxia, Concentric Medical, Talacris, Ferrer, Photothera, Brainsgate, Sygnis, and Ev3; received lecture honoraria from Ferrer; is an employee of the University of California, which holds a patent on retriever devices for stroke. M.J.R. receives salary support from the Michigan Stroke Registry and serves as a member of several AHA GWTG Subcommittees. A. F. H. is a member of the Duke Clinical Research Institute, which serves as the AHA/ASA GWTG data coordinating center; is a recipient of an AHA Pharmaceutical Roundtable grant (0675060N) and has received a research grant from Johnson & Johnson; has received honorarium from AstraZeneca and Amgen. E. D. P. has received research grants from Lilly, Johnson & Johnson, and Bristol-Myers Squibb, Sanofi-Aventis, and Merck-Schering Plough partnership. Dr Peterson serves as Principle investigator of the Data Analytic Center for AHA/ASA's GWTG. R. L. S. is president of the AHA/ASA. L. H. S. serves as chair of the AHA/ASA's GWTG Steering Committee; serves as a consultant to the Research Triangle Institute and to the Massachusetts Department of Public Health, and serves on the Steering Committee for Lundbeck's DIAS4 clinical trial. NR 31 TC 115 Z9 120 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2011 VL 42 IS 10 BP 2983 EP U493 DI 10.1161/STROKEAHA.111.621342 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 824QM UT WOS:000295217100066 PM 21885841 ER PT J AU D'Addio, F Ueno, T Clarkson, M Zhu, B Freeman, GJ Sayegh, MH Ansari, JI Habicht, A AF D'Addio, F. Ueno, T. Clarkson, M. Zhu, B. Freeman, G. J. Sayegh, M. H. Ansari, J. I. Habicht, A. TI CD160IG FUSION PROTEIN TARGETS A NOVEL COSTIMULATORY PATHWAY AND PROLONGS ALLOGRAFT SURVIVAL SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [D'Addio, F.; Ueno, T.; Clarkson, M.; Sayegh, M. H.; Ansari, J. I.; Habicht, A.] Womens Hosp Med Ctr, Transplantat Res Ctr Brigham, Boston, MA USA. [D'Addio, F.; Ueno, T.; Clarkson, M.; Sayegh, M. H.; Ansari, J. I.; Habicht, A.] Childrens Hosp, Boston, MA 02115 USA. [Clarkson, M.] Cork Univ Hosp, Dept Renal Med, Cork, Ireland. [Zhu, B.; Freeman, G. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Habicht, A.] Univ Hosp Munich Grosshadern, Transplant Ctr Munich, Munich, Germany. RI D'Addio, Francesca/F-3417-2017 OI D'Addio, Francesca/0000-0002-0345-0694 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 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD OCT PY 2011 VL 24 SU 3 SI SI BP 25 EP 25 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 822YA UT WOS:000295085300076 ER PT J AU Drummond, IA AF Drummond, Iain A. TI Polycystins, focal adhesions and extracellular matrix interactions SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Polycystin; Focal adhesion; Mechanosensory; Extracellular matrix; Autosomal dominant; Polycystic kidney disease ID KIDNEY-SPECIFIC INACTIVATION; SMOOTH-MUSCLE-CELLS; SUBSTRATE RIGIDITY; EPITHELIAL-CELLS; GENE-EXPRESSION; CYST FORMATION; INTRACRANIAL ANEURYSMS; MECHANICAL STRETCH; DESEASIN MCP-01; PKD-DOMAIN AB Polycystic kidney disease is the most common heritable disease in humans. In addition to epithelial cysts in the kidney, liver and pancreas, patients with autosomal dominant polycystic kidney disease (ADPKD) also suffer from abdominal hernia, intracranial aneurysm, gastrointestinal cysts, and cardiac valvular defects, conditions often associated with altered extracellular matrix production or integrity. Despite more than a decade of work on the principal ADPKD genes, PKD1 and PKD2, questions remain about the basis of cystic disease and the role of extracellular matrix in ADPKD pathology. This review explores the links between polycystins, focal adhesions, and extracellular matrix gene expression. These relationships suggest roles for polycystins in cell-matrix mechanosensory signaling that control matrix production and morphogenesis. This article is part of a Special Issue entitled: Polycystic Kidney Disease. (C) 2011 Elsevier B.V. All rights reserved. C1 [Drummond, Iain A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. [Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, 149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIH [DK053093, DK054711]; PKD foundation FX I thank members of my laboratory for constructive insights into this work and apologize to others whose work was not cited due to constraints on space and time. I.A.D. is supported by grants DK053093 and DK054711 from the NIH and grants from the PKD foundation. NR 82 TC 21 Z9 21 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD OCT PY 2011 VL 1812 IS 10 SI SI BP 1322 EP 1326 DI 10.1016/j.bbadis.2011.03.003 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 822QE UT WOS:000295063900015 PM 21396443 ER PT J AU Schmidt, U Hess, D Bittner, E AF Schmidt, Ulrich Hess, Dean Bittner, Edward TI To decannulate or not to decannulate: A combination of readiness for the floor and floor readiness? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE decannulation; tracheostomy ID WARD MORTALITY; TRACHEOSTOMY; CARE; MANAGEMENT; ICU C1 [Schmidt, Ulrich; Hess, Dean; Bittner, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schmidt, U (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2011 VL 39 IS 10 BP 2360 EP 2361 DI 10.1097/CCM.0b013e318226618a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 821EU UT WOS:000294958500025 PM 21926492 ER PT J AU Branson, R Hess, DR AF Branson, Richard Hess, Dean R. TI Variability-the spice of life? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE automatic tube compensation; breathing pattern variability; mechanical ventilation; positive end-expiratory pressure; spontaneous breathing trial; T piece; weaning ID SPONTANEOUS BREATHING TRIAL; MECHANICAL VENTILATION; INTENSIVE-CARE; VARIATIONAL ACTIVITY; SUPPORT; EXTUBATION; DURATION C1 [Branson, Richard] Univ Cincinnati, Dept Surg, Div Trauma & Crit Care, Cincinnati, OH 45267 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Branson, R (reprint author), Univ Cincinnati, Dept Surg, Div Trauma & Crit Care, 231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 25 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2011 VL 39 IS 10 BP 2363 EP 2364 DI 10.1097/CCM.0b013e31822a5c6b PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 821EU UT WOS:000294958500027 PM 21926494 ER PT J AU Laudanski, K Dohlman, L AF Laudanski, Krzysztof Dohlman, Lena TI Intensive care in poor-resource settings: Solutions are in the hands at home SO CRITICAL CARE MEDICINE LA English DT Letter ID DEVELOPING-WORLD C1 [Laudanski, Krzysztof] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Laudanski, Krzysztof; Dohlman, Lena] Hlth Volunteers Overseas, Washington, DC USA. [Dohlman, Lena] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. RP Laudanski, K (reprint author), Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. OI Laudanski, Krzysztof /0000-0002-7373-0851 NR 6 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2011 VL 39 IS 10 BP 2385 EP 2385 DI 10.1097/CCM.0b013e31822570c7 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 821EU UT WOS:000294958500043 PM 21926511 ER PT J AU Zite, N Borrero, S AF Zite, Nikki Borrero, Sonya TI Female sterilisation in the United States SO EUROPEAN JOURNAL OF CONTRACEPTION AND REPRODUCTIVE HEALTH CARE LA English DT Review DE Tubal sterilisation; Hysteroscopic sterilisation; Contraception; Family planning; United States ID TUBAL-STERILIZATION; CONTRACEPTIVE STERILIZATION; HYSTEROSCOPIC STERILIZATION; PREGNANCY; RATES; WOMEN; RISK AB Female sterilisation is a safe and effective form of permanent birth control. In the United States (US), it is still the second most commonly used form of contraception overall and is the most frequently used method among married women and among women over 30 years of age. Although several European countries have noted a sharp decline in the number of women electing tubal sterilisation in recent years, such trends have not been as obvious in the US. While female sterilisation remains popular, there are considerable system-level barriers to getting the procedure for certain segments of the population as well as emerging concerns about appropriate utilisation of this contraceptive method in light of newer, reversible options and the knowledge that regret after permanent contraception is high. Given the complexity of this decision-making process, it is critical that providers ensure at the very least that women are aware of the potential disadvantages of tubal occlusion and are knowledgeable of other highly effective contraceptive methods that are available but vastly underutilised in the US, namely, vasectomy, intrauterine contraceptives, and implants. C1 [Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN 37920 USA. [Borrero, Sonya] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Zite, N (reprint author), Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, 1928 Alcoa Highway,Suite 118, Knoxville, TN 37920 USA. EM nzite@mc.utmck.edu FU National Center for Research Resources (NCRR) [05 KL2 RR024154-05]; National Institutes of Health (NIH) FX Dr Borrero is funded by grant #05 KL2 RR024154-05 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The content of this publication is solely the responsibility of the authors and it does not necessarily represent the official view of NCRR or NIH. NR 24 TC 7 Z9 7 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1362-5187 J9 EUR J CONTRACEP REPR JI Eur. J. Contracept. Reprod. Health Care PD OCT PY 2011 VL 16 IS 5 BP 336 EP 340 DI 10.3109/13625187.2011.604451 PG 5 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology GA 821WC UT WOS:000295004100003 PM 21848391 ER PT J AU Shelton, RC Goldman, RE Emmons, KM Sorensen, G Allen, JD AF Shelton, Rachel C. Goldman, Roberta E. Emmons, Karen M. Sorensen, Glorian Allen, Jennifer D. TI An Investigation Into the Social Context of Low-Income, Urban Black and Latina Women: Implications for Adherence to Recommended Health Behaviors SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE health disparities; preventive care; women's health ID BREAST-CANCER; PATIENT NAVIGATION; FOLLOW-UP; ETHNIC DISPARITIES; AFRICAN-AMERICAN; MEDICAL-RESEARCH; CARE; PROMOTION; RACE; INTERVENTIONS AB Understanding factors that promote or prevent adherence to recommended health behaviors is essential for developing effective health programs, particularly among lower income populations who carry a disproportionate burden of disease. We conducted in-depth qualitative interviews (n = 64) with low-income Black and Latina women who shared the experience of requiring diagnostic follow-up after having a screening mammography with abnormal findings. We found that in addition to holding negative and fatalistic cancer-related beliefs, the social context of these women was largely defined by multiple challenges and major life stressors, factors that may interfere with their ability to attain health. Factors commonly mentioned included competing health issues, economic hardship, demanding caretaking responsibilities and relationships, insurance-related challenges, distrust of health care providers, and inflexible work policies. Black women also reported discrimination and medical mistrust, whereas Latinas experienced difficulties associated with immigration and social isolation. These results suggest that effective health interventions not only address change among individuals but must also change health care systems and social policies in order to reduce health disparities. C1 [Shelton, Rachel C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Shelton, Rachel C.] Mt Sinai Sch Med, New York, NY USA. [Goldman, Roberta E.] Brown Univ, Warren Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Emmons, Karen M.; Sorensen, Glorian; Allen, Jennifer D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Shelton, RC (reprint author), 772 W 168th St,Room 548, New York, NY 10032 USA. EM rshelton@post.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [R25 CA057711-14, 5 R25-CA057711-14, 5R25-CA081137, R25 CA057711, R25 CA081137] NR 44 TC 28 Z9 28 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2011 VL 38 IS 5 BP 471 EP 481 DI 10.1177/1090198110382502 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 822EJ UT WOS:000295026400006 PM 21856885 ER PT J AU Ahn, AC Kaptchuk, TJ AF Ahn, Andrew C. Kaptchuk, Ted J. TI Spatial anisotropy analyses of subcutaneous tissue layer: potential insights into its biomechanical characteristics SO JOURNAL OF ANATOMY LA English DT Article DE autocorrelation; biomechanic; mechanical; spatial anisotropy; subcutaneous tissue; ultrasound ID FORCE TRANSMISSION; COLLAGEN; STRAIN; ALIGNMENT; SYSTEM; MUSCLE; SKIN AB As the intermediate layer between the muscle and skin, the subcutaneous tissue frequently experiences shear and lateral stresses whenever the body is in motion. However, quantifying such stresses in vivo is difficult. The lack of such measures is partly responsible for our poor understanding of the biomechanical behaviors of subcutaneous tissue. In this study, we employ both ultrasound imaging and a novel spatial anisotropy measure incorporating Moran's I spatial autocorrelation calculations - to investigate the structuromechanical features of subcutaneous tissues within the extremities of 16 healthy volunteers. This approach is based on the understanding that spatial anisotropy can be an effective surrogate for the summative, tensile forces experienced by biological tissue. We found that spatial anisotropy in the arm, thigh and calf was attributed to the echogenic bands spanning the width of the ultrasound images. In both univariable and multivariable analyses, the calf was significantly associated with greater anisotropy compared with the thigh and arm. Spatial anisotropy was inversely related to subcutaneous thickness, and was significantly increased with longitudinally oriented probe images compared with transversely orientated images. Maximum peaks in spatial anisotropy were frequently observed when the longitudinally oriented ultrasound probe was swept across the extremity, suggesting that longitudinal channels with greater tension exist in the subcutaneous layer. These results suggest that subcutaneous biomechanical tension is mediated by collagenous/echogenic bands, greater in the calf compared with the thigh and arm, increased in thinner individuals, and maximal along longitudinal trajectories parallel to the underlying muscle. Spatial anisotropy analysis of ultrasound images has yielded meaningful patterns and may be an effective means to understand the biomechanical strain patterns within the subcutaneous tissue of the extremities. C1 [Ahn, Andrew C.; Kaptchuk, Ted J.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ahn, Andrew C.; Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Ahn, AC (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St,Room 2328, Charlestown, MA 02129 USA. EM aahn1@partners.org FU National Center for Complementary Alternative Medicine (NCCAM) [K23-AT003238, P30AT005895, K24-AT004095]; Clinical Translational Science Award [UL1RR025758] FX This research was supported by grant numbers K23-AT003238, P30AT005895 and K24-AT004095 of the National Center for Complementary Alternative Medicine (NCCAM), and supported in part by a gift from The Bernard Osher Foundation. The project described was supported by Clinical Translational Science Award UL1RR025758 to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Complementary Alternative Medicine or the National Center for Research Resources or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 7 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-8782 J9 J ANAT JI J. Anat. PD OCT PY 2011 VL 219 IS 4 BP 515 EP 524 DI 10.1111/j.1469-7580.2011.01407.x PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA 822NO UT WOS:000295055400008 PM 21722103 ER PT J AU Dutz, J Werth, VP AF Dutz, Jan Werth, Victoria P. TI Cigarette Smoking and Response to Antimalarials in Cutaneous Lupus Erythematosus Patients: Evolution of a Dogma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID BLOOD HYDROXYCHLOROQUINE; RHEUMATOID-ARTHRITIS; SEVERITY INDEX; DISEASE AREA; INSTRUMENT; THERAPY; LESIONS; MARKER; DRUGS; CLASI AB Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patients smokers and nonsmokers who have milder cutaneous lupus. Agreement on a single, validated disease severity measure for CLE would permit comparisons among studies and thereby foster progress in the field. C1 [Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Dutz, Jan] Univ British Columbia, Dept Dermatol & Skin Sci, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24 AR002207, K24 AR002207-09, K24-AR 18 02207] NR 24 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2011 VL 131 IS 10 BP 1968 EP 1970 DI 10.1038/jid.2011.237 PG 3 WC Dermatology SC Dermatology GA 822RV UT WOS:000295068200002 PM 21918570 ER PT J AU Kao, WH Riker, AI Kushwaha, DS Ng, K Enkemann, SA Jove, R Buettner, R Zinn, PO Sanchez, NP Villa, JL D'Andrea, AD Sanchez, JL Kennedy, RD Chen, CC Matta, JL AF Kao, Wynn H. Riker, Adam I. Kushwaha, Deepa S. Ng, Kimberly Enkemann, Steven A. Jove, Richard Buettner, Ralf Zinn, Pascal O. Sanchez, Nestor P. Villa, Jaime L. D'Andrea, Alan D. Sanchez, Jorge L. Kennedy, Richard D. Chen, Clark C. Matta, Jaime L. TI Upregulation of Fanconi Anemia DNA Repair Genes in Melanoma Compared with Non-Melanoma Skin Cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID PATHWAY; INTERFERON; RESISTANCE; ACTIVATION; EXPRESSION; PROTEIN C1 [Kao, Wynn H.; Sanchez, Nestor P.; Sanchez, Jorge L.] Univ Puerto Rico, Sch Med, Dept Dermatol, San Juan, PR 00936 USA. [Kao, Wynn H.] George Washington Univ, Med Ctr, Dept Dermatol, Washington, DC 20037 USA. [Riker, Adam I.] Ochsner Med Ctr, Ochsner Canc Inst, New Orleans, LA USA. [Kushwaha, Deepa S.; Ng, Kimberly; Zinn, Pascal O.; D'Andrea, Alan D.; Kennedy, Richard D.; Chen, Clark C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Enkemann, Steven A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Jove, Richard; Buettner, Ralf] City Hope Comprehens Canc Ctr, Beckman Res Inst, Duarte, CA USA. [Villa, Jaime L.; Matta, Jaime L.] Ponce Sch Med, Dept Pharmacol & Toxicol, Ponce, PR USA. RP Kao, WH (reprint author), Univ Puerto Rico, Sch Med, Dept Dermatol, San Juan, PR 00936 USA. EM wynn_kao@yahoo.com RI Kennedy, Richard/J-3489-2012; Chen, Clark/C-8714-2013 OI Kennedy, Richard/0000-0003-4737-6163; Chen, Clark/0000-0001-6258-9277 FU NCI NIH HHS [P30 CA076292]; NCRR NIH HHS [G12RR003050, G12 RR003050, 2-G12-RR03050-20]; NIDDK NIH HHS [R01 DK043889-19, R01 DK043889] NR 15 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2011 VL 131 IS 10 BP 2139 EP 2142 PG 4 WC Dermatology SC Dermatology GA 822RV UT WOS:000295068200027 PM 21697891 ER PT J AU Travison, TG Basaria, S Storer, TW Jette, AM Miciek, R Farwell, WR Choong, K Lakshman, K Mazer, NA Coviello, AD Knapp, PE Ulloor, J Zhang, AQ Brooks, B Nguyen, AH Eder, R LeBrasseur, N Elmi, A Appleman, E Hede-Brierley, L Bhasin, G Bhatia, A Lazzari, A Davis, S Ni, PS Collins, L Bhasin, S AF Travison, Thomas G. Basaria, Shehzad Storer, Thomas W. Jette, Alan M. Miciek, Renee Farwell, Wildon R. Choong, Karen Lakshman, Kishore Mazer, Norman A. Coviello, Andrea D. Knapp, Philip E. Ulloor, Jagadish Zhang, Anqi Brooks, Brad Nguyen, Ahn-Hoa Eder, Richard LeBrasseur, Nathan Elmi, Ayan Appleman, Erica Hede-Brierley, Leife Bhasin, Geeta Bhatia, Ashmeet Lazzari, Antonio Davis, Samuel Ni, Pengsheng Collins, Lauren Bhasin, Shalender TI Clinical Meaningfulness of the Changes in Muscle Performance and Physical Function Associated With Testosterone Administration in Older Men With Mobility Limitation SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Testosterone; Minimally important difference; Mobility limitation; Older men; Function promoting therapies ID RANDOMIZED CONTROLLED-TRIAL; BODY-COMPOSITION; SKELETAL-MUSCLE; ELDERLY-MEN; DOUBLE-BLIND; STRENGTH; DISABILITY; WOMEN; MASS; LIFE AB Context. Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change. Methods. Men aged 65 years and older, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Primary outcome was leg-press strength. Secondary outcomes included chest-press strength, stair-climb, 40-m walk, muscle mass, physical activity, self-reported function, and fatigue. Proportions of participants exceeding minimally important difference in study arms were compared. Results. Of 209 randomized participants, 165 had follow-up efficacy measures. Mean (SD) age was 74 (5.4) years and short physical performance battery score 7.7 (1.4). Testosterone arm exhibited greater improvements in leg-press strength, chest-press strength and power, and loaded stair-climb than placebo. Compared with placebo, significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths (43% vs 18%, p = .01) and stair-climbing power (28% vs 10%, p = .03) more than minimally important difference. Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass. Physical activity, walking speed, self-reported function, and fatigue did not change. Conclusions. Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power. Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population. C1 [Travison, Thomas G.; Basaria, Shehzad; Storer, Thomas W.; Miciek, Renee; Choong, Karen; Lakshman, Kishore; Mazer, Norman A.; Coviello, Andrea D.; Knapp, Philip E.; Ulloor, Jagadish; Zhang, Anqi; Brooks, Brad; Nguyen, Ahn-Hoa; Eder, Richard; LeBrasseur, Nathan; Elmi, Ayan; Appleman, Erica; Hede-Brierley, Leife; Bhasin, Geeta; Bhatia, Ashmeet; Collins, Lauren; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Dept Med, Boston, MA 02118 USA. [Travison, Thomas G.; Basaria, Shehzad; Storer, Thomas W.; Miciek, Renee; Choong, Karen; Lakshman, Kishore; Mazer, Norman A.; Coviello, Andrea D.; Knapp, Philip E.; Ulloor, Jagadish; Zhang, Anqi; Brooks, Brad; Nguyen, Ahn-Hoa; Eder, Richard; LeBrasseur, Nathan; Elmi, Ayan; Appleman, Erica; Hede-Brierley, Leife; Bhasin, Geeta; Bhatia, Ashmeet; Collins, Lauren; Bhasin, Shalender] Boston Med Ctr, Boston, MA 02118 USA. [Travison, Thomas G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Jette, Alan M.; Ni, Pengsheng] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA. [Farwell, Wildon R.; Lazzari, Antonio; Davis, Samuel] VA Boston Healthcare Syst, Dept Med, Jamaica Plain, MA USA. [Farwell, Wildon R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Aging, Boston, MA 02115 USA. RP Bhasin, S (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Dept Med, 670 Albany St, Boston, MA 02118 USA. EM bhasin@bu.edu OI Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185; LeBrasseur, Nathan/0000-0002-2002-0418 FU National Institutes on Aging [1UO1AG14369]; Boston Claude D. Pepper Older Americans Independence Center [5P30AG031679]; BU Clinical and Translational Science Institute [1UL1RR025771]; Merck and Co. FX This study was supported primarily by a grant from the National Institutes on Aging administered under a cooperative agreement (1UO1AG14369). Additional support was provided by Boston Claude D. Pepper Older Americans Independence Center grant (5P30AG031679) and a BU Clinical and Translational Science Institute grant (1UL1RR025771). Testosterone and placebo gel for the study were provided by Auxilium Pharmaceuticals, Inc., Norristown, PA. The MID Substudy was supported in part by a research grant from Merck and Co. to Boston University. A part of the work was supported by the resources and facilities of the VA Boston Healthcare System. NR 39 TC 59 Z9 62 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2011 VL 66 IS 10 BP 1090 EP 1099 DI 10.1093/gerona/glr100 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 821IW UT WOS:000294969400007 PM 21697501 ER PT J AU Cizginer, S Turner, B Bilge, AR Karaca, C Pitman, MB Brugge, WR AF Cizginer, Sevdenur Turner, Brian Bilge, A. Reyyan Karaca, Cetin Pitman, Martha B. Brugge, William R. TI Cyst Fluid Carcinoembryonic Antigen Is an Accurate Diagnostic Marker of Pancreatic Mucinous Cysts SO PANCREAS LA English DT Article DE carcinoembryonic antigen; diagnostic marker; pancreatic mucinous cysts ID FINE-NEEDLE-ASPIRATION; DIFFERENTIAL-DIAGNOSIS; SEROUS CYSTADENOMA; LESIONS; NEOPLASMS; BIOPSY; CEA; CYTOLOGY; AMYLASE; LEVEL AB Objectives: Endoscopic ultrasound (EUS) may offer a diagnostic tool through the combination of imaging and guided fine-needle aspiration of pancreatic cysts. The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cysts. Methods: The results of EUS imaging, cytology, and cyst fluid biochemical markers were prospectively collected and compared in a large single-center study (776 patients) using histology or malignant cytology as the final diagnostic standard in 198 patients. Results: The mean cyst fluid carcinoembryonic antigen (CEA) was greater in mucinous cysts (4703.0 ng/mL) compared with nonmucinous cysts (25.8 ng/mL) (P = 0.008). When using the optimal cutoff value of 109.9 ng/mL, the CEA was more accurate (86%, receiver operating characteristic area = 0.928) than EUS imaging (48%) and cytology (58%) in predicting a mucinous cyst (P < 0.0001). Malignant cysts had a mean cyst fluid CEA value (2558.2 ng/mL) similar to benign cysts (4700.2 ng/mL). Cytology (75%) more accurately diagnosed malignant cysts than EUS (66%) and CEA (62%) (P < 0.05). Conclusions: Cyst fluid CEA concentration provides a highly accurate test for the diagnosis of a mucinous cyst, but does not distinguish benign from malignant cysts. Cytology is the most accurate test for the diagnosis of a malignant cyst. C1 [Cizginer, Sevdenur; Turner, Brian; Karaca, Cetin; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02116 USA. [Bilge, A. Reyyan] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02116 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 452C, Boston, MA 02116 USA. EM wbrugge@partners.org NR 31 TC 88 Z9 92 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD OCT PY 2011 VL 40 IS 7 BP 1024 EP 1028 DI 10.1097/MPA.0b013e31821bd62f PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 821RT UT WOS:000294992800007 PM 21775920 ER PT J AU Keedy, AW Yee, J Aslam, R Weinstein, S Landeras, LA Shah, JN McQuaid, KR Yeh, BM AF Keedy, Alexander W. Yee, Judy Aslam, Rizwan Weinstein, Stefanie Landeras, Luis A. Shah, Janak N. McQuaid, Kenneth R. Yeh, Benjamin M. TI Reduced Cathartic Bowel Preparation for CT Colonography: Prospective Comparison of 2-L Polyethylene Glycol and Magnesium Citrate SO RADIOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; LOW-FIBER DIET; COLORECTAL-CANCER; PATIENT ACCEPTANCE; SODIUM-PHOSPHATE; CONTROLLED-TRIAL; PERFORMANCE-CHARACTERISTICS; DIAGNOSTIC PERFORMANCE; COLONOSCOPY; VOLUME AB Purpose: To prospectively compare adequacy of colonic cleansing, adequacy of solid stool and fluid tagging, and patient acceptance by using reduced-volume, 2-L polyethylene glycol (PEG) versus magnesium citrate bowel preparations for CT colonography. Materials and Methods: This study was approved by the institutional Committee on Human Research and was compliant with HIPAA; all patients provided written consent. In this randomized, investigator-blinded study, 50 patients underwent oral preparation with either a 2-L PEG or a magnesium citrate solution, tagging with oral contrast agents, and subsequent CT colonography and segmentally unblinded colonoscopy. The residual stool (score 0 [best] to 3 [worst]) and fluid (score 0 [best] to 4 [worst]) burden and tagging adequacy were qualitatively assessed. Residual fluid attenuation was recorded as a quantitative measure of tagging adequacy. Patients completed a tolerance questionnaire within 2 weeks of scanning. Preparations were compared for residual stool and fluid by using generalized estimating equations; the Mann-Whitney test was used to compare the qualitative tagging score, mean residual fluid attenuation, and adverse effects assessed on the patient experience questionnaire. Results: The mean residual stool (0.90 of three) and fluid burden (1.05 of four) scores for PEG were similar to those for magnesium citrate (0.96 [P = .58] and 0.98 [P = .48], respectively). However, the mean fecal and fluid tagging scores were significantly better for PEG (0.48 and 0.28, respectively) than for magnesium citrate (1.52 [P < .01] and 1.28 [P < .01], respectively). Mean residual fluid attenuation was higher for PEG (765 HU) than for magnesium citrate (443 HU, P = .01), and mean interpretation time was shorter for PEG (14.8 minutes) than for magnesium citrate (18.0 minutes, P = .04). Tolerance ratings were not significantly different between preparations. Conclusion: Reduced-volume PEG and magnesium citrate bowel preparations demonstrated adequate cleansing effectiveness for CT colonography, with better tagging and shorter interpretation time observed in the PEG group. Adequate polyp detection was maintained but requires further validation because of the small number of clinically important polyps. C1 [Keedy, Alexander W.; Yee, Judy; Aslam, Rizwan; Weinstein, Stefanie; Landeras, Luis A.; Shah, Janak N.; McQuaid, Kenneth R.; Yeh, Benjamin M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, VAMC, Dept Radiol, San Francisco, CA 94143 USA. RP Yee, J (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, VAMC, Dept Radiol, 4150 Clement St,Box 114, San Francisco, CA 94143 USA. EM Judy.Yee@radiology.ucsf.edu FU National Institutes of Health [UL1 RR024131] FX This research was supported by the National Institutes of Health (grant UL1 RR024131). NR 44 TC 8 Z9 9 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2011 VL 261 IS 1 BP 156 EP 164 DI 10.1148/radiol.11110217 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822IW UT WOS:000295039000017 PM 21873253 ER PT J AU Brisse, HJ McCarville, MB Granata, C Krug, KB Wootton-Gorges, SL Kanegawa, K Giammarile, F Schmidt, M Shulkin, BL Matthay, KK Lewington, VJ Sarnacki, S Hero, B Kaneko, M London, WB Pearson, ADJ Cohn, SL Monclair, T AF Brisse, Herve J. McCarville, M. Beth Granata, Claudio Krug, K. Barbara Wootton-Gorges, Sandra L. Kanegawa, Kimio Giammarile, Francesco Schmidt, Matthias Shulkin, Barry L. Matthay, Katherine K. Lewington, Valerie J. Sarnacki, Sabine Hero, Barbara Kaneko, Michio London, Wendy B. Pearson, Andrew D. J. Cohn, Susan L. Monclair, Tom TI Guidelines for Imaging and Staging of Neuroblastic Tumors: Consensus Report from the International Neuroblastoma Risk Group Project SO RADIOLOGY LA English DT Article ID WHOLE-BODY MRI; NERVOUS-SYSTEM METASTASES; INRG TASK-FORCE; MIBG-SCINTIGRAPHY; ABDOMINAL NEUROBLASTOMA; PEDIATRIC-PATIENTS; NEURO-BLASTOMA; LOCAL-CONTROL; CHILDREN; DIAGNOSIS AB Neuroblastoma is an enigmatic disease entity; some tumors disappear spontaneously without any therapy, while others progress with a fatal outcome despite the implementation of maximal modern therapy. However, strong prognostic factors can accurately predict whether children have "good" or "bad" disease at diagnosis, and the clinical stage is currently the most significant and clinically relevant prognostic factor. Therefore, for an individual patient, proper staging is of paramount importance for risk assessment and selection of optimal treatment. In 2009, the International Neuroblastoma Risk Group (INRG) Project proposed a new staging system designed for tumor staging before any treatment, including surgery. Compared with the focus of the International Neuroblastoma Staging System, which is currently the most used, the focus has now shifted from surgicopathologic findings to imaging findings. The new INRG Staging System includes two stages of localized disease, which are dependent on whether image-defined risk factors (IDRFs) are or are not present. IDRFs are features detected with imaging at the time of diagnosis. The present consensus report was written by the INRG Imaging Committee to optimize imaging and staging and reduce interobserver variability. The rationales for using imaging methods (ultrasonography, magnetic resonance imaging, computed tomography, and scintigraphy), as well as technical guidelines, are described. Definitions of the terms recommended for assessing IDRFs are provided with examples. It is anticipated that the use of standardized nomenclature will contribute substantially to more uniform staging and thereby facilitate comparisons of clinical trials conducted in different parts of the world. (C) RSNA, 2011 C1 [Brisse, Herve J.] Inst Curie, Dept Imaging, F-75005 Paris, France. [McCarville, M. Beth] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [Shulkin, Barry L.] St Jude Childrens Hosp, Div Nucl Med, Memphis, TN 38105 USA. [Granata, Claudio] Osped Gaslini, Dept Radiol, Genoa, Italy. [Krug, K. Barbara] Univ Cologne, Dept Radiol, Cologne, Germany. [Schmidt, Matthias] Univ Cologne, Dept Nucl Med, Cologne, Germany. [Hero, Barbara] Univ Cologne, Dept Pediat Oncol & Hematol, Childrens Hosp, Cologne, Germany. [Wootton-Gorges, Sandra L.] Univ Calif, Dept Radiol, Davis Med Ctr, Sacramento, CA USA. [Wootton-Gorges, Sandra L.] UC Davis Childrens Hosp, Sacramento, CA USA. [Kanegawa, Kimio] Aichi Childrens Hlth & Med Ctr, Dept Radiol, Aichi, Japan. [Giammarile, Francesco] Hosp Civils Lyon, CHLS, Dept Nucl Med, Lyon, France. [Giammarile, Francesco] Fac Med, Lyon, France. [Matthay, Katherine K.] Univ Florida, Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA. [Matthay, Katherine K.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Lewington, Valerie J.] Royal Marsden NHS Fdn Trust, Dept Nucl Med, Sutton, Surrey, England. [Sarnacki, Sabine] Hop Necker Enfants Malad, Dept Pediat Surg, Paris, France. [Kaneko, Michio] Univ Tsukuba, Dept Pediat Surg, Inst Clin Med, Ibaraki, Japan. [London, Wendy B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat,Div Hematol Oncol,Childrens Hosp Bos, Boston, MA 02115 USA. [Pearson, Andrew D. J.] Inst Canc Res, Paediat Sect, Sutton, Surrey, England. [Pearson, Andrew D. J.] Royal Marsden Hosp, Sutton, Surrey, England. [Cohn, Susan L.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Monclair, Tom] Oslo Univ Hosp, Dept Paediat Surg, Rikshosp, Oslo, Norway. RP Brisse, HJ (reprint author), Inst Curie, Dept Imaging, 26 Rue Ulm, F-75005 Paris, France. EM herve.brisse@curie.net OI BRISSE, Herve J./0000-0003-2794-5875; Cohn, Susan/0000-0001-5749-7650 FU Elsevier Masson FX H.J.B. No potential conflicts of interest to disclose. M. B. M. No potential conflicts of interest to disclose. C. G. No potential conflicts of interest to disclose. K. B. K. No potential conflicts of interest to disclose. S. L. W. No potential conflicts of interest to disclose. K. K. No potential conflicts of interest to disclose. F. G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: receives royalties from Elsevier Masson. Other relationships: none to disclose. M. S. No potential conflicts of interest to disclose. B. L. S. No potential conflicts of interest to disclose. K. K. M. No potential conflicts of interest to disclose. V.J.L. No potential conflicts of interest to disclose. S. S. No potential conflicts of interest to disclose. B. H. No potential conflicts of interest to disclose. M. K. No potential conflicts of interest to disclose. W. B. L. No potential conflicts of interest to disclose. A.D.J.P. No potential conflicts of interest to disclose. S. L. C. No potential conflicts of interest to disclose. T. M. No potential conflicts of interest to disclose. NR 63 TC 65 Z9 73 U1 0 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2011 VL 261 IS 1 BP 243 EP 257 DI 10.1148/radiol.11101352 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822IW UT WOS:000295039000027 PM 21586679 ER PT J AU Newman, MA Mani, V Hammond, SM AF Newman, Martin A. Mani, Vidya Hammond, Scott M. TI Deep sequencing of microRNA precursors reveals extensive 3 ' end modification SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE microRNA; miRNA; deep-sequencing ID POSTTRANSCRIPTIONAL REGULATION; SMALL RNAS; C-ELEGANS; ADENYLATION; BIOGENESIS; LIN28; LIN-28; URIDYLATION; EXPRESSION; MATURATION AB MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. An emerging mechanism to control miRNA production is the addition of an oligo-uridine tail to the 39 end of the precursor miRNA. This has been demonstrated for the Let-7 family of miRNAs in embryonic cells. Additionally, nontemplated nucleotides have been found on mature miRNA species, though in most cases it is not known if nucleotide addition occurs at the precursor step or at the mature miRNA. To examine the diversity of nucleotide addition we have developed a high-throughput sequencing method specific for miRNA precursors. Here we report that nontemplated addition is a widespread phenomenon occurring in many miRNA families. As previously reported, Let-7 family members are oligo-uridylated in embryonic cells in a Lin28-dependent manner. However, we find that the fraction of uridylated precursors increases with differentiation, independent of Lin28, and is highest in adult mouse tissues, exceeding 30% of all sequence reads for some Let-7 family members. A similar fraction of sequence reads are modified for many other miRNA families. Mono-uridylation is most common, with cytidine and adenosine modification less frequent but occurring above the expected error rate for Illumina sequencing. Nucleotide addition in cell lines is associated with 3' end degradation, in contrast to adult tissues, where modification occurs predominantly on full-length precursors. This work provides an unprecedented view of the complexity of 3' modification and trimming of miRNA precursors. C1 [Newman, Martin A.; Mani, Vidya; Hammond, Scott M.] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Newman, Martin A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Hammond, SM (reprint author), Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. EM hammond@med.unc.edu FU NIH (NIGMS and ARRA); Department of Cell and Developmental Biology, UNC FX We thank members of the Hammond, Randell, and Hayes lab for advice and support. Work was funded by the NIH (NIGMS and ARRA) and by support from the Department of Cell and Developmental Biology, UNC. Sequence data uploaded to the NCBI-SRA, accession number SRP005265. NR 29 TC 64 Z9 65 U1 0 U2 14 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD OCT PY 2011 VL 17 IS 10 BP 1795 EP 1803 DI 10.1261/rna.2713611 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 821UP UT WOS:000295000200004 PM 21849429 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Patients with anti-HER2 responsive disease: definition and adjuvant therapies SO BREAST LA English DT Article DE HER2; Trastuzumab; Polysomy; Tumor testing ID BREAST-CANCER; HERA TRIAL; TRASTUZUMAB; CHEMOTHERAPY; N9831 AB Treatment of HER2 positive breast cancer is one of the great successes in recent breast oncology. This article will review recent information on patient and tumor selection for anti-HER2 therapy, and new data on optimal use of trastuzumab-based treatments in the adjuvant setting. (C) 2011 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM hburstein@partners.org NR 11 TC 2 Z9 2 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2011 VL 20 SU 3 BP S132 EP S134 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 037CA UT WOS:000311077400024 PM 22015280 ER PT J AU Campone, M Piccart, M Pritchard, KI Xu, C Gnant, M Neven, P Pistilli, B Shtivelband, M Provencher, L Masuda, N El-Hashimy, M Vittori, L Sahmoud, T Baselga, J Hortobagyi, GN AF Campone, Mario Piccart, Martine Pritchard, Kathleen I. Xu, Cindy Gnant, Michael Neven, Patrick Pistilli, Barbara Shtivelband, Mikhail Provencher, Louise Masuda, Norikazu El-Hashimy, Mona Vittori, Luc Sahmoud, Tarek Baselga, Jose Hortobagyi, Gabriel N. TI BOLERO-2: EVEROLIMUS IN COMBINATION WITH EXEMESTANE IN THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ESTROGEN RECEPTOR-POSITIVE ADVANCED BREAST CANCER REFRACTORY TO LETROZOLE OR ANASTROZOLE SO BREAST LA English DT Meeting Abstract C1 [Campone, Mario] Ctr Reg Rene Gauducheau, St Herblain, France. [Piccart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada. [Xu, Cindy; El-Hashimy, Mona; Sahmoud, Tarek] Novartis Pharmaceut, Florham Pk, NJ USA. [Gnant, Michael] Med Univ Vienna, Vienna, Austria. [Neven, Patrick] Catholic Univ Louvain, UZ Leuven, B-3000 Louvain, Belgium. [Pistilli, Barbara] Macerata Hosp, Dept Oncol, Macerata, MC, Italy. [Shtivelband, Mikhail] Ironwood Canc & Res Ctr, Chandler, AZ USA. [Provencher, Louise] Hop St Sacrement, Quebec City, PQ, Canada. [Masuda, Norikazu] Osaka Natl Hosp, Osaka, Japan. [Vittori, Luc] Novartis Pharma AG, Basel, Switzerland. [Baselga, Jose] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2011 VL 20 SU 4 BP S30 EP S30 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 037DM UT WOS:000311082400050 ER EF