FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Britos-Bray, MF Smoot, E Liu, K Thompson, BT Brower, R AF Britos-Bray, M. F. Smoot, E. Liu, K. Thompson, B. T. Brower, R. CA ARDS Network Investigators TI The Value Of PEEP In The Definition Of Acute Lung Injury (ALI) In ARDS Network Clinical Trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Britos-Bray, M. F.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Smoot, E.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brower, R.; ARDS Network Investigators] Johns Hopkins Univ, Baltimore, MD USA. EM mbritos@medicine.umaryland.edu NR 0 TC 0 Z9 0 U1 1 U2 1 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. PY 2010 VL 181 MA A2581 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001494 ER PT J AU Bunyavanich, S Soto-Quiros, M Avila, L Lasky-Su, JA Hunninghake, G Weiss, ST Celedon, JC AF Bunyavanich, S. Soto-Quiros, M. Avila, L. Lasky-Su, J. A. Hunninghake, G. Weiss, S. T. Celedon, J. C. TI Association Between A Genetic Variant In Thymic Stromal Lymphopoietin (TSLP) And Allergic Rhinitis In Boys With Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bunyavanich, S.; Lasky-Su, J. A.; Celedon, J. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bunyavanich, S.] Harvard Univ, Sch Med, Boston, MA USA. [Soto-Quiros, M.; Avila, L.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica. [Hunninghake, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, S. T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. EM sbunyavanich@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 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. PY 2010 VL 181 MA A1331 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000332 ER PT J AU Calfee, CS Thompson, BT Parsons, PE Ware, LB Matthay, MA Wong, HR AF Calfee, C. S. Thompson, B. T. Parsons, P. E. Ware, L. B. Matthay, M. A. Wong, H. R. CA NIH NHLBI ARDS Network TI Plasma IL-8 As A Risk Stratification Tool For Adults With Septic Shock SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Calfee, C. S.; Matthay, M. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parsons, P. E.] Univ Vermont, Burlington, VT USA. [Ware, L. B.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Wong, H. R.] Univ Cincinnati, Cincinnati, OH USA. [NIH NHLBI ARDS Network] NHLBI, NIH, Bethesda, MD 20892 USA. EM carolyn.calfee@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1652 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000652 ER PT J AU Christiani, DC Sheu, C Chen, F Su, L Bajwa, E Zhai, R Nuernberg, AM Clardy, PF Gallagher, D Gong, M Tejera, P Frank, AJ Hakonarson, H Lin, X Thompson, BT AF Christiani, D. C. Sheu, C. Chen, F. Su, L. Bajwa, E. Zhai, R. Nuernberg, A. M. Clardy, P. F. Gallagher, D. Gong, M. Tejera, P. Frank, A. J. Hakonarson, H. Lin, X. Thompson, B. T. TI A Large-scale Genotyping Study Identifies Five Genes Associated With ARDS Development SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Christiani, D. C.; Sheu, C.; Chen, F.; Su, L.; Zhai, R.; Tejera, P.; Lin, X.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bajwa, E.; Nuernberg, A. M.; Frank, A. J.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clardy, P. F.; Gallagher, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Gong, M.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. [Hakonarson, H.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2010 VL 181 MA A1024 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000025 ER PT J AU Danilack, VA Matthess, K Garshick, E Moy, ML AF Danilack, V. A. Matthess, K. Garshick, E. Moy, M. L. TI Daily Step Count As A Measure Of COPD Severity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Danilack, V. A.; Matthess, K.; Moy, M. L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst,Channing Lab, Boston, MA 02115 USA. EM valery.danilack@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1212 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000213 ER PT J AU Danilack, VA Matthess, K Garshick, E Mori, D Moy, ML AF Danilack, V. A. Matthess, K. Garshick, E. Mori, D. Moy, M. L. TI Perceived Barriers To Physical Activity And Walking In Persons With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Danilack, V. A.; Matthess, K.; Moy, M. L.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst,Channing Lab, Boston, MA 02115 USA. [Mori, D.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. EM valery.danilack@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1210 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000211 ER PT J AU de Prost, N Costa, EL Tucci, M Wellman, T Winkler, T Musch, G Harris, R Venegas, J Melo, MFV AF de Prost, N. Costa, E. L. Tucci, M. Wellman, T. Winkler, T. Musch, G. Harris, R. Venegas, J. Melo, M. F. Vidal TI Influence Of Alveolar Flooding On 18F-FDG Kinetics During Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [de Prost, N.; Costa, E. L.; Tucci, M.; Wellman, T.; Winkler, T.; Musch, G.; Harris, R.; Venegas, J.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R.] Harvard Univ, Sch Med, Boston, MA USA. EM nicolasdeprost@gmail.com RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2586 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001499 ER PT J AU de Prost, N Tucci, M Costa, EL Wellman, T Winkler, T Musch, G Harris, R Venegas, J Melo, MFV AF de Prost, N. Tucci, M. Costa, E. L. Wellman, T. Winkler, T. Musch, G. Harris, R. Venegas, J. Melo, M. F. Vidal TI Effect Of Maximal Alveolar Recruitment On Regional Lung Inflammation During Mild Endotoxemic Acute Lung Injury (ALI) In Sheep SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [de Prost, N.; Tucci, M.; Costa, E. L.; Wellman, T.; Winkler, T.; Musch, G.; Harris, R.; Venegas, J.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R.] Harvard Univ, Sch Med, Boston, MA USA. EM nicolasdeprost@gmail.com RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1687 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000687 ER PT J AU Dyer, E Pickerodt, PA Zarndt, R Swenson, ER AF Dyer, E. Pickerodt, P. A. Zarndt, R. Swenson, E. R. TI ERYTHROPOIETIN MITIGATES VENTILATOR-INDUCED LUNG INJURY IN RATS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Dyer, E.; Pickerodt, P. A.; Zarndt, R.; Swenson, E. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM philipp.pickerodt@charite.de NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1684 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000684 ER PT J AU Glavan, BJ Martin, TR Nickerson, D Holden, TD Black, RA Smith, JD Wurfel, MM Edwards, K AF Glavan, B. J. Martin, T. R. Nickerson, D. Holden, T. D. Black, R. A. Smith, J. D. Wurfel, M. M. Edwards, K. TI Common Genetic Variants In The Fas/FasL Pathway Modify The Risk Of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Glavan, B. J.; Nickerson, D.; Holden, T. D.; Black, R. A.; Smith, J. D.; Edwards, K.] Univ Washington, Seattle, WA 98195 USA. [Martin, T. R.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Wurfel, M. M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. EM bglavan@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2706 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001619 ER PT J AU Halonen, J Zanobetti, A Vokonas, P Sparrow, D Schwartz, J AF Halonen, J. Zanobetti, A. Vokonas, P. Sparrow, D. Schwartz, J. TI Relationship Between Outdoor Temperature And Blood Pressure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Halonen, J.; Zanobetti, A.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Halonen, J.] Univ Kuopio, Sch Publ Hlth & Clin Nutr, FIN-70211 Kuopio, Finland. [Vokonas, P.] VA Med Ctr, Boston, MA USA. [Sparrow, D.] VA Boston Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1727 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000727 ER PT J AU Herrero, R Kajikawa, O Wang, Y Matute-Bello, G Fu, X Martin, TR AF Herrero, R. Kajikawa, O. Wang, Y. Matute-Bello, G. Fu, X. Martin, T. R. TI Structural Determinants Of The Biological Activity Of Soluble Fas Ligand In The Lungs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Herrero, R.; Kajikawa, O.] VA Puget Sound, Seattle, WA USA. [Herrero, R.; Kajikawa, O.; Wang, Y.; Matute-Bello, G.; Fu, X.] Univ Washington, Seattle, WA 98195 USA. [Wang, Y.; Fu, X.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Martin, T. R.] VA Puget Sound Healthcare Syst, Seattle, WA USA. EM rherrero@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2707 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001620 ER PT J AU Hoffmann, B Luttmann-Gibson, H Cohen, A Suh, H Coull, B Schwartz, J Stone, P Horton, E Gold, DR AF Hoffmann, B. Luttmann-Gibson, H. Cohen, A. Suh, H. Coull, B. Schwartz, J. Stone, P. Horton, E. Gold, D. R. TI Higher Temperatures And Ozone Reduce Blood Pressure But Not Arterial Stiffness In Diabetic Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hoffmann, B.] Univ Duisburg Essen, Essen, Germany. [Luttmann-Gibson, H.; Suh, H.; Coull, B.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cohen, A.; Horton, E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Stone, P.; Gold, D. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM barbara.hoffmann@uk-essen.de NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1730 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000730 ER PT J AU Hunninghake, G Chu, J Sharma, S Cho, MH Murphy, AJ Carey, VJ Weiss, ST Raby, B AF Hunninghake, G. Chu, J. Sharma, S. Cho, M. H. Murphy, A. J. Carey, V. J. Weiss, S. T. Raby, B. TI The CD4+T-Cell Transcriptome And Serum IgE In Asthma: Evidence For Sexual Dimorphism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hunninghake, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chu, J.; Sharma, S.; Murphy, A. J.; Carey, V. J.] Channing Labs, Boston, MA USA. [Cho, M. H.; Weiss, S. T.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Raby, B.] Harvard Med, Boston, MA USA. EM ghunninghake@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1310 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000311 ER PT J AU Hunninghake, G Washko, GR Fernandez, I Yamashiro, T Ross, JC Estepar, RSJ Lynch, DA Sciurba, FC Brehm, J Diaz, AA Silverman, EK Hatabu, H Rosas, IO AF Hunninghake, G. Washko, G. R. Fernandez, I. Yamashiro, T. Ross, J. C. Estepar, R. S. J. Lynch, D. A. Sciurba, F. C. Brehm, J. Diaz, A. A. Silverman, E. K. Hatabu, H. Rosas, I. O. TI CT Metrics Of Restriction And Emphysema In Smokers With Preclinical Interstitial Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hunninghake, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Washko, G. R.; Diaz, A. A.] Brigham & Womens Hosp, Div Pul & Crit Care Med, Boston, MA 02115 USA. [Fernandez, I.; Estepar, R. S. J.; Brehm, J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Yamashiro, T.; Ross, J. C.; Hatabu, H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Lynch, D. A.] Natl Jewish Hlth, Denver, CO USA. [Sciurba, F. C.] Univ Pittsburgh, Pittsburgh, PA USA. [Brehm, J.] Harvard Univ, Sch Med, Boston, MA USA. [Silverman, E. K.; Rosas, I. O.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM ghunninghake@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1126 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000127 ER PT J AU Huynh, TN Weigt, SS Shapiro, S Kleerup, EC AF Huynh, T. N. Weigt, S. S. Shapiro, S. Kleerup, E. C. TI Characteristics And Prognostic Factors Of Patients With Pulmonary Hypertension Admitted To The Medical ICU SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Huynh, T. N.; Kleerup, E. C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Weigt, S. S.] UCLA Hlth Syst, Los Angeles, CA USA. [Shapiro, S.] VA Greater LA Healthcare, Los Angeles, CA USA. EM thuynh@mednet.ucla.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1640 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000640 ER PT J AU Junaid, I Hoo, GWS Klaustermeyer, WB AF Junaid, I. Hoo, G. W. Soo Klaustermeyer, W. B. TI Severe Angiotensin Converting Enzyme-Inhibitor (ACEI) Associated Angioedema Admitted To An ICU SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Junaid, I.; Klaustermeyer, W. B.] VA Greater Los Angeles Healthcare Syst, West VA, Los Angeles, CA USA. [Hoo, G. W. Soo] West Los Angeles VA, Los Angeles, CA USA. EM imjunaid@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1643 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000643 ER PT J AU Lipke, AB Matute-Bello, G Martin, TR AF Lipke, A. B. Matute-Bello, G. Martin, T. R. TI Febrile-range Hyperthermia Augments Apoptosis Of Alveolar Epithelial Cells By Suppressing NF-kappa B Activity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lipke, A. B.; Matute-Bello, G.] Univ Washington, Seattle, WA 98195 USA. [Martin, T. R.] VA Puget Sound Healthcare Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1366 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000367 ER PT J AU Moy, ML Danilack, VA Matthess, K Garshick, E AF Moy, M. L. Danilack, V. A. Matthess, K. Garshick, E. TI Use Of The Step Activity Monitor And Omron HJ-720ITC In The Home In COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moy, M. L.; Danilack, V. A.; Matthess, K.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst,Channing Lab, Boston, MA 02115 USA. EM marilyn.moy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1214 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000215 ER PT J AU Nelson, B Zhou, X White, M Hartshorn, KL Takahashi, K Kinane, T Koziel, H AF Nelson, B. Zhou, X. White, M. Hartshorn, K. L. Takahashi, K. Kinane, T. Koziel, H. TI THE INFLUENCE OF MANNOSE BINDING LECTIN ON THE LUNG MACROPHAGE RESPONSE TO INFLUENZA A VIRUS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhou, X.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [White, M.; Hartshorn, K. L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Takahashi, K.; Kinane, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koziel, H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM banelson@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2632 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001545 ER PT J AU Nuernberg, AM Zhai, R Su, L Sheu, C Tejera, P Gong, MN Thompson, BT Christiani, DC AF Nuernberg, A. M. Zhai, R. Su, L. Sheu, C. Tejera, P. Gong, M. N. Thompson, B. T. Christiani, D. C. TI Joint Effects Of IGFBP3 And TGFB1 Polymorphisms Increasing Mortality In ARDS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhai, R.; Su, L.; Sheu, C.; Tejera, P.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2703 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001616 ER PT J AU Patel, NR Krishnan, R Hardin, C Chen, C Bole, M Deng, L Butler, J Fredberg, JJ Koziel, H AF Patel, N. R. Krishnan, R. Hardin, C. Chen, C. Bole, M. Deng, L. Butler, J. Fredberg, J. J. Koziel, H. TI Macrophage Physical State And Function Is Determined By The Physical State Of The Environment SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Patel, N. R.; Bole, M.; Koziel, H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Krishnan, R.; Butler, J.; Fredberg, J. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hardin, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chen, C.; Deng, L.] Chongqing Univ, Chongqing 630044, Peoples R China. EM npatel@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1296 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000297 ER PT J AU Ramadas, RA Ewart, SL Medoff, B LeVine, A AF Ramadas, R. A. Ewart, S. L. Medoff, B. LeVine, A. TI IL1F9 STIMULATES CHEMOKINE PRODUCTION AND NEUTROPHIL INFLUX IN MOUSE LUNGS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ramadas, R. A.; Medoff, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramadas, R. A.] Harvard Univ, Boston, MA 02115 USA. [Ewart, S. L.] Michigan State Univ, E Lansing, MI 48824 USA. [LeVine, A.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2800 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001712 ER PT J AU Reinke, LF Griffith, RG Wolpin, S Donesky-Cuenco, D Carrieri-Kohlman, V Nguyen, HQ AF Reinke, L. F. Griffith, R. G. Wolpin, S. Donesky-Cuenco, D. Carrieri-Kohlman, V. Nguyen, H. Q. TI Feasibility Of A Webinar For Coaching Patients With Chronic Obstructive Pulmonary Disease On End-of-Life Communication SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Reinke, L. F.] VA Puget Sound, Seattle, WA USA. [Griffith, R. G.; Wolpin, S.; Nguyen, H. Q.] Univ Washington, Seattle, WA 98195 USA. [Donesky-Cuenco, D.; Carrieri-Kohlman, V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. EM pac6@cornell.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A6766 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771005385 ER PT J AU Shea, BS Brooks, SF Fontaine, BA Chun, J Luster, AD Tager, AM AF Shea, B. S. Brooks, S. F. Fontaine, B. A. Chun, J. Luster, A. D. Tager, A. M. TI Prolonged Exposure To S1P1 Agonists Worsens Vascular Leak, Fibrosis, And Mortality After Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Shea, B. S.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brooks, S. F.; Fontaine, B. A.; Luster, A. D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Chun, J.] Scripps Res Inst, La Jolla, CA 92037 USA. EM bsshea@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1056 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000057 ER PT J AU Sheu, C Zhai, R Chen, F Wang, Z Su, L Tejera, P Gong, MN Bajwa, E Nuernberg, AM Frank, AJ Gallagher, D Clardy, PF Hakonarson, H Lin, X Thompson, BT Christiani, DC AF Sheu, C. Zhai, R. Chen, F. Wang, Z. Su, L. Tejera, P. Gong, M. N. Bajwa, E. Nuernberg, A. M. Frank, A. J. Gallagher, D. Clardy, P. F. Hakonarson, H. Lin, X. Thompson, B. T. Christiani, D. C. TI A Large-Scale Genetic Association Study Identifies Different Susceptibility Loci Of Sepsis-Related And Non-Sepsis-Related ARDS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sheu, C.; Zhai, R.; Chen, F.; Wang, Z.; Su, L.; Tejera, P.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bajwa, E.; Nuernberg, A. M.; Frank, A. J.; Lin, X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallagher, D.; Clardy, P. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hakonarson, H.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. EM sheucc@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2702 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001615 ER PT J AU Sheu, C Gong, MN Zhai, R Chen, F Bajwa, E Gallagher, D Clardy, PF Christiani, DC Thompson, BT AF Sheu, C. Gong, M. N. Zhai, R. Chen, F. Bajwa, E. Gallagher, D. Clardy, P. F. Christiani, D. C. Thompson, B. T. TI Clinical Characteristics And Outcomes Of Sepsis-Related Vs. Non-Sepsis-Related Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sheu, C.; Zhai, R.; Chen, F.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bajwa, E.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallagher, D.; Clardy, P. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM sheucc@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2592 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001505 ER PT J AU Swenson, ER Lamm, WJE Tsang, JYC AF Swenson, E. R. Lamm, W. J. E. Tsang, J. Y. C. TI Regional Carbon Dioxide Tension Mediates Homeostatic Redistribution Of Ventilation In Pulmonary Thromboembolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Swenson, E. R.; Lamm, W. J. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Tsang, J. Y. C.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1925 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001133 ER PT J AU Tse, S Cheung, L Constantin, E Lands, LC AF Tse, S. Cheung, L. Constantin, E. Lands, L. C. TI Prevalence Of Asthma And Obstructive Sleep Apnea In Obese Adolescents With And Without The Metabolic Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tse, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheung, L.] McGill Univ, Fac Med, Montreal, PQ, Canada. [Constantin, E.; Lands, L. C.] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. EM stse@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2436 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001350 ER PT J AU Tucci, MR Costa, EL de Prost, N Winkler, T Wellman, T Musch, G Harris, R Melo, MFV AF Tucci, M. R. Costa, E. L. de Prost, N. Winkler, T. Wellman, T. Musch, G. Harris, R. Melo, M. F. Vidal TI 18F-FDG Uptake And Regional Derecruitment Of The Heterogeneously Inflated Supine Healthy Lung During 16 H Of Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Costa, E. L.; de Prost, N.; Winkler, T.; Wellman, T.; Musch, G.; Harris, R.; Melo, M. F. Vidal] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R.] Harvard Univ, Sch Med, Boston, MA USA. RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1689 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000689 ER PT J AU van den Berg, E van Woensel, JBM Bos, AP Bem, RA Altemeier, WA Martin, TR Matute-Bello, G AF van den Berg, E. van Woensel, J. B. M. Bos, A. P. Bem, R. A. Altemeier, W. A. Martin, T. R. Matute-Bello, G. TI Role Of The Fas/FasL System In A Murine Model Of RSV Infection In Mechanically Ventilated Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [van den Berg, E.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [van Woensel, J. B. M.; Bos, A. P.; Bem, R. A.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Altemeier, W. A.] Univ Washington, Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Martin, T. R.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Matute-Bello, G.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2778 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001691 ER PT J AU Vaporidi, K Iliopoulos, D Francis, RC Bloch, KD Zapol, WM AF Vaporidi, K. Iliopoulos, D. Francis, R. C. Bloch, K. D. Zapol, W. M. TI MicroRNA Expression Profile In A Murine Model Of Ventilator-induced Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Vaporidi, K.] Univ Crete, Sch Med, Iraklion, Greece. [Iliopoulos, D.] Harvard Univ, Sch Med, Boston, MA USA. [Francis, R. C.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bloch, K. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM vaporidi@med.uoc.gr NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2010 VL 181 MA A2031 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001238 ER PT J AU Wan, ES Cho, MH Boutaoui, N Klanderman, BJ Sylvia, JS Ziniti, JP Litonjua, AA Sparrow, D Lange, C Pillai, S Kong, X Anderson, W Tal-Singer, R Lomas, D Bakke, P Gulsvik, A Silverman, EK DeMeo, D AF Wan, E. S. Cho, M. H. Boutaoui, N. Klanderman, B. J. Sylvia, J. S. Ziniti, J. P. Litonjua, A. A. Sparrow, D. Lange, C. Pillai, S. Kong, X. Anderson, W. Tal-Singer, R. Lomas, D. Bakke, P. Gulsvik, A. Silverman, E. K. DeMeo, D. TI Mitochondrial DNA Polymorphisms Are Associated With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wan, E. S.; Cho, M. H.; Boutaoui, N.; Klanderman, B. J.; Sylvia, J. S.; Ziniti, J. P.; Litonjua, A. A.; Bakke, P.; Silverman, E. K.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Sparrow, D.] VA Boston Healthcare, Boston, MA USA. [Lange, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pillai, S.; Anderson, W.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Lomas, D.] Cambridge Inst Med Res, Cambridge, England. [Gulsvik, A.] Univ Bergen, Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2921 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771002034 ER PT J AU Wang, Z Chen, F Sheu, C Zhai, R Su, L Tejera, P Bajwa, E Nuernberg, AM Clardy, PF Gallagher, D Gong, M Frank, AJ Hakonarson, H Lin, X Thompson, BT Christiani, DC AF Wang, Z. Chen, F. Sheu, C. Zhai, R. Su, L. Tejera, P. Bajwa, E. Nuernberg, A. M. Clardy, P. F. Gallagher, D. Gong, M. Frank, A. J. Hakonarson, H. Lin, X. Thompson, B. T. Christiani, D. C. TI Genetic Interactions Between Genes Discovered By Genome-wide Expression Profiling Are Associated With The Risk Of ARDS Development SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, Z.; Chen, F.; Sheu, C.; Zhai, R.; Su, L.; Tejera, P.; Lin, X.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bajwa, E.; Nuernberg, A. M.; Frank, A. J.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clardy, P. F.; Gallagher, D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Gong, M.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. [Hakonarson, H.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. EM mikewang@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001617 ER PT J AU Weng, M Raher, MJ Leyton, P Combs, TP Scherer, PE Bloch, KD Medoff, B AF Weng, M. Raher, M. J. Leyton, P. Combs, T. P. Scherer, P. E. Bloch, K. D. Medoff, B. TI Adiponectin Modulates Pulmonary Vascular Remodeling By Inhibiting Pulmonary Artery Smooth Muscle Cell Proliferation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Weng, M.; Raher, M. J.; Leyton, P.; Medoff, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Combs, T. P.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Scherer, P. E.] Univ Texas Southwestern, Dallas, TX USA. [Bloch, K. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM bmedoff@partners.org NR 0 TC 1 Z9 1 U1 0 U2 1 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. PY 2010 VL 181 MA A1184 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000185 ER PT J AU Winthrop, KL Baxter, R Liu, L McFarland, B Austin, D Varley, C Radcliffe, L Suhler, E Choi, D Rosenbaum, J Herrinton, L AF Winthrop, K. L. Baxter, R. Liu, L. McFarland, B. Austin, D. Varley, C. Radcliffe, L. Suhler, E. Choi, D. Rosenbaum, J. Herrinton, L. TI Mycobacterial Disease In Rheumatoid Arthritis Patients Who Use Anti-tumor Necrosis Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Baxter, R.; Liu, L.; Herrinton, L.] Kasier Permanente Northern Calif, Oakland, CA USA. [McFarland, B.; Varley, C.; Choi, D.; Rosenbaum, J.] Oregon Hlth & Sci Univ, Mailcode CLEI, Portland, OR 97201 USA. [Austin, D.; Suhler, E.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Radcliffe, L.] Portland VA Med Ctr, Portland, OR USA. EM varleyc@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A2603 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001516 ER PT J AU Wong, KK Carretero, J Ramirez, MI Li, J Hinds, A Williams, MC Kathuria, H AF Wong, K. K. Carretero, J. Ramirez, M. I. Li, J. Hinds, A. Williams, M. C. Kathuria, H. TI Increased Ets-1 Positively Correlates With Twist1 Expression In Mouse Non-small Cell Lung Cancer (NSCLC) Progression And Metastases SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wong, K. K.; Carretero, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramirez, M. I.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Li, J.; Hinds, A.; Williams, M. C.; Kathuria, H.] Boston Univ, Med Ctr, Boston, MA 02118 USA. EM hasmeena@bu.edu RI Carretero, Julian/N-5214-2014 OI Carretero, Julian/0000-0001-7269-8506 NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2010 VL 181 MA A2054 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771001261 ER PT J AU Zarndt, R Pickerodt, PA Emery, MJ Swenson, ER AF Zarndt, R. Pickerodt, P. A. Emery, M. J. Swenson, E. R. TI SODIUM NITRITE IS PROTECTIVE IN A RAT MODEL OF VENTILATOR-INDUCED LUNG INJURY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zarndt, R.; Pickerodt, P. A.; Emery, M. J.; Swenson, E. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2010 VL 181 MA A1685 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TP UT WOS:000208771000685 ER PT J AU Woodworth, BA Zhang, SY Tamashiro, E Bhargave, G Palmer, JN Cohen, NA AF Woodworth, Bradford A. Zhang, Shaoyan Tamashiro, Edwin Bhargave, Geeta Palmer, James N. Cohen, Noam A. TI Zinc increases ciliary beat frequency in a calcium-dependent manner SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Rhinologic-Society CY SEP 15, 2007 CL Washington, DC SP Amer Rhinol Soc DE Alternative treatments; calcium; cilia physiology; ciliary beat frequency; mucociliary clearance; nutritional supplements; P2X receptor; SAVA system; zinc ID AIRWAY EPITHELIAL-CELLS; CA2+-SENSING RECEPTORS; NUCLEOTIDE RECEPTOR; INTRACELLULAR CA2+; SENSING RECEPTOR; CYSTIC-FIBROSIS; ATP; MECHANOSENSITIVITY; DESENSITIZATION; MUCOCILIARY AB Background: Dynamic regulation of respiratory ciliary beat frequency (CBF) is regulated by fluxes in intracellular calcium (Ca(2+)). P2X receptors (P2XR) are extracellular ATP-gated, Ca(2+)-permeable, nonselective cation channels. Zinc increases intracellular Ca(2+) in a sodium (Na(+))-free environment through activation of P2XR channels. We hypothesize that topical zinc increases CBF in a Ca(2+)-dependent fashion as a result of this mechanism. Methods: The apical surface of mouse sinonasal air-liquid interface cultures were bathed in zinc in a Na(+)-free solution with or without Ca(2+). High-speed digital video imaging captured and analyzed CBF at a sampling rate of 100 frames/s. Results: CBF significantly increased fourfold over baseline from 5.99 +/- 3.16 Hz to 22.4 +/- 4.33 Hz in the presence of zinc chloride (50 micromoles) and calcium chloride (3 mM). This effect is abolished in the presence of extracellular Na(+) and was pH dependent. Conclusion: Zinc stimulates CBF in the presence of Ca(2+) likely through activation of P2X receptors. Thus, zinc represents a promising agent for stimulation of mucociliary clearance. (Am J Rhinol Allergy 24, 6-10, 2010; doi: 10.2500/ajra.2010.24.3379) C1 [Woodworth, Bradford A.; Zhang, Shaoyan] Univ Alabama, Dept Surg, Div Otolaryngol, Birmingham, AL 35294 USA. [Woodworth, Bradford A.; Zhang, Shaoyan] Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL USA. [Tamashiro, Edwin; Bhargave, Geeta; Palmer, James N.; Cohen, Noam A.] Univ Penn Hlth Syst, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA USA. [Tamashiro, Edwin; Bhargave, Geeta; Palmer, James N.; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Div Otolaryngol Head & Neck Surg, Philadelphia, PA USA. RP Woodworth, BA (reprint author), Univ Alabama, Dept Surg, Div Otolaryngol, BDB 563,1530 3rd Ave S, Birmingham, AL 35294 USA. EM bwoodwo@hotmail.com RI Tamashiro, Edwin/C-5062-2012; OI Tamashiro, Edwin/0000-0002-3153-6292; Cohen, Noam/0000-0002-9462-3932 NR 33 TC 9 Z9 9 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AMJ RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2010 VL 24 IS 1 BP 6 EP 10 DI 10.2500/ajra.2010.24.3379 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 556DW UT WOS:000274570000002 PM 20109308 ER PT J AU Stull, DE Meltzer, EO Krouse, JH Roberts, L Kim, S Frank, L Naclerio, R Lund, V Long, AD AF Stull, Donald E. Meltzer, Eli O. Krouse, John H. Roberts, Laurie Kim, Susan Frank, Lori Naclerio, Robert Lund, Valerie Long, Aidan TI The congestion quantifier five-item test for nasal congestion: Refinement of the congestion quantifier seven-item test SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article DE Allergic rhinitis; congestion; outcomes research; patient-reported outcomes; screener questionnaire ID ALLERGIC RHINITIS; PRODUCTIVITY; VALIDATION; PREVALENCE; SYMPTOMS; OUTCOMES; SLEEP; WORK AB Background: Patients report that nasal congestion is the most bothersome symptom of allergic rhinitis (AR). Recently, a short, patient-reported congestion screener questionnaire, the Congestion Quantifier Seven-Item Test (CQ7), was developed to identify a level of congestion that may warrant patients seeking evaluation and possible treatment. We explored further item reduction of the CQ7 and examined the psychometric properties of this reduced set of items in a 15-day study of patients with confirmed AR or self-identified and clinician-confirmed congestion. Methods: The CQ7 was subjected to item reduction methods and the psychometric properties of the reduced set of items were assessed. Results: Two items were dropped-sinus pressure/pain and impact on work/school-because of lower item-rest correlations. The resulting Congestion Quantifier Five-Item screener (CQ5) performed comparably with the CQ7. Internal consistency reliability of both instruments were identical (alpha = 0.93); test-retest reliability front baseline to day 15 was similar (CQ7, alpha = 0.85, CQ5, alpha = 0.79). Both instruments were comparable in discriminating patients and controls (CQ7, area under the curve [AUC] = 0.97, CQ5, AUC = 0.96). A CQ5 score of 6 provided optimum balance of sensitivity (89.4%), specificity (88.6%), and correct classification (89%) for detecting congestion. Conclusion: The CQ5, a patient-reported outcome screener, is slightly shorter but equally reliable, valid, and responsive as the CQ7 for evaluating differences in levels of severity of nasal congestion. It may have wider applicability than the CQ7 because of exclusion of the work/school impact item. (Am J Rhinol Allergy 24, 34-38, 2010; doi: 10.2500/ajra.2010.24.3394) C1 [Stull, Donald E.] United BioSource Corp, Ctr Hlth Outcomes Res, London WC1A 2NS, England. [Meltzer, Eli O.] Allergy & Asthma Med Grp & Res Ctr, San Diego, CA USA. [Meltzer, Eli O.] Univ Calif San Diego, San Diego, CA 92103 USA. [Krouse, John H.] Wayne State Univ, Dept Otolaryngol Head & Neck Surg, Detroit, MI USA. [Roberts, Laurie; Frank, Lori] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. [Kim, Susan] Schering Plough Corp, Kenilworth, NJ 07033 USA. [Naclerio, Robert] UCL, Inst Larygol & Otolaryngol, London, England. [Lund, Valerie] Univ Chicago, Dept Surg, Sect Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA. [Long, Aidan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stull, DE (reprint author), United BioSource Corp, Ctr Hlth Outcomes Res, 20 Bloomsbury Sq, London WC1A 2NS, England. EM donald.stull@unitedbiosource.com FU Schering-Plough Corporation FX Funding for this research was provided by Schering-Plough Corporation NR 22 TC 5 Z9 5 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AMJ RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2010 VL 24 IS 1 BP 34 EP 38 DI 10.2500/ajra.2010.24.3394 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 556DW UT WOS:000274570000008 PM 20109320 ER PT J AU Forman, HP Crowe, JK Messinger, N Javitt, MC Larson, DB Norbash, A Kaye, A Thrall, JH Hricak, H Kazerooni, EA AF Forman, Howard P. Crowe, John K. Messinger, Neil Javitt, Marcia C. Larson, David B. Norbash, Alexander Kaye, Alan Thrall, James H. Hricak, Hedvig Kazerooni, Ella A. TI Masters of Radiology Panel Discussion: Responding to Health Care Reform and Other Market Pressures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE cost-efficiency; health care reform; hyperefficiency; productivity; reimbursement C1 [Forman, Howard P.] Yale Univ, MBA Program & MBA Execut, New Haven, CT 06520 USA. [Crowe, John K.] Scottsdale Med Imaging, Scottsdale, AZ USA. [Messinger, Neil] Baptist Hlth Syst, Dept Radiol, Miami, FL USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Larson, David B.] Cincinnati Childrens Hosp, Med Ctr, Dept Radiol, Cincinnati, OH USA. [Norbash, Alexander] Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA. [Kaye, Alan] Bridgeport Hosp, Dept Radiol, Westport, CT USA. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, Seattle, WA USA. [Kazerooni, Ella A.] Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. RP Forman, HP (reprint author), Yale Univ, MBA Program & MBA Execut, New Haven, CT 06520 USA. EM howard.forman@yale.edu OI Norbash, Alexander/0000-0003-2986-2563; Hricak, Hedvig/0000-0003-2240-9694 NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2010 VL 194 IS 1 BP 173 EP 177 DI 10.2214/AJR.09.3715 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 535SH UT WOS:000272990500024 PM 20028920 ER PT J AU Prakash, P Kalra, MK Sharma, A Shepard, JAO Digumarthy, SR AF Prakash, Priyanka Kalra, Mannudeep K. Sharma, Amita Shepard, Jo-Anne O. Digumarthy, Subba R. TI FDG PET/CT in Assessment of Pulmonary Lymphangitic Carcinomatosis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest; PET/CT; pulmonary lymphangitic carcinomatosis ID CELL LUNG-CANCER; CT; METASTASES AB OBJECTIVE. The purpose of this study was to assess the role of PET/CT in the diagnosis of pulmonary lymphangitic carcinomatosis. MATERIALS AND METHODS. Integrated PET/CT images of 35 patients (15 men, 20 women; mean age, 64.5 years) with pulmonary lymphangitic carcinomatosis confirmed at follow-up chest CT or histopathologic examination were analyzed retrospectively. Standardized uptake value based on body weight and the initial injected activity was measured in the affected lung, the normal lung, and the mediastinal blood pool. Two radiologists independently assessed abnormal PET activity in the lungs. Both radiologists reviewed the CT images to determine the presence, size, location, and extent of pulmonary lymphangitic carcinomatosis. The data were analyzed to determine the sensitivity and specificity of PET for pulmonary lymphangitic carcinomatosis. RESULTS. Among the 35 patients with pulmonary lymphangitic carcinomatosis, 17 (49%), 13 (37%), and five (14%) patients had diffuse, focal, and bilateral pulmonary lymphangitic carcinomatosis, respectively. Thirty of the 35 patients had nodular septal thickening as the chief CT finding of pulmonary lymphangitic carcinomatosis. Subjective assessment showed a visually identifiable increase in uptake in the region of pulmonary lymphangitic carcinomatosis in 30 of the 35 patients (86%). Four of the other five patients had focal pulmonary lymphangitic carcinomatosis, and one patient had diffuse pulmonary lymphangitic carcinomatosis of the right lung. The specificity of PET/CT for pulmonary lymphangitic carcinomatosis was 100%, and the sensitivity was 86%. The mean standardized uptake value in the region of pulmonary lymphangitic carcinomatosis (1.37 +/- 0.64) was significantly greater than that in normal lung (0.51 +/- 0.29) (p < 0.0001). The standardized uptake ratio of mediastinal blood pool to lymphangitic lung was 1.26 +/- 0.45, and that of blood pool to normal lung was 3.78 +/- 1.37. CONCLUSION. FDG PET/CT has high specificity in the detection of pulmonary lymphangitic carcinomatosis. Focal pulmonary lymphangitic carcinomatosis close to a primary malignant tumor, however, can be missed at PET. C1 [Prakash, Priyanka] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Prakash, Priyanka] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2010 VL 194 IS 1 BP 231 EP 236 DI 10.2214/AJR.09.3059 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 535SH UT WOS:000272990500031 PM 20028927 ER PT J AU Lauwers, GY Black-Schaffer, S Salto-Tellez, M AF Lauwers, Gregory Y. Black-Schaffer, Stephen Salto-Tellez, Manuel TI Molecular Pathology in Contemporary Diagnostic Pathology Laboratory An Opinion for the Active Role of Surgical Pathologists SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material AB "Although in recent years the emphasis in many university pathology departments has been on the biochemical and molecular biological aspects of disease, it is important to bear in mind the fact that hospital pathology laboratories have, in addition, the responsibility of patient care and thus the necessity of expert knowledge in...pathology. Fortunately, our department is large enough to permit a balance of the research effort with the patient-care activities..." Benjamin Castleman, MD, 1966, Former Massachusetts General Hospital Chief of Pathology, 1951 to 1974. C1 [Lauwers, Gregory Y.; Black-Schaffer, Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Black-Schaffer, Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Salto-Tellez, Manuel] Natl Univ Singapore, Natl Univ Hlth Syst, Dept Pathol, Singapore 117548, Singapore. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM glauwers@partners.org NR 0 TC 11 Z9 11 U1 0 U2 0 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 JAN PY 2010 VL 34 IS 1 BP 115 EP 117 PG 3 WC Pathology; Surgery SC Pathology; Surgery GA 540UZ UT WOS:000273366800013 PM 19809276 ER PT J AU Carlson, JW Lyon, E Walton, D Foo, WC Sievers, AC Shulman, LN Farmer, P Nose, V Milner, DA AF Carlson, Joseph W. Lyon, Evan Walton, David Foo, Wai-Chin Sievers, Amy C. Shulman, Lawrence N. Farmer, Paul Nose, Vania Milner, Danny A., Jr. TI Partners in Pathology: A Collaborative Model to Bring Pathology to Resource Poor Settings SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pathology; social justice; health care disparities; health care access AB Pathology provides a critical bridge between the patients, their physicians and the therapeutic and surgical interventions that can be provided to them. Clinicians caring for patients in resource poor settings may provide basic healthcare, which does not include access to pathologic services; however, the value of pathology in alleviating health disparities for Underserved patients is substantial when implemented. Partners in health is a comprehensive, community-based healthcare organization with clinics in 7 countries-most among the poorest in the world-which has the ability to obtain surgical biopsies and, if a pathologic diagnosis can be rendered, provide treatment, and long-term follow-up. Over the past 5 years, pathologists from the Brigham and Women's Hospital have collaborated with clinicians from partners in health to meet this need which included 129 cases from Haiti and Rwanda and a range of pathology: 64 malignancies, 28 normal tissue or nondiagnostic specimens, 16 infectious or inflammatory cases, 8 benign lesions, and other rare entities. Providing pathology services in resource poor settings through collaboration with clinicians working on-site is only hindered by the establishment of a working collaboration; however, the benefits are enormous and include patient access to curative or tailored therapies, logistical management of treatment resources, and exposure of pathologists to unique and challenging cases. C1 [Carlson, Joseph W.; Foo, Wai-Chin; Nose, Vania; Milner, Danny A., Jr.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lyon, Evan; Walton, David; Sievers, Amy C.; Farmer, Paul] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Div Gen Oncol, Boston, MA 02115 USA. RP Milner, DA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM dmilner@partners.org NR 4 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 JAN PY 2010 VL 34 IS 1 BP 118 EP 123 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 540UZ UT WOS:000273366800014 PM 19898229 ER PT J AU Poon, I Lal, LS Ford, ME Braun, UK AF Poon, Ivy Lal, Lincy S. Ford, Marvella E. Braun, Ursula K. TI Racial/Ethnic Differences in Blood Pressure Control and Medication Utilization in a Cohort of Older Veterans with Dementia SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE ethnic groups; race; dementia; hypertension; drug utilization; aged ID ANTIHYPERTENSIVE TREATMENT; AFRICAN-AMERICANS; ALZHEIMER-DISEASE; HYPERTENSION; PREVENTION; AFFAIRS; PREVALENCE; ADHERENCE; COMMUNITY; COMMITTEE AB Hypertension and dementia are common illnesses in geriatric patients, resulting in significant morbidity and mortality. The objective of this study was to investigate racial and ethnic differences in blood pressure control and medication utilization in veterans aged 65 years or older with a diagnosis of both hypertension and dementia. We conducted a retrospective chart review for such veterans who attended the Michael E. DeBakey VA Medical Center outpatient clinics in Houston, Texas, during the period of October 1, 2003, to September 30, 2004. A total of 304 patients (190 Caucasians and 114 African-Americans) were included in the study. The mean number of concurrent antihypertensive medications for African-Americans was higher than for Caucasians (3.2 and 2.8, respectively; P = 0.02). African-American ethnicity was associated with higher use of thiazide diuretics (P = 0.02), dihydropyridine calcium channel blockers (P = 0.04), and clonidine (P = 0.01) than was Caucasian ethnicity. Forty-eight percent of African-Americans achieved adequate blood pressure control, compared with 59% of Caucasians. Mini-mental state exam scores were lower for African-Americans than for Caucasians (17.8 and 21.6, respectively; P = 0.01). The utilization of dementia medications was not found to be different between African-Americans and Caucasians. Veterans in this cohort achieved better blood pressure control than previously reported in other studies consisting of older patients. Physicians might have considered patients' race when prescribing antihypertensive medications reflected by the higher use of thiazide diuretics and calcium channel blockers for African-Americans. C1 [Poon, Ivy] Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, Houston, TX 77004 USA. [Poon, Ivy] Michael E DeBakey VA Med Ctr, Dept Pharm, Houston, TX USA. [Lal, Lincy S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ford, Marvella E.] Med Univ S Carolina, Dept Biostat, Charleston, SC 29425 USA. [Ford, Marvella E.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Braun, Ursula K.] Michael E De Bakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Sect Geriatr, Houston, TX USA. [Braun, Ursula K.] Michael E De Bakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Sect Hlth Serv Res, Houston, TX USA. [Braun, Ursula K.] Baylor Coll Med, Houston, TX 77030 USA. RP Poon, I (reprint author), Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, 3100 Cleburne St, Houston, TX 77004 USA. EM chui_io@tsu.edu FU NIH Center of Excellence in Health Disparity Research (CEDHR); Houston VA HSR&D Center of Excellence [HFP90-020] FX This project was funded by an NIH Center of Excellence in Health Disparity Research (CEDHR) faculty fellowship award at Texas Southern University College of Pharmacy and Health Sciences. This work was supported in part by the Houston VA HSR&D Center of Excellence (HFP90-020). NR 34 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD JAN-FEB PY 2010 VL 17 IS 1 BP 34 EP 41 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 546XR UT WOS:000273849000007 PM 19535967 ER PT J AU Baratelli, F Lee, JM Hazra, S Lin, Y Walser, TC Schaue, D Pak, PS Elashoff, D Reckamp, K Zhang, L Fishbein, MC Sharma, S Dubinett, SM AF Baratelli, Felicita Lee, Jay M. Hazra, Saswati Lin, Ying Walser, Tonya C. Schaue, Dorthe Pak, Peter S. Elashoff, David Reckamp, Karen Zhang, Ling Fishbein, Michael C. Sharma, Sherven Dubinett, Steven M. TI PGE(2) contributes to TGF-beta induced T regulatory cell function in human non-small cell lung cancer SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE T regulatory cells; PGE(2); TGF-beta; non-small cell lung cancer; CD4(+) T cells AB CD4(+)CD25(bright) regulatory T cells (T-reg) play an important role in cancer-mediated immunosuppression. We and others have previously shown that prostaglandin E2 (PGE(2)) and transforming growth factor beta (TGF-beta) induce CD4(+)CD25(bright) FOXP3(+)T(reg). Based on these studies, we investigated the requirement for PGE(2) in T-reg induction by TGF-beta. TGF-beta stimulation of human CD4(+) T cells induced COX-2-dependent production of PGE(2). PGE(2)-neutralizing antibody treatment significantly reduced the suppressive function of TGF-beta-induced T-reg (TGF-beta-T-reg) in vitro. TGF-beta concentration measured in the plasma of non-small cell lung cancer (NSCLC) patients directly correlated with the frequency of circulating CD4(+)CD25(bright)FOXP3(+) T cells. Flow cytometry analysis showed increased FOXP3 expression in circulating CD4(+)CD25(+)HLA-DR- cells of lung cancer patients compared to control subjects. Immunohistochemical analysis revealed co-expression of TGF-beta, COX-2, and FOXP3 in serial sections from resected lung tumor tissues. All together these observations suggest interplay between TGF-beta and COX-2 in the induction of T-reg activities. Interrupting TGF-beta and PGE(2) signaling may be important in therapeutic interventions that aim to limit T-reg function in lung cancer. C1 [Baratelli, Felicita; Lee, Jay M.; Hazra, Saswati; Lin, Ying; Walser, Tonya C.; Schaue, Dorthe; Pak, Peter S.; Elashoff, David; Zhang, Ling; Sharma, Sherven; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, UCLA Lung Canc Res Program, Los Angeles, CA 90095 USA. [Baratelli, Felicita; Hazra, Saswati; Lin, Ying; Walser, Tonya C.; Pak, Peter S.; Sharma, Sherven; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Lee, Jay M.; Pak, Peter S.; Zhang, Ling] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. [Schaue, Dorthe] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Elashoff, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. [Fishbein, Michael C.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Reckamp, Karen] City Hope Natl Med Ctr, Dept Hematol, Duarte, CA USA. [Reckamp, Karen] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA USA. [Sharma, Sherven; Dubinett, Steven M.] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. RP Lee, JM (reprint author), Ronald Reagan UCLA Med Ctr, Sect Thorac Surg, Div Cardiothorac Surg, CHS, Box 957313,Room 64-128,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jay-moonlee@mednet.ucla.edu FU National Institutes of Health [CA-16042, AI-28697, R01 CA111851]; Jonsson Comprehensive Cancer Center; UCLA AIDS Institute; David Geffen School of Medicine at UCLA; UCLA Lung Cancer SPORE [P50 CA90388, 5K12CA076095, 1K23CA131577]; UC Tobacco Related Research Program; Department of Veteran Affairs; Ronald Binder Memorial Fund for Lung Cancer Research; STOP Cancer; Jonsson Cancer Foundation FX Flow cytometry was performed at the UCLA Jonsson Comprehensive Cancer for AIDS Research Flow Cytometry Core Facility that is supported by the National Institutes of Health awards CA-16042 and AI-28697, Jonsson Comprehensive Cancer Center, UCLA AIDS Institute, and David Geffen School of Medicine at UCLA.; This study was supported by the National Institutes of Health Grants R01 CA111851, UCLA Lung Cancer SPORE P50 CA90388, 5K12CA076095, and 1K23CA131577; UC Tobacco Related Research Program; Merit Review Research Funds from the Department of Veteran Affairs; Ronald Binder Memorial Fund for Lung Cancer Research; STOP Cancer; and Jonsson Cancer Foundation. NR 46 TC 30 Z9 32 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2010 VL 2 IS 4 BP 356 EP 367 PG 12 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28QD UT WOS:000208694400002 PM 20733946 ER PT J AU Hirohashi, T Chase, CM Alessandrini, A Colvin, RB Russell, PS Madsen, JC AF Hirohashi, Tsutomu Chase, Catharine M. Alessandrini, Alessandro Colvin, Robert B. Russell, Paul S. Madsen, Joren C. TI Relationship between NK Cells, Regulatory T Cells, and Effector T Cells in the Development of Coronary Allograft Vasculopathy (CAV) in Mouse Heart Transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Hirohashi, Tsutomu; Chase, Catharine M.; Alessandrini, Alessandro; Russell, Paul S.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, MGH Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 14 BP 4 EP 4 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600014 ER PT J AU Aoyama, A Ng, CY Millington, TM Boskovic, S Wain, JC Madsen, JC Kawai, T Allan, JS AF Aoyama, Akihiro Ng, Choo Y. Millington, Timothy M. Boskovic, Svjetlan Wain, John C. Madsen, Joren C. Kawai, Tatsuo Allan, James S. TI Non-Human Primate Lung Allografts Show Enhanced Immunogenicity as Compared to Analogous Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Aoyama, Akihiro; Ng, Choo Y.; Millington, Timothy M.; Boskovic, Svjetlan; Wain, John C.; Madsen, Joren C.; Kawai, Tatsuo; Allan, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 20 BP 5 EP 5 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600020 ER PT J AU Graham, JA Fray, MA de Haseth, S Lee, KM Lian, MM Chase, CM Madsen, JC Markmann, JF Benichou, G Colvin, RB Cosimi, AB Deng, SP Alessandrini, AA AF Graham, Jay A. Fray, Michael A. de Haseth, Stephanie Lee, Kang-Mi Lian, Moh-Moh Chase, Catharine M. Madsen, Joren C. Markmann, James F. Benichou, Gilles Colvin, Robert B. Cosimi, A. B. Deng, Shaoping Alessandrini, Alessandro A. TI Inhibition of the Kinase, GSK-3beta, Potentiates the Suppressive Function of Regulatory T Cells by Decreasing Cellular Death SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Graham, Jay A.; Fray, Michael A.; de Haseth, Stephanie; Lee, Kang-Mi; Lian, Moh-Moh; Chase, Catharine M.; Madsen, Joren C.; Markmann, James F.; Benichou, Gilles; Colvin, Robert B.; Cosimi, A. B.; Deng, Shaoping; Alessandrini, Alessandro A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 38 BP 9 EP 9 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600035 ER PT J AU Miyajima, M Chase, CM Graham, JA Farkash, EA Alessandrini, A Madsen, JC Russell, PS Colvin, RB AF Miyajima, Masahiro Chase, Catharine M. Graham, Jay A. Farkash, Evan A. Alessandrini, Alessandro Madsen, Joren C. Russell, Paul S. Colvin, Robert B. TI Spontaneous Renal Allograft Acceptance in Mice Requires Foxp3 Cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Miyajima, Masahiro; Chase, Catharine M.; Graham, Jay A.; Farkash, Evan A.; Alessandrini, Alessandro; Madsen, Joren C.; Russell, Paul S.; Colvin, Robert B.] Massachusetts Gen Hosp, Transplantat Unit, Pathol Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 40 BP 10 EP 10 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600037 ER PT J AU Porcheray, F DeVito, J Saidman, SL Yeap, B Girouard, TC Paine, R Xue, LX Dargon, I Colvin, RB Wong, WC Zorn, E AF Porcheray, Fabrice DeVito, Julie Saidman, Susan L. Yeap, Beow Girouard, Timothy C. Paine, Rosemary Xue, Lixuan Dargon, Ian Colvin, Robert B. Wong, Waichi Zorn, Emmanuel TI Broad Autoantibody Responses in Chronic Humoral Rejection of Human Kidney Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Porcheray, Fabrice; DeVito, Julie; Paine, Rosemary; Xue, Lixuan; Dargon, Ian; Zorn, Emmanuel] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Saidman, Susan L.; Girouard, Timothy C.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yeap, Beow] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wong, Waichi] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 43 BP 11 EP 11 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600040 ER PT J AU Fernandez, ALP Martins, PN Germana, SK Blanc, AL LeGuern, C AF Fernandez, Anne-Luis P. Martins, Paulo N. Germana, Sharon K. Blanc, Anne-Laurence LeGuern, Christian TI Embryonic Stem Cell-Based Therapy for Transplantation Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Fernandez, Anne-Luis P.; Martins, Paulo N.; Germana, Sharon K.; Blanc, Anne-Laurence; LeGuern, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 48 BP 12 EP 12 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600043 ER PT J AU Germana, S Fernandez, L Martins, P Goldstein, K Denaro, M Hehir, K Down, J Benichou, G LeGuern, C AF Germana, Sharon Fernandez, Luis Martins, Paulo Goldstein, Kaela Denaro, Maria Hehir, Kathleen Down, Julian Benichou, Gilles LeGuern, Christian TI MHC Class II Gene Therapy: A Novel Approach to Donor-Specific Tolerance without Sustained Immunosuppression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Germana, Sharon; Fernandez, Luis; Martins, Paulo; Goldstein, Kaela; Benichou, Gilles; LeGuern, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, TBRC TC, Boston, MA 02115 USA. [Denaro, Maria; Hehir, Kathleen; Down, Julian] Genetix Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 64 BP 16 EP 16 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600059 ER PT J AU Kim, KM Veillette, GR Millington, TM Aoyama, A Meltzer, AJ Sachs, DH Madsen, JC Allan, JS Rosengard, BR AF Kim, Karen M. Veillette, Gregory R. Millington, Timothy M. Aoyama, Akihiro Meltzer, Andrew J. Sachs, David H. Madsen, Joren C. Allan, James S. Rosengard, Bruce R. TI Varying Effects of Donor Brain Death on Lung, Kidney, and Heart Allograft Tolerance in Miniature Swine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Kim, Karen M.; Veillette, Gregory R.; Millington, Timothy M.; Aoyama, Akihiro; Meltzer, Andrew J.; Sachs, David H.; Madsen, Joren C.; Allan, James S.; Rosengard, Bruce R.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 70 BP 17 EP 17 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600064 ER PT J AU Kumar, D Morris, MI Kotton, CN Fischer, SA Michaels, MG Allen, U Blumberg, EA Green, M Humar, A Ison, MG AF Kumar, D. Morris, M. I. Kotton, C. N. Fischer, S. A. Michaels, M. G. Allen, U. Blumberg, E. A. Green, M. Humar, A. Ison, M. G. CA AST Infect Dis Community Practice TI Guidance on Novel Influenza A/H1N1 in Solid Organ Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Guidelines; immunosuppression; pandemic ID STEM-CELL TRANSPLANTATION; VIRUS-INFECTION; PATHOLOGY AB Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS. C1 [Kumar, D.; Humar, A.] Univ Alberta, Edmonton, AB, Canada. [Morris, M. I.] Univ Miami, Miller Sch Med, Div Infect Dis, Miami, FL 33136 USA. [Kotton, C. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fischer, S. A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Michaels, M. G.; Green, M.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Allen, U.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Blumberg, E. A.] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Ison, M. G.] Northwestern Univ, Chicago, IL 60611 USA. RP Kumar, D (reprint author), Univ Alberta, Edmonton, AB, Canada. EM Deepali.kumar@ualberta.ca FU Adamas; Roche; Viropharma; Wyeth; Bristol-Myers Squibb FX D. K., Research support (clinical trial)-Adamas; S. A. F., M. I. M.-none; E. A. B., Research support (clinical trial)-Roche and Viropharma; Consultant-Roche; A. H., Research support-Roche; M. G. I., Research support-Roche (Oseltamivir), Adamas (TCAD), BioCryst (peramivir); M. G. M., Research support-Roche (Oseltamivir); M. G., Research support (clinical trial)-Wyeth; Consultant-Roche, Bristol-Myers Squibb; C. N. K., Research support-Wyeth; U. A., Research support-Roche; Advisory Board, Roche. NR 20 TC 87 Z9 89 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 IS 1 BP 18 EP 25 DI 10.1111/j.1600-6143.2009.02960.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 534FP UT WOS:000272882000007 PM 19958321 ER PT J AU Millington, TM Tena, A Boskovic, S Kawai, T Wain, J Allan, JS Sachs, DH Madsen, JC AF Millington, Timothy M. Tena, Aseda Boskovic, Svjetlan Kawai, Tatsuo Wain, John Allan, James S. Sachs, David H. Madsen, Joren C. TI Regeneration of Naive T-Lymphocytes from Heart-Thymus Grafts Occurs at a Low Level and Is Associated with Prolonged Survival but Not Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplantat, ASE C1 [Millington, Timothy M.; Tena, Aseda; Boskovic, Svjetlan; Kawai, Tatsuo; Wain, John; Allan, James S.; Sachs, David H.; Madsen, Joren C.] Massachusetts Gen Hosp, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 80 BP 19 EP 19 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600073 ER PT J AU Millington, TM Aoyama, A Boskovic, S Allan, JS Benichou, G Kawai, T Cosimi, B Sachs, DH Madsen, JC AF Millington, Timothy M. Aoyama, Akihiro Boskovic, Svjetlan Allan, James S. Benichou, Gilles Kawai, Tatsuo Cosimi, Benedict Sachs, David H. Madsen, Joren C. TI Cardiac Allograft Survival Is Prolonged by the Induction of Mixed Hematopoietic Chimerism Two Months after Heart Transplant SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplantat, ASE C1 [Millington, Timothy M.; Aoyama, Akihiro; Boskovic, Svjetlan; Allan, James S.; Benichou, Gilles; Kawai, Tatsuo; Cosimi, Benedict; Sachs, David H.; Madsen, Joren C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 79 BP 19 EP 19 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600072 ER PT J AU Tocco, G Kant, CD Kim, P Connolly, SE Shea, S Lin, C Yun, SH Benichou, G AF Tocco, Georges Kant, Cavit D. Kim, Pilhan Connolly, Sarah E. Shea, Susan Lin, Charles Yun, Seok-Hyun Benichou, Gilles TI Skin Graft Rejection: Direct or Semi-Direct Allorecognition? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Tocco, Georges; Kant, Cavit D.; Connolly, Sarah E.; Shea, Susan; Benichou, Gilles] Harvard Univ, Massachusetts Gen Hosp, Surg Transplant Ctr, Boston, MA 02115 USA. [Kim, Pilhan; Lin, Charles; Yun, Seok-Hyun] Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 76 BP 19 EP 19 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600070 ER PT J AU Millington, TM Boenisch, O Boskovic, S Najafian, N Sayegh, M Madsen, JC AF Millington, Timothy M. Boenisch, Olaf Boskovic, Svjetlan Najafian, Nader Sayegh, Mohamed Madsen, Joren C. TI Expansion of CD4+CD25+FoxP3+Regulatory T Lymphocytes with Low-Dose Anti-Thymocyte Globulin Leads to Prolonged Survival of Cardiac Allografts but Not Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Millington, Timothy M.; Boskovic, Svjetlan; Madsen, Joren C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boenisch, Olaf; Najafian, Nader; Sayegh, Mohamed] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 82 BP 20 EP 20 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600075 ER PT J AU Wong, WC Devito, J Nguyen, H Sarracino, D Porcheray, F Dargon, I Della Pelle, P Collins, AB Smith, RN Tolkoff-Rubin, N Colvin, R Zorn, E AF Wong, Waichi Devito, Julie Nguyen, Hoa Sarracino, David Porcheray, Fabrice Dargon, Ian Della Pelle, Patricia Collins, A. Bernard Smith, Rex Neal Tolkoff-Rubin, Nina Colvin, Robert Zorn, Emmanuel TI Chronic Humoral Rejection of Human Kidney Allografts Is Associated with Matrix Metalloproteinase-2 Accumulation in Glomeruli and Its Release in the Urine SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American-Society-of-Transplantation Annual Scientific Exchange CY DEC 03-06, 2009 CL Orlando, FL SP Amer Soc Transplatat, ASE C1 [Wong, Waichi; Devito, Julie; Nguyen, Hoa; Sarracino, David; Porcheray, Fabrice; Dargon, Ian; Della Pelle, Patricia; Collins, A. Bernard; Smith, Rex Neal; Tolkoff-Rubin, Nina; Colvin, Robert; Zorn, Emmanuel] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 2 MA 152 BP 35 EP 35 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 544KD UT WOS:000273654600131 ER PT J AU Hanto, R Pavlakis, M Saidman, S Delmonico, FL AF Hanto, Ruthanne Pavlakis, Martha Saidman, Susan Delmonico, Francis L. TI Tracking Declines of Paired Donation Offers Improves Program Efficiency SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons CY JAN 15-17, 2010 CL Ft Lauderdale, FL SP Amer Soc Transplant Surg C1 [Hanto, Ruthanne; Delmonico, Francis L.] New England Organ Bank Inc, Newton, MA USA. [Pavlakis, Martha] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Saidman, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 1 BP 62 EP 62 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 539ZC UT WOS:000273297900061 ER PT J AU Saidi, RF Elias, N Hertl, M Kawai, T Ko, DSC Cosimi, AB AF Saidi, Reza F. Elias, Nahel Hertl, Martin Kawai, Tatsou Ko, Dicken S. C. Cosimi, A. B. TI Pyeloureterostomy or Ureteroneocystostomy in Kidney Transplantation: Is There a Difference? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons CY JAN 15-17, 2010 CL Ft Lauderdale, FL SP Amer Soc Transplant Surg C1 [Saidi, Reza F.; Elias, Nahel; Hertl, Martin; Kawai, Tatsou; Ko, Dicken S. C.; Cosimi, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2010 VL 10 SU 1 BP 65 EP 65 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 539ZC UT WOS:000273297900072 ER PT J AU Castrillo-Viguera, C Grasso, DL Simpson, E Shefner, J Cudkowicz, ME AF Castrillo-Viguera, Carmen Grasso, Daniela L. Simpson, Elizabeth Shefner, Jeremy Cudkowicz, Merit E. TI Clinical significance in the change of decline in ALSFRS-R SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R); outcome measures; clinical trials; regulatory approval ID AMYOTROPHIC-LATERAL-SCLEROSIS; FUNCTIONAL RATING-SCALE; TRIALS AB Our objective was to survey ALS clinicians and researchers regarding what percentage reduction in the ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised) slope they would consider clinically meaningful. A nine-question survey was provided to 65 members of the Northeast ALS Consortium (NEALS). They were asked to rate the clinical relevance of 10-50% changes in decline of the ALSFRS-R slope on a seven-point scale (1-7), where 1='not at all clinically meaningful', 4='somewhat clinically meaningful', and 7='very clinically meaningful'. Ninety per cent of participants rated a 20% change in the decline of the ALSFRS-R score as the percentage in which a somewhat clinically significant change starts to be noted (i.e. score of 4 or higher). All participants endorsed a 25% or higher change in the ALSFRS-R score as at least somewhat clinically meaningful (score of 4 or higher). Ninety-three per cent of the participants viewed a 50% change in decline as very clinically meaningful (score of 7). This survey demonstrated that the majority of clinicians and clinical researchers surveyed believe that a therapy that resulted in a change of 20% or greater in the slope of the ALSFRS-R would be clinically meaningful.25 mm) are at increased risk of globe perforation during performance of intraconal (retrobulbar) eye block. These patients often require glasses or contact lenses for myopia (nearsightedness) as children or young adults. A history of early correction for myopia might, therefore, be a predictor of long AL eyes. One hundred one patients undergoing cataract surgery had AL measured and answered questions about their use of corrective lenses. We found that a history of correction for myopia as a child or young adult was 82%, sensitive and 84% specific for having a measured AL >= 25 mm. Patients with this history may be at increased risk for globe perforation during intraconal block. (Anesth Analg 2010:110:119-21) C1 [Bayes, Joseph] Harvard Univ, Dept Anesthesia, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Rosow, Carl E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Bayes, J (reprint author), Harvard Univ, Dept Anesthesia, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM joseph_bayes@meei.harvard.edu FU Departmental Funds FX Supported by Departmental Funds. NR 8 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2010 VL 110 IS 1 BP 119 EP 121 DI 10.1213/ane.0b013e3181a49cae PG 3 WC Anesthesiology SC Anesthesiology GA 538OL UT WOS:000273193700020 PM 19617586 ER PT J AU Stone, ME Meyer, MR Alston, TA AF Stone, Martha E. Meyer, Marlene R. Alston, Theodore A. TI Elton Romeo Smilie, the Not-Quite Discoverer of Ether Anesthesia SO ANESTHESIA AND ANALGESIA LA English DT Article AB Like William T.G. Morton, Elton Romeo Smilie (1819-1889) was raised in Massachusetts, attended medical school in New England, practiced dentistry there, strove for clinical invention, and moved to Boston. In October 1846, both announced that inhaled ethereal preparations achieved reversible insensibility in surgical patients. Smilie published a report in the Boston Med Surg J 3 wk before Bigelow used that forum to broadcast Morton's Ether Day. Smilie's preparation was an ethereal tincture of opium, and, as he mistakenly believed the opium to be volatile and important, he ceded priority to Morton for ether anesthesia. The two authors collaborated on chloroform, but Smilie soon headed off in the Gold Rush to California. It is tempting to speculate that Charles T. Jackson and Morton were indebted in part to Smilie. (Anesth Analg 2010;110:195-7) C1 [Meyer, Marlene R.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Stone, Martha E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Treadwell Lib, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM talston@partners.org NR 43 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2010 VL 110 IS 1 BP 195 EP 197 DI 10.1213/ane.0b013e3181af7f9a PG 3 WC Anesthesiology SC Anesthesiology GA 538OL UT WOS:000273193700032 PM 19713261 ER PT J AU Cooper, JB Murray, D AF Cooper, Jeffrey B. Murray, David TI Simulation Training and Assessment A More Efficient Method to Develop Expertise than Apprenticeship SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Murray, David] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. RP Cooper, JB (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM jcooper@partners.org OI Murray, David/0000-0001-6264-3210 NR 4 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2010 VL 112 IS 1 BP 8 EP 9 PG 2 WC Anesthesiology SC Anesthesiology GA 540EP UT WOS:000273314200004 PM 19952719 ER PT J AU Frullano, L Catana, C Benner, T Sherry, AD Caravan, P AF Frullano, Luca Catana, Ciprian Benner, Thomas Sherry, A. Dean Caravan, Peter TI Bimodal MR-PET Agent for Quantitative pH Imaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE gadolinium imaging agents magnetic resonance imaging; pH imaging positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; CONTRAST AGENTS; BRAIN C1 [Frullano, Luca; Catana, Ciprian; Benner, Thomas; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sherry, A. Dean] Univ Texas Dallas, Dept Chem, Dallas, TX 75230 USA. [Sherry, A. Dean] Adv Imaging Res Ctr, Dallas, TX USA. RP Caravan, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. FU National Institute of Biomedical Imaging and Bioengineering [R21EB009738] FX This research was supported in part by the National Institute of Biomedical Imaging and Bioengineering, R21EB009738 MR-PET = magnetic resonance positron emission tomography NR 25 TC 71 Z9 72 U1 1 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2010 VL 49 IS 13 BP 2382 EP 2384 DI 10.1002/anie.201000075 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 579LU UT WOS:000276372900021 PM 20191650 ER PT J AU Devaraj, NK Hilderbrand, S Upadhyay, R Mazitschek, R Weissleder, R AF Devaraj, Neal K. Hilderbrand, Scott Upadhyay, Rabi Mazitschek, Ralph Weissleder, Ralph TI Bioorthogonal Turn-On Probes for Imaging Small Molecules inside Living Cells SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bioorthogonal; reactions; cycloaddition; fluorogenic tags; imaging; tetrazine ID COPPER(I)-CATALYZED AZIDE-ALKYNE; CLICK CHEMISTRY; STAUDINGER LIGATION; FLUORESCENT TAXOIDS; CANCER-CELLS; COPPER-FREE; CYCLOADDITION; SYSTEMS; ABSENCE; DYE C1 [Devaraj, Neal K.; Hilderbrand, Scott; Upadhyay, Rabi; Mazitschek, Ralph; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Richard B Simches Res Ctr, 185 Cambridge St,Suite 5 210, Boston, MA 02114 USA. RI Mazitschek, Ralph/E-3741-2013; Devaraj, Neal/B-4712-2014 OI Mazitschek, Ralph/0000-0002-1105-689X; FU NIH [U01-HL080731, T32-CA79443, P50-CA86355, RO1-EB010011] FX We thank Dr Justin Ragains for helpful advice and Alex Chudnovsky for assistance with tissue culture This research was supported in part by NIH grants U01-HL080731, T32-CA79443, P50-CA86355, and RO1-EB010011 NR 42 TC 161 Z9 161 U1 13 U2 120 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2010 VL 49 IS 16 BP 2869 EP 2872 DI 10.1002/anie.200906120 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 589FE UT WOS:000277131200007 PM 20306505 ER PT J AU Eberlin, LS Dill, AL Golby, AJ Ligon, KL Wiseman, JM Cooks, RG Agar, NYR AF Eberlin, Livia S. Dill, Allison L. Golby, Alexandra J. Ligon, Keith L. Wiseman, Justin M. Cooks, R. Graham Agar, Nathalie Y. R. TI Discrimination of Human Astrocytoma Subtypes by Lipid Analysis Using Desorption Electrospray Ionization Imaging Mass Spectrometry SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE gliomas; imaging techniques; molecular pathology; phospholipids; tissue analysis ID HUMAN GLIOMAS; BRAIN-TISSUE; IN-VIVO; PROFILES; EXTRACTS C1 [Eberlin, Livia S.; Dill, Allison L.; Cooks, R. Graham] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Eberlin, Livia S.; Dill, Allison L.; Cooks, R. Graham] Purdue Univ, Ctr Analyt Instrumentat & Dev, W Lafayette, IN 47907 USA. [Golby, Alexandra J.; Ligon, Keith L.; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg,Dept Radiol, Boston, MA 02115 USA. [Golby, Alexandra J.; Ligon, Keith L.; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. [Golby, Alexandra J.; Ligon, Keith L.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wiseman, Justin M.] Prosolia Inc, Indianapolis, IN 46202 USA. RP Cooks, RG (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM cooks@purdue.edu; nagar@bwh.harvard.edu RI Cooks, R/G-1051-2015 OI Cooks, R/0000-0002-9581-9603 FU U.S. National Institutes of Health [1R21EB009459-01]; Brain Science Foundation; Daniel E. Ponton Fund for the Neurosciences; Indiana 21st Century Research and Technology Fund FX This work was supported by the U.S. National Institutes of Health (Grant 1R21EB009459-01) to L.S.E., A.L.D. and R.G.C., and by grants from the Brain Science Foundation, and the Daniel E. Ponton Fund for the Neurosciences to N.Y.R.A. Prosolia acknowledges support from the Indiana 21st Century Research and Technology Fund (J.M.W.). We gratefully acknowledge the assistance of Kristen K. Gill for tissue banking at BWH and Jessica Li of Prosolia for assistance in DESI-MS experiments. NR 24 TC 59 Z9 61 U1 1 U2 38 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2010 VL 49 IS 34 BP 5953 EP 5956 DI 10.1002/anie.201001452 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 641DT UT WOS:000281105600026 PM 20602384 ER PT J AU Popovic, Z Liu, WH Chauhan, VP Lee, J Wong, C Greytak, AB Insin, N Nocera, DG Fukumura, D Jain, RK Bawendi, MG AF Popovic, Zoran Liu, Wenhao Chauhan, Vikash P. Lee, Jungmin Wong, Cliff Greytak, Andrew B. Insin, Numpon Nocera, Daniel G. Fukumura, Dai Jain, Rakesh K. Bawendi, Moungi G. TI A Nanoparticle Size Series for In Vivo Fluorescence Imaging SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; imaging agents; luminescence; microscopy; nanoparticles ID QUANTUM DOTS; SOLID TUMORS; PARTICLES; TRANSPORT C1 [Popovic, Zoran; Liu, Wenhao; Lee, Jungmin; Wong, Cliff; Greytak, Andrew B.; Insin, Numpon; Nocera, Daniel G.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mgb@mit.edu RI Chauhan, Vikash/H-8172-2013; OI Chauhan, Vikash/0000-0001-9126-2302; Greytak, Andrew/0000-0001-8978-6457 FU U.S. National Cancer Institute [R01-CA126642, R01-CA085140, R01-CA115767, P01-CA080124, R01-CA096915]; MIT-Harvard NIH Center for Cancer Nanotechnology Excellence [1U54-CA119349]; MIT DCIF [CHE-980806, DBI-9729592]; ISN [W911NF-07-D-0004]; NSF-MRSEC [DMR-0117795]; NSF-CRS [CHE-0714189]; NSF FX This research was supported by the U.S. National Cancer Institute grants R01-CA126642 (R.K.J., D.F., M.G.B., and D.G.N.), R01-CA085140, R01-CA115767 (R.K.J.), P01-CA080124 (R.K.J. and D.F.), R01-CA096915 (D.F.); by the MIT-Harvard NIH Center for Cancer Nanotechnology Excellence (1U54-CA119349) (M.G.B.); by the MIT DCIF (CHE-980806, DBI-9729592); by the ISN (W911NF-07-D-0004) (M.G.B and D.G.N); by the NSF-MRSEC program (DMR-0117795) via the use of its shared user facilities; and by the NSF-CRS (CHE-0714189). W. L. was supported by a NSF Graduate Research Fellowship. A.B.G. was a Novartis Fellow of the Life Sciences Research Foundation. We would like to thank S. Geyer for valuable help with quantum yield measurements and to J. Cui for the help with FCS measurements. NR 24 TC 127 Z9 128 U1 3 U2 96 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2010 VL 49 IS 46 BP 8649 EP 8652 DI 10.1002/anie.201003142 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 678CC UT WOS:000284045400020 PM 20886481 ER PT J AU Yang, HY Sinicropi-Yao, L Chuzi, S Youn, SJ Clain, A Baer, L Chen, Y McGrath, PJ Fava, M Papakostas, GI AF Yang, Huaiyu Sinicropi-Yao, Lara Chuzi, Sarah Youn, Soo Jeong Clain, Alisabet Baer, Lee Chen, Ying McGrath, Patrick J. Fava, Maurizio Papakostas, George I. TI Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine SO ANNALS OF GENERAL PSYCHIATRY LA English DT Article AB Background: Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD. Methods: A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse. Results: The severities of early (P > 0.05), middle (P > 0.05), late (P > 0.05), or total (P > 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (P > 0.05), oversleeping (P > 0.05), napping (P > 0.05), or total (P > 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Conclusion: The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD. C1 [Yang, Huaiyu; Sinicropi-Yao, Lara; Chuzi, Sarah; Youn, Soo Jeong; Clain, Alisabet; Baer, Lee; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02115 USA. [Chen, Ying; McGrath, Patrick J.] Columbia Univ, New York State Psychiat Inst, Depress Evaluat Serv Ctr, New York, NY USA. RP Yang, HY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02115 USA. EM huaiyuy@stanford.edu RI McGrath, Patrick/I-6410-2013; Papakostas, George/I-6905-2013 OI McGrath, Patrick/0000-0001-7217-7321; Papakostas, George/0000-0002-2465-5103 FU National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; New York State Department of Mental Hygiene; NARSAD; NARSAD, Research Foundation for Mental Hygiene ( New York State); GlaxoSmithKline; Eli Lilly; Organon and Lipha Pharmaceuticals; Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb Company; Cephalon; Eli Lilly Company; Forest Pharmaceuticals Inc; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon Inc; PamLab; LLC; Pfizer Inc; Pharmavite; Roche; Sanofi Aventis; Solvay Pharmaceuticals, Inc.; Synthelabo FX HY, LSY, SC, SJY, YC, AC, and LB declare that they have no competing interests. PJM has received research support from the National Institute of Mental Health, National Institute on Alcohol Abuse and Alcoholism, New York State Department of Mental Hygiene, NARSAD, Research Foundation for Mental Hygiene ( New York State), GlaxoSmithKline, Eli Lilly, Organon and Lipha Pharmaceuticals, and has worked in an advisory/consulting capacity for GlaxoSmithKline, Somerset Pharmaceuticals, Novartis Pharmaceuticals ( 2008), Sanofi Aventis ( 2007) and Roche ( 2008), MF has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi Aventis, Solvay Pharmaceuticals, Inc. and Synthelabo, Wyeth-Ayerst Laboratories, has worked in an advisory/consulting capacity for Abbott Laboratories, Amarin, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc., Biovail Pharmaceuticals, Inc., BrainCells, Inc. Bristol- Myers Squibb Company, Cephalon, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly & Company, EPIX Pharmaceuticals, Fabre- Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lorex Pharmaceuticals, Lundbeck, MedAvante, Inc., Merck, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi Aventis, Sepracor, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, Transcept Pharmaceuticals, Vanda Pharmaceuticals Inc, Wyeth-Ayerst Laboratories, has been a speaker for AstraZeneca, Boehringer- Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Novartis, Organon Inc., Pfizer Inc, PharmaStar, Primedia, Reed- Elsevier and WyethAyerst Laboratories, has equity holdings in Compellis and MedAvante, and has the following royalties/ patents or other income: patent applications for SPCD and for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ, DESS, and SAFER. GIP has served as a consultant to Bristol- Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre, Shire and Wyeth, has received honoraria from Bristol- Myers Squibb, Eli Lilly, Evotec, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Pamlab, Pfizer, Pierre Fabre, Shire, Titan Pharmaceuticals and Wyeth, has received research support from Bristol- Myers Squibb, Forest, National Institute of Mental Health, Pamlab, Pfizer and Precision Human Biolaboratories, and has served on the speakers bureau for Bristol- Myers Squibb and Pfizer. NR 31 TC 4 Z9 6 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-859X J9 ANN GEN PSYCHIATR JI Ann. Gen. Psychiatr. PY 2010 VL 9 AR 10 DI 10.1186/1744-859X-9-10 PG 5 WC Psychiatry SC Psychiatry GA V27IF UT WOS:000208606200010 PM 20187924 ER PT J AU Staley, KJ AF Staley, Kevin J. TI Trauma, Hypoxia and Seizures Induce NKCC1-Dependent Changes in Neuronal GABA Response and Anticonvulsant Efficacy SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Child-Neurology-Society CY OCT 13-16, 2010 CL Providence, RI SP Child Neurol Soc C1 [Staley, Kevin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2010 VL 68 IS 4 SU 14 BP S1 EP S1 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670CP UT WOS:000283398800003 ER PT J AU Magnani, JW Mazzini, MJ Sullivan, LM Williamson, M Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Mazzini, Michael J. Sullivan, Lisa M. Williamson, MaryAnn Ellinor, Patrick T. Benjamin, Emelia J. TI P-Wave Indices, Distribution and Quality Control Assessment (from the Framingham Heart Study) SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiogram; P waves; reproducibility; epidemiology ID PAROXYSMAL ATRIAL-FIBRILLATION; LEFT-VENTRICULAR HYPERTROPHY; YOUNG HEALTHY-MEN; INTERATRIAL BLOCK; DIASTOLIC DYSFUNCTION; OBESE SUBJECTS; SINUS RHYTHM; QT INTERVAL; WEIGHT-LOSS; DISPERSION AB Background: P-wave indices of maximum P-wave duration and P-wave dispersion have been examined in a broad array of cardiovascular and noncardiovascular disease states. The P-wave indices literature has been highly heterogeneous in measurement methodologies, described quality control metrics, and distribution of values. We therefore sought to determine the reproducibility of P-wave indices in a community-based cohort. Methods: P-wave indices were measured in sequential subjects enrolled in the Framingham Heart Study. Electrocardiograms were obtained at the 11th biennial visit of the Original Cohort (n = 250) and the initial visit of the Offspring Cohort (n = 252). We determined the mean P-wave durations, interlead correlations, and P-wave indices. We then chose 20 ECGs, 10 from each cohort, and assessed intrarater and interrater variability. Results: The maximum P-wave duration ranged from 71 to 162 ms with mean of 112 +/- 12 ms. The minimum P-wave duration ranged from 35 to 103 ms with mean of 65 +/- 10 ms. P-wave dispersion ranged from 12 to 82 ms. The mean P-wave dispersion was 48 +/- 12 ms (40-56). The intrarater intraclass correlation coefficient (ICC) was r = 0.80 for maximum P-wave duration and r = 0.82 for P-wave dispersion. The interrater ICC was 0.56 for maximum P-wave duration and 0.70 for P-wave dispersion. Conclusions: We demonstrated excellent intrarater reproducibility and fair interrater reproducibility for calculating P-wave indices. Reproducibility is frequently lacking in studies of P-wave indices, but is an essential component for the field's growth and epidemiologic contribution. Ann Noninvasive Electrocardiol 2010;15(1):77-84 C1 [Magnani, Jared W.; Mazzini, Michael J.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Framingham, MA 01702 USA. [Williamson, MaryAnn] Sch Publ Hlth, Div Med, Boston, MA USA. [Benjamin, Emelia J.] Sch Publ Hlth, Whitaker Cardiovasc Inst, Boston, MA USA. [Sullivan, Lisa M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Benjamin, Emelia J.] NHLBI, Framingham Study, Framingham, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med & Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028] FX This research was supported by an American Heart Association award 09FTF2190028. NR 48 TC 12 Z9 15 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JAN PY 2010 VL 15 IS 1 BP 77 EP 84 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 546OW UT WOS:000273821100012 PM 20146786 ER PT J AU McFarland, LV AF McFarland, Lynne V. TI Probiotics and Diarrhea SO ANNALS OF NUTRITION AND METABOLISM LA English DT Article; Proceedings Paper CT Scientific Symposium on Probiotics in Health and Disease - What Is the Scientific Evidence CY DEC 11, 2009 CL Frankfurt, GERMANY C1 [McFarland, Lynne V.] VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. [McFarland, Lynne V.] Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov NR 5 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2010 VL 57 SU 1 BP 10 EP 11 DI 10.1159/000309016 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 648BH UT WOS:000281664900003 PM 20829585 ER PT J AU Camidge, DR Christensen, J Bang, YJ Shaw, AT Costa, DB Salgia, R Dezube, BJ Shapiro, GI Janne, PA Maki, RG Solomon, B Kwak, EL Tan, W Shreeve, SM Wilner, KD Clark, WJ Iafrate, AJ AF Camidge, D. R. Christensen, J. Bang, Y. J. Shaw, A. T. Costa, D. B. Salgia, R. Dezube, B. J. Shapiro, G. I. Janne, P. A. Maki, R. G. Solomon, B. Kwak, E. L. Tan, W. Shreeve, S. M. Wilner, K. D. Clark, W. J. Iafrate, A. J. TI ALK GENE REARRANGEMENTS AND THE DEVELOPMENT OF PF-02341066 IN NSCLC SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Camidge, D. R.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Christensen, J.; Tan, W.; Shreeve, S. M.; Wilner, K. D.] Pfizer, San Diego, CA USA. [Bang, Y. J.] Seoul Natl Univ, Seoul, South Korea. [Shaw, A. T.; Kwak, E. L.; Iafrate, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Costa, D. B.; Dezube, B. J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Salgia, R.] Univ Chicago, Chicago, IL 60637 USA. [Shapiro, G. I.; Janne, P. A.; Clark, W. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Maki, R. G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, B.] Peter MacCallum Canc Ctr, Melbourne, Australia. NR 0 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800033 ER PT J AU Shapiro, GI AF Shapiro, G. I. TI PRECLINICAL AND CLINICAL DEVELOPMENT OF CYCLIN-DEPENDENT KINASE AND CHECKPOINT KINASE INHIBITORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 27 EP 27 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800049 ER PT J AU Driscoll, J Gootenberg, J Amin, S Pelluru, D Avet-Loiseau, H Minville, S Anderson, K Munshi, N Annunziata, C AF Driscoll, J. Gootenberg, J. Amin, S. Pelluru, D. Avet-Loiseau, H. Minville, S. Anderson, K. Munshi, N. Annunziata, C. TI THE UBIQUITIN LIGASE RNF4 IS INDUCED IN MULTIPLE MYELOMA, PROMOTES BORTEZOMIB RESISTANCE AND INTEGRATES THE SUMOYLATION, UBIQUITINATION AND PROTEASOME PATHWAYS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 8th International Symposium on Targeted Anticancer Therapies CY MAR 04-06, 2010 CL Bethesda, MD C1 [Driscoll, J.; Gootenberg, J.; Annunziata, C.] NCI, NIH, Bethesda, MD 20892 USA. [Amin, S.; Pelluru, D.; Avet-Loiseau, H.; Anderson, K.; Munshi, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minville, S.] Hematol Lab, Nantes, France. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2010 VL 21 SU 2 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA 590OZ UT WOS:000277237800050 ER PT J AU Wang, LM Wong, M Lightwood, JM Cheng, CM AF Wang, Lorraine M. Wong, Maple Lightwood, James M. Cheng, Christine M. TI Black Box Warning Contraindicated Comedications: Concordance Among Three Major Drug Interaction Screening Programs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE black box warning; drug interaction; drug interaction screening program ID PERSONAL DIGITAL ASSISTANT; MEDICATIONS; SUICIDALITY; DEPRESSION; DATABASES; COMPENDIA; SOFTWARE; SSRIS; ALPHA; RISK AB BACKGROUND: Black box warnings represent the strongest safety warning that the Food and Drug Administration can issue for a marketed prescription drug. Some black box warnings recommend against coadministration of specific medications due to an increased risk for serious, perhaps life-threatening, effects. OBJECTIVE: To determine the level of agreement in presence, clinical severity scores level of documentation ratings, and alert content among 3 leading drug interaction screening programs with regard to contraindicated comedications that are mentioned in black box warnings. METHODS: We reviewed the prescribing information for currently marketed prescription drugs with a black box warning that mentioned a contraindicated drug combination. We selected the drug interaction databases Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Comp Lexi-Interact to evaluate the interactions. Discrepancies in the inclusion of interactions and level of agreement in clinical severity scores and level of documentation ratings for each interaction were assessed, using descriptive statistics, Spearman's correlation coefficient, Kendall-Stuart tau-c, and Cronbach's alpha. RESULTS: We identified 11 drugs with black box warnings that contained information on 59 unique contraindicated drug combinations, only 68% of which were covered by any source. Lexi-Comp detected the most interactions (n = 29) and DRUG-REAX the least (n = 18). Only 3 drug combinations were detected and rated as contraindicated or potentially life-threatening in all 3 databases. The severity scores and level of documentation ratings varied widely. CONCLUSIONS: There are discrepancies among major drug interaction screening programs in the inclusion, severity, and level of documentation of contraindicated drug combinations mentioned in black box warnings. Further studies could explore the implications of these inconsistencies, particularly with regard to the integration of black box warning information in clinical practice. Clinicians should consult multiple drug resources to maximize the potential for detecting a potentially severe drug interaction. C1 [Wang, Lorraine M.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. [Wong, Maple] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Cheng, Christine M.] Univ Calif San Francisco, Dept Clin Pharm, Medicat Outcomes Ctr, San Francisco, CA 94143 USA. RP Cheng, CM (reprint author), 521 Parnassus Ave,C-152,Box 0622, San Francisco, CA 94143 USA. EM Chengc@pharmacy.ucsf.edu NR 26 TC 37 Z9 37 U1 1 U2 10 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 2010 VL 44 IS 1 BP 28 EP 34 DI 10.1345/aph.1M475 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543ZO UT WOS:000273620900003 PM 20040698 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Erythropoiesis and the Mystery of an Unexplained Survival Benefit SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Care, Boston, MA USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2010 VL 251 IS 1 BP 5 EP 5 DI 10.1097/SLA.0b013e3181c86f40 PG 1 WC Surgery SC Surgery GA 538SF UT WOS:000273203600002 PM 19934753 ER PT J AU Wang, JP Kulaylat, M Hassett, J Dunn, KB Dayton, M Rockette, H Rajput, A AF Wang, Jiping Kulaylat, Mahmoud Hassett, James Dunn, Kelli Bullard Dayton, Merril Rockette, Howard Rajput, Ashwani TI Should Total Number of Lymph Nodes be Used as a Quality of Care Measure for Stage III Colon Cancer? Reply SO ANNALS OF SURGERY LA English DT Letter ID COLORECTAL-CANCER; RESECTION; RATIO C1 [Wang, Jiping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. [Wang, Jiping] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. [Kulaylat, Mahmoud; Hassett, James; Dunn, Kelli Bullard; Dayton, Merril] SUNY Buffalo, Dept Surg, Buffalo, NY USA. [Rockette, Howard] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Dunn, Kelli Bullard] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Rajput, Ashwani] Univ New Mexico, Hlth Sci Ctr, Dept Surg, Albuquerque, NM 87131 USA. RP Wang, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. EM jwang39@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2010 VL 251 IS 1 BP 184 EP 185 PG 2 WC Surgery SC Surgery GA 538SF UT WOS:000273203600037 ER PT J AU Karlson, EW Chang, SC Cui, J Chibnik, LB Fraser, PA De Vivo, I Costenbader, KH AF Karlson, E. W. Chang, S-C Cui, J. Chibnik, L. B. Fraser, P. A. De Vivo, I. Costenbader, K. H. TI Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CYCLIC CITRULLINATED PEPTIDE; POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; ALCOHOL-CONSUMPTION; BREAST-CANCER; NURSES HEALTH; RISK-FACTORS; SUSCEPTIBILITY; ANTIBODIES; ALLELES AB Background: Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the interaction between heavy smoking and the HLA-SE was conducted. Methods: Blood was obtained from 32 826 women in the Nurses' Health Study and 29 611 women in the Nurses' Health Study II. Incident RA diagnoses were validated by chart review. Controls were matched for age, menopausal status and postmenopausal hormone use. High-resolution HLA-DRB1 genotyping was performed for SE alleles. HLA-SE, smoking, HLA-SE* smoking interactions and RA risk, were assessed using conditional logistic regression models, adjusted for age and reproductive factors. Additive and multiplicative interactions were tested. Results: In all, 439 Caucasian matched pairs were included. Mean age at RA diagnosis was 55.2 years; 62% of cases were seropositive. A modest additive interaction was observed between ever smoking and HLA-SE in seropositive RA risk. A strong additive interaction (attributable proportion due to interaction (AP) = 0.50; p<0.001) and significant multiplicative interaction (p=0.05) were found between heavy smoking (>10 pack-years) and any HLA-SE in seropositive RA risk. The highest risk was in heavy smokers with double copy HL-ASE (odds ratio (OR) 7.47, 95% CI 2.77 to 20.11). Conclusions: A strong gene-environment interaction was observed between HLA-SE and smoking when stratifying by pack-years of smoking rather than by ever smoking. Future studies should assess cumulative exposure to cigarette smoke when testing for genesmoking interactions. C1 [Karlson, E. W.; Cui, J.; Chibnik, L. B.; Fraser, P. A.; Costenbader, K. H.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Karlson, E. W.; Cui, J.; Chibnik, L. B.; Fraser, P. A.; Costenbader, K. H.] Harvard Univ, Sch Med, Boston, MA USA. [Chang, S-C; De Vivo, I.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fraser, P. A.] Immune Dis Inst, Boston, MA USA. [Fraser, P. A.] Genzyme Corp, Boston, MA USA. [De Vivo, I.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Karlson, EW (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM ekarlson@partners.org FU NIH [R01 AR49880, CA87969, P60 AR047782, K24 AR0524-01, BIRCWH K12 HD051959] FX Supported by NIH grants R01 AR49880, CA87969, P60 AR047782, K24 AR0524-01 and BIRCWH K12 HD051959 (supported by NIMH, NIAID, NICHD and OD). KHC is the recipient of an Arthritis Foundation/American College of Rheumatology Arthritis Investigator Award and a Katherine Swan Ginsburg Memorial Award. NR 37 TC 95 Z9 95 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2010 VL 69 IS 1 BP 54 EP 60 DI 10.1136/ard.2008.102962 PG 7 WC Rheumatology SC Rheumatology GA 530LQ UT WOS:000272594100012 PM 19151010 ER PT J AU Jhun, CS Wenk, JF Zhang, ZH Wall, ST Sun, K Sabbah, HN Ratcliffe, MB Guccione, JM AF Jhun, Choon-Sik Wenk, Jonathan F. Zhang, Zhihong Wall, Samuel T. Sun, Kay Sabbah, Hani N. Ratcliffe, Mark B. Guccione, Julius M. TI Effect of Adjustable Passive Constraint on the Failing Left Ventricle: A Finite-Element Model Study SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIAC SUPPORT DEVICE; CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; MECHANICS; STRESS; HYPERTROPHY; DYSFUNCTION; VARIABLES; PATTERNS; REVERSAL AB Background. Passive constraint is used to prevent left ventricular dilation and subsequent remodeling. However, there has been concern about the effect of passive constraint on diastolic left ventricular chamber stiffness and pump function. This study determined the relationship between constraint, diastolic wall stress, chamber stiffness, and pump function. We tested the hypothesis that passive constraint at 3 mm Hg reduces wall stress with minimal change in pump function. Methods. A three-dimensional finite-element model of the globally dilated left ventricle based on left ventricular dimensions obtained in dogs that had undergone serial intracoronary microsphere injection was created. The model was adjusted to match experimentally observed end-diastolic left ventricular volume and midventricular wall thickness. The experimental results used to create the model were previously reported. A pressure of 3, 5, 7, and 9 mm Hg was applied to the epicardium. Fiber stress, end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, and the stroke volume-end-diastolic pressure (Starling) relationship were calculated. Results. As epicardial constraint pressure increased, fiber stress decreased, the end-diastolic pressure-volume relationship shifted to the left, and the Starling relationship shifted down and to the right. The end-systolic pressure-volume relationship did not change. A constraining pressure of 2.3 mm Hg was associated with a 10% reduction in stroke volume, and mean end-diastolic fiber stress was reduced by 18.3% (inner wall), 15.3% (mid wall), and 14.2% (outer wall). Conclusions. Both stress and cardiac output decrease in a linear fashion as the amount of passive constraint is increased. If the reduction in cardiac output is to be less than 10%, passive constraint should not exceed 2.3 mm Hg. On the other hand, this amount of constraint may be sufficient to reverse eccentric hypertrophy after myocardial infarction. (Ann Thorac Surg 2010; 89: 132- 8) (C) 2010 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. Henry Ford Hosp, Detroit, MI 48202 USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov FU National Institutes of Health [5R01 HL077921, 5R01 HL063348, P41 RR08605] FX This work was supported by grants 5R01 HL077921 (J.M.G.), 5R01 HL063348 (Mark B. Ratcliffe), and P41 RR08605 from the National Institutes of Health. NR 34 TC 16 Z9 16 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 JAN PY 2010 VL 89 IS 1 BP 132 EP + DI 10.1016/j.athoracsur.2009.08.075 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 535AU UT WOS:000272939700020 PM 20103222 ER PT J AU Nehra, D Inglessis, I Gaissert, HA AF Nehra, Deepika Inglessis, Ignacio Gaissert, Henning A. TI Complete Pulmonary Venous Occlusion After Radiofrequency Ablation Reply SO ANNALS OF THORACIC SURGERY LA English DT Letter C1 [Nehra, Deepika; Inglessis, Ignacio; Gaissert, Henning A.] Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. RP Nehra, D (reprint author), Massachusetts Gen Hosp, Thorac Surg Unit, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM hgaissert@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2010 VL 89 IS 1 BP 340 EP 340 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 535AU UT WOS:000272939700071 ER PT S AU Parekkadan, B Milwid, JM AF Parekkadan, Biju Milwid, Jack M. BE Yarmush, ML Duncan, JS Gray, ML TI Mesenchymal Stem Cells as Therapeutics SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 12 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE mesenchymal stem cell; immunotherapy; clinical trials; paracrine; extracorporeal bioreactor; conditioned medium ID HUMAN-BONE-MARROW; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; UMBILICAL-CORD BLOOD; VERSUS-HOST-DISEASE; ACUTE-RENAL-FAILURE; MAJOR HISTOCOMPATIBILITY COMPLEX; HEMATOLOGIC MALIGNANCY PATIENTS; ACUTE MYOCARDIAL-INFARCTION; REGULATORY T-CELLS; 1ST BRANCHIAL ARCH AB Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stern cell therapeutics. C1 [Parekkadan, Biju; Milwid, Jack M.] Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. [Parekkadan, Biju; Milwid, Jack M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Milwid, Jack M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Parekkadan, B (reprint author), Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Boston, MA 02114 USA. EM biju_parekkadan@hms.harvard.edu FU NIBIB NIH HHS [R01 EB012521]; NIDDK NIH HHS [1K01DK087770-01, K01 DK087770] NR 185 TC 238 Z9 263 U1 10 U2 82 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3512-0 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2010 VL 12 BP 87 EP 117 DI 10.1146/annurev-bioeng-070909-105309 PG 31 WC Engineering, Biomedical SC Engineering GA BQO42 UT WOS:000281447400004 PM 20415588 ER PT S AU Irimia, D AF Irimia, Daniel BE Yarmush, ML Duncan, JS Gray, ML TI Microfluidic Technologies for Temporal Perturbations of Chemotaxis SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 12 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE microscale; signal transduction processes; signaling networks; neutrophil ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; DICTYOSTELIUM-DISCOIDEUM AMEBAS; SPATIAL CONCENTRATION GRADIENTS; DYNAMIC CHEMICAL SIGNALS; BACTERIAL CHEMOTAXIS; CELL-MIGRATION; NEUTROPHIL CHEMOTAXIS; EUKARYOTIC CHEMOTAXIS; QUANTITATIVE-ANALYSIS; SINGLE CELLS AB Most cells in the body have the ability to change their physical locations during physiologic or pathologic events such as inflammation, wound healing, Or cancer. When cell migration is directed toward sources of cue chemicals, the process is known as chemotaxis, and it requires linking the sensing of chemicals through receptors on the surfaces of the cells to the directional activation of the motility apparatus inside the cells. This link is supported by complex intracellular signaling pathways, and although details regarding the nature of the molecules involved in the signal transduction are well established, far less is known about how different signaling molecules and processes are dynamically interconnected and how slower and faster signaling events take place simultaneously inside moving cells. In this context, advances in microfluidic technologies are enabling the emergence of new tools that facilitate the development of experimental protocols in which the cellular microenvironment is precisely controlled in time and space and in which signaling-associated changes inside cells can be quantitatively measured and compared. These tools could enable new insights into the intricacies of the biological systems that participate in chemotaxis processes and could have the potential to accelerate the development of novel therapeutic strategies to control cell motility and enhance our abilities for medical intervention during health and disease. C1 [Irimia, Daniel] Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02129 USA. [Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Irimia, D (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NIAID NIH HHS [AI076760, R21 AI076760-01A2, R21 AI076760]; NIBIB NIH HHS [EB002503, P41 EB002503, P41 EB002503-07]; NIGMS NIH HHS [R01 GM092804] NR 138 TC 35 Z9 35 U1 2 U2 33 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3512-0 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2010 VL 12 BP 259 EP 284 DI 10.1146/annurev-bioeng-070909-105241 PG 26 WC Engineering, Biomedical SC Engineering GA BQO42 UT WOS:000281447400011 PM 20450351 ER PT S AU Budin, I Szostak, JW AF Budin, Itay Szostak, Jack W. BE Rees, DC Dill, KA Williamson, JR TI Expanding Roles for Diverse Physical Phenomena During the Origin of Life SO ANNUAL REVIEW OF BIOPHYSICS, VOL 39 SE Annual Review of Biophysics LA English DT Review; Book Chapter DE prebiotic; homochirality; RNA world; thermophoresis; protocell ID TEMPLATE-DIRECTED SYNTHESIS; FATTY-ACID VESICLES; AMINO-ACID; PREBIOTIC SYNTHESIS; FLIP-FLOP; ASYMMETRIC AMPLIFICATION; PHOSPHOLIPID-BILAYERS; MONOCARBOXYLIC ACIDS; PHASE HOMOCHIRALITY; MODEL PROTOCELL AB Recent synthetic approaches to understanding the origin of life have yielded insights into plausible pathways for the emergence of the first cells. Here we review current experiments with implications for the origin of life, emphasizing the ability of unexpected physical processes to facilitate the self-assembly and self-replication of the first biological systems. These laboratory efforts have uncovered novel physical mechanisms for the emergence of homochirality; the concentration and purification of prebiotic building blocks; and the ability of the first cells to assemble, grow, divide, and acquire greater complexity. In the absence of evolved biochemical capabilities, such physical processes likely played an essential role in early biology. C1 [Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Budin, I (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 95 TC 56 Z9 58 U1 2 U2 54 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1936-122X BN 978-0-8243-1839-0 J9 ANNU REV BIOPHYS JI Annu. Rev. Biophys. PY 2010 VL 39 BP 245 EP 263 DI 10.1146/annurev.biophys.050708.133753 PG 19 WC Biophysics SC Biophysics GA BPJ16 UT WOS:000278959400013 PM 20192779 ER PT S AU Auluck, PK Caraveo, G Lindquist, S AF Auluck, Pavan K. Caraveo, Gabriela Lindquist, Susan BE Schekman, R Goldstein, L Lehmann, R TI alpha-Synuclein: Membrane Interactions and Toxicity in Parkinson's Disease SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE protein folding; vesicle trafficking; neurodegeneration ID HSP90 CHAPERONE COMPLEX; GENE-EXPRESSION CHANGES; A30P TRANSGENIC MICE; LEWY BODIES; DROSOPHILA MODEL; SUBSTANTIA-NIGRA; IN-VITRO; NEURODEGENERATIVE DISEASES; ENDOPLASMIC-RETICULUM; MANGANESE TOXICITY AB In the late 1990s, mutations in the synaptic protein alpha-synuclein (alpha-syn) were identified in families with hereditary Parkinson's disease (PD). Rapidly, alpha-syn became the target of numerous investigations that have transformed our understanding of the pathogenesis underlying this disorder. alpha-Syn is the major component of Lewy bodies (LBs), cytoplasmic protein aggregates that form in the neurons of PD patients alpha-Syn interacts with lipid membranes and adopts amyloid conformations that deposit within LBs. Work in yeast and other model systems has revealed that alpha-syn-associated toxicity might be the consequence of abnormal membrane interactions and alterations in vesicle trafficking. Here we review evidence regarding alpha-syn's normal interactions with membranes and regulation of synaptic vesicles as well as how overexpression of alpha-syn yields global cellular dysfunction. Finally, we present a model linking vesicle dynamics to toxicity with the sincere hope that understanding these disease mechanisms will lead to the development of novel, potent therapeutics. C1 [Auluck, Pavan K.; Caraveo, Gabriela; Lindquist, Susan] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Auluck, Pavan K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lindquist, Susan] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Lindquist, Susan] MIT, Dept Biol, Cambridge, MA 02142 USA. RP Auluck, PK (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. EM auluck@wi.mit.edu; caraveop@wi.mit.edu; lindquist_admin@wi.mit.edu FU Howard Hughes Medical Institute; NINDS NIH HHS [NS038372] NR 114 TC 213 Z9 218 U1 6 U2 65 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3126-9 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2010 VL 26 BP 211 EP 233 DI 10.1146/annurev.cellbio.042308.113313 PG 23 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BSL42 UT WOS:000284856700009 PM 20500090 ER PT S AU Musunuru, K Domian, IJ Chien, KR AF Musunuru, Kiran Domian, Ibrahim J. Chien, Kenneth R. BE Schekman, R Goldstein, L Lehmann, R TI Stem Cell Models of Cardiac Development and Disease SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 SE Annual Review of Cell and Developmental Biology LA English DT Review; Book Chapter DE cardiovascular disease; congenital heart disease; coronary disease; embryonic stem cells; genetics; induced pluripotent stem cells; myocardial infarction ID CONGENITAL HEART-DISEASE; CARDIOVASCULAR PROGENITOR CELLS; CORONARY-ARTERY-DISEASE; ZINC-FINGER NUCLEASES; HUMAN SOMATIC-CELLS; HOLT-ORAM SYNDROME; MYOCARDIAL-INFARCTION; ALAGILLE-SYNDROME; NKX2.5 MUTATIONS; GENETIC-MODIFICATION AB The past few years have witnessed remarkable advances in stem cell biology and human genetics, and we have arrived at an era in which patient-specific cell and tissue models are now practical. The recent identification of cardiovascular progenitor cells, as well as the identification of genetic variants underlying congenital heart disorders and adult disease, opens the door to the development of human models of human cardiovascular disease. We review the current understanding of the contribution of progenitor cells to cardiogenesis and outline how pluripotent stem cells can be applied to the modeling of cardiovascular disorders of genetic origin. A key challenge will be to implement these models in an efficient manner to develop a molecular understanding of how genes lead to disease and to screen for genes and drugs that modify the disease process. C1 [Musunuru, Kiran] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Musunuru, K (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM kmusunuru@partners.org; idomian@partners.org; kchien@partners.org FU NHLBI NIH HHS [K08 HL091209] NR 96 TC 29 Z9 29 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1081-0706 BN 978-0-8243-3126-9 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev.Biol. PY 2010 VL 26 BP 667 EP 687 DI 10.1146/annurev-cellbio-100109-103948 PG 21 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BSL42 UT WOS:000284856700026 PM 20604707 ER PT S AU Calvo, SE Mootha, VK AF Calvo, Sarah E. Mootha, Vamsi K. BE Chakravarti, A Green, E TI The Mitochondrial Proteome and Human Disease SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 11 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE evolution; mitochondria; organelle; respiratory chain disease; tissue diversity; oxidative phosphorylation ID C-OXIDASE DEFICIENCY; COMPLEX-I; SUBCELLULAR-LOCALIZATION; RESPIRATORY-CHAIN; OXIDATIVE-PHOSPHORYLATION; GENE-EXPRESSION; 2-DIMENSIONAL ELECTROPHORESIS; ETHYLMALONIC ENCEPHALOPATHY; INTEGRATIVE GENOMICS; INTERMITTENT HYPOXIA AB For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondria] disorders are caused by nuclear genome defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle. C1 [Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst MIT, Cambridge, MA 02142 USA. [Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Cambridge, MA 02142 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. RP Calvo, SE (reprint author), Broad Inst MIT, Cambridge, MA 02142 USA. EM vamsi@hms.harvard.edu RI Sincan, Murat /A-3794-2010 FU NIGMS NIH HHS [R01 GM077465, R01GM077465] NR 125 TC 181 Z9 182 U1 5 U2 41 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3711-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2010 VL 11 BP 25 EP 44 DI 10.1146/annurev-genom-082509-141720 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA BRG14 UT WOS:000282662200002 PM 20690818 ER PT S AU Musunuru, K Kathiresan, S AF Musunuru, Kiran Kathiresan, Sekar BE Chakravarti, A Green, E TI Genetics of Coronary Artery Disease SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 11 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE genetics; coronary artery disease; myocardial infarction; genomics; genome-wide association studies ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; HIGH-DENSITY-LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; FASTING PLASMA-GLUCOSE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; SUSCEPTIBILITY LOCUS; TRIGLYCERIDE LEVELS AB Coronary artery disease and its clinical manifestations, including myocardial infarction, are heritable traits, consistent with a role for inherited DNA sequence variation in conferring risk for disease. Knowledge of the new sequence variations in the genome that confer risk has the potential to illuminate new causal biologic pathways in humans and to thereby further improve diagnosis and treatment. Here, we review recent progress in mapping genetic loci related to coronary disease and risk factor phenotypes, including plasma lipoprotein concentrations. Genome-wide linkage (in families) and association (in populations) studies have identified more than a dozen genetic loci related to coronary disease. A key challenge now is to move from mapping loci to pinpointing causal genes and variants, and to develop a molecular understanding of how these genes lead to coronary disease. C1 [Musunuru, Kiran] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02108 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02108 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Musunuru, K (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02108 USA. EM skathiresan@partners.org NR 93 TC 49 Z9 52 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3711-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2010 VL 11 BP 91 EP 108 DI 10.1146/annurev-genom-082509-141637 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA BRG14 UT WOS:000282662200005 PM 20590428 ER PT S AU Hogan, PG Lewis, RS Rao, A AF Hogan, Patrick G. Lewis, Richard S. Rao, Anjana BE Paul, WE Littman, DR Yokoyama, WM TI Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 28 SE Annual Review of Immunology LA English DT Review; Book Chapter DE CRAC channels; store-operated calcium entry; T cell activation; primary immunodeficiencies ID OPERATED CA2+ ENTRY; T-CELL-ACTIVATION; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; FAST CA2+-DEPENDENT INACTIVATION; STROMAL INTERACTION MOLECULE-1; CA2+-SELECTIVE ARC CHANNELS; BEARING DENDRITIC CELLS; NAADP MOBILIZES CALCIUM; STORE-INDEPENDENT MODES; TYROSINE KINASE SYK AB Ca(2+) entry into cells of the peripheral immune system occurs through highly Ca(2+)-selective channels known as CRAC (calcium release-activated calcium) channels. CRAG channels are a very well-characterized example of store-operated Ca(2+) channels, so designated because they open when the endoplasmic reticulum (ER) Ca(2+) store becomes depleted. Physiologically, Ca(2+) is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP(3)). IP(3) binds to IP(3) receptors in the ER membrane and activates Ca(2+) release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca(2+) entry. STIM1 and STIM2 sense the depletion of ER Ca(2+) stores, whereas ORAI1 is a pore subunit of the CRAG channel. In this review, we discuss selected aspects of Ca(2+) signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca(2+) entry. C1 [Hogan, Patrick G.; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA. [Hogan, Patrick G.; Rao, Anjana] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lewis, Richard S.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. RP Hogan, PG (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA. EM hogan@idi.harvard.edu; rslewis@stanford.edu; arao@idi.harvard.edu FU CCR NIH HHS [RC1 DA028422-01]; NIAID NIH HHS [R01 AI040127, R01 AI040127-15, R01 AI084167, R01 AI084167-06]; NIDA NIH HHS [RC1 DA028422, RC1 DA028422-01]; NIGMS NIH HHS [R01 GM045374] NR 227 TC 371 Z9 378 U1 6 U2 50 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3028-6 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2010 VL 28 BP 491 EP 533 DI 10.1146/annurev.immunol.021908.132550 PG 43 WC Immunology SC Immunology GA BOR04 UT WOS:000277363600019 PM 20307213 ER PT S AU Bergwitz, C Juppner, H AF Bergwitz, Clemens Jueppner, Harald TI Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23 SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE PTH; 1,25(OH)(2)-vitamin D; FGF23; phosphate homeostasis ID FAMILIAL TUMORAL CALCINOSIS; FIBROBLAST-GROWTH-FACTOR; HEREDITARY HYPOPHOSPHATEMIC RICKETS; PARATHYROID-HORMONE GENE; HYP MOUSE PHENOTYPE; D-RECEPTOR; IN-VIVO; CA2+-SENSING RECEPTOR; PTH/PTHRP RECEPTOR; TARGETED ABLATION AB In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper. C1 [Bergwitz, Clemens; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM cbergwitz@partners.org FU NIDDK NIH HHS [K08 DK078361, R03 DK089127] NR 104 TC 183 Z9 186 U1 6 U2 43 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0561-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 91 EP 104 DI 10.1146/annurev.med.051308.111339 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600007 PM 20059333 ER PT S AU Sakhuja, R Mauri, L AF Sakhuja, Rahul Mauri, Laura TI Controversies in the Use of Drug-Eluting Stents for Acute Myocardial Infarction: A Critical Appraisal of the Data SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE coronary stent; restenosis; stent thrombosis; clinical trials ID BARE-METAL STENTS; PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; TERM CLINICAL-OUTCOMES; ORAL ANTIPLATELET THERAPY; INTRAVASCULAR ULTRASOUND; FOLLOW-UP; BALLOON ANGIOPLASTY; COST-EFFECTIVENESS; UNCOATED STENTS AB Acute myocardial infarction is a common and life-threatening presentation of coronary artery disease in adults. In the settings of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, significant mortality benefit has been observed in randomized trials of coronary stent procedures compared with medical therapy alone. However, data regarding procedural choices, and particularly stent choices, are limited, and significant controversy exists. Drug-eluting stents were introduced in the United States in 2003 and have been widely adopted based on profound reduction in restenosis. Yet recent years have witnessed a decline in use of drug-eluting stents in the setting of myocardial infarction due to long-term safety concerns. We review the current data regarding drug-eluting stent performance relative to bare metal stents in the setting of acute myocardial infarction with regard to effectiveness, safety, and the need for adjunctive long-term pharmacologic therapy. C1 [Sakhuja, Rahul] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sakhuja, Rahul; Mauri, Laura] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Sakhuja, R (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM rsakhuja@partners.org; lmauri1@partners.org FU Cordis Corporation; Medtronic Vascular FX Dr. Mauri has received consulting fees from Cordis Corporation and Medtronic Vascular. NR 91 TC 6 Z9 6 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0561-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 215 EP 231 DI 10.1146/annurev.med.051508.221014 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600015 PM 20059336 ER PT S AU Rubino, F Schauer, PR Kaplan, LM Cummings, DE AF Rubino, Francesco Schauer, Philip R. Kaplan, Lee M. Cummings, David E. TI Metabolic Surgery to Treat Type 2 Diabetes: Clinical Outcomes and Mechanisms of Action SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE bariatric surgery; gastric bypass; duodenal-jejunal bypass; ghrelin; glucagon-like peptide-1; Diabetes Surgery Summit ID ROUX-EN-Y; GASTRIC-BYPASS-SURGERY; DUODENAL-JEJUNAL BYPASS; MORBIDLY OBESE-PATIENTS; LONG-TERM MORTALITY; BMI LESS-THAN-35 KG/M(2); INTENTIONAL WEIGHT-LOSS; GOTO-KAKIZAKI RATS; BETA-CELL FUNCTION; BODY-MASS INDEX AB Several gastrointestinal (GI) operations that were designed to promote weight loss can powerfully ameliorate type 2 diabetes mellitus (T2DM). Although T2DM is traditionally viewed as a chronic, relentless disease in which delay of end-organ complications is the major treatment goal, GI surgery offers a novel endpoint: complete disease remission. Ample data confirm the excellent safety and efficacy of conventional bariatric operations-especially Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding-to treat T2DM in severely obese patients. Use of experimental procedures as well as conventional bariatric operations is increasingly being explored in less obese diabetic patients, with generally favorable results, although further assessment of risk:benefit profiles is needed. Mounting evidence indicates that certain operations involving intestinal diversions improve glucose homeostasis through varied mechanisms beyond reduced food intake and body weight, for example by modulating gut hormones. Research to elucidate such mechanisms should facilitate the design of novel pharmacotherapeutics and dedicated antidiabetes GI manipulations. Here we review evidence regarding the use and study of GI surgery to treat T2DM, focusing on available published reports as well as results from the Diabetes Surgery Summit (DSS) in Rome and the World Congress on Interventional Therapies for T2DM in New York City. C1 [Rubino, Francesco] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Schauer, Philip R.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Cummings, David E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Rubino, F (reprint author), New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. EM frr2007@med.cornell.edu FU NIH [DK517498, DK61516, DK68384, DK66568, DK17047] FX We earnestly thank the following delegates from the Diabetes Surgery Summit for critical review and appraisal of the content of this article: Ted Adams, Stephanie Amiel, Garth H. Ballantyne, Guenther Boden, Camillo Boza, Henry Buchwald, Marco Castagneto, Ricardo Cohen, David D'Alessio, Aureo L. DePaula, John Dixon, Franco Favretti, Ele Ferrannini, David Flum, Gema Fruhbeck, Michel Gagner, Giovanni Ghirlanda, Allison Goldfine, Peter J. Havel, William H.. Herman, Kelvin Higa, Jacques Himpens, Jens Holst, David Kelley, Samuel Klein, Judith Korner, Antonio Lacy, Harold Lebovitz, Carel LeRoux, Michael Meguid, Geltrude Mingrone, JerryPalmer, Antonio Pontiroli, Walter J. Pories, Eric Ravussin, Denis Richard, William Richards, Donna Ryan, Christopher Saudek, Nicola Scopinaro, Randy Seeley, April D. Strader, Richard Stubbs, Harvey Sugerman, Tessa Van der Merwe, Bruce M. Wolfe. D.C. is supported by NIH grants DK517498, DK61516, DK68384, DK66568, and DK17047. NR 113 TC 191 Z9 204 U1 4 U2 28 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0561-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2010 VL 61 BP 393 EP 411 DI 10.1146/annurev.med.051308.105148 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 559WB UT WOS:000274857600026 PM 20059345 ER PT S AU Sgroi, DC AF Sgroi, Dennis C. TI Preinvasive Breast Cancer SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE flat epithelial atypia; atypical ductal hyperplasia; ductal carcinoma in situ; genetics; gene expression ID CARCINOMA-IN-SITU; COMPARATIVE GENOMIC HYBRIDIZATION; ATYPICAL DUCTAL HYPERPLASIA; GENE-EXPRESSION PROFILES; TERM FOLLOW-UP; PLEOMORPHIC LOBULAR CARCINOMA; CELL-DERIVED FACTOR-1; MAMMARY-CARCINOMA; STEM-CELLS; TUMOR-MICROENVIRONMENT AB Preinvasive breast cancer accounts for approximately one-third of all newly diagnosed breast cancer cases in the United States and constitutes a spectrum of neoplastic lesions with varying degrees of differentiation and clinical behavior. High-through put genetic, epigenetic, and gene-expression analyses have enhanced our understanding of the relationship of these early neoplastic lesions to normal breast tissue, and they strongly suggest that preinvasive breast cancer develops and evolves along two distinct molecular genetic and biological pathways that correlate with tumor grade. Although unique epigenetic and gene-expression changes are not observed in the tumor epithelial compartment during the transition from preinvasive to invasive disease, distinct molecular alterations are observed in the tumor-stromal and myoepithelial cells. This Suggests that the stromal and myoepithelial microenviromnent of preinvasive breast cancer actively participates in the transition from preinvasive to invasive disease. An improved understanding of the transition from preinvasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies. C1 [Sgroi, Dennis C.] Harvard Univ, Sch Med, Dept Pathol, Mol Pathol Res Unit, Boston, MA 02129 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. RP Sgroi, DC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Mol Pathol Res Unit, Boston, MA 02129 USA. EM dsgroi@partners.org FU NCI NIH HHS [R01-1CA112021-01, R01 CA112021] NR 149 TC 29 Z9 29 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4305-7 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2010 VL 5 BP 193 EP 221 DI 10.1146/annurev.pathol.4.110807.092306 PG 29 WC Pathology SC Pathology GA 562DU UT WOS:000275030400009 PM 19824828 ER PT S AU Halassa, MM Haydon, PG AF Halassa, Michael M. Haydon, Philip G. TI Integrated Brain Circuits: Astrocytic Networks Modulate Neuronal Activity and Behavior SO ANNUAL REVIEW OF PHYSIOLOGY SE ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review; Book Chapter DE sleep; ATP; adenosine; NMDA; astrocyte; synapse ID CYSTINE-GLUTAMATE EXCHANGE; SPINAL-CORD-INJURY; REACTIVE ASTROCYTES; GLIAL-CELLS; D-SERINE; IN-VIVO; VESICULAR GLUTAMATE; SLEEP HOMEOSTASIS; CALCIUM WAVES; PROTOPLASMIC ASTROCYTES AB The past decade has seen an explosion of research on roles of neuron-astrocyte interactions in the control of brain function. We highlight recent studies performed on the tripartite synapse, the structure consisting of pre- and postsynaptic elements of the synapse and an associated astrocytic process. Astrocytes respond to neuronal activity and neuro-transmitters, through the activation of metabotropic receptors, and can release the gliotransmitters ATP, o-serine, and glutamate, which act on neurons. Astrocyte-derived ATP modulates synaptic transmission, either directly or through its metabolic product adenosine. o-serine modulates NMDA receptor function, whereas glia-derived glutamate can play important roles in relapse following withdrawal from drugs of abuse. Cell type specific molecular genetics has allowed a new level of examination of the function of astrocytes in brain function and has revealed an important role of these glial cells that is mediated by adenosine accumulation in the control of sleep and in cognitive impairments that follow sleep deprivation. C1 [Halassa, Michael M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Halassa, Michael M.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. [Haydon, Philip G.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. RP Halassa, MM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM philip.haydon@tufts.edu FU NIDA NIH HHS [R01 DA025967, R01 DA025967-01]; NINDS NIH HHS [R01 NS037585, R01 NS037585-13, R01 NS043142, R01 NS043142-11, R01 NS054770, R01 NS054770-06] NR 137 TC 348 Z9 353 U1 5 U2 74 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 BN 978-0-8243-0372-3 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2010 VL 72 BP 335 EP 355 DI 10.1146/annurev-physiol-021909-135843 PG 21 WC Physiology SC Physiology GA 575RK UT WOS:000276085100019 PM 20148679 ER PT S AU Fernandez, ME Allen, JD Mistry, R Kahn, JA AF Fernandez, Maria E. Allen, Jennifer D. Mistry, Ritesh Kahn, Jessica A. BE Fielding, JE Brownson, RC Green, LW TI Integrating Clinical, Community, and Policy Perspectives on Human Papillomavirus Vaccination SO ANNUAL REVIEW OF PUBLIC HEALTH, VOL 31 SE Annual Review of Public Health LA English DT Review; Book Chapter DE human papillomavirus; vaccine; psychosocial factors; theory; policy; health care systems ID RANDOMIZED CONTROLLED-TRIAL; TRANSMITTED INFECTION VACCINATION; HEPATITIS-B VACCINATION; HPV VACCINE; PARTICLE VACCINE; PARENTAL ATTITUDES; CERVICAL-CANCER; YOUNG-WOMEN; ADOLESCENT IMMUNIZATION; UNITED-STATES AB Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause similar to 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HP-V-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This review summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated framework can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research. C1 [Fernandez, Maria E.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Allen, Jennifer D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mistry, Ritesh] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Kahn, Jessica A.] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA. RP Fernandez, ME (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Houston, TX 77030 USA. EM Maria.E.Fernandez@uth.tmc.edu; Jennifer_Allen@dfci.harvard.edu; riteshm@ucla.edu; Jessica.Kahn@cchmc.org RI Allen, Jennifer/M-2113-2015 FU NCCDPHP CDC HHS [U48 DP000057, U48 DP000056, U48 DP000064]; NIAID NIH HHS [R01 AI073713, R01 AI073713-04] NR 117 TC 35 Z9 35 U1 4 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0163-7525 BN 978-0-8243-2731-6 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2010 VL 31 BP 235 EP 252 DI 10.1146/annurev.publhealth.012809.103609 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BOX22 UT WOS:000277908800016 PM 20001821 ER PT B AU Kozanek, M Van de Velde, S Hosseini, A Gill, T Li, GA AF Kozanek, Michal Van de Velde, Samuel Hosseini, Ali Gill, Thomas Li, Guoan BE Yeager, CR TI Biomechanics of ACL Deficiency and Contemporary Reconstruction Techniques SO ANTERIOR CRUCIATE LIGAMENT (ACL): CAUSES OF INJURY, ADVERSE EFFECTS AND TREATMENT OPTIONS SE Muscular System-Anatomy Functions and Injuries LA English DT Article; Book Chapter ID ANTERIOR CRUCIATE-LIGAMENT; IN-SITU FORCES; ACUTE TRAUMATIC HEMARTHROSIS; PATELLAR TENDON AUTOGRAFT; 2-YEAR FOLLOW-UP; ARTHROSCOPICALLY ASSISTED RECONSTRUCTION; MEDIAL COLLATERAL LIGAMENT; DIRECT INVITRO MEASUREMENT; SIMULATED MUSCLE LOADS; KNEE-JOINT MOTION C1 [Kozanek, Michal] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kozanek, M (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. NR 135 TC 0 Z9 0 U1 0 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-993-3 J9 MUSCULAR SYST-ANAT F PY 2010 BP 29 EP 59 PG 31 WC Anatomy & Morphology; Physiology SC Anatomy & Morphology; Physiology GA BPZ66 UT WOS:000280441400002 ER PT J AU Mauldin, PD Salgado, CD Hansen, IS Durup, DT Bosso, JA AF Mauldin, Patrick D. Salgado, Cassandra D. Hansen, Ida Solhoj Durup, Darshana T. Bosso, John A. TI Attributable Hospital Cost and Length of Stay Associated with Health Care-Associated Infections Caused by Antibiotic-Resistant Gram-Negative Bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FOR-DISEASE-CONTROL; ANTIMICROBIAL RESISTANCE; ECONOMIC OUTCOMES; NOSOCOMIAL INFECTIONS; STAPHYLOCOCCUS-AUREUS; ACINETOBACTER-BAUMANNII; PSEUDOMONAS-AERUGINOSA; METHICILLIN-RESISTANCE; KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI AB Determination of the attributable hospital cost and length of stay (LOS) are of critical importance for patients, providers, and payers who must make rational and informed decisions about patient care and the allocation of resources. The objective of the present study was to determine the additional total hospital cost and LOS attributable to health care-associated infections (HAIs) caused by antibiotic-resistant, gram-negative (GN) pathogens. A single-center, retrospective, observational comparative cohort study was performed. The study involved 662 patients admitted from 2000 to 2008 who developed HAIs caused by one of following pathogens: Acinetobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., or Pseudomonas spp. The attributable total hospital cost and LOS for HAIs caused by antibiotic-resistant GN pathogens were determined by comparison with the hospital costs and LOS for a control group with HAIs due to antibiotic-susceptible GN pathogens. Statistical analyses were conducted by using univariate and multivariate analyses. Twenty-nine percent of the HAIs were caused by resistant GN pathogens, and almost 16% involved a multidrug-resistant GN pathogen. The additional total hospital cost and LOS attributable to antibiotic-resistant HAIs caused by GN pathogens were 29.3% (P < 0.0001; 95% confidence interval, 16.23 to 42.35) and 23.8% (P = 0.0003; 95% confidence interval, 11.01 to 36.56) higher than those attributable to HAIs caused by antibiotic-susceptible GN pathogens, respectively. Significant covariates in the multivariate analysis were age >= 12 years, pneumonia, intensive care unit stay, and neutropenia. HAIs caused by antibiotic-resistant GN pathogens were associated with significantly higher total hospital costs and increased LOSs compared to those caused by their susceptible counterparts. This information should be used to assess the potential cost-efficacy of interventions aimed at the prevention of such infections. C1 [Mauldin, Patrick D.; Hansen, Ida Solhoj; Durup, Darshana T.; Bosso, John A.] S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Salgado, Cassandra D.; Bosso, John A.] Med Univ S Carolina, Coll Med, Div Infect Dis, Charleston, SC 29425 USA. RP Bosso, JA (reprint author), S Carolina Coll Pharm, Dept Clin Pharm & Outcome Sci, MUSC Campus,280 Calhoun St,MSC 140, Charleston, SC 29425 USA. EM bossoja@musc.edu FU AstraZeneca Pharmaceuticals LP, Wilmington, DE FX This work was funded, in part, by an investigator-initiated research grant from AstraZeneca Pharmaceuticals LP, Wilmington, DE. NR 43 TC 91 Z9 95 U1 1 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2010 VL 54 IS 1 BP 109 EP 115 DI 10.1128/AAC.01041-09 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 534XQ UT WOS:000272931200013 PM 19841152 ER PT B AU Anwaruddin, S Bhatt, DL AF Anwaruddin, Saif Bhatt, Deepak L. BE Askari, AT Lincoff, AM TI Antiplatelet Therapies in Unstable Angina and Non-ST Segment Elevation Myocardial Infarction SO ANTITHROMBOTIC DRUG THERAPY IN CARDIOVASCULAR DISEASE LA English DT Article; Book Chapter DE Acute coronary syndromes; Aspirin; Clopidogrel; Glycoprotein IIb/IIIa inhibitors; Non-T-segment-elevation myocardial infarction; Percutaneous coronary intervention; ST segment-elevation myocardial infarction; Thienopyridines ID ACUTE CORONARY SYNDROMES; PLATELET GLYCOPROTEIN-IIB/IIIA; PLACEBO-CONTROLLED TRIAL; DRUG-ELUTING STENTS; RANDOMIZED CLINICAL-TRIALS; THIENOPYRIDINE P2Y(12) INHIBITOR; RECURRENT EVENTS CURE; VON-WILLEBRAND-FACTOR; BARE-METAL STENTS; PRASUGREL CS-747 AB The central role of the platelet in the pathophysiology of acute coronary syndromes (ACS) has been well established. The significant morbidity and mortality associated with ACS has fostered great interest and effort in identifying various antiplatelet and antithrombotic regimens as well as developing novel agents in order to abrogate the platelet and its associated prothrombotic effects. Aspirin remains the integral component of all therapeutic strategies for ACS. When used in combination with thienopyridines (i.e., clopidogrel), GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), or both, patients have experienced improved outcomes in this setting. However, with more potent antiplatelet regimens comes an increased risk of bleeding. Thus, the search for more potent antiplatelet agents with a decreased risk of bleeding continues for this patient population. C1 [Anwaruddin, Saif] Western Reserve Heart Care, Hudson, OH USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Cardiol, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. RP Anwaruddin, S (reprint author), Western Reserve Heart Care, Hudson, OH USA. NR 88 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-234-6 PY 2010 BP 145 EP 163 DI 10.1007/978-1-60327-235-3_7 D2 10.1007/978-1-60327-235-3 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BMP79 UT WOS:000273299400007 ER PT B AU Kim, MS Page, RL Casserly, IP AF Kim, Michael S. Page, Robert L. Casserly, Ivan P. BE Askari, AT Lincoff, AM TI Synthetic Factor Xa Inhibition in Acute Coronary Syndromes SO ANTITHROMBOTIC DRUG THERAPY IN CARDIOVASCULAR DISEASE LA English DT Article; Book Chapter DE Fondaparinux; Acute coronary syndrome; Anticoagulant ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; RANDOMIZED-TRIALS; FONDAPARINUX SODIUM; ANTITHROMBIN-III; COLLABORATIVE METAANALYSIS; UNFRACTIONATED HEPARIN; VENOUS THROMBOEMBOLISM; COST-EFFECTIVENESS; HIGH-AFFINITY AB Over the last decade, several advances in the management of patients with acute coronary syndrome have been made. Despite these therapeutic advances, the risk of major adverse cardiovascular events related to acute coronary syndrome remains significant. These findings have led to continued efforts to find more efficacious antiplatelet agents and anticoagulants to help reduce the risk of recurrent ischemic events. This chapter reviews the clinical data pertaining to the novel anticoagulant fondaparinux for the treatment of acute coronary syndrome. C1 [Kim, Michael S.; Casserly, Ivan P.] Univ Colorado Denver, Sect Intervent Cardiol, Aurora, CO USA. [Kim, Michael S.; Page, Robert L.; Casserly, Ivan P.] Hlth Sci Ctr, Aurora, CO USA. [Casserly, Ivan P.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. RP Kim, MS (reprint author), Univ Colorado Denver, Sect Intervent Cardiol, Aurora, CO USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-234-6 PY 2010 BP 203 EP 215 DI 10.1007/978-1-60327-235-3_10 D2 10.1007/978-1-60327-235-3 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BMP79 UT WOS:000273299400010 ER PT J AU Amorosa, VK Slim, J Mounzer, K Bruno, C Hoffman-Terry, M Dorey-Stein, Z Ferrara, T Kostman, JR Lo Re, V AF Amorosa, Valerianna K. Slim, Jihad Mounzer, Karam Bruno, Christopher Hoffman-Terry, Margaret Dorey-Stein, Zachariah Ferrara, Thomas Kostman, Jay R. Lo Re, Vincent, III TI The influence of abacavir and other antiretroviral agents on virological response to HCV therapy among antiretroviral-treated HIV-infected patients SO ANTIVIRAL THERAPY LA English DT Article; Proceedings Paper CT 16th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2009 CL Montreal, CANADA ID CHRONIC HEPATITIS-C; INTERFERON PLUS RIBAVIRIN; HUMAN-IMMUNODEFICIENCY-VIRUS; PEGYLATED INTERFERON; COINFECTED PATIENTS; RECOMMENDATIONS; PROGRESSION; MANAGEMENT; DIAGNOSIS; PANEL AB Background: It remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to HCV therapy. Such data could inform the selection of appropriate antiretrovirals in HIV/HCV-coinfected patients. The aim of this study was to determine if use of abacavir, as well as other antiretrovirals, was associated with reduced response to pegylated interferon (PEG-IFN) plus ribavirin. Methods: A cohort study was performed among antiretroviral-treated HIV/HCV-coinfected patients initiating PEG-IFN plus ribavirin between January 2001 and June 2007 at six sites in the United States. Abacavir and other antiretrovirals represented exposures of interest. Study outcomes included an early virological response (>= 2 log IU/ml decrease in HCV viral load at 12 weeks) and sustained virological response (undetectable HCV viral load 24 weeks after treatment discontinuation). Results: Among 212 patients, 74 (35%) received abacavir. For patients infected with HCV genotype 1 or 4, no differences were observed between abacavir users and non-users in early virological response (26 [40%] versus 53 [44%]; adjusted odds ratio [OR] 1.00; 95% confidence interval [CI] 0.50-2.00) or sustained virological response (8 [13%] versus 13 [12%]; adjusted OR 1.34; 95% CI 0.50-3.62). Among genotype 2 and 3 patients, rates of early virological response (7 [78%] versus 16 [89%]; OR 0.44; 95% CI 0.05-3.76) and sustained virological response (3 [33%] versus 8 [44%]; OR 0.63; 95% CI 0.12-3.32) were also similar between abacavir users and non-users. No association was found between other antiretrovirals and a lack of early or sustained response. Conclusions: Use of abacavir or other antiretroviral medications was not associated with reduced early or sustained virological response rates. C1 [Amorosa, Valerianna K.; Dorey-Stein, Zachariah; Kostman, Jay R.; Lo Re, Vincent, III] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Amorosa, Valerianna K.; Ferrara, Thomas; Lo Re, Vincent, III] Philadelphia Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA USA. [Slim, Jihad] St Michaels Hosp, Div Infect Dis, Newark, NJ 07102 USA. [Mounzer, Karam] Jonathan Lax Treatment Ctr, Philadelphia, PA USA. [Bruno, Christopher] Drexel Univ, Div Infect Dis, Sch Med, Philadelphia, PA 19104 USA. [Hoffman-Terry, Margaret] Lehigh Valley Hosp, Div Infect Dis, Allentown, PA USA. [Lo Re, Vincent, III] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. EM vincenti@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU AHRQ HHS [HS10399, U18 HS010399]; NIAID NIH HHS [K01 AI070001, K01 AI070001-01A1, K01-AI070001] NR 25 TC 19 Z9 20 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 1 BP 91 EP 99 DI 10.3851/IMP1492 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 581MX UT WOS:000276528900010 PM 20167995 ER PT J AU Huckans, M Mitchell, A Pavawalla, S Morasco, BJ Ruimy, S Loftis, JM Rifai, MA Hauser, P AF Huckans, Marilyn Mitchell, Alex Pavawalla, Shital Morasco, Benjamin J. Ruimy, Samantha Loftis, Jennifer M. Rifai, Muhamad A. Hauser, Peter TI The influence of antiviral therapy on psychiatric symptoms among patients with hepatitis C and schizophrenia SO ANTIVIRAL THERAPY LA English DT Article ID SUBSTANCE USE DISORDERS; SEVERE MENTAL-ILLNESS; PREVALENCE; MANAGEMENT; VETERANS; PEOPLE AB Background: Antiviral therapy for chronic infection with HCV is associated with significant neuropsychiatric side effects. Research indicates that patients with mental illness are less likely to receive antiviral therapy, despite limited data regarding the influence of antiviral therapy on psychiatric symptoms in patients with specific psychiatric disorders. The aim of this study was to determine whether antiviral therapy is associated with higher rates of psychiatric symptoms in patients with schizophrenia (SCHZ). Methods: A regional Veterans Healthcare Administration database was used to identify veterans meeting criteria for this retrospective chart review. Patients confirmed to have SCHZ and to have received antiviral therapy for HCV between 1998 and 2006 (n=30) were compared with a control group of demographically matched (age, race and gender) patients with SCHZ who did not receive antiviral therapy (n=30). Clinicians blinded to antiviral therapy status used chart notes to evaluate whether patients exhibited prominent symptoms of SCHZ, depression or mania during a 6 month pre-treatment period, the treatment period and a 6 month post-treatment period (or during equivalent periods for the control group). Results: Groups did not significantly differ in rates of symptoms of SCHZ, depression or mania during any study period. During the treatment period, groups did not significantly differ in rates of emergency room visits or inpatient hospitalizations. Conclusions: Our retrospective chart review suggests that patients with SCHZ experience similar rates of psychiatric symptoms on and off antiviral therapy. Despite limitations and constraints of the methods, our data suggest that SCHZ is not a contraindication to antiviral therapy for HCV. C1 [Huckans, Marilyn; Mitchell, Alex; Morasco, Benjamin J.; Ruimy, Samantha; Loftis, Jennifer M.; Hauser, Peter] Portland VA Med Ctr, NW Hepatitis Resource Ctr C, Portland, OR USA. [Huckans, Marilyn; Mitchell, Alex; Pavawalla, Shital; Morasco, Benjamin J.; Ruimy, Samantha; Hauser, Peter] Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. [Huckans, Marilyn; Loftis, Jennifer M.; Hauser, Peter] Portland VA Med Ctr, Div Res, Portland, OR USA. [Huckans, Marilyn; Morasco, Benjamin J.; Loftis, Jennifer M.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Loftis, Jennifer M.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Rifai, Muhamad A.] Lehigh Valley Hosp, Dept Psychiat, Allentown, PA USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Huckans, M (reprint author), Portland VA Med Ctr, NW Hepatitis Resource Ctr C, Portland, OR USA. EM marilyn.huckans@va.gov FU NIDA NIH HHS [K23 DA023467-01A1, K23 DA023467] NR 16 TC 10 Z9 11 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 1 BP 111 EP 119 DI 10.3851/IMP1493 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 581MX UT WOS:000276528900012 PM 20167997 ER PT J AU Yazdanpanah, Y Wolf, LL Anglaret, X Gobillard, D Walensky, RP Moh, R Danel, C Sloan, CE Losina, E Freedberg, KA AF Yazdanpanah, Yazdan Wolf, Lindsey L. Anglaret, Xavier Gobillard, Delphine Walensky, Rochelle P. Moh, Raoul Danel, Christine Sloan, Caroline E. Losina, Elena Freedberg, Kenneth A. CA CEPAC-Int Investigators TI CD4(+) T-cell-guided structured treatment interruptions of antiretroviral therapy in HIV disease: projecting beyond clinical trials SO ANTIVIRAL THERAPY LA English DT Article ID SCHEDULED TREATMENT INTERRUPTIONS; COTE-DIVOIRE; COST-EFFECTIVENESS; RANDOMIZED-TRIAL; INFECTED PATIENTS; DRUG-RESISTANCE; COTRIMOXAZOLE PROPHYLAXIS; LACTIC-ACIDOSIS; AFRICAN ADULTS; UNITED-STATES AB Background: International trials have shown that CD4(+) T-cell-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4(+) T-cell interruption/reintroduction thresholds than those assessed in actual trials. Methods: Using a model of HIV, we simulated cohorts of African adults with different baseline CD4(+) T-cell counts (<= 200; 201-350; and 351-500 cells/mu l). We varied ART initiation criteria (immediate; CD4(+) T-cell count <350 cells/mu l or >= 350 cells/mu l with severe HIV-related disease; and CD4(+) T-cell count <200 cells/mu l or 200 cells/mu l with severe HIV-related disease), and ART interruption/reintroduction thresholds (350/250; 500/350; and 700/500 cells/mu l). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line therapy was protease inhibitor (PI)-based. Results: STI generally reduced life expectancy compared with continuous ART. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48-69 and 11-30 months compared with continuous ART when interruption/reintroduction thresholds were 350/250 and 500/350 cells/mu l, depending on ART initiation criteria. When patients interrupted/reintroduced ART at 700/500 cells/mu l, life expectancies ranged from 2 months lower to 1 month higher than continuous ART. STI-related life expectancy increased with decreased risk of virological resistance after ART interruptions. Conclusions: STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4(+) T-cell thresholds (700/500 cells/mu l) and use first-line medications with higher resistance barriers, such as PIs. C1 [Yazdanpanah, Yazdan] Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. [Yazdanpanah, Yazdan] Fac Med Lille, EA 2694, F-59045 Lille, France. [Wolf, Lindsey L.; Walensky, Rochelle P.; Sloan, Caroline E.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Anglaret, Xavier; Gobillard, Delphine] Univ Victor Segalen Bordeaux 2, INSERM, U897, Bordeaux, France. [Anglaret, Xavier; Moh, Raoul; Danel, Christine] Programme PAC CI, Abidjan, Cote Ivoire. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Yazdanpanah, Y (reprint author), Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. EM yyazdan@yahoo.com RI Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X FU Agence National de Recherches sur le SIDA et les hepatitis virales (ANRS) [1286, 1269]; National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476, P30 AI42851]; Doris Duke Charitable Foundation FX This research was supported by grants from the Agence National de Recherches sur le SIDA et les hepatitis virales (ANRS 1286 and 1269), the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476 and P30 AI42851) and the Doris Duke Charitable Foundation Clinical Scientist Development Award. The funding sources had no role in the design, analysis, or interpretation of the study or in the decision to submit the manuscript for publication. NR 46 TC 8 Z9 8 U1 2 U2 3 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 3 BP 351 EP 361 DI 10.3851/IMP1542 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 609PZ UT WOS:000278670800008 PM 20516555 ER PT J AU Glesby, MJ Hoover, DR Shi, QH Danoff, A Howard, A Tien, P Merenstein, D Cohen, M Golub, E DeHovitz, J Nowicki, M Anastos, K AF Glesby, Marshall J. Hoover, Donald R. Shi, Qiuhu Danoff, Ann Howard, Andrea Tien, Phyllis Merenstein, Dan Cohen, Mardge Golub, Elizabeth DeHovitz, Jack Nowicki, Marek Anastos, Kathryn TI Glycated haemoglobin in diabetic women with and without HIV infection: data from the Women's Interagency HIV Study SO ANTIVIRAL THERAPY LA English DT Article ID ANTIRETROVIRAL THERAPY; MELLITUS; GLUCOSE; GLYCEMIA; PREVALENCE; DIAGNOSIS; COHORT AB Background: Limited data suggest that glycated haemoglobin (haemoglobin A1c; A1C) values might not reflect glycaemic control accurately in HIV-infected individuals with diabetes. Methods: We evaluated repeated measures of paired fasting glucose and A1C values in 315 HIV-infected and 109 HIV-uninfected diabetic participants in the Women's Interagency HIV Study. Generalized estimating equations used log A1C as the outcome variable, with adjustment for log fasting glucose concentration in all models. Results: An HIV-infected woman on average had 0.9868 times as much A1C (that is, 1.32% lower; 95% confidence interval 0.9734-0.9904) as an HIV-uninfected woman with the same log fasting glucose concentration. In multivariate analyses, HIV serostatus was not associated, but White, other non-Black race, and higher red blood cell mean corpuscular volume (MCV) were statistically associated with lower A1C values. Use of diabetic medication was associated with higher A1C values. In multivariate analyses restricted to HIV-infected women, White and other race, higher MCV, and HCV viraemia were associated with lower A1C values, whereas older age, use of diabetic medications and higher CD4(+) T-cell count were associated with higher A1C values. Use of combination antiretroviral therapy, protease inhibitors, zidovudine, stavudine or abacavir was not associated with A1C values. Conclusions: A1C values were modestly lower in HIV-infected diabetic women relative to HIV-uninfected diabetic women after adjustment for fasting glucose concentration. The difference was abrogated by adjustment for MCV, race and diabetic medication use. Our data suggest that in clinical practice A1C gives a reasonably accurate refection of glycaemic control in HIV-infected diabetic women. C1 [Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY USA. [Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Shi, Qiuhu] New York Med Coll, Sch Hlth Sci & Practice, Valhalla, NY 10595 USA. [Danoff, Ann] NYU, Sch Med, Dept Med, New York, NY USA. [Howard, Andrea] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Tien, Phyllis] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tien, Phyllis] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Merenstein, Dan] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Cohen, Mardge] Stroger Cook Cty Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge] Rush Med Coll, Dept Med, Chicago, IL 60612 USA. [Golub, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [DeHovitz, Jack] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Nowicki, Marek] Univ So Calif, Dept Med, Los Angeles, CA USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Glesby, MJ (reprint author), Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY USA. FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1 AI-31834, UO1-AI-314994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, K24 AI 78884]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131] FX The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1 AI-31834, UO1-AI-314994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant number UL1 RR024131). Additional support for this project was provided by the National Institute of Allergy and Infectious Diseases (K24 AI 78884). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 17 TC 15 Z9 15 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 BP 571 EP 577 DI 10.3851/IMP1557 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800004 PM 20587850 ER PT J AU Schwarze-Zander, C Neibecker, M Othman, S Tural, C Clotet, B Blackard, JT Kupfer, B Luechters, G Chung, RT Rockstroh, JK Spengler, U AF Schwarze-Zander, Carolynne Neibecker, Markus Othman, Sabrina Tural, Cristina Clotet, Bonaventura Blackard, Jason T. Kupfer, Bernd Luechters, Guido Chung, Ray T. Rockstroh, Juergen K. Spengler, Ulrich TI GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4(+) T-cells SO ANTIVIRAL THERAPY LA English DT Article ID LIVER-DISEASE; INFECTION; REPLICATION; VIREMIA AB Background: Coinfection with the flavivirus GB virus C (GBV-C) is frequent in patients suffering from HIV type-1 (HIV-1) infection because of shared routes of transmission. GBV-C coinfection has been proposed to exert a beneficial influence on HIV-1 infection. In vitro studies demonstrated down-regulation of C-C chemokine receptor type 5 (CCR5) as a potential mechanism by which GBV-C modulates HIV-1 disease progression. We therefore studied surface expression of the two major HIV-1 coreceptors, CCR5 and CXC chemokine receptor type 4 (CXCR4), on CD4(+) and CD8(+) T-cells in 128 HIV-1-positive patients stratified with respect to their GBV-C status, immune function and highly active antiretroviral therapy (HAART) status in vivo. Methods: GBV-C infection was studied in 128 HIV-1-infected patients by nested reverse transcriptase PCR. Fluorescence-activated cell sorting analysis was used to measure CCR5 and CXCR4 surface expression on CD4(+) and CD8(+) T-cells. Results: GBV-C RNA replication was detected in 30% (38/128) of patients. In HIV-1-positive patients with advanced immunodeficiency, we found up-regulation of CCR5 surface expression on CD4(+) T-cells; however, in patients with GBV-C coinfection, no up-regulation of CCR5 CD4(+) T-cells was detected. Furthermore, CXCR4 surface expression was reduced in GBV-C-coinfected patients. These findings were independent of HAART status and HIV-1 viral load. HIV-1 coreceptor expression on CD8(+) T-cells was not altered in patients with GBV-C coinfection. Conclusions: GBV-C coinfection in HIV-1 disease leads to reduced expression of the two major HIV-1 coreceptors, CCR5 and CXCR4, on CD4(+) T-cells in patients at an advanced stage of immunodeficiency, providing a possible molecular explanation for the clinical benefit of GBV-C coinfection in late-stage HIV-1 disease. C1 [Schwarze-Zander, Carolynne; Neibecker, Markus; Othman, Sabrina; Rockstroh, Juergen K.; Spengler, Ulrich] Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany. [Tural, Cristina; Clotet, Bonaventura] Univ Autonoma Barcelona, Univ Hosp Germans Trias & Pujol, Irsi Caixa Fdn, Clin HIV Unit, E-08193 Barcelona, Spain. [Blackard, Jason T.] Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH USA. [Kupfer, Bernd] Univ Hosp Bonn, Inst Virol, Bonn, Germany. [Luechters, Guido] Univ Bonn, Res Dev Ctr, D-5300 Bonn, Germany. [Chung, Ray T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Schwarze-Zander, C (reprint author), Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany. EM carolynne.schwarze-zander@ukb.uni-bonn.de FU HW & J Hector foundation; National Institute on Drug Abuse [AI081564] FX This work was funded by the HW & J Hector foundation and the National Institute on Drug Abuse R21 award AI081564 to JTB. NR 17 TC 21 Z9 21 U1 0 U2 4 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 5 BP 745 EP 752 DI 10.3851/IMP1602 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 640DA UT WOS:000281026900007 PM 20710056 ER PT J AU Henrich, TJ Lewine, NRP Lin, N Ratner, L Sagar, M Tsibris, AMN Kuritzkes, DR AF Henrich, T. J. Lewine, N. R. P. Lin, N. Ratner, L. Sagar, M. Tsibris, A. M. N. Kuritzkes, D. R. TI A vicriviroc-resistant HIV-1 subtype C clinical isolate depends strongly on the second extracellular loop of CCR5 for entry SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Henrich, T. J.; Sagar, M.; Kuritzkes, D. R.] Brigham & Womens Hosp, Cambridge, MA USA. [Henrich, T. J.; Lin, N.; Sagar, M.; Tsibris, A. M. N.; Kuritzkes, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Lewine, N. R. P.] Harvard Univ, Cambridge, MA 02138 USA. [Lin, N.; Tsibris, A. M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ratner, L.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A77 EP A77 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300067 ER PT J AU Henrich, TJ Lewine, NRP Lin, N Ratner, L Sagar, M Tsibris, AMN Kuritzkes, DR AF Henrich, T. J. Lewine, N. R. P. Lin, N. Ratner, L. Sagar, M. Tsibris, A. M. N. Kuritzkes, D. R. TI A vicriviroc-resistant HIV-1 subtype C clinical isolate depends strongly on the second extracellular loop of CCR5 for entry SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Henrich, T. J.; Sagar, M.; Kuritzkes, D. R.] Brigham & Womens Hosp, Cambridge, MA USA. [Henrich, T. J.; Lin, N.; Sagar, M.; Tsibris, A. M. N.; Kuritzkes, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Lewine, N. R. P.] Harvard Univ, Cambridge, MA 02138 USA. [Lin, N.; Tsibris, A. M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ratner, L.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 63 BP A77 EP A77 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800082 ER PT J AU Mamputu, JC Falutz, J Pham, MH Potvin, D Soulban, G Grinspoon, S AF Mamputu, J-C Falutz, J. Pham, M. H. Potvin, D. Soulban, G. Grinspoon, S. TI Tesamorelin, a growth hormone-releasing factor analogue, improves inflammatory markers in HIV-infected patients with excess abdominal fat: relationships between changes in inflammatory markers and changes in visceral adipose tissue (VAT) SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Mamputu, J-C; Pham, M. H.; Potvin, D.; Soulban, G.] Theratechnologies Inc, Montreal, PQ, Canada. [Falutz, J.] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. [Grinspoon, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 8 BP A6 EP A7 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KN UT WOS:000287431200021 ER PT J AU Mamputu, JC Falutz, J Pham, MH Potvin, D Soulban, G Grinspoon, S AF Mamputu, J-C Falutz, J. Pham, M. H. Potvin, D. Soulban, G. Grinspoon, S. TI Tesamorelin, a growth hormone-releasing factor analogue, improves inflammatory markers in HIV-infected patients with excess abdominal fat: relationships between changes in inflammatory markers and changes in visceral adipose tissue (VAT) SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 12th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV CY NOV 04-06, 2010 CL London, ENGLAND C1 [Mamputu, J-C; Pham, M. H.; Potvin, D.; Soulban, G.] Theratechnol Inc, Montreal, PQ, Canada. [Falutz, J.] McGill Univ, Montreal Gen Hosp, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. [Grinspoon, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, S.] Harvard Univ, Sch Med, Boston, MA USA. RI Pham, Mirko/P-5510-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 4 BP A6 EP A7 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KQ UT WOS:000287431500007 ER PT J AU Putcharoen, O Kuritzkes, DR Tsibris, AMN AF Putcharoen, O. Kuritzkes, D. R. Tsibris, A. M. N. TI Vicriviroc-resistant HIV-1 clinical isolates exhibit delayed entry kinetics that correct in the presence of drug SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Putcharoen, O.; Kuritzkes, D. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Putcharoen, O.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kuritzkes, D. R.; Tsibris, A. M. N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tsibris, A. M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A75 EP A75 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300065 ER PT J AU Putcharoen, O Kuritzkes, DR Tsibris, AMN AF Putcharoen, O. Kuritzkes, D. R. Tsibris, A. M. N. TI Vicriviroc-resistant HIV-1 clinical isolates exhibit delayed entry kinetics that correct in the presence of drug SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Putcharoen, O.; Kuritzkes, D. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Putcharoen, O.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kuritzkes, D. R.; Tsibris, A. M. N.] Harvard Univ, Sch Med, Boston, MA USA. [Tsibris, A. M. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 61 BP A75 EP A75 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800080 ER PT J AU Stawiski, E Huang, W Tomo, J Frantzell, A Haddad, M Lie, Y Napolitano, L Whitcomb, J Leduc, R Brumme, Z Skowron, G Goetz, M Coakley, E AF Stawiski, E. Huang, W. Tomo, J. Frantzell, A. Haddad, M. Lie, Y. Napolitano, L. Whitcomb, J. Leduc, R. Brumme, Z. Skowron, G. Goetz, M. Coakley, E. TI HIV-1 disease stage significantly correlates with sensitivity of V3 sequence-based predictions of CXCR4 use SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT Workshop on International HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUL 08-12, 2010 CL Dubrovnik, CROATIA SP Univ California, Sch Med C1 [Stawiski, E.; Huang, W.; Tomo, J.; Frantzell, A.; Haddad, M.; Lie, Y.; Napolitano, L.; Whitcomb, J.; Coakley, E.] Monogram Biosci, San Francisco, CA USA. [Leduc, R.] Univ Minnesota, Minneapolis, MN USA. [Brumme, Z.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brumme, Z.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Skowron, G.] Roger Williams Med Ctr, Providence, RI USA. [Skowron, G.] Boston Univ Sch Med, Boston, MA USA. [Goetz, M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 SU 2 BP A131 EP A131 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 722KO UT WOS:000287431300109 ER PT J AU Stawiski, E Huang, W Toma, J Frantzell, A Haddad, M Lie, Y Napolitano, L Whitcomb, J Leduc, R Brumme, Z Skowron, G Goetz, M Coakley, E AF Stawiski, E. Huang, W. Toma, J. Frantzell, A. Haddad, M. Lie, Y. Napolitano, L. Whitcomb, J. Leduc, R. Brumme, Z. Skowron, G. Goetz, M. Coakley, E. TI HIV-1 disease stage significantly correlates with sensitivity of V3 sequence-based predictions of CXCR4 use SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV and Hepatitis Virus Drug Resistance and Curative Strategies Workshop CY JUN 08-12, 2010 CL Dubrovnik, CROATIA C1 [Stawiski, E.; Huang, W.; Toma, J.; Frantzell, A.; Haddad, M.; Lie, Y.; Napolitano, L.; Whitcomb, J.; Coakley, E.] Monogram Biosci, San Francisco, CA USA. [Leduc, R.] Univ Minnesota, Minneapolis, MN USA. [Brumme, Z.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Brumme, Z.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Skowron, G.] Roger Williams Med Ctr, Providence, RI USA. [Skowron, G.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Goetz, M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2010 VL 15 IS 4 MA 105 BP A131 EP A131 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 629QW UT WOS:000280215800124 ER PT J AU Bitran, S Hofmann, SG AF Bitran, Stella Hofmann, Stefan G. TI Effect of affect on social cost bias in social anxiety disorder SO ANXIETY STRESS AND COPING LA English DT Article DE social anxiety; affect; self-regulation; mood induction ID COMORBIDITY SURVEY REPLICATION; PERFORMANCE STANDARDS; AFFECTIVE STATES; PHOBIA; MOOD; PERCEPTION; INFORMATION; INDUCTION; COGNITION; EMOTIONS AB The cognitive model of social anxiety disorder (SAD) assumes that cognitive biases are important maintaining factors of the disorder. Research and theory have highlighted the impact of cognitive self-regulatory processes on affect, but have not sufficiently focused on the influence of affect on self-regulatory cognitions. The present study examined the influence of affect on cognitive self-regulatory mechanisms in SAD by focusing on one critical cognitive bias, estimated social cost. Individuals with SAD (N = 48) and non-anxious controls (N = 48) were randomly assigned to one of three experimental, affect induction conditions (negative, positive, or neutral) before giving a 10-minute impromptu, videotaped speech. As expected, the affect manipulation resulted in changes in estimated social cost. However, this effect was not specific to individuals with SAD. Participants in the positive affect condition in both groups had the highest social cost estimates post-speech challenge. These results suggest that social cost bias is dependent on the affective state in both individuals with SAD and controls. C1 [Bitran, Stella] Massachusetts Gen Hosp, Dept Psychiat, DCRP, Boston, MA 02114 USA. [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02115 USA. RP Bitran, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, DCRP, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM sbitran@partners.org RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 53 TC 1 Z9 1 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2010 VL 23 IS 3 BP 273 EP 287 DI 10.1080/10615801003586846 PG 15 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 574VI UT WOS:000276021900004 PM 20146115 ER PT S AU Levy, J Kiran, S Caplan, D Berardino, A Sandberg, C AF Levy, Joshua Kiran, Swathi Caplan, David Berardino, Alex Sandberg, Chaleece BE Papagno, C TI Development of a Test of Effects of Syntactic Comprehension Disorders on Discourse Comprehension SO AOA2010, 48TH ACADEMY OF APHASIA PROCEEDINGS SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 48th Conference on Academy-of-Aphasia (AOA 2010) CY OCT 24-26, 2010 CL Athens, GREECE SP Acad Aphasia C1 [Levy, Joshua; Caplan, David] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM JWLEVY@PARTNERS.ORG RI Kiran, S/B-1892-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2010 VL 6 BP 164 EP 165 DI 10.1016/j.sbspro.2010.08.081 PG 2 WC Neurosciences; Psychology; Psychology, Multidisciplinary; Social Sciences, Interdisciplinary SC Neurosciences & Neurology; Psychology; Social Sciences - Other Topics GA BTK22 UT WOS:000287140400078 ER PT J AU Dickey, MW Yoo, H AF Dickey, Michael Walsh Yoo, Hyunsoo TI Predicting outcomes for linguistically specific sentence treatment protocols SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Clinical Aphasiology Conference CY MAY 26-30, 2009 CL Keystone, CO DE Aphasia; Treatment; Sentence production; Syntax; Outcomes ID AGRAMMATIC APHASIA; SYNTACTIC COMPLEXITY; MOVEMENT STRUCTURES; UNDERLYING FORMS; BROCAS APHASIA; WH-MOVEMENT; COMPREHENSION; DEFICITS; STROKE AB Background: Linguistically motivated treatment protocols like the Treatment of Underlying Forms (TUF: Thompson Shapiro, 2005) have shown significant success in remediating aphasic individuals' sentence production deficits. However, adults with aphasia are not uniform in their response to TUF: not all individuals trained with TUF successfully acquire the sentence types they are trained on or generalise to untrained sentence types. More research is therefore needed to determine which individuals are most likely to benefit from TUF treatment. Aims: The current study analysed existing TUF treatment studies in an effort to determine what measures may be predictive of TUF outcomes for different aphasic individuals. Three different measures were tested: aphasia severity, auditory comprehension ability, and complex sentence comprehension ability. Methods Procedures: A meta-analysis was conducted based on existing TUF treatment studies drawn from the aphasiological literature. These studies included individual demographic, language-testing, and treatment data from 30 aphasic individuals. Regression analyses were conducted comparing these individuals' improvements on production of treated and untreated sentence types (treatment and generalisation effects) with the three predictor measures (severity, auditory comprehension, and complex sentence comprehension scores). Outcomes Results: Only one of the measures tested, general auditory comprehension, was predictive of the size of individuals' gains on treated sentence types. None of the measures tested was predictive of these individuals' generalisation to untrained structures. Conclusions: The current results suggest that general auditory comprehension appears to be related to improved sentence production following TUF treatment. In contrast, neither overall aphasia severity nor performance with complex sentence stimuli is a strong predictor of TUF treatment outcomes. Interestingly, there were no strong relationships between any of the measures and the generalisation effect scores. These findings suggest that clinicians should consider a patient's general auditory comprehension when deciding whether TUF would be appropriate. They also suggest that partially different cognitive mechanisms may underlie treatment and generalisation effects following treatment, at least for TUF protocols. C1 [Dickey, Michael Walsh] Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Dickey, MW (reprint author), Univ Pittsburgh, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 38 TC 6 Z9 6 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2010 VL 24 IS 6-8 BP 787 EP 801 AR PII 922040489 DI 10.1080/02687030903515354 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 628WL UT WOS:000280154900011 ER PT J AU True, G Bartlett, MR Fink, RB Linebarger, MC Schwartz, M AF True, Gala Bartlett, Megan R. Fink, Ruth B. Linebarger, Marcia C. Schwartz, Myrna TI Perspectives of persons with aphasia towards SentenceShaper To Go: A qualitative study SO APHASIOLOGY LA English DT Article DE Augmentative and alternative communication; Persons with aphasia; Qualitative research methods; Supportive interviewing techniques; Attitudes and preferences ID PROCESSING PROSTHESIS; LANGUAGE PRODUCTION; ALTERNATIVE COMMUNICATION; AAC; SUPPORT; ADULTS; INFORMATIVENESS; DISORDERS; PARTNERS; RATINGS C1 [True, Gala] Ctr Hlth Equ & Res Promot, VA Med Ctr, Philadelphia, PA 19104 USA. [Bartlett, Megan R.; Fink, Ruth B.; Schwartz, Myrna] Moss Rehabil Res Inst, Philadelphia, PA USA. [Linebarger, Marcia C.] Psycholinguist Technol Inc, Jenkintown, PA USA. RP True, G (reprint author), Ctr Hlth Equ & Res Promot, VA Med Ctr, 9th Floor E,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM galatrue@verizon.net FU NIH [1 R01 HD043991] FX The authors wish to thank Jennifer S. Lowery MA CCC/SLP, Michelene Kalinyak-Fliszar MA CCC/SLP, and Roberta Brooks MA CCC/SLP for their assistance with the CIU scoring procedures and modifications. We gratefully acknowledge Paula Sobel MA CCC/SLP for her assistance with the interview validation procedures and Laura MacMullen BA for her help with the literature review and construction of earlier drafts. We also wish to thank the anonymous reviewers for their insightful comments. Support for this study was provided by a grant from the NIH (#1 R01 HD043991; P.I., M. Schwartz). NR 42 TC 3 Z9 3 U1 0 U2 13 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2010 VL 24 IS 9 BP 1032 EP 1050 AR PII 917993626 DI 10.1080/02687030903249350 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA 628WM UT WOS:000280155000004 ER PT J AU Hula, W Donovan, NJ Kendall, DL Gonzalez-Rothi, LJ AF Hula, William Donovan, Neila J. Kendall, Diane L. Gonzalez-Rothi, Leslie J. TI Item response theory analysis of the Western Aphasia Battery SO APHASIOLOGY LA English DT Article DE Aphasia; Item response theory; Rasch analysis; Assessment; Psychometrics ID VALIDITY; STATISTICS; EFFICACY; ADULTS AB Background: The Western Aphasia Battery (WAB) (Kertesz, 1982) is one of the most frequently used tests of general language performance in aphasia, despite significant psychometric limitations. Item response theory (IRT) provides measurement models that may address some of these limitations. Aims: The purposes of this investigation were to evaluate whether the WAB can be productively fit to an IRT model, and to evaluate whether IRT modelling confers psychometric benefits. Methods Procedures: An analysis of WAB data collected from a convenience sample of 101 individuals with chronic aphasia was undertaken. Exploratory factor analysis was conducted to evaluate the dimensionality of the WAB, and a Rasch Partial Credit Model was fit to the data. Item fit statistics and residual correlations were used to test key model assumptions. The distribution of traditional and Rasch-based person scores, and the relationship between ability level and test reliability were also examined. Outcomes Results: Despite reasonable overall fit to the model, a small number of WAB items demonstrated significant misfit, suggesting that they do not productively contribute to the measurement of aphasia severity. A small but substantial minority of individuals also demonstrated inadequate fit to the measurement model. Rasch-based scores were more normally distributed than traditional scores, and score reliability varied substantially across the ability range. Conclusions: These results suggest that the WAB may be productively fit to an IRT-based measurement model, and that such models may be used to improve the psychometric properties of aphasia tests. Benefits include indices of severity and score reliability that are more valid than those currently in use, and the potential for improved efficiency of testing through adaptive administration. C1 [Hula, William] VA Pittsburgh Healthcare Syst, CCC SLP, Pittsburgh, PA 15206 USA. [Hula, William] Univ Pittsburgh, Pittsburgh, PA USA. [Donovan, Neila J.] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Kendall, Diane L.] Univ Washington, Seattle, WA 98195 USA. [Gonzalez-Rothi, Leslie J.] Malcolm Randall VA Med Ctr, Gainesville, FL USA. [Gonzalez-Rothi, Leslie J.] Univ Florida, Gainesville, FL USA. RP Hula, W (reprint author), VA Pittsburgh Healthcare Syst, CCC SLP, 7180 Highland Dr 132A-H, Pittsburgh, PA 15206 USA. EM William.Hula@VA.gov FU VA [C6210M]; VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center; VA RR&D Brain Rehabilitation Research Center of Excellence [B6793C] FX Dr Hula's work was supported by VA RR&D Career Development Award # C6210M and the VA Pittsburgh Healthcare System Geriatric Research Education and Clinical Center. Dr Gonzalez-Rothi's work was supported by the VA RR&D Brain Rehabilitation Research Center of Excellence Award # B6793C. The authors thank Sally Ouimet-Waters, Katherine Malek, Matthew Comer, and Lauren Bislick for their work on data coding, data entry, and data management. An earlier draft of this work was presented to the 2009 Clinical Aphasiology Conference in Keystone, CO. The authors have no conflicts of interest to report. NR 55 TC 5 Z9 5 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2010 VL 24 IS 11 BP 1326 EP 1341 AR PII 920190140 DI 10.1080/02687030903422502 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 659QB UT WOS:000282580900002 ER PT J AU Kutuk, O Basaga, H AF Kutuk, Ozgur Basaga, Huveyda BE Preedy, VR TI Apoptotic Pathways in Mitochondria SO APOPTOSIS SE Modern Insights into Disease from Molecules to Man LA English DT Article; Book Chapter ID CYTOCHROME-C RELEASE; RADIATION-INDUCED APOPTOSIS; SERINE-PROTEASE; BCL-2 FAMILY; DEATH; DYSFUNCTION; INHIBITOR; XIAP; PARL; BAX AB Apoptosis or programmed cell death is a fundamental process for embryogenesis, tissue homeostasis and prevention of oncogenesis. Dysregulated apoptosis contributes to the pathogenesis of many human diseases, such as cancer, diabetes and neurodegenerative disorders. The extrinsic or death receptor-mediated and mitochondrial apoptotic pathways are two main apoptosis pathways in mammalian cells. The most critical step of apoptosis is the release of prodeath proteins including cytochrome c from mitochondria through permeabilization of outer mitochondrial membrane. Smac/DIABLO, AIF, HtrA2 and ARTS are among the other prodeath molecules released from mitochondria. Bcl-2 protein family members act as major regulators of apoptosis by controlling mitochondrial permeabilization. Their function is dictated by protein-protein interactions as a result selective binding patterns of BH3-only proteins with antiapoptotic Bcl-2 proteins. Multidomain proapoptotic Bcl-2 proteins Bax and Bak are crucial for mitochondrial permeabilization and they facilitate the release of cytochrome c from mitochondria by forming pores in the outer mitochondrial membrane. Currently, there are two different models explaining Bax and Bak activation upstream of cytochrome c release. In addition, mitochondrial remodeling by Opa1 and Parl also contributes to apoptosis by controlling mitochondrial cristae junctions. In this chapter we briefly address these concepts to help in understanding the mechanisms of apoptosis regulation by mitochondria. A better understanding of these pathways would allow us to develop novel therapeutic tools for human diseases and to improve preventive measures targeting human health. C1 [Kutuk, Ozgur] Dana Farber Canc Inst, Boston, MA 02115 USA. [Basaga, Huveyda] Sabanci Univ, Biol Sci & Bioengn Program, Fac Engn & Nat Sci, TR-34956 Istanbul, Turkey. RP Kutuk, O (reprint author), Dana Farber Canc Inst, Dana530,44 Binney St, Boston, MA 02115 USA. EM Ozgur_Kutuk@dfci.harvard.edu; huveyda@sabanciuniv.edu NR 30 TC 0 Z9 0 U1 0 U2 1 PU SCIENCE PUBLISHERS INC PI ENFIELD PA MAY ST, PO BOX 699, ENFIELD, NH 03748 USA BN 978-1-57808-583-5 J9 MOD INSIGHTS DIS MOL JI Mod. Insights Dis. Mol. Man PY 2010 BP 3 EP + DI 10.1201/9781439845431-3 D2 10.1201/9781439845431 PG 17 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Pathology SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Pathology GA BTO67 UT WOS:000287577000002 ER PT J AU Wang, ZW Ge, RB Olumi, AF AF Wang, Zongwei Ge, Rongbin Olumi, Aria F. BE Preedy, VR TI Apoptosis in Prostate Cancer SO APOPTOSIS SE Modern Insights into Disease from Molecules to Man LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; TRAIL; CELLS; RESISTANCE; EXPRESSION; C-FLIP(L); LIGAND AB Prostate cancer is the second leading cause of cancer death in American men accounting for over 180,000 new cases and approximately 28,000 deaths annually. Since, aberrant apoptotic pathways contribute to initiation and progression of neoplasia, including prostate cancer, pro-apoptotic agents are attractive for treatment of advanced prostate cancer. Therefore, inhibiting anti-apoptotic molecules or potentiating pro-apoptotic molecules can serve as excellent treatment strategies for treatment of prostate cancer. Alterations in many apoptotic related genes including the Bcl-2 family proteins, NF-kappa B, p53, PTEN/P13K/AKT, caspase and inhibitors of apoptosis proteins (IAP) have been implicated in prostate progression. Moreover, apoptosis related genes also play a significant role on radioresistant and hormone-independent forms of prostate cancer. A promising agent, TRAIL, induces apoptosis in cancer cells, but spares normal cells, therefore, it is an ideal cancer therapeutic agent with minimal cytotoxicity. However, some cancer cells develop resistance to pro-apoptotic agents. Therefore, overcoming resistant cancer cells and identifying patients who may benefit the most from pro-apoptotic therapies is important in treatment of patients with advanced prostate cancer. Defining the apoptotic mediated signal transduction pathways and the intricate molecular interactions will help guide us in developing drugs with less toxicity for appropriately selected patients with prostate cancer and other malignancies. C1 [Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Bertucci Ctr Genitourinary Canc, Sch Med,Dept Urol, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bertucci Ctr Genitourinary Canc, Sch Med,Dept Urol, 55 Fruit St,Yawkey Bldg,Suite 7E, Boston, MA 02114 USA. EM zwang0@partners.org; rge1@partners.org; aolumi@partners.org NR 15 TC 1 Z9 1 U1 0 U2 2 PU SCIENCE PUBLISHERS INC PI ENFIELD PA MAY ST, PO BOX 699, ENFIELD, NH 03748 USA BN 978-1-57808-583-5 J9 MOD INSIGHTS DIS MOL JI Mod. Insights Dis. Mol. Man PY 2010 BP 293 EP 309 DI 10.1201/9781439845431-23 D2 10.1201/9781439845431 PG 17 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental; Pathology SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine; Pathology GA BTO67 UT WOS:000287577000020 ER PT J AU Schreer, JF Lapierre, JL Hammill, MO AF Schreer, Jason F. Lapierre, Jennifer L. Hammill, Michael O. TI Stomach Temperature Telemetry Reveals that Harbor Seal (Phoca vitulina) Pups Primarily Nurse in the Water SO AQUATIC MAMMALS LA English DT Article DE telemetry; stomach temperature; harbor seal; Phoca vitulina; nursing; pups ID FORAGING SUCCESS; LACTATION; CONSUMPTION; WASHINGTON; INGESTION; SEABIRDS; PATTERNS; CONCOLOR; BEHAVIOR; QUANTIFY AB Research on a captive harbor seal (Phoca vitulina) mother-pup pair showed that ingestion of milk caused a decrease in stomach temperature (Hedd et al., 1995). Herein the feasibility of stomach temperature telemetry for measuring nursing behavior was tested in wild harbor seal pups from the St. Lawrence River Estuary. Fifteen pups were outfitted with time-depth recorders, stomach temperature transmitters (STT), and stomach temperature recorders in 2002 and 2003. Twelve pups were recaptured, and seven yielded usable stomach temperature data. Excluding a mortality that lost its transmitter the day of release, transmitter retention time ranged from at least 7 to 22 d (12.5 +/- 1.45 d) based on a STT signal at recapture. Pups that gained more weight had a higher frequency of decreases in stomach temperature (DST) (R(2) = 0.954, p < 0.001). Depth and external temperature data showed that most DST occurred while pups were "in the water" (57%) followed by "just before or after hauling out" (19%), "just before or after entering the water" (15%), and "hauled out" (9%) (chi(2) = 56.376, p < 0.001). The frequency DST did not change with age, and there was no diel pattern of DST, which also did not change with age. These findings indicate that transmitter retention times are sufficient to monitor most of the nursing period for harbor seals, that stomach temperature can be used to quantify nursing characteristics in the field, and that a telemetric technique is needed for harbor seals as most nursing events occur in the water. C1 [Schreer, Jason F.] SUNY Coll Potsdam, Dept Biol, Potsdam, NY 13676 USA. [Lapierre, Jennifer L.] Vet Affairs Greater Los Angeles Hlth Care Syst, Neurobiol Res 151 A3, North Hills, CA 91343 USA. [Lapierre, Jennifer L.] Univ Calif Berkeley, Ctr Sleep Res, Semel Inst Neurosci & Human Behav, Berkeley, CA 94720 USA. [Hammill, Michael O.] Inst Maurice Lamontagne, Dept Fisheries & Oceans, Mont Joli, PQ G5H 3Z4, Canada. RP Schreer, JF (reprint author), SUNY Coll Potsdam, Dept Biol, Potsdam, NY 13676 USA. EM schreejf@potsdam.edu FU SUNY Potsdam; University of Waterloo; Department of Fisheries and Oceans; Natural Sciences and Engineering Research Council of Canada FX All procedures were conducted in accordance with the guidelines set out by the Canadian Council on Animal Care as implemented by the University of Waterloo, Waterloo, Ontario, Canada. We thank Pierre Carter, Erin Copeland, Jean-Francois Gosselin, James Greig, and Geoff Yunker for help in the field and Meghan Ellis for compiling the graphical output. We also thank several reviewers and editors for providing comments to improve this manuscript. This work was supported by SUNY Potsdam, the University of Waterloo, the Department of Fisheries and Oceans, and the Natural Sciences and Engineering Research Council of Canada. JFS thanks XOQ. NR 26 TC 3 Z9 3 U1 2 U2 13 PU EUROPEAN ASSOC AQUATIC MAMMALS PI MOLINE PA C/O DR JEANETTE THOMAS, BIOLOGICAL SCIENCES, WESTERN ILLIONIS UNIV-QUAD CITIES, 3561 60TH STREET, MOLINE, IL 61265 USA SN 0167-5427 J9 AQUAT MAMM JI Aquat. Mamm. PY 2010 VL 36 IS 3 BP 270 EP 277 DI 10.1578/AM.36.3.2010.270 PG 8 WC Marine & Freshwater Biology; Zoology SC Marine & Freshwater Biology; Zoology GA 670UJ UT WOS:000283452500006 ER PT J AU Lindsay, RW Heaton, JT Edwards, C Smitson, C Hadlock, TA AF Lindsay, Robin W. Heaton, James T. Edwards, Colin Smitson, Christopher Hadlock, Tessa A. TI Nimodipine and Acceleration of Functional Recovery of the Facial Nerve After Crush Injury SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID RECURRENT LARYNGEAL NERVE; VASOACTIVE TREATMENT; WHISKER MOVEMENTS; HEARING PRESERVATION; RODENT WHISKING; ADULT-RAT; RESECTION; RECEPTOR; NEURONS; SURGERY AB Objective: To establish whether nimodipine, a calcium channel blocker, accelerates or otherwise improves functional recovery of whisking after facial nerve crush injury in the rat. Methods: Thirty rats underwent exposure of the left main trunk of the facial nerve followed by a standard crush injury and subsequent quantitative facial movement testing. Animals were randomized into an experimental group (n=15) and a control group (n=15). Four days prior to facial nerve manipulation, experimental animals underwent subcutaneous implantation of a nimodipine-secreting pellet. All animals were tested preoperatively and on postoperative days 2, 8 to 17, 20, 22, 24, and 31 using a validated, quantitative whisking kinematics apparatus. Whisks were analyzed for amplitude, velocity, and acceleration. Results: Animals receiving nimodipine demonstrated significantly better whisking on 5 days (postoperative days 9, 11 to 13, and 20) compared with control animals (P <.001, P=.003, P=.009, P=.009, and P=.009, respectively; 1-tailed t test). Overall, the nimodipine-treated animals showed earlier recovery compared with the untreated animals. Conclusions: We demonstrate that nimodipine improves recovery of whisking after facial nerve crush. This finding corroborates the semiquantitative findings of others, and provides complete whisking kinematic data on its effects. Given the low adverse effect profile of nimodipine, there may be clinical implications in its administration in patients experiencing facial nerve injury. C1 [Lindsay, Robin W.; Edwards, Colin; Smitson, Christopher; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lindsay, Robin W.] Natl Naval Med Ctr, Div Otolaryngol Head & Neck Surg, Dept Otolaryngol Head & Neck Surg, Bethesda, MD 20889 USA. RP Lindsay, RW (reprint author), Natl Naval Med Ctr, Div Otolaryngol Head & Neck Surg, Dept Otolaryngol Head & Neck Surg, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM robin_lindsay@meei.harvard.edu FU NINDS NIH HHS [R01 NS071067]; PHS HHS [K-08 DEO15665-01 A2] NR 29 TC 17 Z9 17 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD JAN-FEB PY 2010 VL 12 IS 1 BP 49 EP 52 PG 4 WC Surgery SC Surgery GA 544XC UT WOS:000273692600008 PM 20083741 ER PT J AU Schwartz, CE Kunwar, PS Greve, DN Moran, LR Viner, JC Covino, JM Kagan, J Stewart, SE Snidman, NC Vangel, MG Wallace, SR AF Schwartz, Carl E. Kunwar, Pratap S. Greve, Douglas N. Moran, Lyndsey R. Viner, Jane C. Covino, Jennifer M. Kagan, Jerome Stewart, S. Evelyn Snidman, Nancy C. Vangel, Mark G. Wallace, Stuart R. TI Structural Differences in Adult Orbital and Ventromedial Prefrontal Cortex Predicted by Infant Temperament at 4 Months of Age SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MIDBRAIN PERIAQUEDUCTAL GRAY; HUMAN CEREBRAL-CORTEX; HUMAN ORBITOFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; SURFACE-BASED ANALYSIS; MACAQUE MONKEYS; BEHAVIORAL-INHIBITION; CORTICAL PROJECTIONS; EMOTIONAL RESPONSES; SOCIAL ANXIETY AB Context: The term temperament refers to a biologically based predilection for a distinctive pattern of emotions, cognitions, and behaviors first observed in infancy or early childhood. High-reactive infants are characterized at age 4 months by vigorous motor activity and crying in response to unfamiliar visual, auditory, and olfactory stimuli, whereas low-reactive infants show low motor activity and low vocal distress to the same stimuli. High-reactive infants are biased to become behaviorally inhibited in the second year of life, defined by timidity with unfamiliar people, objects, and situations. In contrast, low-reactive infants are biased to develop into uninhibited children who spontaneously approach novel situations. Objective: To examine whether differences in the structure of the ventromedial or orbitofrontal cerebral cortex at age 18 years are associated with high or low reactivity at 4 months of age. Design: Structural magnetic resonance imaging in a cohort of 18-year-olds enrolled in a longitudinal study. Temperament was determined at 4 months of age by direct observation in the laboratory. Setting: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital. Participants: Seventy-six subjects who were high-reactive or low-reactive infants at 4 months of age. Main Outcome Measure: Cortical thickness. Results: Adults with a low-reactive infant temperament, compared with those categorized as high reactive, showed greater thickness in the left orbitofrontal cortex. Subjects categorized as high reactive in infancy, compared with those previously categorized as low reactive, showed greater thickness in the right ventromedial prefrontal cortex. Conclusions: To our knowledge, this is the first demonstration that temperamental differences measured at 4 months of age have implications for the architecture of human cerebral cortex lasting into adulthood. Understanding the developmental mechanisms that shape these differences may offer new ways to understand mood and anxiety disorders as well as the formation of adult personality. Arch Gen Psychiatry. 2010;67(1):78-84 C1 [Schwartz, Carl E.; Kunwar, Pratap S.; Moran, Lyndsey R.; Viner, Jane C.; Covino, Jennifer M.; Stewart, S. Evelyn; Snidman, Nancy C.; Wallace, Stuart R.] Dept Psychiat, Dev Neuroimaging & Psychopathol Lab, Boston, MA USA. [Greve, Douglas N.] Dept Radiol, Boston, MA USA. [Greve, Douglas N.; Stewart, S. Evelyn; Snidman, Nancy C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Snidman, Nancy C.] Childrens Hosp, Boston, MA 02115 USA. [Schwartz, Carl E.; Kunwar, Pratap S.; Greve, Douglas N.; Vangel, Mark G.; Wallace, Stuart R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kagan, Jerome] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Vangel, Mark G.] Massachusetts Gen Hosp, Gen Clin Res Ctr, Cambridge, MA USA. [Vangel, Mark G.] MIT, Cambridge, MA 02139 USA. RP Schwartz, CE (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Bldg 149,13th St, Boston, MA 02129 USA. EM carl_schwartz@hms.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU National Institutes of Mental Health [5R01MH071467]; Center for Functional Neuroimaging [5P41 RR14075-07]; General Clinical Research Center [5M01RR001066-27]; Harvard Clinical and Translational Science Center [1 UL1 RR025758-01]; Mental Illness and Neuroscience Discovery Institute; Athinoula A. Martinos Center for Biomedical Imaging FX This study was supported by National Institutes of Mental Health grant 5R01MH071467 (Dr Schwartz), National Center for Research Resources grants 5P41 RR14075-07 (Center for Functional Neuroimaging Technologies), 5M01RR001066-27 (General Clinical Research Center), and 1 UL1 RR025758-01 (Harvard Clinical and Translational Science Center), the Mental Illness and Neuroscience Discovery Institute, and the Athinoula A. Martinos Center for Biomedical Imaging. Previous Presentations: Portions of this work were presented at the Symposium on Biological Complexity: Genes, Circuits, and Behavior, sponsored by the Salk Institute, Nature, and Fondation IPSEN; January 10, 2008; La Jolla, California; and at the 47th Annual Meeting of the American College of Neuropsychopharmacology; December 7, 2008; Scottsdale, Arizona. NR 81 TC 33 Z9 33 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2010 VL 67 IS 1 BP 78 EP 84 PG 7 WC Psychiatry SC Psychiatry GA 539NX UT WOS:000273262800010 PM 20048225 ER PT J AU Elkind, MSV Ramakrishnan, P Moon, YP Boden-Albala, B Liu, KM Spitalnik, SL Rundek, T Sacco, RL Paik, MC AF Elkind, Mitchell S. V. Ramakrishnan, Pankajavalli Moon, Yeseon P. Boden-Albala, Bernadette Liu, Khin M. Spitalnik, Steve L. Rundek, Tanja Sacco, Ralph L. Paik, Myunghee C. TI Infectious Burden and Risk of Stroke The Northern Manhattan Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; CORONARY-HEART-DISEASE; 1ST ISCHEMIC-STROKE; CHLAMYDIA-PNEUMONIAE; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; PERIODONTAL-DISEASE; CEREBRAL-ISCHEMIA AB Objective: To determine the association between a composite measure of serological test results for common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2) and stroke risk in a prospective cohort study. Design: Prospective cohort followed up longitudinally for median 8 years. Setting: Northern Manhattan Study. Patients: Randomly selected stroke-free participants from a multiethnic urban community. Main Outcome Measure: Incident stroke and other vascular events. Results: All 5 infectious serological results were available from baseline samples in 1625 participants (mean [SD] age, 68.4 [10.1] years; 64.9% women). Cox proportional hazards models were used to estimate associations of each positive serological test result with stroke. Individual parameter estimates were then combined into a weighted index of infectious burden and used to calculate hazard ratios and confidence intervals for association with risk of stroke and other outcomes, adjusted for risk factors. Each individual infection was positively, though not significantly, associated with stroke risk after adjusting for other risk factors. The infectious burden index was associated with an increased risk of all strokes (adjusted hazard ratio per standard deviation, 1.39; 95% confidence interval, 1.02-1.90) after adjusting for demographics and risk factors. Results were similar after excluding those with coronary disease (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13) and adjusting for inflammatory biomarkers. Conclusions: A quantitative weighted index of infectious burden was associated with risk of first stroke in this cohort. Future studies are needed to confirm these findings and to further define optimal measures of infectious burden as a stroke risk factor. C1 [Elkind, Mitchell S. V.; Moon, Yeseon P.; Boden-Albala, Bernadette] Columbia Univ, Dept Neurol, New York, NY USA. [Liu, Khin M.; Spitalnik, Steve L.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Paik, Myunghee C.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Paik, Myunghee C.] Columbia Univ, Joseph P Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Ramakrishnan, Pankajavalli] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rundek, Tanja; Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Genet, Miami, FL 33136 USA. RP Elkind, MSV (reprint author), Neurol Inst, 710 W 168th St,Box 182, New York, NY 10032 USA. EM mse13@columbia.edu RI Boden Albala, Bernadette/J-5703-2013; OI Boden Albala, Bernadette/0000-0001-5664-2342; Spitalnik, Steven/0000-0002-8528-4561 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R37 29993, R01 48134] FX This research was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke grants R37 29993 (Drs Elkind and Sacco) and R01 48134 (Dr Elkind). NR 44 TC 61 Z9 67 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2010 VL 67 IS 1 BP 33 EP 38 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 542YQ UT WOS:000273535700004 PM 19901154 ER PT J AU Baker, LD Frank, LL Foster-Schubert, K Green, PS Wilkinson, CW McTiernan, A Plymate, SR Fishel, MA Watson, GS Cholerton, BA Duncan, GE Mehta, PD Craft, S AF Baker, Laura D. Frank, Laura L. Foster-Schubert, Karen Green, Pattie S. Wilkinson, Charles W. McTiernan, Anne Plymate, Stephen R. Fishel, Mark A. Watson, G. Stennis Cholerton, Brenna A. Duncan, Glen E. Mehta, Pankaj D. Craft, Suzanne TI Effects of Aerobic Exercise on Mild Cognitive Impairment A Controlled Trial SO ARCHIVES OF NEUROLOGY LA English DT Article ID VERBAL FLUENCY PERFORMANCE; HIGH-INTENSITY EXERCISE; ADRENAL AXIS RESPONSE; ALZHEIMERS-DISEASE; OLDER-ADULTS; NEUROTROPHIC FACTOR; PHYSICAL-ACTIVITY; INSULIN-RESISTANCE; SYNAPTIC PLASTICITY; GENDER-DIFFERENCES AB Objectives: To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design: Six-month, randomized, controlled, clinical trial. Setting: Veterans Affairs Puget Sound Health Care System clinical research unit. Participants: Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age, 70 years). Intervention: Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures: Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and beta-amyloids 40 and 42. Results: Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions: This study provides support, using rigorous controlled methodology, for a potent nonpharmacologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise. C1 [Baker, Laura D.; Frank, Laura L.; Wilkinson, Charles W.; Watson, G. Stennis; Cholerton, Brenna A.; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Foster-Schubert, Karen; Green, Pattie S.; McTiernan, Anne; Plymate, Stephen R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Fishel, Mark A.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Duncan, Glen E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Nutr Sci Program, Seattle, WA 98195 USA. [Baker, Laura D.; Wilkinson, Charles W.; Plymate, Stephen R.; Fishel, Mark A.; Watson, G. Stennis; Cholerton, Brenna A.; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Green, Pattie S.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Foster-Schubert, Karen; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. [Frank, Laura L.] Washington State Univ, Dept Nutr & Exercise Metab, Spokane, WA USA. [Fishel, Mark A.] Landstuhl Reg Med Ctr, Dept Med, Landstuhl, Germany. [Mehta, Pankaj D.] New York State Inst Basic Res Dev Disabil, Dept Immunol, New York, NY USA. RP Baker, LD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ldbaker@uw.edu RI Duncan, Glen/A-3771-2008 OI Duncan, Glen/0000-0001-6909-1869 FU Department of Veterans Affairs; Alzheimer's Association [NIRG-04-1010] FX This study was supported by the Department of Veterans Affairs and Alzheimer's Association grant NIRG-04-1010. NR 83 TC 336 Z9 349 U1 8 U2 102 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2010 VL 67 IS 1 BP 71 EP 79 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 542YQ UT WOS:000273535700010 PM 20065132 ER PT J AU Aiello, LP Shen, LQ AF Aiello, Lloyd Paul Shen, Lucy Q. TI Association of Proliferative Diabetic Retinopathy With Insulin Use and Microalbuminuria Reply SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID ROSIGLITAZONE; ONSET C1 [Aiello, Lloyd Paul] Joslin Diabet Ctr, Bethesda Eye Inst, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Bethesda Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM aiello@joslab.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2010 VL 128 IS 1 BP 146 EP 147 DI 10.1001/archophthalmol.2009.364 PG 3 WC Ophthalmology SC Ophthalmology GA 542XO UT WOS:000273532800029 ER PT J AU Sepulveda, JL Tanhehco, YC Frey, M Guo, LD Cropcho, LJ Gibson, KM Blair, HC AF Sepulveda, Jorge L. Tanhehco, Yvette C. Frey, Monica Guo, Lida Cropcho, Lorna J. Gibson, K. Michael Blair, Harry C. TI Variation in Human Erythrocyte Membrane Unsaturated Fatty Acids Correlation With Cardiovascular Disease SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; SUDDEN CARDIAC DEATH; ADIPOSE-TISSUE; LINOLEIC-ACID; BLOOD; PLASMA; RISK; SERUM; BIOMARKERS AB Context.-Whether cell membrane fatty acid (FA) composition is a useful indicator of vascular disease is unclear. Objective.-To study variation of erythrocyte (RBC) membrane FA in samples from healthy volunteers, hospitalized patients, and cardiac troponin I-elevated patients with myocardial damage without a priori assumptions as to FA composition. Design.-We separated FAs extracted from RBCs by gas chromatography and identified them by mass spectrometry. Fatty acids with abundance greater than 1% of total were quantified and compared: hexadecanoic (C16:0), octadecadienoic (C18:2), cis- and trans-octadecenoic (C18: 1), and eicosatetraenoic (C20:4) acids. Deuterated standards established proportionality of FA recovery. The cis-and trans-C18:1 identification was verified by comparison with standards. Results.-In troponin-positive samples, C18: 2 to C18: 1 ratios were increased 30% compared with healthy controls or with random patient samples. Erythrocyte trans-C18: 1 had a wide variation, similar to 10-fold, in all groups but without differences between groups. Replicates showed that the wide range of RBC trans-FA load is not due to analytic variation. In healthy subjects, the RBC content of lower molecular weight FAs (C16-C18) correlated with serum low-density lipoprotein cholesterol, but despite the established relationship between dietary trans-FA and increased low-density lipoprotein cholesterol, lipid profiles had no correlation with RBC trans-FA content. Conclusions.-Erythrocyte accumulation of unsaturated FA may be a useful indicator of vascular disease, whereas the wide range in trans-FAs suggests that both diet and genetic variation affect RBC trans-FA accumulation. Unsaturated FAs increase membrane fluidity and may reflect a natural response to subclinical vascular changes, which may in turn reflect increased risk of clinical disease. (Arch Pathol Lab Med. 2010; 134: 73-80) C1 [Frey, Monica; Guo, Lida; Cropcho, Lorna J.; Gibson, K. Michael; Blair, Harry C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [Sepulveda, Jorge L.; Tanhehco, Yvette C.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Sepulveda, Jorge L.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Cropcho, Lorna J.; Gibson, K. Michael] Childrens Hosp, Pittsburgh, PA 15213 USA. [Blair, Harry C.] Vet Affairs Med Ctr, Pittsburgh, PA USA. RP Blair, HC (reprint author), Univ Pittsburgh, Dept Pathol, 705 Scaife Hall, Pittsburgh, PA 15261 USA. EM hcblair@imap.pitt.edu FU US Department of Veterans Affairs; National Institutes of Health FX This study was supported in part by the US Department of Veterans Affairs and by the National Institutes of Health. NR 37 TC 13 Z9 13 U1 0 U2 3 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 2010 VL 134 IS 1 BP 73 EP 80 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 542ZV UT WOS:000273539400014 PM 20073608 ER PT J AU Conrad, C AF Conrad, Claudius TI Careful Approach to the ABCs of the Management of Portal Venous Gas Reply SO ARCHIVES OF SURGERY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Conrad, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,White 506, Boston, MA 02114 USA. EM cconrad1@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JAN PY 2010 VL 145 IS 1 BP 104 EP 104 PG 1 WC Surgery SC Surgery GA 544XL UT WOS:000273693700028 ER PT J AU Liu, XQ Miyazaki, M Flowers, MT Sampath, H Zhao, MH Chu, K Paton, CM Joo, DS Ntambi, JM AF Liu, Xueqing Miyazaki, Makoto Flowers, Matthew T. Sampath, Harini Zhao, Minghui Chu, Kiki Paton, Chad M. Joo, Diane Seohee Ntambi, James M. TI Loss of Stearoyl-CoA Desaturase-1 Attenuates Adipocyte Inflammation Effects of Adipocyte-Derived Oleate SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE SCD1; adipocyte; macrophage; endothelial cells; inflammation; oleate; palmitoleate ID INDUCED INSULIN-RESISTANCE; COENZYME-A DESATURASE; NECROSIS-FACTOR-ALPHA; FREE FATTY-ACIDS; ADIPOSE-TISSUE; INNATE IMMUNITY; OBESITY; MICE; ATHEROSCLEROSIS; MACROPHAGES AB Background and Purpose-Adipose inflammation is crucial to the pathogenesis of metabolic disorders. This study aimed at identify the effects of stearoyl-CoA desaturase-1 (SCD1) on the inflammatory response of a paracrine network involving adipocytes, macrophages, and endothelial cells. Methods and Results-Loss of SCD1 in both genetic (Agouti) and diet-induced obesity (high-fat diet) mouse models prevented inflammation in white adipose tissue and improved its basal insulin signaling. In SCD1-deficient mice, white adipose tissue exhibited lower inflammation, with a reduced response to lipopolysaccharide in isolated adipocytes, but not in peritoneal macrophages. Mimicking the in vivo paracrine regulation of white adipose tissue inflammation, SCD1-deficient adipocyte-conditioned medium attenuated the induction of tumor necrosis factor (TNF) alpha/interleukin 1 beta gene expression in RAW264.7 macrophages and reduced the adhesion response in endothelial cells. We further demonstrated that the adipocyte-derived oleate (18:1n9), but not palmitoleate (16:1n7), mediated the inflammation in macrophages and adhesion responses in endothelial cells. Conclusions-Loss of SCD1 attenuates adipocyte inflammation and its paracrine regulation of inflammation in macrophages and endothelial cells. The reduced oleate level is linked to the inflammation-modulating effects of SCD1 deficiency. (Arterioscler Thromb Vasc Biol. 2010;30:31-38.) C1 [Liu, Xueqing; Miyazaki, Makoto; Flowers, Matthew T.; Zhao, Minghui; Chu, Kiki; Paton, Chad M.; Joo, Diane Seohee; Ntambi, James M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Miyazaki, Makoto] Univ Colorado, Dept Med, Div Renal Dis & Hypertens, Denver, CO USA. [Paton, Chad M.; Ntambi, James M.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Chu, Kiki] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Sampath, Harini] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Ntambi, JM (reprint author), Univ Wisconsin, Dept Biochem, 433 Babcock Dr, Madison, WI 53706 USA. EM ntambi@biochem.wisc.edu FU National Institutes of Health [RO1-DK62388]; American Heart Association Fellowship [082J804G] FX This study was supported by grant RO1-DK62388 from the National Institutes of Health (Dr Ntambi). Dr Liu received an American Heart Association Fellowship (082J804G). NR 34 TC 35 Z9 46 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2010 VL 30 IS 1 BP 31 EP U91 DI 10.1161/ATVBAHA.109.195636 PG 27 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 533KL UT WOS:000272822400010 PM 19910642 ER PT J AU Merrill, JT Neuwelt, CM Wallace, DJ Shanahan, JC Latinis, KM Oates, JC Utset, TO Gordon, C Isenberg, DA Hsieh, HJ Zhang, D Brunetta, PG AF Merrill, Joan T. Neuwelt, C. Michael Wallace, Daniel J. Shanahan, Joseph C. Latinis, Kevin M. Oates, James C. Utset, Tammy O. Gordon, Caroline Isenberg, David A. Hsieh, Hsin-Ju Zhang, David Brunetta, Paul G. TI Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus The Randomized, Double-Blind, Phase II/III Systemic Lupus Erythematosus Evaluation of Rituximab Trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID B-CELL DEPLETION; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; PLUS CYCLOPHOSPHAMIDE; LONGITUDINAL ANALYSIS; DISEASE-ACTIVITY; RESISTANT SLE; BILAG INDEX; THERAPY; ANTI-CD20 AB Objective. B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods. Patients entered with >= 1 British Isles Lupus Assessment Group (BILAG) A score or >= 2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results. In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had >= 1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion. The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. C1 [Merrill, Joan T.] Oklahoma Med Res Fdn, Clin Pharmacol Res Program, Oklahoma City, OK 73104 USA. [Neuwelt, C. Michael] Alameda Cty Med Ctr, Oakland, CA USA. [Wallace, Daniel J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Wallace, Daniel J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Shanahan, Joseph C.] Duke Univ, Durham, NC USA. [Latinis, Kevin M.] Univ Kansas, Med Ctr, Kansas City, MO USA. [Oates, James C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Oates, James C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Utset, Tammy O.] Univ Chicago, Chicago, IL 60637 USA. [Gordon, Caroline] Univ Birmingham, Birmingham, W Midlands, England. [Isenberg, David A.] UCL, London, England. [Hsieh, Hsin-Ju; Zhang, David; Brunetta, Paul G.] Genentech Inc, San Francisco, CA 94080 USA. RP Merrill, JT (reprint author), Oklahoma Med Res Fdn, Clin Pharmacol Res Program, MS 22,825 NE 13th St, Oklahoma City, OK 73104 USA. EM JTMmail@aol.com OI Isenberg, David/0000-0001-9514-2455 FU Genentech FX Supported by Genentech. NR 48 TC 428 Z9 454 U1 3 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2010 VL 62 IS 1 BP 222 EP 233 DI 10.1002/art.27233 PG 12 WC Rheumatology SC Rheumatology GA 617JA UT WOS:000279275700024 PM 20039413 ER PT J AU Castelino, FV Varga, J AF Castelino, Flavia V. Varga, John TI Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID GROWTH-FACTOR-BETA; IDIOPATHIC PULMONARY-FIBROSIS; PLACEBO-CONTROLLED TRIAL; CLINICALLY AMYOPATHIC DERMATOMYOSITIS; RESOLUTION COMPUTED-TOMOGRAPHY; TRANSCRIPTION FACTOR EGR-1; SYSTEMIC-SCLEROSIS; RHEUMATOID-ARTHRITIS; IMATINIB MESYLATE; MYCOPHENOLATE-MOFETIL AB Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in understanding and identifying the effector cells, the proinflammatory and profibrotic mediators, and the pathways involved in the pathogenesis of CTD-ILD. Serum biomarkers may provide new insights as risk factors for pulmonary fibrosis and as measures of disease progression. Despite these recent advances, the management of patients with CTD-ILD remains suboptimal. Further studies are therefore urgently needed to better understand these conditions, and to develop effective therapeutic interventions. C1 [Castelino, Flavia V.] Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Varga, John] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. RP Castelino, FV (reprint author), Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM fcastelino@partners.org NR 89 TC 34 Z9 41 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 4 AR 213 DI 10.1186/ar3097 PG 11 WC Rheumatology SC Rheumatology GA 675PB UT WOS:000283841500050 PM 20735863 ER PT J AU Mikuls, TR Gould, KA Bynote, KK Yu, F LeVan, TD Thiele, GM Michaud, KD O'Dell, JR Reimold, AM Hooker, R Caplan, L Johnson, DS Kerr, G Richards, JS Cannon, GW Criswell, LA Noble, JA Bridges, SL Hughes, L Gregersen, PK AF Mikuls, Ted R. Gould, Karen A. Bynote, Kimberly K. Yu, Fang LeVan, Tricia D. Thiele, Geoffrey M. Michaud, Kaleb D. O'Dell, James R. Reimold, Andreas M. Hooker, Roderick Caplan, Liron Johnson, Dannette S. Kerr, Gail Richards, J. Steuart Cannon, Grant W. Criswell, Lindsey A. Noble, Janelle A. Bridges, S. Louis, Jr. Hughes, Laura Gregersen, Peter K. TI Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferase in a cross-sectional study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID CYCLIC CITRULLINATED PEPTIDE; GENE-ENVIRONMENT INTERACTION; SHARED EPITOPE; INFLAMMATORY POLYARTHRITIS; CANCER SUSCEPTIBILITY; DISEASE SEVERITY; NULL GENOTYPE; SMOKING; RISK; ASSOCIATION AB Introduction: A deletion polymorphism in glutathione S-transferase Mu-1 (GSTM1-null) has previously been implicated to play a role in rheumatoid arthritis (RA) risk and progression, although no prior investigations have examined its associations with anticitrullinated protein antibody (ACPA) positivity. The purpose of this study was to examine the associations of GSTM1-null with ACPA positivity in RA and to assess for evidence of interaction between GSTM1 and HLA-DRB1 shared epitope (SE). Methods: Associations of GSTM1-null with ACPA positivity were examined separately in two RA cohorts, the Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 703) and the Study of New-Onset RA (SONORA; n = 610). Interactions were examined by calculating an attributable proportion (AP) due to interaction. Results: A majority of patients in the VARA registry (76%) and SONORA (69%) were positive for ACPA with a similar frequency of GSTM1-null (53% and 52%, respectively) and HLA-DRB1 SE positivity (76% and 71%, respectively). The parameter of patients who had ever smoked was more common in the VARA registry (80%) than in SONORA (65%). GSTM1-null was significantly associated with ACPA positivity in the VARA registry (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.02 to 2.05), but not in SONORA (OR, 1.00; 95% CI, 0.71 to 1.42). There were significant additive interactions between GSTM1 and HLA-DRB1 SE in the VARA registry (AP, 0.49; 95% CI, 0.21 to 0.77; P < 0.001) in ACPA positivity, an interaction replicated in SONORA (AP, 0.38; 95% CI, 0.00 to 0.76; P = 0.050). Conclusions: This study is the first to show that the GSTM1-null genotype, a common genetic variant, exerts significant additive interaction with HLA-DRB1 SE on the risk of ACPA positivity in RA. Since GSTM1 has known antioxidant functions, these data suggest that oxidative stress may be important in the development of RA-specific autoimmunity in genetically susceptible individuals. C1 [Mikuls, Ted R.; Thiele, Geoffrey M.; Michaud, Kaleb D.; O'Dell, James R.] Univ Nebraska Med Ctr, Omaha Vet Affairs Med Ctr, Omaha, NE 68198 USA. [Mikuls, Ted R.; Thiele, Geoffrey M.; Michaud, Kaleb D.; O'Dell, James R.] Univ Nebraska Med Ctr, Nebraska Arthrit Outcomes Res Ctr, Omaha, NE 68198 USA. [Gould, Karen A.; Bynote, Kimberly K.] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA. [Yu, Fang] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. [LeVan, Tricia D.] Univ Nebraska Med Ctr, Dept Med & Epidemiol, Omaha, NE 68198 USA. [Reimold, Andreas M.; Hooker, Roderick] Dallas Vet Affairs Med Ctr, Dept Med, Dallas, TX 75216 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Aurora, CO 80045 USA. [Caplan, Liron] Univ Colorado Denver, Aurora, CO 80045 USA. [Johnson, Dannette S.] Jackson Vet Affairs Med Ctr, Dept Med, Jackson, MS 39216 USA. [Johnson, Dannette S.] Univ Mississippi, Jackson, MS 39216 USA. [Kerr, Gail; Richards, J. Steuart] Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. [Kerr, Gail; Richards, J. Steuart] Georgetown Univ, Washington, DC 20422 USA. [Cannon, Grant W.] Salt Lake City Vet Affairs Med Ctr, Dept Med, Salt Lake City, UT 84132 USA. [Cannon, Grant W.] Univ Utah, Salt Lake City, UT 84132 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Noble, Janelle A.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Bridges, S. Louis, Jr.; Hughes, Laura] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY 11030 USA. RP Mikuls, TR (reprint author), Univ Nebraska Med Ctr, Omaha Vet Affairs Med Ctr, 986270 Nebraska Med Ctr, Omaha, NE 68198 USA. EM tmikuls@unmc.edu RI Yu, Fang/B-9874-2013; OI Thiele, Geoffrey/0000-0001-5688-8596 FU National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [R03 AR054539]; Veterans Health Administration (VHA); Abbott Laboratories; Bristol-Myers Squibb; American College of Rheumatology Research and Education Foundation FX This work was funded by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant R03 AR054539). The VARA Registry has received research support from the Health Services Research & Development (HSR&D) Program of the Veterans Health Administration (VHA) in addition to unrestricted research funds from Abbott Laboratories and Bristol-Myers Squibb. Dr Mikuls receives research support from the VHA (VA Merit) and the American College of Rheumatology Research and Education Foundation. The authors thank Debra Bergman and Bart Hamilton for their assistance in this work and the many U. S. veterans who have generously participated in this research. NR 50 TC 23 Z9 23 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 6 AR R213 DI 10.1186/ar3190 PG 10 WC Rheumatology SC Rheumatology GA 723OQ UT WOS:000287517000023 PM 21087494 ER PT J AU Ramiro, S Machado, P Singh, JA Landewe, RB da Silva, JAP AF Ramiro, Sofia Machado, Pedro Singh, Jasvinder A. Landewe, Robert B. da Silva, Jose Antonio P. TI Applying science in practice: the optimization of biological therapy in rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID PRELIMINARY REMISSION CRITERIA; MINIMAL DISEASE-ACTIVITY; DOUBLE-BLIND; METHOTREXATE MONOTHERAPY; EULAR RECOMMENDATIONS; RECEPTOR INHIBITION; CLINICAL REMISSION; RANDOMIZED-TRIAL; ACTIVITY STATES; ACTIVITY SCORE AB Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to decide. This review explores the application of published evidence to practice, discussing the goals of treatment, the (in) ability to predict individual responses to therapy, and the potential value of indirect comparisons. We suggest that cycling of biological agents, until remission is achieved or until the most effective agent for that individual patient is determined, deserves consideration in the current stage of knowledge. C1 [Machado, Pedro; da Silva, Jose Antonio P.] Hosp Univ Coimbra, Dept Rheumatol, P-3000076 Coimbra, Portugal. [Ramiro, Sofia; Landewe, Robert B.] Maastricht Univ Med Ctr, NL-6202 AZ Maastricht, Netherlands. [Ramiro, Sofia; Landewe, Robert B.] Sch Publ Hlth & Primary Care CAPHRI, NL-6200 MD Maastricht, Netherlands. [Ramiro, Sofia] Hosp Garcia Orta, Dept Rheumatol, P-2801951 Almada, Portugal. [Machado, Pedro] Leiden Univ Med Ctr, Dept Rheumatol, NL-2300 RC Leiden, Netherlands. [Singh, Jasvinder A.] Univ Alabama, Div Rheumatol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP da Silva, JAP (reprint author), Hosp Univ Coimbra, Dept Rheumatol, P-3000076 Coimbra, Portugal. EM jdasilva@huc.min-saude.pt RI Machado, Pedro/C-8621-2013; OI Machado, Pedro/0000-0002-8411-7972; singh, jasvinder/0000-0003-3485-0006; Da Silva, Jose/0000-0002-2782-6780 NR 54 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 6 AR 220 DI 10.1186/ar3149 PG 8 WC Rheumatology SC Rheumatology GA 723OQ UT WOS:000287517000004 PM 21067530 ER PT J AU Shin, JHJ Strle, K Glickstein, LJ Luster, AD Steere, AC AF Shin, Junghee J. Strle, Klemen Glickstein, Lisa J. Luster, Andrew D. Steere, Allen C. TI Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID ERYTHEMA MIGRANS; DENDRITIC CELLS; ADAPTIVE IMMUNITY; PERIPHERAL-BLOOD; CUTTING EDGE; HOST-DEFENSE; T-CELLS; DISEASE; EXPRESSION; INNATE AB Introduction: Joint fluid in patients with Lyme arthritis often contains high levels of CCL4 and CCL2, which are chemoattractants for monocytes and some T cells, and CXCL9 and CXCL10, which are chemoattractants for CD4+ and CD8+ T effector cells. These chemokines are produced primarily by cells of monocyte lineage in T(H)1-type immune responses. Our goal was to begin to learn how infection with Borrelia burgdorferi leads to the secretion of these chemokines, using patient cell samples. We hypothesized that B. burgdorferi stimulates chemokine secretion from monocytes/macrophages in multiple ways, thereby linking innate and adaptive immune responses. Methods: Peripheral blood mononuclear cells (PBMC) from 24 Lyme arthritis patients were stimulated with B. burgdorferi, interferon (IFN)-gamma, or both, and the levels of CCL4, CCL2, CXCL9 and CXCL10 were measured in culture supernatants. CD14+ monocytes/macrophages from PBMC and synovial fluid mononuclear cells (SFMC) were stimulated in the same way, using available samples. CXCR3, the receptor for CXCL9 and CXCL10, and CCR5, the receptor for CCL4, were assessed on T cells from PBMC and SFMC. Results: In patients with Lyme arthritis, B. burgdorferi but not IFN-gamma induced PBMC to secrete CCL4 and CCL2, and B. burgdorferi and IFN-gamma each stimulated the production of CXCL9 and CXCL10. However, with the CD14+ cell fraction, B. burgdorferi alone stimulated the secretion of CCL4; B. burgdorferi and IFN-gamma together induced CCL2 secretion, and IFN-gamma alone stimulated the secretion of CXCL9 and CXCL10. The percentage of T cells expressing CXCR3 or CCR5 was significantly greater in SFMC than PBMC, confirming that T(H)1 effector cells were recruited to inflamed joints. However, when stimulated with B. burgdorferi or IFN-gamma, SFMC and PBMC responded similarly. Conclusions: B. burgdorferi stimulates PBMC or CD14+ monocytes/macrophages directly to secrete CCL4, but spirochetal stimulation of other intermediate cells, which are present in PBMC, is required to induce CD14+ cells to secrete CCL2, CXCL9 and CXCL10. We conclude that B. burgdorferi stimulates monocytes/macrophages directly and indirectly to guide innate and adaptive immune responses in patients with Lyme arthritis. C1 [Shin, Junghee J.; Strle, Klemen; Glickstein, Lisa J.; Luster, Andrew D.; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Boston, MA 02114 USA. RP Steere, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM asteere@partners.org FU National Institutes of Health [AR-20358, AR-007258]; English, Bonter, Mitchell Foundation; Massachusetts General Hospital; Eshe Fund; Walter J. and Lille A. Berbecker Foundation for the study of Lyme disease FX We thank Gail McHugh for help with the collection of patient samples and Colleen Squires for help with preparation of the manuscript. This research was supported by the National Institutes of Health (AR-20358); the English, Bonter, Mitchell Foundation; the Lyme/Arthritis Research Fund at Massachusetts General Hospital; and the Eshe Fund. JJS and KS received support from scholarships from the Walter J. and Lille A. Berbecker Foundation for the study of Lyme disease, and JJS received support from a National Institutes of Health training grant (AR-007258). NR 38 TC 8 Z9 9 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 5 AR R168 DI 10.1186/ar3128 PG 10 WC Rheumatology SC Rheumatology GA 685JV UT WOS:000284625900018 PM 20828409 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Advances in gout: some answers, more questions SO ARTHRITIS RESEARCH & THERAPY LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; SERUM URATE; FEBUXOSTAT; ALLOPURINOL; HYPERURICEMIA; EFFICACY; SAFETY; RISK AB In a previous issue of the journal, Becker and colleagues present efficacy and safety data from a large study comparing febuxostat to allopurinol. The study showed non-inferiority of febuxostat 40 mg/day in lowering serum urate compared to allopurinol 200 to 300 mg/day. More importantly, the study showed a similar frequency of important cardiovascular adverse events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) for febuxostat 40 mg/day (0%), febuxostat 80 mg/day (0.4%) and allopurinol groups (0.4%). Other cardiac adverse event rates (unstable angina, coronary revascularization, cerebral revascularization, transient ischemic attack, venous and peripheral arterial vascular thrombotic event, congestive heart failure, and arrhythmia) were also similar for febuxostat 40 mg/day (1.3%), febuxostat 80 mg/day (1.2%) and allopurinol groups (0.9%). A meta-analysis of safety data from published studies is presented. C1 [Singh, Jasvinder A.] Univ Alabama, Med Serv, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL 35205 USA. [Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped, Rochester, MN 55905 USA. RP Singh, JA (reprint author), Univ Alabama, Med Serv, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 NR 15 TC 5 Z9 7 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2010 VL 12 IS 5 AR 136 DI 10.1186/ar3110 PG 3 WC Rheumatology SC Rheumatology GA 685JV UT WOS:000284625900001 PM 20959031 ER PT B AU Robertson, WJ Asnis, PD AF Robertson, William J. Asnis, Peter D. BE Kelly, BT Philippon, MJ TI Removal of Loose Bodies and Excision of PVNS/Synovial Chondromatosis SO ARTHROSCOPIC TECHNIQUES OF THE HIP: A VISUAL GUIDE SE Visual Arthroscopy Series LA English DT Article; Book Chapter ID SYNOVIAL OSTEOCHONDROMATOSIS; HIP ARTHROSCOPY; DISORDERS C1 [Robertson, William J.] Univ Texas SW Med Ctr Dallas, Dept Orthoped Surg, Dallas, TX 75390 USA. [Asnis, Peter D.] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Robertson, WJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Orthoped Surg, Dallas, TX 75390 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-886-9 J9 VIS ARTHROSC SER PY 2010 BP 49 EP 57 PG 9 WC Orthopedics SC Orthopedics GA BMM92 UT WOS:000272863700004 ER PT J AU Irani, K Pomerantseva, I Hart, AR Sundback, CA Neville, CM Vacanti, JP AF Irani, Katayun Pomerantseva, Irina Hart, Alison R. Sundback, Cathryn A. Neville, Craig M. Vacanti, Joseph P. TI Mechanical Dissociation of Swine Liver to Produce Organoid Units for Tissue Engineering and In Vitro Disease Modeling SO ARTIFICIAL ORGANS LA English DT Article DE Bioartificial liver; Liver slice; Liver-specific function; Organ culture techniques; Oxygen-supplemented flow culture ID OXYGEN-TENSION; CULTURE; SLICES; DIFFERENTIATION; HEPATOCYTES; INTEGRITY AB The complex intricate architecture of the liver is crucial to hepatic function. Standard protocols used for enzymatic digestion to isolate hepatocytes destroy tissue structure and result in significant loss of synthetic, metabolic, and detoxification processes. We describe a process using mechanical dissociation to generate hepatic organoids with preserved intrinsic tissue architecture from swine liver. Oxygen-supplemented perfusion culture better preserved organoid viability, morphology, serum protein synthesis, and urea production, compared with standard and oxygen-supplemented static culture. Hepatic organoids offer an alternative source for hepatic assist devices, engineered liver, disease modeling, and xenobiotic testing. C1 [Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Irani, Katayun; Pomerantseva, Irina; Sundback, Cathryn A.; Neville, Craig M.; Vacanti, Joseph P.] Harvard Univ, Sch Med, Boston, MA USA. [Vacanti, Joseph P.] Massachusetts Gen Hosp Children, Boston, MA USA. [Irani, Katayun] NYU, Sch Med, New York, NY USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Warren 1151,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 10 TC 5 Z9 5 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD JAN PY 2010 VL 34 IS 1 BP 75 EP 78 DI 10.1111/j.1525-1594.2009.00784.x PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 546OX UT WOS:000273821200009 PM 20432518 ER PT J AU Thompson-McCormick, JJ Thomas, JJ Bainivualiku, A Khan, AN Becker, AE AF Thompson-McCormick, Jonas J. Thomas, Jennifer J. Bainivualiku, Asenaca Khan, A. Nisha Becker, Anne E. TI Breakfast skipping as a risk correlate of overweight and obesity in school-going ethnic Fijian adolescent girls SO ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION LA English DT Article DE overweight; obesity; Fiji; breakfast skipping; adolescents ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; EATING PATTERNS; WEIGHT CHANGE; FAMILY MEALS; CHILDREN; HEALTH; BEHAVIORS; CONSUMPTION; PREVALENCE AB The prevalence of overweight and obesity has increased globally, and population data suggest that it is also increasing among ethnic Fijian youth. Among numerous behavioural changes contributing to overweight in youth residing in nations undergoing rapid economic and social change, meal skipping has not been examined as a potential risk factor. The study objectives were to assess the prevalence of overweight, obesity, and breakfast skipping and examine their cross-sectional association in a community sample of school-going ethnic Fijian adolescent girls (n=523). We measured height and weight, and assessed dietary patterns, eating pathology, dimensions of acculturation, and other socio-demographic and cultural data by self-report. We observed a high prevalence of both overweight (41%, including 15% who were obese) and breakfast skipping (68%). In addition, in multivariable analyses unadjusted for eating pathology, we found that more frequent breakfast skipping was associated with greater odds of overweight (odds ratio (OR)=1.15, confidence interval (CI)=1.06, 1.26, p<0.01) and obesity (OR=1.18, CI=1.05, 1.33, p<0.01). Regression models adjusting for eating pathology attenuated this relation so that it was non-significant, but demonstrated that greater eating pathology was associated with greater odds of both overweight and obesity. Future research is necessary to clarify the relation among breakfast skipping, eating pathology, and overweight in ethnic Fijian girls, and to identify whether breakfast skipping may be a modifiable risk factor for overweight in this population. C1 [Becker, Anne E.] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA 02115 USA. [Thompson-McCormick, Jonas J.; Thomas, Jennifer J.; Becker, Anne E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Thomas, Jennifer J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA. [Thomas, Jennifer J.; Becker, Anne E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Bainivualiku, Asenaca] Univ Victoria, Victoria, BC V8W 2Y2, Canada. [Khan, A. Nisha] Minist Hlth, Suva, Fiji. RP Becker, AE (reprint author), Harvard Univ, Dept Global Hlth & Social Med, Sch Med, 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu FU US National Institute of Mental Health [K23 MH068575]; Harvard University; Radcliffe Institute for Advanced Study FX The authors have no conflicts of interest to declare. This study was supported by a grant from the US National Institute of Mental Health (K23 MH068575), a Harvard University Research Enabling Grant, and fellowship support from the Radcliffe Institute for Advanced Study (AEB). NR 66 TC 13 Z9 14 U1 3 U2 8 PU H E C PRESS, HEALTHY EATING CLUB PTY LTD PI MCKINNON PA PO BOX 4121, MCKINNON, VIC 3204, AUSTRALIA SN 0964-7058 J9 ASIA PAC J CLIN NUTR JI Asia Pac. J. Clin. Nutr. PY 2010 VL 19 IS 3 BP 372 EP 382 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 654YR UT WOS:000282207700012 PM 20805082 ER PT B AU Kradin, R AF Kradin, Richard BE Pasqualotto, AC TI The Pathology of Aspergillus Infection SO ASPERGILLOSIS: FROM DIAGNOSIS TO PREVENTION LA English DT Article; Book Chapter DE Aspergillosis; Diagnosis; Histopathology; Tissue ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; NIGER FUNGUS BALL; PULMONARY ASPERGILLOSIS; DISEASE; SPECTRUM AB Aspergillus spp. are responsible for a broad spectrum of human disorders ranging from benign colonisation of mucosal surfaces to life-threatening angioinvasive infection. Diagnosing the array of disorders caused by Aspergillus spp. can be challenging. In the case of the hypersensitivity responses to Aspergillus species, i.e., allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis, and hypersensitivity pneumonitis, the surgical pathologist must be cognisant of their relationship to infection, as fungal organisms may be rare or even absent from the biopsy specimens. Within the gamut of opportunistic infections, Aspergillus species must be distinguished from other fungal mimics; additionally, one must assess whether infection is limited, progressive, or immanently life-threatening. With respect to diagnosis, certain Aspergillus spp. exhibit characteristic morphologic features in tissue that suggest their identity. This chapter examines the pathological changes in tissues due to infection by Aspergillus spp. C1 [Kradin, Richard] Massachusetts Gen Hosp, Dept Pathol, Infect Dis Pathol, Boston, MA 02114 USA. [Kradin, Richard] Massachusetts Gen Hosp, Dept Pulm Crit Care Med, Infect Dis Pathol, Boston, MA 02114 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, Infect Dis Pathol, Boston, MA 02114 USA. EM rkradin@partners.org NR 18 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2407-7 PY 2010 BP 87 EP 104 DI 10.1007/978-90-481-2408-4_6 PG 18 WC Dermatology; Mycology SC Dermatology; Mycology GA BMJ13 UT WOS:000272541500006 ER PT S AU Naghavi, M Falk, E Nasir, K Hecht, HS Budoff, MJ Fayad, ZA Berman, DS Shah, PK AF Naghavi, Morteza Falk, Erling Nasir, Khurram Hecht, Harvey S. Budoff, Matthew J. Fayad, Zahi A. Berman, Daniel S. Shah, Prediman K. BE Naghavi, M TI Approach to Atherosclerosis as a Disease: Primary Prevention Based on the Detection and Treatment of Asymptomatic Atherosclerosis SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Atherosclerosis; Asymptomatic Atherosclerosis; Subclinical Atherosclerosis; Noninvasive Screening; Cardiovascular Risk Factors; Framingham Risk Score; Vulnerable Patient; Genetic Susceptibility ID ISCHEMIC-HEART-DISEASE; PANEL-III GUIDELINES; CARDIOVASCULAR-DISEASE; RISK-FACTORS AB Atherosclerosis is a pervasive and malignant disease of the arterial circulation. It is by far the most frequent cause of angina, heart attack (including sudden coronary death), and peripheral arterial disease and is responsible for many cases of stroke. Yet, many individuals, even those with advanced disease, are unaware because they have no symptoms. In 30-50% of these individuals, the first indicator of atherosclerosis is a heart attack, which often is fatal (sudden, unexpected death). Since there are many pharmacologic and non-pharmacologic therapies to reduce the risk of heart attack and stroke, early detection of atherosclerosis itself, before symptoms occur, can provide a major opportunity to prevent many such events. Since effective screening could confer great public health benefit, it may seem surprising that screening for subclinical atherosclerosis has not yet been incorporated into national and international clinical guidelines. Therapeutic strategies targeted to key at-risk vulnerable patients can reduce the heavy economic burden of symptomatic and end-stage care for cardiovascular disease (CVD). There have been two main reasons for this conservative strategy. Firstly, there has been a lack of data convincingly demonstrating that screening for subclinical atherosclerosis improves the assessment of risk beyond that provided by traditional risk factors, such as smoking, hypertension, hypercholesterolemia, and diabetes. Secondly, appropriate instruments for detection of subclinical atherosclerosis have not been widely available to clinicians. The authors of this chapter believe that recent developments have provided us with the requisite data as well as with the necessary methodology. Furthermore, highly effective and safe therapies against atherosclerosis and heart attack are available. C1 [Naghavi, Morteza] Soc Heart Attack Prevent & Eradicat SHAPE, Houston, TX 77024 USA. [Falk, Erling] Aarhus Univ Hosp, Dept Cardiol Res, DK-8000 Aarhus, Denmark. [Nasir, Khurram] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hecht, Harvey S.] Lenox Hill Hosp, Dept Intervent Cardiol, New York, NY 10021 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, BioMed CT Reading Ctr, Torrance, CA 90509 USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Dept Cardiol, New York, NY USA. [Berman, Daniel S.] Cedars Sinai Med Sch, Dept Cardiac Imaging & Nucl Cardiol, Los Angeles, CA USA. [Shah, Prediman K.] Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. [Shah, Prediman K.] Cedars Sinai Med Ctr, Atherosclerosis Res Ctr, Los Angeles, CA 90048 USA. RP Naghavi, M (reprint author), Soc Heart Attack Prevent & Eradicat SHAPE, 710 N Post Oak,Suite 400, Houston, TX 77024 USA. NR 15 TC 0 Z9 0 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 77 EP 85 DI 10.1007/978-1-60327-179-0_6 D2 10.1007/978-1-60327-179-0 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100006 ER PT S AU Pandey, S Nasir, K AF Pandey, Shivda Nasir, Khurram BE Naghavi, M TI Family History: An Index of Genetic and Environmental Predisposition to Coronary Artery Disease SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Carotid IMT; Coronary artery calcification; Family history of heart disease; Framingham risk score ID INDEPENDENT RISK-FACTOR; PARENTAL CARDIOVASCULAR-DISEASE; INTIMA-MEDIA THICKNESS; PANEL III GUIDELINES; MIDDLE-AGED ADULTS; HEART-DISEASE; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; HIGH PREVALENCE; SUBCLINICAL ATHEROSCLEROSIS AB It is well known that family history of coronary heart disease reflects genetic predisposition to develop atherosclerosis. Individuals with a family history of premature CHD are at a significantly increased risk for CHD events. They form a potential target population for early, aggressive primary prevention strategies. However, the conventional cardiovascular risk factors (age, total cholesterol, smoking, HDL cholesterol, and systolic blood pressure) are precisely characterized and incorporated in the Framingham Risk evaluation algorithm. They do not include family history information as a criterion to guide primary prevention endeavors. Emerging evidence indicates that subjects with positive family history are unequivocally a high-risk group and candidates for prompt primary prevention efforts. In this chapter, we have highlighted overwhelming evidence indicating positive family history of CHD to be associated with an independent predictor of subclinical CHD markers, such as assessed CAC, Carotid-IMT, flow-mediated dilatation, among various others. On the basis of these facts, we propose following modifications in the risk prediction algorithm currently being used. Individuals in the Framingham low risk category, (estimated 10-year coronary mortality <10%) with family history, can be considered as intermediate risk and be targets for further risk stratification using CAC testing. On the other hand, those within the "intermediate-risk" range should be considered as high risk and treated aggressively as CHD equivalent with LDL goals of less than 70 mg/dl, and lipid lowering therapy be initiated, if LDL >= 100 mg/dl. We believe that this will be a cost effective approach in utilizing appropriate therapies and advance risk stratifying tools, such as CAC testing, in this vulnerable population. C1 [Pandey, Shivda] Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Nasir, Khurram] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Pandey, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. NR 52 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 169 EP 178 DI 10.1007/978-1-60327-179-0_12 D2 10.1007/978-1-60327-179-0 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100012 ER PT S AU Cury, RC Soni, A Blankstein, R AF Cury, Ricardo C. Soni, Anand Blankstein, Ron BE Naghavi, M TI Noninvasive Imaging of the Vulnerable Myocardium: Cardiac MRI and CT Based SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Angina; Computed tomography; Diagnosis; Magnetic resonance imaging; Myocardial infarction ID CORONARY-ARTERY-DISEASE; ENHANCED MAGNETIC-RESONANCE; MULTIDETECTOR COMPUTED-TOMOGRAPHY; DELAYED CONTRAST ENHANCEMENT; POSITRON-EMISSION-TOMOGRAPHY; INFARCT SIZE; ADENOSINE STRESS; MICROVASCULAR OBSTRUCTION; 1ST-PASS PERFUSION; PROGNOSTIC-SIGNIFICANCE AB Multiple noninvasive imagine modalities can be used for the evaluation of the vulnerable myocardium. In this chapter, the applications of advanced cardiac imaging with cardiac MRI and cardiac CT are reviewed for the assessment of myocardial perfusion, viability, infarct size, and myocardium at risk. The accurate characterization of the vulnerable myocardium can provide important information that can guide therapeutics by detection of myocardial ischemia under stress conditions, the detection and characterization of myocardial infarct (size, transmural and circumferential extent), or the assessment of myocardium at risk (myocardial edema, microvascular obstruction, "grey zone"). Modalities with high spatial resolution and excellent tissue characterization, such as cardiac MRI and CT, will permit to obtain this type of information. Animal and human data will be reviewed and will be placed in clinical perspective, taking into account the limitations of each modality. Finally, we aim to demonstrate that the search and characterization of the vulnerable myocardium can help and provide important information in the overall characterization and management of the vulnerable patient. C1 [Cury, Ricardo C.; Soni, Anand; Blankstein, Ron] Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Cury, Ricardo C.; Soni, Anand; Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA USA. RP Cury, RC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. NR 73 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 433 EP 451 DI 10.1007/978-1-60327-179-0_32 D2 10.1007/978-1-60327-179-0 PG 19 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100032 ER PT S AU Goldstein, JA Muller, JE AF Goldstein, James A. Muller, James E. BE Naghavi, M TI Intravascular Characterization of Vulnerable Coronary Plaque SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Ruptured plaque; Vulnerable plaque; IVUS; Near-infrared spectroscopy ID OPTICAL COHERENCE TOMOGRAPHY; RADIOFREQUENCY DATA-ANALYSIS; ACUTE MYOCARDIAL-INFARCTION; NEAR-INFRARED SPECTROSCOPY; THIN-CAP FIBROATHEROMA; ATHEROSCLEROTIC PLAQUES; MAGNETIC-RESONANCE; IN-VIVO; ANGIOSCOPIC EVALUATION; ARTERY-DISEASE AB Acute coronary syndromes result from rupture of macrophage-rich, inflamed thin-capped fibroatheroma with superimposed thrombus formation. Ruptured plaques are felt to arise from precursor "vulnerable" lesions that are presumed to be at high risk of disruption. Observations now document that many patients with ACS harbor multiple complex unstable plaques, supporting the concept that plaque instability is not merely a local vascular accident, but instead reflects more systemic pathophysiologic processes. The recognition of the ubiquity of substantial but nonflow limiting lesions that may serve as the fodder for subsequent plaque rupture has resulted in a paradigm shift in thinking about the pathophysiology of coronary artery disease, with the focus no longer solely on the degree of arterial lumina! narrowing. This chapter will review: (1) Definitions of vulnerable plaque; (2) Limitations of conventional angiography for detection of vulnerable plaque; (3) Nonangiographic invasive methods to image vulnerable plaques; (4) Invasive technologies to characterize plaque including IVUS, angioscopy, NIR spectroscopy, optical coherence tomography (OCT), catheter-based MRI and thermography. C1 [Goldstein, James A.] William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48072 USA. [Muller, James E.] Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. RP Goldstein, JA (reprint author), William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48072 USA. NR 87 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 461 EP 473 DI 10.1007/978-1-60327-179-0_34 D2 10.1007/978-1-60327-179-0 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100034 ER PT S AU Shaw, LJ Blankenstein, R AF Shaw, Leslee J. Blankenstein, Ron BE Naghavi, M TI Cost Effectiveness of Screening Atherosclerosis SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Atherosclerosis; Cost effectiveness; Screening ID CORONARY-HEART-DISEASE; PANEL III GUIDELINES; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; IDENTIFY PATIENTS; RISK; CALCIUM; ADULTS; WOMEN AB There remains a significant detection gap for cardiovascular disease that could be reduced provided that screening programs are employed, directed toward at-risk patient populations. However, given the current state of the healthcare system and the spiraling healthcare costs, expansion of current coverage decisions to include screening beyond cancer is incomprehensible. Data are unfolding that current tests are highly accurate at detecting risk and provide significant improvements in our global risk scores, such as the Framingham risk score. This chapter reviews the methods applied toward evaluating the economics of screening including cost-effectiveness principles. In addition to the presentation of screening cost models, this chapter introduces the concept of an early intervention model as a means to avert the enormous burden of symptomatic care in this country. Ongoing dialog about the importance of cost considerations and focused evaluations to consider the benefits and the risks of cardiovascular screening are important steps toward devising a platform for reducing the burden of atherosclerosis in this country. C1 [Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. [Blankenstein, Ron] Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Blankenstein, Ron] Harvard Univ, Sch Med, Boston, MA USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. NR 23 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 537 EP 547 DI 10.1007/978-1-60327-179-0_40 D2 10.1007/978-1-60327-179-0 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100040 ER PT S AU Santos, RD Nasir, K Blumenthal, RS AF Santos, Raul D. Nasir, Khurram Blumenthal, Roger S. BE Naghavi, M TI LDL Targeted Therapies SO ASYMPTOMATIC ATHEROSCLEROSIS: PATHOPHYSIOLOGY, DETECTION AND TREATMENT SE Contemporary Cardiology LA English DT Article; Book Chapter DE Atherosclerosis; Cardiovascular disease; LDL-cholesterol; Lipid lowering therapy; Statins ID CORONARY-HEART-DISEASE; LIPID-LOWERING THERAPY; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; DENSITY-LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED-TRIAL; COA REDUCTASE INHIBITORS; DOUBLE-BLIND TRIAL; STATIN THERAPY; ARTERY-DISEASE AB LDL-cholesterol (LDL-C) levels arc directly associated with the prevalence of coronary heart disease. Epidemiological and ecological studies have clearly shown that populations with LDL-C levels significantly lower than those found in western countries have a very low prevalence of coronary heart disease, despite the presence of other risk factors for atherosclerosis. It has been demonstrated that LDL-C reduction with statins not only reduces atherosclerosis progression but can induce its regression, if intensive LDL-C reduction, around 40-50%, is achieved. Most importantly there is a linear relation between LDL-C lowering and cardiovascular disease reduction; for each 1 mmol/L (39 mg/dL) there is similar to 21% decrease in any major vascular event including death, myocardial infarction, stroke and myocardial revascularization as shown by a meta-analysis involving 90,056 patients who had participated in 14 statin trials. These findings were reinforced by another meta-analysis of more than 27,000 coronary heart disease individuals showing that intensive LDL-C lowering was superior to conventional therapy. Subjects considered to be at high risk by clinical stratification must be treated with intensive LDL-C lowering. Also, it has been proposed that asymptomatic subjects not considered at high risk by clinical stratification but otherwise presenting with a high subclinical atherosclerotic burden, must be treated in the same manner. C1 [Santos, Raul D.] Cardiovasc Specialists PA, Lewisville, TX USA. [Nasir, Khurram] Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Nasir, Khurram] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Blumenthal, Roger S.] Johns Hopkins Univ Hosp, Prevent Cardiol Ctr, Baltimore, MD 21287 USA. RP Santos, RD (reprint author), Cardiovasc Specialists PA, Lewisville, TX USA. NR 51 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-178-3 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 605 EP 619 DI 10.1007/978-1-60327-179-0_47 D2 10.1007/978-1-60327-179-0 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BOC89 UT WOS:000276203100047 ER PT J AU Moore, KJ Rayner, K AF Moore, Kathryn J. Rayner, Katey BE George, SJ Johnson, J TI Macrophage Foam Cell Formation: The Pathways to Cholesterol Engorgement SO ATHEROSCLEROSIS: MOLECULAR AND CELLULAR MECHANISMS LA English DT Article; Book Chapter ID LOW-DENSITY-LIPOPROTEIN; SECRETORY PHOSPHOLIPASE A(2); SCAVENGER RECEPTOR CD36; ATHEROSCLEROTIC LESION FORMATION; SPHINGOMYELINASE INDUCES AGGREGATION; MONOCYTE-DERIVED MACROPHAGES; HUMAN AORTIC PROTEOGLYCANS; CLASS-A OVEREXPRESSION; CASSETTE TRANSPORTER 1; GROUP IIA C1 [Moore, Kathryn J.; Rayner, Katey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Lipid Metab Unit, Boston, MA 02114 USA. RP Moore, KJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Lipid Metab Unit, Boston, MA 02114 USA. NR 112 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-527-32448-4 PY 2010 BP 231 EP 254 D2 10.1002/9783527629589 PG 24 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BUA22 UT WOS:000288600300013 ER PT J AU Lee, J Nadol, JB Eddington, DK AF Lee, Joonhan Nadol, Joseph B., Jr. Eddington, Donald K. TI Depth of Electrode Insertion and Postoperative Performance in Humans with Cochlear Implants: A Histopathologic Study SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Cochlear implant; Word recognition; Depth of electrode insertion ID SPIRAL GANGLION-CELLS; SPEECH-PERCEPTION; WORD RECOGNITION; RECONSTRUCTION; MORPHOLOGY; POSITION; NUMBER AB The depth of electrode insertion of a multichannel cochlear implant has been suggested as a clinical variable that may correlate with word recognition using the implant. The current study evaluates this relationship using the human temporal bone collection at the Massachusetts Eye and Ear Infirmary. Twenty-seven temporal bones of subjects with cochlear implants were studied. Temporal bones were removed at autopsy, fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned, and reconstructed by two-dimensional methods. Three measures of length were made from each subject's reconstruction: (1) depth of insertion (DI) of the cochlear implant electrode array, from the round window to the array's apical tip; (2) inserted length (IL) from the cochleostomy to the apical tip of the array, and (3) cochlear duct length (CDL) from the round window to the helicotrema. The active electrode length (AEL) was defined as the distance between the most apical and most basal electrodes of the array. Stepwise re-gression was used to identify whether subsets of six metrics associated with insertion depth (DI, DI/AEL, DI/CDL, IL, IL/AEL and IL/CDL), duration of deafness, sound-processing strategy, potential for central impairment and age at implantation accounted for significant across-subject variance in the last recorded NU-6 word score measured during each subject's life. Age at implantation and potential for central impairment account for significant percentages of the across-subject variance in NU-6 word scores for the 27 subjects studied. None of the insertion metrics accounted for significant performance variance, even when the variance associated with the other variables was controlled. These results, together with those of previous studies, are consistent with a relatively weak association between electrode insertion depth and speech reception. Copyright (C) 2010 S. Karger AG, Basel C1 [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Lee, Joonhan; Nadol, Joseph B., Jr.; Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lee, Joonhan; Nadol, Joseph B., Jr.; Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Nadol, Joseph B., Jr.; Eddington, Donald K.] MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Lee, Joonhan] Chosun Univ, Coll Med, Dept Otolaryngol Head & Neck Surg, Kwangju, South Korea. RP Eddington, DK (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, 243 Charles St, Boston, MA 02114 USA. EM don_eddington@meei.harvard.edu FU NIH (NIDCD) [R01DC000152] FX This work was supported by funding from the NIH (NIDCD) grant R01DC000152 Electron Microscopy of the Human Inner Ear. NR 20 TC 24 Z9 24 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2010 VL 15 IS 5 BP 323 EP 331 DI 10.1159/000289571 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 570LL UT WOS:000275679500007 PM 20203481 ER PT J AU Makary, C Shin, J Caruso, P Curtin, H Merchant, S AF Makary, Chadi Shin, Jennifer Caruso, Paul Curtin, Hugh Merchant, Saumil TI A Histological Study of Scala Communis with Radiological Implications SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Cochlea; Inner ear anomalies; Mondini defect; Scala communis; Mesoderm ID HUMAN EMBRYO; CLASSIFICATION; MALFORMATIONS; COCHLEAE; CAPSULE; EAR AB Objectives: Scala communis or interscalar septum (IS) defect is a developmental abnormality of the inner ear characterized by a dehiscence in the partition separating the turns of the cochlea. The goals of the present study were to (1) study this anomaly and describe its characteristics compared to control ears using a histological analysis of temporal bones, (2) discuss radiological implications regarding its diagnosis, and (3) describe its embryological derivation. Methods: Out of 1775 temporal bones assessed, 22 specimens were found to have scala communis in cochleae containing all 3 turns (basal, middle and apical). These 22 ears were studied in detail by qualitative and quantitative methods using light microscopy. Results: Scala communis occurred as an isolated inner ear anomaly, or in association with other congenital cochlear and/or vestibular anomalies. The defect occurred most often between the middle and apical turns of the cochlea. Compared to control ears, scala communis ears were found to have a smaller modiolar area (p < 0.0001) and flattening of the interscalar ridge (point of attachment of the IS to the inner lumen of the cochlea; p < 0.0001). Scala communis was compatible with normal hearing. Conclusions: Flattening of the interscalar ridge has the potential to improve the diagnosis of scala communis in patients using CT scanning. The anomaly may result from a mesodermal defect such as excessive resorption of mesenchyme during the formation of the scalae, an error in the formation of bone, or both. Copyright (C) 2010 S. Karger AG, Basel C1 [Makary, Chadi] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Makary, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Chadi_Makary@meei.harvard.edu RI Shin, Jennifer/A-3169-2016 FU NIDCD NIH HHS [U24 DC008559, U24DC008559] NR 26 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2010 VL 15 IS 6 BP 383 EP 393 DI 10.1159/000307345 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 584LB UT WOS:000276752200005 PM 20389062 ER PT B AU Herbert, MR AF Herbert, Martha R. BE Chauhan, A Chauhan, V Brown, WT TI Autism: The Centrality of Active Pathophysiology and the Shift from Static to Chronic Dynamic Encephalopathy SO Autism: Oxidative Stress, Inflammation, and Immune Abnormalities LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE SPECTROSCOPY; GENE-ENVIRONMENT INTERACTIONS; MATERNAL IMMUNE ACTIVATION; FETAL-BRAIN-DEVELOPMENT; N-ACETYL-ASPARTATE; FRAGILE-X-SYNDROME; SPECTRUM DISORDERS; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; PROPIONIC-ACID C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA 02129 USA. RP Herbert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA 02129 USA. EM mherbert1@partners.org NR 195 TC 2 Z9 2 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-6887-0; 978-1-4200-6881-8 PY 2010 BP 343 EP 387 PG 45 WC Neurosciences SC Neurosciences & Neurology GA BC5HI UT WOS:000353288800019 ER PT B AU Marques, L Chosak, A Phan, DM Fama, J Franklin, S Wilhelm, S AF Marques, Luana Chosak, Anne Phan, Dieu-My Fama, Jeanne Franklin, Shana Wilhelm, Sabine BE Otto, MW Hofmann, SG TI Avoiding Treatment Failures in Obsessive Compulsive Disorder SO AVOIDING TREATMENT FAILURES IN THE ANXIETY DISORDERS SE Series in Anxiety and Related Disorders LA English DT Article; Book Chapter ID COGNITIVE-BEHAVIOR THERAPY; POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; CLINICAL CHARACTERISTICS; CONTROLLED-TRIAL; PHARMACOLOGICAL-TREATMENTS; PERSONALITY-DISORDER; INTRUSIVE THOUGHTS; D-CYCLOSERINE; CASE SERIES C1 [Marques, Luana; Chosak, Anne] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Marques, Luana; Chosak, Anne; Phan, Dieu-My; Fama, Jeanne; Franklin, Shana; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA USA. [Phan, Dieu-My] Massachusetts Gen Hosp, Body Dysmorph Disorder Clin, Boston, MA 02114 USA. [Franklin, Shana; Wilhelm, Sabine] Massachusetts Gen Hosp, OCD, Boston, MA 02114 USA. [Franklin, Shana; Wilhelm, Sabine] Massachusetts Gen Hosp, Related Disorders Clin, Boston, MA 02114 USA. RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM lmarques@partners.org RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 101 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0611-3 J9 SER ANXIETY RELAT DI PY 2010 BP 125 EP 145 DI 10.1007/978-1-4419-0612-0_8 D2 10.1007/978-1-4419-0612-0 PG 21 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BMP28 UT WOS:000273267500008 ER PT B AU Greer, J Graham, J Safren, S AF Greer, Joseph Graham, Jessica Safren, Steven BE Otto, MW Hofmann, SG TI Resolving Treatment Complications Associated with Comorbid Medical Conditions SO AVOIDING TREATMENT FAILURES IN THE ANXIETY DISORDERS SE Series in Anxiety and Related Disorders LA English DT Article; Book Chapter ID QUALITY-OF-LIFE; CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; MULTIDISCIPLINARY SYMPTOM CONTROL; COGNITIVE-BEHAVIORAL THERAPY; PSYCHOSOCIAL RISK-FACTORS; PANIC DISORDER PATIENTS; ISCHEMIC-HEART-DISEASE; DEPRESSION CBT-AD; DSM-IV DISORDERS C1 [Greer, Joseph] Williams Coll, Bronfman Sci Ctr, Dept Psychol, Williamstown, MA 01267 USA. [Safren, Steven] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Safren, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Graham, Jessica] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. RP Greer, J (reprint author), Williams Coll, Bronfman Sci Ctr, Dept Psychol, Williamstown, MA 01267 USA. EM joseph.greer@williams.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 175 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0611-3 J9 SER ANXIETY RELAT DI PY 2010 BP 317 EP 346 DI 10.1007/978-1-4419-0612-0_17 D2 10.1007/978-1-4419-0612-0 PG 30 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BMP28 UT WOS:000273267500017 ER PT B AU Micco, JA Ehrenreich, JT AF Micco, Jamie A. Ehrenreich, Jill T. BE Otto, MW Hofmann, SG TI Resolving Treatment Complications in Children and Adolescents SO AVOIDING TREATMENT FAILURES IN THE ANXIETY DISORDERS SE Series in Anxiety and Related Disorders LA English DT Editorial Material; Book Chapter ID CHILDHOOD ANXIETY DISORDERS; COGNITIVE-BEHAVIORAL TREATMENT; RANDOMIZED CLINICAL-TRIAL; DSM-III DISORDERS; DEPRESSIVE-DISORDERS; SOCIAL PHOBIA; CO-MORBIDITY; PARENTAL INVOLVEMENT; SEPARATION ANXIETY; COMMUNITY SAMPLE C1 [Ehrenreich, Jill T.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Micco, Jamie A.] Massachusetts Gen Hosp, Cambridge, MA USA. [Micco, Jamie A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ehrenreich, JT (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. EM jehrenreich@psy.miami.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 94 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0611-3 J9 SER ANXIETY RELAT DI PY 2010 BP 347 EP 370 DI 10.1007/978-1-4419-0612-0_18 D2 10.1007/978-1-4419-0612-0 PG 24 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BMP28 UT WOS:000273267500018 ER PT S AU Danial, NN Gimenez-Cassina, A Tondera, D AF Danial, Nika N. Gimenez-Cassina, Alfredo Tondera, Daniel BE Hetz, C TI Homeostatic Functions of BCL-2 Proteins beyond Apoptosis SO BCL-2 PROTEIN FAMILY: ESSENTIAL REGULATORS OF CELL DEATH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID ENDOPLASMIC-RETICULUM STRESS; MITOCHONDRIAL OUTER-MEMBRANE; CELL-CYCLE ENTRY; DEPENDENT ANION CHANNEL; DYNAMIN-RELATED GTPASE; DNA-DAMAGE RESPONSE; INOSITOL TRISPHOSPHATE RECEPTOR; PERMEABILITY TRANSITION PORE; INTRACELLULAR CA2+ STORES; CYTOCHROME-C RELEASE AB Since its introduction in 1930 by physiologist Walter Bradford Cannon, the concept of homeostasis remains the cardinal tenet of biologic regulation. Cells have evolved a highly integrated network of control mechanisms, including positive and negative feedback loops, to safeguard homeostasis in face of a wide range of stimuli. Such control mechanisms ultimately orchestrate cell death, division and repair in a manner concordant with cellular energy and ionic balance to achieve proper biologic fitness. The interdependence of these homeostatic pathways is also evidenced by shared control points that decode intra- and extracellular cues into defined effector responses. As critical control points of the intrinsic apoptotic pathway, the BCL-2 family of cell death regulators plays an important role in cellular homeostasis.(1-3) The different anti- and pro-apoptotic members of this family form a highly selective network of functional interactions that ultimately governs the permeabilization of the mitochondrial outer membrane and subsequent release of apoptogenic factors such as cytochrome c.(4) The advent of loss- and gain-of-function genetic models for the various BCL-2 family proteins has not only provided important insights into apoptosis mechanisms but also uncovered unanticipated roles for these proteins in other physiologic pathways beyond apoptosis (Fig. 1). Here, we turn our attention to these alternative cellular functions for BCL-2 proteins. We begin with a brief introduction of the cast of characters originally known for their capacity to regulate apoptosis and continue to highlight recent advances that have shaped and reshaped our views on their physiologic relevance in integration of apoptosis with other homeostatic pathways. C1 [Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Danial, NN (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM nika_danial@dfci.harvard.edu NR 261 TC 25 Z9 27 U1 2 U2 12 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6705-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 687 BP 1 EP 32 D2 10.1007/978-1-4419-6706-0 PG 32 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BQA75 UT WOS:000280523400001 PM 20919635 ER PT S AU Vo, TT Letai, A AF Vo, Thanh-Trang Letai, Anthony BE Hetz, C TI BH3-Only Proteins and Their Effects on Cancer SO BCL-2 PROTEIN FAMILY: ESSENTIAL REGULATORS OF CELL DEATH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID FAMILY-MEMBER BIM; BCL-X-L; GLUCOCORTICOID-INDUCED APOPTOSIS; SURVIVAL-PROMOTING PROTEINS; RENAL-CELL CARCINOMA; BH3 MIMETIC ABT-737; PROAPOPTOTIC PROTEIN; CYTOCHROME-C; LYMPHOID-CELLS; MEMBRANE PERMEABILIZATION AB Apoptosis, a form of cellular suicide is a key mechanism involved in the clearance of cells that are dysfunctional, superfluous or infected. For this reason, the cell needs mechanisms to sense death cues and relay death signals to the apoptotic machinery involved in cellular execution. In the intrinsic apoptotic pathway, a subclass of BCL-2 family proteins called the BH3-only proteins are responsible for triggering apoptosis in response to varied cellular stress cues. The mechanisms by which they are regulated are tied to the type of cellular stress they sense. Once triggered, they interact with other BCL-2 family proteins to cause mitochondrial outer membrane permeabilization which in turn results in the activation of serine proteases necessary for cell killing. Failure to properly sense death cues and relay the death signal can have a major impact on cancer. This chapter will discuss our current models of how BH3-only proteins function as well as their impact on carcinogenesis and cancer treatment. C1 [Letai, Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letai, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NCI NIH HHS [R01 CA129974] NR 124 TC 7 Z9 7 U1 1 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6705-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 687 BP 49 EP 63 D2 10.1007/978-1-4419-6706-0 PG 15 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BQA75 UT WOS:000280523400003 PM 20919637 ER PT S AU Levitt, JJ Bobrow, L Lucia, D Srinivasan, P AF Levitt, James J. Bobrow, Laurel Lucia, Diandra Srinivasan, Padmapriya BE Swerdlow, NR TI A Selective Review of Volumetric and Morphometric Imaging in Schizophrenia SO BEHAVIORAL NEUROBIOLOGY OF SCHIZOPHRENIA AND ITS TREATMENT SE Current Topics in Behavioral Neurosciences LA English DT Review; Book Chapter DE Anterior cingulate gyrus; Amygdala; Caudate nucleus 32; Entorhinal cortex; Fusiform gyrus; Hippocampus; Heschl's gyrus; Inferior frontal gyrus; Inferior temporal gyrus; Middle frontal gyrus; Middle temporal gyrus; Orbitofrontal cortex; Parahippocampal cortex; Planum temporale; Prefrontal cortex; Straight gyrus; Superior frontal gyrus; Superior temporal gyrus; Temporal pole ID GRAY-MATTER VOLUME; CAUDATE-NUCLEUS VOLUME; SCHIZOTYPAL PERSONALITY-DISORDER; NEUROLEPTIC-NAIVE SCHIZOPHRENIA; 1ST-EPISODE AFFECTIVE PSYCHOSIS; ANTERIOR HIPPOCAMPAL VOLUME; SUPERIOR TEMPORAL GYRUS; CINGULATE GYRUS; PREFRONTAL CORTEX; PLANUM TEMPORALE AB Brain imaging studies have long supported that schizophrenia is a disorder of the brain, involving many discrete and widely spread regions. Generally, studies have shown decreases in cortical gray matter (GM) volume. Here, we selectively review recent papers studying GM volume changes in schizophrenia subjects, both first-episode (FE) and chronic, in an attempt to quantify and better understand differences between healthy and patient groups. We focused on the cortical GM of the prefrontal cortex, limbic and paralimbic structures, temporal lobe, and one subcortical structure (the caudate nucleus). We performed a search of the electronic journal database PsycINFO using the keywords "schizophrenia" and "MRI," and selected for papers published between 2001 and 2008. We then screened for only those studies utilizing manual or manually edited tracing methodologies for determining regions of interest (ROIs). Each region of interest was indexed independently; thus, one paper might yield results for numerous brain regions. Our review found that in almost all ROIs, cortical GM volume was decreased in the patient populations. The only exception was the caudate nucleus most studies reviewed showed no change, while one study showed an increase in volume; this region, however, is particularly sensitive to medication effects. The reductions were seen in both FE and chronic schizophrenia. These results clearly support that schizophrenia is an anatomical disorder of the brain, and specifically that schizophrenia patients tend to have decreased cortical GM in regions involved in higher cognition and emotional processing. That these reductions were found in both FE and chronic subjects supports that brain abnormalities are present at the onset of illness, and are not simply a consequence of chronicity. Additional studies assessing morphometry at different phases of the illness, including prodromal stages, together with longitudinal studies will elucidate further the role of progression in this disorder. C1 [Levitt, James J.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02301 USA. [Levitt, James J.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA. [Levitt, James J.; Bobrow, Laurel; Lucia, Diandra; Srinivasan, Padmapriya] Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neuroimaging Lab,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Levitt, JJ (reprint author), Harvard Univ, Dept Psychiat, Sch Med, Brockton Campus,116A4,940 Belmont St, Brockton, MA 02301 USA. EM james_levitt@hms.harvard.edu; laurel@bwh.harvard.edu; diandra@bwh.harvard.edu; priya@bwh.harvard.edu NR 70 TC 47 Z9 48 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-13716-7 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2010 VL 4 BP 243 EP 281 DI 10.1007/7854_2010_53 D2 10.1007/978-3-642-13717-4 PG 39 WC Neurosciences SC Neurosciences & Neurology GA BQY42 UT WOS:000282104600009 PM 21312403 ER PT S AU Kalkstein, S Hurford, I Gur, RC AF Kalkstein, Solomon Hurford, Irene Gur, Ruben C. BE Swerdlow, NR TI Neurocognition in Schizophrenia SO BEHAVIORAL NEUROBIOLOGY OF SCHIZOPHRENIA AND ITS TREATMENT SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Cognition; Endophenotypes; Memory; Neuropsychology; Schizophrenia ID COGNITIVE DEFICITS; SOCIAL COGNITION; HIGH-RISK; 1ST-EPISODE SCHIZOPHRENIA; NEURODEVELOPMENTAL MODEL; EMOTION RECOGNITION; MEMORY IMPAIRMENT; HEALTHY CONTROLS; METAANALYSIS; ENDOPHENOTYPES AB Neuropsychological deficits among schizophrenia patients have been consistently documented in research over the past 20 years and are reviewed in this chapter. Discussion of general abilities is presented as a background and is followed by analysis of functioning in specific cognitive domains. Overall intellectual deficits are indicated by results from both general intelligence tests and composite test battery scores. Within specific cognitive domains, effect size differences are noted in numerous areas, including attention, with indications that working memory is affected more severely than simple attention, likely due to inclusion of an executive component in such tasks. There is also evidence of slowed processing speed among schizophrenia patients, likely contributing to deficits in other domains which rely on rapid and efficient assimilation of information. Executive impairments have been found on tests assessing set-shifting abilities, selective attention, and inhibition of inappropriate responses. Learning and memory deficits have been demonstrated extensively, with some evidence that recall of verbal material is more affected than recall of visual information, and that recognition abilities are comparatively less impaired than recall for both modalities. Receptive and expressive language abilities are compromised in schizophrenia patients, as well as visual perceptual, constructional, and fine motor skills. Social cognition is an area of particular importance due to its relevance to functional outcome. Deficits in expression and recognition of facial and prosodic affect have been demonstrated, although subjective experience of emotion appears to be relatively well preserved. Neuropsychological deficits described in this review appear to generally remain stable throughout adulthood, supporting neurodevelopmental, rather than neurodegenerative, models of the illness. Finally, cognitive deficits are increasingly used as endophenotypes, which is likely an important direction of future research. C1 [Kalkstein, Solomon; Hurford, Irene; Gur, Ruben C.] Univ Penn, Sch Med, Dept Psychiat, Schizophrenia Res Ctr,Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Kalkstein, Solomon; Hurford, Irene] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kalkstein, S (reprint author), Univ Penn, Sch Med, Dept Psychiat, Schizophrenia Res Ctr,Neuropsychiat Sect, 10th Floor,Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM solomon.kalkstein@va.gov; ihurford@upenn.edu; gur@bblmail.psycha.upenn.edu NR 95 TC 76 Z9 77 U1 3 U2 14 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-13716-7 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2010 VL 4 BP 373 EP 390 DI 10.1007/7854_2010_42 D2 10.1007/978-3-642-13717-4 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BQY42 UT WOS:000282104600013 PM 21312407 ER PT J AU Prentky, RA Li, NC Righthand, S Schuler, A Cavanaugh, D Lee, AF AF Prentky, Robert A. Li, Nien-Chen Righthand, Sue Schuler, Ann Cavanaugh, Deborah Lee, Austin F. TI Assessing Risk of Sexually Abusive Behavior Among Youth in a Child Welfare Sample SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID JUVENILE SEX OFFENDERS; RECIDIVISM; VIOLENCE; REGISTRATION; VALIDITY; POLICIES AB Statutory management of juvenile sexual offenders demands reliable, valid methods for assessing the risk posed by these youth. This study examined the predictive validity of the J-SOAP-II using samples of adolescent and pre-adolescent boys who were wards of the Massachusetts Department of Social Services. The base rate for sexual recidivism among the adolescents (14-16%) is generally in line with what has been reported. The equivalent base rate for the pre-adolescents (25-28%), however, was notably higher. Although the J-SOAP-II was developed for adolescents, the scale also worked with the pre-adolescents in predicting sexual recidivism over 7 years, with AUC values of 0.77, 0.74, 0.77, and 0.80 for Scales 1, 3, 4, and Total among the pre-adolescents and AUC values of 0.80, 0.82, and 0.83 for Scales 1, 4, and Total among the adolescents. Discussion focuses on extant J-SOAP research and sample dependent variability, as well as social policy implications. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Prentky, Robert A.] Fairleigh Dickinson Univ, Teaneck, NJ USA. [Li, Nien-Chen] Boston Univ, Boston, MA 02215 USA. [Righthand, Sue] Univ Maine, Orono, ME 04469 USA. [Lee, Austin F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Austin F.] Renmin Univ, Sch Stat, Beijing, Peoples R China. RP Prentky, RA (reprint author), Fairleigh Dickinson Univ, Teaneck, NJ USA. EM rprentky@fdu.edu NR 53 TC 18 Z9 19 U1 3 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PD JAN-FEB PY 2010 VL 28 IS 1 BP 24 EP 45 DI 10.1002/bsl.920 PG 22 WC Psychology, Applied; Law SC Psychology; Government & Law GA 560NP UT WOS:000274909700002 PM 20101590 ER PT J AU Najmi, S Reese, H Wilhelm, S Fama, J Beck, C Wegner, DM AF Najmi, Sadia Reese, Hannah Wilhelm, Sabine Fama, Jeanne Beck, Celeste Wegner, Daniel M. TI Learning the Futility of the Thought Suppression Enterprise in Normal Experience and in Obsessive Compulsive Disorder SO BEHAVIOURAL AND COGNITIVE PSYCHOTHERAPY LA English DT Article DE Suppression; obsessive-compulsive disorder; beliefs; intrusive thoughts ID ACUTE STRESS DISORDER; MENTAL CONTROL; INTRUSIVE THOUGHTS; BELIEFS QUESTIONNAIRE; INDIVIDUALS; RELIABILITY; DEPRESSION; VALIDATION; FREQUENCY; APPRAISAL AB Background: The belief that we can control our thoughts is not inevitably adaptive, particularly when it fuels mental control activities that have ironic unintended consequences. The conviction that the mind can and should be control led can prompt people to Suppress unwanted thoughts, and so can set the stage for the intrusive return of those very thoughts. An important question is whether or not these beliefs about the control of thoughts can be reduced experimentally. One possibility is that behavioral experiments aimed at revealing the ironic return of suppressed thoughts might create a lesson that Could reduce unrealistic belief, about the control of thoughts. Aims: The present research assessed the influence of the thought Suppression demonstration on belief's about the control of thoughts in a non-clinical sample, and among individuals with obsessive-compulsive disorder (OCD). Method: In Study 1, we assessed the effect of the thought Suppression demonstration on beliefs about the control of thoughts among low and high obsessive individuals in the non-clinical population (N = 62). In Study 2, we conducted a similar Study with individuals with OCD (N = 29). Results: Results suggest that high obsessive individuals in the non-clinical population are able to learn the futility of suppression through the thought suppression demonstration and to after their faulty belief., about the control of thoughts; however, for individuals with OCD, the demonstration may be insufficient for altering underlying beliefs. Conclusions: For individuals with OCD, the connection between suppressing a neutral thought in the suppression demonstration and suppressing a personally relevant obsession may need to be stated explicitly in order to affect their obsessive beliefs. C1 [Najmi, Sadia] San Diego State Univ, Univ Calif San Diego, Joint Doctoral Program, Ctr Understanding & Treating Anxiety, San Diego, CA 92120 USA. [Wilhelm, Sabine; Fama, Jeanne] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wilhelm, Sabine; Fama, Jeanne] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Najmi, S (reprint author), San Diego State Univ, Univ Calif San Diego, Joint Doctoral Program, Ctr Understanding & Treating Anxiety, 6386 Alvarado Ct,Suite 301, San Diego, CA 92120 USA. EM najmi.sadia@gmail.com NR 44 TC 4 Z9 4 U1 2 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1352-4658 J9 BEHAV COGN PSYCHOTH JI Behav. Cognit. Psychther. PD JAN PY 2010 VL 38 IS 1 BP 1 EP 14 DI 10.1017/S1352465809990439 PG 14 WC Psychology, Clinical SC Psychology GA 540CG UT WOS:000273307700001 PM 19852877 ER PT J AU Stoodley, CJ Valera, EM Schmahmann, JD AF Stoodley, Catherine J. Valera, Eve M. Schmahmann, Jeremy D. TI An fMRI study of intra-individual functional topography in the human cerebellum SO BEHAVIOURAL NEUROLOGY LA English DT Article DE Cerebellum; topography; functional MRI; cognition; motor ID POSITRON-EMISSION-TOMOGRAPHY; COGNITIVE-AFFECTIVE SYNDROME; VERBAL WORKING-MEMORY; WORD-STEM COMPLETION; BLOOD-FLOW CHANGES; MENTAL ROTATION; RHESUS-MONKEY; HUMAN BRAIN; CORTICOPONTOCEREBELLAR PATHWAY; PREFRONTAL CORTEX AB Neuroimaging studies report cerebellar activation during both motor and non-motor paradigms, and suggest a functional topography within the cerebellum. Sensorimotor tasks activate the anterior lobe, parts of lobule VI, and lobule VIII, whereas higher-level tasks activate lobules VI and VII in the posterior lobe. To determine whether these activation patterns are evident at a single-subject level, we conducted functional magnetic resonance imaging (fMRI) during live tasks investigating sensorimotor (finger tapping), language (verb generation), spatial (mental rotation), working memory (N-back), and emotional processing (viewing images from the International Affective Picture System). Finger tapping activated the ipsilateral anterior lobe (lobules IV-V) as well as lobules VI and VIII. Activation during verb generation was found in right lobules VII and VIIIA. Mental rotation activated left-lateralized clusters in lobules VII-VIIIA, VI-Crus I, and midline VIIAt. The N-back task showed bilateral activation in right lobules VI-Crus I and left lobules VIIB-VIIIA. Cerebellar activation was evident bilaterally in lobule VI while viewing arousing vs. neutral images. This fMRI study provides the first proof of principle demonstration that there is topographic organization of motor execution vs. cognitive/emotional domains within the cerebellum of a single individual, likely reflecting the anatomical specificity of cerebro-cerebellar circuits underlying different task domains. Inter-subject variability of motor and non-motor topography remains to be determined. C1 [Stoodley, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Boston, MA 02114 USA. [Stoodley, Catherine J.; Valera, Eve M.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. [Stoodley, Catherine J.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Lab Neuroanat & Cerebellar Neurobiol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Boston, MA 02114 USA. [Valera, Eve M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Stoodley, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM cstoodley@partners.org RI Stoodley, Catherine/P-2081-2016 OI Stoodley, Catherine/0000-0003-2629-0213 FU The National Center for Research Resources [P41RR14075]; Massachusetts General Hospital Fund for Medical Discovery; National Institutes of Health [071535]; Birmingham Foundation; MINDlink Foundation FX This study was supported in part by The National Center for Research Resources (P41RR14075); the Massachusetts General Hospital Fund for Medical Discovery (CJS); the National Institutes of Health (071535, EMV); and the Birmingham Foundation and MINDlink Foundation (JDS). The authors would like to thank Larry Seidman for the use of the N-back task, Peter Hansen for providing stimuli for the mental rotation task, Janet Sherman for help with the psychometric test battery, and Scott Slotnick for helpful discussion. NR 100 TC 48 Z9 48 U1 4 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2010 VL 23 IS 1-2 SI SI BP 65 EP 79 DI 10.3233/BEN-2010-0268 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 661IY UT WOS:000282721000007 PM 20714062 ER PT B AU Faquin, WC Michael, CW Renshaw, AA Vielh, P AF Faquin, William C. Michael, Claire W. Renshaw, Andrew A. Vielh, Philippe BE Ali, SZ Cibas, ES TI Follicular Neoplasm, Hurthle Cell Type/Suspicious for a Follicular Neoplasm, Hurthle Cell Type SO BETHESDA SYSTEM FOR REPORTING THYROID CYTOPATHOLOGY: DEFINITIONS, CRITERIA AND EXPLANATORY NOTES LA English DT Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiration State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst ID FINE-NEEDLE-ASPIRATION; THYROID LESIONS; MALIGNANCY; CARCINOMA; DIAGNOSIS; ACCURACY; CYTOLOGY; CRITERIA; CANCER; BIOPSY C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Michael, Claire W.] Univ Michigan, Ctr Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. [Vielh, Philippe] Inst Gustave Roussy, Dept Pathol, Rue Camille Desmoulins, F-94800 Villejuif, France. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 20 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-87665-8 PY 2010 BP 59 EP + DI 10.1007/978-0-387-87666-5_6 PG 3 WC Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BOC73 UT WOS:000276194800006 ER PT B AU Pitman, MB Oertel, YC Geisinger, KR AF Pitman, Martha B. Oertel, Yolanda C. Geisinger, Kim R. BE Ali, SZ Cibas, ES TI Medullary Thyroid Carcinoma SO BETHESDA SYSTEM FOR REPORTING THYROID CYTOPATHOLOGY: DEFINITIONS, CRITERIA AND EXPLANATORY NOTES LA English DT Proceedings Paper CT National-Cancer-Institute Conference on Thyroid Fine-Needle Aspiration State of the Science CY OCT 22-23, 2007 CL Bethesda, MD SP Natl Canc Inst ID FINE-NEEDLE-ASPIRATION; SCIENCE CONFERENCE; CANCER; DIAGNOSIS; SYNOPSIS; CYTOLOGY; STATE C1 [Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Oertel, Yolanda C.] Washington Hosp Ctr, Dept Pathol, Washington, DC USA. [Geisinger, Kim R.] Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-87665-8 PY 2010 BP 117 EP + DI 10.1007/978-0-387-87666-5_9 PG 3 WC Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BOC73 UT WOS:000276194800009 ER PT J AU Li, HG Huang, PL Zhang, DW Sun, YT Chen, HC Zhang, J Huang, PL Kong, XP Lee-Huang, S AF Li, Hui-Guang Huang, Philip L. Zhang, Dawei Sun, Yongtao Chen, Hao-Chia Zhang, John Huang, Paul L. Kong, Xiang-Peng Lee-Huang, Sylvia TI A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AIDS; HIV-1; Antiviral; Anti-tumor; Adenosine glycosidase; Plant protein ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; MAP30; INHIBITION; BINDING; GAP-31; AGENTS; TRICHOSANTHIN; EXPRESSION; MECHANISM AB We report here the high-resolution atomic Structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third. GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA. (C) 2009 Elsevier Inc. All rights reserved. C1 [Li, Hui-Guang; Zhang, Dawei; Sun, Yongtao; Kong, Xiang-Peng; Lee-Huang, Sylvia] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. [Huang, Philip L.] Amer Biosci, Boston, MA 02114 USA. [Chen, Hao-Chia] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. [Zhang, John] NYU, Dept Chem, New York, NY 10003 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. RI Zhang, Dawei/C-5981-2008; OI Lee-Huang, Sylvia/0000-0003-3302-241X; Kong, Xiang-Peng/0000-0001-5773-2681 FU JT Research; National Center for Complementary and Alternative Medicine (NCCAM) [R01-AT01383]; National Institute of Allergy and Infectious Diseases (NIAID), NIH [R01-A131343] FX We thank staff members at X-ray beamlines X12B and X26C of NSLS and 19D of APS for assistance with data collections. This work was supported in part by a JT Research Grant to S.L -H. and X.PK S.L.-H. also acknowledges the support of research Grant R01-AT01383 from the National Center for Complementary and Alternative Medicine (NCCAM) and Grant R01-A131343 from the National Institute of Allergy and Infectious Diseases (NIAID), NIH. NR 23 TC 11 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2010 VL 391 IS 1 BP 340 EP 345 DI 10.1016/j.bbrc.2009.11.060 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500061 PM 19913503 ER PT J AU Chen, WL Kajiya, M Giro, G Ouhara, K Mackler, HE Mawardi, H Boisvert, H Duncan, MJ Sato, K Kawai, T AF Chen, Weilin Kajiya, Mikihito Giro, Gabriela Ouhara, Kazuhisa Mackler, Harrison E. Mawardi, Hani Boisvert, Heike Duncan, Margaret J. Sato, Kimihiro Kawai, Toshihisa TI Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Hydrogen sulfide; Epithelial cells; IL-8; Bacteria; Porphyromonas gingivalis; Gingipain; Pathogenesis; Hydrogen; Innate immune response; Periodontal disease ID INTERCELLULAR-ADHESION MOLECULE-1; TOLL-LIKE RECEPTOR-2; PORPHYROMONAS-GINGIVALIS; ACTIVATION; EXPRESSION; LIPOPOLYSACCHARIDE; INTERLEUKIN-8; INFLAMMATION; HOST; PERIODONTITIS AB Hydrogen Sulfide (H(2)S) a volatile Sulfur compound, is implicated as a cause of inflammation. especially when it is produced by bacteria colonizing gastrointestinal organs However, It IS Unclear if H(2)S produced by periodontal pathogens affects the inflammatory responses mediated by oral/gingival epithelial cells Therefore. the aims Of this Study were (1) to compare the in vitro production of H(2)S among. 14 strains of Oral bacteria and (2) to evaluate the effects of H(2)S on inflammatory response induced in host oral/gingival epithelial cells Porphyromonas gingivalis (Pg) produced the most H(2)S in Culture, Which, in turn resulted in the promotion of proinflammatory cytokine IL-8 from both gingival and Oral epithelial cells The up-regulation of IL-8 expression was reproduced by the exogenously applied H(2)S Furthermore. the Mutant Strains of Pg that do not produce major Soluble Virulent factors. ie gingival, still showed the Production Of H(2)S. as well as the promotion of epithelial IL-8 production. which was abrogated by H(2)S scavenging reagents These results demonstrated that Pg produces a concentration of H(2)S capable of Up-regulating-IL-8 expression induced in gingival and oral epithelial cells, revealing a possible mechanism that may promote the inflammation in periodontal disease (C) 2009 Elsevier Inc. All rights reserved C1 [Chen, Weilin; Kajiya, Mikihito; Giro, Gabriela; Ouhara, Kazuhisa; Mackler, Harrison E.; Mawardi, Hani; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. [Boisvert, Heike; Duncan, Margaret J.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Giro, Gabriela] UNESP, Dept Oral Diag & Surg, Sch Dent Araraquara, Jaboticabal, SP, Brazil. [Sato, Kimihiro] Skyview Enterprises, New York, NY USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. RI Giro, Gabriela/D-2746-2009 OI Giro, Gabriela/0000-0002-7590-8158 FU Skyview Enterprises; NIH [DE-018310, DE-015931]; Howard Hughes Medical Institute FX This study was Supported by a research grant from Skyview Enterprises and NIH Grants DE-018310 and DE-015931. We thank Dr Koji Nakayama at Kyushu University, Japan, for the strains of Pg KDP112 and Pg KDP137 as well as Lin Martin and Tina Yaskell in the Department of Periodontology at The Forsyth Institute for providing the strains of other periodontal bacteria used in this Study. We also acknowledge Olive Tang's assistance in conducting the laboratory assays. Weilin Chen was Supported by The Forsyth Education Outreach Program, and Harrison Mackler was Supported by the Medical Fellows Program from the Howard Hughes Medical Institute. NR 32 TC 15 Z9 16 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 1 PY 2010 VL 391 IS 1 BP 645 EP 650 DI 10.1016/j.bbrc.2009.11.113 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 544AV UT WOS:000273624500113 PM 19932683 ER PT J AU Marusyk, A Polyak, K AF Marusyk, Andriy Polyak, Kornelia TI Tumor heterogeneity: Causes and consequences SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Diversity; Selection; Evolution ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COMPARATIVE GENOMIC HYBRIDIZATION; CHRONIC MYELOID-LEUKEMIA; CANCER STEM-CELLS; BREAST-CANCER; CLONAL EVOLUTION; GENETIC-HETEROGENEITY; PROSTATE-CANCER; SOLID TUMORS; INTRATUMOR HETEROGENEITY AB With rare exceptions, spontaneous tumors originate from a single cell. Yet, at the time of clinical diagnosis, the majority of human tumors display startling heterogeneity in many morphological and physiological features, such as expression of cell surface receptors, proliferative and angiogenic potential. To a substantial extent, this heterogeneity might be attributed to morphological and epigenetic plasticity, but there is also strong evidence for the co-existence of genetically divergent tumor cell clones within tumors. In this perspective, we summarize the sources of intra-tumor phenotypic heterogeneity with emphasis on genetic heterogeneity. We review experimental evidence for the existence of both intra-tumor clonal heterogeneity as well as frequent evolutionary divergence between primary tumors and metastatic outgrowths. Furthermore, we discuss potential biological and clinical implications of intra-tumor clonal heterogeneity. (C) 2009 Elsevier B.V. All rights reserved. C1 [Marusyk, Andriy; Polyak, Kornelia] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_polyak@dfci.harvard.edu FU Breast Cancer Research Foundation; National Cancer Institute [P01CA080111]; U.S. Department of Defense [W81XWH-09-1-0131, BC087579] FX We would like to thank Franzisca Michor and members of the Polyak laboratory for their critical reading of this manuscript. This work was supported by grants from the Breast Cancer Research Foundation, National Cancer Institute (P01CA080111), and U.S. Department of Defense (W81XWH-09-1-0131 and BC087579). We apologize to all authors whose publication we may have omitted. NR 151 TC 384 Z9 401 U1 13 U2 87 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JAN PY 2010 VL 1805 IS 1 BP 105 EP 117 DI 10.1016/j.bbcan.2009.11.002 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 557JP UT WOS:000274665700011 PM 19931353 ER PT J AU Tassa, C Duffner, JL Lewis, TA Weissleder, R Schreiber, SL Koehler, AN Shaw, SY AF Tassa, Carlos Duffner, Jay L. Lewis, Timothy A. Weissleder, Ralph Schreiber, Stuart L. Koehler, Angela N. Shaw, Stanley Y. TI Binding Affinity and Kinetic Analysis of Targeted Small Molecule-Modified Nanoparticles SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PROTEIN CORONA; MULTIVALENT; PLATFORM; LIGANDS; PROBES; CELLS AB Nanoparticles bearing surface-conjugated targeting ligands are increasingly being explored for it variety of biomedical applications. The multivalent conjugation of targeting ligands on the surface of nanoparticles is presumed to enhance binding to the desired target. However, given the complexities inherent in the interactions of nanoparticle surfaces with proteins, and the Structural diversity of nanoparticle scaffolds and targeting ligands, Our understanding of flow conjugation of targeting ligands affects nanoparticle binding remains incomplete. Here, we use surface plasmon resonance (SPR) to directly and quantitatively study the affinity and binding kinetics of nanoparticles that display small molecules conjugated to their surface. We studied the interaction between I single protein target and it Structurally related series of targeting ligands whose intrinsic affinity varies over a 4500-fold range and performed SPR at protein densities that reflect endogenous receptor densities. We report that even weak small molecule targeting ligands can significantly enhance target-specific avidity (by up to 4 orders of magnitude) through multivalent interactions and also observe it Much broader range of kinetic effects than has been previously reported. Quantitative measurement of how the affinity and kinetics of nanoparticle binding vary as a function of different surface conjugations is a rapid, generalizable approach to nanoparticle characterization that can inform the design of nanoparticles for biomedical applications. C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard & MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Shaw, SY (reprint author), Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM shaw.stanley@mgh.harvard.edu FU National Institutes of Health, National Heart Lung Blood Institute [HL077186, HL80731]; National Institutes of Health, National Cancer Institute [CA119349]; Broad Institute of Harvard and MIT FX This work has been supported by the National Institutes of Health, National Heart Lung Blood Institute (HL077186 to S.Y.S., HL80731 to S.Y.S., S.L.S., and R.W.), and National Cancer Institute (CA119349 to R.W.); and the Broad Institute of Harvard and MIT (to S.Y.S., R.W., and S.L.S.). The authors acknowledge Dr. Kara Herlihy for SPR support, and Jason Fuller, Katie Doud, Dr. Ralph Mazitschek, Dr. Eric Yi Sun, Dr. Lee Josephson, Dr. Greg Thurber, Dr. Karl Munger, and Dr. Hiroyuki Hayakawa for reagents and comments. NR 26 TC 90 Z9 91 U1 8 U2 58 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 JAN PY 2010 VL 21 IS 1 BP 14 EP 19 DI 10.1021/bc900438a PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 544KB UT WOS:000273654400002 PM 20028085 ER PT J AU Evans, KC Dougherty, DD Schmid, AM Scannell, E McCallister, A Benson, H Dusek, JA Lazar, SW AF Evans, K. C. Dougherty, D. D. Schmid, A. M. Scannell, E. McCallister, A. Benson, H. Dusek, J. A. Lazar, S. W. TI Event-related fMRI reveals synchronized limbic and paralimbic activity with each breath SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y CY OCT 05-07, 2008 CL Ann Arbor, MI SP Int Soc Advancement Respiratory Psychophysiol C1 [Evans, K. C.; Dougherty, D. D.; Scannell, E.; McCallister, A.; Lazar, S. W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Evans, K. C.; Dougherty, D. D.; Scannell, E.; McCallister, A.; Lazar, S. W.] Harvard Univ, Sch Med, Boston, MA USA. [Schmid, A. M.] Pecept Informat Inc, Waltham, MA USA. [Benson, H.; Dusek, J. A.] Benson Henry Inst Mind Body Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2010 VL 83 IS 1 BP 66 EP 66 PG 1 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 548FB UT WOS:000273944000024 ER PT J AU Evans, KC Dougherty, DD Schmid, AM Scannell, E McCallister, A Benson, H Dusek, JA Lazar, SW AF Evans, K. C. Dougherty, D. D. Schmid, A. M. Scannell, E. McCallister, A. Benson, H. Dusek, J. A. Lazar, S. W. TI Every breath you take: event-related fMRI identifies cortico-limbic-bulbar circuitry modulation with breathing during meditation SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y CY OCT 05-07, 2008 CL Ann Arbor, MI SP Int Soc Advancement Respiratory Psychophysiol C1 [Evans, K. C.; Dougherty, D. D.; Scannell, E.; McCallister, A.; Lazar, S. W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Evans, K. C.; Dougherty, D. D.; Scannell, E.; McCallister, A.; Lazar, S. W.] Harvard Univ, Sch Med, Boston, MA USA. [Schmid, A. M.] Pecept Informat Inc, Waltham, MA USA. [Benson, H.; Dusek, J. A.] Benson Henry Inst Mind Body Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2010 VL 83 IS 1 BP 68 EP 68 PG 1 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 548FB UT WOS:000273944000030 ER PT J AU Treister, NS Stevenson, K Kim, H Woo, SB Soiffer, R Cutler, C AF Treister, Nathaniel S. Stevenson, Kristen Kim, Haesook Woo, Sook-Bin Soiffer, Robert Cutler, Corey TI Oral Chronic Graft-versus-Host Disease Scoring Using the NIH Consensus Criteria SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Oral; Chronic graft-versus-host disease; Hematopoietic cell transplantation ID STEM-CELL TRANSPLANTATION; DEVELOPMENT PROJECT; CLINICAL-TRIALS; MARROW-TRANSPLANTATION; SUPERFICIAL MUCOCELES; BONE-MARROW; RECIPIENTS; CARE AB The National Institutes of Health (NIH) Oral chronic Graft-versus-Host Disease (cGVHD) Activity Assessment Instrument is intended to be simple to use and to provide a reproducible objective measure of disease activity over time. The objective of this study was to assess inter- and intraobserver variability in the component and composite scores in patients evaluated with oral cGVHD. Twenty-four clinicians (bone marrow transplant [BMT] oncologists: BMTE, n = 16; BMT midlevel providers: BMT MLP; n = 4; and oral medicine experts [OME], n = 4), from 6 major transplant centers scored high-quality intraoral photographs of 12 patients. The same photographs were evaluated 1 week later by the same evaluators. An intraclass correlation coefficient (ICC) was used to calculate intrarater reliability and interrater agreement was analyzed using a weighted K statistic: 0 <= kappa <= 0.20 = poor, 0.21 <= kappa <= 0.40 = fair, 0.41 <= kappa <= 0.60 = moderate, 0.61 <= kappa <= 0.80 = good, 0.81 <= kappa <= 1.00 = very good. Data on participant experiences and demographics were also collected. Mean interrater reliability for each element was poor to moderate (range: 0.15-0.46). Overall mean kappa scores were highest for ulcers (0.46), followed by erythema (0.23), and lowest for lichenoid (0.15) and mucoceles (0.14). Kappa scores were higher in OME compared with BMTE and BMT MLP in ulcers and erythema (eg, 0.85, 0.44, 0.33 for ulcers, respectively), but similar in lichenoid and mucoceles. Overall intrarater reliability in all groups was very good (>= 0.90) and highest for ulcers (0.97, 0.85, 0.94). Although 75% of OME were comfortable with their abilities to score the cases, approximately 50% of BMTE and BMT MLP were uncomfortable. The majority felt that their evaluations were accurate; however, 84% agreed that formal training is required. Interrater variability of the oral cGVHD instrument is unacceptable for the purposes of clinical trials. Greater concordance among OME, high intrarater reliability, and participant feedback suggests that formal training may significantly decrease variability. Parallel investigations must be completed using the other organ specific instruments prior to any revision and widespread prospective utilization of these tools as research endpoints. Biol Blood Marrow Transplant 16: 108-114 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Treister, Nathaniel S.; Woo, Sook-Bin] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [Treister, Nathaniel S.; Woo, Sook-Bin] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Stevenson, Kristen; Kim, Haesook] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Soiffer, Robert; Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Soiffer, Robert; Cutler, Corey] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor,BC-3-028, Boston, MA 02120 USA. EM ntreister@partners.org FU Stem Cell Cyclists of the Pan-Mass Challenge FX The authors would like to thank all of the clinicians that participated in this study for their time and care in completing the evaluations. They are particularly grateful for the contributions of Mr. Terrence Hanscom and Ms. Marianne O'Shea for their help with preparing the study packets and data coordination and processing.; Financial disclosure: C. Cutler is supported by the Stem Cell Cyclists of the Pan-Mass Challenge. NR 29 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2010 VL 16 IS 1 BP 108 EP 114 DI 10.1016/j.bbmt.2009.09.010 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 584DM UT WOS:000276730600012 PM 19772943 ER PT J AU Shioda, T Shioda, K Ellis, H Rosenthal, NL Coser, KR AF Shioda, Toshi Shioda, Keiko Ellis, Haley Rosenthal, Noel L. Coser, Kathryn R. TI Xenoestrogen-Induced Sex Reversal of Chicken Embryonic Testes Involves Specific CpG Dinucleotide Demethylation at a DNA Hypomethylation Dip in CYP19A1/Aromatase Promoter SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Shioda, Toshi; Shioda, Keiko; Ellis, Haley; Rosenthal, Noel L.; Coser, Kathryn R.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 31 BP 58 EP 58 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300029 ER PT J AU Shum, WWC Belleannee, C Brown, D Breton, S AF Shum, Winnie W. C. Belleannee, Clemence Brown, Dennis Breton, Sylvie TI Regulation of Vacuolar H+-ATPase (V-ATPase) Recycling Via a RhoA- and ROCKII-Dependent Pathway in Epididymal Clear Cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [Shum, Winnie W. C.; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 87 BP 69 EP 69 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300082 ER PT J AU Krull, AL Zhang, L Arango, NA Teixeira, J Pru, JK AF Krull, Amanda L. Zhang, Ling Arango, Nelson A. Teixeira, Jose Pru, James K. TI A Potential Role for Mesenchymal-to-Epithelial Transition During Endometrial Regeneration SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 Washington State Univ, Pullman, WA 99164 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 156 BP 84 EP 85 PG 2 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300148 ER PT J AU White, YAR Wood, AW AF White, Yvonne A. R. Wood, Antony W. TI Development of a Novel Vertebrate Model of Postnatal Oogenesis SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 [White, Yvonne A. R.; Wood, Antony W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 317 BP 120 EP 120 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300294 ER PT J AU Hill, JW Burgess, A Bruning, JC Lowell, BB Elmquist, JK Abraham, NG AF Hill, Jennifer W. Burgess, Angela Bruning, Jens C. Lowell, Bradford B. Elmquist, Joel K. Abraham, Nader G. TI The Metabolic Syndrome and Ovarian Dysfunction in Mice. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 Univ Toledo, Sch Med, Toledo, OH 43606 USA. Univ Cologne, Cologne, Germany. BIDMC, Boston, MA USA. UT SW, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 588 BP 176 EP 176 PG 1 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300541 ER PT J AU Woods, DC Tilly, JL AF Woods, Dori C. Tilly, Jonathan L. TI Germ Cell Specification from Murine Embryonic Stem Cells: A Model for the Identification of Irreversible Meiotic Commitment. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 31-AUG 03, 2010 CL Milwaukee, WI SP Soc Study Reproduct C1 Harvard Univ, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2010 SU S MA 710 BP 200 EP 201 PG 2 WC Reproductive Biology SC Reproductive Biology GA 682DY UT WOS:000284381300642 ER PT J AU Lowery, JL Datta, N Rutledge, GC AF Lowery, Joseph L. Datta, Neha Rutledge, Gregory C. TI Effect of fiber diameter, pore size and seeding method on growth of human dermal fibroblasts in electrospun poly(epsilon-caprolactone) fibrous mats SO BIOMATERIALS LA English DT Article DE Electrospinning; Tissue scaffold; Porosity; Perfusion ID TISSUE ENGINEERING SCAFFOLDS; MECHANICAL-PROPERTIES; IN-VITRO; CELLULAR INFILTRATION; PERFUSION BIOREACTOR; NANOFIBERS; MICROFIBER; POLYMER; MATRIX; MESHES AB Nonwoven fiber mats of poly(E-caprolactone) (PCL) and PCL blended with poly(ethylene oxide) (PEO) were generated by electrospinning. Differential scanning calorimetry, scanning electron microscopy, and gravimetric measurement confirm the removal of PEO after immersion in water, as well as an increase in the PCL crystallinity. The reorganization of PCL resulted in the macroscopic alteration of the electrospun mat, decreasing the peak pore diameter up to a factor of 3 while only minimally affecting the fiber diameter. This technique was used to create electrospun PCL scaffolds with similar fiber diameters but different pore diameters to examine the effect of pore diameter on cell growth. Human Dermal Fibroblasts (HDF) were seeded into multiple samples using a perfusion seeding technique to guarantee successful cell deposition. Fluorescence analysis at 7, 14, and 21 days found that cells proliferated at a faster rate on scaffolds with peak pore diameters greater than 6 pm, as determined by mercury porosimetry. Cell conformation was also found to change as the peak pore diameter grew from 12 to 23 pm; cells began aligning along single fibers instead of attaching to multiple fibers. Knowledge of the effect of void architecture on cell proliferation and conformation could lead to the development of more effective scaffolds for tissue engineering. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Lowery, Joseph L.; Datta, Neha; Rutledge, Gregory C.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Lowery, Joseph L.; Rutledge, Gregory C.] MIT, Inst Soldier Nanotechnol, Cambridge, MA 02139 USA. [Datta, Neha] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Datta, Neha] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Rutledge, GC (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rutledge@mit.edu FU Nicolas G. and Dorothea K. Dumbros Scholarship and Fellowship Fund (JLL); Wellman Center for Photomedicine Graduate Fellowship; U.S. Army through the Institute for Soldier Nanotechnologies [DAAD-19-02-D-0002] FX This work was supported in part by the Nicolas G. and Dorothea K. Dumbros Scholarship and Fellowship Fund (JLL), the Wellman Center for Photomedicine Graduate Fellowship (ND), and the U.S. Army through the Institute for Soldier Nanotechnologies, under Contract DAAD-19-02-D-0002 with the U.S. Army Research Office. The content does not necessarily reflect the position of the Government, and no official endorsement should be inferred. We are grateful to the Massachusetts General Hospital for their generation donation of supplies and equipment access, and to the Kochevar group for providing the Human Dermal Fibroblasts. We are also grateful to Dr. Chris Love, for helpful comments on the cell culture experiments. NR 47 TC 164 Z9 170 U1 9 U2 94 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2010 VL 31 IS 3 BP 491 EP 504 DI 10.1016/j.biomaterials.2009.09.072 PG 14 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 532IA UT WOS:000272739200013 PM 19822363 ER PT B AU Howe, E Holton, K Nair, S Schlauch, D Sinha, R Quackenbush, J AF Howe, Eleanor Holton, Kristina Nair, Sarita Schlauch, Daniel Sinha, Raktim Quackenbush, John BE Ochs, MF Casagrande, JT Davuluri, RV TI MeV: MultiExperiment Viewer SO BIOMEDICAL INFORMATICS FOR CANCER RESEARCH LA English DT Article; Book Chapter ID GENE SET ENRICHMENT; MICROARRAY DATA; EXPRESSION; SYSTEM AB Multi Experiment Viewer (MeV) is a freely available software application that puts modern bioinformatics tools for integrative data analysis in the hands of bench biologists. MeV is a versatile microarray data analysis tool, incorporating sophisticated algorithms for clustering, visualization, classification, statistical analysis, and biological theme discovery from single or multiple experiments. This chapter gives an overview of MeV technical details and its use in a real setting. C1 [Howe, Eleanor; Holton, Kristina; Nair, Sarita; Schlauch, Daniel; Sinha, Raktim; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 822A, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 17 TC 22 Z9 22 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5712-2 PY 2010 BP 267 EP 277 DI 10.1007/978-1-4419-5714-6_15 D2 10.1007/978-1-4419-5714-6 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology GA BOO43 UT WOS:000277148600015 ER PT B AU Blackford, A Parmigiani, G AF Blackford, Amanda Parmigiani, Giovanni BE Ochs, MF Casagrande, JT Davuluri, RV TI Familial Cancer Risk Assessment Using BayesMendel SO BIOMEDICAL INFORMATICS FOR CANCER RESEARCH LA English DT Article; Book Chapter ID NONPOLYPOSIS COLORECTAL-CANCER; BREAST-CANCER; OVARIAN-CANCER; BRCA2 MUTATIONS; COLON-CANCER; CARRIER PROBABILITIES; SUSCEPTIBILITY GENES; ASHKENAZI JEWS; PREVALENCE; WOMEN AB BayesMendel is an open-source software program created to provide individuals with personalized risk for carrying an inherited mutation of a cancer-causing gene and for developing cancer related to this mutation. BayesMendel is freely available as an R package (http://astor.som.jhmi.edu/BayesMendel/) or within the Cancer Gene software program (http://www4.utsouthwestern.edu/breasthealth/cagene/). Documentation for the R package is available on the web (http://astor.som.jhmi.edu/BayesMendel/BayesMendel.pdf) and questions can be directed to BayesMendel@jhu.edu. C1 [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Blackford, Amanda] Johns Hopkins Univ, Div Oncol Biostat & Bioinformat, Baltimore, MD 21205 USA. RP Parmigiani, G (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM gp@jimmy.harvard.edu NR 51 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-5712-2 PY 2010 BP 301 EP 314 DI 10.1007/978-1-4419-5714-6_18 D2 10.1007/978-1-4419-5714-6 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Mathematical & Computational Biology GA BOO43 UT WOS:000277148600018 ER PT J AU Martyn, DC Cortese, JF Tyndall, E Dick, J Mazitschek, R Munoz, B Clardy, J AF Martyn, Derek C. Cortese, Joseph F. Tyndall, Erin Dick, Justin Mazitschek, Ralph Munoz, Benito Clardy, Jon TI Antiplasmodial activity of piperazine sulfonamides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Malaria; Antiplasmodial; Thiourea ID PLASMODIUM-FALCIPARUM; BIOACTIVATION; INHIBITORS; DISCOVERY; FURAN AB A high-throughput screening program identified two piperazine sulfonamides with activity against Plasmodium falciparum. Both screening positives had three structural features with potential liabilities: furanyl, thiourea and nitrophenyl groups. The furan could be replaced with no loss of activity, replacement of the nitrophenyl led to some loss of activity, and any attempt to replace the thiourea led to a significant decrease in activity, which implicates this reactive functional group's role in the antiplasmodial activity of this compound class. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Martyn, Derek C.; Cortese, Joseph F.; Tyndall, Erin; Dick, Justin; Mazitschek, Ralph; Munoz, Benito; Clardy, Jon] Infect Dis Initiat, Broad Inst, Cambridge, MA 02142 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02142 USA. [Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Clardy, J (reprint author), Infect Dis Initiat, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM jon_clardy@hms.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU Medicines for Malaria Venture and Genzyme Corporation; Genzyme Corporation FX The authors received funding from the Medicines for Malaria Venture and Genzyme Corporation. Genzyme Corporation funded these studies on a not-for-profit basis. NR 24 TC 10 Z9 10 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2010 VL 20 IS 1 BP 218 EP 221 DI 10.1016/j.bmcl.2009.10.130 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 534ZG UT WOS:000272935600046 PM 19914069 ER PT J AU Martyn, DC Nijjar, A Celatka, CA Mazitschek, R Cortese, JF Tyndall, E Liu, HL Fitzgerald, MM O'Shea, TJ Danthi, S Clardy, J AF Martyn, Derek C. Nijjar, Amarjit Celatka, Cassandra A. Mazitschek, Ralph Cortese, Joseph F. Tyndall, Erin Liu, Hanlan Fitzgerald, Maria M. O'Shea, Thomas J. Danthi, Sanjay Clardy, Jon TI Synthesis and antiplasmodial activity of novel 2,4-diaminopyrimidines SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Malaria; Antiplasmodials; Diaminopyrimidines; Log D; Microsomal clearance; hERG Inhibition ID PLASMODIUM-FALCIPARUM; ANTIMALARIAL ACTIVITY; DRUG-THERAPY; INHIBITORS; CHANNEL AB Two sets of diaminopyrimidines, totalling 45 compounds, were synthesized and assayed against Plasmodium falciparum. The SAR was relatively shallow, with only the presence of a 2-(pyrrolidin-1-yl)ethyl group at R(2) significantly affecting activity. A subsequent series addressed high Log D values by introducing more polar side groups, with the most active compounds possessing diazepine and N-benzyl-4-aminopiperidyl groups at R(1)/R(2). A final series attempted to address high in vitro microsomal clearance by replacing the C6-Me group with CF(3), however antiplasmodial activity decreased without any improvement in clearance. The C6-CF(3) group decreased hERG inhibition, probably as a result of decreased amine basicity at C2/C4. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Martyn, Derek C.; Mazitschek, Ralph; Cortese, Joseph F.; Tyndall, Erin; Clardy, Jon] Infect Dis Initiat, Broad Inst, Cambridge, MA 02142 USA. [Nijjar, Amarjit; Celatka, Cassandra A.; Liu, Hanlan; Fitzgerald, Maria M.; O'Shea, Thomas J.; Danthi, Sanjay] Genzyme Corp, Drug & Biomat R&D, Waltham, MA 02451 USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02142 USA. [Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Clardy, J (reprint author), Infect Dis Initiat, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM jon_clardy@hms.harvard.edu RI Mazitschek, Ralph/E-3741-2013; Danthi, Simhan/B-7639-2014 OI Mazitschek, Ralph/0000-0002-1105-689X; FU Medicines for Malaria Venture; Broad Institute of MIT and Harvard SPARC; Genzyme Corporation FX The authors received funding from the Medicines for Malaria Venture, Broad Institute of MIT and Harvard SPARC, and Genzyme Corporation. Genzyme Corporation funded these studies on a not-for-profit basis. NR 25 TC 9 Z9 9 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2010 VL 20 IS 1 BP 228 EP 231 DI 10.1016/j.bmcl.2009.10.133 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 534ZG UT WOS:000272935600048 PM 19914064 ER PT S AU Chen, ACH Huang, YY Sharma, SK Hamblin, MR AF Chen, Aaron C-H Huang, Ying-Ying Sharma, Sulbha K. Hamblin, Michael R. BE Chen, WR TI Can Dendritic Cells See Light? SO BIOPHOTONICS AND IMMUNE RESPONSES V SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses V CY JAN 25, 2010 CL San Francisco, CA SP SPIE DE photobiomodulation; low level laser therapy; bone marrow derived dendritic cells; markers of maturation and activation; confocal microscopy; flow cytometry ID NF-KAPPA-B; CYTOCHROME-C-OXIDASE; ACTIVATION; THERAPY; ALPHA; TIME AB There are many reports showing that low-level light/laser therapy (LLLT) can enhance wound healing, upregulate cell proliferation and has anti-apoptotic effects by activating intracellular protective genes. In the field of immune response study, it is not known with any certainty whether light/laser is pro-inflammatory or anti-inflammatory. Increasingly in recent times dendritic cells have been found to play an important role in inflammation and the immunological response. In this study, we try to look at the impact of low level near infrared light (810-nm) on murine bone-marrow derived dendritic cells. Changes in surface markers, including MHC II, CD80 and CD11c and the secretion of interleukins induced by light may provide additional evidence to reveal the mystery of how light affects the maturation of dendritic cells as well how these light-induced mature dendritic cells would affect the activation of adaptive immune response. C1 [Chen, Aaron C-H; Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 17 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7961-7 J9 PROC SPIE PY 2010 VL 7565 AR 756504 DI 10.1117/12.842959 PG 7 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BSG32 UT WOS:000284364000003 ER PT S AU Mroz, P Huang, YY Hamblin, MR AF Mroz, Pawel Huang, Ying-Ying Hamblin, Michael R. BE Chen, WR TI Photodynamic Therapy for Cancer and Activation of Immune Response SO BIOPHOTONICS AND IMMUNE RESPONSES V SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biophotonics and Immune Responses V CY JAN 25, 2010 CL San Francisco, CA SP SPIE DE photodynamic therapy; anti-tumor immunity; regulatory T-cells; CpG oligonucleotides; low dose cyclophosphamide ID REGULATORY T-CELLS; LOW-DOSE CYCLOPHOSPHAMIDE; TRANSCRIPTION FACTOR FOXP3; HEAT-SHOCK PROTEINS; IN-VIVO; ANTITUMOR IMMUNITY; DENDRITIC CELLS; TUMOR-IMMUNITY; TGF-BETA; MEDIATED SUPPRESSION AB Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study. C1 [Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Mroz, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 56 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7961-7 J9 PROC SPIE PY 2010 VL 7565 AR 756503 DI 10.1117/12.841031 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BSG32 UT WOS:000284364000002 ER PT J AU Bacskai, BJ Kuchibhotla, KV Lattarulo, C Hyman, BT AF Bacskai, Brian J. Kuchibhotla, Kishore V. Lattarulo, Carli Hyman, Bradley T. TI Dysregulation of Intracellular Calcium in Alzheimer's Disease SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Bacskai, Brian J.; Kuchibhotla, Kishore V.; Lattarulo, Carli; Hyman, Bradley T.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 3A EP 3A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762000013 ER PT J AU Jennings, LD Song, LK Reinherz, EL Collier, RJ AF Jennings, Laura D. Song, Likai Reinherz, Ellis L. Collier, R. John TI Probing Interactions Within Anthrax Toxin by Electron Paramagnetic Resonance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Jennings, Laura D.; Song, Likai; Reinherz, Ellis L.; Collier, R. John] Harvard Univ, Sch Med, Boston, MA USA. [Song, Likai; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 110A EP 110A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001045 ER PT J AU Hamouda, AK Stewart, D Husain, SS Cohen, JB AF Hamouda, Ayman K. Stewart, Deidre Husain, S. Shaukat Cohen, Jonathan B. TI A Transmembrane Binding Site at a Subunit Interface for Torpedo Nicotinic Acetylcholine Receptor Potentiators And Inhibitors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hamouda, Ayman K.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, Deidre; Husain, S. Shaukat] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 131A EP 131A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001149 ER PT J AU Kim, YH Chung, EH Wang, XH Erramilli, S So, PTC AF Kim, Yang-Hyo Chung, Euiheon Wang, Xihua Erramilli, Shyamsunder So, Peter T. C. TI Sub-Diffraction Limited Wide Field Imaging and Microfabrication Based on Surface Plasmons SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Kim, Yang-Hyo; So, Peter T. C.] MIT, Cambridge, MA 02139 USA. [Chung, Euiheon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Xihua] Univ Toronto, Toronto, ON, Canada. [Erramilli, Shyamsunder] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 180A EP 180A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001402 ER PT J AU Gulbahce, N Yan, H Vidal, M Barabasi, AL AF Gulbahce, Natali Yan, Han Vidal, Marc Barabasi, Albert-Laszlo TI Viral Disease Networks SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Gulbahce, Natali; Barabasi, Albert-Laszlo] Northeastern Univ, Boston, MA 02115 USA. [Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yan, Han; Vidal, Marc] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 196A EP 196A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762001485 ER PT J AU Cantero, MD Cantiello, HF AF del Rocio Cantero, Maria Cantiello, Horacio F. TI Regulation by Calcium of Polycystin-2 (TRPP2) and Hetero-Complexes with TRPC1 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [del Rocio Cantero, Maria] Inst Invest Cardiol, Buenos Aires, Argentina. [Cantiello, Horacio F.] Massachusetts Gen Hosp, Charlestown, MA USA. [Cantiello, Horacio F.] Inst Invest Cardiol, Buenos Aires, DF, Argentina. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 339A EP 339A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762003193 ER PT J AU Klemm, AH Kienle, S Bonakdar, N Goldmann, WH Alonso, JL AF Klemm, Anna H. Kienle, Sandra Bonakdar, Navid Goldmann, Wolfgang H. Alonso, Jose-Luis TI Mechanochemical Signaling in Glomerular Podocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Klemm, Anna H.; Kienle, Sandra; Bonakdar, Navid; Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, D-91054 Erlangen, Germany. [Alonso, Jose-Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 497A EP 497A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762004503 ER PT J AU Hobai, IA Weiss, E Armoundas, A Buys, E Brouckaert, P Colucci, WS AF Hobai, Ion A. Weiss, Eric Armoundas, Antonis Buys, Emmanuel Brouckaert, Peter Colucci, Wilson S. TI The Role of Soluble Guanylate Cyclase in Sepsis-Induced Cardiomyopathy in Mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Hobai, Ion A.; Weiss, Eric; Armoundas, Antonis; Buys, Emmanuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hobai, Ion A.; Colucci, Wilson S.] Boston Univ Med Ctr, Boston, MA USA. [Brouckaert, Peter] Univ Ghent VIB, Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 552A EP 552A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762005244 ER PT J AU Chiara, DC Dostalova, Z Liu, AP Zhou, XJ Forman, SA Miller, KW Cohen, JB AF Chiara, David C. Dostalova, Zuzana Liu, Aiping Zhou, Xiaojuan Forman, Stuart A. Miller, Keith W. Cohen, Jonathan B. TI Characterization of the Etomidate Binding Site in Expressed alpha 1 beta 3 GABA(A)R by Photoaffinity Labeling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 [Chiara, David C.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Boston, MA USA. [Dostalova, Zuzana; Liu, Aiping; Zhou, Xiaojuan; Forman, Stuart A.; Miller, Keith W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2010 VL 98 IS 3 SU 1 BP 704A EP 704A PG 1 WC Biophysics SC Biophysics GA V29QD UT WOS:000208762007007 ER PT J AU Cho, CH Park, J Tilles, AW Berthiaume, F Toner, M Yarmush, ML AF Cho, Cheul H. Park, Jaesung Tilles, Arno W. Berthiaume, Francois Toner, Mehmet Yarmush, Martin L. TI Layered patterning of hepatocytes in co-culture systems using microfabricated stencils SO BIOTECHNIQUES LA English DT Article DE hepatocytes; co-culture; layered cell patterning; cellular interactions; fibroblasts ID CELL-CELL INTERACTIONS; OXYGEN-UPTAKE RATES; MESENCHYMAL TRANSITION; NONPARENCHYMAL CELLS; GENE-EXPRESSION; IN-VITRO; LIVER; CULTURE; SPHEROIDS; CADHERIN AB Microfabrication and micropatterning techniques in tissue engineering offer great potential for creating and controlling microenvironments in which cell behavior can be observed. Here we present a novel approach to generate layered patterning of hepatocytes on micropatterned fibroblast feeder layers using microfabricated polydimethylsiloxane (PDMS) stencils. We fabricated PDMS stencils to pattern circular holes with diameters of 500 mu m. Hepatocytes were co-cultured with 3T3-J2 fibroblasts in two types of patterns to evaluate and characterize the cellular interactions in the co-culture systems. Results of this study demonstrated uniform intracellular albumin staining and E-cadherin expression, increased liver-specific functions, and active glycogen synthesis in the hepatocytes when the heterotypic interface between hepatocytes and fibroblasts was increased by the layered patterning technique. This patterning technique can be a useful experimental tool for applications in basic science, drug screening, and tissue engineering, as well as in the design of bioartificial liver devices. C1 [Yarmush, Martin L.] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM cho@njit.edu; jpark@postech.ac.kr; ireis@sbi.org FU National Institutes of Health (NIH) [R01 DK43371, K08 DK066040, K18 DK076819]; NIH BioMEMS Resource Center [P41 EB02503]; Shriners Hospitals for Children FX This study was partially supported by the National Institutes of Health (NIH; grant nos. R01 DK43371, K08 DK066040, and K18 DK076819), the NIH BioMEMS Resource Center (grant no. P41 EB02503), and the Shriners Hospitals for Children. The authors would like to thank Avrum Leeder and Chris Pohun Chen for the isolation of hepatocytes from rat livers. This paper is subject to the NIH Public Access Policy. NR 31 TC 43 Z9 44 U1 2 U2 19 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2010 VL 48 IS 1 BP 47 EP 52 DI 10.2144/000113317 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 594TJ UT WOS:000277560900007 PM 20078427 ER PT J AU Santucci, AK Gold, MA Akers, AY Borrero, S Schwarz, EB AF Santucci, Aimee K. Gold, Melanie A. Akers, Aletha Y. Borrero, Sonya Schwarz, Eleanor Bimla TI Women's Perspectives on Counseling about Risks for Medication-Induced Birth Defects SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 21st International Conference of the Organization-of-Teratology-Information-Specialists CY JUN 28-JUL 01, 2008 CL Monterey, CA SP Org Teratol Soc Informat Specialists DE birth defects; counseling; contraception; medications; teratogens; qualitative ID PREGNANCY AB PURPOSE: This qualitative study explored women's experiences with counseling about medication-induced birth defects, as well as how and when they would like to receive information on medication-induced birth defects from their health care providers (HCPs). METHODS: We conducted four focus groups with 36 women of reproductive age (18-45 years old) in Pittsburgh, Pennsylvania. Twenty-one women were using medications to treat a chronic health condition, and two were pregnant. Content analysis was performed by three independent coders using a grounded theory approach. Discrepancies were resolved by consensus. RESULTS: Women reported depending on their HCPs for information about the risks of teratogenic effects of medications on a pregnancy, but felt the information they had been provided was not always comprehensive. Women want HCPs to initiate discussions about potentially teratogenic medications at the time the medications are prescribed, regardless of whether the woman is sexually active or planning a pregnancy. Women want clear information about all potential outcomes for a fetus. Factors women reported as being critical to effective teratogenic risk counseling included privacy, sufficient time to discuss the topic, and a trusting relationship with their HCP. CONCLUSIONS: Women of reproductive age think that providing information about the possible teratogenic effects of medications could be improved by routine discussions of teratogenic risks at the time medications are prescribed. Birth Defects Research (Part A) 88:64-69, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Santucci, Aimee K.; Borrero, Sonya; Schwarz, Eleanor Bimla] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gold, Melanie A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15261 USA. [Akers, Aletha Y.; Schwarz, Eleanor Bimla] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Borrero, Sonya; Schwarz, Eleanor Bimla] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Schwarz, EB (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM schwarzeb@upmc.edu OI Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU AHRQ HHS [R18 HS017093, R18 HS017093-01]; NICHD NIH HHS [K23 HD051585, K23 HD051585-04] NR 11 TC 12 Z9 13 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2010 VL 88 IS 1 BP 64 EP 69 DI 10.1002/bdra.20618 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 548FG UT WOS:000273944500009 PM 19637252 ER PT J AU Rauh-Hain, JA del Carmen, M Horowitz, NS Alarcon, IA Ko, E Goodman, AK Olawaiye, AB AF Rauh-Hain, J. A. del Carmen, M. Horowitz, N. S. Alarcon, I. A. Ko, E. Goodman, A. K. Olawaiye, A. B. TI Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Bowel obstruction; ovarian cancer; prognosis ID GYNECOLOGIC-ONCOLOGY-GROUP; STAGE-III; CYTOREDUCTIVE SURGERY; PROGNOSTIC-FACTORS; SURGICAL-MANAGEMENT; PALLIATIVE SURGERY; CARCINOMA; SURVIVAL; PACLITAXEL; CISPLATIN AB Objective To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women. Design Retrospective cohort study. Setting Dedicated gynaecological oncology service of a large tertiary institution. Population Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction). Methods Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. Main outcome measures Progression-free survival (PFS) and overall survival (OS). Results Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction. Conclusions Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer. C1 [Olawaiye, A. B.] Univ Pittsburgh, Med Ctr, Div Gynecol Oncol, Magee Womens Hosp,Dept Obstet Gynecol & Reprod Sc, Pittsburgh, PA 15213 USA. [Rauh-Hain, J. A.; Ko, E.] Harvard Univ, Sch Med, Boston, MA USA. [del Carmen, M.; Goodman, A. K.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol, Boston, MA 02114 USA. [Horowitz, N. S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Alarcon, I. A.] Tufts Univ, Sch Med, Dept Med, St Elizabeths Med Ctr, Boston, MA 02111 USA. RP Olawaiye, AB (reprint author), Univ Pittsburgh, Med Ctr, Div Gynecol Oncol, Magee Womens Hosp,Dept Obstet Gynecol & Reprod Sc, 300 Halkett St, Pittsburgh, PA 15213 USA. EM olawaiyea@mail.magee.edu NR 36 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2010 VL 117 IS 1 BP 32 EP 38 DI 10.1111/j.1471-0528.2009.02416.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 530CN UT WOS:000272566600007 PM 20002368 ER PT J AU Lee, PS Bhan, I Thadhani, R AF Lee, Po Shun Bhan, Ishir Thadhani, Ravi TI The Potential Role of Plasma Gelsolin in Dialysis-Related Protein-Energy Wasting SO BLOOD PURIFICATION LA English DT Article; Proceedings Paper CT 12th International Conference on Dialysis CY JAN 20-22, 2010 CL New Orleans, LA DE Gelsolin; Protein-energy malnutrition; Wasting syndrome; Kidney failure; Renal dialysis ID CIRCULATING ACTIN; DISEASE; MORTALITY; OUTCOMES; SEPSIS; ACID AB Protein-energy wasting (PEW) is increasingly recognized to be a prevalent and significant contributor to the clinical deterioration of patients with chronic kidney disease (CKD). While factors reflecting various aspects of PEW correlate with outcomes in CKD, the mechanism linking PEW and CKD outcomes is not completely understood. Plasma gelsolin (pGSN) is a highly abundant circulating protein that is depleted by inflammatory mediators and mainly produced by muscles. Recent data documenting the prognostic ability of low pGSN levels in hemodialysis patients suggests that circulating pGSN levels incorporate the degree of systemic inflammation and muscle wasting. Therefore, pGSN deficiency appears to be a powerful biomarker and a potential therapeutic target in CKD patients. Copyright (C) 2010 S. Karger AG, Basel C1 [Bhan, Ishir; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Lee, Po Shun] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU NIEHS NIH HHS [P30 ES002109] NR 25 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 J9 BLOOD PURIFICAT JI Blood Purif. PY 2010 VL 29 IS 2 BP 99 EP 101 DI 10.1159/000245632 PG 3 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 543CE UT WOS:000273546700005 PM 20093811 ER PT J AU Seok, J Kaushal, A Davis, RW Xiao, WZ AF Seok, Junhee Kaushal, Amit Davis, Ronald W. Xiao, Wenzhong TI Knowledge-based analysis of microarrays for the discovery of transcriptional regulation relationships SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 8th Asia Pacific Bioinformatics Conference CY JAN 18-21, 2010 CL Bangalore, INDIA ID GENE-EXPRESSION DATA; NETWORK; GENOME; YEAST; RECONSTRUCTION; PREDICTION; PROFILES; PATTERNS; MODULES AB Background: The large amount of high-throughput genomic data has facilitated the discovery of the regulatory relationships between transcription factors and their target genes. While early methods for discovery of transcriptional regulation relationships from microarray data often focused on the high-throughput experimental data alone, more recent approaches have explored the integration of external knowledge bases of gene interactions. Results: In this work, we develop an algorithm that provides improved performance in the prediction of transcriptional regulatory relationships by supplementing the analysis of microarray data with a new method of integrating information from an existing knowledge base. Using a well-known dataset of yeast microarrays and the Yeast Proteome Database, a comprehensive collection of known information of yeast genes, we show that knowledge-based predictions demonstrate better sensitivity and specificity in inferring new transcriptional interactions than predictions from microarray data alone. We also show that comprehensive, direct and high-quality knowledge bases provide better prediction performance. Comparison of our results with ChIP-chip data and growth fitness data suggests that our predicted genome-wide regulatory pairs in yeast are reasonable candidates for follow-up biological verification. Conclusion: High quality, comprehensive, and direct knowledge bases, when combined with appropriate bioinformatic algorithms, can significantly improve the discovery of gene regulatory relationships from high throughput gene expression data. C1 [Seok, Junhee; Kaushal, Amit; Davis, Ronald W.; Xiao, Wenzhong] Stanford Genome Technol Ctr, Palo Alto, CA 94305 USA. [Seok, Junhee] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. [Xiao, Wenzhong] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seok, J (reprint author), Stanford Genome Technol Ctr, 955 Calif Ave, Palo Alto, CA 94305 USA. EM jseok@stanford.edu; akaushal@stanford.edu; dbowe@stanford.edu; wzxiao@stanford.edu OI xiao, wenzhong/0000-0003-4944-6380 FU NHGRI NIH HHS [P01-HG00205]; NIGMS NIH HHS [U54-GM62119] NR 24 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2010 VL 11 SU 1 AR S8 DI 10.1186/1471-2105-11-S1-S8 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 548NE UT WOS:000273969500009 PM 20122245 ER PT J AU Garber, CE Greaney, ML Riebe, D Nigg, CR Burbank, PA Clark, PG AF Garber, Carol Ewing Greaney, Mary L. Riebe, Deborah Nigg, Claudio R. Burbank, Patricia A. Clark, Phillip G. TI Physical and mental health-related correlates of physical function in community dwelling older adults: a cross sectional study SO BMC GERIATRICS LA English DT Article AB Background: Physical function is the ability to perform both basic and instrumental activities of daily living, and the ability of older adults to reside in the community depends to a large extent on their level of physical function. Multiple physical and health-related variables may differentially affect physical function, but they have not been well characterized. The purpose of this investigation was to identify and examine physical and mental health-related correlates of physical function in a sample of community-dwelling older adults. Methods: Nine hundred and four community dwelling older men (n = 263) and women (n = 641) with a mean (95% Confidence Interval) age of 76.6 (76.1, 77.1) years underwent tests of physical function (Timed Up and Go; TUG), Body Mass Index (BMI) was calculated from measured height and weight, and data were collected on self-reported health quality of life (SF-36), falls during the past 6 months, number of medications per day, depression (Geriatric Depression Scale; GDS), social support, and sociodemographic variables. Results: Subjects completed the TUG in 8.7 (8.2, 9.2) seconds and expended 6,976 (6,669, 7,284) Kcal.wk(-1) in physical activity. The older persons had a mean BMI of 27.6 (27.2, 28.0), 62% took 3 or more medications per day, and 14.4% had fallen one or more times over the last 6 months. Mean scores on the Mental Component Summary (MCS) was 50.6 (50.2, 51,0) and the Physical Component Summary (PCS) was 41.3 (40.8, 41.8). Multiple sequential regression analysis showed that, after adjustment for TUG floor surface correlates of physical function included age, sex, education, physical activity (weekly energy expenditure), general health, bodily pain, number of medications taken per day, depression and Body Mass Index. Further, there is a dose response relationship such that greater degree of physical function impairment is associated with poorer scores on physical health-related variables. Conclusions: Physical function in community-dwelling older adults is associated with several physical and mental health-related factors. Further study examining the nature of the relationships between these variables is needed. C1 [Garber, Carol Ewing] Columbia Univ, Program Movement Sci & Educ, Dept Behav Sci, Teachers Coll, New York, NY 10027 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Riebe, Deborah] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Nigg, Claudio R.] Univ Hawaii, Dept Publ Hlth Studies Social & Behav Sci, Honolulu, HI 96822 USA. [Burbank, Patricia A.] Univ Rhode Isl, Coll Nursing, Kingston, RI 02881 USA. [Clark, Phillip G.] Univ Rhode Isl, Program Gerontol, Kingston, RI 02881 USA. RP Garber, CE (reprint author), Columbia Univ, Program Movement Sci & Educ, Dept Behav Sci, Teachers Coll, 525 West 120th St,Box 199, New York, NY 10027 USA. EM garber@tc.columbia.edu OI Garber, Carol/0000-0002-1268-576X FU National Institutes of Health (National Institute of Aging) [1-RO1 AG16588-01] FX Funded by National Institutes of Health (National Institute of Aging) grant number 1-RO1 AG16588-01 awarded to the University of Rhode Island, Phillip G. Clark, Principal Investigator. We gratefully acknowledge the work of Faith D. Lees in coordinating the SENIOR study intervention, data collection, and data management. NR 78 TC 28 Z9 29 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PY 2010 VL 10 AR 6 DI 10.1186/1471-2318-10-6 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA V29EL UT WOS:000208731600006 PM 20128902 ER PT J AU Hung, WW Liu, S Boockvar, KS AF Hung, William W. Liu, Sophia Boockvar, Kenneth S. TI A prospective study of symptoms, function, and medication use during acute illness in nursing home residents: design, rationale and cohort description SO BMC GERIATRICS LA English DT Article AB Background: Nursing home residents are at high risk for developing acute illnesses. Compared with community dwelling adults, nursing home residents are often more frail, prone to multiple medical problems and symptoms, and are at higher risk for adverse outcomes from acute illnesses. In addition, because of polypharmacy and the high burden of chronic disease, nursing home residents are particularly vulnerable to disruptions in transitions of care such as medication interruptions in the setting of acute illness. In order to better estimate the effect of acute illness on nursing home residents, we have initiated a prospective cohort which will allow us to observe patterns of acute illnesses and the consequence of acute illnesses, including symptoms and function, among nursing home residents. We also aim to examine the patterns of medication interruption, and identify patient, provider and environmental factors that influence continuity of medication prescribing at different points of care transition. Methods: This is a prospective cohort of nursing home residents residing in two nursing homes in a metropolitan area. Baseline characteristics including age, gender, race, and comorbid conditions are recorded. Participants are followed longitudinally for a planned period of 3 years. We record acute illness incidence and characteristics, and measure symptoms including depression, pain, withdrawal symptoms, and function using standardized scales. Results: 76 nursing home residents have been followed for a median of 666 days to date. At baseline, mean age of residents was 74.4 (+/- 11.9); 32% were female; 59% were white. The most common chronic conditions were dementia (41%), depression (38%), congestive heart failure (25%) and chronic obstructive lung disease (27%). Mean pain score was 4.7 (+/- 3.6) on a scale of 0 to 10; Geriatric Depression Scale (GDS-15) score was 5.2 (+/- 4.4). During follow up, 138 acute illness episodes were identified, for an incidence of 1.5 (SD 2.0) episodes per resident per year; 74% were managed in the nursing home and 26% managed in the acute care setting. Conclusion: In this report, we describe the conceptual model and methods of designing a longitudinal cohort to measure acute illness patterns and symptoms among nursing home residents, and describe the characteristics of our cohort at baseline. In our planned analysis, we will further estimate the effect of the use and interruption of medications on withdrawal and relapse symptoms and illness outcomes. C1 [Hung, William W.; Boockvar, Kenneth S.] James J Peters VA Med Ctr, Ctr Study Hlth Care Syst & Sites Care, Dept Veteran Affairs HSR&D Serv, Bronx, NY 10468 USA. [Hung, William W.; Boockvar, Kenneth S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Liu, Sophia] New York Presbyterian Columbia Univ Med Ctr, Dept Anesthesiol, New York, NY 10032 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, Res Inst Aging, New York, NY 10025 USA. RP Hung, WW (reprint author), James J Peters VA Med Ctr, Ctr Study Hlth Care Syst & Sites Care, Dept Veteran Affairs HSR&D Serv, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM william.hung@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 NR 32 TC 7 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PY 2010 VL 10 AR 47 DI 10.1186/1471-2318-10-47 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA V29EL UT WOS:000208731600047 PM 20630095 ER PT J AU Ma, J Strub, P Camargo, CA Xiao, L Ayala, E Gardner, CD Buist, AS Haskell, WL Lavori, PW Wilson, SR AF Ma, Jun Strub, Peg Camargo, Carlos A., Jr. Xiao, Lan Ayala, Estela Gardner, Christopher D. Buist, A. Sonia Haskell, William L. Lavori, Phillip W. Wilson, Sandra R. TI The Breathe Easier through Weight Loss Lifestyle (BE WELL) Intervention: A randomized controlled trial SO BMC PULMONARY MEDICINE LA English DT Article AB Background: Obesity and asthma have reached epidemic proportions in the US. Their concurrent rise over the last 30 years suggests that they may be connected. Numerous observational studies support a temporally-correct, dose-response relationship between body mass index (BMI) and incident asthma. Weight loss, either induced by surgery or caloric restriction, has been reported to improve asthma symptoms and lung function. Due to methodological shortcomings of previous studies, however, well-controlled trials are needed to investigate the efficacy of weight loss strategies to improve asthma control in obese individuals. Methods/Design: BE WELL is a 2-arm parallel randomized clinical trial (RCT) of the efficacy of an evidence-based, comprehensive, behavioral weight loss intervention, focusing on diet, physical activity, and behavioral therapy, as adjunct therapy to usual care in the management of asthma in obese adults. Trial participants (n = 324) are patients aged 18 to 70 years who have suboptimally controlled, persistent asthma, BMI between 30.0 and 44.9 kg/m(2), and who do not have serious comorbidities (e. g., diabetes, heart disease, stroke). The 12-month weight loss intervention to be studied is based on the principles of the highly successful Diabetes Prevention Program lifestyle intervention. Intervention participants will attend 13 weekly group sessions over a four-month period, followed by two monthly individual sessions, and will then receive individualized counseling primarily by phone, at least bi-monthly, for the remainder of the intervention. Follow-up assessment will occur at six and 12 months. The primary outcome variable is the overall score on the Juniper Asthma Control Questionnaire measured at 12 months. Secondary outcomes include lung function, asthma-specific and general quality of life, asthma medication use, asthma-related and total health care utilization. Potential mediators (e. g., weight loss and change in physical activity level and nutrient intake) and moderators (e. g., socio-demographic characteristics and comorbidities) of the intervention effects also will be examined. Discussion: This RCT holds considerable potential for illuminating the nature of the obesity-asthma relationship and advancing current guidelines for treating obese adults with asthma, which may lead to reduced morbidity and mortality related to the comorbidity of the two disorders. C1 [Ma, Jun; Xiao, Lan; Ayala, Estela; Wilson, Sandra R.] Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. [Strub, Peg] San Francisco Med Ctr, Dept Allergy Asthma & Immunol, Permanente Med Grp, San Francisco, CA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Ayala, Estela] Stanford Univ, Dept Pulm Med & Crit Care, Sch Med, Stanford, CA 94305 USA. [Gardner, Christopher D.; Haskell, William L.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Buist, A. Sonia] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lavori, Phillip W.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. RP Ma, J (reprint author), Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. EM maj@pamfri.org FU AstraZeneca; Critical Therapeutics; Dey; Genentech; GSK; Merck; Novartis; Respironics; Schering-Plough; National Heart, Lung and Blood Institute [R01HL094466] FX Dr. Camargo has received financial support from a variety of groups for participation in conferences, consulting, and medical research. During 2005 to 2010, industry sponsors with an interest in asthma were AstraZeneca, Critical Therapeutics, Dey, Genentech, GSK, Merck, Novartis, Respironics, and Schering-Plough. Dr. Buist is a member of advisory boards for AstraZeneca, Merck, GSK, Sepracor, Pfizer and Novartis.; The project described is supported by Award Number R01HL094466 from the National Heart, Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health. The authors would like to acknowledge the Diabetes Prevention Support Center of the University of Pittsburgh Diabetes Institute for the development of and the training and support for implementation and maintenance of the Group Lifestyle Balance program. NR 76 TC 18 Z9 18 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2466 J9 BMC PULM MED JI BMC Pulm. Med. PY 2010 VL 10 AR 16 DI 10.1186/1471-2466-10-16 PG 14 WC Respiratory System SC Respiratory System GA V27DA UT WOS:000208592700016 PM 20334686 ER PT J AU Tranah, GJ Parimi, N Blackwell, T Ancoli-Israel, S Ensrud, KE Cauley, JA Redline, S Lane, N Paudel, ML Hillier, TA Yaffe, K Cummings, SR Stone, KL AF Tranah, Gregory J. Parimi, Neeta Blackwell, Terri Ancoli-Israel, Sonia Ensrud, Kristine E. Cauley, Jane A. Redline, Susan Lane, Nancy Paudel, Misti L. Hillier, Teresa A. Yaffe, Kristine Cummings, Steven R. Stone, Katie L. TI Postmenopausal hormones and sleep quality in the elderly: a population based study SO BMC WOMENS HEALTH LA English DT Article AB Background: Sleep disturbance and insomnia are commonly reported by postmenopausal women. However, the relationship between hormone therapy (HT) and sleep disturbances in postmenopausal community-dwelling adults is understudied. Using data from the multicenter Study of Osteoporotic Fractures (SOF), we tested the relationship between HT and sleep-wake estimated from actigraphy. Methods: Sleep-wake was ascertained by wrist actigraphy in 3,123 women aged 84 +/- 4 years (range 77-99) from the Study of Osteoporotic Fractures (SOF). This sample represents 30% of the original SOF study and 64% of participants seen at this visit. Data were collected for a mean of 4 consecutive 24-hour periods. Sleep parameters measured objectively included total sleep time, sleep efficiency (SE), sleep latency, wake after sleep onset (WASO), and nap time. All analyses were adjusted for potential confounders (age, clinic site, race, BMI, cognitive function, physical activity, depression, anxiety, education, marital status, age at menopause, alcohol use, prior hysterectomy, and medical conditions). Results: Actigraphy measurements were available for 424 current, 1,289 past, and 1,410 never users of HT. Women currently using HT had a shorter WASO time (76 vs. 82 minutes, P = 0.03) and fewer long-wake (>= 5 minutes) episodes (6.5 vs. 7.1, P = 0.004) than never users. Past HT users had longer total sleep time than never users (413 vs. 403 minutes, P = 0.002). Women who never used HT had elevated odds of SE <70% (OR, 1.37; 95%CI, 0.98-1.92) and significantly higher odds of WASO >= 90 minutes (OR, 1.37; 95%CI, 1.02-1.83) and >= 8 long-wake episodes (OR, 1.58; 95%CI, 1.18-2.12) when compared to current HT users. Conclusions: Postmenopausal women currently using HT had improved sleep quality for two out of five objective measures: shorter WASO and fewer long-wake episodes. The mechanism behind these associations is not clear. For postmenopausal women, starting HT use should be considered carefully in balance with other risks since the vascular side-effects of hormone replacement may exceed its beneficial effects on sleep. C1 [Tranah, Gregory J.; Parimi, Neeta; Blackwell, Terri; Cummings, Steven R.; Stone, Katie L.] CPMC Res Inst, San Francisco, CA 94120 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Ensrud, Kristine E.; Paudel, Misti L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Redline, Susan] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Redline, Susan] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA. [Lane, Nancy] Univ Calif Davis, Sch Med, Dept Med, Sacramento, CA 95817 USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res NW Hawaii, Portland, OR 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. RP Tranah, GJ (reprint author), CPMC Res Inst, San Francisco, CA 94120 USA. EM gtranah@sfcc-cpmc.net OI Cauley, Jane A/0000-0003-0752-4408 FU NIH [AG05407, AR35582, AG05394, AR35584, AR35583, AR46238, AG005407, AG08415, AG027576-22, AG005394-22A1, AG027574-22A1] FX This work was supported by grants from the NIH: AG05407, AR35582, AG05394, AR35584, AR35583, AR46238, AG005407, AG08415, AG027576-22, AG005394-22A1, AG027574-22A1. NR 48 TC 11 Z9 11 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6874 J9 BMC WOMENS HEALTH JI BMC Womens Health PY 2010 VL 10 AR 15 DI 10.1186/1472-6874-10-15 PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology SC Public, Environmental & Occupational Health; Obstetrics & Gynecology GA V27IS UT WOS:000208607500015 PM 20441593 ER PT J AU Warden, SJ Robling, AG Haney, EM Turner, CH Bliziotes, MM AF Warden, Stuart J. Robling, Alexander G. Haney, Elizabeth M. Turner, Charles H. Bliziotes, Michael M. TI The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5) SO BONE LA English DT Review DE Antidepressants; Enterochromaffin cells; Hormones; Osteoporosis; Serotonin ID BONE-MINERAL DENSITY; TRYPTOPHAN-HYDROXYLASE INHIBITORS; REUPTAKE INHIBITORS; TRICYCLIC ANTIDEPRESSANTS; GASTROINTESTINAL-TRACT; ESTROGEN-DEFICIENCY; 5-HT TRANSPORTER; WNT CORECEPTOR; GROWING RATS; MICE AB Novel molecular pathways obligatory for bone health are being rapidly identified. One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT) mediation of the complete skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Mounting evidence supports 5-HT as an important regulatory compound in bone with previous evidence demonstrating that bone cells possess functional pathways for responding to 5-HT. In addition, there is growing evidence that potentiation of 5-HT signaling via inhibition of the 5-HT transporter (5-HTT) has significant skeletal effects. The later is clinically significant as the 5-HTT is a popular target of pharmaceutical agents, such as selective serotonin reuptake inhibitors (SSRIs), used for the management of major depressive disorder and other affective conditions. The observation that 5-HT mediates the complete skeletal effects of LRP5 represents a significant paradigm shift from the traditional view that LRP5 located on the cell surface membrane of osteoblasts exerts direct skeletal effects via Wnt/beta-catenin signaling. This paper discusses the mounting evidence for skeletal effects of 5-HT and the ability of gut-derived 5-HT to satisfactorily explain the skeletal effects of LRP5. (C) 2009 Elsevier Inc. All rights reserved. C1 [Warden, Stuart J.] Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Indianapolis, IN 46202 USA. [Bliziotes, Michael M.] Portland VA Med Ctr, Portland, OR 97239 USA. [Haney, Elizabeth M.; Bliziotes, Michael M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Warden, Stuart J.; Robling, Alexander G.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Turner, Charles H.] Indiana Univ Purdue Univ, Dept Biomed Engn, Purdue Sch Engn & Technol, Indianapolis, IN 46202 USA. RP Warden, SJ (reprint author), Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Indianapolis, IN 46202 USA. EM stwarden@iupui.edu RI Warden, Stuart/C-5287-2012; OI Warden, Stuart/0000-0002-6415-4936 FU National Institutes of Health [AR-052018, AR-051926, AR-53237] FX Completion of this review was enabled by support from National Institutes of Health grants AR-052018 (to M.M.B.), AR-051926 (to E.M.H.) and AR-53237 (to A.G.R.). NR 58 TC 37 Z9 41 U1 0 U2 2 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 JAN PY 2010 VL 46 IS 1 BP 4 EP 12 DI 10.1016/j.bone.2009.06.029 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550LN UT WOS:000274129400001 PM 19591966 ER PT J AU Haney, EM Warden, SJ Bliziotes, MM AF Haney, Elizabeth M. Warden, Stuart J. Bliziotes, M. Michael TI Effects of selective serotonin reuptake inhibitors on bone health in adults: Time for recommendations about screening, prevention and management? SO BONE LA English DT Review DE Bone; Depression; Serotonin; Selective serotonin reuptake inhibitor; Screening; Epidemiology; Neurotransmitter ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; SYSTEM-ACTIVE MEDICATIONS; NURSING-HOME RESIDENTS; PROTON PUMP INHIBITORS; MINERAL DENSITY; OLDER WOMEN; DEPRESSIVE SYMPTOMS; HIP FRACTURE; POSTMENOPAUSAL WOMEN; RISK-FACTOR AB Evidence regarding a functional serotonin (5-hydroxytryptamine) signaling system in bone has generated considerable recent interest. The specific biochemical nature of serotoninergic pathways and their direct and/or indirect effects on bone metabolism are still unclear. Clinical evidence supports an effect of serotonin and altered serotonin signaling on bone metabolism. Serotonin is involved in the pathophysiology of depression, and therefore studies of depression and antidepressant treatments (as modulators of the serotonin system) are relevant with regard to bone outcomes. Studies on the effect of depression on bone mineral density (BMD) and fractures have been mixed. Studies on the associations between antidepressant use and BMD and/or fractures are more consistent. SSRIs have been associated with lower BMD and increased rates of bone loss, as well as increased rates of fracture after accounting for falls. These studies are limited by confounding because depression is potentially associated with both the outcome of interest (BMD and fracture) and the exposure (SSRIs). With Mounting evidence for an effect on bone, this review considers the question of causality and whether selective serotonin reuptake inhibitors should be considered among those medications that contribute to bone loss, and therefore prompt clinicians to evaluate BMD proactively. Future research will be required to confirm the serotoninergic effects on bone and the biochemical pathways involved, and to identify clinical implications for treatment based on this novel pathway. (C) 2009 Published by Elsevier Inc. C1 [Bliziotes, M. Michael] Portland VA Med Ctr, Portland, OR 97239 USA. [Warden, Stuart J.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Warden, Stuart J.] Indiana Univ, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Indianapolis, IN 46202 USA. [Haney, Elizabeth M.; Bliziotes, M. Michael] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. RP Haney, EM (reprint author), Oregon Hlth & Sci Univ, Dept Med, L-475,SW Sam Jackson Pk Rd, Portland, OR 97219 USA. EM haneye@ohsu.edu RI Warden, Stuart/C-5287-2012; OI Warden, Stuart/0000-0002-6415-4936 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [051926] FX Dr. Haney is supported by a K23 award (051926) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 67 TC 45 Z9 48 U1 2 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 JAN PY 2010 VL 46 IS 1 BP 13 EP 17 DI 10.1016/j.bone.2009.07.083 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550LN UT WOS:000274129400002 PM 19664737 ER PT J AU Selvarajah, S Zielenska, M Squire, JA Park, PC AF Selvarajah, Shamini Zielenska, Maria Squire, Jeremy A. Park, Paul C. BE Heymann, D TI Genetic Aspects of Bone Tumors SO BONE CANCER: PROGRESSION AND THERAPEUTIC APPROACHES LA English DT Article; Book Chapter ID COMPARATIVE GENOMIC HYBRIDIZATION; SOFT-TISSUE TUMORS; ENCHONDROMATOSIS OLLIERS-DISEASE; P-GLYCOPROTEIN EXPRESSION; HIGH-GRADE OSTEOSARCOMAS; OF-THE-LITERATURE; EWING-SARCOMA; MOLECULAR-GENETICS; CYTOGENETIC CHARACTERIZATION; CHROMOSOMAL INSTABILITY C1 [Selvarajah, Shamini] Dana Farber Canc Inst, Ctr Med Oncol Pathol, Boston, MA 02115 USA. [Zielenska, Maria] Hosp Sick Children, Dept Pediat Lab Med & Pathobiol, Toronto, ON M5G 1X8, Canada. [Zielenska, Maria] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Squire, Jeremy A.; Park, Paul C.] Queens Univ, Dept Pathol & Mol Med, Richardson Labs, Kingston, ON, Canada. RP Selvarajah, S (reprint author), Dana Farber Canc Inst, Ctr Med Oncol Pathol, Jimmy Fund Bldg 215G, Boston, MA 02115 USA. OI Squire, Jeremy/0000-0002-9863-468X NR 110 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095388-5 PY 2010 BP 161 EP 170 DI 10.1016/B978-0-12-374895-9.00013-X PG 10 WC Oncology SC Oncology GA BEM02 UT WOS:000317291400015 ER PT J AU Kiank, C Tache, Y Larauche, M AF Kiank, Cornelia Tache, Yvette Larauche, Muriel TI Stress-related modulation of inflammation in experimental models of bowel disease and post-infectious irritable bowel syndrome: Role of corticotropin-releasing factor receptors SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Review DE Corticotropin-releasing factor; Inflammatory bowel disease; Irritable bowel syndrome; Inflammation; Stress ID FACTOR SIGNALING PATHWAYS; ENTERIC NERVOUS-SYSTEM; MAST-CELLS; INTESTINAL INFLAMMATION; DENDRITIC CELL; COLONIC-MUCOSA; MATERNAL-DEPRIVATION; FACTOR CRF; IN-VITRO; HORMONE AB The interaction between gut inflammatory processes and stress is gaining increasing recognition. Corticotropin-releasing factor (CRF)-receptor activation in the brain is well established as a key signaling pathway initiating the various components of the stress response including in the viscera. In addition, a local CRF signaling system has been recently established in the gut. This review summarize the present knowledge on mechanisms through which both brain and gut CRF receptors modulate intestinal inflammatory processes and its relevance towards increased inflammatory bowel disease (IBD) activity and post-infectious irritable bowel syndrome (IBS) susceptibility induced by stress. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kiank, Cornelia; Tache, Yvette; Larauche, Muriel] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr Anim Core, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Kiank, C (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr Anim Core, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,CURE Bldg 115,Room 111, Los Angeles, CA 90073 USA. EM ckiank@mednet.ucla.edu OI Vacca, Giovanni/0000-0002-0864-1887; Larauche, Muriel/0000-0003-3320-3675 FU German Research Foundation [KI 1389/2-1]; Veteran Administration Research Career Scientist Award; NIHDDK [R01 DK33061, R01 DK57238, R01 DK33506] FX The authors thank Miss Eugenia Hu for reviewing the manuscript. Dr. C. Kiank is supported by the German Research Foundation Grant KI 1389/2-1 and Dr. Y. Tache is in receipt of Veteran Administration Research Career Scientist Award and NIHDDK R01 Grants DK33061, DK57238 and DK33506. NR 93 TC 38 Z9 41 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2010 VL 24 IS 1 BP 41 EP 48 DI 10.1016/j.bbi.2009.08.006 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 531OE UT WOS:000272676400006 PM 19698778 ER PT J AU Chiambretto, P Moroni, L Guarnerio, C Bertolotti, G Prigerson, HG AF Chiambretto, Paola Moroni, Loretta Guarnerio, Chiara Bertolotti, Giorgio Prigerson, Holly G. TI Prolonged grief and depression in caregivers of patients in vegetative state SO BRAIN INJURY LA English DT Article DE Prolonged grief disorder; caregiver; vegetative state ID TRAUMATIC GRIEF; CRITERIA; ATTITUDES; DISORDER; SCALE; RISK; LIFE AB Methods and procedures: Forty-five caregivers of 41 patients in vegetative or minimally conscious state in-hospital for long-term care. The questionnaire Prolonged Grief 12 (PG-12) assessed the presence of Prolonged Grief Disorder; the Depression Questionnaire (DQ) assessed the presence of a clinically significant depressive state. Main outcomes and results: Three conditions of psychiatric illness emerged: Prolonged Grief Disorder only (n = 9; 20%), depression only (n = 7; 15.5%) and Prolonged Grief Disorder together with depression (n = 7; 15.5%). There was no association (V = 0.203) between diagnosis of Prolonged Grief Disorder and the presence of a clinically significant depressive state. Caregiver's syndromal-level grief was associated with patients' young age (p = 0.028) and with younger age of caregiver (p = 0.029). Caregiver's syndromal-level depression was associated with less time from the event (p = 0.003). Conclusions: Caregiver's grief symptoms are distinct from their depressive symptoms among family members and each disorder has distinct risk factors. C1 [Chiambretto, Paola] Private Hosp Le Betulle, Psychiat Unit, Appiano Gentile, Como, Italy. [Moroni, Loretta; Bertolotti, Giorgio] Tradate Va Inst, Psychol Unit, IRCCS, Salvatore Maugeri Fdn, San Giovanni Rotondo, Italy. [Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Chiambretto, P (reprint author), Private Hosp Le Betulle, Psychiat Unit, Appiano Gentile, Como, Italy. EM chiambretto@yahoo.it OI bertolotti, giorgio/0000-0002-3079-1945 NR 34 TC 24 Z9 24 U1 1 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PY 2010 VL 24 IS 4 BP 581 EP 588 DI 10.3109/02699051003610490 PG 8 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 570ML UT WOS:000275682300002 PM 20235760 ER PT J AU Goldstein, G Allen, DN Caponigro, JM AF Goldstein, Gerald Allen, Daniel N. Caponigro, Janelle M. TI A retrospective study of heterogeneity in neurocognitive profiles associated with traumatic brain injury SO BRAIN INJURY LA English DT Article DE Brain injury; assessment; cluster analysis; intelligence ID VERBAL-LEARNING TEST; PATTERNS; SUBTYPES; PERFORMANCE AB Research design: The study was retrospective, applying cluster analyses and associated statistical tests to an established database. Methods and procedures: Neuropsychological data from veterans with brain trauma were cluster analysed using the WAIS-R and Halstead-Reitan Battery (HRB). External validity of the cluster solutions was evaluated. Experimental interventions: The study was based upon use of an established database that contained cognitive test data and information regarding diagnosis and clinical history. Main outcomes and results: The WAIS-R clusters described sub-groups with near normal function, preserved verbal but impaired problem-solving abilities or global impairment. The HRB clusters differed in level of performance with Near Normal, Moderately Impaired and Globally Impaired clusters. Cluster membership was associated with age and employment status, but not with neurological findings. Conclusion: The outcome of traumatic brain injury is heterogeneous and mainly associated with demographic considerations. C1 [Goldstein, Gerald; Caponigro, Janelle M.] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA 15206 USA. [Allen, Daniel N.] Univ Nevada Las Vegas, Dept Psychol, Las Vegas, NV USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, MIRECC, 7180 Highland Dr 151R, Pittsburgh, PA 15206 USA. EM ggold@nb.net FU DVA VISN IV Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA; Medical Research Service, Department of Veterans Affairs FX This research was supported by the DVA VISN IV Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA and the Medical Research Service, Department of Veterans Affairs. NR 23 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PY 2010 VL 24 IS 4 BP 625 EP 635 DI 10.3109/02699051003670882 PG 11 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 570ML UT WOS:000275682300007 PM 20235765 ER PT J AU Idbaih, A Criniere, E Ligon, KL Delattre, O Delattre, JY AF Idbaih, Ahmed Criniere, Emmanuelle Ligon, Keith L. Delattre, Olivier Delattre, Jean-Yves TI Array-Based Genomics in Glioma Research SO BRAIN PATHOLOGY LA English DT Review DE glioma; array; genomic; comparative genomic hybridization (CGH); single nucleotide polymorphism (SNP) ID HUMAN-MALIGNANT GLIOMAS; GLIOBLASTOMA-MULTIFORME; HIGH-RESOLUTION; COPY NUMBER; ANAPLASTIC OLIGODENDROGLIOMAS; PILOCYTIC ASTROCYTOMAS; MIXED OLIGOASTROCYTOMAS; HYBRIDIZATION; TUMORS; CGH AB Over the years, several relevant biomarkers with a potential clinical interest have been identified in gliomas using various techniques, such as karyotype, microsatellite analysis, fluorescent in situ hybridization and chromosome comparative genomic hybridization. Despite their pivotal contribution to our understanding of gliomas biology, clinical application of these approaches has been limited by technological and clinical complexities. In contrast, genomic arrays (array-based comparative genomic hybridization and single nucleotide polymorphisms array) have emerged as promising technologies for clinical use in the setting of gliomas. Indeed, their feasibility and reliability have been rigorously assessed in gliomas and are discussed in this review. The well-known genomic biomarkers in gliomas are in fact readily and reliably identified using genomic arrays. Moreover, it detects a multitude of new cryptic genomic markers, with potential biological and/or clinical significances. The main studies dedicated to genomic characterization of gliomas using genomic arrays are reviewed here. Interestingly, several recurrent genomic signatures have been reported by different teams, suggesting the validity of these genomic patterns. In light of this, genomic arrays are relatively simple and cost-effective techniques whose implementation in molecular diagnostic laboratories should be encouraged as a valuable clinical tool for management of glioma patients. C1 [Idbaih, Ahmed; Criniere, Emmanuelle; Delattre, Jean-Yves] INSERM, U711, Paris, France. [Idbaih, Ahmed; Criniere, Emmanuelle; Delattre, Jean-Yves] Univ Paris 06, Grp Hosp Pitie Salpetriere, Lab Biol Interact Neurone Glie, F-75013 Paris, France. [Idbaih, Ahmed; Delattre, Jean-Yves] Grp Hosp Pitie Salpetriere, AP HP, Serv Neurol Mazarin, F-75634 Paris, France. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Delattre, Olivier] Inst Curie, INSERM, U830, Sect Rech,Lab Pathol Mol Canc, Paris, France. RP Idbaih, A (reprint author), Univ Paris 06, INSERM, Unite U711, Lab Biol Interact Neurone Glie, Hop Pitie Salpetriere 47-83,Blvd Hop, F-75013 Paris, France. EM ahmed.idbaih@gmail.com OI Ligon, Keith/0000-0002-7733-600X FU INSERM; Ligue Nationale Contre le Cancer FX This work was supported by grants from the INSERM, and the Carte d'Identite des Tumeurs (CIT) program of the Ligue Nationale Contre le Cancer. NR 54 TC 9 Z9 10 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2010 VL 20 IS 1 BP 28 EP 38 DI 10.1111/j.1750-3639.2009.00274.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 528IL UT WOS:000272437500003 PM 19298630 ER PT B AU Erban, JK Smith, BL Taghian, AG AF Erban, John K. Smith, Barbara L. Taghian, Alphonse G. BE Taghian, AG Smith, BL Erban, JK TI Importance of the Multidisciplinary Approach to Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter C1 [Erban, John K.; Smith, Barbara L.; Taghian, Alphonse G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Erban, John K.] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Erban, John K.] Massachusetts Gen Hosp, Clin Programs, Boston, MA 02114 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Breast Program, Boston, MA 02114 USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, Boston, MA 02114 USA. RP Erban, JK (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000001 ER PT B AU Shannon, KM Ryan, PD AF Shannon, Kristen Mahoney Ryan, Paula D. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach to the Prevention and Screening of Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID BRCA2 MUTATION CARRIERS; DIFFUSE GASTRIC-CANCER; GENOME-WIDE ASSOCIATION; LI-FRAUMENI-SYNDROME; BILATERAL PROPHYLACTIC MASTECTOMY; P53 GERMLINE MUTATIONS; E-CADHERIN MUTATIONS; OVARIAN-CANCER; FAMILY-HISTORY; COWDEN-SYNDROME C1 [Shannon, Kristen Mahoney] Massachusetts Gen Hosp, Ctr Canc Risk Assessment, Boston, MA 02114 USA. [Ryan, Paula D.] Massachusetts Gen Hosp, Div Hematol Oncol, Breast & Ovarian Canc Genet & Risk Assessment Cli, Boston, MA 02114 USA. [Ryan, Paula D.] Harvard Univ, Sch Med, Boston, MA USA. RP Shannon, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc Risk Assessment, Boston, MA 02114 USA. NR 131 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 3 EP 17 PG 15 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000002 ER PT B AU Freer, PE Kopans, DB AF Freer, Phoebe E. Kopans, Daniel B. BE Taghian, AG Smith, BL Erban, JK TI Screening for Breast Cancer: Mammography and Other Modalities SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CARCINOMA IN-SITU; FOLLOW-UP; INHERITED PREDISPOSITION; SOCIETY GUIDELINES; RANDOMIZED-TRIAL; HODGKINS-DISEASE; SELF-EXAMINATION; FAMILY-HISTORY; DEATH RATES; WOMEN C1 [Kopans, Daniel B.] Harvard Univ, Sch Med, Boston, MA USA. [Freer, Phoebe E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Breast Imaging Div, Boston, MA 02115 USA. RP Freer, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Breast Imaging Div, Boston, MA 02115 USA. NR 75 TC 2 Z9 2 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 18 EP 36 PG 19 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000003 ER PT B AU Lake, M Mitchell, G AF Lake, Martha Mitchell, Gwendolyn BE Taghian, AG Smith, BL Erban, JK TI Intake of New Patients for Multidisciplinary Clinics SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter C1 [Lake, Martha; Mitchell, Gwendolyn] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. RP Lake, M (reprint author), Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 37 EP 40 PG 4 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000004 ER PT B AU Rafferty, EA AF Rafferty, Elizabeth A. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Issues for Newly Diagnosed Patients SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CORE-NEEDLE-BIOPSY; NONPALPABLE BREAST-LESIONS; ATYPICAL DUCTAL HYPERPLASIA; CARCINOMA-IN-SITU; VACUUM-ASSISTED BIOPSY; IMAGING-HISTOLOGIC DISCORDANCE; RADIAL SCARS; PAPILLARY LESIONS; SURGICAL BIOPSY; PATHOLOGICAL CORRELATION C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rafferty, EA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 41 EP 49 PG 9 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000005 ER PT B AU Brachtel, EF AF Brachtel, Elena F. BE Taghian, AG Smith, BL Erban, JK TI Surgical Pathology SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CARCINOMA-IN-SITU; METASTATIC BREAST-CARCINOMA; FLAT EPITHELIAL ATYPIA; SENTINEL LYMPH-NODES; TOUCH PREP ANALYSIS; ESTROGEN-RECEPTOR; INTRAOPERATIVE EVALUATION; NEOADJUVANT CHEMOTHERAPY; EXCISION SPECIMENS; IMPRINT CYTOLOGY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Brachtel, EF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 50 EP 63 PG 14 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000006 ER PT B AU Younger, J AF Younger, Jerry BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach to Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Younger, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 64 EP 67 PG 4 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000007 ER PT B AU Guancial, EA Isakoff, SJ AF Guancial, Elizabeth A. Isakoff, Steven J. BE Taghian, AG Smith, BL Erban, JK TI Diagnosis and Initial Evaluation SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID BREAST-CANCER; FERTILITY PRESERVATION; RISK; WOMEN; TAMOXIFEN C1 [Isakoff, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 68 EP 75 PG 8 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000008 ER PT B AU Ruddy, KJ Partridge, AH AF Ruddy, Kathryn J. Partridge, Ann H. BE Taghian, AG Smith, BL Erban, JK TI Fertility and Pregnancy Considerations SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID BREAST-CANCER PATIENTS; CHEMOTHERAPY-INDUCED AMENORRHEA; CRYOPRESERVED OVARIAN TISSUE; ADJUVANT CHEMOTHERAPY; YOUNG-WOMEN; PREMENOPAUSAL WOMEN; EMBRYO CRYOPRESERVATION; PRESERVE FERTILITY; RANDOMIZED-TRIAL; CYCLOPHOSPHAMIDE C1 [Ruddy, Kathryn J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Ruddy, KJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 68 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 76 EP 81 PG 6 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000009 ER PT B AU Pandalai, PK Mariciani, VC Lerwill, MF Roche, CA Hughes, KS AF Pandalai, Prakash K. Mariciani, Veronica C. Lerwill, Melinda F. Roche, Constance A. Hughes, Kevin S. BE Taghian, AG Smith, BL Erban, JK TI Medical and Surgical Management of Atypical Hyperplasia and Lobular Carcinoma in situ SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID BREAST-CANCER RISK; CORE NEEDLE-BIOPSY; TERM FOLLOW-UP; DUCTAL HYPERPLASIA; NURSES HEALTH; DISEASE; INSITU; LESIONS; WOMEN; TAMOXIFEN C1 [Mariciani, Veronica C.] Hosp Barros Luco, Hosp Padre Hurtado, Santiago, Chile. [Lerwill, Melinda F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Roche, Constance A.] Massachusetts Gen Hosp, Avon Comprehens Breast Ctr, Boston, MA 02114 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Hughes, Kevin S.] Harvard Univ, Sch Med, Boston, MA USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 83 EP 91 PG 9 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000010 ER PT B AU Specht, M AF Specht, Michelle BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in the Treatment of Ductal Carcinoma in situ SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID INVASIVE BREAST-CARCINOMA; SKIN-SPARING MASTECTOMY; TERM-FOLLOW-UP; LOCAL RECURRENCE; CONSERVING SURGERY; NIPPLE INVOLVEMENT; RANDOMIZED-TRIAL; WOMEN; CANCER; BIOPSY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. RP Specht, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 93 EP 98 PG 6 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000011 ER PT B AU Racsa, M Hirsch, AE MacDonald, SM AF Racsa, Margarita Hirsch, Ariel E. MacDonald, Shannon M. BE Taghian, AG Smith, BL Erban, JK TI Radiation Treatment of DCIS SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CARCINOMA-IN-SITU; EARLY BREAST-CANCER; SURGICAL ADJUVANT BREAST; RANDOMIZED CONTROLLED-TRIAL; 20-YEAR FOLLOW-UP; DUCTAL CARCINOMA; LOCAL RECURRENCE; INTRADUCTAL-CARCINOMA; CONSERVING SURGERY; CONSERVATIVE TREATMENT C1 [Racsa, Margarita] Massachusetts Gen Hosp, N Shore Med Ctr, Peabody, MA USA. [MacDonald, Shannon M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Hirsch, Ariel E.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. RP Racsa, M (reprint author), Massachusetts Gen Hosp, N Shore Med Ctr, Peabody, MA USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 99 EP 110 PG 12 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000012 ER PT B AU Murphy, JE Moy, B AF Murphy, Janet E. Moy, Beverly BE Taghian, AG Smith, BL Erban, JK TI Medical Oncology Treatment of DCIS SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CARCINOMA-IN-SITU; RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; RISK-FACTORS; NODE BIOPSY; TAMOXIFEN; WOMEN; INSITU; GRADE; RECOMMENDATIONS C1 [Moy, Beverly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 111 EP 115 PG 5 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000013 ER PT B AU Smith, BL AF Smith, Barbara L. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in the Treatment of Early Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SKIN-SPARING MASTECTOMY; LYMPH-NODE BIOPSY; QUALITY-OF-LIFE; CONTRALATERAL PROPHYLACTIC MASTECTOMY; MULTIPLE-WIRE LOCALIZATION; 20-YEAR FOLLOW-UP; SENTINEL-NODE; AXILLARY DISSECTION; LOCAL RECURRENCE; CONSERVING SURGERY C1 [Smith, Barbara L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Breast Program, Boston, MA 02114 USA. RP Smith, BL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 117 EP 124 PG 8 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000014 ER PT B AU Bellon, JR AF Bellon, Jennifer R. BE Taghian, AG Smith, BL Erban, JK TI Radiation Treatment of Early-Stage Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID COLLAGEN VASCULAR-DISEASE; RANDOMIZED CLINICAL-TRIAL; SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP; CONSERVING THERAPY; CONSERVATIVE SURGERY; RADIOTHERAPY HYPOFRACTIONATION; POSTOPERATIVE RADIOTHERAPY; UK STANDARDIZATION; ESTROGEN-RECEPTOR C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 125 EP 131 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000015 ER PT B AU Gold, J Burstein, HJ AF Gold, Julie Burstein, Harold J. BE Taghian, AG Smith, BL Erban, JK TI Medical Oncology Treatment of Early-Stage Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SURGICAL ADJUVANT BREAST; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; TRIAL COMPARING DOXORUBICIN; QUALITY-OF-LIFE; BOWEL PROJECT; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; PREMENOPAUSAL WOMEN; UPDATED FINDINGS C1 [Gold, Julie] No Westchester Hosp Canc Treatment & Wellness Ctr, Mt Kisco Med Grp, Mt Kisco, NY USA. [Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Gold, J (reprint author), No Westchester Hosp Canc Treatment & Wellness Ctr, Mt Kisco Med Grp, Mt Kisco, NY USA. NR 92 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 132 EP 144 PG 13 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000016 ER PT B AU Smith, BL AF Smith, Barbara L. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in the Treatment of Locally Advanced Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID LYMPH-NODE BIOPSY; SKIN-SPARING MASTECTOMY; INTERNAL MAMMARY NODES; SURGICAL ADJUVANT BREAST; NEOADJUVANT CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; SENTINEL NODE; CONTRALATERAL BREAST; REGIONAL RECURRENCE; IRRADIATION C1 [Smith, Barbara L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Breast Program, Boston, MA 02114 USA. RP Smith, BL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 145 EP 151 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000017 ER PT B AU El-Din, MAA Taghian, AG AF El-Din, Mohamed A. Alm Taghian, Alphonse G. BE Taghian, AG Smith, BL Erban, JK TI Radiation Treatment of Locally Advanced Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SURGICAL ADJUVANT BREAST; CLINICAL-PRACTICE GUIDELINES; COOPERATIVE-ONCOLOGY-GROUP; MEDIAN FOLLOW-UP; LOCOREGIONAL RECURRENCE PATTERNS; COMBINED-MODALITY APPROACH; POSITIVE AXILLARY NODES; CHEST-WALL IRRADIATION; TUMORS 5 CM; RANDOMIZED-TRIAL C1 [El-Din, Mohamed A. Alm] Tanta Fac Med, Tanta, Egypt. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, Boston, MA 02114 USA. [Taghian, Alphonse G.] Harvard Univ, Sch Med, Boston, MA USA. RP El-Din, MAA (reprint author), Tanta Fac Med, Tanta, Egypt. NR 143 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 152 EP 164 PG 13 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000018 ER PT B AU Isakoff, SJ AF Isakoff, Steven J. BE Taghian, AG Smith, BL Erban, JK TI Medical Oncology Treatment of Locally Advanced Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SURGICAL ADJUVANT BREAST; III RANDOMIZED GEPARTRIO; PROJECT PROTOCOL B-27; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; PHASE-III; DOXORUBICIN-CYCLOPHOSPHAMIDE; PROGNOSTIC-SIGNIFICANCE; RECEPTOR STATUS; STAGE-II C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Isakoff, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 165 EP 173 PG 9 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000019 ER PT B AU Isakoff, SJ Ellisen, LW AF Isakoff, Steven J. Ellisen, Leif W. BE Taghian, AG Smith, BL Erban, JK TI Incorporating Translational Research in the Treatment of Locally Advanced Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID NEOADJUVANT CHEMOTHERAPY C1 [Isakoff, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Isakoff, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 174 EP 176 PG 3 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000020 ER PT B AU Kim, LS Antony, AK Liao, EC Austen, WG AF Kim, Liza S. Antony, Anuja Kandanatt Liao, Eric C. Austen, William G., Jr. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in Breast Reconstruction SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID FREE TRAM FLAP; SKIN-SPARING MASTECTOMY; LATISSIMUS-DORSI FLAP; POSTMASTECTOMY RADIATION-THERAPY; ABDOMINIS MUSCULOCUTANEOUS FLAP; INTERNAL MAMMARY PERFORATORS; SURGEONS 12-YEAR EXPERIENCE; AREOLA COMPLEX INVOLVEMENT; PERMANENT TISSUE EXPANDER; DONOR-SITE COMPLICATIONS C1 [Antony, Anuja Kandanatt] Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02115 USA. [Liao, Eric C.; Austen, William G., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02115 USA. NR 177 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 177 EP 190 PG 14 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000021 ER PT B AU Murphy, CD Golshan, M AF Murphy, Colleen D. Golshan, Mehra BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in the Treatment of Metastatic Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID IV BREAST-CANCER; PRIMARY TUMOR; INTACT PRIMARY; SURVIVAL; RESECTION; SURGERY; THERAPY; SITE C1 [Murphy, Colleen D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. [Golshan, Mehra] Brigham & Womens Hosp, Dana Farber Canc Inst, Breast Surg Serv, Boston, MA 02115 USA. RP Murphy, CD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Surg Oncol, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 197 EP 201 PG 5 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000023 ER PT B AU Wong, JS AF Wong, Julia S. BE Taghian, AG Smith, BL Erban, JK TI Radiation Management of Metastatic Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SPINAL-CORD COMPRESSION; BREAST-CANCER; PROGNOSTIC-FACTORS; BRAIN METASTASES; RANDOMIZED-TRIAL; PRIMARY TUMOR; STEREOTACTIC RADIOSURGERY; CHOROIDAL METASTASES; SURGICAL RESECTION; BONE METASTASES C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wong, JS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 202 EP 207 PG 6 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000024 ER PT B AU Ibrahim, N Erban, JK AF Ibrahim, Nageatte Erban, John K. BE Taghian, AG Smith, BL Erban, JK TI Medical Oncology Management of Metastatic Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID ADVANCED BREAST-CANCER; PHASE-II TRIAL; HEAVILY PRETREATED PATIENTS; FIRST-LINE THERAPY; PEGYLATED LIPOSOMAL DOXORUBICIN; DOCETAXEL COMBINATION THERAPY; LONG-TERM SURVIVAL; BRAIN METASTASES; RADIOFREQUENCY ABLATION; POSTMENOPAUSAL WOMEN C1 [Ibrahim, Nageatte] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Erban, John K.] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Erban, John K.] Massachusetts Gen Hosp, Clin Programs, Boston, MA 02114 USA. RP Ibrahim, N (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 148 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 208 EP 220 PG 13 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000025 ER PT B AU Singer, M Furlani, C AF Singer, Marybeth Furlani, Catherine BE Taghian, AG Smith, BL Erban, JK TI Palliative Care for Metastatic Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID BREAST-CANCER; NEED C1 [Singer, Marybeth; Furlani, Catherine] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. RP Singer, M (reprint author), Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 221 EP 228 PG 8 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000026 ER PT B AU Kirstein, L El-Din, MAA Taghian, AG AF Kirstein, Laurie El-Din, Mohamed A. Alm Taghian, Alphonse G. BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach in the Management of Locally Recurrent Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SENTINEL-LYMPH-NODE; EARLY BREAST-CANCER; CLINICAL-PRACTICE GUIDELINES; COMPARING TOTAL MASTECTOMY; SURGICAL ADJUVANT BREAST; LOCO-REGIONAL RECURRENCE; 20-YEAR FOLLOW-UP; CONSERVATIVE SURGERY; TUMOR RECURRENCE; CONSERVING THERAPY C1 [Kirstein, Laurie] Beth Israel Deaconess Med Ctr, Appel Venet Breast Ctr, New York, NY 10003 USA. [El-Din, Mohamed A. Alm] Tanta Fac Med, Tanta, Egypt. [Taghian, Alphonse G.] Harvard Univ, Sch Med, Boston, MA USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, Boston, MA 02114 USA. RP Kirstein, L (reprint author), Beth Israel Deaconess Med Ctr, Appel Venet Breast Ctr, New York, NY 10003 USA. NR 83 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 229 EP 239 PG 11 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000027 ER PT B AU Kuter, I AF Kuter, Irene BE Taghian, AG Smith, BL Erban, JK TI Medical Oncology Management of Locally Recurrent Disease SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID NEGATIVE BREAST-CANCER; ISOLATED LOCOREGIONAL RECURRENCE; HIGH-DOSE CHEMOTHERAPY; RADIATION-THERAPY; PREMENOPAUSAL WOMEN; CONSERVING THERAPY; TUMOR RECURRENCE; BRAIN METASTASES; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02115 USA. RP Kuter, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02115 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 240 EP 246 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000028 ER PT B AU Schapira, L AF Schapira, Lidia BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Approach to the Patient's Quality of Life SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CANCER-RELATED FATIGUE; ADVANCED BREAST-CANCER; YOUNG-WOMEN; FERTILITY PRESERVATION; PSYCHIATRIC MORBIDITY; GERIATRIC ASSESSMENT; BODY-IMAGE; INSTRUMENT; SURVIVORS; ONCOLOGY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Schapira, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 247 EP 257 PG 11 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000029 ER PT B AU O'Toole, J Russell, TA AF O'Toole, Jean Russell, Tara A. BE Taghian, AG Smith, BL Erban, JK TI Lymphedema: A modern Approach to Evaluation and Treatment SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID CANCER-RELATED LYMPHEDEMA; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; UPPER EXTREMITY LYMPHEDEMA; INTENSIVE DECONGESTIVE PHYSIOTHERAPY; MANUAL LYMPHATIC DRAINAGE; NODE BIOPSY LOWERS; BREAST-CANCER; AXILLARY DISSECTION; ARM LYMPHEDEMA C1 [O'Toole, Jean] Massachusetts Gen Hosp, Phys Therapy Serv, Boston, MA 02114 USA. [Russell, Tara A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Lymphedema Studies Program, Boston, MA 02114 USA. RP O'Toole, J (reprint author), Massachusetts Gen Hosp, Phys Therapy Serv, Boston, MA 02114 USA. NR 103 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 258 EP 268 PG 11 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000030 ER PT B AU Braun, IM Greenberg, DB AF Braun, Ilana Monica Greenberg, Donna Beth BE Taghian, AG Smith, BL Erban, JK TI Psychiatric Issues in Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID MAJOR DEPRESSION; SUICIDE RISK; DISTRESS; REGISTER; THERAPY C1 [Braun, Ilana Monica] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenberg, Donna Beth] Harvard Univ, Sch Med, Boston, MA USA. [Greenberg, Donna Beth] Massachusetts Gen Hosp, Psychiat Oncol Serv, Boston, MA 02114 USA. RP Braun, IM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 269 EP 275 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000031 ER PT B AU Moy, B AF Moy, Beverly BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Considerations: Racial Disparities in Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID LYMPH-NODE BIOPSY; COMPARING TOTAL MASTECTOMY; SURGICAL ADJUVANT BREAST; AFRICAN-AMERICAN WOMEN; CONSERVING SURGERY; CLINICAL-TRIALS; WHITE WOMEN; IMMEDIATE RECONSTRUCTION; RANDOMIZED-TRIALS; RADIATION-THERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Moy, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 68 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 277 EP 282 PG 6 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000032 ER PT B AU Krag, K Schoenthaler, R Yu, J AF Krag, Karen Schoenthaler, Robin Yu, Jeanne BE Taghian, AG Smith, BL Erban, JK TI Multidisciplinary Breast Cancer Care in the Community SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SURGEONS; OUTCOMES; TRENDS C1 [Krag, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. [Schoenthaler, Robin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Emerson Hosp, Concord, MA USA. [Yu, Jeanne] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Krag, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 283 EP 287 PG 5 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000033 ER PT B AU Wheeler, A Smith, BL AF Wheeler, Amanda Smith, Barbara L. BE Taghian, AG Smith, BL Erban, JK TI Future Directions in the Treatment of Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID NIPPLE-SPARING MASTECTOMY; OPTICAL COHERENCE TOMOGRAPHY; INTRAOPERATIVE MARGIN ASSESSMENT; GUIDED RADIOFREQUENCY ABLATION; POSITRON-EMISSION-TOMOGRAPHY; FOCUSED ULTRASOUND SURGERY; LYMPH-NODE METASTASES; CARCINOMA IN-SITU; NEOADJUVANT CHEMOTHERAPY; INSTITUTIONAL EXPERIENCE C1 [Wheeler, Amanda] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Smith, Barbara L.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Breast Program, Boston, MA 02114 USA. RP Wheeler, A (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. NR 84 TC 0 Z9 0 U1 1 U2 3 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 289 EP 297 PG 9 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000034 ER PT B AU MacDonald, SM Taghian, AG AF MacDonald, Shannon M. Taghian, Alphonse G. BE Taghian, AG Smith, BL Erban, JK TI Evolving Innovations for Breast Radiotherapy SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID INTENSITY-MODULATED RADIOTHERAPY; ACTIVE BREATHING CONTROL; PULMONARY COMPLICATION PROBABILITIES; PROTON RADIATION-THERAPY; CANCER-COOPERATIVE-GROUP; 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY; CONSERVING SURGERY; RESPIRATORY MANEUVERS C1 [MacDonald, Shannon M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Taghian, Alphonse G.] Harvard Univ, Sch Med, Boston, MA USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 87 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 298 EP 307 PG 10 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000035 ER PT B AU Strasser-Weippl, K Goss, PE AF Strasser-Weippl, Kathrin Goss, Paul E. BE Taghian, AG Smith, BL Erban, JK TI Hormonal Therapy in the Treatment of Breast Cancer SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID EXTENDED ADJUVANT THERAPY; QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; LETROZOLE VS. PLACEBO; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; NCICCTG MA.17; UPDATED FINDINGS; ATAC ARIMIDEX; COMPLETING 5 C1 [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Dept Med 1, Vienna, Austria. [Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA. [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Strasser-Weippl, K (reprint author), Wilhelminen Hosp, Dept Med 1, Vienna, Austria. NR 49 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 308 EP 314 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000036 ER PT B AU Ellisen, LW Sgroi, D AF Ellisen, Leif W. Sgroi, Dennis BE Taghian, AG Smith, BL Erban, JK TI Gene Expression Profiling: Personalized Treatment SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID NEGATIVE BREAST-CANCER; MOLECULAR PORTRAITS; ADJUVANT TAMOXIFEN; PROGNOSIS; CHEMOTHERAPY; ESTROGEN; RECEPTOR; SUBTYPES; CHEMOSENSITIVITY; GRADE C1 [Ellisen, Leif W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Sgroi, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 315 EP 321 PG 7 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000037 ER PT B AU Freedman, RA Winer, EP AF Freedman, Rachel A. Winer, Eric P. BE Taghian, AG Smith, BL Erban, JK TI Future Directions in Breast Cancer Clinical Trials SO BREAST CANCER: A MULTIDISCIPLINARY APPROACH TO DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID SURGICAL ADJUVANT CHEMOTHERAPY; COMPARING TOTAL MASTECTOMY; 1ST REPORT; FOLLOW-UP; COMBINATION CHEMOTHERAPY; RADICAL MASTECTOMY; RANDOMIZED-TRIALS; NEU ONCOGENE; HIGH-RISK; TAMOXIFEN C1 [Freedman, Rachel A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Winer, Eric P.] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-44-0 PY 2010 BP 322 EP 327 PG 6 WC Oncology SC Oncology GA BMS01 UT WOS:000273433000038 ER PT J AU Kotsopoulos, J Chen, WY Gates, MA Tworoger, SS Hankinson, SE Rosner, BA AF Kotsopoulos, Joanne Chen, Wendy Y. Gates, Margaret A. Tworoger, Shelley S. Hankinson, Susan E. Rosner, Bernard A. TI Risk factors for ductal and lobular breast cancer: results from the nurses' health study SO BREAST CANCER RESEARCH LA English DT Article ID MENOPAUSAL HORMONE-THERAPY; DIFFERENT HISTOLOGIC TYPES; WOMEN 65-79 YEARS; POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; REPLACEMENT THERAPY; RECEPTOR STATUS; ANTHROPOMETRIC FACTORS; TUMOR CHARACTERISTICS; UNITED-STATES AB Introduction: Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study. Methods: Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. Results: The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het >= 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. Conclusions: These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology. C1 [Kotsopoulos, Joanne; Chen, Wendy Y.; Gates, Margaret A.; Tworoger, Shelley S.; Hankinson, Susan E.; Rosner, Bernard A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Kotsopoulos, Joanne; Chen, Wendy Y.; Gates, Margaret A.; Tworoger, Shelley S.; Hankinson, Susan E.; Rosner, Bernard A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gates, Margaret A.; Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Chen, WY (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM wychen@partners.org OI Tworoger, Shelley/0000-0002-6986-7046 FU National Cancer Institute [P01 CA87969, T32 CA009001]; National Cancer Institute of Canada FX The authors thank the study participants of the Nurses' Health Study for their dedication to this study and their contribution to this research. This research was supported by research grant P01 CA87969 from the National Cancer Institute. JK is a Research Fellow of the Canadian Cancer Society supported through an award from the National Cancer Institute of Canada. MAG was supported by training grant T32 CA009001 from the National Cancer Institute. NR 47 TC 20 Z9 20 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 6 AR R106 DI 10.1186/bcr2790 PG 11 WC Oncology SC Oncology GA 739WJ UT WOS:000288751500017 PM 21143857 ER PT J AU O'Day, E Lal, A AF O'Day, Elizabeth Lal, Ashish TI MicroRNAs and their target gene networks in breast cancer SO BREAST CANCER RESEARCH LA English DT Review ID TRANSCRIPTIONAL REPRESSORS ZEB1; CELL-PROLIFERATION; E-CADHERIN; TUMOR-SUPPRESSOR; MIR-200 FAMILY; MESSENGER-RNA; MESENCHYMAL TRANSITION; CAENORHABDITIS-ELEGANS; EPITHELIAL PHENOTYPE; PROTEIN-SYNTHESIS AB MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that post-transcriptionally inhibit gene expression. Many miRNAs have been implicated in several human cancers, including breast cancer. Here we describe the association between altered miRNA signatures and breast cancer tumorigenesis and metastasis. The loss of several tumor suppressor miRNAs (miR-206, miR-17-5p, miR-125a, miR-125b, miR-200, let-7, miR-34 and miR-31) and the overexpression of certain oncogenic miRNAs (miR-21, miR-155, miR-10b, miR-373 and miR-520c) have been observed in many breast cancers. The gene networks orchestrated by these miRNAs are still largely unknown, although key targets have been identified that may contribute to the disease phenotype. Here we report how the observed perturbations in miRNA expression profiles may lead to disruption of key pathways involved in breast cancer. C1 [Lal, Ashish] Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lal, A (reprint author), Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, Boston, MA 02115 USA. EM alal@idi.harvard.edu RI Xie, Huangming/B-2260-2012 NR 79 TC 196 Z9 203 U1 4 U2 44 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 2 AR 201 DI 10.1186/bcr2484 PG 10 WC Oncology SC Oncology GA 622AT UT WOS:000279631100003 PM 20346098 ER PT J AU Tung, ND Miron, A Schnitt, SJ Gautam, S Fetten, K Kaplan, J Yassin, Y Buraimoh, A Kim, JY Szasz, AM Tian, RY Wang, ZC Collins, LC Brock, J Krag, K Legare, RD Sgroi, D Ryan, PD Silver, DP Garber, JE Richardson, AL AF Tung, Nadine Miron, Alexander Schnitt, Stuart J. Gautam, Shiva Fetten, Katharina Kaplan, Jennifer Yassin, Yosuf Buraimoh, Ayodele Kim, Ji-Young Szasz, Attila M. Tian, Ruiyang Wang, Zhigang C. Collins, Laura C. Brock, Jane Krag, Karen Legare, Robert D. Sgroi, Dennis Ryan, Paula D. Silver, Daniel P. Garber, Judy E. Richardson, Andrea L. TI Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers SO BREAST CANCER RESEARCH LA English DT Article ID BASAL EPITHELIAL PHENOTYPE; PROMOTER METHYLATION; MUTATION CARRIERS; EXPRESSION PROFILES; GERMLINE MUTATIONS; CARCINOMAS; WOMEN; HETEROZYGOSITY; TUMORS; GRADE AB Introduction: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER-breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. Methods: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER-invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. Results: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at diagnosis was not significantly different between first invasive ER+ BRCA1 breast cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years, respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were significantly more likely than those that lost wt BRCA1 to have a low mitotic rate (odds ratio (OR), 5.16; 95% CI, 1.91 to infinity). BRCA1 cancers with loss of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7; 95% CI, 1.85 to infinity). Conclusions: We found no difference in the prevalence of loss of wt BRCA1 between ER+ and ER-invasive BRCA1-associated breast cancers. Our findings suggest that many of the newer therapies for BRCA1 breast cancers designed to exploit the BRCA1 deficiency in these cancers may also be effective in ER+ cancers that develop in this population. C1 [Tung, Nadine; Fetten, Katharina] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Miron, Alexander; Yassin, Yosuf; Buraimoh, Ayodele; Tian, Ruiyang; Wang, Zhigang C.; Silver, Daniel P.; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Schnitt, Stuart J.; Kaplan, Jennifer; Collins, Laura C.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Gautam, Shiva] Beth Israel Deaconess Med Ctr, Dept Biostat, Boston, MA 02215 USA. [Kim, Ji-Young] CHA Gangnam Med Ctr, Dept Pathol, Seoul 135081, South Korea. [Krag, Karen] MGH N Shore Canc Ctr, Program Oncol, Danvers, MA 01923 USA. [Legare, Robert D.] Brown Univ, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02905 USA. [Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ryan, Paula D.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Garber, Judy E.] Dana Farber Canc Inst, Div Populat Sci & Adult Oncol, Boston, MA 02115 USA. [Kim, Ji-Young; Szasz, Attila M.; Brock, Jane; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Szasz, Attila M.] Semmelweis Univ, Dept Pathol 2, H-01091 Budapest, Hungary. [Silver, Daniel P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tung, Nadine; Miron, Alexander; Schnitt, Stuart J.; Wang, Zhigang C.; Collins, Laura C.; Brock, Jane; Sgroi, Dennis; Ryan, Paula D.; Silver, Daniel P.; Garber, Judy E.; Richardson, Andrea L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tung, ND (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Brookline Ave, Boston, MA 02215 USA. EM ntung@bidmc.harvard.edu; Andrea_Richardson@dfci.harvard.edu OI Szasz, Attila Marcell/0000-0003-2739-4196 FU Breast Cancer Research Foundation; Dana Farber/Harvard Cancer Center [CA 006516, CA 089393]; Avon Foundation FX This research was supported by grants from the Breast Cancer Research Foundation, the Dana Farber/Harvard Cancer Center (CA 006516), the Dana Farber/Harvard Cancer Center SPORE in breast cancer (CA 089393), and the Avon Foundation. NR 46 TC 12 Z9 12 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 6 AR R95 DI 10.1186/bcr2776 PG 13 WC Oncology SC Oncology GA 739WJ UT WOS:000288751500006 PM 21080930 ER PT J AU Tung, N Wang, YH Collins, LC Kaplan, J Li, HL Gelman, R Comander, AH Gallagher, B Fetten, K Krag, K Stoeckert, KA Legare, RD Sgroi, D Ryan, PD Garber, JE Schnitt, SJ AF Tung, Nadine Wang, Yihong Collins, Laura C. Kaplan, Jennifer Li, Hailun Gelman, Rebecca Comander, Amy H. Gallagher, Bridget Fetten, Katharina Krag, Karen Stoeckert, Kathryn A. Legare, Robert D. Sgroi, Dennis Ryan, Paula D. Garber, Judy E. Schnitt, Stuart J. TI Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features SO BREAST CANCER RESEARCH LA English DT Article ID BASAL EPITHELIAL PHENOTYPE; GERMLINE MUTATIONS; WOMEN; CARCINOMAS; GRADE; POPULATION; TUMORS; AGE AB Introduction: Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptor-negative (ER-) and also typically lack expression of progesterone receptor (PR) and HER2 overexpression. We undertook a study to assess the clinical factors that predict for an estrogen receptor positive (ER+) breast cancer in BRCA1 mutation carriers and to characterize the pathologic features of these tumors. Methods: Clinical characteristics of BRCA1 carriers with 58 ER+ and 114 ER-first invasive breast cancers were compared. Pathologic features of BRCA1 ER+ cancers were compared to those of BRCA1 ER-cancers and to age-matched ER+ sporadic cancers. Results: BRCA1 carriers aged >= 50 at diagnosis of first invasive breast cancer were more likely to have an ER+ cancer compared to those aged < 50 (57% vs 29%, P = 0.005). ER+ BRCA1 cancers were less likely than ER BRCA1 cancers to have "BRCA-associated" features such as high mitotic activity, geographic necrosis/fibrotic focus, and pushing margins (RR 0.06, 0.22, 0.24; P < 0.001, 0.02, 0.03 respectively). When compared to sporadic ER+ cancers, ER + BRCA1 cancers were more often of invasive ductal type (RR 2.4, P = 0.03), with a high mitotic rate (RR 5.0, P = 0.006) and absent or mild lymphocytic infiltrate (RR 10.2, P = 0.04). Conclusions: BRCA1 carriers who are older at first breast cancer diagnosis are more likely to have ER+ tumors than younger BRCA1 carriers. These ER+ cancers appear pathologically "intermediate" between ER BRCA1 cancers and ER + sporadic breast cancers raising the possibility that either some ER+ BRCA1 cancers are incidental or that there is a unique mechanism by which these cancers develop. C1 [Tung, Nadine; Comander, Amy H.; Gallagher, Bridget; Fetten, Katharina] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Tung, Nadine; Wang, Yihong; Collins, Laura C.; Kaplan, Jennifer; Gelman, Rebecca; Comander, Amy H.; Sgroi, Dennis; Ryan, Paula D.; Garber, Judy E.; Schnitt, Stuart J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wang, Yihong; Collins, Laura C.; Kaplan, Jennifer; Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Li, Hailun; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Krag, Karen] N Shore Med Ctr, Program Oncol, Danvers, MA 01923 USA. [Stoeckert, Kathryn A.; Garber, Judy E.] Dana Farber Canc Inst, Div Populat Sci & Adult Oncol, Boston, MA 02115 USA. [Legare, Robert D.] Brown Univ, Women & Infants Hosp, Program Womens Oncol, Providence, RI 02905 USA. [Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ryan, Paula D.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Tung, ND (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Brookline Ave, Boston, MA 02215 USA. EM ntung@bidmc.harvard.edu FU Breast Cancer Research Foundation; Dana Farber/Harvard Cancer Center [CA 006516]; Dana Farber/Harvard Cancer Center Breast SPORE [CA 089393] FX This research was supported by grants from the Breast Cancer Research Foundation, the Dana Farber/Harvard Cancer Center (CA 006516), and the Dana Farber/Harvard Cancer Center Breast SPORE (CA 089393). NR 27 TC 39 Z9 40 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 1 AR R12 DI 10.1186/bcr2478 PG 9 WC Oncology SC Oncology GA 587JD UT WOS:000276986300018 PM 20149218 ER PT J AU Weng, DS Cunin, MC Song, BZ Price, BD Eller, MS Gilchrest, BA Calderwood, SK Gong, JL AF Weng, Desheng Cunin, Monique C. Song, Baizheng Price, Brendan D. Eller, Mark S. Gilchrest, Barbara A. Calderwood, Stuart K. Gong, Jianlin TI Radiosensitization of mammary carcinoma cells by telomere homolog oligonucleotide pretreatment SO BREAST CANCER RESEARCH LA English DT Article ID FANCONI-ANEMIA PROTEINS; OVERHANG-SPECIFIC DNA; DOUBLE-STRAND BREAKS; DAMAGE RESPONSES; SENESCENCE; APOPTOSIS; CANCER; INDUCTION; TOLERANCE; MECHANISM AB Introduction: Ionizing radiation (IR) is a widely used approach to cancer therapy, ranking second only to surgery in rate of utilization. Responses of cancer patients to radiotherapy depend in part on the intrinsic radiosensitivity of the tumor cells. Thus, promoting tumor cell sensitivity to IR could significantly enhance the treatment outcome and quality of life for patients. Methods: Mammary tumor cells were treated by a 16-base phosphodiester-linked oligonucleotide homologous to the telomere G-rich sequence TTAGGG (T-oligo: GGTTAGGTGTAGGTTT) or a control-oligo (the partial complement, TAACCCTAACCCTAAC) followed by IR. The inhibition of tumor cell growth in vitro was assessed by cell counting and clonogenic cell survival assay. The tumorigenesis of tumor cells after various treatments was measured by tumor growth in mice. The mechanism underlying the radiosensitization by T-oligo was explored by immunofluorescent determination of phosphorylated histone H2AX (gamma H2AX) foci, beta-galactosidase staining, comet and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assays. The efficacy of the combined treatment was assessed in a spontaneous murine mammary tumor model. Results: Pretreatment of tumor cells with T-oligo for 24 hours in vitro enhanced both senescence and apoptosis of irradiated tumor cells and reduced clonogenic potential. Radiosensitization by T-oligo was associated with increased formation and/or delayed resolution of gamma H2AX DNA damage foci and fragmented DNA. T-oligo also caused radiosensitization in two in vivo mammary tumor models. Indeed, combined T-oligo and IR-treatment in vivo led to a substantial reduction in tumor growth. Of further significance, treatment with T-oligo and IR led to synergistic inhibition of the growth of spontaneous mammary carcinomas. Despite these profound antitumor properties, T-oligo and IR caused no detectable side effects under our experimental conditions. Conclusions: Pretreatment with T-oligo sensitizes mammary tumor cells to radiation in both in vitro and in vivo settings with minimal or no normal tissue side effects. C1 [Weng, Desheng; Cunin, Monique C.; Song, Baizheng; Gong, Jianlin] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA. [Price, Brendan D.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Eller, Mark S.; Gilchrest, Barbara A.] Boston Univ, Dept Dermatol, Sch Med, Boston, MA 02118 USA. [Calderwood, Stuart K.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Gong, JL (reprint author), Boston Univ, Dept Med, Sch Med, 72 E Concord St, Boston, MA 02118 USA. EM jgong@bu.edu FU Susan G. Komen for the Cure [BCTR0503792] FX This work is supported by a grant from Susan G. Komen for the Cure (BCTR0503792) and institutional funding. NR 35 TC 4 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2010 VL 12 IS 5 AR R71 DI 10.1186/bcr2639 PG 11 WC Oncology SC Oncology GA 697IG UT WOS:000285506100006 PM 20846433 ER PT J AU Garwood, ER Kumar, AS Baehner, FL Moore, DH Au, A Hylton, N Flowers, CI Garber, J Lesnikoski, BA Hwang, ES Olopade, O Port, ER Campbell, M Esserman, LJ AF Garwood, Elisabeth R. Kumar, Anjali S. Baehner, Frederick L. Moore, Dan H. Au, Alfred Hylton, Nola Flowers, Chris I. Garber, Judy Lesnikoski, Beth-Ann Hwang, E. Shelley Olopade, Olofunmilao Port, Elisa Rush Campbell, Michael Esserman, Laura J. TI Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Statin(s); Breast cancer; DCIS ductal carcinoma in situ; HMG-CoA reductase inhibitors; Cancer prevention ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; STATIN USE; RANDOMIZED-TRIALS; NITRIC-OXIDE; RISK; METAANALYSIS; CHOLESTEROL; PREVENTION; TAMOXIFEN AB The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen-receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P < 0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers. C1 [Esserman, Laura J.] Carol F Buck Breast Care Ctr, San Francisco, CA 94115 USA. [Garwood, Elisabeth R.; Hwang, E. Shelley; Campbell, Michael; Esserman, Laura J.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Garwood, Elisabeth R.] Penn State Univ, Coll Med, Hershey, PA USA. [Kumar, Anjali S.] Univ Calif E Bay, Dept Surg, Oakland, CA USA. [Baehner, Frederick L.; Au, Alfred] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Moore, Dan H.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Hylton, Nola; Flowers, Chris I.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Lesnikoski, Beth-Ann] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Garber, Judy] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Olopade, Olofunmilao] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Port, Elisa Rush] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. RP Esserman, LJ (reprint author), Carol F Buck Breast Care Ctr, 1600 Divisadero St,Box 1710, San Francisco, CA 94115 USA. EM laura.esserman@ucsfmedctr.org FU Breast Cancer Research Foundation; Doris Duke Charitable Foundation; Association of Women Surgeons FX We are grateful to the Breast Cancer Research Foundation for funding the clinical trial, and to Larry Norton for his support of this project, the Doris Duke Charitable Foundation for funding the research fellowship for Liz Garwood, the Association of Women Surgeons for funding the fellowship for Anjali Kumar, and to Novartis for providing fluvastatin for the trial. We thank Pamela Derish for her assistance editing this manuscript and Loretta Chan, Jessica Gibbs, Hannah Green, Margaret Hill, Bernadette Libao, Carleen Gentry, John Parr, Juan Lessing and Rajiv Sharma for their work and contributions that made the completion of this manuscript possible. Support for this study was generously provided by the Breast Cancer Research Foundation and in part, by the Doris Duke Charitable Foundation and the Association of Women Surgeons. NR 43 TC 60 Z9 61 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2010 VL 119 IS 1 BP 137 EP 144 DI 10.1007/s10549-009-0507-x PG 8 WC Oncology SC Oncology GA 530CL UT WOS:000272566400015 PM 19728082 ER PT J AU de Azambuja, E McCaskill-Stevens, W Francis, P Quinaux, E Crown, JPA Vicente, M Giuliani, R Nordenskjold, B Gutierez, J Andersson, M Vila, MM Jakesz, R Demol, J Dewar, J Santoro, A Lluch, A Olsen, S Gelber, RD Leo, A Piccart-Gebhart, M AF de Azambuja, Evandro McCaskill-Stevens, Worta Francis, Prudence Quinaux, Emmanuel Crown, John P. A. Vicente, Malou Giuliani, Rosa Nordenskjold, Bo Gutierez, Jorge Andersson, Michael Vila, Mireia Margeli Jakesz, Raimund Demol, Jan Dewar, Joanna Santoro, Armando Lluch, Ana Olsen, Steven Gelber, Richard D. Di Leo, Angelo Piccart-Gebhart, Martine TI The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Obesity; BMI; Adjuvant chemotherapy; Docetaxel; Node-positive ID COLON-CANCER; OBESITY; ESTROGEN; OUTCOMES; PROGNOSIS; WEIGHT; METAANALYSIS; RECURRENCE; WOMEN AB Background: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. Patients and methods: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI a parts per thousand yen 30 kg/mA(2). Results: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for non-obese and 70.0% for obese patients (HR 1.20; P = 0.041). In a multivariate model, obesity remained an independent prognostic factor for OS and DFS. Conclusions: In this study, obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed. C1 [de Azambuja, Evandro; Piccart-Gebhart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium. [de Azambuja, Evandro; Piccart-Gebhart, Martine] ULB, B-1000 Brussels, Belgium. [McCaskill-Stevens, Worta] NCI, NIH, Bethesda, MD 20892 USA. [Francis, Prudence] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence] St Vincents Hosp, Australian New Zealand Breast Canc Trials Grp, Melbourne, Vic, Australia. [Francis, Prudence] Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Francis, Prudence] Int Breast Canc Study Grp, Bern, Switzerland. [Quinaux, Emmanuel] Int Inst Drug Dev, Louvain, Belgium. [Crown, John P. A.] St Vincents Hosp, Dublin 4, Ireland. [Vicente, Malou] Br EAST Data Ctr, Brussels, Belgium. [Giuliani, Rosa] S Camillo Forlanini Hosp, Med Oncol Unit, Rome, Italy. [Nordenskjold, Bo] Univ Sjukhuset, Linkoping, Sweden. [Gutierez, Jorge] Clin Las Condes, Santiago, Chile. [Andersson, Michael] Copenhagen Univ Hosp, Rigshosp, Finsen Ctr, Dept Oncol, Copenhagen, Denmark. [Vila, Mireia Margeli] Hosp Badalona Germans Trias & Pujol, Badalona, Spain. [Jakesz, Raimund] Univ Vienna, Gen Hosp, Vienna, Austria. [Demol, Jan] Heilig Hart Ziekenhuis, Roeselare, Belgium. [Dewar, Joanna] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Santoro, Armando] Ist Clin Humanitas, Rozzano, Italy. [Lluch, Ana] Hosp Clin Univ, Valencia, Spain. [Olsen, Steven] Sanofi Aventis, Paris, France. [Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Di Leo, Angelo] Hosp Prato, Sandro Pitigliani Med Oncol Unit, Prato, Italy. RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 125, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Francis, Prudence/J-4003-2012 FU National Health and Medical Research Council [100925, 351164] FX We thank the patients, physicians, nurses and data managers who participated in BIG 02-98 and the staff at the central offices of the cooperative groups. The following cooperative groups participated: Breast European Adjuvant Studies Team, International Breast Cancer Study Group (including Australian New Zealand Breast Cancer Trials Group), Irish Clinical Oncology Research Group, Grupo Espanol de Investigacion en Cancer de Mama, Danish Breast Cancer Cooperative Group, Swedish Breast Cancer Group, Austrian Breast and Colorectal Cancer Study Group and Grupo Oncologico Cooperative Chileno De Investigacion. The BIG 02-98 trial was supported by the National Health and Medical Research Council (project grants 100925 and 351164 to Australian New Zealand Breast Cancer Trials Group). NR 31 TC 65 Z9 66 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2010 VL 119 IS 1 BP 145 EP 153 DI 10.1007/s10549-009-0512-0 PG 9 WC Oncology SC Oncology GA 530CL UT WOS:000272566400016 PM 19731015 ER PT J AU Chen, DT Nasir, A Culhane, A Venkataramu, C Fulp, W Rubio, R Wang, T Agrawal, D McCarthy, SM Gruidl, M Bloom, G Anderson, T White, J Quackenbush, J Yeatman, T AF Chen, Dung-Tsa Nasir, Aejaz Culhane, Aedin Venkataramu, Chinnambally Fulp, William Rubio, Renee Wang, Tao Agrawal, Deepak McCarthy, Susan M. Gruidl, Mike Bloom, Gregory Anderson, Tove White, Joe Quackenbush, John Yeatman, Timothy TI Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Pre malignant changes; Malignancy risk; Proliferative biology ID EXPRESSION SIGNATURE; MOLECULAR PORTRAITS; LOCAL RECURRENCE; CANCER SURVIVAL; CARCINOMAS; EPITHELIUM; HETEROZYGOSITY; IDENTIFICATION; PROFILES; ADJACENT AB Historical data have indicated the potential for the histologically-normal breast to harbor pre-malignant changes at the molecular level. We postulated that a histologically-normal tissue with "tumor-like" gene expression pattern might harbor substantial risk for future cancer development. Genes associated with these high-risk tissues were considered to be "malignancy-risk genes". From a total of 90 breast cancer patients, we collected a set of 143 histologically-normal breast tissues derived from patients harboring breast cancer who underwent curative mastectomy, as well as a set of 42 invasive ductal carcinomas (IDC) of various histologic grades. All samples were assessed for global gene expression differences using microarray analysis. For the purpose of this study we defined normal breast tissue to include histologically normal and benign lesions. Here we report the discovery of a "malignancy-risk" gene signature that may portend risk of breast cancer development in benign, but molecularly-abnormal, breast tissue. Pathway analysis showed that the malignancy-risk signature had a dramatic enrichment for genes with proliferative function, but appears to be independent of ER, PR, and HER2 status. The signature was validated by RT-PCR, with a high correlation (Pearson correlation = 0.95 with P < 0.0001) with microarray data. These results suggest a predictive role for the malignancy-risk signature in normal breast tissue. Proliferative biology dominates the earliest stages of tumor development. C1 [Chen, Dung-Tsa; Fulp, William; Yeatman, Timothy] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA. [Culhane, Aedin; Rubio, Renee; Anderson, Tove; White, Joe; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wang, Tao] Univ S Florida, Dept Epidemiol & Biostat, Tampa, FL 33612 USA. [Bloom, Gregory] H Lee Moffitt Canc Ctr & Res Inst, Biomed Informat Dept, Tampa, FL 33612 USA. RP Yeatman, T (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA. EM Timothy.Yeatman@moffitt.org FU National Cancer Institute [R01CA112215, R01 CA 098522] FX This Research is funded by National Cancer Institute grant R01CA112215 (I: TJY) and National Cancer Institute Grant R01 CA 098522(PI: TJY). We thank Magaly Mendez for assistance in manuscript preparation, the Histology Core for the technical support, and Drs. Khakpour, McBride, and Yamauchi for helpful discussion. The authors gratefully acknowledge the helpful comments by anonymous referees NR 35 TC 67 Z9 69 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2010 VL 119 IS 2 BP 335 EP 346 DI 10.1007/s10549-009-0344-y PG 12 WC Oncology SC Oncology GA 534MQ UT WOS:000272902200008 PM 19266279 ER PT J AU Ramsey, SD Zeliadt, SB Richardson, LC Pollack, LA Linden, H Blough, DK Cheteri, MK Tock, L Nagy, K Anderson, N AF Ramsey, Scott D. Zeliadt, Steven B. Richardson, Lisa C. Pollack, Lori A. Linden, Hannah Blough, David K. Cheteri, Mahesh Keitheri Tock, Lauri Nagy, Krisztina Anderson, Nancy TI Discontinuation of Radiation Treatment among Medicaid-Enrolled Women with Local and Regional Stage Breast Cancer SO BREAST JOURNAL LA English DT Article DE breast cancer; medicaid; radiation treatment discontinuation ID CARCINOMA-IN-SITU; SURGICAL ADJUVANT BREAST; CONSERVING TREATMENT; COLORECTAL-CANCER; THERAPY; CHEMOTHERAPY; RADIOTHERAPY; INSURANCE; SURVIVAL; RACE AB For women with nonmetastatic breast cancer, radiation therapy is recommended as a necessary component of the breast conserving surgery (BCS) treatment option. The degree to which Medicaid-enrolled women complete recommended radiation therapy protocols is not known. We evaluate radiation treatment completion rates for Medicaid enrollees aged 18-64 diagnosed with breast cancer. We determine clinical and socio-demographic factors associated with not starting treatment, and with interruptions or not completing radiation treatment. Using data from the Washington State Cancer Registry linked to Medicaid enrollment and claims records, we identified Medicaid enrollees diagnosed with breast cancer from 1997 to 2003 who received BCS. Among the 402 women who met inclusion criteria, 105 (26%) did not receive any radiation. Factors significantly associated with not receiving radiation included in situ disease and non-English as a primary language. Among those who received at least one radiation treatment, 65 (22%) failed to complete therapy and 71 (24%) patients had at least one 5 to 30 day gap in treatment. We found no significant predictors of interruptions in treatment or early discontinuation. A substantial proportion of Medicaid-insured women who are eligible for radiation therapy following BCS either fail to receive any treatment, experience significant interruptions during therapy, or do not complete a minimum course of treatment. More effort is needed to ensure this vulnerable population receives adequate radiation following BCS. C1 [Ramsey, Scott D.; Zeliadt, Steven B.; Tock, Lauri] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Zeliadt, Steven B.] Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Richardson, Lisa C.; Pollack, Lori A.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Linden, Hannah] Univ Washington, Div Oncol, Seattle, WA 98195 USA. [Blough, David K.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Cheteri, Mahesh Keitheri] Washington State Canc Registry, Washington State Dept Hlth, Olympia, WA USA. [Nagy, Krisztina] Univ Washington, Dept Econ, Seattle, WA 98195 USA. [Anderson, Nancy] Dept Social & Hlth Serv, Olympia, WA USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU Centers for Disease Control and Prevention, Prevention Research Centers Program, through the University of Washington Health Promotion Research Center [1-U48-DP-000050 SIP 7-05] FX This publication was supported by Cooperative Agreement Number 1-U48-DP-000050 SIP 7-05 from the Centers for Disease Control and Prevention, Prevention Research Centers Program, through the University of Washington Health Promotion Research Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. NR 35 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2010 VL 16 IS 1 BP 20 EP 27 DI 10.1111/j.1524-4741.2009.00865.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 542FL UT WOS:000273478300005 PM 19929888 ER PT J AU Ozanne, EM Wittenberg, E Garber, JE Weeks, JC AF Ozanne, Elissa M. Wittenberg, Eve Garber, Judy E. Weeks, Jane C. TI Breast Cancer Prevention: Patient Decision Making and Risk Communication in the High Risk Setting SO BREAST JOURNAL LA English DT Article DE breast cancer; decision making; genetic mutations; genetic testing; risk communication; risk perception ID BILATERAL PROPHYLACTIC MASTECTOMY; FAMILY-HISTORY; MEDICAL ENCOUNTER; MUTATION CARRIERS; HEALTH BELIEFS; BRCA2 MUTATION; WOMEN; INFORMATION; MAMMOGRAPHY; INVOLVEMENT AB The purpose of this study was to investigate prevention decision making among women at high risk for breast cancer, including patient preferences for preventive interventions, patient understanding of disease risk, and patient preferences for risk communication methods, and the corresponding physician understanding of these factors. A prospective interview and survey study was conducted of consecutive new patients seen at a cancer risk and prevention clinic and their physicians. One hundred and forty-six of 217 eligible patients participated and completed all components of the study (67%), and they were seen by a four physicians. Women's preferences for prevention intervention varied widely across women but were stable across time. Physicians were very often unable to predict their patients' preferences for prevention efforts. Patients overestimated their risk of disease, and physicians overestimated the decrease in perceived risk resulting from counseling (p < 0.001). As risk stratification for breast cancer improves, and prevention options become more tolerable, it becomes increasingly important to appropriately counsel women considering such options. This study provides insight into the decision making process of women at high risk for breast cancer and highlights the importance of addressing patient preferences for interventions and risk perception during risk assessment and counseling consultations. C1 [Ozanne, Elissa M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wittenberg, Eve] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Garber, Judy E.; Weeks, Jane C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. RP Ozanne, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM elissa@mgh-ita.org FU Friends of the Dana-Farber Cancer Institute; American Cancer Society [MRSG112037]; Susan G. Komen Breast Cancer Foundation; Agency for Healthcare Research and Quality [1 K02 HS014010] FX This work was supported by the Friends of the Dana-Farber Cancer Institute. E. Ozanne's work on this project was supported in part by grant number MRSG112037 from the American Cancer Society and by a grant from the Susan G. Komen Breast Cancer Foundation. E Wittenberg's work on this project was supported in part by grant number 1 K02 HS014010 from the Agency for Healthcare Research and Quality. These funding agreements ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. NR 34 TC 13 Z9 13 U1 3 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-122X J9 BREAST J JI Breast J. PD JAN-FEB PY 2010 VL 16 IS 1 BP 38 EP 47 DI 10.1111/j.1524-4741.2009.00857.x PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 542FL UT WOS:000273478300008 PM 19889168 ER PT J AU Miller, AJ Tsao, H AF Miller, A. J. Tsao, H. TI New insights into pigmentary pathways and skin cancer SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE melanoma; skin cancer; tanning; ultraviolet ID ULTRAVIOLET-B RADIATION; P53 CODON-72 POLYMORPHISM; SQUAMOUS-CELL CARCINOMA; INDUCED DNA-DAMAGE; MELANOCORTIN-1 RECEPTOR; MALIGNANT-MELANOMA; RISK-FACTORS; TRANSCRIPTIONAL ACTIVATION; FOLLICULAR MELANOGENESIS; GENETIC-DETERMINANTS AB P>The ability of cells to respond to and to mitigate environmental stress is crucial for their survival. Constitutive and facultative pigmentation have evolved in order for human skin to contend with high levels of terrestrial ultraviolet radiation (UVR). When this melanin 'shield' is compromised, individuals are exposed to increased skin cancer risk. The purpose of this review is to discuss new insights into the genetic basis of phenotypic risk factors for skin cancer, their connection to pigmentation and tanning, the precise molecular connections linking UVR to the tanning response, and potential methods of modulating pigmentation that avoid genotoxic damage. Highly translational implications of this research include a scientific basis on which to counsel patients regarding the carcinogenicity of UVR exposure related to tanning and potential new tanning agents that may actually protect against skin cancer by circumventing the need for UVR exposure. C1 [Tsao, H.] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, H.] Massachusetts Gen Hosp, MGH Canc Ctr, MGH Melanoma & Pigmented Les Ctr, Boston, MA 02114 USA. [Miller, A. J.] Mayo Clin, Dept Dermatol, Rochester, MN 55905 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. EM htsao@partners.org FU National Institutes of Health; American Cancer Society FX H.T. is supported by grants from the National Institutes of Health, the American Cancer Society and by the generous donors to the MGH on behalf of melanoma research. A.M. thanks the continued support of Mark Pittelkow. NR 75 TC 21 Z9 23 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2010 VL 162 IS 1 BP 22 EP 28 DI 10.1111/j.1365-2133.2009.09565.x PG 7 WC Dermatology SC Dermatology GA 534FY UT WOS:000272882900004 PM 19863502 ER PT J AU Chauncey, TR Gundacker, H Shadman, M List, AF Dakhil, SR Erba, HP Slovak, ML Chen, IM Willman, CL Kopecky, KJ Appelbaum, FR AF Chauncey, Thomas R. Gundacker, Holly Shadman, Mazyar List, Alan F. Dakhil, Shaker R. Erba, Harry P. Slovak, Marilyn L. Chen, I-Ming Willman, Cheryl L. Kopecky, Kenneth J. Appelbaum, Frederick R. TI Sequential phase II Southwest Oncology Group studies (S0112 and S0301) of daunorubicin and cytarabine by continuous infusion, without and with ciclosporin, in older patients with previously untreated acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; P-glycoprotein; multi-drug resistance; ciclosporin; chemoresistance ID MULTIDRUG-RESISTANCE INHIBITOR; RISK MYELODYSPLASTIC SYNDROME; GROUP-B; P-GLYCOPROTEIN; INDUCTION CHEMOTHERAPY; TREATMENT OUTCOMES; MODULATOR PSC-833; ELDERLY-PATIENTS; DOSE-ESCALATION; AML AB P>Attempts to overcome multi-drug resistance in acute myeloid leukaemia (AML) have been limited by toxicities. To investigate the effect of reducing peak drug levels, we performed sequential phase II studies using continuous infusion daunorubicin and cytarabine without (AD) and then with ciclosporin (ADC) in older patients with AML. Untreated patients (age 56+ years) received daunorubicin (45 mg/m2 per day for 3 d) and cytarabine (200 mg/m2 per day for 7 d), both by continuous infusion, without (S0112, 60 patients) and then with (S0301, 50 patients) the addition of ciclosporin. Complete response (CR) rates were 38% on S0112 and 44% on S0301. Fatal induction toxicities occurred in 17% and 12% respectively, arising primarily from infection and haemorrhage. Median overall and relapse-free survival was 7 and 8 months for AD respectively, and 6 and 14 months for ADC. Patients with phenotypic or functional P-glycoprotein had somewhat higher CR rates with ADC than AD, although confidence intervals overlapped. In these sequential trials, continuous infusion AD produced CR rates comparable to those with bolus daunorubicin. The addition of ciclosporin did not cause undue toxicities, produced a similar CR rate, and possibly improved relapse-free survival. Further correlate analyses did not identify a subpopulation specifically benefitting from the addition of ciclosporin. C1 [Chauncey, Thomas R.] Univ Washington, VA Puget Sound Hlth Care Syst 111, Seattle, WA 98108 USA. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chauncey, Thomas R.; Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Gundacker, Holly; Shadman, Mazyar; Kopecky, Kenneth J.] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Dakhil, Shaker R.] Wichita CCOP, Wichita, KS USA. [Erba, Harry P.] Univ Michigan, Ann Arbor, MI 48109 USA. [Slovak, Marilyn L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Albuquerque, NM 87131 USA. RP Chauncey, TR (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst 111, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tchaunce@u.washington.edu FU National Cancer Institute, DHHS [CA32102, CA38926, CA04919, CA11083, CA12644, CA13612, CA20319, CA27057, CA35090, CA35119, CA35128, CA35176, CA35178, CA35261, CA35431, CA37981, CA45807, CA45808, CA46113, CA46282, CA46441, CA58416, CA58658, CA58861, CA63845, CA67575, CA74647, CA76462] FX This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA04919, CA11083, CA12644, CA13612, CA20319, CA27057, CA35090, CA35119, CA35128, CA35176, CA35178, CA35261, CA35431, CA37981, CA45807, CA45808, CA46113, CA46282, CA46441, CA58416, CA58658, CA58861, CA63845, CA67575, CA74647 and CA76462. NR 40 TC 15 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2010 VL 148 IS 1 BP 48 EP 58 DI 10.1111/j.1365-2141.2009.07919.x PG 11 WC Hematology SC Hematology GA 533ZB UT WOS:000272864000005 PM 19821823 ER PT J AU Litzow, MR Othus, M Cripe, LD Gore, SD Lazarus, HM Lee, SJ Bennett, JM Paietta, EM Dewald, GW Rowe, JM Tallman, MS AF Litzow, Mark R. Othus, Megan Cripe, Larry D. Gore, Steven D. Lazarus, Hillard M. Lee, Sandra J. Bennett, John M. Paietta, Elisabeth M. Dewald, Gordon W. Rowe, Jacob M. Tallman, Martin S. CA Eastern Cooperative Oncology Grp L TI Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; relapse; gemtuzumab ozogamicin; liposomal daunorubicin; topotecan ID ACUTE MYELOGENOUS LEUKEMIA; LIPOSOMAL DAUNORUBICIN DAUNOXOME; ACUTE MYELOBLASTIC-LEUKEMIA; TOPOISOMERASE-I-INHIBITOR; PHASE-I; GEMTUZUMAB OZOGAMICIN; MYELODYSPLASTIC SYNDROME; POOR-PROGNOSIS; ARA-C; TOPOTECAN AB P>The treatment of relapsed acute myeloid leukaemia (AML) remains unsatisfactory. We conducted a phase II randomized trial where patients received intermediate-dose cytarabine for 4 d followed by gemtuzumab ozogamicin on day 5 (Arm A), or combined with liposomal daunorubicin for 3 d (Arm B), or cytarabine given for 5 d combined with cyclophosphamide for 3 d and topotecan by continuous infusion for 5 d (Arm C). Eligible patients had primary refractory AML, a first relapse after a remission of < 1 year, or a second or greater relapse. The primary objective of this trial was attainment of a conventional complete remission (CR) or a CR without platelet recovery (CRp) in at least 40% of patients. The CR/CRp rates for the 82 eligible patients were 3/26 (12%) in Arm A, 2/29 (7%) in Arm B, and 1/27 (4%) in Arm C. No patients who had relapsed within 6 months of initial CR or who had suffered multiple relapses responded. More than 95% of patients subsequently died of AML. No unexpected toxicities were encountered. We conclude that none of these three regimens were effective enough in the treatment of high-risk relapsed or refractory AML to warrant further study. This trial was registered at http://www.clinicaltrials.gov as #NCT00005962. C1 [Litzow, Mark R.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Othus, Megan; Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. [Cripe, Larry D.] Indiana Univ, Indianapolis, IN 46204 USA. [Gore, Steven D.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Ireland Canc Ctr, Cleveland, OH USA. [Bennett, John M.] Univ Rochester, Ctr Canc, Rochester, NY USA. [Paietta, Elisabeth M.] Our Lady Mercy Canc Ctr, Bronx, NY USA. [Dewald, Gordon W.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Rowe, Jacob M.] Rambam Med Ctr, Dept Hematol, Haifa, Israel. [Rowe, Jacob M.] Rambam Med Ctr, BMT, Haifa, Israel. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Litzow, MR (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM litzow.mark@mayo.edu FU NCI NIH HHS [U24 CA114737, CA11083, CA14548, CA21115, U10 CA011083, U10 CA014548, U10 CA021115, U10 CA021115-31, T32 CA009337, CA49883, CA23318, U10 CA049883, U10 CA023318, CA66636, CA13650, CA14958, CA16116, CA17145, U10 CA013650, U10 CA014958, U10 CA016116, U10 CA017145, U10 CA066636] NR 42 TC 32 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2010 VL 148 IS 2 BP 217 EP 225 DI 10.1111/j.1365-2141.2009.07917.x PG 9 WC Hematology SC Hematology GA 534GJ UT WOS:000272884100004 PM 19804455 ER PT J AU Flaherty, KT AF Flaherty, Keith T. TI Where Does the Combination of Sorafenib and Interferon in Renal Cell Carcinoma Stand? SO CANCER LA English DT Editorial Material ID RANDOMIZED PHASE-II; ALPHA; TRIAL; BEVACIZUMAB; SUNITINIB; 1ST-LINE; CANCER C1 [Flaherty, Keith T.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Dev Theraupeut, Boston, MA 02114 USA. EM kflaherty@partners.org NR 15 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2010 VL 116 IS 1 BP 4 EP 7 DI 10.1002/cncr.24688 PG 4 WC Oncology SC Oncology GA 547DA UT WOS:000273864600003 PM 19890962 ER PT J AU Sonis, S Treister, N Chawla, S Demetri, G Haluska, F AF Sonis, Stephen Treister, Nathaniel Chawla, Sant Demetri, George Haluska, Frank TI Preliminary Characterization of Oral Lesions Associated With Inhibitors of Mammalian Target of Rapamycin in Cancer Patients SO CANCER LA English DT Article DE mammalian target of rapamycin inhibitor; mucositis; aphthous stomatitis; cancer ID APHTHOUS ULCERATION; MTOR INHIBITORS; THERAPY; MUCOSITIS; SIROLIMUS AB BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose-limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor-associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis. METHODS: Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK-8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed. RESULTS: Treatment-emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs. CONCLUSIONS: OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010;116:210-5. (C) 2070 American Cancer Society. C1 [Sonis, Stephen; Treister, Nathaniel] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. [Demetri, George] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Sonis, Stephen; Treister, Nathaniel] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Chawla, Sant] Sarcoma Oncol Ctr, Santa Monica, CA USA. [Demetri, George] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Haluska, Frank] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. RP Sonis, S (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org FU Novartis; Pfizer; Ariad; Johnson Johnson; Bristol-Myers Squibb; Infinity Pharmaceuticals; Daiichi-Sankyo FX Dr. Demetri has received research support from the following: Novartis, Pfizer, Ariad, Johnson & Johnson, Bristol-Myers Squibb, Infinity Pharmaceuticals, and Daiichi-Sankyo. He has acted as a consultant for the following: Novartis, Pfizer, Ariad, Johnson & Johnson, Genentech, Infinity Pharmaceuticals, ZioPharm, Alnylam, Ideral Bayer, EMD-Serono, Amgen, PamGene, Plexxikon, N-of-One, and Kollran Pharmaceuticals. He has received honorarium from the following: Novartis and Pfizer. Dr. Demetri has acted as a member of the Scientific Advisory Boards for the following: ZioPharm, PamGene, Plexxikon, and N-of-One, and has acted as Chair of Scientific Advisory Boards for Kolltan Pharmaceuticals. In addition, he has received equity from Plexxikon, N-of-One, and Kolltan Pharmaceuticals. Dr. Haluska is employed by and has equity in Ariad, Inc. This study was funded by Ariad, Inc. NR 18 TC 65 Z9 66 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2010 VL 116 IS 1 BP 210 EP 215 DI 10.1002/cncr.24696 PG 6 WC Oncology SC Oncology GA 547DA UT WOS:000273864600027 PM 19862817 ER PT J AU Ruffin, MT Normolle, DP Evelegh, MJ Baron, JA Bresalier, RS Marcon, NE Syngal, S Turgeon, DK Tuck, MK Brenner, DE AF Ruffin, Mack T. Normolle, Daniel P. Evelegh, Michael J. Baron, John A. Bresalier, Robert S. Marcon, Norman E. Syngal, Sapna Turgeon, D. Kim Tuck, Melissa K. Brenner, Dean E. TI Rectal mucosal quantitative galactose oxidase-Schiff reaction as an early detection biomarker for colorectal cancer: Comparison to fecal occult stool blood test SO CANCER BIOMARKERS LA English DT Article DE Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/prevention & control; Carcinoma/diagnosis; Galactose Oxidase; Predictive Value of Tests ID COLON CANCER AB The galactose oxidase-Schiff (GOS) reaction detects D-galactose-beta-[1,,3]-N-acetyl-D-galactosamine. This is a T-antigen expressed in mucus from malignant cells and colonic mucosa adjacent to cancer but not in normal mucosa. Previous studies using a qualitative GOS assay proved to he of limited value for the detection of colorectal neoplasia. We used a newly developed quantitative GOS assay to determine its potential as an early detection biomarker for colorectal cancer. We completed a multi-center, prospective, cross-sectional cohort validation study consisting of 70 normal controls, 23 high-risk normal patients (polyp history or family history of colorectal cancer (CRC) with currently normal colonoscopy), 137 patients with adenomatous polyps, and 69 with colorectal cancers. Prior to colonoscopy, two samples of stool were collected via a rectal exam: one for FOBT, and one for GOS. The area under the ROC curve (AUC) for detecting colonic adenomas and cancer for normal colons, computed with logistic regression was 0.69 for GOS, 0.62 for FOBT, and 0.73 for GOS combined with FOBT. Adding GOS to FOBT did not significantly change the ROC of FOBT alone. GOS does not appear to be a suitable marker of colorectal neoplasia. C1 [Ruffin, Mack T.] Univ Michigan, Med Ctr, Dept Family Med, Ann Arbor, MI 48104 USA. [Normolle, Daniel P.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Evelegh, Michael J.] McMaster Univ, Hamilton, ON, Canada. [Baron, John A.] Dartmouth Med Sch, Hanover, NH USA. [Bresalier, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Marcon, Norman E.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turgeon, D. Kim; Tuck, Melissa K.; Brenner, Dean E.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Brenner, Dean E.] VA Med Ctr, Ann Arbor, MI USA. RP Ruffin, MT (reprint author), Univ Michigan, Med Ctr, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA. EM mruffin@umich.edu OI Normolle, Daniel/0000-0001-8675-5014; Ruffin, Mack/0000-0001-8336-478X FU NIH [5-U01-CA-086400]; Great Lakes New England Clinical Epidemiological Center, Early Detection Research Network, PreMD, Inc. FX The financial support for this manuscript was provided by the following: NIH 5-U01-CA-086400, Great Lakes New England Clinical Epidemiological Center, Early Detection Research Network, PreMD, Inc. NR 4 TC 0 Z9 0 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2010 VL 8 IS 2 BP 109 EP 112 DI 10.3233/CBM-2011-0206 PG 4 WC Oncology SC Oncology GA 835IY UT WOS:000296031300008 PM 21896998 ER PT J AU Tabernero, MD Lv, LL Anderson, KS AF Dolores Tabernero, Maria Lv, Lin-Li Anderson, Karen S. TI Autoantibody profiles as biomarkers of breast cancer SO CANCER BIOMARKERS LA English DT Article ID HUMORAL IMMUNE-RESPONSE; POSTTRANSLATIONAL PROTEIN MODIFICATIONS; SERUM P53 ANTIBODIES; LUNG-CANCER; PROSTATE-CANCER; TUMOR-ANTIGENS; OVARIAN-CANCER; ANTI-P53 ANTIBODIES; BIOLOGICAL PARAMETERS; MAMMOGRAPHIC DENSITY AB Breast cancer is the second leading cause of cancer death in women in the United States. While mammography and breast magnetic resonance imaging (MRI) improve detection of early disease, there remains an unmet need for biomarkers for risk stratification, early detection, prediction, and disease prognosis. Sera from patients with breast cancer contain specific autoantibodies (AAb) to tumor antigens that develop as part of the natural immune response to cancer-associated changes in protein structure and expression. The recent development of proteomic tools for AAb detection, including protein microarrays, reverse-phase protein immunoblots, and phage display have identified a number of potential AAb biomarkers for clinical development. Immune response signatures have been identified that are highly specific, but with variable sensitivities for cancer detection. This review focuses on the detection and application of AAb signatures as biomarkers for breast cancer detection and monitoring. C1 [Anderson, Karen S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dolores Tabernero, Maria] Univ Hosp Salamanca, Res Unit, Salamanca, Spain. [Dolores Tabernero, Maria] Ctr Canc Res CIC IBMCC CSIC USAL Salamanca, Salamanca, Spain. [Lv, Lin-Li] Southeast Univ, Inst Nephrol, Zhongda Hosp, Nanjing, Peoples R China. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 77Ave Louis Pasteur, Boston, MA 02115 USA. EM kanderson@partners.org FU NCI/Early Detection Research Network [5U01CA117374-02]; Fondo de Investigaciones Sanitarias; Instituto de Salud Carlos III; Ministerio de Sanidad y Consumo, Madrid, Spain FX This review was supported by grants from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain (M.D.T.; FIS/BA09/90057), and the NCI/Early Detection Research Network (K.S.A.; 5U01CA117374-02). NR 111 TC 5 Z9 5 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2010 VL 6 IS 5-6 BP 247 EP 256 DI 10.3233/CBM-2009-0139 PG 10 WC Oncology SC Oncology GA 661SY UT WOS:000282749600003 PM 20938085 ER PT J AU Do, YK Carpenter, WR Spain, P Clark, JA Hamilton, RJ Galanko, JA Jackman, A Talcott, JA Godley, PA AF Do, Young Kyung Carpenter, William R. Spain, Pamela Clark, Jack A. Hamilton, Robert J. Galanko, Joseph A. Jackman, Anne Talcott, James A. Godley, Paul A. TI Race, healthcare access and physician trust among prostate cancer patients SO CANCER CAUSES & CONTROL LA English DT Article DE Race; Disparity; Prostate neoplasm; Healthcare utilization; Trust ID QUALITY-OF-LIFE; AFRICAN-AMERICAN MEN; RACIAL-DIFFERENCES; UNITED-STATES; RADICAL PROSTATECTOMY; MEDICARE RECIPIENTS; AGGRESSIVE THERAPY; CLINICAL STAGE; OLDER MEN; OUTCOMES AB To study the effect of healthcare access and other characteristics on physician trust among black and white prostate cancer patients. A three-timepoint follow-up telephone survey after cancer diagnosis was conducted. This study analyzed data on 474 patients and their 1,320 interviews over three time periods. Among other subpopulations, black patients who delayed seeking care had physician trust levels that were far lower than that of both Caucasians as well as that of the black patients overall. Black patients had greater variability in their levels of physician trust compared to their white counterparts. Both race and access are important in explaining overall lower levels and greater variability in physician trust among black prostate cancer patients. Access barriers among black patients may spill over to the clinical encounter in the form of less physician trust, potentially contributing to racial disparities in treatment received and subsequent outcomes. Policy efforts to address the racial disparities in prostate cancer should prioritize improving healthcare access among minority groups. C1 [Do, Young Kyung; Carpenter, William R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Do, Young Kyung] Duke NUS Grad Med Sch Singapore, Program Hlth Serv & Syst Res, Singapore 169857, Singapore. [Carpenter, William R.; Godley, Paul A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Carpenter, William R.; Spain, Pamela; Jackman, Anne; Godley, Paul A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Clark, Jack A.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hamilton, Robert J.] Univ Toronto, Dept Urol Surg, Toronto, ON, Canada. [Galanko, Joseph A.; Godley, Paul A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. [Talcott, James A.] Harvard Univ, Sch Med, Boston, MA USA. RP Carpenter, WR (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, 1102F McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM bill.carpenter@unc.edu RI Carpenter, William/E-5125-2013; OI Clark, Jack/0000-0002-7424-1670; Hamilton, Robert/0000-0002-6715-5934 FU Agency for Healthcare Research and Quality [5P01HS010861]; Duke Endowment; UNC Program on Health Outcomes; National Center on Minority Health and Health Disparities [1P60MD00244]; National Cancer Institute [1U01CA114629, 2R25CA057726]; Department of Defense [PC060911]; NIH [P30 DK 034987] FX This project was supported by the Agency for Healthcare Research and Quality-Grant No: 5P01HS010861, The Duke Endowment, the UNC Program on Health Outcomes, National Center on Minority Health and Health Disparities-Grant 1P60MD00244, National Cancer Institute-Grants 1U01CA114629 and 2R25CA057726, Department of Defense-Grant PC060911, and NIH-Grant P30 DK 034987. NR 52 TC 21 Z9 21 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2010 VL 21 IS 1 BP 31 EP 40 DI 10.1007/s10552-009-9431-y PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543FB UT WOS:000273555400004 PM 19777359 ER PT J AU Whitman, EJ Pomerantz, M Chen, YM Chamberlin, MM Furusato, B Gao, C Ali, A Ravindranath, L Dobi, A Sestrehenn, IA McLeod, DG Srivastava, S Freedman, M Petrovics, G AF Whitman, Eric J. Pomerantz, Mark Chen, Yongmei Chamberlin, Michael M. Furusato, Bungo Gao, Chunling Ali, Amina Ravindranath, Lakshmi Dobi, Albert Sestrehenn, Isabell A. McLeod, David G. Srivastava, Shiv Freedman, Matthew Petrovics, Gyorgy TI Prostate Cancer Risk Allele Specific for African Descent Associates with Pathologic Stage at Prostatectomy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID 5 GENETIC-VARIANTS; GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; LOCUS; CONFIRMATION; POPULATIONS; AMERICANS; MORTALITY; MULTIPLE; MEN AB Purpose: A region on chromosome 8q24 was recently identified as a novel prostate cancer risk locus. Inherited variation in this region is associated with prostate cancer risk in the general population (21-58%), and specific alleles show a strong association in African-American men. This study was designed to evaluate associations between 8q24 risk alleles and clinical variables, such as pathologic stage, age at diagnosis, and recurrence, in a case series of African-American men. Experimental Design: Peripheral blood DNA samples from 114 African-American men with prostate cancer, including 106 who had undergone radical prostatectomy, were genotyped for six single-nucleotide polymorphisms on three 8q24 regions. The presence of these single-nucleotide polymorphisms was compared with clinicopathologic and follow-up data after radical prostatectomy. Results: The mean age of diagnosis and follow-up time were 57.4 (+/-8.9) years and 49.1 (+/-31.6) months, respectively. Patients carrying the Broad11934905 A risk allele, which is specific for African ancestry, were more likely to have a higher pathologic stage (pT(3-4)) than individuals with the wild type (odds ratio, 4.48; 95%, confidence interval, 1.42-14.14; P = 0.011). A trend toward increased frequency of and shorter time to biochemical recurrence was noted in patients with this risk allele on Kaplan-Meier unadjusted survival analysis (P = 0.076). Conclusions: The Broad11934905 polymorphism at 8q24, which is only found in people of African ancestry, is associated with an increase in non-organ-con fined prostate cancer at prostatectomy. In addition, for those with this risk allele, there is a trend toward early biochemical recurrence that requires validation in larger studies. Cancer Epidemiol Biomarkers Prev; 19(1); 1-8. @2010 AACR. C1 [Whitman, Eric J.; Chamberlin, Michael M.; Ali, Amina; McLeod, David G.] Walter Reed Army Med Ctr, Dept Surg, Urol Serv, Washington, DC USA. [Furusato, Bungo; Sestrehenn, Isabell A.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Chen, Yongmei; Furusato, Bungo; Gao, Chunling; Ravindranath, Lakshmi; Dobi, Albert; McLeod, David G.; Srivastava, Shiv; Petrovics, Gyorgy] Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, Rockville, MD USA. [Pomerantz, Mark; Freedman, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dobi, Albert; McLeod, David G.; Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, US Mil Canc Inst, Bethesda, MD USA. RP Freedman, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM freedman@broad.mit.edu; gpetrovics@cpdr.org OI Furusato, Bungo/0000-0003-4614-9882 NR 26 TC 21 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2010 VL 19 IS 1 BP 1 EP 8 DI 10.1158/1055-9965.EPI-08-1111 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700001 PM 20056617 ER PT J AU Veierod, MB Adami, HO Lund, E Armstrong, BK Weiderpass, E AF Veierod, Marit Bragelien Adami, Hans-Olov Lund, Eiliv Armstrong, Bruce Konrad Weiderpass, Elisabete TI Sun and Solarium Exposure and Melanoma Risk: Effects of Age, Pigmentary Characteristics, and Nevi SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; POOLED ANALYSIS; ATYPICAL NEVI; SKIN CANCERS; WOMEN; METAANALYSIS; POPULATION; ASSOCIATION; AUSTRALIA; RADIATION AB Background: Few prospective studies have analyzed solar and artificial (solarium) UV exposure and melanoma risk. We mvestigated these associations in a Norwegian-Swedish cohort study and addressed effect modification by age, pigmentary characteristics, and nevi. Methods: The cohort included women ages 30 to 50 years at enrollment from 1991 to 1992. Host factors and exposure to sun and solariums in life decades were collected by questionnaire at enrollment. Relative risks (RR) with 95% confidence intervals (Cl) were estimated by Poisson regression. Results: Among 106,366 women with complete follow-Lip through 2005, 412 melanoma cases were diagnosed. Hair color and large, asymmetric nevi on the legs were strongly associated with melanoma risk (P(trend) < 0.001), and the RR for >= 2 nevi increased from brown/black to blond/yellow to red-haired women (RRs, 1.72, 3.30, and 4.95, respectively; P(interaction) = 0.18). Melanoma risk increased significantly with the number of sunburns and bathing vacations in the first three age decades (P(trend) <= 0.04) and solarium use at ages 30 to 39 and 40 to 49 years [RRs for solarium use >= 1 time/mo 1.49 (95% CI, 1.11-2.00) and 1.61 (95% CI 1.10-2.35), respectively; P(trend) <= 0.02]. Risk of melanoma associated with sunburns, bathing vacations, and solarium use increased with accumulating exposure across additional decades of life. Conclusions: Melanoma risk seems to continue to increase with accumulating intermittent sun exposure and solarium use in early adulthood. Apparently, super-multiplicative joint effects of nevi and hair color identify people with red hair and multiple nevi as a very high risk group and suggest important gene-gene interactions involving MC1R in melanoma etiology. Cancer Epidemiol Biomarkers Prev, 19(1); 111-20. (C)2010 AACR. C1 [Veierod, Marit Bragelien] Univ Oslo, Inst Basic Med Sci, Dept Biostat, N-0317 Oslo, Norway. [Adami, Hans-Olov; Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Adami, Hans-Olov] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Adami, Hans-Olov] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Lund, Eiliv; Weiderpass, Elisabete] Univ Tromso, Inst Community Med, Tromso, Norway. [Armstrong, Bruce Konrad] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Weiderpass, Elisabete] Canc Registry Norway, Dept Etiol Res, Oslo, Norway. [Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland. RP Veierod, MB (reprint author), Univ Oslo, Inst Basic Med Sci, Dept Biostat, POB 1122, N-0317 Oslo, Norway. EM m.b.veierod@medisin.uio.no RI Armstrong, Bruce/K-9464-2015; Weiderpass, Elisabete/M-4029-2016; OI Armstrong, Bruce/0000-0001-8940-7525; Weiderpass, Elisabete/0000-0003-2237-0128; Veierod, Marit B./0000-0002-2083-2758 FU Swedish Board of Science [VR 2006-1100-42495-41, VR 345-2004-1935]; Swedish Cancer Society [4691-B04-03XCC] FX Swedish Board of Science (VR 2006-1100-42495-41, VR 345-2004-1935) and the Swedish Cancer Society (4691-B04-03XCC). NR 36 TC 88 Z9 89 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 JAN PY 2010 VL 19 IS 1 BP 111 EP 120 DI 10.1158/1055-9965.EPI-09-0567 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 543OA UT WOS:000273586700013 PM 20056629 ER PT J AU Isakoff, SJ AF Isakoff, Steven J. TI Triple-Negative Breast Cancer Role of Specific Chemotherapy Agents SO CANCER JOURNAL LA English DT Review DE triple-negative breast cancer; basal-like breast cancer; chemotherapy; cisplatin; carboplatin; neoadjuvant; metastatic ID PATHOLOGICAL COMPLETE RESPONSE; PLATINUM-BASED CHEMOTHERAPY; SURGICAL ADJUVANT BREAST; ESTROGEN-RECEPTOR STATUS; PHASE-II; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; WEEKLY PACLITAXEL; CLINICOPATHOLOGICAL CHARACTERISTICS; MOLECULAR SUBTYPES AB Cytotoxic chemotherapy remains the mainstay of treatment for triple-negative breast cancer (TNBC) despite the promise of new targeted and biologic agents. Many studies have shown significant benefit of chemotherapy in the neoadjuvant, adjuvant, and metastatic treatment of TNBC. Neoadjuvant chemotherapy studies have consistently reported higher response rates in TNBC than non-TNBC, and pathologic complete response has been shown to predict improved long-term outcomes for TNBC. Although the specific adjuvant regimens that may be most effective for TNBC are still being determined, third-generation chemotherapy regimens using dose dense or metronomic polychemotherapy are among the most effective tools presently available. The role of specific chemotherapy agents in the treatment of TNBC remains incompletely defined and warrants careful review to ensure that the most effective therapy is delivered while minimizing unnecessary toxicity. Platinum agents have seen renewed interest in TNBC based on a growing body of preclinical and clinical data suggesting encouraging activity. Taxanes and anthracyclines are active in TNBC and remain important agents but have not shown specific benefit over non-TNBC. Capecitabine has limited reported data in TNBC, but some reports suggest differential activity in TNBC compared with hormone receptor-positive breast cancer. TNBC is itself a heterogeneous group in which subgroups such as BRCA1 mutation carriers may have particular sensitivity to platinum agents and relatively less sensitivity to taxanes. Therefore, the identification of additional molecular biomarkers to predict response to specific chemotherapy is required to further improve treatment strategies with the current menu of chemotherapy options and future combinations with targeted therapies. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. RP Isakoff, SJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. EM sisakoff@partners.org FU NIH/NCI [3P30CA006516-44S2]; Harvard-MIT FX This work was supported by Golfers Against Cancer, Avon Partners for Progress Award NIH/NCI 3P30CA006516-44S2, and the Clinical Investigator Training Program of Harvard-MIT. NR 77 TC 95 Z9 98 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2010 VL 16 IS 1 BP 53 EP 61 DI 10.1097/PPO.0b013e3181d24ff7 PG 9 WC Oncology SC Oncology GA 582EJ UT WOS:000276578600009 PM 20164691 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Barnett Rosenberg: In Memoriam (1924-2009) Obituary SO CANCER RESEARCH LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 1 TC 3 Z9 3 U1 1 U2 3 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 JAN 1 PY 2010 VL 70 IS 1 BP 428 EP 429 DI 10.1158/0008-5472.CAN-09-4146 PG 2 WC Oncology SC Oncology GA 606EH UT WOS:000278404300046 ER PT J AU Yoshida, T Okamoto, I Okamoto, W Hatashita, E Yamada, Y Kuwata, K Nishio, K Fukuoka, M Janne, PA Nakagawa, K AF Yoshida, Takeshi Okamoto, Isamu Okamoto, Wataru Hatashita, Erina Yamada, Yuki Kuwata, Kiyoko Nishio, Kazuto Fukuoka, Masahiro Janne, Pasi A. Nakagawa, Kazuhiko TI Effects of Src inhibitors on cell growth and epidermal growth factor receptor and MET signaling in gefitinib-resistant non-small cell lung cancer cells with acquired MET amplification SO CANCER SCIENCE LA English DT Article ID C-SRC; GENE-MUTATIONS; CLINICAL-IMPLICATIONS; FAMILY KINASES; EGF RECEPTOR; ERLOTINIB; SURVIVAL; TUMORS; ACTIVATION; LINES AB The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as gefitinib and erlotinib in non-small cell lung cancer (NSCLC) is often limited by the emergence of drug resistance conferred either by a secondary T790M mutation of EGFR or by acquired amplification of the MET gene. We now show that the extent of activation of the tyrosine kinase Src is markedly increased in gefitinib-resistant NSCLC (HCC827 GR) cells with MET amplification compared with that in the gefitinib-sensitive parental (HCC827) cells. In contrast, the extent of Src activation did not differ between gefitinib-resistant NSCLC (PC9/ZD) cells harboring the T790M mutation of EGFR and the corresponding gefitinib-sensitive parental (PC9) cells. This activation of Src in HCC827 GR cells was largely abolished by the MET-TKI PHA-665752 but was only partially inhibited by gefitinib, suggesting that Src activation is more dependent on MET signaling than on EGFR signaling in gefitinib-resistant NSCLC cells with MET amplification. Src inhibitors blocked Akt and Erk signaling pathways, resulting in both suppression of cell growth and induction of apoptosis, in HCC827 GR cells as effectively as did the combination of gefitinib and PHA-665752. Furthermore, Src inhibitor dasatinib inhibited tumor growth in HCC827 GR xenografts to a significantly greater extent than did treatment with gefitinib alone. These results provide a rationale for clinical targeting of Src in gefitinib-resistant NSCLC with MET amplification. (Cancer Sci 2009). C1 [Yoshida, Takeshi; Okamoto, Isamu; Okamoto, Wataru; Hatashita, Erina; Yamada, Yuki; Kuwata, Kiyoko; Nakagawa, Kazuhiko] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 589, Japan. [Nishio, Kazuto] Kinki Univ, Sch Med, Dept Genome Biol, Osaka 589, Japan. [Fukuoka, Masahiro] Kinki Univ, Sch Med, Dept Med Oncol, Sakai Hosp,Minami Ku, Osaka 589, Japan. [Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Okamoto, I (reprint author), Kinki Univ, Sch Med, Dept Med Oncol, Osaka 589, Japan. EM chi-okamoto@dotd.med.kindai.ac.jp NR 42 TC 35 Z9 36 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JAN PY 2010 VL 101 IS 1 BP 167 EP 172 DI 10.1111/j.1349-7006.2009.01368.x PG 6 WC Oncology SC Oncology GA 530ZM UT WOS:000272631500024 PM 19804422 ER PT S AU Li, J Makrigiorgos, GM AF Li, Jin Makrigiorgos, G. Mike BE Webb, M TI s-RT-MELT: A Novel Technology for Mutation Screening SO CANCER SUSCEPTIBILITY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cancer; Mutation detection; Low-level somatic mutation; SNP; Surveyor (TM); Melting curve; Low denaturation temperatures ID CELL LUNG-CANCER; RESISTANCE; GEFITINIB; PATHWAYS AB The last growing understanding of genetic pathways that mediate cancer etiology, biology, and personalized medicine leads to an increasing need fOr extensive and reliable mutaticm screening on a population or on a single patient basis. Here we describe s-RT-M ELT, a novel technology that enables expanded-throughput enzymatic mutation scanning in clinical cancer samples tOr germline or low-level somatic mutations, or for SNP genotyping. CC-clamp-containing PCR products from tumor and normal cells are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in parallel. Mismatches arc converted to double strand breaks using a DNA endonuclease (SurveyorTm), and poly A oligonticleotide tails are enzymatically attached at the position of the mutations. A novel application of PCR that operates at low denaturation temperatures enables the selective amplification of mutationcontaining DNA fragments and high-throughput, closed-tube mutation scanning via melting curve analysis on conventional or nanotechnology real-time PCR platfOrms. We have applied s-RT-M ELT in the screening of TP53 and EGER mutations in cell lines and clinical samples and demonstrate its advantages fOr rapid, multiplexed mutation scanning in cancer. C1 [Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil, Boston, MA 02115 USA. [Li, Jin; Makrigiorgos, G. Mike] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Div DNA Repair & Med Phys & Biophys,Sch Med, Boston, MA 02115 USA. [Li, Jin; Makrigiorgos, G. Mike] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Li, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil, 44 Binney St, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-758-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 653 BP 207 EP 219 DI 10.1007/978-1-60761-759-4_12 D2 10.1007/978-1-60761-759-4 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BQW51 UT WOS:000282015000012 PM 20721745 ER PT J AU Artandi, SE DePinho, RA AF Artandi, Steven E. DePinho, Ronald A. TI Telomeres and telomerase in cancer SO CARCINOGENESIS LA English DT Review ID DOMINANT DYSKERATOSIS-CONGENITA; DNA-DAMAGE RESPONSE; HUMAN BREAST-CANCER; REVERSE-TRANSCRIPTASE; DYSFUNCTIONAL TELOMERES; MAMMALIAN TELOMERES; CATALYTIC SUBUNIT; TUMOR-SUPPRESSOR; LIFE-SPAN; IN-SITU AB Myriad genetic and epigenetic alterations are required to drive normal cells toward malignant transformation. These somatic events commandeer many signaling pathways that cooperate to endow aspiring cancer cells with a full range of biological capabilities needed to grow, disseminate and ultimately kill its host. Cancer genomes are highly rearranged and are characterized by complex translocations and regional copy number alterations that target loci harboring cancer-relevant genes. Efforts to uncover the underlying mechanisms driving genome instability in cancer have revealed a prominent role for telomeres. Telomeres are nucleoprotein structures that protect the ends of eukaryotic chromosomes and are particularly vulnerable due to progressive shortening during each round of DNA replication and, thus, a lifetime of tissue renewal places the organism at risk for increasing chromosomal instability. Indeed, telomere erosion has been documented in aging tissues and hyperproliferative disease states-conditions strongly associated with increased cancer risk. Telomere dysfunction can produce the opposing pathophysiological states of degenerative aging or cancer with the specific outcome dictated by the integrity of DNA damage checkpoint responses. In most advanced cancers, telomerase is reactivated and serves to maintain telomere length and emerging data have also documented the capacity of telomerase to directly regulate cancer-promoting pathways. This review covers the role of telomeres and telomerase in the biology of normal tissue stem/progenitor cells and in the development of cancer. C1 [Artandi, Steven E.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Artandi, SE (reprint author), Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. EM sartandi@stanford.edu; ronald_depinho@dfci.harvard.edu FU NCI NIH HHS [R01 CA084628] NR 161 TC 334 Z9 350 U1 14 U2 96 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2010 VL 31 IS 1 BP 9 EP 18 DI 10.1093/carcin/bgp268 PG 10 WC Oncology SC Oncology GA 542KW UT WOS:000273493100002 PM 19887512 ER PT B AU Mansour, M Donaldson, D AF Mansour, Moussa Donaldson, David BE Sigg, DC Laizzo, PA Xiao, YF He, B TI Invasive Electroanatomical Mapping and Navigation SO CARDIAC ELECTROPHYSIOLOGY METHODS AND MODELS LA English DT Article; Book Chapter ID ATRIAL-FIBRILLATION; CATHETER ABLATION; INTEGRATION AB An overview of electroanatomical mapping is described, including its history and current application in treating patients with atrial and ventricular arrhythmias Using a roving catheter in 3D space relative to a fixed reference, electroanatomical mapping provides the electrophysiologist with important location and electrical data to carefully guide catheter ablation procedures Both magnetic-based mapping and impedance based mapping are briefly discussed C1 [Mansour, Moussa; Donaldson, David] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6657-5 PY 2010 BP 349 EP 356 DI 10.1007/978-1-4419-6658-2_17 D2 10.1007/978-1-4419-6658-2 PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA BSV98 UT WOS:000285942300017 ER PT J AU Milo-Cotter, O Teerlink, JR Metra, M Felker, GM Ponikowski, P Voors, AA Edwards, C Weatherley, BD Greenberg, B Filippatos, G Unemori, E Teichman, SL Cotter, G AF Milo-Cotter, Olga Teerlink, John R. Metra, Marco Felker, G. Michael Ponikowski, Piotr Voors, Adriaan A. Edwards, Christopher Weatherley, Beth Davison Greenberg, Barry Filippatos, Gerassimos Unemori, Elaine Teichman, Sam L. Cotter, Gad TI Low Lymphocyte Ratio as a Novel Prognostic Factor in Acute Heart Failure: Results from the Pre-RELAX-AHF Study SO CARDIOLOGY LA English DT Article DE White blood cells; Lymphocytes; Heart failure ID COUNT; MORTALITY; TRANSPLANT; APOPTOSIS; SURVIVAL; DEATH; RISK AB Background: Previous studies have suggested that a lower lymphocyte ratio (Ly%) in the white blood cell (WBC) differential count is related to worse outcomes in patients with acute heart failure (AHF) and other cardiovascular disorders. Methods: In the Pre-RELAX-AHF study, 234 patients with AHF, systolic blood pressure >125 mm Hg and brain natriuretic peptide >= 350 pg/ml or equivalent were randomized to 1 of 4 intravenous doses of relaxin or placebo and followed up for 6 months following randomization. Complete blood count and differential were performed by a central laboratory at baseline and then daily to day 5 and on day 14. Results: The WBC count by itself was not associated with measures of disease severity or outcome, and patients with Ly% <13% had similar baseline characteristics to patients with Ly% >13%, except for a higher baseline WBC count, elevated baseline glucose, older age and higher rates of peripheral vascular disease. However, patients with Ly% <13% had less improvement of dyspnea, greater worsening of heart failure, longer length of initial hospital stay and fewer days alive and out of hospital. Statistical significance was reached for all-cause death by days 60 and 180 (hazard ratio = 1.11 per percent decrease, 95% confidence interval 1.03-1.19; p = 0.0048). Conclusions: Despite no association with any baseline characteristic known to strongly predict outcome in AHF, low Ly% is associated with less symptom relief and worse in-hospital and postdischarge clinical outcomes. Copyright (C) 2010 S. Karger AG, Basel C1 [Milo-Cotter, Olga; Edwards, Christopher; Weatherley, Beth Davison; Cotter, Gad] Momentum Res, Durham, NC 27707 USA. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Greenberg, Barry] Univ Calif San Diego, MD Adv Heart Failure Treatment Program, San Diego, CA 92103 USA. [Unemori, Elaine; Teichman, Sam L.] Corthera, San Mateo, CA USA. [Metra, Marco] Univ Brescia, Dept Expt & Appl Sci, Sect Cardiovasc Dis, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Dept Hlth Sci, Mil Hosp, Dept Cardiol, Wroclaw, Poland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Filippatos, Gerassimos] Athens Univ Hosp Attikon, Athens, Greece. RP Milo-Cotter, O (reprint author), Momentum Res, 3100 Tower Blvd,Suite 802, Durham, NC 27707 USA. EM olgacotter@momentum-research.com RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568 NR 18 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 117 IS 3 BP 190 EP 196 DI 10.1159/000321416 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 714JI UT WOS:000286805500007 PM 21088400 ER PT J AU Elmariah, S Rajamannan, NM AF Elmariah, Sammy Rajamannan, Nalini M. TI Medical Therapy for Calcific Aortic Stenosis: The Use of Bisphosphonates SO CARDIOLOGY LA English DT Editorial Material ID VALVULAR HEART-DISEASE; BONE-RESORPTION; ALENDRONATE; CHOLESTEROL; RABBITS; VITRO C1 [Rajamannan, Nalini M.] Northwestern Univ, Feinberg Sch Med, Div Cardiol & Pathol, Chicago, IL 60611 USA. [Elmariah, Sammy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Rajamannan, NM (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol & Pathol, 300 E Chicago,Tarry 12-717, Chicago, IL 60611 USA. EM n-rajamannan@northwestern.edu FU NHLBI NIH HHS [R01 HL085591] NR 21 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 117 IS 3 BP 229 EP 230 DI 10.1159/000322902 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 714JI UT WOS:000286805500016 PM 21212671 ER PT J AU La Fountaine, MF Wecht, JM Rosado-Rivera, D Cirnigliaro, CM Spungen, AM Bauman, WA AF La Fountaine, Michael F. Wecht, Jill M. Rosado-Rivera, Dwindally Cirnigliaro, Christopher M. Spungen, Ann M. Bauman, William A. TI The QT Variability Index and Cardiac Autonomic Modulation: Perspectives from Apparently Healthy Men with Spinal Cord Injury SO CARDIOLOGY LA English DT Article DE Spinal cord injury; QT interval; Autonomic nervous system; QT variability ID HEART-RATE-VARIABILITY; NERVOUS-SYSTEM ACTIVITY; INTERVAL VARIABILITY; REPOLARIZATION LABILITY; ELECTROCARDIOGRAPHIC FINDINGS; VENTRICULAR REPOLARIZATION; SPECTRAL-ANALYSIS; DEATH; RISK; CARDIOMYOPATHY AB Objective: To describe the effect of spinal cord injury (SCI) on the QT variability index (QTVI). Methods: Digital electrocardiograms from 113 age-matched men (40 with tetraplegia, 26 with high paraplegia, 17 low paraplegia and 31 controls) were analyzed. RR interval, heart rate (HR) variability [total power (TP(RR)), low frequency (LF(RR)) and high frequency (HF(RR))], QT interval duration, Bazett HR-corrected QT (QTc), QT interval variance (QTVN) and QTVI were compared. Results: Significant group main effects were present for RR, QTc, TP(RR) and LF(RR), but not QT duration, QTVN or HF(RR). Post hoc comparisons revealed the following: (1) longer RR in controls versus subjects with high paraplegia and low paraplegia, and in subjects with tetraplegia versus high paraplegia and low paraplegia; (2) QTc was longer in subjects with low paraplegia versus controls and shorter in subjects with tetraplegia versus high paraplegia, and (3) TP(RR) and LF(RR) were different in controls and subjects with high paraplegia compared to those with low paraplegia. QTVI was significantly elevated in all SCI groups compared to controls. Significant negative correlations between QTVI and HF(RR) were observed in all SCI groups, and TP(RR) and LF(RR) in subjects with tetraplegia and high paraplegia only. Age was negatively correlated in controls. Conclusions: QTVI is negatively affected in otherwise healthy SCI men compared to age-matched controls. This observation appears to reflect the attenuation of vagal modulation, sympathetic impairment above the sixth thoracic vertebra and/or a heightened degree of cardiovascular disease risk. Copyright (C) 2011 S. Karger AG, Basel C1 [La Fountaine, Michael F.] Mt Sinai Sch Med, Ctr Excellence Med Consequences Spinal Cord Injur, James J Peters VA Med Ctr, Bronx, NY 10468 USA. [La Fountaine, Michael F.] Mt Sinai Sch Med, Dept Med, Bronx, NY 10468 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, Bronx, NY 10468 USA. RP La Fountaine, MF (reprint author), Mt Sinai Sch Med, Ctr Excellence Med Consequences Spinal Cord Injur, James J Peters VA Med Ctr, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM michael.lafountaine@va.gov FU Veteran Affairs Rehabilitation Research and Development Service [B4162C, B3600R]; James J. Peters VA Medical Center FX This research was supported by the Veteran Affairs Rehabilitation Research and Development Service (No. B4162C, No. B3600R) and the James J. Peters VA Medical Center. NR 28 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 117 IS 4 BP 253 EP 259 DI 10.1159/000323337 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741PP UT WOS:000288876300003 PM 21252534 ER PT J AU Fernandez-Friera, L Solis, J Passeri, J Handschumacher, MD Levine, RA Picard, MH AF Fernandez-Friera, L. Solis, J. Passeri, J. Handschumacher, M. D. Levine, R. A. Picard, M. H. TI Improved Assessment of the Mitral Annulus Using Real-Time Three-Dimensional Transesophageal Echocardiography SO CARDIOLOGY LA English DT Meeting Abstract C1 [Fernandez-Friera, L.] Mt Sinai Hosp, New York, NY USA. [Solis, J.; Passeri, J.; Handschumacher, M. D.; Levine, R. A.; Picard, M. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2010 VL 115 IS 4 BP 268 EP 268 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 584TD UT WOS:000276774900046 ER PT J AU Mohammed, AA Januzzi, JL AF Mohammed, Asim A. Januzzi, James L., Jr. TI Clinical Applications of Highly Sensitive Troponin Assays SO CARDIOLOGY IN REVIEW LA English DT Review DE cardiac troponin; acute myocardial infarction; myocardial ischemia ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; JOINT EUROPEAN-SOCIETY; 99TH PERCENTILE CUTOFF; CARDIAC TROPONIN; I ASSAY; NATRIURETIC PEPTIDE; UNSTABLE ANGINA; EARLY-DIAGNOSIS; HEART-FAILURE AB Cardiac troponin is the biomarker of choice for the diagnosis of acute myocardial infarction. Recent consensus recommendations have adopted a concentration of troponin above the 99th percentile of a healthy population to diagnose myocardial infarction. Until recently, there was no assay capable of achieving recommended precision; however, with the development of "highly sensitive" troponin assays, it is now possible to accurately measure troponin concentrations at and below the current 99th percentile of a healthy population. These assays have enormous potential in not only identifying more patients with acute myocardial infarction, and providing superior risk prediction in those so afflicted, in addition highly sensitive troponins assays may be useful for long-term risk assessment of the patient with coronary disease. In this article, we will review the clinical applications, novel concepts, challenges, and limitations of using highly sensitive troponins assays. C1 Harvard Univ, Div Cardiol, Dept Med, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Dennis and Marilyn Barry Fellowship in Cardiology; Balson Fund for Cardiovascular Research FX Supported by the *Dennis and Marilyn Barry Fellowship in Cardiology (to A.A.M.), and also by the dagger Balson Fund for Cardiovascular Research (to J.L,J.). NR 74 TC 27 Z9 27 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1061-5377 J9 CARDIOL REV JI Cardiol. Rev. PD JAN-FEB PY 2010 VL 18 IS 1 BP 12 EP 19 DI 10.1097/CRD.0b013e3181c42f96 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 534FL UT WOS:000272881600002 PM 20010334 ER PT J AU Orea-Tejeda, A Sanchez-Gonzalez, LR Castillo-Martinez, L Vaidespino-Trejo, A Sanchez-Santillan, RN Keirns-Davies, C Colin-Ramirez, E Montano-Hernandez, P Dorantes-Garcia, J AF Orea-Tejeda, Arturo Sanchez-Gonzalez, Luis R. Castillo-Martinez, Lilia Vaidespino-Trejo, Adrian Sanchez-Santillan, Rocio N. Keirns-Davies, Candace Colin-Ramirez, Eloisa Montano-Hernandez, Patricia Dorantes-Garcia, Joel TI Prognostic value of cardiac troponin T elevation is independent of renal function and clinical findings in heart failure patients SO CARDIOLOGY JOURNAL LA English DT Article DE troponin elevation; clinical findings; kidney and heart failure ID ACUTE CORONARY SYNDROMES; LEFT-VENTRICULAR MASS; DILATED CARDIOMYOPATHY; BIOCHEMICAL MARKERS; MORTALITY; INJURY; HEMODIALYSIS; DYSFUNCTION; DIAGNOSIS; DISEASE AB Background: The aim of this study is to determine the prevalence and prognostic value of elevated cardiac troponin (cTnT) and its association with clinical characteristics according to renal function status in patients with stable heart failure. Methods: In a prospective observational study, 152 consecutive Patients from the Heart Failure Clinic of the INCMNSZ were followed for a period of 42 months. All underwent clinical evaluation, echocardiography, and determination of body composition by electric bioimpedance to identify hypervolemia. Concentrations of cTnT were quantified by immunoassay with electrochemoluminescence and >= 0.02 ng/mL levels were considered elevated. Also glomerular filtration rate (eGFR) was estimated using the Cockcroft-Gault equation. Results: Elevated cTnT was significantly associated with increased all-cause mortality in the observational period even ater adjusting for eGFR < 60 mL/min/1.73 m(2) and clinical findings such as hypertension, functional class, loop diuretics, angiotensin converting enzyme Inhibitors, pulmonary pressure, and hypervolemia in Cox regression analysis with a hazard, ratio of 4.58 (95% confidence interval: 1.84-11.45). Conclusions: Heart failure Patients with elevated cardiac-specific troponin T are at increased risk of death independently of the presence of chronic kidney disease. (Cardiol J 2010; 17, 1: 42-48) C1 [Castillo-Martinez, Lilia] INCMNSZ, Heart Failure Clin, Mexico City 03100, DF, Mexico. [Orea-Tejeda, Arturo; Castillo-Martinez, Lilia; Colin-Ramirez, Eloisa; Dorantes-Garcia, Joel] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Mexico City, DF, Mexico. [Keirns-Davies, Candace] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Castillo-Martinez, L (reprint author), INCMNSZ, Heart Failure Clin, Prov 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM caml1225@yahoo.com RI Castillo-Martinez, Lilia/H-3750-2013 NR 32 TC 6 Z9 6 U1 0 U2 1 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1897-5593 J9 CARDIOL J JI Cardiol. J. PD JAN PY 2010 VL 17 IS 1 BP 42 EP 48 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 557YB UT WOS:000274705300007 PM 20104456 ER PT B AU Rubin, MF Townsend, RR AF Rubin, M. F. Townsend, R. R. BE Berbari, AE Mancia, G TI Stroke SO CARDIORENAL SYNDROME: MECHANISMS, RISK AND TREATMENT LA English DT Article; Book Chapter DE Hypertension; Stroke; Proteinuria; Dyslipidemia; Anemia; CKD; ESRD ID CHRONIC-KIDNEY-DISEASE; ANGIOTENSIN RECEPTOR BLOCKERS; CONVERTING ENZYME-INHIBITORS; EVALUATION PROGRAM KEEP; STAGE RENAL-DISEASE; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; INTRACEREBRAL HEMORRHAGE; SECONDARY PREVENTION; DIABETES-MELLITUS AB Stroke is a devastating co-morbidity in chronic kidney disease that is several -fold more common than in the general population. Although traditional cardiovascular risk factors account for much of the stroke risk in CKD, some risk factors like anemia and dyslipidemia are challenging to address in view of recent clinical trial data that do not seem to provide the full degree of expected benefit from risk factor correction as reviewed herein. Others such as hypertension and proteinuria reduction remain mainstays in stroke prevention. C1 [Rubin, M. F.] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Townsend, R. R.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Rubin, MF (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG ITALIA PI MILAN PA MILAN, ITALY BN 978-88-470-1462-6 PY 2010 BP 205 EP 215 DI 10.1007/978-88-470-1463-3_15 D2 10.1007/978-88-470-1463-3 PG 11 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA BQU34 UT WOS:000281864600015 ER PT S AU Bellomo, R Palevsky, PM Bagshaw, SM Gibney, N McAlister, FA Honore, PM Joannes-Boyau, O Prowle, J Haase, M Cruz, DN Ronco, C AF Bellomo, Rinaldo Palevsky, Paul M. Bagshaw, Sean M. Gibney, Noel McAlister, Finlay A. Honore, Patrick M. Joannes-Boyau, Olivier Prowle, John Haase, Michael Cruz, Dinna N. Ronco, Claudio BE Ronco, C Bellomo, R McCullough, PA TI Recent Trials in Critical Care Nephrology SO CARDIORENAL SYNDROMES IN CRITICAL CARE SE Contributions to Nephrology LA English DT Article; Proceedings Paper CT 19th International Vicenza Course on Critical Care Nephrology CY JUN 08-11, 2010 CL Vicenza, ITALY SP Congress Ctr Ente Fiera ID RANDOMIZED CONTROLLED-TRIAL; ILL PATIENTS; HEMOFILTRATION; INTENSITY; THERAPY; FAILURE; SEPSIS AB Several large observational studies or randomized controlled trials in the field of critical care nephrology have been completed and reported, or recently completed or have recently begun recruitment. These studies provide important information to guide our appreciation of current practice and consider new potentially effective intervention for the prevention or attenuation of acute kidney injury or suggest new avenues for the use of renal replacement therapy (RRT) in the treatment of sepsis. In particular, two studies, the ATN study and the RENAL study (both multicenter randomized controlled trials of >1,000 patients) provide, for the first time, level I evidence to guide the practice of RRT in critically ill patients and to better define the optimal intensity of such RAT in this setting. Clinicians practicing in the field of critical care nephrology need to be aware of these trials, their details, their findings or design or current recruitment rate and likely time of completion to continue to offer their patients the highest level of evidence-based medical care. Copyright (C) 2010 S. Karger AG, Basel C1 [Bellomo, Rinaldo; Prowle, John] Austin Hosp, Dept Intens Care, Melbourne, Vic 3084, Australia. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bagshaw, Sean M.; Gibney, Noel] Univ Alberta, Fac Med & Dent, Div Crit Care Med, Edmonton, AB, Canada. [McAlister, Finlay A.] Univ Alberta, Dept Med, Fac Med & Dent, Edmonton, AB, Canada. [Honore, Patrick M.] Queen Astrid Mil Hosp, Burns Ctr, Brussels, Belgium. [Joannes-Boyau, Olivier] Univ Bordeaux 2, Haut Leveque Univ Hosp Bordeaux, Pessac, France. [Haase, Michael] Charite Hosp, Dept Intens Care & Nephrol, Berlin, Germany. [Cruz, Dinna N.; Ronco, Claudio] San Bortolo Hosp, Int Renal Res Inst, Dept Nephrol Dialysis &Transplantat, Vicenza, Italy. RP Bellomo, R (reprint author), Monash Univ, Sch Publ Hlth & Prevent Med, Australian & New Zealand Intens Care Res Ctr, Melbourne, Vic 3004, Australia. EM rinaldo.bellomo@med.monash.edu.au; rinaldo.bellomo@med.monash.edu.au RI McAlister, Finlay/C-4151-2013; Prowle, John/D-5014-2009; OI Prowle, John/0000-0002-5002-2721; Palevsky, Paul/0000-0002-7334-5400; GIBNEY, NOEL/0000-0003-3376-0535 NR 12 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 978-3-8055-9472-1 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2010 VL 165 BP 299 EP 309 DI 10.1159/000313770 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA BQO22 UT WOS:000281438400033 PM 20427981 ER PT J AU Johansson, I Holgerson, PL Kressin, NR Nunn, ME Tanner, AC AF Johansson, I. Holgerson, P. Lif Kressin, N. R. Nunn, M. E. Tanner, A. C. TI Snacking Habits and Caries in Young Children SO CARIES RESEARCH LA English DT Article DE Breast-feeding; Caries; Children; Snacks ID EARLY-CHILDHOOD CARIES; DENTAL-CARIES; ORAL-HEALTH; UNITED-STATES; 4-YEAR-OLD CHILDREN; BRAZILIAN CHILDREN; FEEDING-HABITS; PREVALENCE; FOOD; EXPERIENCE AB Dental caries is caused by a combination of infection and diet. This disease, if left untreated, may lead to pain, and impair the quality of life, nutritional status and development of young children. The objective was to investigate the association between snacking and caries in a population at high risk of dental caries. American preschool children (n = 1,206) were recruited in the offices of paediatricians. Data on sociodemographic characteristics, oral hygiene, breast-feeding, use of bottle and snacking were collected by questionnaire. Plaque presence, the number of teeth and their caries status (deft) were scored. The children sampled were 61% Black, 27% White and 10% Asian. Of the 1- to 2-, 2- to 3- and 3- to 4-year-old children, 93.8, 82.4 and 77.3% were caries free, and their mean caries scores were 0.16, 0.58 and 0.93, respectively. Multivariate partial least squares (PLS) modelling revealed plaque presence, lowest income, descriptors for tooth exposure time (number of teeth and age) and cariogenic challenge (total intake of sugar-containing snacks and chips/crisps, and chips intake with a sugar-containing drink) to be associated with more caries. These differences were also found in univariate analyses; in addition, children who continued breast-feeding after falling asleep had significantly higher deft values than those who did not. PLS modelling revealed that eating chips clustered with eating many sweet snacks, candies, popcorn and ice cream. We conclude that, in addition to the traditional risk indicators for caries - presence of plaque, sugar intake and socioeconomic status -, consumption of chips was associated with caries in young children. Copyright (C) 2010 S. Karger AG, Basel C1 [Johansson, I.; Holgerson, P. Lif] Umea Univ, Dept Odontol, SE-90187 Umea, Sweden. [Kressin, N. R.] Boston Univ, Dept Med, Gen Internal Med Sect, Healthcare Dispar Res Program,Sch Med, Boston, MA 02215 USA. [Kressin, N. R.] VA Boston Healthcare Syst, Boston, MA USA. [Tanner, A. C.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Tanner, A. C.] Harvard Univ, Sch Dent Med, Dept Mol Genet, Forsyth Inst, Boston, MA 02115 USA. RP Johansson, I (reprint author), Umea Univ, Dept Odontol, SE-90187 Umea, Sweden. EM ingegerd.johansson@odont.umu.se OI Kressin, Nancy/0000-0003-2767-4286 FU NIH/National Institute of Dental and Craniofacial Research [U54 DE-014264, K24 DE-000419, DE-015847, DE-019275]; County Council of Vasterbotten, Sweden FX The study was supported by the NIH/National Institute of Dental and Craniofacial Research grants U54 DE-014264, K24 DE-000419, DE-015847 (A.C.T.) and DE-019275 (M.E.N.), and by the County Council of Vasterbotten, Sweden (I.J.,P.L.H.). NR 45 TC 33 Z9 35 U1 6 U2 25 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 EI 1421-976X J9 CARIES RES JI Caries Res. PY 2010 VL 44 IS 5 BP 421 EP 430 DI 10.1159/000318569 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 654MY UT WOS:000282173600001 PM 20720422 ER PT J AU Kanasi, E Dewhirst, FE Chalmers, NI Kent, R Moore, A Hughes, CV Pradhan, N Loo, CY Tanner, ACR AF Kanasi, E. Dewhirst, F. E. Chalmers, N. I. Kent, R., Jr. Moore, A. Hughes, C. V. Pradhan, N. Loo, C. Y. Tanner, A. C. R. TI Clonal Analysis of the Microbiota of Severe Early Childhood Caries SO CARIES RESEARCH LA English DT Article DE Bifidobacteria; Clonal analysis; PCR; Severe early childhood caries; Streptococcus mutans ID MOLECULAR ANALYSIS; DENTAL-CARIES; BACTERIAL DIVERSITY; PERMANENT TEETH; ROOT CARIES; CHILDREN; PLAQUE; MICROFLORA; LESIONS; BIFIDOBACTERIA AB Background/Aims: Severe early childhood caries is a microbial infection that severely compromises the dentition of young children. The aim of this study was to characterize the microbiota of severe early childhood caries. Methods: Dental plaque samples from 2- to 6-year-old children were analyzed using 16S rRNA gene cloning and sequencing, and by specific PCR amplification for Streptococcus mutans and Bifidobacteriaceae species. Results: Children with severe caries (n = 39) had more dental plaque and gingival inflammation than caries-free children (n = 41). Analysis of phylotypes from operational taxonomic unit analysis of 16S rRNA clonal metalibraries from severe caries and caries-free children indicated that while libraries differed significantly (p < 0.0001), there was increased diversity than detected in this clonal analysis. Using the Human Oral Microbiome Database, 139 different taxa were identified. Within the limits of this study, caries-associated taxa included Granulicatella elegans (p < 0.01) and Veillonella sp. HOT-780 (p < 0.01). The species associated with caries-free children included Capnocytophaga gingivalis (p < 0.01), Abiotrophia defectiva (p < 0.01), Lachnospiraceae sp. HOT- 100 (p < 0.05), Streptococcus sanguinis (p < 0.05) and Streptococcus cristatus (p < 0.05). By specific PCR, S. mutans (p < 0.005) and Bifidobacteriaceae spp. (p < 0.0001) were significantly associated with severe caries. Conclusion: Clonal analysis of 80 children identified a diverse microbiota that differed between severe caries and caries-free children, but the association of S. mutans with caries was from specific PCR analysis, not from clonal analysis, of samples. Copyright (C) 2010 S. Karger AG, Basel C1 [Kanasi, E.; Dewhirst, F. E.; Chalmers, N. I.; Tanner, A. C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. [Kent, R., Jr.] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Dewhirst, F. E.; Tanner, A. C. R.] Harvard Univ, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. [Moore, A.] Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. [Hughes, C. V.] Boston Univ, Dept Pediat Dent, Goldman Sch Dent Med, Boston, MA 02215 USA. [Pradhan, N.; Loo, C. Y.] Tufts Univ, Tufts Sch Dent Med, Dept Pediat Dent, Boston, MA 02111 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM annetanner@forsyth.org RI Hughes, Christopher/E-1438-2014 FU Public Health Service [DE-014264, DE-015847, DE-016937, DE-007151, DE-007327]; NIDCR; Medical Faculty/PhD training grant, Umea University, Sweden FX We acknowledge Mohammed Dahlan, Rachel Montgomery, Benita Demirza, Caroline Young, David Okuji and Sam Merabi for subject recruitment and clinical measurements and Sara Barbuto for assistance with clone sequencing. We thank Patrick Schloss, Department of Microbiology & Immunology, University of Michigan, Ann Arbor, Mich., USA, for reviewing the manuscript and providing helpful feedback. This work was supported by Public Health Service Grants the DE-014264 (A.T.), DE-015847 (A.T.), DE-016937 (F.D.), DE-007151 (E.K.), DE-007327 (N.C.and E.K.) from NIDCR and a Medical Faculty/PhD training grant, Umea University, Sweden (E.K.). NR 50 TC 72 Z9 78 U1 3 U2 23 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PY 2010 VL 44 IS 5 BP 485 EP 497 DI 10.1159/000320158 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 654MY UT WOS:000282173600010 PM 20861633 ER PT J AU Myllyharju, J Schipani, E AF Myllyharju, Johanna Schipani, Ernestina TI Extracellular matrix genes as hypoxia-inducible targets SO CELL AND TISSUE RESEARCH LA English DT Review DE Hypoxia; Hypoxia-inducible factor; Extracellular matrix; Cartilage; Joint ID COLLAGEN PROLYL 4-HYDROXYLASE; HUMAN ERYTHROPOIETIN GENE; SYNOVIAL JOINT FORMATION; LYSYL OXIDASE; IN-VITRO; TRANSCRIPTIONAL ACTIVATION; PROLINE HYDROXYLATION; ENDOPLASMIC-RETICULUM; FACTOR (HIF)-1-ALPHA; CELL-FUNCTION AB Low oxygen tension, i.e., hypoxia, is a pathophysiological component involved in many human disorders but is also a critically important phenomenon in normal development and differentiation. The ability of cells to survive under hypoxia or to adapt to it depends on a family of hypoxia-inducible transcription factors (HIFs) that induce the expression of a number of genes involved in hematopoiesis, angiogenesis, iron transport, glucose utilization, resistance to oxidative stress, cell proliferation, survival and apoptosis, and extracellular matrix homeostasis. We introduce here the recently identified molecular mechanisms responsible for the oxygen-dependent stability and activity of HIF, after which we focus on extracellular matrix genes as HIF targets. The vital role of the hypoxia response pathway in chondrogenesis and joint development is then discussed. C1 [Myllyharju, Johanna] Univ Oulu, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu 90014, Finland. [Myllyharju, Johanna] Univ Oulu, Dept Med Biochem & Mol Biol, Oulu 90014, Finland. [Schipani, Ernestina] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Schipani, Ernestina] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Myllyharju, J (reprint author), Univ Oulu, Oulu Ctr Cell Matrix Res, Bioctr Oulu, Oulu 90014, Finland. EM johanna.myllyharju@oulu.fi FU NIAMS NIH HHS [R01 AR048191, R01 AR048191-08] NR 115 TC 21 Z9 22 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2010 VL 339 IS 1 BP 19 EP 29 DI 10.1007/s00441-009-0841-7 PG 11 WC Cell Biology SC Cell Biology GA 548IF UT WOS:000273953300003 PM 19662436 ER PT S AU Ferraro, F Lo Celso, C Scadden, D AF Ferraro, Francesca Lo Celso, Cristina Scadden, David BE Meshorer, E Plath, K TI ADULT STEM CELLS AND THEIR NICHES SO CELL BIOLOGY OF STEM CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID HEMATOPOIETIC PROGENITOR CELLS; EXPERIMENTAL MELANOMA METASTASIS; HEPATIC STELLATE CELLS; SKELETAL-MUSCLE FIBERS; SELF-RENEWAL; BONE-MARROW; HAIR FOLLICLE; ENDOTHELIAL-CELLS; LYMPHOBLASTIC-LEUKEMIA; DROSOPHILA OVARY AB Stem cells participate in dynamic physiologic systems that dictate the outcome of developmental events and organismal stress, Since these cells are fundamental to tissue maintenance and repair, the signals they receive play a critical role in the integrity of the organism. Much work has focused on stem cell identification and the molecular pathways involved in their regulation. Yet, we understand little about how these pathways achieve physiologically responsive stem cell functions. This chapter will review the state of our understanding of stem cells in the context of their microenvironment regarding the relation between stem cell niche dysfunction, carcinogenesis and aging. C1 [Scadden, David] Harvard Univ, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA. RP Scadden, D (reprint author), Harvard Univ, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol, 185 Cambridge St, Boston, MA 02115 USA. EM dscadden@mgh.harvard.edu FU NHLBI NIH HHS [U01 HL100402, R01 HL044851, R01 HL097794] NR 105 TC 15 Z9 16 U1 0 U2 12 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-7036-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 695 BP 155 EP 168 D2 10.1007/978-1-4419-7037-4 PG 14 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BQJ64 UT WOS:000281178600011 PM 21222205 ER PT B AU Ji, JY Dyson, NJ AF Ji, Jun-Yuan Dyson, Nicholas J. BE Enders, GH TI Interplay Between Cyclin-Dependent Kinases and E2F-Dependent Transcription SO CELL CYCLE DEREGULATION IN CANCER SE Contemporary Cancer Research LA English DT Article; Book Chapter ID RNA-POLYMERASE-II; TUMOR-SUPPRESSOR PROTEIN; UBIQUITIN-PROTEASOME PATHWAY; MAMMALIAN MEDIATOR COMPLEX; HUMAN CDK8 SUBCOMPLEX; E2F FAMILY-MEMBERS; BINDING IN-VITRO; YEAST-CELL CYCLE; S-PHASE; RETINOBLASTOMA PROTEIN AB Precise control of cell proliferation is essential for normal development and survival of all multi-cellular organisms. The deregulation of cell proliferation is a fundamental feature of all types of cancer. One of the key regulators of cell proliferation is the E2F transcription factor. E2F controls the expression of many genes that are required for cells to divide and elevated E2F activity is found in most tumor cells. The activation and inactivation of E2F are tightly linked to the activation of cyclin-dependent kinases (CDKs). In normal cells, these connections allow the periodic oscillations in CDK cycle to be coupled with temporal programs of gene expression. Multiple CDK cyclin complexes (including CDK1/2-CycA, CDK1/2-CycB, and CDK7-CycH) have been shown to directly phosphorylate E2F or its dimerization partner DP. However, in recent genetic studies, one of the strongest modifiers of E2F-dependent phenotypes was cdk8, a kinase that had not previously been linked to E2F. In this review, we summarize the effects of CDKs on E2F1 activity and describe a model that may explain the role of CDK8-CycC in E2F regulation. Since CDKs can both increase and decrease E2F activity, understanding the interplay between E2F and CDK cyclin complexes may suggest therapeutic approaches to efficiently block cancer cell proliferation. C1 [Ji, Jun-Yuan; Dyson, Nicholas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Canc Ctr, Charlestown, MA 02129 USA. [Ji, Jun-Yuan] Texas A&M Hlth Sci Ctr, Dept Mol & Cellular Med, College Stn, TX 77843 USA. RP Ji, JY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Canc Ctr, Charlestown, MA 02129 USA. EM ji@medicine.tamhsc.edu; dyson@helix.mgh.harvard.edu NR 135 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1769-0 J9 CONTEMP CANCER RES JI Cont. Canc. Res. PY 2010 BP 23 EP 41 DI 10.1007/978-1-4419-1770-6_2 D2 10.1007/978-1-4419-1770-6 PG 19 WC Oncology SC Oncology GA BOK36 UT WOS:000276890600002 ER PT B AU Johnson, N Shapiro, GI AF Johnson, Neil Shapiro, Geoffrey I. BE Enders, GH TI Targeting Cyclin-Dependent Kinases for Cancer Therapy SO CELL CYCLE DEREGULATION IN CANCER SE Contemporary Cancer Research LA English DT Article; Book Chapter ID MANTLE-CELL LYMPHOMA; STRAND-BREAK REPAIR; DNA END RESECTION; FLAVOPIRIDOL INDUCES APOPTOSIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN TUMOR XENOGRAFTS; S-PHASE; HOMOLOGOUS RECOMBINATION; INHIBITOR FLAVOPIRIDOL; CHECKPOINT ACTIVATION AB Cyclin-dependent kinase (cdk) activity is universally deregulated in cancer. Therefore, cancer cells may be more sensitive to cdk inhibition than normal cells. Currently, novel classes of inhibitors of cdk4/6 and cdk2/1 are under development, capable of inducing G1 or S/G2 cell cycle arrest, respectively. Transcriptional cdk inhibition affects RNA polymerase II activity and may alter the apoptotic threshold of cancer cells by compromising expression of highly sensitive short half-life transcripts. Compounds that concomitantly disrupt cell cycle progression and transcriptional control may therefore have potential as single agents. Additionally, cdk inhibition may modulate cyclin D1 expression, facilitating synergism with signal transduction inhibitors, as well as p53 and E2F-1 activities, contributing to apoptotic responses. Cdk activity has also been implicated in DNA damage-induced checkpoint control and repair, suggesting promise for chemotherapy/cdk inhibitor combinations. Further preclinical mechanistic experiments, as well as pharmacodynamic assessments accompanying clinical trials, will be necessary to establish cdk inhibition as an anti-cancer strategy. C1 [Johnson, Neil; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, Neil; Shapiro, Geoffrey I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Johnson, Neil; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM neil_johnson@dfci.harvard.edu; geoffrey_shapiro@dfci.harvard.edu NR 120 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1769-0 J9 CONTEMP CANCER RES JI Cont. Canc. Res. PY 2010 BP 167 EP 185 DI 10.1007/978-1-4419-1770-6_11 D2 10.1007/978-1-4419-1770-6 PG 19 WC Oncology SC Oncology GA BOK36 UT WOS:000276890600011 ER PT J AU Yu, D Song, G Poon, CS Teng, YD AF Yu, D. Song, G. Poon, C. -S. Teng, Y. D. TI Human Neural Stem Cell-Mediated Restoration of Respiratory Function Following Spinal Cord Injury in Rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 17th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 29-MAY 01, 2010 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 [Yu, D.; Teng, Y. D.] Harvard Univ, Sch Med, Dept Neurosurg, BWH CHB, Boston, MA 02115 USA. [Yu, D.; Teng, Y. D.] Harvard Univ, Sch Med, Dept PM&R, SRH, Boston, MA 02115 USA. [Yu, D.; Teng, Y. D.] VA Boston Healthcare Syst, Div SCI Res, Boston, MA USA. [Song, G.; Poon, C. -S.] Harvard Univ, MIT, Hlth Sci & Technol Program, Cambridge, MA 02139 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 3 BP 367 EP 368 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 592ZB UT WOS:000277419400114 ER PT J AU Soto-Gutierrez, A Yagi, H Uygun, BE Navarro-Alvarez, N Uygun, K Kobayashi, N Yang, YG Yarmush, ML AF Soto-Gutierrez, Alejandro Yagi, Hiroshi Uygun, Basak E. Navarro-Alvarez, Nalu Uygun, Korkut Kobayashi, Naoya Yang, Yong-Guang Yarmush, Martin L. TI Cell Delivery: From Cell Transplantation to Organ Engineering SO CELL TRANSPLANTATION LA English DT Review DE Cell transplant; Organ engineering; Decellularized matrices; Natural scaffolds ID EMBRYONIC STEM-CELLS; ASSEMBLING PEPTIDE NANOFIBER; VIVO GENE-THERAPY; HEPATOCYTE TRANSPLANTATION; IN-VITRO; EXTRACELLULAR-MATRIX; FETAL LIVER; RAT-LIVER; FAMILIAL HYPERCHOLESTEROLEMIA; STEM/PROGENITOR CELLS AB Cell populations derived from adult tissue and stem cells possess a great expectation for the treatment of several diseases. Great efforts have been made to generate cells with therapeutic impact from stem cells. However, it is clear that the development of systems to deliver such cells to induce efficient engraftment, growth, and function is a real necessity. Biologic and artificial scaffolds have received significant attention for their potential therapeutic application when use to form tissues in vitro and facilitate engraftment in vivo. Ultimately more sophisticated methods for decellularization of organs have been successfully used in tissue engineering and regenerative medicine applications. These decellularized tissues and organs appear to provide bioactive molecules and bioinductive properties to induce homing, differentiation, and proliferation of cells. The combination of decellularized organs and stem cells may dramatically improve the survival, engraftment, and fate control of transplanted stem cells and their ultimate clinical utility, opening the doors to a new era of organ engineering. C1 [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Uygun, Basak E.; Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Uygun, Basak E.; Uygun, Korkut; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Uygun, Basak E.; Uygun, Korkut; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Navarro-Alvarez, Nalu; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Kobayashi, Naoya] Okayama Univ, Dept Surg, Grad Sch Med & Dent, Okayama, Japan. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Soto-Gutierrez, A (reprint author), Childrens Hosp Pittsburgh, Dept Surg, Transplantat Sect, 3511 Rangos Res Bldg,530 45th St, Pittsburgh, PA 15201 USA. EM alejandro.sotogutierrez@chp.edu; ireis@sbi.org RI Uygun, Basak/I-1792-2012 OI Uygun, Basak/0000-0002-2600-7900 FU American Liver Foundation; US National Institutes of Health (NIH) [K99DK083556-01] FX We thank the support of the American Liver Foundation to A.S.G. Funding from the US National Institutes of Health (NIH) K99DK083556-01 to A.S.G supported this work. NR 66 TC 31 Z9 32 U1 1 U2 31 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 6-7 BP 655 EP 665 DI 10.3727/096368910X508753 PG 11 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 663CL UT WOS:000282860500003 PM 20525441 ER PT J AU Yagi, H Soto-Gutierrez, A Parekkadan, B Kitagawa, Y Tompkins, RG Kobayashi, N Yarmush, ML AF Yagi, Hiroshi Soto-Gutierrez, Alejandro Parekkadan, Biju Kitagawa, Yuko Tompkins, Ronald G. Kobayashi, Naoya Yarmush, Martin L. TI Mesenchymal Stem Cells: Mechanisms of Immunomodulation and Homing SO CELL TRANSPLANTATION LA English DT Review DE Immunosuppression; T-cell proliferation; Stem cell migration; Interferon-gamma (IFN-gamma); Nuclear factor-kappa B (NF-kappa B) ID MARROW STROMAL CELLS; TOLL-LIKE RECEPTORS; BREAST-CANCER METASTASIS; VERSUS-HOST-DISEASE; REGULATORY T-CELLS; BONE-MARROW; DENDRITIC CELLS; IN-VIVO; IFN-GAMMA; INDOLEAMINE 2,3-DIOXYGENASE AB Mesenchymal stem cell (MSC) transplantation has been explored as a new clinical approach to repair injured tissue. A growing corpus of studies have highlighted two important aspects of MSC therapy: 1) MSCs can modulate T-cell-mediated immunological responses, and (2) systemically administered MSCs home to sites of ischemia or injury. In this review, we describe the known mechanisms of immunomodulation and homing of MSCs. First, we examine the low immunogenicity of MSCs and their antigen presentation capabilities. Next, we discuss the paracrine interactions between MSCs and innate [dendritic cells (DC)] and adaptive immune cells (T lymphocytes) with a focus on prostaglandin E(2) (PGE(2)), indoleamine 2,3-dioxygenase (IDO), and toll-like receptor (TLR) signaling pathways. We transition to outline the steps of activation, rolling/adhesion, and transmigration of MSCs into target tissues during inflammatory or ischemic conditions. These aspects of MSC grafts immunomodulation and homing are contextualized to understand a reported side effect of MSC therapy, cancer development. C1 [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Parekkadan, Biju; Tompkins, Ronald G.; Yarmush, Martin L.] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Parekkadan, Biju; Tompkins, Ronald G.; Yarmush, Martin L.] Harvard Univ, Sch Med, Boston, MA USA. [Yagi, Hiroshi; Kitagawa, Yuko] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. [Kobayashi, Naoya] Okayama Univ, Dept Surg, Grad Sch Med & Dent, Okayama, Japan. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [K99 DK083556, K99 DK083556-02, R00 DK083556] NR 108 TC 273 Z9 293 U1 8 U2 89 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 6-7 BP 667 EP 679 DI 10.3727/096368910X508762 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 663CL UT WOS:000282860500004 PM 20525442 ER PT J AU van Poll, D Nahmias, Y Soto-Gutierrez, A Ghasemi, M Yagi, H Kobayashi, N Yarmush, ML Hertl, M AF van Poll, Daan Nahmias, Yakoov Soto-Gutierrez, Alejandro Ghasemi, Mitra Yagi, Hiroshi Kobayashi, Naoya Yarmush, Martin L. Hertl, Martin TI Human Immune Reactivity Against Liver Sinusoidal Endothelial Cells From GalT alpha(1,3)GalT-Deficient Pigs SO CELL TRANSPLANTATION LA English DT Article DE Xenotransplantation; Liver endothelial cells; GalT alpha(1,3)GalT-knockout pigs ID HUMAN NATURAL ANTIBODIES; GENE-KNOCKOUT PIGS; HEART-TRANSPLANTATION; XENOTRANSPLANTATION; HEPATOCYTES; REJECTION; SURVIVAL; BABOONS; TARGETS; DONORS AB Elimination of galactose-alpha( 1,3)galactose (Gal) expression in pig organs has been previously shown to prevent hyperacute xenograft rejection. However, naturally present antibodies to non-Gal epitopes activate endothelial cells, leading to acute humoral xenograft rejection. Still, it is unknown whether xenogeneic pig liver sinusoidal endothelial cells (LSECs) from alpha(1,3)galactosyltransferase (GalT)-deficient pigs are damaged by antibody and complement-mediated mechanisms. The present study examined the xeno-antibody response of LSECs from GalT-deficient and wild pigs. Isolated LSEC from wild-type and GalT pigs were expose to human and baboon sera; IgM and IgG binding was analyzed by flow cytometry. Complement activation (C3a and CH50) was quantified in vitro from serum-exposed LSEC cultures using Enzyme-Linked Immuno-Sorbent assay (ELISA). Levels of complement-activated cytotoxicity (CAC) were also determined by a fluorescent Live Dead Assay and by the quantification of LDH release. IgM binding to GalT knockout (KO) LSECs was significantly lower (80% human and 87% baboon) compare to wild-type pig LSEC. IgG binding was low in all groups. Moreover, complement activation (C3a and CHSO) levels released following exposure to human or baboon sera were importantly reduced (42% human and 52% baboon), CAC in GalT KO LSECs was reduced by 60% in human serum and by 72% in baboon serum when compared to wildtype LSECs, and LDH release levels were reduced by 37% and 57%, respectively. LSECs from GalT KO pigs exhibit a significant protection to humoral-induced cell damage compared to LSECs from wild pigs when exposed to human serum. Although insufficient to inhibit xenogeneic reactivity completely, transgenic GalT KO expression on pig livers might contribute to a successful application of clinical xenotransplantation in combination with other protective strategies. C1 [Ghasemi, Mitra; Hertl, Martin] Massachusetts Gen Hosp, Transplant Unit, Dept Surg, Boston, MA 02114 USA. [van Poll, Daan; Nahmias, Yakoov; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [van Poll, Daan; Nahmias, Yakoov; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [van Poll, Daan; Nahmias, Yakoov; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Kobayashi, Naoya] Okayama Univ, Dept Surg, Grad Sch Med & Dent, Okayama, Japan. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Hertl, M (reprint author), Massachusetts Gen Hosp, Transplant Unit, Dept Surg, 55 Fruit St,White 546, Boston, MA 02114 USA. EM mhertl@partners.org RI Nahmias, Yaakov/H-4725-2013 FU NIDDK NIH HHS [K99 DK083556, K99 DK083556-02, R00 DK083556] NR 20 TC 8 Z9 8 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 6-7 BP 783 EP 789 DI 10.3727/096368910X508898 PG 7 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 663CL UT WOS:000282860500017 PM 20573304 ER PT J AU Soto-Gutierrez, A Navarro-Alvarez, N Yagi, H Nahmias, Y Yarmush, ML Kobayashi, N AF Soto-Gutierrez, Alejandro Navarro-Alvarez, Nalu Yagi, Hiroshi Nahmias, Yakoov Yarmush, Martin L. Kobayashi, Naoya TI Engineering of an Hepatic Organoid to Develop Liver Assist Devices SO CELL TRANSPLANTATION LA English DT Article DE Organoid; Liver support; Liver cell therapy; Liver failure ID CELL-DERIVED HEPATOCYTES; NONPARENCHYMAL CELLS; BIOARTIFICIAL LIVER; IN-VITRO; ESTABLISHMENT; FAILURE; DIFFERENTIATION; TRANSPLANTATION; COCULTURE; CULTURE AB Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver-specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents. Hepatocytes only or in combination with human nonparenchymal liver cell lines (endothelial, cholangiocytes, and stellate cells) were cultured in Matrigel. Ultrastructural analysis showed that the hepatocyte-decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and lumen. The sinusoid-like structures retained albumin secretion and drug metabolism capabilities. In addition, LADs containing cocultures of human liver nonparenchymal cells were transplanted in animals for a week; the liver tissue formed sophisticated structures resembling the liver. These results demonstrate the importance of nonparenchymal cells in the cellular composition of LADs. The novelty of the culture's sinusoid-like organization and function strongly support the integration of liver nonparenchymal units into hepatocyte coculture-based LADs as a potential destination therapy for liver failure. C1 [Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalu; Kobayashi, Naoya] Okayama Univ, Dept Surg, Grad Sch Med & Dent, Okayama, Japan. [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Nahmias, Yakoov; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Nahmias, Yakoov; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Nahmias, Yakoov; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Soto-Gutierrez, A (reprint author), Childrens Hosp Pittsburgh, Dept Surg, Transplantat Sect, 3511 Rangos Res Bldg,530 45th St, Pittsburgh, PA 15201 USA. EM alejandro.sotogutierrez@chp.edu RI Nahmias, Yaakov/H-4725-2013 FU American Liver Foundation; US National Institutes of Health (NIH) [K99DK083556-01] FX We thank the support of the American Liver Foundation to A.S.G. Funding from the US National Institutes of Health (NIH) K99DK083556-01 to A.S.G supported this work. NR 22 TC 21 Z9 22 U1 0 U2 13 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 6-7 BP 815 EP 822 DI 10.3727/096368910X508933 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 663CL UT WOS:000282860500021 PM 20573303 ER PT J AU Yagi, H Soto-Gutierrez, A Kitagawa, Y Tilles, AW Tompkins, RG Yarmush, ML AF Yagi, Hiroshi Soto-Gutierrez, Alejandro Kitagawa, Yuko Tilles, Arno W. Tompkins, Ronald G. Yarmush, Martin L. TI Bone Marrow Mesenchymal Stromal Cells Attenuate Organ Injury Induced by LPS and Burn SO CELL TRANSPLANTATION LA English DT Article DE Anti-inflammation; Antiapoptosis; Sepsis; Burn; Lipopolysaccharide (LPS); Systemic inflammatory response syndrome (SIRS); Multiple organ injury ID SYSTEMIC INFLAMMATORY RESPONSE; DYSFUNCTION SYNDROME MODS; STEM-CELLS; MYOCARDIAL-INFARCTION; RENAL-FAILURE; SYNDROME SIRS; SEPSIS; KINASE; RAT; TRANSPLANTATION AB Bone marrow mesenchymal stromal cells (MSCs) suppress immune cell responses and have beneficial effects in various inflammatory-related immune disorders. A therapeutic modality for systemic inflammation and its consequences is not available yet. Thus, this work investigates the therapeutic effects of MSCs in injury models induced by lipopolysaccharide (LPS) or burn. Gene expression was analyzed in MSCs when exposed to inflammatory serum from injured animals and it showed remarkable alterations compared to normal culture. In addition, injured animals were transplanted intramuscularly with MSCs. Forty-eight hours after cell transplantation, kidney, lung, and liver were analyzed for infiltration of inflammatory cells and TUNEL-expressing cells. Results showed that MSCs attenuate injury by reducing the infiltration of inflammatory cells in various target organs and by reducing cell death. These data suggest that MSCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for systemic inflammatory-based disorders. C1 [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Tilles, Arno W.; Tompkins, Ronald G.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Tilles, Arno W.; Tompkins, Ronald G.; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Engn Med, Boston, MA 02115 USA. [Kitagawa, Yuko] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [K99 DK083556-02, K99 DK083556, R00 DK083556] NR 42 TC 41 Z9 48 U1 1 U2 8 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 6-7 BP 823 EP 830 DI 10.3727/096368910X508942 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 663CL UT WOS:000282860500022 PM 20573305 ER PT J AU Prochazka, V Gumulec, J Jaluvka, F Salounova, D Jonszta, T Czerny, D Krajca, J Urbanec, R Klement, P Martinek, J Klement, GL AF Prochazka, V. Gumulec, J. Jaluvka, F. Salounova, D. Jonszta, T. Czerny, D. Krajca, J. Urbanec, R. Klement, P. Martinek, J. Klement, G. L. TI Cell Therapy, a New Standard in Management of Chronic Critical Limb Ischemia and Foot Ulcer SO CELL TRANSPLANTATION LA English DT Article DE Critical limb ischemia (CLI); Diabetic foot ulcer; Autologous bone marrow stem cells (ABMSC); Lymphopenia of bone marrow ID ENDOTHELIAL PROGENITOR CELLS; BONE-MARROW-CELLS; HEMATOPOIETIC STEM-CELLS; POSTNATAL NEOVASCULARIZATION; DIABETIC FOOT; GROWTH-FACTOR; AUTOLOGOUS TRANSPLANTATION; MONONUCLEAR-CELLS; IN-VIVO; ANGIOGENESIS AB Fifty percent of diabetics (7% of general population) suffer from peripheral arterial occlusive disease, which may lead to amputation due to critical limb ischemia (CLI). The aim of our study was to prevent major limb amputation (MLA) in this group of patients using a local application of autologous bone marrow stem cells (ABMSC) concentrate. A total of 96 patients with CLI and foot ulcer (FU) were randomized into groups I and II. Patients in group I (n = 42, 36 males, 6 females, 66.2 +/- 10.6 years) underwent local treatment with ABMSC while those in group II (n = 54, control, 42 males, 12 females, 64.1 +/- 8.6 years) received standard medical care. The frequency of major limb amputation in groups I and II was 21% and 44% within the 120 days of follow up, respectively (p < 0.05). Only in salvaged limbs of group I both toe pressure and toe brachial index increased (from 22.66 +/- 5.32 to 25.63 +/- 4.75 mmHg and from 0.14 +/- 0.03 to 0.17 +/- 0.03, respectively, mean +/- SEM). The CD34(+) cell counts in bone marrow concentrate (BMC) decreased (correlation, p = 0.024) with age, even though there was no correlation between age and healing. An unexpected finding was made of relative, bone marrow lymphopenia in the initial bone marrow concentrates in patients who failed ABMSC therapy (21% of MLA). This difference was statistically significant (p < 0.040). We conclude ABMSC therapy results in 79% limb salvage in patients suffering from CLI and FU. In the remaining 21% lymphopenia and thrombocytopenia were identified as potential causative factors, suggesting that at least a partial correction with platelet supplementation may be beneficial. C1 [Prochazka, V.] Univ Ostrava, Univ Hosp Ostrava, Dept Radiol, Radiodiagnost Inst, CZ-70852 Ostrava, Czech Republic. [Gumulec, J.] Univ Ostrava, Univ Hosp Ostrava, Hematooncol Ctr, CZ-70852 Ostrava, Czech Republic. [Jaluvka, F.; Urbanec, R.] Univ Ostrava, Univ Hosp Ostrava, Surg Clin, CZ-70852 Ostrava, Czech Republic. [Jaluvka, F.; Urbanec, R.] Univ Ostrava, Univ Hosp Ostrava, Dept Anaesthesiol, CZ-70852 Ostrava, Czech Republic. [Salounova, D.] Tech Univ Ostrava, Dept Math Methods Econ, VSB, CZ-70833 Ostrava, Czech Republic. [Klement, P.] McMaster Univ, Henderson Res Ctr, Hamilton, ON, Canada. [Martinek, J.] JG Mendel Canc Ctr, Clin Lab, Novy Jicin, Czech Republic. [Klement, G. L.] Harvard Med Univ, Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Prochazka, V (reprint author), Univ Ostrava, Univ Hosp Ostrava, Dept Radiol, Radiodiagnost Inst, Ave 17 Listopadu 1790, CZ-70852 Ostrava, Czech Republic. EM angio@vol.cz RI Prochazka, Vaclav/I-5422-2016 OI Prochazka, Vaclav/0000-0002-2410-2314 FU Moravian-Silesian Region Government [MSK-99/OVZ/08/006-1] FX This clinical study was supported by the grant from the Moravian-Silesian Region Government (MSK-99/OVZ/08/006-1). NR 46 TC 54 Z9 58 U1 2 U2 7 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 11 BP 1413 EP 1424 DI 10.3727/096368910X514170 PG 12 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 704VY UT WOS:000286084900005 PM 20529449 ER PT J AU Hamamoto, Y Akashi, T Inada, A Bonner-Weir, S Weir, GC AF Hamamoto, Yoshiyuki Akashi, Tomoyuki Inada, Akari Bonner-Weir, Susan Weir, Gordon C. TI Lack of Evidence for Recipient Precursor Cells Replenishing beta-Cells in Transplanted Islets SO CELL TRANSPLANTATION LA English DT Article DE Islet precursor cell; Islet transplantation; Regeneration; Bone marrow; Stem cell ID MESENCHYMAL STEM-CELLS; BONE-MARROW-CELLS; PANCREATIC-ISLETS; IN-VIVO; ENDOTHELIAL-CELLS; MICE; REGENERATION; HEPATOCYTES; REVERSAL; INJURY AB Bone marrow and tissue precursor cells have been postulated to replenish grafts of transplanted islets. Several investigators have reported that bone marrow cells can promote the regeneration of injured islets. In this study, we investigated the potential of recipient-derived precursor cells to form new pancreatic endocrine cells in islet grafts transplanted under the kidney capsule. Mouse insulin promoter (MIP)-green fluorescence protein (GFP) mice, which express GFP only in beta-cells, or beta-actin GFP mice, which express GFP ubiquitously, were used to determine if the recipient-derived cells differentiate into beta-cells or other types of endocrine cells. We transplanted MIP-GFP islets into wild-type mice, wild-type islets into MIP-GFP mice, beta-actin GFP islets into wild-type mice, and wild-type islets into beta-actin GFP mice. beta-Actin GFP bone marrow cells were then injected into wild-type mice to evaluate the potential role of bone marrow stem cells to provide new islet cells to the graft. No beta-cells with green fluorescence were seen in the graft when wildtype islets were transplanted into MIP-GFP mice. When wild-type islets were transplanted into beta-actin GFP mice, no beta-cells with GFP staining could be identified in the grafts. Similarly, no endocrine cells with GFP staining could be identified in the grafts after injection of beta-actin GFP bone marrow cells into wild-type islet-transplanted wild-type mice. This study provides further support for the concept that recipient precursor cells do not produce new beta-cells in grafts of transplanted islets. C1 [Hamamoto, Yoshiyuki; Akashi, Tomoyuki; Inada, Akari; Bonner-Weir, Susan; Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Div Res, Boston, MA 02215 USA. [Hamamoto, Yoshiyuki; Akashi, Tomoyuki; Inada, Akari; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hamamoto, Yoshiyuki] Kitano Hosp, Inst Med, Tazuke Kofukai Fdn, Ctr Diabet & Endocrinol, Osaka, Japan. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU National Institute of Health [U19DK61251, DK36836]; Juvenile Diabetes Research Foundation; Diabetes Research and Wellness Foundation; Sumitomo Life Social Welfare Services Foundation (Osaka, Japan) FX We thank Jennifer Lock for her technical assistance. This study was supported by grants from the National Institute of Health (U19DK61251), the Juvenile Diabetes Research Foundation, and the Diabetes Research and Wellness Foundation. Help was also provided by the Advanced Microscopy Core of Joslin Diabetes and Endocrinology Research Center (DERC) supported by the National Institutes of Health (DK36836). Yoshiyuki Hamamoto is the recipient of the grant from Sumitomo Life Social Welfare Services Foundation (Osaka, Japan). NR 37 TC 6 Z9 6 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2010 VL 19 IS 12 BP 1563 EP 1572 DI 10.3727/096368910X515881 PG 10 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 720OF UT WOS:000287289300005 PM 20719077 ER PT J AU Barbon, CM Yang, M Wands, GD Ramesh, R Slusher, BS Hedley, ML Luby, TM AF Barbon, Christine M. Yang, Min Wands, Gregory D. Ramesh, Radha Slusher, Barbara S. Hedley, Mary Lynne Luby, Thomas M. TI Consecutive low doses of cyclophosphamide preferentially target T-regs and potentiate T cell responses induced by DNA PLG microparticle immunization SO CELLULAR IMMUNOLOGY LA English DT Article DE Poly(lactide-co-glycolide); PLG; Regulatory T cell; Avidity; Epitope-spreading; CYP1B1; Cyclophosphamide; Vaccine; Immunization; Treg ID IMMUNOLOGICAL SELF-TOLERANCE; CO-GLYCOLIDE MICROPARTICLES; ANTIGEN CYTOCHROME P4501B1; MURINE MELANOMA MODEL; GROWTH-FACTOR-BETA; REGULATORY-CELLS; IMMUNE-RESPONSE; IN-VIVO; TUMOR-IMMUNITY; CANCER-IMMUNOTHERAPY AB Cyclophosphamide in combination with immunotherapeutic approaches preferentially impinges on T-reg activity and allows for robust generation of T cell effectors. Reduced dosages of cyclophosphamide are necessary to restrict its cytotoxic effects to the negative regulatory cell populations while sparing effector lymphocytes. We investigated cyclophosphamide dosing in combination with ZYC300, a PLG-encapsulated plasmid DNA vaccine which encodes the cytochrome P450 family member, CYP1B1, a known human tumor-associated antigen. In mice, three consecutive, low doses of cyclophosphamide comprised a superior regimen in enhancing the magnitude, diversity of epitopes, and avidity to individual epitopes of specific T cell responses when compared to regimens that used either a single low or a single high dose. Consecutive low doses of cyclophosphamide predominantly targeted T-regs while sparing overall T lymphocyte counts. Thus, we report the synergistic activity of pharmacologic T-reg depletion with cyclophosphamide on quantitatively and qualitatively increasing T cell responses to a known human tumor-associated antigen. (C) 2010 Elsevier Inc. All rights reserved. C1 [Barbon, Christine M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Yang, Min; Wands, Gregory D.; Ramesh, Radha; Slusher, Barbara S.; Hedley, Mary Lynne; Luby, Thomas M.] Eisai Res Inst Inc, Andover, MA USA. RP Barbon, CM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ChristineM_Barbon@DFCI.harvard.edu NR 73 TC 15 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2010 VL 262 IS 2 BP 150 EP 161 DI 10.1016/j.cellimm.2010.02.007 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 582LO UT WOS:000276599100012 PM 20206921 ER PT J AU Lapaquette, P Glasser, AL Huett, A Xavier, RJ Darfeuille-Michaud, A AF Lapaquette, Pierre Glasser, Anne-Lise Huett, Alan Xavier, Ramnik J. Darfeuille-Michaud, Arlette TI Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly SO CELLULAR MICROBIOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ESCHERICHIA-COLI; ILEAL MUCOSA; LISTERIA-MONOCYTOGENES; MICROBIAL ANTIGENS; EPITHELIAL-CELLS; HIGH PREVALENCE; IRGM; SUSCEPTIBILITY AB Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to invade and to replicate within intestinal epithelial cells. Recent genome-wide association studies have highlighted the autophagy pathway as being associated with CD risk. In the present study we investigated whether defects in autophagy enhance replication of commensal and pathogenic Escherichia coli and CD-associated AIEC. We show that functional autophagy limits intracellular AIEC replication and that a subpopulation of the intracellular bacteria is located within LC3-positive autophagosomes. In IRGM and ATG16L1 deficient cells intracellular AIEC LF82 bacteria have enhanced replication. Surprisingly autophagy deficiency did not interfere with the ability of intracellular bacteria to survive and/or replicate for any other E. coli strains tested, including non-pathogenic, environmental, commensal, or pathogenic strains involved in gastroenteritis. Together these findings demonstrate a central role for autophagy restraining Adherent-Invasive E. coli strains associated with ileal CD. AIEC infection in patients with polymorphisms in autophagy genes may have a significant impact on the outcome of intestinal inflammation. C1 [Lapaquette, Pierre; Glasser, Anne-Lise; Darfeuille-Michaud, Arlette] Univ Clermont 1, JE2526, USC INRA 2018, F-63001 Clermont Ferrand, France. [Glasser, Anne-Lise; Darfeuille-Michaud, Arlette] Inst Univ Technol Genie Biol, F-63172 Aubiere, France. [Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02141 USA. [Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02141 USA. RP Darfeuille-Michaud, A (reprint author), Univ Clermont 1, JE2526, USC INRA 2018, F-63001 Clermont Ferrand, France. EM arlette.darfeuille-michaud@u-clermont1.fr FU Ministere de la Recherche et de la Technologie [JE2526]; INRA [USC-2018]; Association F. Aupetit (AFA); European Commission; NIH [AI062773, DK83756, DK043351] FX This study was supported by the Ministere de la Recherche et de la Technologie (JE2526), INRA (USC-2018) and by grants from the Association F. Aupetit (AFA), and European Commission through FP7 IBDase project. RJX is supported by the following grants from the NIH: AI062773, DK83756 and DK043351. We thank Professor Noboru Mizushima ( Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan) for providing MEFs deficient in Atg5, Professor Tamotsu Yoshimori (Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan) who kindly provided GFP-LC3, GFP-Atg5 and mAtg5 plamids. We also thank Christelle Blavignac and Claire Sczepaniak (CICS, Universite d'Auvergne, France) for technical assistance with electron microscopy and the CICS platform for confocal microscopy. NR 52 TC 142 Z9 147 U1 1 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JAN PY 2010 VL 12 IS 1 BP 99 EP 113 DI 10.1111/j.1462-5822.2009.01381.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 538CQ UT WOS:000273162200009 PM 19747213 ER PT J AU Yan, X Shen, H Jiang, HJ Hu, D Zhang, CS Wang, J Wu, XQ AF Yan, Xin Shen, Hua Jiang, Hongjian Hu, Dan Zhang, Chengsheng Wang, Jun Wu, Xinqi TI External Qi of Yan Xin Qigong Induces Apoptosis and Inhibits Migration and Invasion of Estrogen-Independent Breast Cancer Cells Through Suppression of Akt/NF-kappa B Signaling SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Breast cancer; Akt; NF-kappa B; External Qi of Yan Xin Qigong; Apoptosis; Metastasis ID CYTOCHROME-C RELEASE; PHOSPHATIDYLINOSITOL 3-KINASE; CASPASE ACTIVATION; MAJOR CULPRIT; IN-VITRO; PATHWAY; GROWTH; THERAPY; CONTRIBUTES; PROTEIN AB The antitumor effects of external Qi of Yan Xin Qigong (YXQ-EQ) have been widely described over the past three decades. To gain a better understanding of the mechanisms underlying YXQ-EQ's antitumor effects, in the present study we investigated its effects on growth, migration, invasion and apoptosis of breast cancer cells and the underlying molecular mechanisms. We show that YXQ-EQ treatment caused a time-dependent reduction in viability, blocked clonogenic growth and induced apoptosis in estrogen-independent breast cancer MDA-MB-231 cells. Furthermore, YXQ-EQ treatment blocked migration and invasion of MDA-MB-231 cells. Biochemically, YXQ-EQ treatment markedly inhibited constitutive and EGF-induced Akt phosphorylation. YXQ-EQ also substantially repressed NF-kappa B activity, resulting in decreased expression of anti-apoptotic Bcl-2, Bcl-X(L), XIAP and survivin proteins. These findings suggest that YXQ-EQ may induce apoptosis and inhibition of migration and invasion of MDA-MB-231 cells through the repression of Akt/NF-kappa B signaling. Copyright (C) 2010 S. Karger AG, Basel C1 [Jiang, Hongjian; Wu, Xinqi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jiang, Hongjian; Hu, Dan; Wu, Xinqi] Harvard Univ, Sch Med, Boston, MA USA. [Jiang, Hongjian; Wu, Xinqi] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zhang, Chengsheng] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Yan, Xin] Chongqing Inst Tradit Chinese Med, Chongqing, Peoples R China. [Yan, Xin; Shen, Hua; Wang, Jun] New Med Sci Res Inst, New York, NY USA. RP Wu, XQ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM xwu1@partners.org RI Hu, Dan/D-9642-2015 FU Yan Xin Foundation FX This work was supported in part by Yan Xin Foundation. NR 58 TC 7 Z9 7 U1 2 U2 24 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2010 VL 25 IS 2-3 BP 263 EP 270 DI 10.1159/000276560 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 543DY UT WOS:000273551900011 PM 20110687 ER PT S AU Xie, HF Laiosa, CV Graf, T AF Xie, Huafeng Laiosa, Catherine V. Graf, Thomas BE Ding, S TI Reprogramming of Committed Lymphoid Cells by Enforced Transcription Factor Expression SO CELLULAR PROGRAMMING AND REPROGRAMMING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reprogramming; Hematopoiesis; Transcription factor; Retrovirus; Lineage commitment ID HEMATOPOIETIC STEM-CELLS; LONG-TERM; PLASTICITY; DIFFERENTIATION; MACROPHAGES; BIOLOGY AB Reprogramming of committed cells from one lineage to another is possible in the hematopoietic system using enforced expression of transcription factors. Here we describe methods to convert committed B and T progenitors into macrophages. In order to obtain a labeled population of starting cells, we employ a lineage ancestry system using a cross between lineage-specific Cre recombinase mice and Rosa26 reporter mice. After infection of these well-defined cell populations with a transcription factor containing retroviral vector that also harbors an infection marker, cells are cultured under conditions permissive for both lymphoid and myeloid development. Multicolor flow cytomctry is then used to monitor changes in marker expression on the cell surface reflecting changes in cellular identity. These protocols may be modified to trace cellular reprogramming induced by other transcription factors and in other cellular contexts. C1 [Xie, Huafeng] Dana Farber Canc Inst, Boston, MA 02115 USA. [Laiosa, Catherine V.] Mt Sinai Hosp, New York, NY 10029 USA. [Graf, Thomas] Ctr Genom Regulat, Barcelona, Spain. [Graf, Thomas] ICREA, Barcelona, Spain. RP Xie, HF (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Graf, Thomas/B-4252-2015 OI Graf, Thomas/0000-0003-2774-4117 NR 17 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-690-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 636 BP 219 EP 232 DI 10.1007/978-1-60761-691-7_14 D2 10.1007/978-1-60761-691-7 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOK46 UT WOS:000276891700014 PM 20336526 ER PT S AU Yeh, JRJ Munson, KM AF Yeh, Jing-Ruey J. Munson, Kathleen M. BE Ding, S TI Zebrafish Small Molecule Screen in Reprogramming/Cell Fate Modulation SO CELLULAR PROGRAMMING AND REPROGRAMMING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Chemical screen; Zebrafish; Hematopoiesis; AML; Leukemia; Reprogramming; Cell fate; In vivo; Erythroid; Myeloid AB Embryonic zebrafish have long been used for lineage-tracing studies. In zebrafish embryos, the cell fate identities can be determined by whole-mount in situ hybridization, or by visualization of live embryos if using fluorescent reporter lines. We use embryonic zebrafish to study the effects of a leukemic oncogene AML1-ETO on modulating hematopoietic cell fate. Induced expression of AML1-ETO is able to efficiently reprogram hematopoietic progenitor cells from erythroid to myeloid cell fate. Using the zebrafish model of AML1-ETO, we performed a chemical screen to identify small molecules that suppress the cell fate switch in the presence of AML1-ETO. The methods discussed herein may be broadly applicable for identifying small molecules that modulate other cell fate decisions. C1 [Yeh, Jing-Ruey J.; Munson, Kathleen M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA USA. [Yeh, Jing-Ruey J.; Munson, Kathleen M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Yeh, JRJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA USA. FU NCI NIH HHS [R01 CA118498, R01 CA140188]; NIA NIH HHS [K01 AG031300-01A1, K01 AG031300, K01 AG031300-02, AG031300, K01 AG031300-03] NR 4 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-690-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 636 BP 317 EP 327 DI 10.1007/978-1-60761-691-7_20 D2 10.1007/978-1-60761-691-7 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOK46 UT WOS:000276891700020 PM 20336532 ER PT J AU Soo, Y Singhal, AB Leung, T Yu, S Mak, H Hao, Q Leung, H Lam, W Wong, LKS AF Soo, Y. Singhal, A. B. Leung, T. Yu, S. Mak, H. Hao, Q. Leung, H. Lam, W. Wong, L. K. S. TI Reversible cerebral vasoconstriction syndrome with posterior leucoencephalopathy after oral contraceptive pills SO CEPHALALGIA LA English DT Article DE reversible cerebral vasoconstriction syndrome; posterior leucoencephalopathy ID GUILLAIN-BARRE-SYNDROME; THUNDERCLAP HEADACHE; VASOSPASM; ANGIOPATHY; STROKE; DRUGS AB Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset recurrent 'thunderclap' headaches with reversible multifocal narrowing of the cerebral arteries, often associated with focal neurological deficits from ischaemic or haemorrhagic stroke. It has been associated with exposure to vasoconstrictive drugs, pregnancy, migraine, and a variety of other conditions. Whereas the pathophysiology of RCVS remains unclear, changes in the levels of female hormones are considered important because RCVS predominantly affects women and is frequently associated with pregnancy. We report a patient with angiographically confirmed RCVS whose MRI showed reversible brain oedema, suggesting an overlap between RCVS and the reversible posterior leucoencephalopathy syndrome. The only identified risk factor was oral contraceptive pills started 1 month prior to onset, supporting a role for female reproductive hormones in precipitating this overlap syndrome. C1 [Soo, Y.; Leung, T.; Hao, Q.; Leung, H.; Wong, L. K. S.] Chinese Univ Hong Kong, Div Neurol, Dept Med & Therapeut, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. [Singhal, A. B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Singhal, A. B.] Harvard Univ, Sch Med, Boston, MA USA. [Yu, S.; Mak, H.; Lam, W.] Chinese Univ Hong Kong, Dept Diagnost Radiol & Organ Imaging, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. RP Wong, LKS (reprint author), Chinese Univ Hong Kong, Div Neurol, Dept Med & Therapeut, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China. EM ks-wong@cuhk.edu.hk RI Leung, Thomas /O-8567-2015; Wong, Ka Sing Lawrence/N-3434-2015 OI Wong, Ka Sing Lawrence/0000-0002-2031-9866 NR 18 TC 11 Z9 11 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JAN PY 2010 VL 30 IS 1 BP 42 EP 45 DI 10.1111/j.1468-2982.2009.01868.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 557ED UT WOS:000274651500005 PM 20511194 ER PT J AU Hashimoto, R Lee, K Preus, A McCarley, RW Wible, CG AF Hashimoto, Ryu-ichiro Lee, KangUk Preus, Alexander McCarley, Robert W. Wible, Cynthia G. TI An fMRI Study of Functional Abnormalities in the Verbal Working Memory System and the Relationship to Clinical Symptoms in Chronic Schizophrenia SO CEREBRAL CORTEX LA English DT Article DE fMRI; functional connectivity; schizophrenia; verbal working memory ID SUPERIOR TEMPORAL SULCUS; SHORT-TERM-MEMORY; AUDITORY HALLUCINATIONS; HUMAN BRAIN; CONDUCTION APHASIA; CORTEX ACTIVATION; PLANUM TEMPORALE; WORD PRODUCTION; MATTER CHANGES; SOCIAL BRAIN AB There has been evidence for functional abnormalities of the verbal working memory system in schizophrenia. Verbal working memory crucially involves the interplay between the anterior and posterior language systems, and previous studies have shown converging evidence for abnormalities in the posterior language system in schizophrenia. In this functional magnetic resonance imaging study, we measured cortical activity in chronic schizophrenic patients and matched healthy controls during auditory and visual verbal working memory tasks. We employed 1) regional analyses specifically targeting the posterior language system and 2) analyses of functional connectivity between anterior and posterior language regions. We performed these analyses separately for each memory stage and modality. In the regional analyses, the left sylvian-parietal-temporal (Spt) area consistently showed reduced activation during encoding and retrieval stages in schizophrenia. Magnitudes of activation in the left posterior superior temporal sulcus were correlated with the severity of delusions at every memory stage. Functional connectivity analyses revealed reduced connectivity between the left Spt and the anterior insula during the encoding of auditory words. In addition, the connectivity strength was correlated with the severity of auditory hallucinations. These findings identify abnormal components in the verbal working memory system and illustrate their possible overlap with the mechanisms of core schizophrenic symptoms. C1 [Hashimoto, Ryu-ichiro; Lee, KangUk; Preus, Alexander; McCarley, Robert W.; Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Hashimoto, Ryu-ichiro; Lee, KangUk; Preus, Alexander; McCarley, Robert W.; Wible, Cynthia G.] Brockton VA Med Ctr, Dept Psychiat, Brockton, MA 02301 USA. [Hashimoto, Ryu-ichiro; Lee, KangUk; Preus, Alexander; McCarley, Robert W.; Wible, Cynthia G.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. [McCarley, Robert W.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP Hashimoto, R (reprint author), Univ Calif Davis, Ctr Mind & Brain, 202 Cousteau Pl,Suite 250, Davis, CA 95618 USA. EM rhashimoto@ucdavis.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU The National Institute of Mental Health [RO1 MH067080-01A2] FX The National Institute of Mental Health (RO1 MH067080-01A2) to C.G.W; the Department of Veterans Affairs, a Research Enhancement Award Program to R. W. M. NR 99 TC 30 Z9 31 U1 5 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2010 VL 20 IS 1 BP 46 EP 60 DI 10.1093/cercor/bhp079 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 531RH UT WOS:000272685000005 PM 19395526 ER PT J AU Hachinski, V Donnan, GA Gorelick, PB Hacke, W Cramer, SC Kaste, M Fisher, M Brainin, M Buchan, AM Lo, EH Skolnick, BE Furie, KL Hankey, GJ Kivipelto, M Morris, J Rothwell, PM Sacco, RL Smith, SC Wang, YL Bryer, A Ford, GA Iadecola, C Martins, SCO Saver, J Skvortsova, V Bayley, M Bednar, MM Duncan, P Enney, L Finklestein, S Jones, TA Kalra, L Kleim, J Nitkin, R Teasell, R Weiller, C Desai, B Goldberg, MP Heiss, WD Saarelma, O Schwamm, LH Shinohara, Y Trivedi, B Wahlgren, N Wong, LK Hakim, A Norrving, B Prudhomme, S Bornstein, NM Davis, SM Goldstein, LB Leys, D Tuomilehto, J AF Hachinski, Vladimir Donnan, Geoffrey A. Gorelick, Philip B. Hacke, Werner Cramer, Steven C. Kaste, Markku Fisher, Marc Brainin, Michael Buchan, Alastair M. Lo, Eng H. Skolnick, Brett E. Furie, Karen L. Hankey, Graeme J. Kivipelto, Miia Morris, John Rothwell, Peter M. Sacco, Ralph L. Smith, Sidney C., Jr. Wang, Yulun Bryer, Alan Ford, Gary A. Iadecola, Costantino Martins, Sheila C. O. Saver, Jeff Skvortsova, Veronika Bayley, Mark Bednar, Martin M. Duncan, Pamela Enney, Lori Finklestein, Seth Jones, Theresa A. Kalra, Lalit Kleim, Jeff Nitkin, Ralph Teasell, Robert Weiller, Cornelius Desai, Bhupat Goldberg, Mark P. Heiss, Wolf-Dieter Saarelma, Osmo Schwamm, Lee H. Shinohara, Yukito Trivedi, Bhargava Wahlgren, Nils Wong, Lawrence K. Hakim, Antoine Norrving, Bo Prudhomme, Stephen Bornstein, Natan M. Davis, Stephen M. Goldstein, Larry B. Leys, Didier Tuomilehto, Jaakko TI Stroke: Working toward a Prioritized World Agenda SO CEREBROVASCULAR DISEASES LA English DT Article DE Prevention; Rehabilitation; Stroke; Translational; Treatment ID RECOMMENDATIONS; VALIDATION; CENTERS; SCREEN AB Background and Purpose: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods: Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (e. g., social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions: To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. Copyright (C) 2010 American Heart Association. Inc., S. Karger AG, Basel, and John Wiley & Sons, Inc. C1 [Hachinski, Vladimir] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON N6A 5A5, Canada. [Teasell, Robert] St Josephs Healthcare London, London, ON, Canada. [Bayley, Mark] Toronto Rehabil Inst, Toronto, ON, Canada. [Hakim, Antoine] Univ Ottawa, Canadian Stroke Network, Ottawa, ON, Canada. [Hakim, Antoine] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Donnan, Geoffrey A.] Florey Neurosci Inst, Carlton S Victoria, Australia. [Davis, Stephen M.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Davis, Stephen M.] Univ Melbourne, Melbourne, Vic, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Gorelick, Philip B.] Univ Illinois, Chicago, IL USA. [Trivedi, Bhargava] So Illinois Healthcare, Carbondale, IL USA. [Cramer, Steven C.] Univ Calif Irvine, Orange, CA 92668 USA. [Desai, Bhupat] Pomona Valley Hosp Med Ctr, Pomona, CA USA. [Wang, Yulun] InTouch Hlth, Goleta, CA USA. [Saver, Jeff] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA. [Lo, Eng H.; Furie, Karen L.] Massachusetts Gen Hosp, Charlestown, MA USA. [Finklestein, Seth] Biotrofix Inc, Waltham, MA USA. [Skolnick, Brett E.] Novo Nordisk AS, Princeton, NJ USA. [Morris, John; Goldberg, Mark P.] Washington Univ, Sch Med, St Louis, MO USA. [Sacco, Ralph L.] Univ Miami, AHA, Miami, FL USA. [Kleim, Jeff] Univ Florida, Gainesville, FL USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Duncan, Pamela; Goldstein, Larry B.] Duke Univ, Durham, NC USA. [Enney, Lori] GlaxoSmithKline Inc, Durham, NC USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Iadecola, Costantino] Weill Cornell Med Coll, New York, NY USA. [Bednar, Martin M.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA. [Jones, Theresa A.] Univ Texas Austin, Austin, TX 78712 USA. [Nitkin, Ralph] NICHHD, Natl Ctr Med Rehabil, NIH, Rockville, MD USA. [Prudhomme, Stephen] Amer Heart Assoc, Dallas, TX USA. [Hacke, Werner] Univ Heidelberg, Heidelberg, Germany. [Weiller, Cornelius] Univ Freiburg, Freiburg, Germany. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany. [Kaste, Markku] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Saarelma, Osmo] Terveystalo Med Ctr, Helsinki, Finland. [Brainin, Michael] Univ Donau Univ Krems, Krems, Austria. [Buchan, Alastair M.] Univ Oxford, Oxford, England. [Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Ford, Gary A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Kalra, Lalit] Kings Coll London, London WC2R 2LS, England. [Wahlgren, Nils] Karolinska Inst, Stockholm, Sweden. [Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden. [Smith, Sidney C., Jr.] World Heart Federat, Geneva, Switzerland. [Bryer, Alan] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Bryer, Alan] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Martins, Sheila C. O.] Hosp Clin, Porto Alegre, RS, Brazil. [Skvortsova, Veronika] Russian State Res Stroke Inst, Moscow, Russia. [Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan. [Wong, Lawrence K.] Chinese Univ Hong Kong, Sha Tin, Hong Kong, Peoples R China. [Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Leys, Didier] Univ Lille Nord France, Lille, France. RP Hachinski, V (reprint author), Univ Western Ontario, Univ Hosp, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM Vladimir.Hachinski@lhsc.on.ca RI Skolnick, Brett/B-5140-2009; Buchan, Alastair/B-9095-2009; OI Buchan, Alastair/0000-0002-2918-5200; Norrving, Bo/0000-0002-8024-5096; Schwamm, Lee/0000-0003-0592-9145; Kivipelto, Miia/0000-0003-0992-3875; Donnan, Geoffrey/0000-0001-6324-3403; Saver, Jeffrey/0000-0001-9141-2251; Kaste, Markku/0000-0001-6557-6412 FU AHA/ASA; World Federation of Neurology; WSO; ESO; European Stroke Conference; Canadian Stroke Network; Heart & Stroke Foundation; Lippincott Williams Wilkins; National Institute of Neurological Disorders and Stroke FX We thank Gary Houser and his Stroke Group for expert help in organizing the Synergium. Warm thanks to Yvette Ballantyne and the AHA staff for help with the organization and registration for the Synergium. We thank the supporting organizations of the Synergium: AHA/ASA, World Federation of Neurology, WSO, ESO, European Stroke Conference, Canadian Stroke Network, Heart & Stroke Foundation Centre for Stroke Recovery, and Lippincott Williams & Wilkins. The views and conclusions of the synergium are that of the participants and contributors and not necessarily those of the supporting organizations.; The Synergium authors appreciate the input of Drs Walter Koroshetz and Petra Kaufmann as well as the financial support of the National Institute of Neurological Disorders and Stroke. NR 8 TC 14 Z9 14 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 2 BP 127 EP 147 DI 10.1159/000315099 PG 21 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XB UT WOS:000280461800004 PM 20516682 ER PT J AU Guo, SZ Stins, M Ning, MM Lo, EH AF Guo, Shuzhen Stins, Monique Ning, MingMing Lo, Eng H. TI Amelioration of Inflammation and Cytotoxicity by Dipyridamole in Brain Endothelial Cells SO CEREBROVASCULAR DISEASES LA English DT Article DE Neurovascular; Inflammation; Blood-brain barrier; Stroke ID NECROSIS-FACTOR-ALPHA; CEREBRAL-ARTERY OCCLUSION; ASPIRIN PLUS DIPYRIDAMOLE; GENE KNOCK-OUT; MATRIX METALLOPROTEINASES; CEREBROVASCULAR-DISEASE; NEUTROPHIL ADHESION; IN-VITRO; ISCHEMIA; STROKE AB Background: Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults. Methods: Human brain endothelial cells were grown in culture, and exposed to TNF alpha (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase- 2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability. Results: Exposure of human brain endothelial cells to TNF alpha (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNF alpha did not alter PECAM-1. Dipyridamole (1-5 mu M) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult. Conclusions: These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in stroke patients remains to be elucidated. Copyright (C) 2010 S. Karger AG, Basel C1 [Guo, Shuzhen; Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Guo, Shuzhen; Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Clin Prote Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stins, Monique] Johns Hopkins Med Ctr, Dept Neurol, Baltimore, MD USA. RP Guo, SZ (reprint author), MGH E 149-2401, Boston, MA 02129 USA. EM sguo@partners.org FU NIH; American Heart Association; Boehringer-Ingelheim FX This study was supported in part by grants from the NIH, a Bugher award from the American Heart Association, and a grant from Boehringer-Ingelheim to S. NR 37 TC 23 Z9 23 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 3 BP 290 EP 296 DI 10.1159/000319072 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XD UT WOS:000280462000010 PM 20664263 ER PT J AU Jacqmin, M Herve, D Viswanathan, A Guichard, JP During, M Dichgans, M Chabriat, H AF Jacqmin, Mathilde Herve, Dominique Viswanathan, Anand Guichard, Jean-Pierre During, Marco Dichgans, Martin Chabriat, Hugues TI Confluent Thalamic Hyperintensities in CADASIL SO CEREBROVASCULAR DISEASES LA English DT Article DE Thalamus; CADASIL; MRI; T(2)-hyperintensities; Demyelination ID AUTOSOMAL-DOMINANT ARTERIOPATHY; CONDITION CAUSING STROKE; SUBCORTICAL INFARCTS; LACUNAR LESIONS; LEUKOENCEPHALOPATHY; BRAIN; DEMENTIA; MATTER; PATTERNS; DISEASE AB Background: CADASIL is responsible for diffuse hyperintensities in the white matter on FLAIR images. These lesions are often associated with focal lesions in the basal ganglia such as lacunar infarctions. The prevalence and significance of diffuse or confluent thalamic hyperintensities (CTH) remain unknown. Methods: The frequency of hyperintensities on FLAIR images in the thalamus was assessed in 147 CADASIL patients, and signal abnormalities on both FLAIR and T(1)-weighted images were categorized as focal/punctuate or diffuse/confluent by the same reader. The areas of increased diffusion were also analyzed on apparent diffusion coefficient maps. The association of CTH with vascular risk factors, the main clinical manifestations of the disease and MRI markers (brain parenchymal fraction, volume of white matter hyperintensities, volume of lacunar infarcts and number of microbleeds) was analyzed with generalized linear regression models. Results: CTH were detected in 12% of the CADASIL subjects in association with hypointensities on T(1)-weighted images. CTH corresponded to areas of increased diffusion apparent diffusion coefficient maps. CTH were found significantly associated with age and independently related to the volume of white matter hyperintensities but not to that of lacunar infarctions or to cerebral atrophy after adjustment for age and sex. No significant association was found between CTH and global cognitive performances. Conclusion: CTH are observed on FLAIR images in a sizeable proportion of CADASIL patients. They are mainly related to the extent of white matter hyperintensities and do not correlate with cognitive decline. Demyelination and/or loss of glial cells appear to be the most plausible cause of these confluent signal changes in the thalamus. Copyright (C) 2010 S. Karger AG, Basel C1 [Jacqmin, Mathilde; Herve, Dominique; Chabriat, Hugues] CHU Lariboisiere, Serv Neurol, Ctr Reference Malad Rares Vaisseaux Cerveau & Oei, INSERM,U740,APHP, Paris, France. [Guichard, Jean-Pierre] CHU Lariboisiere, Serv Neuroradiol, APHP, Paris, France. [Chabriat, Hugues] Univ Paris 07, INSERM, UMR740, Fac Med Villemin, Paris, France. [Viswanathan, Anand] Harvard Univ, Sch Med, Boston, MA USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. [During, Marco; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany. RP Chabriat, H (reprint author), Hop Lariboisiere, Serv Neurol, 2 Rue Ambroise Pare, FR-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI Chabriat, Hugues/G-5699-2010 OI Chabriat, Hugues/0000-0001-8436-6074 FU DRC/APHP [AOR 02-001] FX This work was supported by PHRC grant AOR 02-001 (DRC/APHP) and performed with the help of ARNEVA (Association de Recherche en Neurologie Vasculaire), Hopital Lariboisiere, France, and under the corporate patronage of the Bouygues Company. NR 30 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 3 BP 308 EP 313 DI 10.1159/000319607 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XD UT WOS:000280462000013 PM 20664266 ER PT J AU Silva, GS Lima, FO Camargo, ECS Smith, WS Lev, MH Harris, GJ Halpern, EF Koroshetz, W Furie, KL AF Silva, Gisele S. Lima, Fabricio O. Camargo, Erica C. S. Smith, Wade S. Lev, Michael H. Harris, Gordon J. Halpern, Elkan F. Koroshetz, Walter Furie, Karen L. TI Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion SO CEREBROVASCULAR DISEASES LA English DT Article DE Sex differences; Ischemic stroke; CT angiography ID TISSUE-PLASMINOGEN ACTIVATOR; SEX-BASED DIFFERENCES; CARE; REGISTRY; WOMEN; TRIAL; MORTALITY AB Background: The reasons for gender disparities in stroke outcome remain unclear, and little is known about the value of acute neuroimaging characteristics in elucidating differential stroke outcomes between the sexes. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography (CTA) was performed in all patients within 24 h of symptom onset. CTA source images were used to evaluate lesion volume. The primary outcome measure was a modified Rankin scale (mRS) score >= 3 at 6 months. Results: We evaluated 676 consecutive patients (322 women). Women were older than men (p < 0.01), more frequently had a prestroke mRS >0 (p < 0.01), and had higher admission National Institutes of Health Stroke scale scores (p = 0.01). More women had intracranial artery occlusions than men (46 vs. 33.1%, p = 0.01), but there was no significant difference between ischemic lesion volumes (p = 0.21). Using multiple regression, female gender remained an independent predictor of poor mRS scores at 6 months (odds ratio 1.57; 95% confidence interval 1.02-2.36) after adjustment for clinical and imaging covariates. Conclusion: Compared with men, women are less likely to achieve independence after acute ischemic stroke. The disparity in stroke outcome is not explained by differences in ischemic lesion volume or the presence of intracranial artery occlusions. Copyright (C) 2010 S. Karger AG, Basel C1 [Silva, Gisele S.; Lima, Fabricio O.; Camargo, Erica C. S.; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lev, Michael H.; Harris, Gordon J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Silva, Gisele S.] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Silva, GS (reprint author), 741 Altino Arantes Ave,Apt 81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; National Institutes of Health [P50NS051343]; Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Lakeside Foundation FX Sources of funding: supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392 and National Institutes of Health grant P50NS051343. We gratefully acknowledge the support of the Deane Institute for Integrative Research in Stroke and Atrial Fibrillation and the Lakeside Foundation. NR 32 TC 21 Z9 21 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 30 IS 5 BP 470 EP 475 DI 10.1159/000317088 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 661TY UT WOS:000282752200006 PM 20733301 ER PT J AU Hannon, N Sheehan, O Kelly, L Marnane, M Merwick, A Moore, A Kyne, L Duggan, J Moroney, J McCormack, PME Daly, L Fitz-Simon, N Harris, D Horgan, G Williams, EB Furie, KL Kelly, PJ AF Hannon, Niamh Sheehan, Orla Kelly, Lisa Marnane, Michael Merwick, Aine Moore, Alan Kyne, Lorraine Duggan, Joseph Moroney, Joan McCormack, Patricia M. E. Daly, Leslie Fitz-Simon, Nicola Harris, Dawn Horgan, Gillian Williams, Emma B. Furie, Karen L. Kelly, Peter J. TI Stroke Associated with Atrial Fibrillation - Incidence and Early Outcomes in the North Dublin Population Stroke Study SO CEREBROVASCULAR DISEASES LA English DT Article DE Atrial fibrillation; Stroke prevention; Anticoagulation ID ACUTE ISCHEMIC-STROKE; RISK-FACTORS; PREVALENCE; MORTALITY; ANTICOAGULATION; PROGNOSIS; THERAPY AB Background: Prospective population-based studies are important to accurately determine the incidence and characteristics of stroke associated with atrial fibrillation (AF), while avoiding selection bias which may complicate hospital-based studies. Methods: We investigated AF-associated stroke within the North Dublin Population Stroke Study, a prospective cohort study of stroke/transient ischaemic attack in 294,592 individuals, according to recommended criteria for rigorous stroke epidemiological studies. Results: Of 568 stroke patients ascertained in the first year, 31.2% (177/568) were associated with AF (90.4%, i.e. 160/177 ischaemic infarcts). The crude incidence rate of all AF-associated stroke was 60/100,000 person-years (95% CI = 52-70). Prior stroke was almost twice as common in AF compared to non-AF groups (21.9 vs. 12.8%, p = 0.01). The frequency of AF progressively increased across ischaemic stroke patients stratified by increasing stroke severity (NIHSS 0-4, 29.7%; 5-9, 38.1%; 10-14, 43.8%; >= 15, 53.3%, p < 0.0001). The 90-day trajectory of recovery of AF-associated stroke was identical to that of non-AF stroke, but Rankin scores in AF stroke remained higher at 7, 28 and 90 days (p < 0.001 for all). Discussion: AF-associated stroke occurred in one third of all patients and was associated with a distinct profile of recurrent, severe and disabling stroke. Targeted strategies to increase anticoagulation rates may provide a substantial benefit to prevent severe disabling stroke at a population level. Copyright (C) 2009 S. Karger AG, Basel C1 [Kelly, Peter J.] Mater Univ Hosp, Catherine McAuley Res Ctr, Neurovasc Clin Sci Unit, Dublin 7, Ireland. [Moore, Alan; Moroney, Joan] Beaumont Hosp, Dublin 9, Ireland. [McCormack, Patricia M. E.] Connolly Hosp, Dublin, Ireland. [Daly, Leslie; Fitz-Simon, Nicola] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland. [Furie, Karen L.] Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Mater Univ Hosp, Catherine McAuley Res Ctr, Neurovasc Clin Sci Unit, Nelson St, Dublin 7, Ireland. EM ndpss@mater.ie RI Merwick, Aine/L-9754-2013 OI Merwick, Aine/0000-0001-7533-0117 FU NINDS NIH HHS [P50NS051343, P50 NS051343] NR 29 TC 71 Z9 73 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 29 IS 1 BP 43 EP 49 DI 10.1159/000255973 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 523WU UT WOS:000272106300007 PM 19893311 ER PT J AU Silva, GS Lima, FO Camargo, ECS Smith, WS Singhal, AB Greer, DM Ay, H Lev, MH Harris, GJ Halpern, EF Sonni, S Koroshetz, W Furie, KL AF Silva, Gisele S. Lima, Fabricio O. Camargo, Erica C. S. Smith, Wade S. Singhal, Aneesh B. Greer, David M. Ay, Hakan Lev, Michael H. Harris, Gordon J. Halpern, Elkan F. Sonni, Shruti Koroshetz, Walter Furie, Karen L. TI Wake-Up Stroke: Clinical and Neuroimaging Characteristics SO CEREBROVASCULAR DISEASES LA English DT Article DE Wake-up stroke; Computed tomography angiography; Computed tomography perfusion; Ischemic penumbra ID ACUTE ISCHEMIC-STROKE; PERFUSION COMPUTED-TOMOGRAPHY; INTRACEREBRAL HEMORRHAGE; THROMBOLYTIC THERAPY; SOURCE IMAGES; DIFFUSION; TRIAL; ONSET; MRI; CT AB Background: Approximately 25% of ischemic stroke patients awaken with neurological deficits. In these patients, in whom the time from symptom onset is uncertain, brain imaging is a potential strategy to characterize the ischemia duration and the presence of salvageable brain tissue. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography and CT perfusion (CTP) were performed in patients within 24 h of symptom onset. The patients were classified into 'known onset', 'indefinite onset but not on awakening' and 'wake-up stroke' groups. Results: Of 676 patients evaluated, 420 had known-onset strokes, 131 wake-up strokes and 125 strokes with an indefinite time of symptom onset. Ischemic lesion volumes were higher in patients with indefinite-onset strokes ( p = 0.04). The frequencies of CTP mismatch and of large-vessel intracranial occlusions were similar among the groups ( p = 0.9 and p = 0.2, respectively). Conclusion: The considerable prevalence of CTP mismatch and of intracranial artery occlusions in our patients with wake-up strokes suggests that arterial and perfusion imaging might be particularly important in this population. Revised indications for thrombolysis by using imaging-based protocols might offer these patients the prospect of receiving acute stroke treatment even without a clear time of symptom onset. Copyright (C) 2010 S. Karger AG, Basel C1 [Silva, Gisele S.; Lima, Fabricio O.; Camargo, Erica C. S.; Singhal, Aneesh B.; Greer, David M.; Sonni, Shruti; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ay, Hakan; Lev, Michael H.; Harris, Gordon J.; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter] NINDS, Bethesda, MD 20892 USA. [Silva, Gisele S.] Univ Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Silva, GS (reprint author), 741 Altino Arantes Ave Apt 81, BR-04042033 Sao Paulo, Brazil. EM giselesampaio@hotmail.com RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU NIH [AHRQ R01 HS11392] FX This study was supported by NIH grant AHRQ R01 HS11392 (K.L.F.). NR 23 TC 45 Z9 45 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2010 VL 29 IS 4 BP 336 EP 342 DI 10.1159/000278929 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 588DU UT WOS:000277048400004 PM 20130399 ER PT S AU Lucas, MR AF Lucas, Michele R. BE Raffa, RB Tallarida, RJ TI The Impact of Chemo Brain on the Patient with a High-Grade Glioma SO CHEMO FOG: CANCER CHEMOTHERAPY-RELATED COGNITIVE IMPARIMENT SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID QUALITY-OF-LIFE; TUMORS AB Health-related quality of life for patients with high-grade gliomas has always been poor. The multiple insults to the brain-tumor existence and surgical procedures, irradiation, the level of stress and anxiety suffered and the adjuvant medications-steroids and anti-convulsants, all combine to diminish their health-related quality of life. Prior to the development of chemotherapy agents capable of penetrating the blood brain barrier, prognosis was 6 to 18 months. Life expectancy was short and there was little time to address the health-related quality of life. The newer agents have served to extend life, but have added another condition to the existing poor health-related quality of life, i.e., chemo brain. Chemo brain affects all cognitive function. The patients have great difficulty processing information. They have reduced attentional and concentration capability and cannot learn new information. The overall impact on their lives renders them unemployable and places a great burden on their families and on society. This chapter provides an overview of the patient experience and the burden placed on their families and on society. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Lucas, MR (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St YAW 9E, Boston, MA 02114 USA. EM mrlucas@partners.org NR 16 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6305-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 678 BP 21 EP 25 D2 10.1007/978-1-4419-6306-2 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA BPI52 UT WOS:000278923900005 PM 20738003 ER PT S AU Dietrich, J AF Dietrich, Joerg BE Raffa, RB Tallarida, RJ TI Chemotherapy Associated Central Nervous System Damage SO CHEMO FOG: CANCER CHEMOTHERAPY-RELATED COGNITIVE IMPARIMENT SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID NEURAL STEM-CELLS; BREAST-CANCER PATIENTS; RECEIVING ADJUVANT CHEMOTHERAPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; STANDARD-DOSE CHEMOTHERAPY; GLIAL PRECURSOR CELL; WHITE-MATTER CHANGES; ADULT HUMAN BRAIN; COGNITIVE FUNCTION; SUBVENTRICULAR ZONE AB Chemotherapy is commonly associated with harmful effects to multiple organ systems, including the central nervous system (CNS). Neurotoxicity may manifest as both acute and delayed complications, which is particularly a concern for long-term survivors. Patients may experience a wide range of neurotoxic syndromes, ranging from neuro-vascular complications and focal neurological deficits to generalized neurological decline with cognitive impairment, cortical atrophy and white matter abnormalities. Along with the use of more aggressive and combined treatment modalities and prolonged survival of cancer patients, neurological complications have been observed with increasing frequency. The mechanisms by which cancer therapy, including chemotherapy and radiation, result in neurological complications, have been poorly understood. Recent studies have now started to unravel the cell-biological basis for commonly seen neurotoxic syndromes and have provided compelling explanations for delayed neurological complications, such as cognitive decline, progressive myelin disruption and brain atrophy. C1 [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MGH Canc Ctr, Boston, MA 02114 USA. [Dietrich, Joerg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. RP Dietrich, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MGH Canc Ctr, 55 Fruit St Yawkey 9E, Boston, MA 02114 USA. EM jdietrich1@partners.org NR 82 TC 13 Z9 14 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6305-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 678 BP 77 EP 85 D2 10.1007/978-1-4419-6306-2 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA BPI52 UT WOS:000278923900011 PM 20738009 ER PT J AU Ogale, SS Lee, TA Au, DH Boudreau, DM Sullivan, SD AF Ogale, Sarika S. Lee, Todd A. Au, David H. Boudreau, Denise M. Sullivan, Sean D. TI Cardiovascular Events Associated With Ipratropium Bromide in COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; RISK; ANTICHOLINERGICS; MORTALITY; DEATH; EXACERBATIONS; METAANALYSIS; HEALTH; ASTHMA AB Background: Studies have suggested an increased risk of cardiovascular morbidity and mortality associated with the use of ipratropium bromide. We sought to examine the association between ipratropium bromide use and the risk of cardiovascular events (CVEs). Methods: We performed a cohort study of 82,717 US veterans with a new diagnosis of COPD between 1999 and 2002. Subjects were followed until they had their first hospitalization for a CVE (acute coronary syndrome, heart failure, or cardiac dysrhythmia), they died, or the end of the Study period (September 30,2004). Cumulative anticholinergic exposure was calculated as the number 4 30-day equivalents (ipratropium bromide) within the past year. We used Cox regression models with time-dependent covariates to estimate the risk of CAT associated with anticholinergic exposure and to adjust for potential confounders, including markers of COPD severity and cardiovascular risk. Results: We identified 6,234 CVEs (44% heart failure, 28% acute coronary syndrome, 28% dysrhythmia). Compared with subjects not exposed to anticholinergics within the past year, any exposure to anticholinergics within the past 6 months was associated with an increased risk of CVE (hazard ratio [95% CI] for <= four and > four 30-day equivalents: 1.40 [1.30-1.51] and 1.23 [1.13-1.36], respectively). Among subjects who received anticholinergics more than 6 months prior, there did not appear to be elevated risk of a CVE. Conclusions: We found an increased risk of CVEs associated with the use of ipratropium bromide within the past 6 months. These findings are consistent with previous concerns raised about the cardiovascular safety of ipratropium bromide. CHEST 2010; 137(1):13-19 C1 [Lee, Todd A.] Hines VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Ogale, Sarika S.; Boudreau, Denise M.; Sullivan, Sean D.] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Dept Pharm, Seattle, WA 98195 USA. [Lee, Todd A.] Univ Illinois, Ctr Pharmacoecon Res, Chicago, IL USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Practice, Chicago, IL USA. [Au, David H.] Univ Washington, Hlth Serv Res & Dev, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Au, David H.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Boudreau, Denise M.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. RP Lee, TA (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151-H, Hines, IL 60141 USA. EM todd.lee@va.gov FU US Department of Veterans Affairs Health Services Research and Development [IIR 03-307] FX This research was funded by the US Department of Veterans Affairs Health Services Research and Development (IIR 03-307) NR 14 TC 43 Z9 44 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2010 VL 137 IS 1 BP 13 EP 19 DI 10.1378/chest.08-2367 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 542DK UT WOS:000273471500007 PM 19363211 ER PT J AU Platt, AB Kuna, ST Field, SH Chen, Z Gupta, R Roche, DE Christie, JD Asch, DA AF Platt, Alec B. Kuna, Samuel T. Field, Samuel H. Chen, Zhen Gupta, Rajesh Roche, Dominic E. Christie, Jason D. Asch, David A. TI Adherence to Sleep Apnea Therapy and Use of Lipid-Lowering Drugs A Study of the Healthy-User Effect SO CHEST LA English DT Article ID POSITIVE AIRWAY PRESSURE; PLACEBO-CONTROLLED TRIAL; INDEPENDENT RISK-FACTOR; BLOOD-PRESSURE; CARDIOVASCULAR OUTCOMES; MEDICATION ADHERENCE; PRACTICE PARAMETERS; DAYTIME SLEEPINESS; FOLLOW-UP; CPAP USE AB Background: Evidence that continuous positive airway pressure (CPAP) reduces cardiovascular morbidity comes largely from observational studies. This association may be confounded if CPAP adherents are healthier in ways not measured by investigators. We assessed whether patients adhering to lipid-lowering medications were more adherent to CPAP. Methods: This was a retrospective cohort study undertaken at the Philadelphia Veterans Affairs (VA) Medical Center (2005-2006) of consecutive patients on lipid-lowering therapy newly initiating CPAP for obstructive sleep apnea. Adherence to medications dispensed via the VA closed-pharmacy system was measured as the proportion of days covered (>= 80% vs <80%) in the year prior to CPAP initiation. CPAP adherence was defined as >= 4 h/d of "mask-on" time, measured electronically daily during the first week of CPAP, We examined the association between medication adherence and CPAP adherence using multivariable logistic regression. Results: Complete data were available for 117 of 142 (81.5%) subjects. After adjustment for age, race, medical comorbidity, and sleep apnea-related clinical factors, subjects with low medication adherence demonstrated a 40.1% (95% CI, 30.0-51.0) probability of using CPAP >= 4 h/d compared with 55.2% (95% CI, 46.9-63.1) for subjects with adequate (>= 80%) medication adherence (adjusted for comparison, odds ratio (OR) = 1.8 [95% CI, 1.0-3.3], P = .04). Married patients were more adherent to medications and CPAP; inclusion of this factor reduced to nonsignificance the association of medication and CPAP adherence (OR = 1.6 [95% CI, 0.9-2.8], P = .12). Conclusion: Patients consistently refilling lipid-lowering medications were more adherent to CPAP, suggesting that differences in medication adherence or other health-promoting behaviors should be investigated in future nonrandomized, observational studies linking CPAP adherence and cardiovascular outcomes. CHEST 2010; 137(1).102-108 C1 [Platt, Alec B.; Kuna, Samuel T.; Field, Samuel H.; Roche, Dominic E.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Gupta, Rajesh] Philadelphia Vet Affairs Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA USA. [Kuna, Samuel T.; Christie, Jason D.; Asch, David A.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Christie, Jason D.; Asch, David A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Platt, Alec B.] Reading Hosp Med Ctr, Reading, PA USA. [Field, Samuel H.] Univ N Carolina, FPG Child Dev Inst, Chapel Hill, NC USA. [Chen, Zhen] NICHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Platt, AB (reprint author), 2608 Keiser Blvd, Wyomissing, PA 19610 USA. EM alecplatt@gmail.com OI Asch, David/0000-0002-7970-286X FU Center for Health Equity Research and Promotion; Philadelphia VA Medical Center, Philadelphia, PA; National Institutes of Health [T-32 HL07713-14] FX This study was supported by grant funding to Dr Platt from Center for Health Equity Research and Promotion, Philadelphia VA Medical Center, Philadelphia, PA. Dr Platt was supported by a training grant from National Institutes of Health [Grant T-32 HL07713-14]. NR 51 TC 23 Z9 25 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2010 VL 137 IS 1 BP 102 EP 108 DI 10.1378/chest.09-0842 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 542DK UT WOS:000273471500019 PM 19820075 ER PT J AU Kasper, J AF Kasper, Jennifer TI The Relevance of U.S. Ratification of the Convention on the Rights of the Child for Child Health: A Matter of Equity and Social Justice SO CHILD WELFARE LA English DT Article ID UNITED-STATES; CARE; PROGRAM; ASTHMA; INDEX; PEDIATRICS; MORTALITY; POVERTY; HUNGER; YOUTH AB The United Nations Convention on the Rights of the Child (CRC) is a universally accepted tool to understand the social underpinnings of child health that medicine alone cannot address. Injustices plague U.S. society: Child poverty has been increasing since 2000, and the gap between the wealthiest and poorest is growing. Poverty is a toxic stress on child health and well-being. Three articles from the CRC help frame how to address this: nondiscrimination, the right to enjoy the highest attainable standard of health and access to health care, and the right to a standard of living adequate for complete development. C1 [Kasper, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kasper, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kasper, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 48 TC 1 Z9 1 U1 2 U2 6 PU CHILD WELFARE LEAGUE AMER INC PI ARLINGTON PA 2345 CRYSTAL DR, STE 250, ARLINGTON, VA 22202 USA SN 0009-4021 J9 CHILD WELFARE JI Child Welf. PY 2010 VL 89 IS 5 SI SI BP 21 EP 36 PG 16 WC Family Studies; Social Work SC Family Studies; Social Work GA 721DQ UT WOS:000287333400003 PM 21361155 ER PT J AU Peterson, PN Rumsfeld, JS Liang, L Albert, NM Hernandez, AF Peterson, ED Fonarow, GC Masoudi, FA AF Peterson, Pamela N. Rumsfeld, John S. Liang, Li Albert, Nancy M. Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. Masoudi, Frederick A. CA Amer Heart Assoc Get Guidelines TI A Validated Risk Score for In-Hospital Mortality in Patients With Heart Failure From the American Heart Association Get With the Guidelines Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE epidemiology; heart failure; mortality; registries; risk factors ID PREDICTING MORTALITY; MODEL; STRATIFICATION; SURVIVAL AB Background-Effective risk stratification can inform clinical decision-making. Our objective was to derive and validate a risk score for in-hospital mortality in patients hospitalized with heart failure using American Heart Association Get With the Guidelines-Heart Failure (GWTG-HF) program data. Methods and Results-A cohort of 39 783 patients admitted January 1, 2005, to June 26, 2007, to 198 hospitals participating in GWTG-HF was divided into derivation (70%, n = 27 850) and validation (30%, n = 11 933) samples. Multivariable logistic regression identified predictors of in-hospital mortality in the derivation sample from candidate demographic, medical history, and laboratory variables collected at admission. In-hospital mortality rate was 2.86% (n = 1139). Age, systolic blood pressure, blood urea nitrogen, heart rate, sodium, chronic obstructive pulmonary disease, and nonblack race were predictive of in-hospital mortality. The model had good discrimination in the derivation and validation datasets (c-index, 0.75 in each). Effect estimates from the entire sample were used to generate a mortality risk score. The predicted probability of in-hospital mortality varied more than 24-fold across deciles (range, 0.4% to 9.7%) and corresponded with observed mortality rates. The model had the same operating characteristics among those with preserved and impaired left ventricular systolic function. The morality risk score can be calculated on the Web-based calculator available with the GWTG-HF data entry tool. Conclusions-The GWTG-HF risk score uses commonly available clinical variables to predict in-hospital mortality and provides clinicians with a validated tool for risk stratification that is applicable to a broad spectrum of patients with heart failure, including those with preserved left ventricular systolic function. (Circ Cardiovasc Qual Outcomes. 2010; 3: 25-32.) C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Peterson, Pamela N.; Rumsfeld, John S.; Masoudi, Frederick A.] Univ Colorado Denver, Denver, CO USA. [Peterson, Pamela N.; Rumsfeld, John S.; Masoudi, Frederick A.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Liang, Li; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Albert, Nancy M.] Cleveland Clin, Cleveland, OH 44106 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Masoudi, FA (reprint author), Div Cardiol, Mail Code 0960,777 Bannock St, Denver, CO 80204 USA. EM fred.masoudi@ucdenver.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU GlaxoSmithKline; American Heart Association Pharmaceutical Roundtable [067001N]; American Heart Association [0675060N]; Johnson Johnson/Scios; Medtronic; Merck; Novartis; AstraZeneca; Amgen; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; American College of Cardiology; Oklahoma Foundation for Medical Quality FX GWTG-HF was supported in part by an unrestricted educational grant from GlaxoSmithKline. Dr Peterson is supported by an American Heart Association Pharmaceutical Roundtable Grant (067001N) and an American Heart Association Young Investigator Database Research Seed Grant. Dr Hernandez is supported by an American Heart Association Pharmaceutical Roundtable grant (0675060N).; Dr Hernandez has received research funding from Johnson & Johnson/Scios, Medtronic, and Merck and honoraria from Medtronic, Novartis, and AstraZeneca. Dr Fonarow has received research funding from the National Heart, Lung, and Blood Institute, honoraria from GlaxoSmithKline, Medtronic, and Novartis, and serves as a consultant for GlaxoSmithKline, Medtronic, and Novartis. Dr Masoudi has received research funding from Amgen, the National Heart, Lung, and Blood Institute, and the Agency for Healthcare Research and Quality; has served on advisory boards for Amgen and United Healthcare; and has contracts with the American College of Cardiology and the Oklahoma Foundation for Medical Quality. NR 18 TC 82 Z9 87 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2010 VL 3 IS 1 BP 25 EP 32 DI 10.1161/CIRCOUTCOMES.109.854877 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PR UT WOS:000276080000007 PM 20123668 ER PT J AU Ko, DT Ross, JS Wang, YF Krumholz, HM AF Ko, Dennis T. Ross, Joseph S. Wang, Yongfei Krumholz, Harlan M. TI Determinants of Cardiac Catheterization Use in Older Medicare Patients With Acute Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiac catheterization; acute myocardial infarction; determinants of use; Medicare beneficiaries ID ACUTE CORONARY SYNDROMES; ASSOCIATION TASK-FORCE; TREATMENT-RISK PARADOX; BASE-LINE RISK; GLOBAL REGISTRY; PRACTICE GUIDELINES; ACC/AHA GUIDELINES; REGIONAL-VARIATION; RACIAL-DIFFERENCES; AMERICAN-COLLEGE AB Background-Cardiac catheterization is substantially underused among higher-risk patients with acute myocardial infarction (AMI) with appropriate indications but overused among patients with inappropriate indications. We sought to determine the importance of anticipated benefit and anticipated harm on the use of cardiac catheterization among older patients with AMI. Methods and Results-We performed an analysis of Medicare fee-for-service beneficiaries hospitalized with an AMI between 1998 and 2001. Multivariate models were developed to determine relative importance of anticipated benefit (baseline cardiovascular risk), anticipated harm (bleeding risk, comorbidities), and demographic factors (age, sex, race, regional invasive intensity) in predicting cardiac catheterization use within 60 days of AMI admission. Analyses were stratified by American College of Cardiology/American Heart Association class I or II as appropriate, and class III as inappropriate. Determinants of reduced likelihood of cardiac catheterization among 42 241 AMI patients with appropriate indications included (in order of importance) older age (likelihood chi(2) = 1309.5), higher bleeding risk score (likelihood chi(2) = 471.2), more comorbidities (likelihood chi(2) = 276.6), female sex (likelihood chi(2) = 162.9), hospitalization in low (likelihood chi(2) = 67.9) or intermediate intensity invasive regions (likelihood chi(2) = 22.4) (all P < 0.001), and baseline cardiovascular risk (likelihood chi(2) = 6.4, P = 0.01). Among 2398 AMI patients with inappropriate indications, significant determinants of greater procedure likelihood included younger age, male sex, lower bleeding risk score, and fewer comorbidities. Conclusions-Regardless of the procedure indication, the decision to perform cardiac catheterization in this population appears largely driven by demographic factors and potential harm rather than potential benefit of the procedure. (Circ Cardiovasc Qual Outcomes. 2010; 3: 54-62.) C1 [Wang, Yongfei; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Robert Wood Johnson Clin Scholars Program,Sect Hl, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. HSR&D Targeted Res Enhancement Program, Bronx, NY USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada. Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu OI Ko, Dennis/0000-0001-6840-8051 FU Canadian Institutes of Health Research; Heart and Stroke Foundation of Ontario; Department of Veterans Affairs Health Services Research and Development Service [TRP-02-149]; US Department of Health and Human Services [HHSM-500-2005-CO001C] FX Dr Ko is supported by a New Investigator Award from the Canadian Institutes of Health Research and a Clinician Scientist Award from the Heart and Stroke Foundation of Ontario. Dr Ross is currently supported by Department of Veterans Affairs Health Services Research and Development Service project TRP-02-149.; The analyses on which this publication is based were performed under contract HHSM-500-2005-CO001C, entitled "Utilization and Quality Control Quality Improvement Organization for the State (commonwealth) of Colorado," sponsored by the Centers for Medicare and Medicaid Services, an agency of the US Department of Health and Human Services. The content of the publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. The Centers for Medicare & Medicaid Services did not play a role in the design and conduct of the study or in the analysis and interpretation of the data. NR 35 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2010 VL 3 IS 1 BP 54 EP U90 DI 10.1161/CIRCOUTCOMES.109.858456 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575PR UT WOS:000276080000011 PM 20123672 ER PT J AU Ross, JS Chen, J Lin, Z Bueno, H Curtis, JP Keenan, PS Normand, SLT Schreiner, G Spertus, JA Vidan, MT Wang, YF Wang, Y Krumholz, HM AF Ross, Joseph S. Chen, Jersey Lin, Zhenqiu Bueno, Hector Curtis, Jeptha P. Keenan, Patricia S. Normand, Sharon-Lise T. Schreiner, Geoffrey Spertus, John A. Vidan, Maria T. Wang, Yongfei Wang, Yun Krumholz, Harlan M. TI Recent National Trends in Readmission Rates After Heart Failure Hospitalization SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; health policy; hospitalizations/rehospitalizations; epidemiology; congestive; Centers for Medicare and Medicaid Services (US); patient readmission; United States/epidemiology ID DISEASE MANAGEMENT PROGRAMS; OF-CARDIOLOGY FOUNDATION; SCIENTIFIC STATEMENT; CLINICAL-OUTCOMES; OLDER PATIENTS; HEALTH-CARE; QUALITY; METAANALYSIS; INTERVENTION; ASSOCIATION AB Background-In July 2009, Medicare began publicly reporting hospitals' risk-standardized 30-day all-cause readmission rates (RSRRs) among fee-for-service beneficiaries discharged after hospitalization for heart failure from all the US acute care nonfederal hospitals. No recent national trends in RSRRs have been reported, and it is not known whether hospital-specific performance is improving or variation in performance is decreasing. Methods and Results-We used 2004-2006 Medicare administrative data to identify all fee-for-service beneficiaries admitted to a US acute care hospital for heart failure and discharged alive. We estimated mean annual RSRRs, a National Quality Forum-endorsed metric for quality, using 2-level hierarchical models that accounted for age, sex, and multiple comorbidities; variation in quality was estimated by the SD of the RSRRs. There were 570 996 distinct hospitalizations for heart failure in which the patient was discharged alive in 4728 hospitals in 2004, 544 550 in 4694 hospitals in 2005, and 501 234 in 4674 hospitals in 2006. Unadjusted 30-day all-cause readmission rates were virtually identical over this period: 23.0% in 2004, 23.3% in 2005, and 22.9% in 2006. The mean and SD of RSRRs were also similar: mean (SD) of 23.7% (1.3) in 2004, 23.9% (1.4) in 2005, and 23.8% (1.4) in 2006, suggesting similar hospital variation throughout the study period. Conclusions-National mean and RSRR distributions among Medicare beneficiaries discharged after hospitalization for heart failure have not changed in recent years, indicating that there was neither improvement in hospital readmission rates nor in hospital variations in rates over this time period. (Circ Heart Fail. 2010; 3: 97-103.) C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. [Ross, Joseph S.] Mt Sinai Sch Med, Dept Palliat Med, New York, NY 10029 USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA. [Chen, Jersey; Curtis, Jeptha P.; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Chen, Jersey; Lin, Zhenqiu; Curtis, Jeptha P.; Schreiner, Geoffrey; Wang, Yongfei; Wang, Yun; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Bueno, Hector] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid, Spain. [Keenan, Patricia S.; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Sch Publ Hlth, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Spertus, John A.] Univ Missouri, Sch Med, Dept Med, Cardiol Sect, Kansas City, MO 64108 USA. [Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Vidan, Maria T.] Hosp Gen Univ Gregorio Maranon, Dept Geriatr Med, Madrid, Spain. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM joseph.ross@mssm.edu RI BUENO, HECTOR/I-3910-2015 OI BUENO, HECTOR/0000-0003-0277-7596 FU Centers for Medicare & Medicaid Services [HHSM-500-2005-CO001C]; agency of the US Department of Health and Human Services; National Institute on Aging [K08 AG032886]; Beeson; Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain [BA08/90010, BA08/90012] FX The analyses upon which this publication is based were performed under contract HHSM-500-2005-CO001C, entitled "Utilization and Quality Control Quality Improvement Organization for the State (Commonwealth) of Colorado," funded by the Centers for Medicare & Medicaid Services, an agency of the US Department of Health and Human Services. Dr Ross is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. Dr Bueno was supported by grant BA08/90010 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain. Dr Vidan was supported by grant BA08/90012 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain. NR 28 TC 185 Z9 189 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2010 VL 3 IS 1 BP 97 EP 103 DI 10.1161/CIRCHEARTFAILURE.109.885210 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 545MA UT WOS:000273735100015 PM 19903931 ER PT S AU Schneeberger, EE AF Schneeberger, Eveline E. BE Yu, ASL TI Morphological Studies of Claudins in the Tight Junction SO CLAUDINS SE Current Topics in Membranes LA English DT Review; Book Chapter ID INTEGRAL MEMBRANE-PROTEINS; CANINE KIDNEY-CELLS; ZONULAE-OCCLUDENTES; EPITHELIAL-CELLS; MDCK CELLS; STEADY-STATE; OCCLUDIN; STRANDS; CHOLESTEROL; EXPRESSION AB OVERVIEW Claudins are small (20-27 kDa), integral tight junction proteins that span the plasma membrane four times, forming two external loops that are joined by a short cytoplasmic segment and with both N- and C-termini located in the cytoplasm. To date, 24 distinct claudins have been identified. Site-directed mutagenesis experiments indicate that specific amino acid sequences in the first external loop of the claudins determines the ion selectivity of tight junctions, while a cluster of aromatic residues on the second loop appears to provide a strong binding site between claudins expressed on adjacent cells. Combinations of different claudins are expressed in the cell-specific tight junction strands of polarized cells, where they appear to form heterologous ion pores in the paracellular space. Moreover, fluorescence recovery after photobleaching studies in epithelia with established tight junctions suggest that, in contrast to occludin, claudin-1 appears largely immobile in the plane of the membrane. Although a great deal has been learned regarding the molecular organization of the tight junction, there still remain gaps in our knowledge with regard to the regulation, under physiological and pathological conditions, of this important structure. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Charlestown, MA USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Charlestown, MA USA. NR 58 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 978-0-12-381039-7 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2010 VL 65 BP 21 EP 37 DI 10.1016/S1063-5823(10)65002-8 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BPZ47 UT WOS:000280437500002 ER PT S AU Paidassi, H Acharya, M Lacy-Hulbert, A AF Paidassi, Helena Acharya, Mridu Lacy-Hulbert, Adam BE Mevorach, D TI Alpha (v) integrins license regulatory T cells to apoptotic cells and self-associated antigens SO CLEARANCE OF DYING CELLS IN HEALTHY AND DISEASED IMMUNE SYSTEMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Clearance of Dying Cells in a Healthy and Diseased Immune System CY MAY 09-11, 2010 CL Jerusalem, ISRAEL DE integrins; apoptosis; phagocytosis; TGF-beta; regulatory T cells; colitis ID MESENTERIC LYMPH-NODES; DENDRITIC CELLS; VITRONECTIN RECEPTOR; RETINOIC-ACID; ALPHA-V-BETA-5 INTEGRIN; TGF-BETA; MEDIATED PHAGOCYTOSIS; ULCERATIVE-COLITIS; MACROPHAGES; DIFFERENTIATION AB Defects in apoptotic cell clearance are thought to contribute to autoimmunity by failure to induce tolerance, coupled with accumulation of immunogenic material. However, little is known about the contribution of apoptosis to immune responses at mucosal sites, where regulatory T cells (T-reg cells) and other immune cells play an essential active role in maintaining tolerance to self-associated antigens. In recent studies, we have found that alpha(v) integrins have an important role in apoptotic cell phagocytosis and induction of T-reg cells in the intestine, and deletion of alpha(v) from myeloid cells causes colitis associated with failed apoptotic cell removal and loss of T-reg cells. Our data show that activation of transforming growth factor (TGF)-beta by alpha(v)beta(8) on dendritic cells (DCs) is essential for generating Treg cells and inducing mucosa! tolerance. These results provide a mechanism by which tolerance to apoptotic cell derived and associated antigens is maintained by DC "licensing" at sites of high TGF-beta expression. C1 [Paidassi, Helena; Acharya, Mridu; Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Program Dev Immunol, Dept Pediat, Boston, MA 02114 USA. [Paidassi, Helena] Univ Edinburgh, MRC Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. RP Lacy-Hulbert, A (reprint author), Massachusetts Gen Hosp, Program Dev Immunol, Dept Pediat, GRJ1402,55 Fruit St, Boston, MA 02114 USA. EM alacy-hulbert@partners.org RI Paidassi, Helena/M-5739-2014; OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Paidassi, Helena/0000-0001-9915-4365 FU Hood Pediatric Research Foundation; Crohn's and Colitis Foundation of America; UK Medical Research Council FX Work in the laboratory is supported by grants from the Hood Pediatric Research Foundation and Crohn's and Colitis Foundation of America (both to ALH). HP is supported by a grant from the UK Medical Research Council to Professor John Savill, University of Edinburgh, UK, who we thank for support and useful discussion. NR 51 TC 6 Z9 6 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-797-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1209 BP 68 EP 76 DI 10.1111/j.1749-6632.2010.05783.x PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BSK31 UT WOS:000284743200010 PM 20958318 ER PT J AU Banda, NK Levitt, B Wood, AK Takahashi, K Stahl, GL Holers, VM Arend, WP AF Banda, N. K. Levitt, B. Wood, A. K. Takahashi, K. Stahl, G. L. Holers, V. M. Arend, W. P. TI Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE alternative pathway; arthritis; complement; immune complexes; inflammation ID TRANSLATIONAL MINIREVIEW SERIES; COLLAGEN-INDUCED ARTHRITIS; ALTERNATIVE PATHWAY; INNATE IMMUNITY; FACTOR-H; 2 PARTS; CONVERTASE; PROPERDIN; MICE; AMPLIFICATION AB P>The alternative pathway (AP) of complement alone is capable of mediating immune complex-induced arthritis in the collagen antibody-induced arthritis (CAIA) model in mice. Whether the classical pathway (CP) or lectin pathway (LP) alone can mediate CAIA is not known. Using mice genetically deficient in different complement components, our results reported herein establish that the CP and LP alone are each incapable of mediating CAIA. A lower level or absence of C3 and/or C5 activation by the CP may be possible explanations for the importance of the AP in CAIA and in many murine models of disease. In addition, other investigators have reported that CP C5 convertase activity is absent in mouse sera. To address these questions, we employed an in vitro system of adherent immunoglobulin (Ig)G-induced complement activation using plates coated with murine anti-collagen monoclonal antibody (mAb). These experiments used complement-deficient mouse sera and wild-type mouse or normal human sera under conditions inactivating either the CP (Ca++ deficiency) or the AP (mAb inhibitory to factor B). Robust generation of both C3a and C5a by either the AP or CP alone were observed with both mouse and human sera, although there were some small differences between the species of sera. We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP. C1 [Banda, N. K.; Levitt, B.; Wood, A. K.; Holers, V. M.; Arend, W. P.] Univ Colorado Denver, Div Rheumatol, Aurora, CO 80045 USA. [Takahashi, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stahl, G. L.] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. RP Arend, WP (reprint author), Univ Colorado Denver, Div Rheumatol B115, 1775 Aurora Court,POB 6511, Aurora, CO 80045 USA. EM william.arend@ucdenver.edu FU NIH [AR-51749] FX This work was supported by NIH Grant no. AR-51749. NR 28 TC 15 Z9 16 U1 4 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2010 VL 159 IS 1 BP 100 EP 108 DI 10.1111/j.1365-2249.2009.04035.x PG 9 WC Immunology SC Immunology GA 525CU UT WOS:000272191500011 PM 19843088 ER PT J AU Anderson, S Chapman, JG Oyama, TT Komers, R AF Anderson, Sharon Chapman, Justin G. Oyama, Terry T. Komers, Radko TI Effect of orchiectomy on renal function in control and diabetic rats with chronic inhibition of nitric oxide SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE diabetic nephropathy; glomerular filtration rate; nitric oxide inhibition; orchiectomy; proteinuria; renal plasma flow ID SPONTANEOUSLY HYPERTENSIVE-RATS; ENDOTHELIAL DYSFUNCTION; VASCULAR REACTIVITY; GENDER-DIFFERENCES; OXIDATIVE STRESS; URINARY ALBUMIN; TESTOSTERONE; DISEASE; PROGRESSION; MEN AB P>Male gender is associated with higher blood pressure (BP) and more rapid loss of renal function in a spectrum of clinical and experimental renal diseases, including diabetic nephropathy. Consequently, modulation of testosterone levels could exert beneficial effects in the diabetic kidney. The aim of the present study was to determine whether testosterone deficiency (orchiectomy) could influence BP and renal function in streptozotocin-diabetic rats, with or without accelerated endothelial dysfunction achieved by chronic inhibition of nitric oxide (NO) synthesis using NG-nitro-l-arginine methyl ester (l-NAME; 40-100 mg/L in the drinking water for 2 weeks), as well as in age-matched non-diabetic rats subjected to the same interventions. Orchiectomy did not affect l-NAME-induced increases in BP in non-diabetic or diabetic rats. In non-diabetic rats, orchiectomy prevented l-NAME-induced increases in proteinuria. These effects on proteinuria were not observed in diabetic rats. In non-diabetic rats, orchiectomy had no effect on renal haemodynamics in animals receiving vehicle and did not affect l-NAME-induced changes in renal haemodynamics, characterized by reductions in renal plasma flow (RPF) and higher filtration fractions (FF). In intact diabetic rats, l-NAME treatment resulted in lower RPF. This difference was not observed in diabetic rats subjected to orchiectomy, although l-NAME-treated diabetic orchiectomized rats had lower RPF and higher FF compared with vehicle-treated intact diabetic rats. In conclusion, we report modest beneficial effects of orchiectomy on proteinuria in normal, but not in diabetic, rats with inhibition of NO production. This suggests that testosterone reduction does not attenuate the deleterious impact of the diabetic metabolic milieu in the kidney. C1 [Anderson, Sharon; Chapman, Justin G.; Oyama, Terry T.; Komers, Radko] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Anderson, Sharon] Portland VA Med Ctr, Portland, OR USA. RP Komers, R (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM komersr@ohsu.edu FU National Institutes of Health [DK 63 231]; VA Merit Review FX These studies were supported by a National Institutes of Health grant (DK 63 231) and by VA Merit Review grant (to SA). NR 23 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD JAN PY 2010 VL 37 IS 1 BP 19 EP 23 DI 10.1111/j.1440-1681.2009.05206.x PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 533PD UT WOS:000272835800007 PM 19473197 ER PT J AU Bryan, CL Beard, KS Pott, GB Rahkola, J Gardner, EM Janoff, EN Shapiro, L AF Bryan, Courtney L. Beard, K. Scott Pott, Gregory B. Rahkola, Jeremy Gardner, Edward M. Janoff, Edward N. Shapiro, Leland TI HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations SO CLINICAL AND INVESTIGATIVE MEDICINE LA English DT Article ID IN-VITRO; DEFICIENCY; ALPHA(1)-ANTITRYPSIN; DISEASE; MECHANISMS; INHIBITOR; PROTEASE AB Purpose: Several observations suggest the presence of HIV-suppressive factors in the fluid phase of blood. Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may function as an endogenous HIV suppressor. Therefore, we assessed serum AAT concentrations for association with HIV infection. Methods: In this cross-sectional study, serum AAT concentrations were measured in 66 persons with HIV infection and in 45 healthy persons (Controls). In the HIV-infected group, antiretroviral therapy (ART) use was assessed and CD4(+) T cell levels and plasma HIV RNA were quantified. Results: Median AAT concentration was significantly lower in the HIV-infected group (1.64 mg/mL) in comparison with Controls (1.94 mg/mL; p=0.001). AAT reduction was most pronounced in the HIV-infected subgroup with CD4+ T cell levels >200 cells/mu L in comparison with Controls (p<0.01). Serum AAT concentrations <1.0 % mg/mL are clinically significant, and concentrations below this level were identified in 4.5% of the HIV-infected group and in no Control subjects. No association between AAT levels and viral load or use of ART was observed in HIV-infected subjects. Conclusion: The association between reduced serum AAT concentration and HIV infection is consistent with a role for AAT as an endogenous HIV suppressor. C1 [Bryan, Courtney L.; Beard, K. Scott; Pott, Gregory B.; Rahkola, Jeremy; Janoff, Edward N.; Shapiro, Leland] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. [Bryan, Courtney L.; Beard, K. Scott; Pott, Gregory B.; Rahkola, Jeremy; Gardner, Edward M.; Janoff, Edward N.; Shapiro, Leland] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Gardner, Edward M.] Denver Publ Hlth, Dept Publ Hlth, Denver, CO USA. [Rahkola, Jeremy; Janoff, Edward N.] Mucosal & Vaccine Res Program Colorado MAVRC, Dept Med, Denver, CO USA. RP Shapiro, L (reprint author), Denver Vet Affairs Med Ctr, Dept Med, 1055 Clermont St,Box 111L, Denver, CO 80220 USA. EM leland.shapiro@ucdenver.edu FU Campbell Foundation; Veterans Affairs Research Service; Mucosal and Vaccine Research Program Colorado (MAVRC); Baxter Catalyst FX Campbell Foundation and Baxter Catalyst awards to Leland Shapiro, MD, and Veterans Affairs Research Service and Mucosal and Vaccine Research Program Colorado (MAVRC) to Edward N. Janoff, MD NR 21 TC 11 Z9 12 U1 2 U2 2 PU CANADIAN SOC CLINICAL INVESTIGATION PI OTTAWA PA CSCI HEAD OFFICE, 774 ECHO DRIVE, OTTAWA, ON K1S 5N8, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med. PY 2010 VL 33 IS 6 BP E384 EP E389 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 699FV UT WOS:000285650200006 PM 21134340 ER PT J AU Galimberti, F Thompson, SL Liu, X Li, H Memoli, V Green, SR DiRenzo, J Greninger, P Sharma, SV Settleman, J Compton, DA Dmitrovsky, E AF Galimberti, Fabrizio Thompson, Sarah L. Liu, Xi Li, Hua Memoli, Vincent Green, Simon R. DiRenzo, James Greninger, Patricia Sharma, Sreenath V. Settleman, Jeff Compton, Duane A. Dmitrovsky, Ethan TI Targeting the Cyclin E-Cdk-2 Complex Represses Lung Cancer Growth by Triggering Anaphase Catastrophe SO CLINICAL CANCER RESEARCH LA English DT Article ID GENOTYPE-CORRELATED SENSITIVITY; BRONCHIAL EPITHELIAL-CELLS; CYC202 R-ROSCOVITINE; ABL TYROSINE KINASE; FACTOR RECEPTOR; RETINOIC ACID; CHROMOSOMAL INSTABILITY; MITOTIC SPINDLE; NUCLEAR-PROTEIN; BREAST-CANCER AB Purpose: Cyclin-dependent kinases (Cdk) and their associated cyclins are targets for lung cancer therapy and chemoprevention given their frequent deregulation in lung carcinogenesis. This study uncovered previously unrecognized consequences of targeting the cyclin E-Cdk-2 complex in lung cancer. Experimental Design: Cyclin E, Cdk-1, and Cdk-2 were individually targeted for repression with siRNAs in lung cancer cell lines. Cdk-2 was also pharmacologically inhibited with the reversible kinase inhibitor seliciclib. Potential reversibility of seliciclib effects was assessed in washout experiments. Findings were extended to a large panel of cancer cell lines using a robotic-based platform. Consequences of cyclin E-Cdk-2 inhibition on chromosome stability and on in vivo tumorigenicity were explored as were effects of combining seliciclib with different taxanes in lung cancer cell lines. Results: Targeting the cyclin E-Cdk-2 complex, but not Cdk-1, resulted in marked growth inhibition through the induction of multipolar anaphases triggering apoptosis. Treatment with the Cdk-2 kinase inhibitor seliciclib reduced lung cancer formation in a murine syngeneic lung cancer model and decreased immunohistochemical detection of the proliferation markers Ki-67 and cyclin D1 in lung dysplasia spontaneously arising in a transgenic cyclin E-driven mouse model. Combining seliciclib with a taxane resulted in augmented growth inhibition and apoptosis in lung cancer cells. Pharmacogenomic analysis revealed that lung cancer cell lines with mutant ras were especially sensitive to seliciclib. Conclusions: Induction of multipolar anaphases leading to anaphase catastrophe is a previously unrecognized mechanism engaged by targeting the cyclin E-Cdk-2 complex. This exerts substantial antineoplastic effects in the lung. Clin Cancer Res; 16(1); 109-20. (C)2010 AACR. C1 [Galimberti, Fabrizio; Liu, Xi; Li, Hua; DiRenzo, James; Dmitrovsky, Ethan] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. [Thompson, Sarah L.; Compton, Duane A.] Dartmouth Med Sch, Dept Biochem, Hanover, NH 03755 USA. [Memoli, Vincent] Dartmouth Med Sch, Dept Pathol, Hanover, NH 03755 USA. [Dmitrovsky, Ethan] Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. [Memoli, Vincent; DiRenzo, James; Compton, Duane A.; Dmitrovsky, Ethan] Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH 03755 USA. [Memoli, Vincent; DiRenzo, James; Compton, Duane A.; Dmitrovsky, Ethan] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Greninger, Patricia; Sharma, Sreenath V.; Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. [Green, Simon R.] Cyclacel Ltd, Dundee, Scotland. RP Dmitrovsky, E (reprint author), Dartmouth Med Sch, Dept Pharmacol & Toxicol, Remsen 7650, Hanover, NH 03755 USA. EM ethan.dmitrovsky@dartmouth.edu OI Compton, Duane/0000-0002-4445-9118 FU NIH; National Cancer Institute [RO1-CA087546, RO1-CA111422, RO1-GM51542, T32-GM008704]; Samuel Waxman Cancer Research Foundation; American Lung Association; Cyclacel Ltd.; F.M. Kirby Foundation FX NIH and National Cancer Institute grants RO1-CA087546 (E. Dmitrovsky), RO1-CA111422 (E. Dmitrovsky), RO1-GM51542 (D.A. Compton), and T32-GM008704 (S.L. Thompson) as well as by Samuel Waxman Cancer Research Foundation grants (E. Dmitrovsky and J. Settleman), the American Lung Association (X. Liu), and partly by a research grant from Cyclacel Ltd. (E. Dmitrovsky). E. Dmitrovsky is an American Cancer Society Clinical Research Professor supported by a generous gift from the F.M. Kirby Foundation. NR 49 TC 29 Z9 29 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2010 VL 16 IS 1 BP 109 EP 120 DI 10.1158/1078-0432.CCR-09-2151 PG 12 WC Oncology SC Oncology GA 606EI UT WOS:000278404500012 PM 20028770 ER PT J AU Batista, LM Crandell, D Lima, FO Greer, DM AF Batista, Leonardo M. Crandell, David Lima, Fabricio O. Greer, David M. TI Pharmacokinetics of Extended-Release Dipyridamole following Administration through a Gastrostomy Tube An Open-Label, Case-Control, Two-Centre Study SO CLINICAL DRUG INVESTIGATION LA English DT Article ID STROKE; PREVENTION; DYSPHAGIA; DIAGNOSIS; PLASMA AB Background: Many stroke survivors have severe dysphagia and are unable to take antithrombotic medications orally. Objective: To evaluate whether dipyridamole concentrations achieved in the plasma of patients taking an extended-release formulation of the medication through a gastrostomy tube (G-tube) are therapeutic and similar to those achieved in the plasma of patients who receive the drug orally. Methods: This was an open-label, case-control, two-centre study conducted in two academic centres in a metropolitan area. Patients included were those admitted following an acute cerebral infarction, with an indication for antiplatelet therapy for secondary prevention. Twelve patients with severe dysphagia requiring G-tube placement were cases, and 12 patients who were able to swallow safely served as controls. The components of Aggrenox (R) (extended-release dipyridamole/aspirin [acetylsalicylic acid]), suspended in water, were administered twice daily for 5 days through the G-tube. The 12 control patients without dysphagia took the medication orally. Dipyridamole plasma concentrations were compared between the groups at three different timepoints on the fifth day: 2, 6 and 12 hours after administration. The main outcome measure was dipyridamole plasma concentrations on day 5 at all three timepoints. Results: No significant difference in dipyridamole plasma concentrations between the groups was found at 2 hours (p = 0.18), 6 hours (p = 0.92) or 12 hours (p = 0.69). Conclusion: Dipyridamole plasma concentrations obtained following administration of extended-release dipyridamole through a G-tube in dysphagic patients achieved similar therapeutic levels to those obtained in patients taking the medication orally. C1 [Batista, Leonardo M.; Lima, Fabricio O.; Greer, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Res Ctr,Dept Neurol, Boston, MA USA. [Crandell, David] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr, Suite 720,55 Fruit St, Boston, MA 02114 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 FU Boehringer Ingelheim Pharmaceuticals, Inc. FX This study was supported in part by Boehringer Ingelheim Pharmaceuticals, Inc. The sponsor played no role in the conduct, preparation or design of the study; the collection, management, analysis or interpretation of the data; or the preparation, review or approval of the manuscript. Drs Greer and Crandell have received research support for this study from Boehringer Ingelheim Pharmaceuticals, Inc. Dr Greer has served on the speaker's bureau for Boehringer Ingelheim Pharmaceuticals, Inc. Drs Batista and Lima have no conflicts of interest that are directly relevant to the content of this study. The authors thank Dr Wendy Adams, PhD, forensic toxicologist, for being very supportive concerning the drug concentration determination. The authors also greatly appreciate the contribution of Allison Dipietro in the enrolment of the patients and her help with the regulatory paperwork. NR 10 TC 1 Z9 1 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-2563 J9 CLIN DRUG INVEST JI Clin. Drug Invest. PY 2010 VL 30 IS 7 BP 483 EP 488 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 617QS UT WOS:000279296600006 PM 20433215 ER PT J AU Nachtigall, LB Valassi, E Lo, J McCarty, D Passeri, J Biller, BMK Miller, KK Utz, A Grinspoon, S Lawson, EA Klibanski, A AF Nachtigall, Lisa B. Valassi, Elena Lo, Janet McCarty, David Passeri, Jonathan Biller, Beverly M. K. Miller, Karen K. Utz, Andrea Grinspoon, Steven Lawson, Elizabeth A. Klibanski, Anne TI Gender effects on cardiac valvular function in hyperprolactinaemic patients receiving cabergoline: a retrospective study SO CLINICAL ENDOCRINOLOGY LA English DT Article ID HEART-DISEASE; DOPAMINE AGONISTS; DOPPLER-ECHOCARDIOGRAPHY; TRICUSPID REGURGITATION; INCREASED PREVALENCE; VALVE REGURGITATION; RISK; PROLACTINOMA AB P>Background Ergot-derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson's disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial. Objective To determine whether there is an association of cabergoline and valvular function in patients with hyperprolactinaemia according to gender. Design Case-record retrospective study. Setting Outpatient neuroendocrine clinical centre at a tertiary care hospital. Study participants One hundred patients (48 men and 52 women) with hyperprolactinaemia who had an echocardiogram while receiving cabergoline for at least 6 months. Controls One hundred controls (48 men and 52 women) selected from Massachusetts general hospital (MGH) database of echocardiograms without clinically significant findings, matched to patients for age, gender, body mass index (BMI) and hypertension. Main outcome measure Echocardiogram. Results There were no significant differences in valvular function in patients compared with controls. However, women patients had a higher prevalence of mild tricuspid regurgitation (TR) than female controls (15 center dot 4%vs. 1 center dot 9%, P = 0.03). Among men only, patients had more trace TR than controls (68 center dot 8%vs. 45 center dot 8%, P = 0.02). The mild valvular regurgitation in patients was not clinically significant and did not correlate with dose, duration or cumulative dose. Conclusions Overall cabergoline was not associated with valvulopathy. However, subdivided by gender, hyperprolactinaemic men and women had higher prevalence of trace or mild TR, respectively, compared with gender matched controls. There may be gender differences in valvular dysfunction associated with cabergoline. Longer term, larger studies are necessary to evaluate definitively an effect of cabergoline on valvular function in hyperprolactinaemic patients. C1 [Nachtigall, Lisa B.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. [McCarty, David; Passeri, Jonathan] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nachtigall, LB (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, 0 Emerson Pl,Suite 112, Boston, MA 02114 USA. EM lnachtigall@partners.org FU Pfizer; Foundation for Women's Wellness, New York, NY FX Beverly M.K. Biller is a recipient of research grants and consulting honoraria from Pfizer. Anne Klibanski is a recipient of an investigator initiated grant from Pfizer. This study was supported by a grant from the Foundation for Women's Wellness, New York, NY. NR 20 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2010 VL 72 IS 1 BP 53 EP 58 DI 10.1111/j.1365-2265.2009.03608.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 532SX UT WOS:000272771200010 PM 19508591 ER PT B AU Yachimski, PS Friedman, LS AF Yachimski, Patrick S. Friedman, Lawrence S. BE Dancygier, H TI Risk of Surgery in Patients with Liver Disease SO CLINICAL HEPATOLOGY, VOL 2: PRINCIPLES AND PRACTICE OF HEPATOBILIARY DISEASES LA English DT Article; Book Chapter ID INTRAHEPATIC PORTOSYSTEMIC SHUNT; RECOMBINANT FACTOR VIIA; GASTRIC BYPASS-SURGERY; FATAL HEPATIC-FAILURE; ACUTE-RENAL-FAILURE; CIRRHOTIC-PATIENTS; LAPAROSCOPIC CHOLECYSTECTOMY; OBSTRUCTIVE-JAUNDICE; HEPATOCELLULAR-CARCINOMA; TRANSPLANT CANDIDATES C1 [Yachimski, Patrick S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Yachimski, Patrick S.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Friedman, Lawrence S.] Harvard Univ, Sch Med, Newton, MA 02462 USA. [Friedman, Lawrence S.] Tufts Univ, Newton Wellesley Hosp, Massachusetts Gen Hosp, Dept Med,Sch Med, Newton, MA 02462 USA. RP Yachimski, PS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. NR 92 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-04509-7 PY 2010 BP 1383 EP 1399 DI 10.1007/978-3-642-04519-6_104 D2 10.1007/978-3-642-04519-6 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BMN80 UT WOS:000272986000050 ER PT J AU Ventura, E Islam, T Gee, MS Mahmood, U Braschi, M Harisinghani, MG AF Ventura, Elisa Islam, Tina Gee, Michael S. Mahmood, Umar Braschi, Marta Harisinghani, Mukesh G. TI Detection of nodal metastatic disease in patients with non-small cell lung cancer: comparison of positron emission tomography (PET), contrast-enhanced computed tomography (CT), and combined PET-CT SO CLINICAL IMAGING LA English DT Article DE Non-small cell lung cancer; Lymph nodes; PET-CT; Diagnostic accuracy ID FDG-PET; SCAN; MEDIASTINUM; CARCINOMA; FUSION; NUMBER; SIZE AB Of 31 patients with lung cancer, 19 underwent PET-CT and 12 had CT followed by PET. Thoracic lymph nodes were sampled by mediastinoscopy or thoracotomy. Sensitivities, specificities, positive (PPV), and negative predictive values (NPV) were calculated based on histopathology. Ninety nodes (41 malignant) were identified. Sensitivity, specificity, PPV, and NPV were 94%, 73%, 66%, and 96% for PET-CT, respectively. In 12 patients who underwent PET and CT separately, these values were 90%, 31%, 64%, and 71% for PET and 81%, 50%, 69%, and 66% for CT, respectively. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ventura, Elisa; Islam, Tina; Gee, Michael S.; Mahmood, Umar; Braschi, Marta; Harisinghani, Mukesh G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Islam, Tina; Gee, Michael S.; Mahmood, Umar; Braschi, Marta; Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Islam, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM islam.tina@mgh.harvard.edu NR 24 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JAN-FEB PY 2010 VL 34 IS 1 BP 20 EP 28 DI 10.1016/j.clinimag.2009.03.012 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 624HR UT WOS:000279808800004 PM 20122515 ER PT J AU Bradshaw, E Elyaman, W Raddassi, K Mousissian, N Greer, A Orban, T Gottlieb, P Kent, S Hafler, D AF Bradshaw, Elizabeth Elyaman, Wassim Raddassi, Khadir Mousissian, Narine Greer, Allison Orban, Tihamer Gottlieb, Peter Kent, Sally Hafler, David TI Monocytes from Patients with Type 1 Diabetes Have Increased Gene Expression of Pro-inflammatory Cytokines or IL-10 SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Bradshaw, Elizabeth; Elyaman, Wassim; Raddassi, Khadir; Mousissian, Narine; Greer, Allison; Kent, Sally] Brigham & Womens Hosp, Boston, MA 02115 USA. [Orban, Tihamer] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Gottlieb, Peter] Univ Colorado Denver, Aurora, CO USA. [Hafler, David] Yale Univ, Sch Med, New Haven, CT USA. RI e-, a/F-9947-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S19 EP S19 DI 10.1016/j.clim.2010.03.061 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700045 ER PT J AU Castelino, F Brooks, S Funke, M Chun, J Luster, A Tager, AM AF Castelino, Flavia Brooks, Sarah Funke, Manuela Chun, Jerold Luster, Andrew Tager, Andrew Martin TI Loss of LPA1 Signaling Protects Against Dermal Fibrosis in a Mouse Model of Systemic Sclerosis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Castelino, Flavia; Brooks, Sarah; Funke, Manuela; Luster, Andrew; Tager, Andrew Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chun, Jerold] Scripps Res Inst, La Jolla, CA USA. NR 0 TC 0 Z9 0 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S56 EP S56 DI 10.1016/j.clim.2010.03.170 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700154 ER PT J AU Castillo, IW Lui, QQ Ottoboni, L Briskin, R Alter, G Hafler, D De Jager, P AF Castillo, Irene Wood Lui, Qingquan Ottoboni, Linda Briskin, Rebeccah Alter, Galit Hafler, David De Jager, Phillip TI The PhenoGenetic Project: A Living Biobank Enabling the Study of Human Genetic and Immunologic Variation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Castillo, Irene Wood; Ottoboni, Linda; Briskin, Rebeccah; De Jager, Phillip] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hafler, David] Yale Univ, Sch Med, New Haven, CT USA. [Lui, Qingquan; Alter, Galit] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S118 EP S119 DI 10.1016/j.clim.2010.03.355 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700339 ER PT J AU Exley, M Nowak, M Yue, S Scheuplein, F Arredouani, MS Sanda, M Sasada, T Balk, S AF Exley, Mark Nowak, Michael Yue, Simon Scheuplein, Felix Arredouani, M. Simo Sanda, Martin Sasada, Tetsuro Balk, Steven TI Exploiting the Good Guys: Th1 Antiviral & Antitumor Human & Mouse NKT Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Exley, Mark; Nowak, Michael; Yue, Simon; Scheuplein, Felix; Arredouani, M. Simo; Sanda, Martin; Balk, Steven] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sasada, Tetsuro] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S34 EP S34 DI 10.1016/j.clim.2010.03.105 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700089 ER PT J AU Fricke, J Seung, E Vassor, V Tager, AM Gandhi, RT Walker, B Irvine, D Kavanagh, D AF Fricke, Jennifer Seung, Edward Vassor, Valerie Tager, Andrew Martin Gandhi, Rajesh Tim Walker, Bruce Irvine, Darrell Kavanagh, Daniel TI Synthetic mRNA-loaded Nanoparticles Elicit Mucosal IL-17(+) and IFN gamma(+) T Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Fricke, Jennifer; Seung, Edward; Vassor, Valerie; Tager, Andrew Martin; Gandhi, Rajesh Tim; Walker, Bruce; Irvine, Darrell; Kavanagh, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S137 EP S137 DI 10.1016/j.clim.2010.03.416 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700400 ER PT J AU Gardet, A Benita, Y Ballester, I Sands, B Korzenik, J Daly, M Xavier, R Podolsky, D AF Gardet, Agnes Benita, Yair Ballester, Isabel Sands, Bruce Korzenik, Joshua Daly, Mark Xavier, Ramnik Podolsky, Daniel TI LRRK2 is an Interferon-gamma Target Involved in Immune Responses SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Gardet, Agnes; Benita, Yair; Ballester, Isabel; Sands, Bruce; Korzenik, Joshua; Daly, Mark; Xavier, Ramnik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Podolsky, Daniel] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RI Benita, Yair/E-3094-2012 NR 0 TC 1 Z9 1 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S56 EP S56 DI 10.1016/j.ctim.2010.03.171 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700155 ER PT J AU Gordo, S Schubert, D Vardhana, S Seth, N Pyrdol, J Raddassi, K Hafler, D Dustin, M Wucherpfennig, K AF Gordo, Susana Schubert, David Vardhana, Santosh Seth, Nilufer Pyrdol, Jason Raddassi, Khadir Hafler, David Dustin, Michael Wucherpfennig, Kai TI Efficient Activation of Self-reactive T Cells from MS Patients with Altered Synapse Formation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Gordo, Susana; Schubert, David; Seth, Nilufer; Pyrdol, Jason; Wucherpfennig, Kai] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vardhana, Santosh; Dustin, Michael] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. [Raddassi, Khadir; Hafler, David] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S8 EP S8 DI 10.1016/j.dim.2010.03.031 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700015 ER PT J AU Leavenworth, J Wenander, CS Kim, NJ Lu, LR Spee, P Cantor, H AF Leavenworth, Jianmei Wenander, Carola Schellack Kim, Nye-Jung Lu, Linrong Spee, Pieter Cantor, Harvey TI Blockade of CD94/NKG2A Prevents EAE SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Wenander, Carola Schellack; Spee, Pieter] Novo Nordisk A S, Malov, Denmark. [Leavenworth, Jianmei; Kim, Nye-Jung; Cantor, Harvey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lu, Linrong] Zhejiang Univ, Sch Med, Hangzhou 310003, Peoples R China. NR 0 TC 1 Z9 1 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S7 EP S8 DI 10.1016/j.clim.2010.03.029 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700013 ER PT J AU Lee, LYH Butovsky, O Wei, Y Hayase, M Waeber, C Moskowitz, M Weiner, H AF Lee, Laurel Yong-Hwa Butovsky, Oleg Wei, Ying Hayase, Makoto Waeber, Christian Moskowitz, Michael Weiner, Howard TI The Role of Ly6C+Inflammatory Spleen-derived Monocytes in an Animal Model of Brain lschemia SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Lee, Laurel Yong-Hwa; Butovsky, Oleg; Weiner, Howard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wei, Ying; Hayase, Makoto; Waeber, Christian; Moskowitz, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S97 EP S97 DI 10.1016/j.clim.2010.03.292 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700276 ER PT J AU Li, H Saito, T Sykes, M AF Li, Haowei Saito, Toshiki Sykes, Megan TI Role of Granzyme B in the Antitumor Effects Induced by Recipient Lymphocyte Infusion in Mixed Bone Marrow Chimeras SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Li, Haowei; Saito, Toshiki; Sykes, Megan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S12 EP S12 DI 10.1016/j.clim.2010.03.043 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700027 ER PT J AU Nabatian, A Bashir, M Werth, V AF Nabatian, Adam Bashir, Muhammad Werth, Victoria TI Immunologic Actions of Glycosaminoglycans in Cutaneous Lupus Erythematosus Et Dermatomyositis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Nabatian, Adam; Bashir, Muhammad; Werth, Victoria] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S85 EP S85 DI 10.1016/j.clim.2010.03.256 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700240 ER PT J AU Nguyen, D Eston, M Snapper, S AF Nguyen, Deanna Eston, Michelle Snapper, Scott TI Aberrant Innate Immune Cells can Induce Normal T Cells to Become Colitogenic SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Nguyen, Deanna; Eston, Michelle; Snapper, Scott] Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S35 EP S35 DI 10.1016/j.clim.2010.03.109 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700093 ER PT J AU Paul, E Latchman, Y Kirby, A Koh, A Njoroge, S Feliu, M Sharpe, A Daly, M Colvin, R AF Paul, Elahna Latchman, Yvette Kirby, Andrew Koh, Anna Njoroge, Sarah Feliu, Marianela Sharpe, Arlene Daly, Mark Colvin, Robert TI CD48 Deficiency Precipitates Autoimmune Glomerulonephritis in Lupus Prone Mice SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Paul, Elahna; Kirby, Andrew; Koh, Anna; Njoroge, Sarah; Feliu, Marianela; Daly, Mark; Colvin, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Latchman, Yvette] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Sharpe, Arlene] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S10 EP S10 DI 10.1016/j.clim.2010.03.036 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700020 ER PT J AU Quintana, F Santiago, A Yeste, A Tukpah, AM Blanco, LR Garber, J Snapper, S Mittal, A Oukka, M Weiner, H AF Quintana, Francisco Santiago, Andrezza Yeste, Ada Tukpah, Ann-Marcia Blanco, Lorena Riol Garber, John Snapper, Scott Mittal, Akanksha Oukka, Mohamed Weiner, Howard TI AHR Controls the Production of Mucosal IL-22 by CD4+T Cells and NK Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Quintana, Francisco; Santiago, Andrezza; Yeste, Ada; Tukpah, Ann-Marcia; Blanco, Lorena Riol; Mittal, Akanksha; Oukka, Mohamed; Weiner, Howard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garber, John; Snapper, Scott] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S29 EP S29 DI 10.1016/j.clim.2010.03.090 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700074 ER PT J AU Riemer, A Keskin, D Reinhold, B Zhang, GL Anderson, K Brusic, V Reinherz, E AF Riemer, Angelika Keskin, Derin Reinhold, Bruce Zhang, Guanglan Anderson, Karen Brusic, Vladimir Reinherz, Ellis TI Mass Spectrometry Identifies a Single Dominant T Cell Epitope on HPV16-transformed HLA-A0201+Tumor Cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Keskin, Derin; Reinhold, Bruce; Zhang, Guanglan; Anderson, Karen; Brusic, Vladimir; Reinherz, Ellis] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Riemer, Angelika] Med Univ Vienna, Vienna, Austria. NR 0 TC 0 Z9 0 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S106 EP S106 DI 10.1016/j.dim.2010.03.319 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700303 ER PT J AU Rossin, E Cotsapas, C Roychaudhuri, S Lage, K Xavier, R Daly, M AF Rossin, Elizabeth Cotsapas, Chris Roychaudhuri, Soumya Lage, Kasper Xavier, Ramnik Daly, Mark TI The Use of Protein-protein Interaction in Loci Associated to Crohn's and Rheumatoid Arthritis Reveals Evidence of Risk Spread Across Functional Networks SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Rossin, Elizabeth; Cotsapas, Chris; Roychaudhuri, Soumya; Lage, Kasper; Xavier, Ramnik; Daly, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S119 EP S119 DI 10.1016/j.clim.2010.03.356 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700340 ER PT J AU Schubert, D Gordo, S Vardhana, S Pyrdol, J Seth, N Raddassi, K Hafler, D Dustin, M Wucherpfennig, K AF Schubert, David Gordo, Susana Vardhana, Santosh Pyrdol, Jason Seth, Nilufer Raddassi, Khadir Hafler, David Dustin, Michael Wucherpfennig, Kai TI Altered Synapse Formation by Self-reactive T Cells from MS Patients SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Schubert, David; Gordo, Susana; Pyrdol, Jason; Wucherpfennig, Kai] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vardhana, Santosh; Dustin, Michael] NYU, New York, NY USA. [Seth, Nilufer] Pfizer, Cambridge, MA USA. [Raddassi, Khadir; Hafler, David] Brigham & Womens Hosp, Boston, MA 02115 USA. OI Vardhana, Santosha/0000-0002-3100-1298 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S75 EP S76 DI 10.1016/j.clim.2010.03.227 PG 2 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700211 ER PT J AU Sethi, D Schubert, D Wilbuer, K Wucherpfennig, K AF Sethi, Dhruv Schubert, David Wilbuer, Kathrin Wucherpfennig, Kai TI Structural Characterization of an Unusual Binding Mode of a Myelin-specific T Cell Receptor SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Sethi, Dhruv; Schubert, David; Wilbuer, Kathrin; Wucherpfennig, Kai] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S71 EP S71 DI 10.1016/j.clim.2010.03.216 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700200 ER PT J AU Spinelli, J Sykes, M Kurtz, J AF Spinelli, Joia Sykes, Megan Kurtz, Josef TI Reversal of Autoimmunity by Induction of Mixed Hematopoietic Chimerism: Evidence for Non-deletional Mechanisms SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Sykes, Megan; Kurtz, Josef] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Spinelli, Joia] Univ Cambridge Emmanuel Coll, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2010 VL 135 SU S BP S91 EP S91 DI 10.1016/j.clim.2010.03.272 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700256 ER PT J AU Surolia, I Pirnie, S Chellappa, V Annaiah, C Moya, J Bell, D Haider, K Taylor, K De Jager, P Behrens, T Hafler, D Sands, B Murali, M Gregersen, P Pillai, S AF Surolia, Ira Pirnie, Stephan Chellappa, Vasant Annaiah, Cariappa Moya, Jesse Bell, Daphne Haider, Khaleda Taylor, Kendra De Jager, Phillip Behrens, Tim Hafler, David Sands, Bruce Murali, Mandakolathur Gregersen, Peter Pillai, Shiv TI Regulation of Immunological Tolerance and Autoimmunity by the Enzyme Sialic Acid Acetylesterase (SIAE) SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 24-27, 2010 CL Boston, MA SP Federat Clin Immunol Soc C1 [Surolia, Ira] Univ Toledo, Med Ctr, Toledo, OH 43606 USA. [Pirnie, Stephan; Chellappa, Vasant; Annaiah, Cariappa; Moya, Jesse; Bell, Daphne; Haider, Khaleda; Taylor, Kendra; De Jager, Phillip; Behrens, Tim; Hafler, David; Sands, Bruce; Murali, Mandakolathur; Gregersen, Peter; Pillai, Shiv] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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. PY 2010 VL 135 SU S BP S16 EP S16 DI 10.1016/j.clim.2010.03.054 PG 1 WC Immunology SC Immunology GA 599ZS UT WOS:000277953700038 ER PT J AU Branda, JA Aguero-Rosenfeld, ME Ferraro, MJ Johnson, BJB Wormser, GP Steere, AC AF Branda, John A. Aguero-Rosenfeld, Maria E. Ferraro, Mary Jane Johnson, Barbara J. B. Wormser, Gary P. Steere, Allen C. TI 2-Tiered Antibody Testing for Early and Late Lyme Disease Using Only an Immunoglobulin G Blot with the Addition of a VlsE Band as the Second-Tier Test SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; BORRELIA-BURGDORFERI; CLINICAL-DIAGNOSIS; C6 PEPTIDE; IGG ELISA; SERODIAGNOSIS; OVERDIAGNOSIS; RESPONSES; ACCURACY AB Background. Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection. Methods. Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed. Results. With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and >= 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity. Conclusions. Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity. C1 [Branda, John A.] Massachusetts Gen Hosp, Clin Microbiol Lab, Dept Pathol, Boston, MA 02114 USA. [Ferraro, Mary Jane; Steere, Allen C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ferraro, Mary Jane; Steere, Allen C.] Harvard Univ, Sch Med, Boston, MA USA. [Aguero-Rosenfeld, Maria E.; Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. [Aguero-Rosenfeld, Maria E.] New York Med Coll, Dept Pathol, Div Infect Dis, Valhalla, NY 10595 USA. [Johnson, Barbara J. B.] Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO USA. RP Branda, JA (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, Dept Pathol, GRB 526, Boston, MA 02114 USA. EM branda.john@mgh.harvard.edu FU Viramed Biotech AG; Diasorin. G. P. W.; Immunetics, BioRad Laboratories, and Diasorin FX A. C. S. received a research grant from Viramed Biotech AG to fund this study. J. A. B. has received a research grant from Diasorin. G. P. W. has received research grants from Immunetics, BioRad Laboratories, and Diasorin. M. J. F. is a member of the scientific advisory board at bioMerieux. All other authors: no conflicts. NR 24 TC 40 Z9 40 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2010 VL 50 IS 1 BP 20 EP 26 DI 10.1086/648674 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539YO UT WOS:000273296500004 PM 19947857 ER PT J AU Lehman, D Tseng, CW Eells, S Miller, LG Fan, XM Beenhouwer, DO Liu, GY AF Lehman, Deborah Tseng, Ching Wen Eells, Samantha Miller, Loren G. Fan, Xuemo Beenhouwer, David O. Liu, George Y. TI Staphylococcus aureus Panton-Valentine Leukocidin Targets Muscle Tissues in a Child with Myositis and Necrotizing Fasciitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID VIRULENCE DETERMINANT; SKIN INFECTIONS; GENES; PNEUMONIA; DISEASE; PYOMYOSITIS; USA300; CLONE; LUNG AB The incidence of myositis has been increasing since the advent of the epidemic of community-associated methicillin-resistant Staphylococcus aureus infection, and Panton-Valentine leukocidin has been implicated as a factor contributing to more-severe muscle injury. We report a case of severe myositis accompanying septic osteomyelitis and necrotizing fasciitis caused by a Panton-Valentine leukocidin-positive S. aureus strain. Immunostaining showed strong binding of the Panton-Valentine leukocidin toxin to necrotic muscle tissues. C1 [Lehman, Deborah; Tseng, Ching Wen; Liu, George Y.] Cedars Sinai Med Ctr, Div Pediat Infect Dis, Los Angeles, CA 90048 USA. [Tseng, Ching Wen; Liu, George Y.] Cedars Sinai Med Ctr, Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Fan, Xuemo] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Lehman, Deborah; Tseng, Ching Wen; Liu, George Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Beenhouwer, David O.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Beenhouwer, David O.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Eells, Samantha; Miller, Loren G.] Univ Calif Los Angeles, Los Angeles BioMed Res Inst Harbor, Torrance, CA USA. [Eells, Samantha; Miller, Loren G.] Univ Calif Los Angeles, Div Infect Dis, Torrance, CA USA. RP Liu, GY (reprint author), Cedars Sinai Med Ctr, Div Pediat Infect Dis, NT4221, Los Angeles, CA 90048 USA. EM george.liu@cshs.org FU Burroughs-Wellcome Career; National Institutes of Health [AI074832] FX Financial support. Burroughs-Wellcome Career Award and National Institutes of Health (AI074832 to G. Y. L.). NR 22 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2010 VL 50 IS 1 BP 69 EP 72 DI 10.1086/649217 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539YO UT WOS:000273296500011 PM 19995216 ER PT J AU Seltzer, B AF Seltzer, Ben TI Galantamine-ER for the treatment of mild-to-moderate Alzheimer's disease SO CLINICAL INTERVENTIONS IN AGING LA English DT Review DE galantamine; cholinesterase inhibitors; Alzheimer's disease AB An extended release form of the cholinesterase inhibitor (ChEI) drug galantamine (galantamine-ER) was developed, chiefly to increase adherence to medication regimes in patients with mild-to-moderate Alzheimer's disease (AD). Except for predicted differences in (C-max) and t(max), comparable doses of once daily galantamine-ER and regular, immediate release galantamine, (galantamine-IR), are pharmacologically equivalent. A 24-week randomized, double-blind, placebo-and active-controlled, multicenter phase III trial, which compared galantamine-IR, galantamine-ER and placebo in subjects with mild to moderate AD (mini-mental state examination [MMSE] score range, 10 to 24) showed that both formulations of galantamine were significantly better than placebo in terms of cognition, although not with regard to global change. There was no difference in drug-related adverse events between galantamine-ER and galantamine-IR. Since its release onto the market galantamine-ER has enjoyed wide popularity and a recent surveillance study suggests that it has the highest 1-year persistence rate of all the ChEIs. C1 Harvard Univ, VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Dept Neurol,Sch Med, Boston, MA 02130 USA. RP Seltzer, B (reprint author), Harvard Univ, VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Dept Neurol,Sch Med, 150 S Huntington Ave, Boston, MA 02130 USA. EM bseltzer@partners.org FU Geriatric Research, Education, and Clinical Center, VA Boston Healthcare System; Janssen FX Supported by the Geriatric Research, Education, and Clinical Center, VA Boston Healthcare System.; The author has received research funding and honoraria for speaking from Janssen. NR 60 TC 13 Z9 14 U1 2 U2 10 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9092 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2010 VL 5 BP 1 EP 6 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA V21XA UT WOS:000208239100001 PM 20169037 ER PT J AU Forrest, GN Tamura, K AF Forrest, Graeme N. Tamura, Kimberly TI Rifampin Combination Therapy for Nonmycobacterial Infections SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID RESISTANT STAPHYLOCOCCUS-AUREUS; PROSTHETIC VALVE ENDOCARDITIS; IN-VITRO ACTIVITY; VANCOMYCIN PLUS RIFAMPIN; ACINETOBACTER-BAUMANNII INFECTIONS; LEGIONELLA-PNEUMOPHILA PNEUMONIA; COAGULASE-NEGATIVE STAPHYLOCOCCI; RIFABUTIN DRUG-INTERACTIONS; SERUM BACTERICIDAL ACTIVITY; CENTRAL VENOUS CATHETERS AB The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities. C1 [Forrest, Graeme N.; Tamura, Kimberly] Portland VA Med Ctr, Portland, OR 97239 USA. [Forrest, Graeme N.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Forrest, GN (reprint author), Portland VA Med Ctr, 3701 SW US Vet Hosp Rd,Mail Code P3-ID, Portland, OR 97239 USA. EM forrestg@ohsu.edu NR 279 TC 75 Z9 78 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JAN PY 2010 VL 23 IS 1 BP 14 EP 34 DI 10.1128/CMR.00034-09 PG 21 WC Microbiology SC Microbiology GA 542QW UT WOS:000273511000001 PM 20065324 ER PT B AU Reimer, P Schima, W Lauenstein, T Saini, S AF Reimer, Peter Schima, Wolfgang Lauenstein, Thomas Saini, Sanjay BE Reimer, P Parizel, PM Meaney, JFM Stichnoth, FA TI Abdomen: Liver, Spleen, Biliary System, Pancreas, and GI Tract SO CLINICAL MR IMAGING: A PRACTICAL APPROACH, THIRD EDITION LA English DT Article; Book Chapter ID MR-IMAGING FINDINGS; HEPATOCELLULAR-CARCINOMA; PATHOLOGICAL CORRELATION; CROHNS-DISEASE; LESIONS; COLONOGRAPHY; DIAGNOSIS; NODULES; BENIGN; BOWEL C1 [Reimer, Peter] Klinikum Karlsruhe, Dept Radiol, D-76133 Karlsruhe, Germany. [Lauenstein, Thomas] Univ Hosp Essen, Dept Radiol, D-45122 Essen, Germany. [Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Schima, Wolfgang] Krankenhaus Gottlicher Heiland, Abt Radiol, A-1170 Vienna, Austria. RP Reimer, P (reprint author), Klinikum Karlsruhe, Dept Radiol, Moltkestr 90, D-76133 Karlsruhe, Germany. EM p.reimer@web.de; p.reimer@web.de NR 39 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-74501-3 PY 2010 BP 357 EP 417 DI 10.1007/978-3-540-74504-4_6 D2 10.1007/978-3-540-74504-4 PG 61 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BOL35 UT WOS:000276939200006 ER PT J AU Johnson, AL Storzbach, D Binder, LM Barkhuizen, A Anger, WK Salinsky, MC Tun, SM Rohlman, DS AF Johnson, Amy L. Storzbach, Daniel Binder, Laurence M. Barkhuizen, Andre Anger, W. Kent Salinsky, Martin C. Tun, Saw-Myo Rohlman, Diane S. TI MMPI-2 PROFILES: FIBROMYALGIA PATIENTS COMPARED TO EPILEPTIC AND NON-EPILEPTIC SEIZURE PATIENTS SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Fibromyalgia; Veterans; MMPI-2 ID FAKE BAD SCALE; CEREBRAL BLOOD-FLOW; RHEUMATOID-ARTHRITIS; UNEXPLAINED SYMPTOMS; PSYCHOSOCIAL FACTORS; CHRONIC PAIN; DEPRESSION; HEALTH; WOMEN; VETERANS AB We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES) patients, and Gulf War veteran healthy controls. Both PNES and FM are medically unexplained conditions. In previous MMPI-2 research PNES patients were shown to have significantly higher Hs and Hy clinical scales than ES patients. In the present research the FM group had significantly higher Hs and Hy scale scores than both the ES group and the healthy control group. There was no significant difference between the FM and PNES Hs scale scores; however, the FM Hy scale score was significantly lower than the PNES Hy scale score. Present findings indicate a high level of psychological distress in the FM group. C1 [Johnson, Amy L.; Storzbach, Daniel; Tun, Saw-Myo] Portland VA Med Ctr, Portland, OR 97239 USA. [Storzbach, Daniel; Binder, Laurence M.; Barkhuizen, Andre; Anger, W. Kent; Salinsky, Martin C.; Rohlman, Diane S.] Oregon Hlth & Sci Univ, Beaverton, OR USA. RP Johnson, AL (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM amy.johnson2@va.gov NR 64 TC 8 Z9 9 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 2 BP 220 EP 234 DI 10.1080/13854040903266902 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 566HR UT WOS:000275361200003 PM 19859855 ER PT J AU Foley, J Ettenhofer, M Wright, MJ Siddiqi, I Choi, M Thames, AD Mason, K Castellon, S Hinkin, CH AF Foley, Jessica Ettenhofer, Mark Wright, Matthew J. Siddiqi, Iraj Choi, Melissa Thames, April D. Mason, Karen Castellon, Steven Hinkin, Charles H. TI NEUROCOGNITIVE FUNCTIONING IN HIV-1 INFECTION: EFFECTS OF CEREBROVASCULAR RISK FACTORS AND AGE SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Cerebrovascular; HIV/AIDS; Neurocognitive; Aging ID IMMUNODEFICIENCY-VIRUS-INFECTION; INTIMA-MEDIA THICKNESS; AIDS DEMENTIA COMPLEX; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; COGNITIVE FUNCTION; MEDICATION ADHERENCE; KUNGSHOLMEN PROJECT; CARDIOVASCULAR RISK; DIABETES-MELLITUS AB This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age > 50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = -2.071; p = .04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p = .002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment. C1 [Foley, Jessica; Ettenhofer, Mark; Castellon, Steven; Hinkin, Charles H.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Siddiqi, Iraj] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Wright, Matthew J.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Choi, Melissa; Thames, April D.; Castellon, Steven; Hinkin, Charles H.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Mason, Karen] Calif State Univ Dominguez Hills, Los Angeles, CA USA. RP Foley, J (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,C8-746, Los Angeles, CA 90095 USA. EM jmfoley@ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU NIMH [R01 MH58522]; [5 T32 MH19535] FX Funding was as follows: (1) NIMH R01 MH58522: Cognitive deficits and medication adherence in HIV/AIDS to CHH; (2) 5 T32 MH19535: Neuropsychology of HIV/AIDS to CHH. NR 89 TC 34 Z9 34 U1 4 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 2 BP 265 EP 285 DI 10.1080/13854040903482830 PG 21 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 566HR UT WOS:000275361200006 PM 20162495 ER PT J AU Goldstein, G AF Goldstein, Gerald TI ADVOCACY FOR NEUROPSYCHOLOGY IN THE PUBLIC SECTOR: THE VA EXPERIENCE SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Veterans; Advocacy; Neuropsychology; Geropsychology ID ACADEMY AB In this paper important advocacy areas for the VA are described with implications for other psychologists working in institutional settings in the public sector, and some advice is provided concerning how best to advocate in the VA. Distinctions among advocacy issues that are of concern to the general public, those that are of concern to all psychologists involved in healthcare, and those specifically related to clinical neuropsychology are made. C1 [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM ggold@nb.net FU Medical Research Service, Department of Veterans Affairs FX This work was supported by the Medical Research Service, Department of Veterans Affairs. NR 11 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 3 SI SI BP 401 EP 416 DI 10.1080/13854040903313597 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 589ZL UT WOS:000277192600003 PM 20373221 ER PT J AU Hilsabeck, RC Martin, EM AF Hilsabeck, Robin C. Martin, Eileen M. TI WOMEN AND ADVANCEMENT IN NEUROPSYCHOLOGY: REAL-LIFE LESSONS LEARNED SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Leadership; Advancement; Advocacy; Women; Neuropsychology ID ASSOCIATION PRACTICE SURVEY; CLINICAL NEUROPSYCHOLOGY; ACADEMIC MEDICINE; UNITED-STATES; LEADERSHIP; NATIONAL-ACADEMY-OF-NEUROPSYCHOLOGY/DIVISION-40; FACULTY; GENDER AB The number of women in neuropsychology has been increasing over the past 20 years while the number of women in senior and leadership positions within neuropsychology has not. The field of neuropsychology has much to gain by facilitating the advancement of women into leadership roles, including access to some of the brightest and creative minds in the field. The purpose of this article is to offer practical advice about how to overcome barriers and advance within neuropsychology. Suggestions for professional organizations, women, and mentors of women are provided that will likely benefit trainees and junior colleagues regardless of their gender. C1 [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Psychol Serv 116B, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Martin, Eileen M.] Univ Illinois, Chicago, IL USA. RP Hilsabeck, RC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Psychol Serv 116B, S Texas Vet Hlth Care Syst, 7400 Merton Winter Blvd, San Antonio, TX 78229 USA. EM Hilsabeck@uthscsa.edu FU NIDA NIH HHS [R01 DA012828, R01 DA12828]; NINDS NIH HHS [K23 NS051244] NR 15 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 3 SI SI BP 481 EP 492 DI 10.1080/13854040802360566 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 589ZL UT WOS:000277192600008 PM 18841516 ER PT J AU Barker, MD Horner, MD Bachman, DL AF Barker, Marie D. Horner, Michael David Bachman, David L. TI Embedded Indices of Effort In The Repeatable Battery For The Assessment of Neuropsychological Status (Rbans) In A Geriatric Sample SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Effort; Motivation; Repeatable Battery for the Assessment of Neuropsychological Status; RBANS; Geriatric ID MEMORY MALINGERING TOMM; ALZHEIMERS-DISEASE; COGNITIVELY INTACT; NORMATIVE DATA; VALIDITY; SPECIFICITY; SENSITIVITY; DEPRESSION; SYMPTOMS; DEMENTIA AB The clinical utility of embedded indices of effort in the RBANS was examined in a geriatric sample. Patients were classified as providing suspect effort (n = 45) or probable good effort (n = 258) using the TOMM and clinical consensus. Following the methodology of Silverberg and colleagues (2007), selected individual subtests and a summary Effort Index were evaluated. Setting specificity at approximately 85% yielded cut-offs of 15 on List Recognition, 8 on Digit Span, and 3 on the Effort Index. The modest sensitivity (51.1-64.4%) suggests that the indices should be used in conjunction with additional effort measures. In addition, the RBANS Picture Naming subtest was examined and showed modest sensitivity to detect suboptimal effort, but did not show notable incremental validity for detecting suboptimal effort beyond the Effort Index. C1 [Barker, Marie D.; Horner, Michael David; Bachman, David L.] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29407 USA. [Barker, Marie D.; Horner, Michael David; Bachman, David L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Barker, Marie D.] Univ Florida, Gainesville, FL USA. RP Barker, MD (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29407 USA. EM barker.marie@gmail.com NR 32 TC 18 Z9 18 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 6 BP 1064 EP 1077 AR PII 922905051 DI 10.1080/13854046.2010.486009 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 636WE UT WOS:000280773600007 PM 20544558 ER PT J AU Bangen, KJ Delano-Wood, L Wierenga, CE Stricker, NH Hesselink, JR Bondi, MW AF Bangen, Katherine J. Delano-Wood, Lisa Wierenga, Christina E. Stricker, Nikki H. Hesselink, John R. Bondi, Mark W. TI Dementia Following Herpes Zoster Encephalitis SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Herpes zoster; Encephalitis; MRI; Cognition; Dementia ID POSTHERPETIC NEURALGIA; SIMPLEX ENCEPHALITIS; OLDER-ADULTS; MANAGEMENT; ACYCLOVIR; PAIN AB We studied the rare case of an older adult with dementia following herpes zoster encephalitis (HZE). This 71-year-old woman presented to us approximately 1 year following resolution of a rapid-onset episode of HZE, and subsequently underwent neuropsychological and neuroimaging examinations. Cognitive assessment revealed impairments in general cognitive functioning, verbal and nonverbal memory, executive functions, speed of information processing, attention/working memory, and motor skills. The patient's neuroimaging data, when compared to a demographically similar healthy control sample (n = 9), demonstrated moderate central and perisylvian brain volume loss, several subcortical lesions in the white matter, and resting state whole brain and hippocampal hypoperfusion. These findings highlight neuropsychological changes evident in a dementia syndrome of this type, and they suggest that early identification and treatment of HZE has implications for the preservation of long-term cognitive functioning. C1 [Bangen, Katherine J.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, La Jolla, CA 92093 USA. [Delano-Wood, Lisa] Vet Med Res Fdn, San Diego, CA USA. [Delano-Wood, Lisa; Wierenga, Christina E.; Bondi, Mark W.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Wierenga, Christina E.; Bondi, Mark W.] VA San Diego Healthcare Syst, San Diego, CA USA. [Stricker, Nikki H.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Hesselink, John R.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Hesselink, John R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Bondi, MW (reprint author), VA San Diego Healthcare Syst 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM mbondi@ucsd.edu FU National Institutes of Health [F31 NS059193, P50 AG05131, K24 AG026431, RO1 AG012674]; Alzheimer's Association [IIRG-07-59343] FX The authors gratefully acknowledge the assistance of staff, patients, and volunteers of the UCSD Alzheimer's Disease Research Center. This work was supported by grants from the National Institutes of Health (F31 NS059193 [KJB], P50 AG05131 [DPS], K24 AG026431, RO1 AG012674, and by grant IIRG-07-59343 from the Alzheimer's Association [MWB]). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Alzheimer's Association or the National Institutes of Health. NR 33 TC 9 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 7 BP 1193 EP 1203 AR PII 922503641 DI 10.1080/13854041003736778 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 659UM UT WOS:000282592400007 PM 20503134 ER PT J AU Solomon, RE Boone, KB Miora, D Skidmore, S Cottingham, M Victor, T Ziegler, E Zeller, M AF Solomon, Ryan E. Boone, Kyle Brauer Miora, Deborah Skidmore, Sherry Cottingham, Maria Victor, Tara Ziegler, Elizabeth Zeller, Michelle TI Use of the WAIS-III Picture Completion Subtest as an Embedded Measure of Response Bias SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Response bias; Picture completion; Malingering ID SUSPECT EFFORT; RECOGNITION TRIAL; SENSITIVITY; PERFORMANCE; DEFICITS; SCORES; SPECIFICITY AB In the present study a large sample of credible patients (n = 172) scored significantly higher than a large sample of noncredible participants (n = 195) on several WAIS-III Picture Completion variables: Age Adjusted Scaled Score, raw score, a oRarely Missedo index (the nine items least often missed by credible participants), a oRarely Correcto index (nine items correct 26% of the time in noncredible participants and with at least a 25 percentage-point lower endorsement rate as compared to credible participants), and a oMost Discrepanto index (the six items that were the most discrepant in correct endorsement between groupsat least a 40 percentage point difference). Comparison of the various scores showed that the oMost Discrepanto index outperformed all the others in identifying response bias (nearly 65% sensitivity at 92.8% specificity as compared to at most 59% sensitivity for the other scores). While no differences in Picture Completion scores were observed between less-educated (12 years) and better-educated (epsilon 12 years) credible participants, noncredible participants with 12 years of education scored significantly poorer than noncredible participants with 12 or more years of education. On the oMost Discrepanto index, 76.7% of less-educated noncredible participants were detected as compared to 58.3% of better-educated noncredible participants. Results of the current study suggest that the Picture Completion subtest of the WAIS-III is an effective measure of response bias, and that it may have a unique role in identifying suboptimal effort in less-educated test takers. C1 [Solomon, Ryan E.; Boone, Kyle Brauer; Miora, Deborah; Skidmore, Sherry] Alliant Int Univ, Calif Sch Forens Studies, Los Angeles, CA USA. [Cottingham, Maria] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA. [Victor, Tara] Calif State Univ Dominguez Hills, Carson, CA 90747 USA. [Ziegler, Elizabeth] VA Med Ctr Spokane, Washington, DC USA. [Zeller, Michelle] W Los Angeles VA, Los Angeles, CA USA. RP Solomon, RE (reprint author), Alliant Int Univ, Calif Sch Forens Studies, Los Angeles, CA USA. EM rsolomon@alliant.edu NR 27 TC 9 Z9 9 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2010 VL 24 IS 7 BP 1243 EP 1256 AR PII 927591054 DI 10.1080/13854046.2010.514864 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 659UM UT WOS:000282592400010 PM 20924983 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Normal Anatomy SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Vermillion; Vestibule; Oral cavity proper; Oropharynx; Fauces; Palatoglossal arch; Palatopharyngeal arch; Retromolar trigone; Pterygomandibular raphe; Buccinator muscle; Muscles of mastication; Stenson duct; Wharton duct; Waldeyer ring; Lingual papillae; Tonsils; Tongue; Palate; Mucosa; Floor of mouth; Mucogingival junction; Parotid papilla; Palatal rugae; Periosteum; Gingival margin; Interdental papilla; Cementoenamel junction; Cementum; Enamel; Pulp; Foramen cecum; Incisive papilla; Apical foramen; Periodondal ligament; Trigeminal nerve; Temporomandibular joint; Parotid gland; Submandibular gland; Sublingual gland; Minor salivary glands; Lingual nerve; Inferior alveolar nerve; Cervical lymph nodes AB Knowledge of normal anatomy and physiology of the oral cavity provides a basis for understanding and recognizing pathology. This chapter provides a review and overview of surface landmarks and underlying anatomy of the oral cavity in the context of diagnosing conditions that are detailed throughout the remainder of the book. The oral mucosa, palate. tongue, floor of mouth, dentition, salivary glands, and cervical lymphatic drainage are specifically highlighted. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 9 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 1 EP 15 DI 10.1007/978-1-60327-520-0_1 D2 10.1007/978-1-60327-520-0 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500001 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Variants of Normal and Common Benign Conditions SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Melanocytes; Melanin; Physiologic pigmentation; Melanotic macule; Melanoma; Fordyce granule; Sebaceous gland; Gingival graft; Free gingival graft; Lingual tonsil; Tonsil; Fissured tongue; Geographic tongue; Benign migratory glossitis; Stomatitis erythema migrans; Erythema migrans; Median rhomboid glossitis; Fibroma; Irritation fibroma; Traumatic fibroma; Inflammatory papillary hyperplasia; Epulis fissuratum; Torus; Mandibular torus; Maxillary torus; Exostosis; Ankyloglossia; Frenula ID DIAGNOSIS; TONGUE AB Fundamental to diagnosing oral pathologic conditions is the ability to recognize the spectrum of clinical findings that represents variation of normal within the population. The range of such variation is wide and findings can be very subtle or notably prominent. Some are purely developmental, while others have a clear inflammatory or traumatic etiology. This chapter describes the most commonly encountered variations of normal and benign conditions encountered in the oral cavity, with specific guidelines for diagnosis and management, when clinically indicated. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 17 EP 26 DI 10.1007/978-1-60327-520-0_2 D2 10.1007/978-1-60327-520-0 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500002 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Diagnostic Tests and Studies SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Saliva; Salivary glands; Culture; Herpes simplex virus; Varicella zoster virus; Direct fluorescence antibody test; Polymerase chain reaction; Cytomegalovirus; Radiographs; Computed tomography; Magnetic resonance imagine; Positron emission tomography; Ultrasonography; Scintigraphy; Sialography; Photography; Cytology; Fine needle aspiration biopsy; Biopsy; Direct immunofluorescence; Brush cytology; Toluidine blue ID MAXILLOFACIAL PATHOLOGY; ORAL-CANCER AB Diagnostic tests and studies often provide essential clinical data necessary to arrive at the correct diagnosis of various oral pathological conditions. In many cases, negative findings are just as revealing as positive findings. The most important considerations are when, why, and how to order certain studies, how to interpret the results, and what to do with the information obtained. This chapter emphasizes a rational approach to the utilization and interpretation of culture, imaging, and tissue-based diagnostic studies for the evaluation of patients with oral pathological conditions. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 27 EP 40 DI 10.1007/978-1-60327-520-0_3 D2 10.1007/978-1-60327-520-0 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500003 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI White Lesions SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Hypertrophy; Hyperplasia; Keratin; Acanthosis; Hyperkeratosis; Leukoedema; Li nea alba; Lichen planus; Morsicatio; Leukoplakia; Hairy tongue; Filiform papillae; Candidiasis; Oral hairy leukoplakia; Nicotinicstomatitis; Smoker's palate; Tobacco pouch keratosis; White sponge nevus; Exfoliative cheilitis; Angular cheilitis ID ALVEOLAR RIDGE KERATOSIS; LEUKOPLAKIA AB The oral mucosa is normally semitranslucent. allowing the color of underlying tissues to show through to a variable degree. Lesions may appear white secondary to increased thickness of the epithelium or decreased submucosal vascularity, however, the etiology of white lesions is quite varied. This chapter reviews commonly seen white lesions of the oral cavity, with attention to differential diagnosis and treatment recommendations. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 6 TC 0 Z9 0 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 41 EP 48 DI 10.1007/978-1-60327-520-0_4 D2 10.1007/978-1-60327-520-0 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500004 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Immune-Mediated and Allergic Conditions SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Angioedema; C1 esterase deficiency; ACE inhibitors; Orofacial granulomatosis; Melkersson-Rosenthal syndrome; Crohn disease; Ulcerative colitis; Inflammatory bowel disease; Sarcoidosis; Traumatic ulcerative granuloma; Aphthous stomatitis; Aphthous ulcer; Canker sore; Minor aphthous ulcer; Major aphthous ulcer; Herpetiform aphthous ulcer; Severe aphthous stomatitis; Behcet disease; Skin pathergy test; Erythema multiforme; Oral lichen planus; Lichen planus; Lichenoid hypersensitivity reaction; Desquamative gingivitis; Pemphigus vulgaris; Pemphigoid; Mucous membrane pemphigoid; Linear IgA disease; Nikolsky sign; Paraneoplastic pemphigus; Epidermolysis bullosa acquisita ID ORAL MUCOSAL DISEASE; OROFACIAL GRANULOMATOSIS; LICHEN-PLANUS; VII AB A wide variety of immune-mediated conditions can affect the orofacial region. These range from localized immune responses, Such as contact hypersensitivity, to systemic diseases with distinct and often prominent oral manifestations, such as the autoimmune vesiculobullous disorders. Oral lesions may precede the appearance of findings in other areas of the body or may represent the sole manifestation of the disease. Establishing the correct diagnosis is critical, as management strategies can vary considerably from one entity to the next. This chapter reviews the most commonly encountered immune-mediated conditions that have prominent oral manifestations, with specific guidelines for the use and interpretation of diagnostic tests and biopsy, and management strategies. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 49 EP 68 DI 10.1007/978-1-60327-520-0_5 D2 10.1007/978-1-60327-520-0 PG 20 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500005 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Pigmented Lesions SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Physiologic pigmentation; Exogenous pigmentation; Endogenous pigmentation; Melanin; Melanocyte; Bilirubin; Melanotic macule; Nevus; Smoker's melanosis; Addison disease; Cushing syndrome; Peutz-Jeghers syndrome; Amalgam tattoo; Hemochromatosis; Ferritin; Hemoiderin; Varix; Hemangioma; Vascular malformation; Pyogenic granuloma; Kaposi sarcoma; Hematoma; Petechiae; Osler-Weber-Rendu syndrome ID OF-THE-LITERATURE AB Unusual or abnormal coloration of the oral mucosa can arise from a variety of exogenous (extrinsic) or endogenous (intrinsic) sources. Pigmentation varies widely and may be present in a generalized fashion throughout the oral cavity or as an isolated focal lesion. This chapter discusses the etiology and presentation of pigmented lesions as well as certain systemic conditions associated with oral pigmentation. Diagnostic and treatment guidelines are provided. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 69 EP 80 DI 10.1007/978-1-60327-520-0_6 D2 10.1007/978-1-60327-520-0 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500006 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Oral Infections SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Caries; Cavities; Periodontal disease; Abscess; Periapical abscess; Periapical granuloma; Periapical radiolucency; Periodontal abscess; Streptococcus mutans; Ludwig angina; Necrotizing fasciitis; Mediastinitis; Trismus; Endodontic therapy; Root canal therapy; Neutropenia; Calculus; Tartar; Plaque; Periodontal disease; Furcation; Pericoronitis; Inflammatory gingival hyperplasia; Nifedipine; Phenytoin; Cyclosporine; Acute necrotizing stomatitis; Parotitis; Paramyxovirus; Mumps; Epstein-Barr virus; Cytomegalovirus; HIV; Candida Abicans; Candidiasis; Thrush; Pseudomembranous candidiasis; Hyperplastic candidiasis; Erythematous candidiasis; Angular cheilitis; Aspergillosis; Cryptococcosis; Blastomycosis; Histoplasmosis; Paracoccidioidomycosis; Mucormycosis; Human papilloma virus; Enterovitus; Shingles; Postherpetic neuralgia; Ramsay Hunt syndrome; Herpes zoster oticus; Mononucleosis; Oral hairy leukoplakia; Post-transplant lymphoproliferative disease; Squamous cell carcinoma; Squamous papilloma; Verruca vulgaris; Condyloma acuminaten; Focal epithelial hyperplasia; Heck disease; Coxsackievirus; Herpangina; Hand-foot-and-mouth disease AB Bacterial, fungal, and viral infections are frequently encountered in the oral cavity. There is no single feature characterizing infection in the mouth, and in many cases the clinical appearance may be similar to that of noninfectious conditions. Careful history taking and examination, identification of risk factors, and appropriate utilization and interpretation of diagnostic tests are critical for determining the correct diagnosis and initiating appropriate therapy. This chapter provides a rational approach to assessing, diagnosing, and managing patients with oral infections, with a special emphasis on those with underlying immunosuppression. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 11 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 81 EP 101 DI 10.1007/978-1-60327-520-0_7 D2 10.1007/978-1-60327-520-0 PG 21 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500007 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Salivary Gland Disease SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Saliva; Mucocele; Ranula; Mylohyoid muscle; Mucus retention cyst; Sialadenitis; Sialolithiasis; Sialagogue; Necrotizing sialometaplasia; Sialosis; Xerostomia; Sjogren syndrome; Sicca syndrome; Lymphoma; Radiation therapy; Osteoradionecrosis; Radioactive iodine; Neoplasia; Pleomorphic adenoma; Warthin tumor; Mucoepidermoid carcinoma; Adenoid cystic carcinoma; Acinic cell carcinoma; Polymorphous low-grade carcinoma AB Saliva serves a variety of important functions, many of which are not appreciated until salivary flow decreases. A wide spectrum of pathologic conditions, including inflammatory, infectious, and neoplastic, affect the major and minor salivary glands, resulting in potentially significant morbidity and diminished quality of life for the patient. This chapter provides a review of conditions affecting the salivary glands, with attention to the more common entities that are likely to be encountered in clinical practice along with relevant practical treatment guidelines. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 103 EP 111 DI 10.1007/978-1-60327-520-0_8 D2 10.1007/978-1-60327-520-0 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500008 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Oral Cancer SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Oral cancer; Squamous cell carcinoma; Carcinogen; Smokeless tobacco; Synergistic effect; Betel; Dyskeratosis congenita; Fanconi anemia; Plummer-Vinson syndrome; Sanguinaria; Exophytic; Tobacco; Alcohol; Fixation; Induration; Verrucous carcinoma; Dysplasia; Carcinoma-in-situ; Cytology; Biopsy; Actinic cheilitis; Leukoplakia; Erythroplakia; Proliferative verrucous leukoplakia; Tobacco pouch keratosis; Oral submucous fibrosis; Lichen planus; Cancer staging; Metastasis; Mucositis; Osteoradionecrosis; Xerostomia; Radiation therapy; Chemotherapy; Hyperbaric oxygen therapy ID OF-THE-LITERATURE; DYSKERATOSIS-CONGENITA; EPITHELIAL DYSPLASIA; NECK-CANCER; HEAD; LEUKOPLAKIA; CARCINOMA; DISEASE; LESIONS AB Oral cancer imposes a significant burden on public health in the USA and many parts of the world. The morbidity of the disease and its treatment can be quite substantial, resulting in disfigurement, pain, impaired speech and swallowing, and overall decreased quality of life. Unfortunately, overall 5-year survival remains approximately 50%, which has not improved significantly over time despite technological advances in treatment. This chapter outlines the epidemiology, major known risk factors, and clinical features of oral malignant and premalignant lesions as well as management guidelines. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org NR 21 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 113 EP 128 DI 10.1007/978-1-60327-520-0_9 D2 10.1007/978-1-60327-520-0 PG 16 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500009 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Orofacial Pain Conditions SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Nociceptive; Allodynia; Neuropathic pain; Dysesthesia; Odontogenic pain; Referred pain; Temporomandibular joint pain; Arthralgia; Myofascial pain disorder; Parafunctional activity; Bruxism; Trigger point; Crepitus; Atypical facial pain; Persistent idiopathic facial pain; Atypical odontalgia; Trigeminal neuralgia; Glossopharyngeal neuralgia; Occipital neuralgia; Burning mouth syndrome; Stomatodynia AB Orofacial pain is a common symptom that causes significant morbidity. The majority of orofacial pain disorders can be classified as odontogenic, myofascial, temporomandibular joint-related, and new ropathic. A careful history accompanied by a comprehensive examination in most cases is sufficient to determine the correct diagnosis, although laboratory tests and imaging studies may be indicated. Careful explanation of the diagnosis and establishment of realistic treatment goals are critically important for successful outcomes. This chapter provides a rational approach to the evaluation, diagnosis, and management of patients with orofacial pain. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 129 EP 138 DI 10.1007/978-I-60327-520-0_10 D2 10.1007/978-1-60327-520-0 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500010 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Oral Manifestations of Systemic Disease SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Systemic lupus erythematosus; Lichenoid inflammation; Sjogren syndrome; Discoid lupus; Scleroderma; Graft-versus-host disease; Inflammatory bowel disease; Crohn disease; Angular cheilitis; Orofacial granulomatosis; Ulcerative colitis; Pyostomatitis vegetans; Gardner syndrome; Peutz-Jeghers syndrome; Wegener granulomatosis; Antineutrophilic cytoplasmic antibody; Sarcoidosis; Heerfordt syndrome; Angiotensin converting enzyme; Human immunodeficiency syndrome; Iron deficiency anemia; Plummer-Vinson syndrome; Pernicious anemia; Intrinsic factor; Thrombocytopenia; Cyclic neutropenia; Lymphoma; Midline lethal granuloma; Leukemia; Cowden syndrome; Jaundice; Bisphosphonate-associated osteonecrosis; Sequestra ID OF-THE-LITERATURE; LUPUS-ERYTHEMATOSUS; SARCOIDOSIS; DIAGNOSIS; LESIONS AB Lesions inside the oral cavity can be associated with a number of systemic conditions, representing important indicators of active disease or heralding the onset of disease. Recognition of such lesions may facilitate prompt diagnosis and treatment of underlying disease with overall improvement in patients' quality of life. In some cases, oral findings persist despite adequate systemic management of disease, necessitating targeted ancillary care measures. This chapter reviews the presentation and management of oral findings that may be seen in association with systemic conditions, including autoimmune, gastrointestinal, and granulomatous disorders. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 139 EP 157 DI 10.1007/978-1-60327-520-0_11 D2 10.1007/978-1-60327-520-0 PG 19 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500011 ER PT B AU Bruch, JM Treister, NS AF Bruch, Jean M. Treister, Nathaniel S. BA Bruch, JM Treister, NS BF Bruch, JM Treister, NS TI Prescribing Guidelines for Commonly Used Medications SO CLINICAL ORAL MEDICINE AND PATHOLOGY LA English DT Article; Book Chapter DE Food and drug administration; Cream; Ointment; Gel; Solutions; Candidiasis; Fluconazole; Clotrimazole; Nystatin; Fluocinonide; Clobetasol propionate; Dexamathastone; Tacrolimus; Prednisone; Methylprednisolone; Azathioprine; Colchicine; Dapsone; Hydroxychloroquine; Mycophenolate mofetil; Pentoxyfilline; Thalidomide; Penicillin; Clindamycin; Metronidazole; Amoxicillin/clavulanic acid; Chlorhexidine gluconate; Acyclovir; Valacyclovir; Pilocarpine; Cevimeline; Fluoride; Ibuprofren; Ketoprofen; Clonazepam; Gabapentin; Carbamezapine; Amitriptyline; Nortriptyline; Magic mouthwash; Morphine AB A wide range of topical and systemic medications are used in the management of oral medicine conditions. The vast majority of these therapies are not FDA approved for the specific conditions discussed in this book and are therefore considered "off-label" indications. This chapter provides very specific prescribing guidelines and considerations to ensure that the included medications are used in an appropriate and effective manner for the management of oral diseases. C1 [Bruch, Jean M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Treister, Nathaniel S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bruch, JM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM jean_bruch@meei.harvard.edu; ntreister@partners.org; jean_bruch@meei.harvard.edu; ntreister@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-519-4 PY 2010 BP 159 EP 163 DI 10.1007/978-1-60327-520-0_12 D2 10.1007/978-1-60327-520-0 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BMI83 UT WOS:000272512500012 ER PT J AU Bozic, KJ Kurtz, SM Lau, E Ong, K Chiu, V Vail, TP Rubash, HE Berry, DJ AF Bozic, Kevin J. Kurtz, Steven M. Lau, Edmund Ong, Kevin Chiu, Vanessa Vail, Thomas P. Rubash, Harry E. Berry, Daniel J. TI The Epidemiology of Revision Total Knee Arthroplasty in the United States SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Scientific Meeting of the Knee-Society CY FEB, 2009 CL Las Vegas, NV SP Knee Soc ID TERM FOLLOW-UP; 2-STAGE REIMPLANTATION; JOINT REPLACEMENT; SURVIVORSHIP; POPULATION; PROSTHESIS; OSTEOLYSIS; FAILURE; MODES; HIP AB Understanding the cause of failure and type of revision total knee arthroplasty (TKA) procedures performed in the United States is essential in guiding research, implant design, and clinical decision making in TKA. We assessed the causes of failure and specific types of revision TKA procedures performed in the United States using newly implemented ICD-9-CM diagnosis and procedure codes related to revision TKA data from the Nationwide Inpatient Sample (NIS) database. Clinical, demographic, and economic data were reviewed and analyzed from 60,355 revision TKA procedures performed in the United States between October 1, 2005 and December 31, 2006. The most common causes of revision TKA were infection (25.2%) and implant loosening (16.1%), and the most common type of revision TKA procedure reported was all component revision (35.2%). Revision TKA procedures were most commonly performed in large, urban, non-teaching hospitals in Medicare patients ages 65 to 74. The average length of hospital stay (LOS) for all revision TKA procedures was 5.1 days, and the average total charges were $49,360. However, average LOS, average charges, and procedure frequencies varied considerably by census region, hospital type, and procedure performed. C1 [Bozic, Kevin J.; Chiu, Vanessa; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Bozic, Kevin J.; Chiu, Vanessa] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Kurtz, Steven M.; Ong, Kevin] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund] Exponent Inc, Menlo Pk, CA USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus Ave,MU320W, San Francisco, CA 94143 USA. EM bozick@orthosurg.ucsf.edu NR 29 TC 273 Z9 290 U1 5 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2010 VL 468 IS 1 BP 45 EP 51 DI 10.1007/s11999-009-0945-0 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 558SU UT WOS:000274767200008 PM 19554385 ER PT J AU Haggerty, G Blake, M Naraine, M Siefert, C Blais, MA AF Haggerty, Greg Blake, Margaret Naraine, Melissa Siefert, Caleb Blais, Mark A. TI Construct Validity of the Schwartz Outcome Scale-10: Comparisons to Interpersonal Distress, Adult Attachment, Alexithymia, the Five-Factor Model, Romantic Relationship Length and Ratings of Childhood Memories SO CLINICAL PSYCHOLOGY & PSYCHOTHERAPY LA English DT Article DE Schwartz Outcome Scale-10; Attachment; Alexithymia; Early Memories; Interpersonal Distress ID VALIDATION; INVENTORY; VERSION; STYLES AB The Schwartz Outcome Scale-10 (SOS-10) is a 10-item questionnaire that measures the broad domain of psychological well-being and quality of life. The SOS-10 is easy to administer and score. Past research has shown its utility, reliability and validity in different clinical settings (i.e., inpatient, outpatient and non-psychiatry medical settings) and with diverse clinical populations in measuring treatment outcome. The present study looks to extend the construct validity of the SOS-10 to assessing quality of life and psychological health in non-clinical samples as well. The results reveal that the SOS-10 is associated in predicted ways with established measures of attachment, interpersonal distress, alexithymia and the big five model whose construct validity and psychometric soundness has been well documented. The SOS-10 was also associated in predicted ways with ratings of childhood memories and the length of the participants' longest romantic relationship. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Haggerty, Greg] Nassau Univ, Med Ctr, Garden City, NY USA. [Blake, Margaret] Bellevue Hosp Ctr, New York, NY 10016 USA. [Naraine, Melissa] Zucker Hillside Hosp, Long Isl Jewish Med Ctr, New Hyde Pk, NY USA. [Siefert, Caleb; Blais, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Haggerty, G (reprint author), 18 Sexton Rd, Syosset, NY 11791 USA. EM Ghag541@aol.com NR 20 TC 12 Z9 12 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1063-3995 J9 CLIN PSYCHOL PSYCHOT JI Clin. Psychol. Psychother. PD JAN-FEB PY 2010 VL 17 IS 1 BP 44 EP 50 DI 10.1002/cpp.643 PG 7 WC Psychology, Clinical SC Psychology GA 557YD UT WOS:000274705500005 PM 19701959 ER PT J AU Abujudeh, HH Kaewlai, R Kodsi, SE Hamill, MA AF Abujudeh, H. H. Kaewlai, R. Kodsi, S. E. Hamill, M. A. TI Improving quality of communications in emergency radiology with a computerized whiteboard system SO CLINICAL RADIOLOGY LA English DT Article C1 [Abujudeh, H. H.; Kaewlai, R.; Hamill, M. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abujudeh, H. H.; Kaewlai, R.; Hamill, M. A.] Harvard Univ, Sch Med, Boston, MA USA. [Kodsi, S. E.] Tufts Med Ctr, Dept Radiol, Boston, MA USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 213, Boston, MA 02114 USA. EM habujudeh@partners.org OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 8 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JAN PY 2010 VL 65 IS 1 BP 56 EP 62 DI 10.1016/j.crad.2009.05.015 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 548KO UT WOS:000273961400009 PM 20103422 ER PT J AU Ademi, Z Liew, D Hollingsworth, B Wolfe, R Steg, GP Bhatt, DL Reid, CM AF Ademi, Zanfina Liew, Danny Hollingsworth, Bruce Wolfe, Rory Steg, Gabriel P. Bhatt, Deepak L. Reid, Christopher M. CA REACH Registry Investigators TI The Economic Implications of Treating Atherothrombotic Disease in Australia, From the Government Perspective SO CLINICAL THERAPEUTICS LA English DT Article DE aged; atherothrombosis; direct health care costs ID PERIPHERAL ARTERIAL-DISEASE; CARDIOVASCULAR RISK-FACTORS; BURDEN; COST; OUTPATIENTS; PREVENTION; MANAGEMENT; CORONARY AB Background: The management of atherothrombotic disease is responsible for a large proportion of direct medical costs in most countries, imposing a substantial financial burden on health care payers. There is limited knowledge about direct per-person medical Costs using a "bottom-up" approach. Objective: This study was designed to estimate the per-person direct medical costs incurred by community-based subjects in Australia who have or are at high risk for atherothrombotic disease. The perspective was a governmental one, at the federal level for pharmaceuticals and at the state level for hospitalizations. Methods: One-year follow-up data were obtained for Australian participants in the international REACH (Reduction of Atherothrornbosis for Continued Health) Registry who were aged 45 years and had either established atherothrombotic disease (coronary artery disease, cerebrovascular disease, or peripheral artery disease [PAD]) or 3 risk factors for atherothrombotic disease. Information was extracted on the use of cardiovascular medications, hospitalizations, general practice visits, clinical pathology and imaging studies, and use of rehabilitation services. Bottom-up costing was undertaken by assigning unit costs to each health care item, based on Australian government reimbursement data for 2006-2007. Costs were estimated in Australian dollars. Results: Data for 2873 Australian participants in the REACH Registry were included in the analysis. Mean (SD) annual pharmaceutical costs per person were A$1388 (A$645). Mean ambulatory care costs per person were A$704 (A$492), and mean hospitallzation costs were A$10,711 (A$-10,494). Compared with participants with >= 3 risk factors (adjusted for age and sex), participants with 2 to 3 affected vascular territories incurred A$160 more in mean pharmaceutical costs (95% C1, 78 to 256) and A$181 more in ambulatory care costs (95% CI, 107 to 252). Mean ambulatory care costs were A$132 greater among participants with PAD only relative to those with >= 3 risk factors (95% Cl, 19 to 272). Hospital costs were not significantly increased with an increasing number of affected vascular territories. I-lie greatest difference]it direct hospital costs (A$943) was between participants with PAD relative to those with >= 3 risk factors (95% CI, -564 to 3545). Conclusions: From the government perspective, management of atherothrombotic disease in Australia was costly during the period Studied, particularly among those with PAD only or disease affecting 2 to 3 Vascular territories. Hospitalization accounted for the majority of health care expenditure associated with atherothrombotic disease, although the number of hospitalized participants was relatively small. (Clin Ther. 201,0;32:119-132) (C) 2010 Excerpta Medica Inc. C1 [Ademi, Zanfina; Wolfe, Rory; Reid, Christopher M.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Liew, Danny] Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, Australia. [Hollingsworth, Bruce] Monash Univ, Ctr Hlth Econ, Melbourne, Vic 3004, Australia. [Steg, Gabriel P.] Univ Paris 07, INSERM, U698, Paris, France. [Steg, Gabriel P.] AP HP, Paris, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ademi, Z (reprint author), Monash Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth & Prevent Med, Alfred Hosp, Commercial Rd, Melbourne, Vic 3004, Australia. EM Zanfina.Ademi@med.monash.edu.au OI Liew, Danny/0000-0002-0131-623X; Hollingsworth, Bruce/0000-0002-4314-6523 FU Monash University; Australian Research Council [LP077532] FX This work was supported by Monash University. It was also supported In part by the Australian Research Council Linkage Project LP077532. NR 35 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JAN PY 2010 VL 32 IS 1 BP 119 EP 132 DI 10.1016/j.clinthera.2010.01.009 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 562TU UT WOS:000275078600013 PM 20171418 ER PT J AU Greer, DM AF Greer, David M. TI Aspirin and Antiplatelet Agent Resistance Implications for Prevention of Secondary Stroke SO CNS DRUGS LA English DT Review ID CORONARY-ARTERY-DISEASE; TRANSIENT ISCHEMIC ATTACK; ACUTE MYOCARDIAL-INFARCTION; OF-FUNCTION POLYMORPHISM; PLATELET-FUNCTION TESTS; HIGH-RISK PATIENTS; CLOPIDOGREL RESISTANCE; CARDIOVASCULAR EVENTS; HEALTHY-VOLUNTEERS; ATHEROTHROMBOTIC EVENTS AB Oral antiplatelet drugs, including aspirin, clopidogrel and extended-release dipyridamole, are widely prescribed for the secondary prevention of vascular events, including stroke. Despite the benefits of antiplatelet therapy, 10-20% of patients experience a recurrent vascular event while taking antiplatelet medication. This article discusses the concept of antiplatelet resistance in general, focusing on aspirin resistance in particular, as a poorly defined cause of recurrent vascular events. Factors such as the lack of a standardized method to diagnose aspirin resistance and a poor clinical correlation with laboratory assays make the treatment of aspirin nonresponders difficult. In addition, there are confounding conditions such as diabetes mellitus that can affect aspirin resistance and determine a different course of treatment for these patients. Other antiplatelet options may also have resistant subpopulations; thus, alternative strategies for the secondary stroke patient must be explored. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, ACC 739A,55 Fruit St, Boston, MA 02114 USA. FU Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) FX This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). Writing and editorial assistance was provided by Michele S. Olsher, PhD, and Julia Wenniger, PhD, of Publication CONNEXION (Newtown, PA, USA), which was contracted by BIPI for these services. Dr Greer meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), was fully responsible for all content and editorial decisions and was involved at all stages of manuscript development. Dr Greer has received speaker's honoraria from BIPI for educational talks, as well as research grant support from BIPI . NR 85 TC 8 Z9 9 U1 2 U2 4 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2010 VL 24 IS 12 BP 1027 EP 1040 DI 10.2165/11539160-0000000000-00000 PG 14 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 698CT UT WOS:000285569800004 PM 20932071 ER PT J AU Surman, C Hammerness, P Petty, C Doyle, R Chu, N Gebhard, N Williams, C Biederman, J AF Surman, Craig Hammerness, Paul Petty, Carter Doyle, Robert Chu, Nicole Gebhard, Nitzah Williams, Courtney Biederman, Joseph TI Atomoxetine in the Treatment of Adults with Subthreshold and/or Late Onset Attention-Deficit Hyperactivity Disorder-Not Otherwise Specified (ADHD-NOS): A Prospective Open-Label 6-Week Study SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Adults; Atomoxetine; Attention deficit hyperactivity disorder; Clinical trial ID DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; METHYLPHENIDATE; PLACEBO; GENETICS; TRIAL AB The objective of this study was to evaluate the efficacy and tolerability of atomoxetine hydrochloride (ATX) in the treatment of adults with atypical manifestations of attention-deficit hyperactivity disorder (ADHD) (not otherwise specified [NOS]). We hypothesized that treatment with ATX will be safe and efficacious for the treatment of adults with ADHD-NOS. This was a 6-week, open-label, prospective treatment study of ATX monotherapy in 45 adult patients with ADHD-NOS assessed using standardized instruments for diagnosis and a robust oral daily dose of up to 1.2 mg/kg/day or 120 mg/day. Symptom severity was assessed with the adult ADHD Investigator Symptom Report Scale (AISRS) and Clinical Global Impression Scale. Treatment with ATX at an average daily dose of 78.7 +/- 27.8 mg was associated with a statistically and clinically significant reduction in ADHD symptoms relative to baseline as assessed through the (AISRS) (-12.1 +/- 8.4; P < 0.001). Using a categorical definition of response (CGI-I much or very much improved), a majority (N = 29; 64%) of subjects were rated as improved at study endpoint. Treatment with ATX was relatively well tolerated. These open-label results suggest that ATX may be safe and effective in the treatment of adults meeting criteria for ADHD-NOS and support the need for further controlled clinical trials of ATX in this population. C1 [Surman, Craig] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Surman, C (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. EM csurman@partners.org FU Eli-Lilly and company FX This research was supported by funding from Eli-Lilly and company. NR 24 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 1 BP 6 EP 12 DI 10.1111/j.1755-5949.2009.00124.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 541VY UT WOS:000273450300003 PM 20070786 ER PT J AU Mischoulon, D Pedrelli, P Wurtman, J Vangel, M Wurtman, R AF Mischoulon, David Pedrelli, Paola Wurtman, Judith Vangel, Mark Wurtman, Richard TI Report of Two Double-Blind Randomized Placebo-Controlled Pilot Studies of a Carbohydrate-Rich Nutrient Mixture for Treatment of Seasonal Affective Disorder (SAD) SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Carbohydrate; Depression; SAD; Seasonal affective disorder; Serotonin ID COGNITIVE-BEHAVIORAL THERAPY; LIGHT THERAPY; NONSEASONAL DEPRESSION; CONTROLLED-TRIAL; RATING-SCALE; OPEN-LABEL; EFFICACY; WOMEN; MOOD; COMBINATION AB We investigated a carbohydrate-rich nutrient-drink mix for treatment of seasonal affective disorder (SAD). This mixture may contribute to brain serotonin synthesis, potentially exerting an antidepressant effect and controlling carbohydrate cravings. Two successive double-blind placebo-controlled studies were performed. In Study 1, 18 subjects (50% women; mean age 43 +/- 15 years) with SCID-diagnosed SAD were randomized to 12 days of twice daily carbohydrate beverage (CHO) containing mixed starches, or a placebo beverage (PRO) containing the CHO mix plus casein protein to dampen serotonin synthesis. Following a 2-day washout, subjects were crossed over to the other treatment for 12 days. In Study 2, 32 subjects (63% women; mean age 46 +/- 14 years) with SCID-diagnosed SAD were randomized to 21 days of CHO or PRO. Efficacy in both studies was determined by the first 17 items of the Hamilton Depression Rating Scale (HAM-D-28), an appetite questionnaire, and regular weighing. In Study 1, response rates were 50% for both groups. Remission rates favored CHO (50% vs. 38%), as did the decrease in the HAM-D-17 score, but differences were nonsignificant. In Study 2, response rates were 71% for CHO and 76% for PRO, and remission rates were 71% for each group. Both treatment groups experienced significant improvement in HAM-D-17 scores within 1 week of treatment, which continued through the entire study period. Weight change did not differ significantly between treatment groups in either study. The drink mix was well tolerated and treatment adherence was high. Both the active and placebo intervention were effective in alleviating symptoms of SAD. Replication studies in larger samples appear warranted. C1 [Mischoulon, David; Pedrelli, Paola] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mischoulon, David; Wurtman, Judith; Vangel, Mark; Wurtman, Richard] MIT, Clin Res Ctr, Cambridge, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM dmischoulon@partners.org FU National Institutes of Health [MO1-RR01066]; SwissMedica FX This research was supported in part by a General Clinical Research Center grant from the National Institutes of Health (MO1-RR01066) awarded to the Massachusetts Institute of Technology General Clinical Research Center, and by SwissMedica. SwissMedica was not involved in the study design, data collection or analysis, manuscript preparation, or publication decisions. The authors thank Janine McDermott, M.S., and Rita Tsay, R.D., for their technical assistance, and the nursing and nutritional staff of the MIT Clinical Research Center for their help with patient care. We also thank Alisabet Clain, M.S., and Lee Baer, Ph.D., for additional statistical advice. NR 47 TC 3 Z9 3 U1 5 U2 13 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 1 BP 13 EP 24 DI 10.1111/j.1755-5949.2009.00082.x PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 541VY UT WOS:000273450300004 PM 19769596 ER PT J AU Iosifescu, DV AF Iosifescu, Dan V. TI GABA-A Receptor Modulators: Can they Offer any Improvement over Benzodiazepines in the Treatment of Anxiety Disorders? SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Iosifescu, DV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org NR 5 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 2 BP 61 EP 62 DI 10.1111/j.1755-5949.2009.00127.x PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 564LB UT WOS:000275214600001 PM 20415836 ER PT J AU Biederman, J Joshi, G Mick, E Doyle, R Georgiopoulos, A Hammerness, P Kotarski, M Williams, C Wozniak, J AF Biederman, Joseph Joshi, Gagan Mick, Eric Doyle, Robert Georgiopoulos, Anna Hammerness, Paul Kotarski, Meghan Williams, Courtney Wozniak, Janet TI A Prospective Open-Label Trial of Lamotrigine Monotherapy in Children and Adolescents with Bipolar Disorder SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Bipolar disorder; Children; Lamotrigine ID PLACEBO-CONTROLLED TRIALS; MANIA RATING-SCALE; DOUBLE-BLIND; DIVALPROEX SODIUM; EXTENDED-RELEASE; I-DISORDER; DEPRESSION; RISPERIDONE; OLANZAPINE; LITHIUM AB Aim: To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. Method: This was a 12-week, open-label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. Results: Thirty-nine children with bipolar disorder (YMRS at entry: 31.6 +/- 5.5) were enrolled in the study and 22 (56%) completed the 12-week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 +/- 128.3 in subjects < 12 years of age (N = 22) and 219.1 +/- 172.2 mg/day in children 12-17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (-14.9 +/- 9.7, P < 0.001) at endpoint. Lamotrigine treatment also resulted in significant improvement in the severity of depressive, attention-deficit/hyperactivity disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 +/- 18.0 kg vs. 47.2 +/- 17.9 kg, P = 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Conclusions: Open-label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo-controlled, double-blind studies are warranted to confirm these findings. C1 [Biederman, Joseph; Joshi, Gagan; Mick, Eric; Doyle, Robert; Georgiopoulos, Anna; Hammerness, Paul; Kotarski, Meghan; Williams, Courtney; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Biederman, Joseph; Joshi, Gagan; Mick, Eric; Doyle, Robert; Georgiopoulos, Anna; Hammerness, Paul; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Biederman, J (reprint author), 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbierderman@partners.org OI Mick, Eric/0000-0001-8505-8145 FU Kimmerly-Neal Fund for the Study of Cognition and Psychiatric Disorders in Children; Pediatric Psychopharmacology Council Fund FX Funding source: This work is supported by the Kimmerly-Neal Fund for the Study of Cognition and Psychiatric Disorders in Children and the Pediatric Psychopharmacology Council Fund. NR 51 TC 21 Z9 21 U1 2 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 2 BP 91 EP 102 DI 10.1111/j.1755-5949.2009.00121.x PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 564LB UT WOS:000275214600005 PM 20415838 ER PT J AU Nierenberg, AA Rapaport, MH Schettler, PJ Howland, RH Smith, JA Edwards, D Schneider, T Mischoulon, D AF Nierenberg, Andrew A. Rapaport, Mark Hyman Schettler, Pamela J. Howland, Robert H. Smith, Juliana A. Edwards, Deidre Schneider, Trisha Mischoulon, David TI Deficits in Psychological Well-Being and Quality-of-Life in Minor Depression: Implications for DSM-V SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Minor Depression; Psychological Well-Being; Quality of Life ID MAJOR DEPRESSION; PRIMARY CARE; DISORDER; PREVALENCE; INVENTORY; RECOVERY; ANXIETY AB Method: Ninety-three subjects entering a treatment study for Min D were assessed using the QOL, Enjoyment and satisfaction questionnaire (Q-LES-Q), and the Psychological Well-Being Scale (PWBS). Scores were compared with major depressive disorder (MDD) and normative community samples. Results: Even though subjects had mild depressive severity, Q-LES-Q total scores for the Min D sample averaged nearly two standard deviations below the community norm. Almost 40% of Min D cases had Q-LES-Q scores in the lowest 1% of the population. Responses to most Q-LES-Q items were closer to subjects with MDD than to community norms. Mean standardized PWB scores were extremely low for subscales of Environmental Mastery and Self-Acceptance, low for Purpose in Life and Positive Relations with others, but within the normal range for Personal Growth and Autonomy. QOL and PWB measures had low correlations with depressive symptom severity, and scores were similar in the presence or absence of a prior history of MDD. Conclusions: Mild depressive symptoms with Min D are associated with major deficits in QOL and PWB measures of environmental mastery and poor self-acceptance. Our findings suggest that diminished QOL and PWB may be intrinsic cognitive aspects of Min D with or without a history of MDD. It may be unnecessary in the DSM IV-TR to exclude the diagnosis of Min D if a subject has had a past episode of MDD. center dot Minor depression exists along a continuum of depression. center dot Deficits in psychological well-being and quality-of-life in minor depression are severe. center dot No difference in these measures if minor depression existed with or without a history of major depression. C1 [Nierenberg, Andrew A.; Rapaport, Mark Hyman; Schettler, Pamela J.; Howland, Robert H.; Smith, Juliana A.; Edwards, Deidre; Schneider, Trisha; Mischoulon, David] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM anierenberg@partners.org RI Howland, Robert/K-6937-2015 OI Howland, Robert/0000-0002-6533-6010 FU NIMH; NCCAM [R01MH61758] FX Supported in part by NIMH and NCCAM R01MH61758. NR 35 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 4 BP 208 EP 216 DI 10.1111/j.1755-5949.2009.00108.x PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 619OL UT WOS:000279439400002 PM 20236139 ER PT J AU Deckersbach, T Nierenberg, AA Kessler, R Lund, HG Ametrano, RM Sachs, G Rauch, SL Dougherty, D AF Deckersbach, Thilo Nierenberg, Andrew A. Kessler, Ronald Lund, Hannah G. Ametrano, Rebecca M. Sachs, Gary Rauch, Scott L. Dougherty, Darin TI Cognitive Rehabilitation for Bipolar Disorder: An Open Trial for Employed Patients with Residual Depressive Symptoms SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Bipolar disorder; Cognitive impairment; Cognitive remediation; Occupational functioning; Psychosocial functioning ID TREATMENT ENHANCEMENT PROGRAM; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; SOCIAL RHYTHM THERAPY; FUNCTIONAL IMPAIRMENT; I DISORDER; RELAPSE PREVENTION; WORK PERFORMANCE; RATING-SCALE; STEP-BD; DSM-IV AB Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, individuals with bipolar disorder often continue to experience impairments in psychosocial functioning, particularly occupational functioning. Two determinants of psychosocial functioning of euthymic (neither fully depressed nor manic) individuals with bipolar disorder are residual depressive symptoms and cognitive impairment (i.e., difficulties with executive functioning, attention, and memory). The present study explored whether a new cognitive remediation (CR) treatment designed to treat residual depressive symptoms and, for the first time to the best of our knowledge, address cognitive impairment would be associated with improvement in psychosocial functioning in individuals with bipolar disorder. Following a neuropsychological and clinical assessment 18 individuals with DSM-IV bipolar disorder were treated with 14 individual sessions of CR. Results indicated that at the end of treatment, as well as at the 3-months follow-up, patients showed lower residual depressive symptoms, and increased occupational, as well as overall psychosocial functioning. Pretreatment neuropsychological impairment predicted treatment response. Improvements in executive functioning were associated with improvements in occupational functioning. These findings suggest that treating residual depressive symptoms and cognitive impairment may be an avenue to improving occupational and overall functioning in individuals with bipolar disorder. C1 [Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Deckersbach, Thilo; Nierenberg, Andrew A.; Kessler, Ronald; Lund, Hannah G.; Ametrano, Rebecca M.; Rauch, Scott L.; Dougherty, Darin] Harvard Univ, Sch Med, Boston, MA USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Bipolar Clin, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM tdeckersbach@partners.org FU NIMH [1K23MH074895-01A2] FX This work was supported by a K-23 NIMH Career Award 1K23MH074895-01A2) to Thilo Deckersbach. Part of this research has been presented at the annual meeting of the 41st and 42nd Annual Convention of the Association for Behavioral and Cognitive Therapies (ABCT) and the Eighth International Conference for Bipolar Disorder, Pittsburgh, 2009. NR 50 TC 83 Z9 87 U1 2 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 5 BP 298 EP 307 DI 10.1111/j.1755-5949.2009.00110.x PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 647TY UT WOS:000281643500010 PM 19895584 ER PT J AU Chandler, GM Iosifescu, DV Pollack, MH Targum, SD Fava, M AF Chandler, Gregory M. Iosifescu, Dan V. Pollack, Mark H. Targum, Steven D. Fava, Maurizio TI Validation of the Massachusetts General Hospital Antidepressant Treatment History Questionnaire (ATRQ) SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Self-rated scale; Validation; Treatment resistant depression ID MAJOR DEPRESSIVE DISORDER; TREATMENT-RESISTANT DEPRESSION; STAR-ASTERISK-D; ADJUNCTIVE THERAPY; DOUBLE-BLIND; EFFICACY; SAFETY; ARIPIPRAZOLE; MULTICENTER; DEFINITION AB The low rate of response to antidepressants in treatment resistant depression (TRD) justifies studies of next-step therapies following a treatment failure. In TRD clinical trials, it is important to verify the accurate diagnosis of treatment resistance for all enrolled subjects using a reliable and valid instrument. Self-rated scales can reduce the impact of investigator bias and reduce the time burden for clinical researchers. The Massachusetts General Hospital (MGH) Antidepressant Treatment Response Questionnaire (ATRQ) is a self-rated scale used to determine treatment resistance in major depressive disorder (MDD). The ADAPT-A study is a multi-center double-blind, placebo-controlled study of low-dose aripiprazole adjunctive to ADT among outpatients with TRD. At the screening assessment, potential subjects completed the MGH ATRQ. The ADAPT-A medical monitors subsequently performed remote patient interviews and obtained detailed medication histories. The data obtained from the MGH ATRQ and by the medical monitors were compared for congruency. Of the 186 patients enrolled by the local sites, no subjects deemed treatment resistant by the MGH ATRQ were found to be nonresistant by the medical monitors. In 76.3% (n = 142) of the subjects, the number of failed adequate antidepressant trials reported by the MGH ATRQ was concordant with the data collected by medical monitors. In 16.1% (n = 30) of all cases, the medical monitors found a greater number of failed trials; in 7.5% (n = 14) of cases, the medical monitors found fewer failed medication trials. The discrepancy was by more than one medication trial in only 4.0% (n = 7) of cases. We found the MGH ATRQ to be relatively concordant in its assessment of treatment resistance in depression compared with independent clinical researchers. Although the MGH ATRQ tended to underreport the number of unsuccessful treatment trials relative to the clinical interviews, its accuracy in cases it detected was confirmed by raters. C1 [Chandler, Gregory M.; Iosifescu, Dan V.; Pollack, Mark H.; Targum, Steven D.; Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network, Boston, MA 02114 USA. [Chandler, Gregory M.; Iosifescu, Dan V.; Pollack, Mark H.; Targum, Steven D.; Fava, Maurizio] Inst CTNI, Boston, MA USA. [Chandler, Gregory M.; Iosifescu, Dan V.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. RP Chandler, GM (reprint author), Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave,Suite FG20, Toronto, ON M4N 3M5, Canada. EM chandlergreg@gmail.com NR 14 TC 36 Z9 36 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2010 VL 16 IS 5 BP 322 EP 325 DI 10.1111/j.1755-5949.2009.00102.x PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 647TY UT WOS:000281643500013 PM 19769599 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Something Borrowed, Something Blue: Why is Bipolar Disorder an Orphan? SO CNS SPECTRUMS LA English DT Editorial Material ID LITHIUM MAINTENANCE TREATMENT; CONTROLLED 18-MONTH TRIAL; DOUBLE-BLIND; PSYCHOSOCIAL DISABILITY; II DISORDERS; DEPRESSION; PLACEBO; LAMOTRIGINE; EFFICACY; COMBINATION C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 38 TC 7 Z9 7 U1 1 U2 2 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JAN PY 2010 VL 15 IS 1 BP 15 EP 16 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 554LN UT WOS:000274436600001 PM 20394180 ER PT J AU Pedrelli, P Baer, L Iosifescu, DV Fava, M AF Pedrelli, Paola Baer, Lee Iosifescu, Dan V. Fava, Maurizio TI Relationship Between Residual Symptoms of Depression and Self-reported Cognitive Impairment SO CNS SPECTRUMS LA English DT Article ID ANTIDEPRESSANT TREATMENT; PREVALENCE; DISEASE; APATHY AB Objective: The present study aimed to investigate the associations between residual symptoms of depression and specific self-reported symptoms in several cognitive domains. Methods: The study investigated 117 patients with partially or fully remitted major depressive disorder (MDD) after treatment with antidepressant medications. Results: Fatigue was significantly associated with inability to focus, alertness, and feeling "blue"; low interest and difficulty with concentration were associated with apathy. No associations were found between deficits in the cognitive domains considered and residual symptoms such as self-blaming, feeling worthless, feeling hopeless, having suicidal thoughts, difficulty with sleep, and lack of appetite. Conclusion:, Among MDD remitted patients endorsing residual symptoms such as fatigue and feeling "blue", deficits in a range of cognitive domains should be carefully assessed and treated. CNS Spectr. 2010; 15(1):46-51 C1 [Pedrelli, Paola; Iosifescu, Dan V.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Baer, Lee] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Iosifescu, Dan V.] Massachusetts Gen Hosp, Bipolar Trials Network, Boston, MA 02114 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pedrelli, P (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM ppedrelli@partners.org FU Eli Lilly and Company FX This activity is supported by an educational grant from Eli Lilly and Company. NR 21 TC 11 Z9 12 U1 1 U2 3 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JAN PY 2010 VL 15 IS 1 BP 46 EP 51 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 554LN UT WOS:000274436600005 PM 20394184 ER PT J AU Anderson, A Singh, JA AF Anderson, Amy Singh, Jasvinder A. TI Pegloticase for chronic gout SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID TREATMENT-FAILURE GOUT; URATE OXIDASE; RHEUMATOID-ARTHRITIS; REFRACTORY GOUT; HYPERURICEMIA; URICASE; EPIDEMIOLOGY; RASBURICASE; QUALITY; LIFE AB Background Pegloticase is a potential new treatment option for patients with chronic gout intolerant to other urate-lowering therapies. Objectives To assess safety (adverse events, death) and efficacy (pain, function, frequency of flares, quality of life, uric acid level, radiographic damage) of pegloticase in various doses or as compared to placebo or other interventions for treatment of hyperuricemia in patients with chronic gout. Search strategy We searched six databases: The Cochrane Central Register of Controlled Trials (CENTRAL), via The Cochrane Library, OVID MEDLINE, CINAHL (via EBSCOHost), OVID SPORTdiscus, EMBASE and the Science Citation Index (Web of Science). Selection criteria All published randomized controlled trials (RCTs) or controlled clinical trials that compared various doses of pegloticase alone or pegloticase alone or in combination with other urate-lowering or anti-inflammatory medications to placebo alone or placebo in combination with these medications, in patients with gout. Data collection and analysis Two review authors (AA, JS) independently extracted data from the included trials, including trial and population characteristics, primary and secondary outcomes. For dichotomous and continuous outcomes, we calculated the risk ratio and mean difference, respectively with 95% confidence interval. Major outcomes were: (a) Efficacy: frequency of gout flares and change in serum uric acid; and (b) safety: adverse events, serious adverse events, withdrawals and death. Minor/secondary outcomes were pain, patient/physician global assessment, tophus burden, health related quality of life, function and radiographic progression. Main results Only one open-label, phase-II RCT (n = 41) met the selection criteria that compared various doses of pegloticase without comparison to placebo or another treatment. Patients were randomized to one of the four doses of pegloticase for 12 to 14 weeks -4mg every 2 weeks, 8mg every 2 weeks, 8mg every 4 weeks and 12mg every 4 weeks. Percent responders (uric acid below 6 mg/dl 80% or more time) in the four dose groups were 56%, 88%, 52% and 62%. Percent time without hyperuricemia (uric acid below 6 mg/dl) was 78%, 92%, 76% and 76% respectively. No between dose differences were noted. Most common adverse events (10% or more patients) included nephrolithiasis, arthralgia, anemia, dyspnea, headache, muscle spasms, nausea and pyrexia. 89% reported one or more gout flares during the study. Pain, patient/physician global, function, quality of life, tophus size/regression and radiographic progression were not reported in this study. Authors' conclusions There are no published double-blind, placebo-controlled RCTs of pegloticase. More evidence is needed to assess risks/benefits of pegloticase in patients with chronic gout. C1 [Anderson, Amy] Univ Alabama, Dept Med, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Anderson, Amy] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Anderson, Amy] Univ Minnesota, Minneapolis, MN USA. RP Singh, JA (reprint author), Univ Alabama, Dept Med, Birmingham VA Med Ctr, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU Takeda; Savient; AMGEN pharmaceuticals; National Institues of Health; Department of Veterans Affairs; Arthritis Foundation; University of Minnesota; Minnesota Medical Foundation; Cochrane Collaboration; Minneapolis VA Medical Center, Minneapolis, USA; NIH CTSA, (Mayo Clinic Center for Clinical and Translational Research), USA [1 KL2 RR024151-01] FX JS - Research grants from Takeda, Savient and AMGEN pharmaceuticals; Consultant/honraria-Savient, Abbott and URL pharmaceuticals; Research grants from National Institues of Health, Department of Veterans Affairs, Arthritis Foundation, University of Minnesota, Minnesota Medical Foundation and Cochrane Collaboration. AA-None; Internal sources; Minneapolis VA Medical Center, Minneapolis, MN 55417, USA.; External sources; NIH CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research), USA. 75% time-protection for research NR 64 TC 7 Z9 7 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 3 AR CD008335 DI 10.1002/14651858.CD008335.pub2 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA 570ZP UT WOS:000275717700003 PM 20238366 ER PT J AU Sena, DF Ramchand, K Lindsley, K AF Sena, Dayse F. Ramchand, Kanchan Lindsley, Kristina TI Neuroprotection for treatment of glaucoma in adults SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID NORMAL-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; RETINAL GANGLION-CELLS; INTRAOCULAR-PRESSURE REDUCTION; OCULAR HYPERTENSION; CLINICAL-TRIAL; OPTIC NEUROPATHY; VISUAL FUNCTION; EYE SURVEY; LATANOPROST AB Background Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the commonest form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The treatment can target extracellular factors such as reducing IOP, or cellular factors derived from the optic nerve itself such as blocking intracellular death signals. Objectives The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents, either topical or oral, for slowing the progression of OAG in adults. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 4, 2009), MEDLINE (January 1960 to January 2010), EMBASE (January 1980 to January 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2010) and ClinicalTrials.gov (http://clinicaltrials.gov). (5 January 2010). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 5 January 2010. Selection criteria This review was limited to randomized controlled trials (RCTs) in which topical or oral treatments were used to prevent retinal ganglion cell death. Our population of interest was adults with OAG. As the primary outcome for this review was the proportion of participants who developed any progression of visual field loss at five years post intervention, only trials with at least five years of follow-up were included. Data collection and analysis Two review authors independently reviewed titles and abstracts from the literature searches. Full text copies of relevant or potentially relevant studies were obtained and re-evaluated for inclusion. There were no trials identified for this review, thus we performed no data extraction or meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until additional study details are provided. Reasons for excluding studies from the review were documented. Main results In accordance with the selection criteria for inclusion, we identified no studies relevant for this review. The results of short-term trials and other studies are discussed in this review. Authors' conclusions Although neuroprotective agents are intended to act as pharmacological antagonists to prevent cell death, the evidence that they are effective in preventing retinal ganglion cell death, and thus preserving vision in patients with OAG, has not been demonstrated. Longterm RCTs are needed to determine whether or not neuroprotective agents may be beneficial for individuals with OAG. C1 [Sena, Dayse F.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lindsley, Kristina] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Clin Trials, Baltimore, MD USA. RP Sena, DF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,Connecting Bldg 703, Boston, MA 02114 USA. EM dsena@partners.org FU National Eye Institute, National Institutes of Health, USA [N-01-EY-2-1003] FX External sources; Contract N-01-EY-2-1003, National Eye Institute, National Institutes of Health, USA. NR 82 TC 9 Z9 9 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 2 AR CD006539 DI 10.1002/14651858.CD006539.pub2 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 557FD UT WOS:000274654100013 PM 20166085 ER PT J AU Singh, JA Sperling, J Buchbinder, R McMaken, K AF Singh, Jasvinder A. Sperling, John Buchbinder, Rachelle McMaken, Kelly TI Surgery for shoulder osteoarthritis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID KEELED GLENOID COMPONENTS; RANDOMIZED-TRIAL; PRIMARY-CARE; ARTHROPLASTY; PAIN; HEMIARTHROPLASTY; LIFE; INSTABILITY; PREVALENCE; DISABILITY AB Background Surgical treatment including shoulder arthroplasty is a treatment option for patients with advanced osteoarthritis of the shoulder who have failed conservative treatment. Objectives To determine the benefit and harm of surgery in patients with osteoarthritis of the shoulder confirmed on X-ray who do not respond to analgesics and NSAIDs. Search strategy We searched: The Cochrane Central Register of Controlled Trials (CENTRAL), via The Cochrane Library; OVIDMEDLINE; CINAHL (via EBSCOHost); OVID SPORTdiscus; EMBASE; and Science Citation Index (Web of Science). Selection criteria All randomized clinical trials (RCTs) or quasi-randomized trials including adults with osteoarthritis of the shoulder joint (PICO-patients) comparing surgical techniques (total shoulder arthroplasty, hemiarthroplasty, implant types and fixation-intervention) versus placebo or sham surgery, non-surgical modalities, no treatment, or comparison of one type of surgical technique to another (comparison) with patient-reported outcomes (pain, function, quality of life etc.) or revision rates (outcomes). Data collection and analysis We reviewed titles and abstracts for inclusion, extracted study and outcomes data and assessed the risk of bias of included studies. For categorical outcomes, we calculated the risk ratio (with 95% confidence interval (CI)) and for continuous outcomes, the mean difference (95% CI). Main results Seven studies (238 patients) were included for analyses. None of the studies compared shoulder surgery to sham surgery, non-surgical modalities or placebo. Two studies compared hemiarthroplasty to total shoulder arthroplasty; three compared keeled and pegged humeral components; and one each compared navigation surgery to conventional and all-polyethylene to metal-backed implant. Two studies (88 patients) compared hemiarthroplasty to total shoulder arthroplasty. Patients who underwent hemiarthroplasty had statistically significantly worse functional scores on American Shoulder and Elbow Surgeons Shoulder Scale (100 point scale; higher = better) at 24 to 34 month follow-up compared to those who underwent total shoulder arthroplasty (mean difference, -10.05; 95% CI, -18.97 to -1.13; 2 studies, 88 patients), but no statistically significant differences between hemiarthroplasty and TSA were noted for pain scores (mean difference, 7.8; 95% CI, -5.33 to 20.93; 1 study, 41 patients), quality of life on short-form 36 physical component summary (mean difference, 0.80; 95% CI, -6.63 to 8.23; 1 study, 41 patients) and adverse events (Risk ratio, 1.19; 95% CI, 0.37 to 3.81; 1 study, 41 patients), respectively. A non-statistically significant trend towards higher revision rate in hemiarthroplasty compared to total shoulder arthroplasty was noted (Risk ratio, 6.18; 95% CI, 0.77 to 49.52; 2 studies, 88 patients; P = 0.09). Authors' conclusions Total shoulder arthroplasty seems to offer an advantage in terms of shoulder function, with no other clinical benefits over hemiarthroplasty. More studies are needed to compare clinical outcomes of surgery using different components and techniques in patients with osteoarthritis of the shoulder. There is a need for studies comparing shoulder surgery to sham, placebo and other non-surgical treatment options. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Sperling, John] Mayo Clin, Sch Med, Rochester, MN USA. [Buchbinder, Rachelle] Monash Univ, Dept Epidemiol & Prevent Med, Cabrini Hosp, Monash Dept Clin Epidemiol, Malvern, Australia. [McMaken, Kelly] Univ Minnesota, Minneapolis, MN USA. [McMaken, Kelly] Minneapolis VA Med Ctr, Minneapolis, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com RI Buchbinder, Rachelle/G-2952-2011 FU Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; Bristol-Myers Squibb; Abbott; Parker Institute: Musculoskeletal Statistics Unit; Oak Foundation; Minneapolis and Birmingham VA Medical Centers; University of Alabama at Birmingham, AL, USA FX JAS - speaker honoraria from Abbott; research and travel grants from Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient and URL pharmaceuticals.; RB - research grant and consultant fee from Bristol-Myers Squibb and Abbott. The Parker Institute: Musculoskeletal Statistics Unit is sponsored, and acknowledges The Oak Foundation.; Internal sources; Minneapolis and Birmingham VA Medical Centers and University of Alabama at Birmingham, AL, USA. NR 53 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 10 AR CD008089 DI 10.1002/14651858.CD008089.pub2 PG 46 WC Medicine, General & Internal SC General & Internal Medicine GA 659TS UT WOS:000282590400009 PM 20927773 ER PT J AU Singh, JA Fitzgerald, PM AF Singh, Jasvinder A. Fitzgerald, Patrick M. TI Botulinum toxin for shoulder pain SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CHRONIC MYOFASCIAL PAIN; MODIFIED RANKIN SCALE; DOUBLE-BLIND; PRIMARY-CARE; RHEUMATOID-ARTHRITIS; SUBSCAPULAR MUSCLE; SPASTIC HEMIPLEGIA; CONTROLLED-TRIAL; BARTHEL INDEX; TENNIS ELBOW AB Background Recent evidence suggests an anti-nociceptive effect of botulinum toxin. Objectives To compare the efficacy and safety of botulinum toxin in comparison to placebo or other treatment options for shoulder pain. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (T h e Cochrane Library), Ovid MEDLINE, CINAHL (via EBSCOhost), Ovid SPORTDiscus, EMBASE and Science Citation Index. Selection criteria Randomized controlled trials (RCTs) comparing botulinum toxin with placebo or active treatment in people with shoulder pain were included. Data collection and analysis For continuous measures we calculated mean difference (MD), and for categorical measures risk ratio (RR) (with 95% confidence interval (CI)). Main results Six RCTs with 164 patients were included. Five RCTs in participants with post-stroke shoulder pain indicated that compared with placebo, a single intramuscular injection of botulinum toxin A significantly reduced pain at three to six months post-injection (MD -1.2 points, 95% CI -2.4 to -0.07; 0 to 10 point scale) but not at one month (MD -1.1 points, 95% CI -2.9 to 0.7). Shoulder external rotation was increased at one month (MD 9.8, 95% CI 0.2 to 19.4) but not at three to six months. Shoulder abduction, external rotation or spasticity did not differ between groups, nor did the number of adverse events (RR 1.46, 95% CI 0.6 to 24.3). One RCT in arthritis-related shoulder pain indicated that botulinum toxin reduced pain severity (MD -2.0, 95% CI -3.7 to -0.3; 10 point scale) and shoulder disability with a reduction in Shoulder Pain and Disability Index score (MD -13.4, 95% CI -24.9 to -1.9; 100 point scale) when compared with placebo. Shoulder abduction was improved (MD 13.8 degrees, 95% CI 3.2 to 44.0). Serious adverse events did not differ between groups (RR 0.35, 95% CI: 0.11, 1.12). Authors' conclusions The results should be interpreted with caution due to few studies with small sample sizes and high risk of bias. Botulinum toxin A injections seem to reduce pain severity and improve shoulder function and range of motion when compared with placebo in patients with shoulder pain due to spastic hemiplegia or arthritis. It is unclear if the benefit of pain relief in post-stroke shoulder pain at three to six months but not at one month is due to limitations of the evidence, which includes small sample sizes with imprecise estimates, or a delayed onset of action. More studies with safety data are needed. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Fitzgerald, Patrick M.] Minneapolis VA Med Ctr, Minneapolis, MN USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU Birmingham VA Medical Center, Minneapolis, USA, USA; NIH, USA; Amgen; Allergan; Takeda; Savient pharmaceuticals; URL pharmaceuticals; Wyeth pharmaceuticals FX JS: speaker honoraria from Abbott pharmaceuticals; research grants from Amgen, Allergan, Takeda and Savient pharmaceuticals; consultant fee from Savient and URL pharmaceuticals; travel grants from Allergan and Wyeth pharmaceuticals.; SOURCES OF SUPPORT; Internal sources; Birmingham VA Medical Center, Minneapolis, USA, USA.; Research time protection; External sources; NIH CTSA KL2 Award (Mayo Clinic), USA, Not specified.; 75% time protection for research NR 71 TC 9 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 9 AR CD008271 DI 10.1002/14651858.CD008271.pub2 PG 48 WC Medicine, General & Internal SC General & Internal Medicine GA 647PC UT WOS:000281629700033 PM 20824874 ER PT J AU Singh, JA Beg, S Lopez-Olivo, MA AF Singh, Jasvinder A. Beg, Saba Lopez-Olivo, Maria Angeles TI Tocilizumab for rheumatoid arthritis SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; PLACEBO-CONTROLLED TRIAL; DISEASE-ACTIVITY SCORE; DOUBLE-BLIND; IL-6 RECEPTOR; PRELIMINARY DEFINITION; INADEQUATE RESPONSE; INHIBITION; CRITERIA; THERAPY AB Background Tocilizumab, a new biologic that inhibits interleukin-6, is approved for treatment of rheumatoid arthritis (RA) in Europe, Japan and the US. Objectives To assess the efficacy and safety of tocilizumab in patients with RA using the data from published randomized or quasi-randomized controlled trials (RCTs). Search strategy We performed a search of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) up to issue 3, 2009; OVID MEDLINE(1966 to 1 October 2009); CINAHL(1982 to 2009); EMBASE (1980 to week 39, 2009); Science Citation Index (Web of Science) (1945 to 2009) and Current Controlled Trials. Selection criteria Tocilizumab alone or in combination with disease-modifying anti-rheumatic drugs (DMARDs) or biologics compared to placebo or other DMARDs or biologics. Data collection and analysis Two review authors independently extracted all data including major (ACR50, adverse events, serious adverse events, withdrawals, specific adverse events) and secondary outcomes. We calculated the risk ratio for dichotomous outcomes and mean difference for continuous outcomes. Main results Eight RCTs were included in this systematic review with 3334 participants; 2233 treated with tocilizumab and 1101 controls. Of the 2233, 1561 were treated with tocilizumab 8 mg/kg every four weeks, which is the approved dose. In patients taking concomitant methotrexate, compared to placebo, tocilizumab-treated patients were four times more likely to achieve ACR50 (absolute %, 38.8% versus 9.6%), 11 times more likely to achieve Disease Activity Score (DAS) remission (absolute %, 30.5% versus 2.7%), 1.8 times more likely to achieve clinically meaningful decrease in Health Assessment Questionnaire (HAQ/mHAQ) scores (absolute %, 60.5% versus 34%), 1.2 times more likely to have any adverse event (absolute %, 74% versus 65%) and 0.6 times less likely to withdraw from therapy for any reason (absolute %, 8.1% versus 14.9%). With the limitation that none of the studies were powered for safety as primary outcome, there were no statistically significant differences in serious adverse effects, or withdrawals due to adverse events. A significant increase in total, HDL and LDL cholesterol and triglyceride level was seen in the tocilizumab treated patients. Authors' conclusions Tocilizumab is beneficial in decreasingRA disease activity and improving function. Tocilizumab treatment was associated with significant increase in cholesterol levels and in total adverse events. Larger safety studies are needed to address these safety concerns. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Beg, Saba] Univ Minnesota, Minneapolis, MN USA. [Beg, Saba] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Lopez-Olivo, Maria Angeles] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com NR 57 TC 26 Z9 26 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 7 AR CD008331 DI 10.1002/14651858.CD008331.pub2 PG 307 WC Medicine, General & Internal SC General & Internal Medicine GA 622AR UT WOS:000279630900028 PM 20614469 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter TI Comparative Effectiveness Research: Challenges for Medical Journals SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Editorial Material DE Evidence synthesis; Study methodology C1 [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Helfand, Mark] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Grimshaw, Jeremy] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Sox, HC (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. EM helfand@ohsu.edu RI Knottnerus, Johannes/A-3829-2009 FU Public Library of Science FX The PLoS Medicine Editors are each paid a salary by the Public Library of Science, and they contributed to this editorial during their salaried time. The other authors received no specific funding for this article. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 4 AR ED000003 DI 10.1002/14651858.ED00003 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA V34NI UT WOS:000209092700002 ER PT J AU Tovey, D Dellavalle, R AF Tovey, David Dellavalle, Robert TI Cochrane in the United States of America SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Editorial Material DE The Cochrane Library C1 [Tovey, David] Cochrane Editorial Unit, London SE1 2LP, England. [Dellavalle, Robert] Univ Colorado, Dept Dermatol, Sch Med, Denver VA Med Ctr, Denver, CO 80220 USA. RP Tovey, D (reprint author), Cochrane Editorial Unit, 29 Queen Elizabeth St, London SE1 2LP, England. EM dtovey@cochrane.org; robert.dellavalle@ucdenver.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 4 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2010 IS 9 AR ED000010 DI 10.1002/14651858.ED000010 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA V34NN UT WOS:000209093200001 ER PT J AU Gutman, R DeDe, G Michaud, J Liu, JS Caplan, D AF Gutman, Roee DeDe, Gayle Michaud, Jennifer Liu, Jun S. Caplan, David TI Rasch models of aphasic performance on syntactic comprehension tests SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article DE Rasch models; Aphasic; Syntactic comprehension ID DISTRIBUTIONS; DEFICITS AB Responses of 42 people with aphasia to 11 sentence types in enactment and sentence-picture matching tasks were characterized using Rasch models that varied in the inclusion of the factors of task, sentence type, and patient group. The best fitting models required the factors of task and patient group but not sentence type. The results provide evidence that aphasic syntactic comprehension is best accounted for by models that include different estimates of patient ability in different tasks and different difficulty of all sentences in different groups of patients, but that do not include different estimates of patient ability for different types of sentences. C1 [Gutman, Roee; Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA USA. [DeDe, Gayle] Univ Arizona, Dept Speech Language & Hearing Sci, Tucson, AZ USA. [Michaud, Jennifer; Caplan, David] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM dcaplan@partners.org RI Gutman, Roee/J-2355-2014 OI Gutman, Roee/0000-0001-7095-3016 FU NIDCD NIH HHS [R01 DC000942-14, R01 DC000942] NR 21 TC 6 Z9 6 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PY 2010 VL 27 IS 3 BP 230 EP 244 AR PII 928967047 DI 10.1080/02643294.2010.512285 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA 675XX UT WOS:000283875400002 PM 21058076 ER PT B AU Shi, Y Buffenstein, R Van Remmen, H AF Shi, Yun Buffenstein, Rochelle Van Remmen, Holly BE Wolf, NS TI Mitochondria, Oxidative Damage and Longevity: What Can Comparative Biology Teach Us? SO COMPARATIVE BIOLOGY OF AGING LA English DT Article; Book Chapter DE Mitochondria; Aging; Oxidative damage; Reactive oxygen species; Metabolic rate ID FREE-RADICAL PRODUCTION; MAXIMUM LIFE-SPAN; NAKED MOLE-RAT; HYDROGEN-PEROXIDE PRODUCTION; LONGEST-LIVING RODENT; AGE-RELATED-CHANGES; BUTYL-ALPHA-PHENYLNITRONE; ELECTRON-TRANSPORT CHAIN; SHORT-LIVED RAT; PROTEIN OXIDATION AB The most studied theory of aging is the oxidative stress theory of aging, and evidence supporting or disputing the theory has come primarily from investigations using common model organisms such as C elegans, Drosophila, and laboratory rodent models. However, studies using more non-traditional animal models offer an excellent opportunity to critically evaluate different aging hypotheses. The advantage of studying a broader spectrum of species is that one can significantly expand the amount of information obtained on a wide range of biological phenotypes/traits such as life span, body weight, and metabolic rate. In addition, the ultimate validity of a hypothesis/theory can be more critically tested using as many samples, in this case, species as possible. In this chapter we present evidence regarding different aspects of oxidative stress theory of aging with special emphasis on metabolic rate, reactive oxygen species generation, and oxidative damage to macromolecules. The purpose of the chapter is to initiate the integration of current knowledge and also to inspire readers to consider the advantages and power of using a comparative biology approach to study aging. C1 [Buffenstein, Rochelle; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Physiol Cellular & Struct Biol, San Antonio, TX 78229 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. [Shi, Yun] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Physiol, San Antonio, TX 78229 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Physiol Cellular & Struct Biol, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu NR 96 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-3464-9 PY 2010 BP 163 EP 190 DI 10.1007/978-90-481-3465-6_8 D2 10.1007/978-90-481-3465-6 PG 28 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA BNP40 UT WOS:000275173300008 ER PT J AU Kiernan, TJ Yan, BP Jaff, MR AF Kiernan, Thomas J. Yan, Bryan P. Jaff, Michael R. BE Schillinger, M Minar, E TI Preprocedural Imaging in Peripheral Arterial Disease SO COMPLEX CASES IN PERIPHERAL VASCULAR INTERVENTIONS LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE ANGIOGRAPHY; ENHANCED MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; ROW CT ANGIOGRAPHY; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CAROTID-ARTERY; CONVENTIONAL ANGIOGRAPHY; DUPLEX ULTRASOUND; DIAGNOSTIC PERFORMANCE; ROTATIONAL ANGIOGRAPHY C1 [Kiernan, Thomas J.; Yan, Bryan P.; Jaff, Michael R.] Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Kiernan, TJ (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02114 USA. RI Yan, Bryan/P-5928-2015 NR 58 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-84184-732-0 PY 2010 BP 22 EP 40 D2 10.3109/9781841847320 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BD5MD UT WOS:000361601300005 ER PT S AU Mahajerin, A Gelfand, EV AF Mahajerin, Ali Gelfand, Eli V. BE Toth, PP Cannon, CP TI Unstable Angina and Non-ST Elevation Myocardial Infarction SO COMPREHENSIVE CARDIOVASCULAR MEDICINE IN THE PRIMARY CARE SETTING SE Contemporary Cardiology LA English DT Article; Book Chapter DE Atherosclerotic plaque; Unstable angina; Heparin; Myocardial infarction; Troponin ID ACUTE CORONARY SYNDROMES; PLATELET GLYCOPROTEIN IIB/IIIA; RANDOMIZED CONTROLLED-TRIAL; CARDIAC MAGNETIC-RESONANCE; PLACEBO-CONTROLLED TRIAL; ESTROGEN PLUS PROGESTIN; HIGH-RISK PATIENTS; SCANDINAVIAN SIMVASTATIN SURVIVAL; ISCHEMIA-MODIFIED ALBUMIN; SEGMENT-ELEVATION C1 [Mahajerin, Ali; Gelfand, Eli V.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. RP Mahajerin, A (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. NR 121 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-962-8 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 195 EP 225 DI 10.1007/978-1-60327-963-5_10 D2 10.1007/978-1-60327-963-5 PG 31 WC Cardiac & Cardiovascular Systems; Medicine, General & Internal SC Cardiovascular System & Cardiology; General & Internal Medicine GA BQH27 UT WOS:000281004300010 ER PT S AU Donnelly, P Hoffmann, U AF Donnelly, Patrick Hoffmann, Udo BE Toth, PP Cannon, CP TI Cardiac Computed Tomography SO COMPREHENSIVE CARDIOVASCULAR MEDICINE IN THE PRIMARY CARE SETTING SE Contemporary Cardiology LA English DT Article; Book Chapter DE Cardiac computed tomography; Cardiac and coronary anatomy; Electrocardiographic synchronization; Contrast nephropathy ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY ANOMALIES; LEFT-VENTRICULAR FUNCTION; MULTIDETECTOR ROW CT; EMERGENCY-DEPARTMENT PATIENTS; AORTIC-VALVE STENOSIS; 64-SECTION SPIRAL CT; ACUTE CHEST-PAIN; DUAL-SOURCE CT; MAGNETIC-RESONANCE C1 [Donnelly, Patrick; Hoffmann, Udo] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Donnelly, P (reprint author), Harvard Univ, Sch Med, Cardiac MR PET CT Program, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 72 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-60327-962-8 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2010 BP 535 EP 566 DI 10.1007/978-1-60327-963-5_27 D2 10.1007/978-1-60327-963-5 PG 32 WC Cardiac & Cardiovascular Systems; Medicine, General & Internal SC Cardiovascular System & Cardiology; General & Internal Medicine GA BQH27 UT WOS:000281004300027 ER PT B AU Wenk, JF Jhun, CS Zhang, ZH Sun, K Burger, M Einstein, D Ratcliffe, M Guccione, JM AF Wenk, Jonathan F. Jhun, Choon-Sik Zhang, Zhihong Sun, Kay Burger, Mike Einstein, Dan Ratcliffe, Mark Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI In Vivo Left Ventricular Geometry and Boundary Conditions SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID ENGINEERING MECHANICS; SUCCESSIVE STATES; IMAGING DATA; FINITE; FORMULATION; MYOCARDIUM; ELEMENTS; STRAIN AB The first basic biomechanics modeling step outlined in the introductory chapter is to define the geometric configuration. In Chapters 12 and 14 we demonstrate the application of either simple (i.e., axisymmetric truncated ellipsoid) or complex (i.e., fully 3-D) left ventricular (LV) geometric models or finite element (FE) meshes. This chapter is primarily concerned with an instructive review of the methodology we have used to create both types of FE meshes, which relies on the "parametric" meshing software TrueGrid (R). Since TrueGrid is rather expensive. Section 1.6 describes the use of free software executables available from the Pacific Northwest National Laboratory. The second basic biomechanics modeling step (determine mechanical properties) is addressed in the next three chapters. The third and fourth basic biomechanics modeling steps (governing equations and boundary conditions) are discussed briefly at the end of this chapter. C1 [Wenk, Jonathan F.; Jhun, Choon-Sik; Zhang, Zhihong; Sun, Kay; Ratcliffe, Mark; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Wenk, Jonathan F.; Jhun, Choon-Sik; Zhang, Zhihong; Sun, Kay; Ratcliffe, Mark; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Burger, Mike] XYZ Sci Applicat Inc, Livermore, CA USA. [Einstein, Dan] Pacific NW Natl Lab, Olympia, WA USA. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM jwenk1@gmail.com; csjhun@gmail.com; guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 11 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 3 EP 21 DI 10.1007/978-1-4419-0730-1_l D2 10.1007/978-1-4419-0730-1 PG 19 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800001 ER PT B AU Jhun, CS Wenk, JF Sun, K Guccione, JM AF Jhun, Choon-Sik Wenk, Jonathan F. Sun, Kay Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Constitutive Equations and Model Validation SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID CANINE LEFT-VENTRICLE; CARDIAC-MUSCLE; ACTIVE CONTRACTION; FIBER STRESS; DEFORMATION; MYOCARDIUM; MECHANICS; DEACTIVATION; ACTIVATION; KINETICS AB Of the Four basic biomechanics modeling steps outlined in the Introduction. determining the constitutive equations for cardiovascular tissue is often the most difficult step, especially when the tissue properties vary with time and sarcomere length history, its is the case with contracting myocardium. Using a cylindrical model to study transmural variations in stress and strain rather than a finite element model of the entire left ventricle allows for the implementation of a time- and sarcomere length history-dependent constitutive equation. The cylindrical model simulations can then be repeated with progressively simpler constitutive equations and the resulting transmural stress and strain distributions compared to determine under what conditions the moll computationally efficient constitutive equations are valid. This chapter is primarily concerned with an instructive review of the constitutive equations we have implemented in cylindrical and finite element models of the passive and beating left ventricle, including that of diseased and surgically treated hearts. The last section of this chapter is concerned with experimental measurements that we have used to validate these models. C1 [Jhun, Choon-Sik; Wenk, Jonathan F.; Sun, Kay; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Jhun, Choon-Sik; Wenk, Jonathan F.; Sun, Kay; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 23 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 41 EP 54 DI 10.1007/978-1-4419-0730-1_3 D2 10.1007/978-1-4419-0730-1 PG 14 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800003 ER PT B AU Wenk, JF Jhun, CS Sun, K Stander, N Guccione, JM AF Wenk, Jonathan F. Jhun, Choon-Sik Sun, Kay Stander, Nielen Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Determination of Myocardial Material Properties by Optimization SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID LEFT-VENTRICULAR ANEURYSM; LARGE ELASTIC DEFORMATIONS; CANINE LEFT-VENTRICLE; FINITE-ELEMENT-METHOD; MECHANICAL DYSFUNCTION; 3-DIMENSIONAL STRAIN; BORDER ZONE; MR-IMAGES; MODEL; STRESS AB The previous chapter includes a computationally efficient strain energy function for describing the three-dimensional relationship between stress and strain in passive myocardial material properties, the material parameters of which were formally optimized using left ventricular pressure and epicardial strain measurements in a cylindrical model. Results from such a model are confined at best to the equatorial region of the left ventricle. A finite element model of the entire left ventricle is required to determine regional variations in myocardial material properties. The most important or at least interesting finding from such a study is that myocardial contractility in the (border zone) region adjacent to a myocardial infarction is much less than (typically only hall) that in regions remote from the myocardial infarction. This finding has been confirmed with active stress measurements in skinned muscle fibers dissected from these regions. This chapter is concerned with brief descriptions of the studies from our laboratory that have led up to our current knowledge concerning regional variations of myocardial contractility in infarcted left ventricles. C1 [Wenk, Jonathan F.; Jhun, Choon-Sik; Sun, Kay; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Wenk, Jonathan F.; Jhun, Choon-Sik; Sun, Kay; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Stander, Nielen] Livermore Software Technol Corp, Livermore, CA USA. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 28 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 55 EP 72 DI 10.1007/978-1-4419-0730-1_4 D2 10.1007/978-1-4419-0730-1 PG 18 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800004 ER PT B AU Ge, L Kassab, GS AF Ge, Liang Kassab, G. S. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Turbulence in the Cardiovascular System: Aortic Aneurysm as an Illustrative Example SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID SHEAR-STRESS; CAROTID BIFURCATION; ENDOTHELIAL-CELLS; PULSATILE FLOW; ENLARGEMENT AB Turbulence is a fluid regime characterized by chaotic and stochastic changes of flow. The onset of turbulence can occur under disease conditions and is known to have adverse effects on the function of the cardiovascular (CV) system. This chapter outlines the basic features of turbulence in the CV system. As a specific example. simulation of turbulent flow in an abdominal aortic aneurysm (AAA) is presented. The simulated results show that transition to turbulence occurs in large aneurysms with high Reynolds number. Onset of turbulence is seen to drastically change the distribution of wall shear stress and fluid pressure. The general implications are enumerated. C1 [Ge, Liang] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Ge, Liang] San Francisco VA Med Ctr, San Francisco, CA USA. [Kassab, G. S.] IUPUI, Dept Biomed Engn, Dept Cellular & Integrat Physiol, Dept Surg,Indiana Ctr Vasc Biol & Med, Indianapolis, IN 46202 USA. [Kassab, G. S.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. RP Ge, L (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM gkassab@iupui.edu; gkassab@iupui.edu NR 24 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 159 EP 176 DI 10.1007/978-1-4419-0710-1_10 D2 10.1007/978-1-4419-0730-1 PG 18 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800010 ER PT B AU Wenk, JF Jhun, CS Sun, K Ratcliffe, MB Guccione, JM AF Wenk, Jonathan F. Jhun, Choon-Sik Sun, Kay Ratcliffe, Mark B. Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Surgical Left Ventricular Remodeling Procedures SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID FINITE-ELEMENT MODEL; VOLUME REDUCTION SURGERY; CANINE LEFT-VENTRICLE; MYOCARDIAL-INFARCTION; 3-DIMENSIONAL STRAIN; STRESS-ANALYSIS; ANEURYSM; RESTORATION; MECHANICS; REPAIR AB Perhaps the most straightforward clinical application of validated regional ventricular mechanics models for diseased hearts is the simulation of a novel surgical procedure or medical device for treating heart failure or ischemic cardiomyopathy. In each study our cardiac biomechanics laboratory uses one of two different approaches: (I) an axisymmetric truncated ellipsoidal model with left ventricular (LV) cavity and wall volumes typical of the failing human heart or animal model of heart failure to determine efficacy of the surgical procedure or device; or (2) an animal- or patient-specific fully 3-D model of the infarcted IN created using echocardiography or MRI to optimize the design of the surgical procedure or device. This chapter is concerned with brief descriptions of the studies From our laboratory that provide the best examples of these two approaches. C1 [Wenk, Jonathan F.; Jhun, Choon-Sik; Sun, Kay; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Wenk, Jonathan F.; Jhun, Choon-Sik; Sun, Kay; Ratcliffe, Mark B.; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM jwenk1@gmail.com; csjhun@gmail.com; guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 24 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 197 EP 210 DI 10.1007/978-1-4419-0730-1_12 D2 10.1007/978-1-4419-0730-1 PG 14 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800012 ER PT B AU Jhun, CS Gundiah, N Sun, K Sabbah, HN Tseng, EE Ratcliffe, MB Guccione, JM AF Jhun, Choon-Sik Gundiah, Namrata Sun, Kay Sabbah, Hani N. Tseng, E. Elaine Ratcliffe, Mark B. Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Passive Left Ventricular Constraint Devices SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID CARDIAC SUPPORT DEVICE; ACUTE MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; HEART-FAILURE; WALL STRESS; SURVIVAL; MECHANICS; VOLUME; MODEL; SHAPE AB Both myocardial infarction and volume overloading associated with regurgitant valve lesions lead to eccentric left. ventricular (LV) hypertrophy. The mechanism is presumed to be positive feedback between diastolic LV wall stress and eccentric LV hypertrophy. Further, in each case, an increase in LV sire is an important adverse prognostic finding. The experience with skeletal muscle cardiomyoplasty led to the hypothesis that passive constraint of LV enlargement would interrupt the diastolic stress and eccentric hypertrophy cycle, in addition to halting and possibly reversing the adverse LV remodeling. A number of passive constraint devices such as the Acorn CorCap (TM) Cardiac Support Device (CSD), Paracor Medical HeartNet (TM) Ventricular Support System (VSS), and Myocor (TM) Myosplint (R) have been used. Most recently, an Adjustable Fluid Filled Balloon CSD was proposed by Ghanta and colleagues. In this chapter we model the effect of passive constraint devices, with the exception of the Paracor Medical HeartNet (TM) VSS. on the LV stroke volume/end-diastolic pressure (Starling) relationship and regional distributions of stress in the local muscle fiber direction. C1 [Jhun, Choon-Sik; Sun, Kay; Tseng, E. Elaine; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Jhun, Choon-Sik; Sun, Kay; Tseng, E. Elaine; Ratcliffe, Mark B.; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Sabbah, Hani N.] Henry Ford Hosp, Detroit, MI 48202 USA. [Gundiah, Namrata] Indian Inst Sci, Dept Mech Engn, Bangalore 560012, Karnataka, India. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM csjhun@gmail.com; guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 27 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 211 EP 226 DI 10.1007/978-1-4419-0730-1_13 D2 10.1007/978-1-4419-0730-1 PG 16 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800013 ER PT B AU Wall, ST Wenk, JF Jhun, CS Guccione, JM AF Wall, Samuel T. Wenk, Jonathan F. Jhun, Choon-Sik Guccione, Julius M. BE Guccione, JM Kassab, GS Ratcliffe, MB TI Left Ventricular Implantation of Biomaterials SO COMPUTATIONAL CARDIOVASCULAR MECHANICS: MODELING AND APPLICATIONS IN HEART FAILURE LA English DT Article; Book Chapter ID FINITE-ELEMENT MODEL; CARDIOMYOPATHY AB In recent years, there has been a significant effort to restore heart function by the addition of stem cells directly into the myocardium. These cells are normally carried in a synthetic extracellular matrix and implanted into the injured heart. While there has been little demonstration of actual tissue regeneration using such methods, there has been long-term improvement from these techniques, and surprisingly, from the implantation of biomaterials alone, without any included cells. This has in fact led to therapies that directly add passive materials into the ventricle to help prevent heart failure. Therefore, theoretically evaluating the addition of passive material volumes into the myocardium is of clinical importance to understand the mechanisms for the improvement of ventricular mechanics and for optimizing such treatments. In this chapter we discuss the role of finite element studies in investigating the direct addition of non-contractile materials into the myocardium. C1 [Wall, Samuel T.; Wenk, Jonathan F.; Jhun, Choon-Sik; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Wall, Samuel T.; Wenk, Jonathan F.; Jhun, Choon-Sik; Guccione, Julius M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM jwenk1@gmail.com; csjhun@gmail.com; guccionej@surgery.ucsf.edu; guccionej@surgery.ucsf.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0729-5 PY 2010 BP 227 EP 238 DI 10.1007/978-1-4419-0730-1_14 D2 10.1007/978-1-4419-0730-1 PG 12 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Surgery SC Cardiovascular System & Cardiology; Engineering; Surgery GA BNM97 UT WOS:000275006800014 ER PT S AU Pappalardo, F Halling-Brown, M Pennisi, M Chiacchio, F Sansom, CE Shepherd, AJ Moss, DS Motta, S Brusic, V AF Pappalardo, Francesco Halling-Brown, Mark Pennisi, Marzio Chiacchio, Ferdinando Sansom, Clare E. Shepherd, Adrian J. Moss, David S. Motta, Santo Brusic, Vladimir BE Masulli, F Peterson, LE Tagliaferri, R TI The ImmunoGrid Simulator: How to Use It SO COMPUTATIONAL INTELLIGENCE METHODS FOR BIOINFORMATICS AND BIOSTATISTICS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 6th International Meeting on Computational Intelligence Methods for Bioinformatics and Biostatistics CY OCT 15-17, 2009 CL Genoa, ITALY SP Univ Genoa, Dept Comp & Informat Sci, Univ Salerno, Dept Math & Comp Sci, Grp Nazl Calcolo Sci ID T-CELL EPITOPES; CLASS-I BINDING; MHC CLASS-I; IMMUNE-SYSTEM; PROTEASOMAL CLEAVAGE; PEPTIDE BINDING; DRUG DISCOVERY; PREDICTION; MOLECULES; RESOURCE AB In this paper we present the ImmunoGrid project, whose goal is to develop an immune system simulator which integrates molecular and system level models with Grid computing resources for large-scale tasks and databases. We introduce the models and the technologies used in the ImmunoGrid Simulator, showing how to use them through the ImmunoGrid web interface. The ImmunoGrid project has proved that simulators can be used in conjunction with grid technologies for drug and vaccine discovery, demonstrating that it is possible to drastically reduce the developing time of such products. C1 [Pappalardo, Francesco; Pennisi, Marzio; Chiacchio, Ferdinando; Motta, Santo] Univ Catania, Dept Math & Comp Sci, I-95124 Catania, Italy. [Motta, Santo] Univ Catania, Fac Pharm, I-95124 Catania, Italy. [Pappalardo, Francesco] CNR, Istituto applicaz calcolo Mauro Picone, Rome, Italy. [Sansom, Clare E.; Shepherd, Adrian J.; Moss, David S.] Univ London Birkbeck Coll, Inst Struct & Mol Bio, Dept Biol Sci, London WC1E 7HX, England. [Brusic, Vladimir] Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. [Halling-Brown, Mark] Inst Canc Res, Surrey, England. RP Pappalardo, F (reprint author), Univ Catania, Dept Math & Comp Sci, I-95124 Catania, Italy. EM francesco@dmi.unict.it; mhallingbrown@icr.ac.uk; mpennisi@dmi.unict.it; fchiacchio@dmi.unict.it; c.sansom@mail.cryst.bbk.ac.uk; a.shepherd@mail.cryst.bbk.ac.uk; d.moss@mail.cryst.bbk.ac.uk; motta@dmi.unict.it; vladimir_brusic@dfci.harvard.edu RI Motta, Santo/I-5177-2012; Pappalardo, Francesco/C-5832-2011; Pennisi, Marzio/G-4618-2015; OI Pappalardo, Francesco/0000-0003-1668-3320; Pennisi, Marzio/0000-0003-0231-7653; Motta, Santo/0000-0003-3533-2972 NR 71 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-14570-4 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2010 VL 6160 BP 1 EP + PG 6 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BST14 UT WOS:000285734400001 ER PT S AU Davis, KA Hancock, KE Delgutte, B AF Davis, Kevin A. Hancock, Kenneth E. Delgutte, Bertrand BE Meddis, R LopezPoveda, EA Fay, RR Popper, AN TI Computational Models of Inferior Colliculus Neurons SO COMPUTATIONAL MODELS OF THE AUDITORY SYSTEM SE Springer Handbook of Auditory Research LA English DT Article; Book Chapter ID DORSAL COCHLEAR NUCLEUS; AMPLITUDE-MODULATED TONES; SUPERIOR OLIVARY COMPLEX; BINAURAL RESPONSE PROPERTIES; SPATIAL RECEPTIVE-FIELDS; AUDITORY-NERVE FIBERS; INTERAURAL TEMPORAL DISPARITIES; HIGH-FREQUENCY NEURONS; SINGLE-UNIT RESPONSES; STEADY-STATE VOWELS C1 [Davis, Kevin A.] Univ Rochester, Dept Biomed Engn, Rochester, NY 14642 USA. [Davis, Kevin A.] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY 14642 USA. [Hancock, Kenneth E.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Davis, KA (reprint author), Univ Rochester, Dept Biomed Engn, 601 Elmwood Ave, Rochester, NY 14642 USA. EM kevin_davis@urmc.rochester.edu; Ken_Hancock@meei.harvard.edu; Bertrand_Delgutte@meei.harvard.edu NR 150 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0947-2657 BN 978-1-4419-1370-8 J9 SPRINGER HANDB AUDIT JI Springer Handb. Audit. Res. PY 2010 VL 35 BP 129 EP 176 DI 10.1007/978-1-4419-5934-8_6 D2 10.1007/978-1-4419-5934-8 PG 48 WC Computer Science, Interdisciplinary Applications; Otorhinolaryngology SC Computer Science; Otorhinolaryngology GA BPG81 UT WOS:000278828700006 ER PT S AU Magagnin, V Mauri, M Cipresso, P Mainardi, L Brown, EN Cerutti, S Villamira, M Barbieri, R AF Magagnin, V. Mauri, M. Cipresso, P. Mainardi, L. Brown, E. N. Cerutti, S. Villamira, M. Barbieri, R. BE Murray, A TI Heart Rate Variability and Respiratory Sinus Arrhythmia Assessment of Affective States by Bivariate Autoregressive Spectral analysis SO COMPUTING IN CARDIOLOGY 2010, VOL 37 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 37th Annual Conference of the Computing-in-Cardiology CY SEP 26-29, 2010 CL Belfast, NORTH IRELAND SP Comp Cardiol, EMB, IEEE, Univ Ulster, Medtronic, HeartSine, Drager, GE Healthcare, Mortara, Univ Rochester, Telemetr & Holter ECG Warehouse Project, Zoll, Inst Phys, IBM ID COMPUTER AB The study of emotions elicited by human-computer interactions is a promising field that could lead to the identification of specific patterns of affective states. We present a heart rate variability (HRV) assessment of the autonomic nervous system (ANS) response and respiratory sinus arrhythmia during PC-mediated stimuli by means of standard and multivariate autoregressive spectral methods. 35 healthy volunteers were exposed to computer-mediated tasks during data collection. The stimuli were designed to elicit: relaxation (R), engagement (E) and stress (S); half of the subjects were exposed to E before S (RES) while the other to S before E (RSE). HRV measures clearly separate the ANS response among R, S and E. Less significant differences are found between E and S in RSE, suggesting that S stimuli may cause a lasting response affecting the E period. Results from the bivariate analysis indicate a disruption of the cardio-respiratory coupling during non-relax conditions. C1 [Magagnin, V.] Ist Ortoped IRCCS Galeazzi, Milan, Italy. RP Barbieri, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM rbarbieri1@partners.org OI Barbieri, Riccardo/0000-0001-9381-3833; Cipresso, Pietro/0000-0002-0662-7678 FU NHLBI NIH HHS [R01 HL084502, R01 HL084502-04]; NIH HHS [DP1 OD003646] NR 16 TC 11 Z9 11 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4244-7318-2 J9 COMPUT CARDIOL CONF PY 2010 VL 37 BP 145 EP 148 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Engineering; Mathematical & Computational Biology GA BJL83 UT WOS:000328956000037 PM 22158520 ER PT S AU Perz, S Kufner, R Englmeier, KH Meisinger, C Kaab, S Sinner, MF Wichmann, HE AF Perz, Siegfried Kuefner, Roswitha Englmeier, Karl-Hans Meisinger, Christine Kaeaeb, Stefan Sinner, Moritz F. Wichmann, H-Erich BE Murray, A TI Quality of Electrocardiographic Records in Population Studies: What Can we Achieve? SO COMPUTING IN CARDIOLOGY 2010, VOL 37 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 37th Annual Conference of the Computing-in-Cardiology CY SEP 26-29, 2010 CL Belfast, NORTH IRELAND SP Comp Cardiol, EMB, IEEE, Univ Ulster, Medtronic, HeartSine, Drager, GE Healthcare, Mortara, Univ Rochester, Telemetr & Holter ECG Warehouse Project, Zoll, Inst Phys, IBM AB Measurement precision and validity of the diagnostic interpretation are to a major extent associated with the noise interference in routinely recorded electrocardiograms (ECGs). In order to provide appropriate quality in the population-based KORA-F4 study, we applied a multi-stage monitoring of the resting ECG recording including a comprehensive training of the technicians to enhance their skills for appropriate electrode application, artefact recognition and prevention, and in addition, computerized measurement of the noise superimposing the ECG. ECGs of predominantly good quality were obtained from 98.3% (3028/3080) of the study participants. The quality achieved is a precondition for reliable estimates of population-based ECG characteristics, especially when valid phenotyping for serial ECG analyses and genetic association studies is required. C1 [Perz, Siegfried] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany. [Meisinger, Christine; Wichmann, H-Erich] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Kaeaeb, Stefan; Sinner, Moritz F.] Univ Munich, Dept Internal Med 1, Munich, Germany. [Sinner, Moritz F.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Perz, S (reprint author), German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany. EM perz@helmholtz-muenchen.de OI Englmeier, Karl-Hans/0000-0001-6028-5392; Meisinger, Christa/0000-0002-9026-6544 NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4244-7318-2 J9 COMPUT CARDIOL CONF PY 2010 VL 37 BP 705 EP 708 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Engineering; Mathematical & Computational Biology GA BJL83 UT WOS:000328956000177 ER PT S AU Citi, L Klerman, EB Brown, EN Barbieri, R AF Citi, L. Klerman, E. B. Brown, E. N. Barbieri, R. BE Murray, A TI Point Process Heart Rate Variability Assessment during Sleep Deprivation SO COMPUTING IN CARDIOLOGY 2010, VOL 37 SE Computing in Cardiology Conference LA English DT Proceedings Paper CT 37th Annual Conference of the Computing-in-Cardiology CY SEP 26-29, 2010 CL Belfast, NORTH IRELAND SP Comp Cardiol, EMB, IEEE, Univ Ulster, Medtronic, HeartSine, Drager, GE Healthcare, Mortara, Univ Rochester, Telemetr & Holter ECG Warehouse Project, Zoll, Inst Phys, IBM ID SYMPATHOVAGAL BALANCE; PERFORMANCE AB To investigate the potential relationships between Heart Rate Variability (HRV) and objective performance-subjective alertness measures during sleep deprivation, a novel point process algorithm was applied to ECG data from healthy young subjects in a 52-hour Constant Routine protocol that includes sleep deprivation. Our algorithm is able to estimate the time-varying behavior of the HRV spectral indexes in an on-line instantaneous method. Results demonstrate the ability of our framework to provide high time-resolution sympatho-vagal dynamics as measured by spectral low frequency (LF) and high frequency (HF) power. Correlation analysis on individual subjects reveals a relevant correspondence between LF/HF and subjective alertness during the initial hours of sleep deprivation. At longer times awake, high correlation levels between LF/HF and objective performance indicate an increasing sympathetic drive as performance measures worsen. These results suggest that our point-process based HRV assessment could aid in real-time prediction of performance-alertness. C1 [Citi, L.] Harvard Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149,13th St, Charlestown, MA 02129 USA. [Citi, L.; Brown, E. N.; Barbieri, R.] Harvard Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Citi, L.; Brown, E. N.; Barbieri, R.] MIT, Dept Brain & Congnit Sci, Cambridge, MA USA. [Klerman, E. B.] Harvard Med Sch, Brigham & Womens Hosp, Div Sleep Med, Boston, MA USA. RP Citi, L (reprint author), Harvard Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149,13th St, Charlestown, MA 02129 USA. EM lciti@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833 FU National Institutes of Health (NIH) [R01-HL084502, R01-DA015644, DP1-OD003646, P01-AG09975, K02-HD045459, NCRR-GCRC-M01-RR02636, RC2-HL101340]; NSBRI [NASA NCC 9-58, HFP01604] FX This work was supported by National Institutes of Health (NIH) Grants R01-HL084502 (R.B); R01- DA015644 and DP1-OD003646 (E.N.B); P01-AG09975, K02-HD045459 (E.B.K.), NCRR-GCRC-M01-RR02636, RC2-HL101340 (E.B.K.), and NSBRI (through NASA NCC 9-58) Grant HFP01604 (E.B.K). NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2325-887X BN 978-1-4244-7318-2 J9 COMPUT CARDIOL CONF PY 2010 VL 37 BP 721 EP 724 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Cardiovascular System & Cardiology; Engineering; Mathematical & Computational Biology GA BJL83 UT WOS:000328956000181 PM 22517071 ER PT J AU Cantillon-Murphy, P Wald, LL Zahn, M Adalsteinsson, E AF Cantillon-Murphy, Padraig Wald, Lawrence L. Zahn, Markus Adalsteinsson, Elfar TI Proposing Magnetic Nanoparticle Hyperthermia in Low-Field MRI SO CONCEPTS IN MAGNETIC RESONANCE PART A LA English DT Article DE magnetic nanoparticles; hyperthermia; heating; RF relaxation; combined MRI/hyperthermia ID DEPOSITION; PARTICLES; THERAPY; FLUID AB This work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyperthermia source perpendicular to the MRI B(0) field which operates in a similar manner to the MRI RF excitation field, B(t), but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence, This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B(0), the nanoparticles' suspension magnetization rapidly saturates with increasing B(0). Therefore, the proposal is best suited to low-field MRI systems when magnetic saturation is incomplete. in addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B(t) held used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady-state temperature rises in small spherical tumors of up to 10 degrees C are conceivable with careful selection of the nanoparticle radius and concentration, RF hyperthermia held amplitude and frequency. (C) 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 30-47, 2010. C1 [Cantillon-Murphy, Padraig] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Cantillon-Murphy, Padraig; Zahn, Markus; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wald, Lawrence L.; Adalsteinsson, Elfar] Massachusetts Gen Hosp, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Cantillon-Murphy, P (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St,Thorn Room 1123, Boston, MA 02115 USA. EM padraig@mit.edu RI Adalsteinsson, Elfar/F-2477-2010; Wald, Lawrence/D-4151-2009; OI Cantillon-Murphy, Padraig/0000-0001-6679-2889 NR 31 TC 5 Z9 5 U1 3 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1546-6086 J9 CONCEPT MAGN RESON A JI Concepts Magn. Reson. Part A PD JAN PY 2010 VL 36A IS 1 BP 36 EP 47 DI 10.1002/cmr.a.20153 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 568LQ UT WOS:000275524200003 ER PT S AU Sankaran, VG Xu, JA Orkin, SH AF Sankaran, Vijay G. Xu, Jian Orkin, Stuart H. BE Vichinsky, EP Neufeld, EJ TI Transcriptional silencing of fetal hemoglobin by BCL11A SO COOLEY'S ANEMIA: NINTH SYMPOSIUM SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th Cooleys Anemia Symposium CY OCT 21-24, 2009 CL New York Acad Sci, New York, NY SP Cooleys Anemia Fdn, New York Acad Sci HO New York Acad Sci DE thalassemia; fetal hemoglobin; globin switching; BCL11A; transcription ID SICKLE-CELL-DISEASE; GENOME-WIDE ASSOCIATION; GLOBIN GENE-EXPRESSION; BETA-THALASSEMIA; RISK-FACTORS; INDUCTION; PHENOTYPE; HBS1L-MYB; REGION; ADULTS AB The beta-thalassemia syndromes arc a major global health problem. Increased levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms seen in this disease. By taking advantage of the natural variation in the level of HbF in various populations, we and others identified several common genetic variants in three major loci that regulate HbF levels. One of these variants resides in the gene BCL11A. We have studied the role of this gene product and established that BCL11A maintains silencing of gamma-glabin expression in adult erythroid cells and functions as a direct transcriptional regulator of the fetal to adult hemoglobin switch in humans. Moreover, we found that BCL11A plays a central role in the evolutionarily divergent globin gene switches of mammals. As a factor critical for gamma-globin gene silencing, BCL11A should be considered as a therapeutic target to increase Fibrin a directed manner in beta-thalassemia patients. C1 [Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Harvard Stern Cell Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Harvard Stern Cell Inst,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_orkin@dtci.harvard.edu FU Howard Hughes Medical Institute NR 28 TC 20 Z9 22 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-782-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1202 BP 64 EP 68 DI 10.1111/j.1749-6632.2010.05574.x PG 5 WC Hematology; Multidisciplinary Sciences SC Hematology; Science & Technology - Other Topics GA BRM50 UT WOS:000283099600011 PM 20712774 ER PT S AU Jun, JJ Siracuse-Lee, DE Daly, MK Dohlman, CH AF Jun, Jason J. Siracuse-Lee, Donna E. Daly, Mary K. Dohlman, Claes H. BE Reinhard, T Larkin, F TI Keratoprosthesis SO CORNEA AND EXTERNAL EYE DISEASE: CORNEAL ALLOTRANSPLANTATION, ALLERGIC DISEASE AND TRACHOMA SE Essentials in Ophthalmology LA English DT Article; Book Chapter ID BOSTON TYPE-1 KERATOPROSTHESIS; OSTEO-ODONTO-KERATOPROSTHESIS; STEVENS-JOHNSON-SYNDROME; PENETRATING KERATOPLASTY; CORNEAL TRANSPLANTATION; RISK-FACTORS; GRAFT-SURVIVAL; IN-VIVO; BLINDNESS; OUTCOMES C1 [Jun, Jason J.; Siracuse-Lee, Donna E.; Daly, Mary K.] Vet Affairs Boston Healthcare Syst, Jamaica Plain, MA USA. [Daly, Mary K.] Boston Univ, Eye Associates Inc, Boston, MA 02118 USA. [Siracuse-Lee, Donna E.; Daly, Mary K.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Dohlman, Claes H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. RP Jun, JJ (reprint author), Vet Affairs Boston Healthcare Syst, Jamaica Plain, MA USA. NR 59 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1612-3212 BN 978-3-540-85543-9 J9 ESSENT OPHTHALMOL PY 2010 BP 137 EP 144 DI 10.1007/978-3-540-85544-6_10 D2 10.1007/978-3-540-85544-6 PG 8 WC Ophthalmology SC Ophthalmology GA BNK81 UT WOS:000274815600010 ER PT B AU Hollander, DA AF Hollander, David A. BA Trattler, WB Majmudar, PA Luchs, JI Swartz, TS BF Trattler, WB Majmudar, PA Luchs, JI Swartz, TS TI ANTERIOR SEGMENT NEOPLASIA SO CORNEA HANDBOOK LA English DT Article; Book Chapter ID SQUAMOUS-CELL CARCINOMA; PRIMARY ACQUIRED MELANOSIS; TOPICAL MITOMYCIN-C; CONJUNCTIVAL INTRAEPITHELIAL NEOPLASIA; SEBACEOUS GLAND CARCINOMA; LYMPHOID-TISSUE LYMPHOMA; IMMUNODEFICIENCY-VIRUS-INFECTION; MALIGNANT FIBROUS HISTIOCYTOMA; HUMAN-PAPILLOMAVIRUS DNA; OCULAR ADNEXAL LYMPHOMA C1 Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. RP Hollander, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. NR 238 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-842-5 PY 2010 BP 163 EP 189 PG 27 WC Ophthalmology SC Ophthalmology GA BNG60 UT WOS:000274515200010 ER PT B AU Hamrah, P Eiferman, RA AF Hamrah, Pedram Eiferman, Richard A. BA Trattler, WB Majmudar, PA Luchs, JI Swartz, TS BF Trattler, WB Majmudar, PA Luchs, JI Swartz, TS TI CORNEAL TRAUMA AND BURNS SO CORNEA HANDBOOK LA English DT Article; Book Chapter C1 [Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Hamrah, Pedram] Harvard Univ, Sch Med, Ocular Surface Imaging Ctr, Boston, MA USA. [Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Eiferman, Richard A.] Univ Louisville, Louisville, KY 40292 USA. RP Hamrah, P (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-55642-842-5 PY 2010 BP 191 EP 200 PG 10 WC Ophthalmology SC Ophthalmology GA BNG60 UT WOS:000274515200011 ER PT J AU Gibbons, CJ Stirman, SW Brown, GK Beck, AT AF Gibbons, Carly J. Stirman, Shannon Wiltsey Brown, Gregory K. Beck, Aaron T. TI Engagement and Retention of Suicide Attempters in Clinical Research Challenges and Solutions SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE suicide; retention; attrition; cognitive therapy ID RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; THERAPEUTIC-COMMUNITY; PREDICTORS; DISORDERS; ATTRITION; MEN AB Background: High attrition rates in longitudinal research can limit study generalizability, threaten internal validity, and decrease statistical power. Research has demonstrated that there can be significant differences between participants who complete a research study and those who drop out prematurely, and that treatment outcomes may be dependent on retention in a treatment protocol. Aims: The current paper describes the challenges encountered when implementing a randomized controlled trial of cognitive therapy for the prevention of suicide attempts and the solutions developed to overcome these problems. Methods: Problems unique to suicide attempters are discussed, and strategies successfully implemented to boost retention rates are provided. Results: The methods implemented appeared to increase retention rates in the randomized controlled trial. Conclusions: Many steps can be taken to work with this difficult population, and researchers are encouraged to be as involved and flexible with participants as possible. C1 [Stirman, Shannon Wiltsey] VA Boston Healthcare Syst 116B 3, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Gibbons, Carly J.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Gibbons, Carly J.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Stirman, Shannon Wiltsey] Boston Univ, Div Psychiat, Boston Med Ctr, Boston, MA 02215 USA. [Brown, Gregory K.; Beck, Aaron T.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Stirman, SW (reprint author), VA Boston Healthcare Syst 116B 3, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM shannon.wiltsey-stirman@va.gov FU NICHD NIH HHS [R01 HD060915]; NIGMS NIH HHS [R01 GM060915]; NIMH NIH HHS [R00 MH080100-04, P20 MH071905, R01 MH60915, R00 MH080100, P20 MH71905, K99 MH080100, K99MH080100]; PHS HHS [R37 CCR316866] NR 19 TC 8 Z9 8 U1 2 U2 5 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 J9 CRISIS JI Crisis PY 2010 VL 31 IS 2 BP 62 EP 68 DI 10.1027/0227-5910/a000018 PG 7 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 588SP UT WOS:000277094400002 PM 20418211 ER PT J AU Siddiki, H Kojicic, M Li, GX Yilmaz, M Thompson, TB Hubmayr, RD Gajic, O AF Siddiki, Hassan Kojicic, Marija Li, Guangxi Yilmaz, Murat Thompson, Taylor B. Hubmayr, Rolf D. Gajic, Ognjen TI Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials SO CRITICAL CARE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; MECHANICALLY VENTILATED PATIENTS; RESTING ENERGY-EXPENDITURE; III PROGNOSTIC SYSTEM; HOSPITAL MORTALITY; PREDICTORS; SURVIVAL; FAILURE; RISK; MECHANISMS AB Introduction: Dead-space fraction (Vd/Vt) has been shown to be a powerful predictor of mortality in acute lung injury (ALI) patients. The measurement of Vd/Vt is based on the analysis of expired CO2 which is not a part of standard practice thus limiting widespread clinical application of this method. The objective of this study was to determine prognostic value of Vd/Vt estimated from routinely collected pulmonary variables. Methods: Secondary analysis of the original data from two prospective studies of ALI patients. Estimated Vd/Vt was calculated using the rearranged alveolar gas equation: Vd / Vt = 1-[(0.86 x (V) over dotCO(2est)) / (VE x PaCO2)] where (V) over dotCO(2est) is the estimated CO2 production calculated from the Harris Benedict equation, minute ventilation (VE) is obtained from the ventilator rate and expired tidal volume and PaCO2 from arterial gas analysis. Logistic regression models were created to determine the prognostic value of estimated Vd/Vt. Results: One hundred and nine patients in Mayo Clinic validation cohort and 1896 patients in ARDS-net cohort demonstrated an increase in percent mortality for every 10% increase in Vd/Vt in a dose response fashion. After adjustment for non-pulmonary and pulmonary prognostic variables, both day 1 (adjusted odds ratio-OR = 1.07, 95%CI 1.03 to 1.13) and day 3 (OR = 1.12, 95% CI 1.06 to 1.18) estimated dead-space fraction predicted hospital mortality. Conclusions: Elevated estimated Vd/Vt predicts mortality in ALI patients in a dose response manner. A modified alveolar gas equation may be of clinical value for a rapid bedside estimation of Vd/Vt, utilizing routinely collected clinical data. C1 [Kojicic, Marija; Li, Guangxi; Hubmayr, Rolf D.; Gajic, Ognjen] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Dept Internal Med, Rochester, MN 55905 USA. [Siddiki, Hassan] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN 55905 USA. [Yilmaz, Murat] Akdeniz Univ, Dept Anesthesiol & Crit Care, TR-0709 Antalya, Turkey. [Thompson, Taylor B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit,Med Intens Care Un, Boston, MA 02114 USA. RP Gajic, O (reprint author), Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Dept Internal Med, 200 1stSt, Rochester, MN 55905 USA. EM gajic.ognjen@mayo.edu NR 40 TC 28 Z9 31 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2010 VL 14 IS 4 AR R141 DI 10.1186/cc9206 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 680JJ UT WOS:000284227900016 PM 20670411 ER PT J AU Bellani, G Musch, G Messa, C Pesenti, A AF Bellani, Giacomo Musch, Guido Messa, Cristina Pesenti, Antonio TI (18)-F-fluorodeoxyglucose positron emission tomography/computed tomography study in acute lung injury/acute respiratory distress syndrome reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 [Bellani, Giacomo; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Monza, Italy. [Bellani, Giacomo; Pesenti, Antonio] Osped San Gerardo, Dept Perioperat Med & Intens Care, Monza, Italy. [Musch, Guido] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Messa, Cristina] Univ Milano Bicocca, Ctr Bioimmagini Mol, Milan, Italy. RP Bellani, G (reprint author), Univ Milano Bicocca, Dept Expt Med, Monza, Italy. RI Bellani, Giacomo/D-2379-2010; Pesenti, Antonio/H-7483-2012 OI Bellani, Giacomo/0000-0002-3089-205X; NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2010 VL 38 IS 1 BP 348 EP 348 DI 10.1097/CCM.0b013e3181c546c5 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 539AE UT WOS:000273224800084 ER PT J AU Mailloux, AW Young, MRI AF Mailloux, Adam W. Young, M. Rita I. TI Regulatory T-cell Trafficking: From Thymic Development to Tumor-Induced Immune Suppression SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE regulatory T cell; Treg; migration; trafficking; localization; chemokine; inflammation; cancer; immune suppression ID TRANSCRIPTION FACTOR FOXP3; DRAINING LYMPH-NODES; BONE-MARROW; DENDRITIC CELLS; CHEMOKINE RECEPTOR; HEPATOCELLULAR-CARCINOMA; PERIPHERAL-BLOOD; EPITHELIAL-CELLS; HUMAN THYMOCYTES; OVARIAN-CANCER AB Regulatory T cells (Tregs) have become a priority for many investigators in immunology due to their potent immunosuppressive and tolerogenic effects. While Treg activity is required for normal immune homeostasis, dysregulation of their numbers can induce autoimmunity or aid in the pathogenesis of disease. Therefore, great effort has been made to understand the mechanisms by which Tregs accumulate in different areas of the body. Like other lymphocytes, Tregs migrate in response to a network of chemotactic stimuli involving chemokines, chemokine receptors, integrins, and their corresponding ligands. However, many of these stimuli are exclusive to Tregs, inducing their migration while leaving conventional populations unaffected. It is these selective stimuli that result in increased ratios of Tregs among conventional effector populations, leading to changes in immune suppression and homeostasis. This review explores selective Treg trafficking during thymic Treg development, migration to secondary lymphoid tissues and emigration into the periphery during homeostatic conditions, inflammation, and the tumor microenvironment, placing emphasis on stimuli :hat selectively recruits Tregs to target locations. C1 [Young, M. Rita I.] Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. [Mailloux, Adam W.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Program Immunol, Tampa, FL 33612 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM adam.mailloux@moffitt.org; rita.young@va.gov FU National Cancer Institute (NCI) [T32 CA115308] FX We would like to acknowledge the financial assistance and research resources of the T32 Tumor Immunology Training Grant; T32 CA115308, Program Leader, Julie Y. Djeu, Ph.D. (2007 -2012), provided by the National Cancer Institute (NCI). NR 125 TC 25 Z9 28 U1 0 U2 7 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2010 VL 30 IS 5 BP 435 EP 447 PG 13 WC Immunology SC Immunology GA 683VL UT WOS:000284505500003 PM 21083525 ER PT J AU Henrickson, HC Crowther, JH Harrington, EF AF Henrickson, Heather C. Crowther, Janis H. Harrington, Ellen F. TI Ethnic Identity and Maladaptive Eating: Expectancies About Eating and Thinness in African American Women SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY LA English DT Article DE eating expectancies; ethnic identity; eating attitudes and behaviors; African American women ID COLLEGE-WOMEN; BULIMIC SYMPTOMATOLOGY; DIETING EXPECTANCIES; BODY-IMAGE; DISORDERS; SYMPTOMS; ATTITUDES; BLACK; SIMILARITIES; BEHAVIORS AB This research investigated cultural factors and expectancies about eating and thinness among 93 African American women. Participants completed the Multigroup Ethnic Identity Measure (MEIM), Eating Expectancy Inventory and Thinness and Restricting Expectancy Inventory (EEI, TREI), and Eating Attitudes Test (EAT). The MEIM assessed affective and developmental aspects of one's own cultural identity, along with attitudes toward other groups. Further, expectancies that eating manages negative affect and thinness leads to life improvement were examined using the EEI and TREI. As hypothesized, those with strong expectancies about eating and thinness showed a significant negative relationship between ethnic identity and maladaptive eating patterns, whereas those with strong expectancies regarding thinness showed a significant positive relationship between other group orientation and maladaptive eating patterns. The results suggest one's identification with their own culture versus another culture is important to developing maladaptive eating patterns, if they feel that eating and thinness play a role in their affect management and life improvement. These factors may help understand who is more vulnerable to the development of disordered eating patterns, and therefore direct treatment among African American women. C1 [Henrickson, Heather C.] Cleveland Clin, Dept Psychiat & Psychol, Cleveland, OH 44195 USA. [Crowther, Janis H.] Kent State Univ, Dept Psychol, Kent, OH USA. [Harrington, Ellen F.] VA Boston Healthcare Syst, Womens Hlth Serv Div, Boston, MA USA. RP Henrickson, HC (reprint author), Cleveland Clin, Dept Psychiat & Psychol, 9500 Euclid Ave,P57, Cleveland, OH 44195 USA. EM heathercarmela@hotmail.com NR 30 TC 23 Z9 23 U1 3 U2 9 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1099-9809 J9 CULT DIVERS ETHN MIN JI Cult. Divers. Ethn. Minor. Psychol. PD JAN PY 2010 VL 16 IS 1 BP 87 EP 93 DI 10.1037/a0013455 PG 7 WC Ethnic Studies; Psychology, Social SC Ethnic Studies; Psychology GA 555OP UT WOS:000274522100010 PM 20099968 ER PT J AU Ay, H AF Ay, Hakan TI Advances in the Diagnosis of Etiologic Subtypes of Ischemic Stroke SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Ischemic stroke; Etiology; Classification ID RISK-FACTORS; CLINICAL-TRIALS; CAUSATIVE CLASSIFICATION; INTEROBSERVER; RELIABILITY; REGISTRY; SYSTEM; RECURRENCE; AGREEMENT; STENOSIS AB A fundamental goal of etiologic stroke classification is to generate subgroups with discrete phenotypic, therapeutic, and prognostic features. Accurate stroke classification requires integration of multiple aspects of diagnostic stroke evaluation in a standardized manner. Diagnostic test findings can be simply organized into major etiologic groups to create a phenotypic subtype, or they can be reduced to a single causative subtype through a decision-making process. It is essential for a classification system to provide consistent results across different raters in different clinical settings. Comparability of subtype assignments is the key to valid communication of research results across the field. This article highlights important theoretical aspects of etiologic stroke classification and reviews major etiologic classification systems that have benefited from recent advances in etiologic stroke evaluation. C1 [Ay, Hakan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Ay, Hakan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Ay, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org FU National Institutes of Health [R01-NS059710] FX This work is supported by National Institutes of Health grant R01-NS059710. NR 30 TC 17 Z9 17 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JAN PY 2010 VL 10 IS 1 BP 14 EP 20 DI 10.1007/s11910-009-0074-x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 560YC UT WOS:000274940400001 PM 20425221 ER PT J AU Wen, PY Norden, AD Drappatz, J Quant, E AF Wen, Patrick Y. Norden, Andrew D. Drappatz, Jan Quant, Eudocia TI Response Assessment Challenges in Clinical Trials of Gliomas SO CURRENT ONCOLOGY REPORTS LA English DT Article DE High-grade glioma; Response criteria; Pseudoprogression ID RECURRENT MALIGNANT GLIOMA; BEVACIZUMAB PLUS IRINOTECAN; HIGH-GRADE GLIOMAS; MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; ANTI-ANGIOGENIC THERAPY; ADULT BRAIN-TUMORS; RADIATION-THERAPY; PHASE-II; CONCOMITANT RADIOCHEMOTHERAPY AB Accurate, reproducible criteria for determining tumor response and progression after therapy are critical for optimal patient care and effective evaluation of novel therapeutic agents. Currently, the most widely used criteria for determining treatment response in gliomas is based on two-dimensional tumor measurements using neuroimaging studies (Macdonald criteria). In recent years, the limitation of these criteria, which only address the contrast-enhancing component of the tumor, have become increasingly apparent. This review discusses challenges that have emerged in assessing response in patients with gliomas and approaches being introduced to address them. C1 [Wen, Patrick Y.; Norden, Andrew D.; Drappatz, Jan; Quant, Eudocia] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wen, Patrick Y.; Norden, Andrew D.; Drappatz, Jan; Quant, Eudocia] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org; anorden@partners.org; jdrappatz@partners.org; equant@partners.org NR 74 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JAN PY 2010 VL 12 IS 1 BP 68 EP 75 DI 10.1007/s11912-009-0078-3 PG 8 WC Oncology SC Oncology GA 723IA UT WOS:000287498900011 PM 20425610 ER PT J AU Rohatgi, R Flores, D AF Rohatgi, Rajeev Flores, Daniel TI Intratubular hydrodynamic forces influence tubulointerstitial fibrosis in the kidney SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE fibrosis; hydrodynamic forces; inflammation; signaling; tubule ID CORTICAL COLLECTING DUCT; RENAL EPITHELIAL-CELLS; THICK ASCENDING LIMB; FLUID SHEAR-STRESS; PROTEIN-1 GENE-EXPRESSION; PROXIMAL TUBULE CELLS; ENDOTHELIAL-CELLS; NITRIC-OXIDE; URETERAL OBSTRUCTION; PRIMARY CILIUM AB Purpose of review Renal epithelial cells respond to mechanical stimuli with immediate transduction events (e.g. activation of ion channels), intermediate biological responses (e.g. changes in gene expression), and long-term cellular adaptation (e.g. protein expression). Progressive renal disease is characterized by disturbed glomerular hydrodynamics that contributes to glomerulosclerosis but how intratubular biomechanical forces contribute to tubulointerstital inflammation and fibrosis is poorly understood. Recent findings In-vivo and in-vitro models of obstructive uropathy demonstrate that tubular stretch induces robust expression of transforming growth factor beta-1, activation of tubular apoptosis, and induction of nuclear factor-kappa B signaling, which contribute to the inflammatory and fibrotic milieu. Nonobstructive structural kidney diseases associated with nephron loss follow a course characterized by compensatory increases of single nephron glomerular filtration rate and tubular flow rate. Resulting increases in tubular fluid shear stress reduce tissue-plasminogen activator and urokinase enzymatic activity, which diminishes breakdown of extracellular matrix. In models of high dietary Na intake, which increases tubular flow, urinary transforming growth factor beta-1 concentrations and renal mitogen-activated protein kinase activity are increased. Summary In conclusion, intratubular biomechanical forces, stretch, and fluid shear stress generate changes in intracellular signaling and gene expression that contribute to the pathobiology of obstructive and nonobstructive kidney disease. C1 [Rohatgi, Rajeev; Flores, Daniel] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Rohatgi, Rajeev] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Rohatgi, Rajeev] James J Peters VA Med Ctr, Bronx, NY USA. RP Rohatgi, R (reprint author), Mt Sinai Sch Med, Dept Med, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Rajeev.Rohatgi@mssm.edu FU National Institutes of Health [K08 DK062172]; PKD Foundation; Norman S. Coplon Extramural FX The present work was supported by grants from the National Institutes of Health K08 DK062172 (RR), PKD Foundation Standard Grant (RR) and The Norman S. Coplon Extramural Grant Program (RR). We would like to thank Dr Lisa M. Satlin for the constructive criticism during the preparation of the manuscript. NR 55 TC 28 Z9 34 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2010 VL 19 IS 1 BP 65 EP 71 DI 10.1097/MNH.0b013e32833327f3 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 537LR UT WOS:000273114900011 PM 19851105 ER PT J AU Nagami, GT Kraut, JA AF Nagami, Glenn T. Kraut, Jeffrey A. TI Acid-base regulation of angiotensin receptors in the kidney SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE acidosis; ammonia excretion; nephron; type 1 Ang II receptor; urinary acidification ID THICK ASCENDING LIMB; CHRONIC METABOLIC-ACIDOSIS; MEDULLARY COLLECTING DUCT; II-BINDING-SITES; PROXIMAL BICARBONATE ABSORPTION; LATE DISTAL TUBULE; PERFUSED IN-VITRO; H+-K+-ATPASE; AMMONIA PRODUCTION; INTERCALATED CELLS AB Purpose of review Angiotensin II (Ang II) is a major systemic regulator of blood pressure, blood volume, and acid-base homeostasis. However, the effects of local Ang II signaling in the kidney are less well known. Here we review the impact of Ang II on acid-base transport in specific nephron segments and discuss the recently described role of acid loading in sensitizing the proximal tubule to Ang II. Recent findings Recent studies suggest that Ang II signaling is necessary for a normal kidney response to acid loads. Under acidic conditions, tubule cells upregulate type 1 Ang II receptors, amplifying the effects of Ang II. Site of action may also affect Ang II activity, as Ang II can produce divergent effects when acting on the luminal versus basolateral aspects of tubule cells. High luminal concentrations of Ang II and its precursors may facilitate coordinated acid-base transport and metabolic activity throughout the nephron. Summary Local Ang II signaling in the kidney directly modulates acid-base transport and metabolism, providing an additional mechanism by which the renin-angiotensin-aldosterone system regulates acid-base balance. The segment-specific and acid-stimulated responses of the tubule to Ang II are diverse and merit further exploration for their adaptive and potentially maladaptive roles. C1 [Nagami, Glenn T.; Kraut, Jeffrey A.] VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA 90073 USA. [Nagami, Glenn T.; Kraut, Jeffrey A.] VA Greater Los Angeles Healthcare Syst, Nephrol Res Lab, Dept Med, Los Angeles, CA 90073 USA. [Nagami, Glenn T.; Kraut, Jeffrey A.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. [Nagami, Glenn T.; Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Membrane Biol Lab, Los Angeles, CA 90095 USA. RP Nagami, GT (reprint author), VA Greater Los Angeles Healthcare Syst, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM glenn.nagami@va.gov FU Department of Veterans Affairs FX The present work was supported, in part, by medical research funds from the Department of Veterans Affairs. NR 68 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2010 VL 19 IS 1 BP 91 EP 97 DI 10.1097/MNH.0b013e32833289fd PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 537LR UT WOS:000273114900015 PM 19816174 ER PT J AU Shah, AS Chen, SH AF Shah, Ankoor S. Chen, Sherleen H. TI Cataract surgery and diabetes SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE bevacizumab; cataract surgery; diabetic retinopathy; macular edema; panretinal photocoagulation; triamcinolone ID INTRAVITREAL BEVACIZUMAB INJECTION; INTRAOCULAR-LENS IMPLANTATION; MACULAR EDEMA; RANDOMIZED-TRIAL; FOCAL/GRID PHOTOCOAGULATION; TRIAMCINOLONE ACETONIDE; VISUAL OUTCOMES; NATURAL-HISTORY; RETINOPATHY; PHACOEMULSIFICATION AB Purpose of review Recent studies have focused on interventions to minimize progression of retinal disease in diabetic patients undergoing cataract surgery. Here, we review the evidence for progression of diabetic retinal disease with cataract surgery and critically analyze the interventions proposed to minimize it. Recent findings Peri-operative intravitreal bevacizumab, sub-Tenon's triamcinolone, and panretinal photocoagulation (PRP) after cataract surgery (instead of before) have been examined as ways to improve cataract surgery results in diabetic patients. The bevacizumab and triamcinolone results are promising, but the inclusion criteria are variable, the sample sizes are small, and the follow-up is short. Postsurgery PRP shows improved cataract surgery results in diabetics with more severe retinopathy up to 1 year after surgery. Summary Recent studies do not support the generalized conclusion that phacoemusification surgery causes progression of retinopathy and macular edema in all diabetic patients. In certain populations of diabetic patients undergoing cataract surgery, peri-operative triamcinolone and bevacizumab may blunt the progression of diabetic macular edema and diabetic retinopathy. The optimal timing of PRP in relation to cataract surgery in patients with more severe retinopathy warrants further evaluation. C1 [Chen, Sherleen H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Comprehens Ophthalmol & Cataract Surger Serv, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. [Shah, Ankoor S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Eye Trauma Serv, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. RP Chen, SH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Comprehens Ophthalmol & Cataract Surger Serv, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM sherleen_chen@meei.harvard.edu NR 29 TC 16 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD JAN PY 2010 VL 21 IS 1 BP 4 EP 9 DI 10.1097/ICU.0b013e328333e9c1 PG 6 WC Ophthalmology SC Ophthalmology GA 537LT UT WOS:000273115100002 PM 19935423 ER PT J AU Naseri, A McLeod, SD AF Naseri, Ayman McLeod, Stephen D. TI Cataract surgery after refractive surgery SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE cataract; laser in-situ keratomileusis; postlaser in-situ keratomileusis; power calculation; refractive surgery ID INTRAOCULAR-LENS POWER; IN-SITU KERATOMILEUSIS; MYOPIC PHOTOREFRACTIVE KERATECTOMY; CORNEAL POWER; EYES; LASIK; FORMULA; ADJUSTMENT; KERATOMETRY; KERATOTOMY AB Purpose of review To review recent contributions addressing the challenge of intraocular lens (IOL) calculation in patients undergoing cataract extraction following corneal refractive surgery. Recent findings Although several articles have provided excellent summaries of IOL selection in patients wherein prerefractive surgery data are available, numerous authors have recently described approaches to attempt more accurate IOL power calculations for patients who present with no reliable clinical information regarding their refractive history. Additionally, results have been reported using the Scheimpflug camera system to measure corneal power in an attempt to resolve the most important potential source of error for IOL determination in these patients. Summary IOL selection in patients undergoing cataract surgery after corneal refractive surgery continues to be a challenging and complex issue despite numerous strategies and formulas described in the literature. Current focus seems to be directed toward approaches that do not require preoperative refractive surgery information. Due to the relative dearth of comparative clinical outcomes data, the optimal solution to this ongoing clinical problem has yet to be determined. Until such data are available, many cataract surgeons compare the results of multiple formulas to assist them in IOL selection for these patients. C1 [Naseri, Ayman; McLeod, Stephen D.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Naseri, Ayman; McLeod, Stephen D.] Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA USA. [Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA USA. RP McLeod, SD (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way, San Francisco, CA 94143 USA. EM McLeodS@vision.ucsf.edu FU Man May See, San Francisco, California, USA; Prevent Blindness, New York, New York, USA. FX The present study is supported in part by an unrestricted grant from That Man May See, San Francisco, California, USA and an unrestricted grant from Research to Prevent Blindness, New York, New York, USA. NR 39 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD JAN PY 2010 VL 21 IS 1 BP 35 EP 38 DI 10.1097/ICU.0b013e328333e9ab PG 4 WC Ophthalmology SC Ophthalmology GA 537LT UT WOS:000273115100007 PM 19996749 ER PT J AU Clarke, JT Werth, VP AF Clarke, Jennie T. Werth, Victoria P. TI Rheumatic manifestations of skin disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE cutaneous lupus erythematosus; dermatomyositis; rheumatoid arthritis; scleroderma ID CUTANEOUS LUPUS-ERYTHEMATOSUS; INTERSTITIAL GRANULOMATOUS DERMATITIS; SYSTEMIC-SCLEROSIS PATIENTS; SEVERITY INDEX; IMATINIB MESYLATE; ALPHA INHIBITORS; D-PENICILLAMINE; DOUBLE-BLIND; THERAPY; DERMATOMYOSITIS AB Purpose of review There is an increasing interest in improving the understanding of pathophysiology, outcome measures, and therapies of rheumatic skin disease. Increasingly, studies are using the skin as a primary endpoint for evaluating therapies. This will review the current state of the art for the most common rheumatic skin diseases. Recent findings A number of medications, including biologics such as tumor necrosis factor a and interferon, have been associated with onset of cutaneous lupus. The cutaneous lupus erythematosus area and severity index has been further validated and utilized in a number of studies. Smoking continues to be associated both with presence and refractoriness of cutaneous lupus erythematosus to therapy. There are several tools now available for evaluating the skin disease of dermatomyositis, but there is a need for new effective therapies. Measurement of skin disease in scleroderma continues to be a challenge, and there is a need for more effective therapies. Several studies show efficacy of intravenous iloprost for severe Raynaud's and skin ulcers, and of bosentan for digital ulcers. Summary The present review covers new outcome measures, treatments, and unusual manifestations of cutaneous lupus, dermatomyositis, scleroderma, and rheumatoid arthritis. There have been a number of new studies related to validation of disease activity measures, as well as their use in evaluation of new therapies for these conditions. Validated outcome measures are required to perform meaningful studies, and will facilitate organized epidemiologic, quality of life, and therapeutic studies. C1 [Clarke, Jennie T.] Penn State Hershey Med Ctr, Dept Dermatol, Hershey, PA USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, 3600 Spruce St,2 Rhoads Pavil, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIH [K24-AR 02207]; V.A. Merit Review Grant FX The present study was supported by NIH K24-AR 02207 and a V.A. Merit Review Grant. NR 74 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2010 VL 22 IS 1 BP 78 EP 84 DI 10.1097/BOR.0b013e328333b9e2 PG 7 WC Rheumatology SC Rheumatology GA 534JI UT WOS:000272892000013 PM 19851110 ER PT J AU Moriceau, G Ory, B Gobin, B Verrecchia, F Gouin, F Blanchard, F Redini, F Heymann, D AF Moriceau, G. Ory, B. Gobin, B. Verrecchia, F. Gouin, F. Blanchard, F. Redini, F. Heymann, D. TI Therapeutic Approach of Primary Bone Tumours by Bisphosphonates SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Bisphosphosphonates; primary bone tumors; sarcoma; giant cell tumor of bone ID GIANT-CELL TUMOR; HUMAN OSTEOSARCOMA CELLS; NITROGEN-CONTAINING BISPHOSPHONATE; GROWTH IN-VITRO; ZOLEDRONIC ACID; APPENDICULAR OSTEOSARCOMA; MURINE OSTEOSARCOMA; RAT OSTEOSARCOMA; 3RD-GENERATION BISPHOSPHONATE; MULTIPLE-MYELOMA AB Bone tumours can be dissociated in two main categories: i) primary bone tumours (benign or malignant) including mainly osteosarcoma and other sarcomas. ii) and giant cell tumour and bone metastases originate from others cancer (Breast, prostate, kidney cancer, etc). These tumours are able to destroy or/and induce a new calcified matrix. However, the first step of bone tumour development is associated with an induction of bone resorption and the establishment of a vicious cycle between the osteoclasts and the tumour growth. Indeed, bone resorption contributes to the pathogenesis of bone tumour by the release of cytokines (IL6, TNF alpha) which govern the bone tumour's development and which are trapped into the bone matrix. Bisphosphonates (BPs) are chemical compounds of P-C-P structure with a high affinity for bone hydroxyapatite crystals. Thus, they have been used as a carrier for radio nucleotides to develop novel approaches of bone imaging. BPs exert also indirect anti-tumour activities in vivo. Indeed, BPs directly interfere with the bone microenvironment and target osteoclasts, endothelial cells and immune cells (tumour-associated macrophages, gamma 9 delta 2 T cells). BPs induce tumour cell death in vitro and same activity is suspected in vivo. The present review summarizes the mechanisms of actions of BPs as well as their clinical interests in bone primary tumours. C1 [Moriceau, G.; Gobin, B.; Verrecchia, F.; Gouin, F.; Blanchard, F.; Redini, F.; Heymann, D.] INSERM UMR S 957, F-44035 Nantes 1, France. [Moriceau, G.; Gobin, B.; Verrecchia, F.; Gouin, F.; Blanchard, F.; Redini, F.; Heymann, D.] Univ Nantes, Nantes Atlantique Univ, Lab Physiopathol Resorpt Osseuse & Therapie Tumeu, EA3822, F-44035 Nantes, France. [Ory, B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ory, B.] Harvard Univ, Sch Med, Boston, MA USA. [Gouin, F.; Heymann, D.] CHU Nantes, Hotel Dieu, F-44035 Nantes 01, France. RP Heymann, D (reprint author), INSERM UMR S 957, 1 Rue Gaston Veil, F-44035 Nantes 1, France. EM dominique.heymann@univ-nantes.fr RI ory, benjamin/K-8231-2015; gouin, francois/L-1478-2015; REDINI, Francoise/K-7981-2015; Blanchard, Frederic/K-8018-2015 NR 105 TC 21 Z9 22 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2010 VL 16 IS 27 BP 2981 EP 2987 DI 10.2174/138161210793563554 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 685PS UT WOS:000284641200005 PM 20722622 ER PT J AU Al-Abbadi, MA Bloom, LI Fatheree, LA Haack, LA Minkowitz, G Wilbur, DC Austin, MR AF Al-Abbadi, Mousa A. Bloom, Leonard I. Fatheree, Lisa A. Haack, Lori A. Minkowitz, Gerald Wilbur, David C. Austin, Marshall R. TI Adequate reimbursement is crucial to support cost-effective rapid on-site cytopathology evaluations SO CYTOJOURNAL LA English DT Editorial Material C1 [Al-Abbadi, Mousa A.] E Teneesee State Univ, Dept Pathol, James H Quillen VA Med Ctr, Johnson City, TN USA. [Bloom, Leonard I.] Univ Tennessee, Ctr Hlth Sci, Dept Pathol, Memphis, TN 38163 USA. [Fatheree, Lisa A.] Coll Amer Pathologists, Northfield, IL USA. [Haack, Lori A.] Univ Wisconsin Hosp & Clin, Clin Labs, Madison, WI 53792 USA. [Minkowitz, Gerald] Minkowitz Pathol, Dept Pathol, Brooklyn, NY USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Austin, Marshall R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Al-Abbadi, MA (reprint author), E Teneesee State Univ, Dept Pathol, James H Quillen VA Med Ctr, Johnson City, TN USA. EM mousa.al-abbadi@va.gov; lbloom@uthsc.edu; lfather@cap.org; lhaack@uwhealth.org; gminkowitz@mac.com; dwilbur@partners.org; austrm@mail.magee.edu NR 12 TC 10 Z9 10 U1 0 U2 2 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-5963 J9 CYTOJOURNAL JI CytoJournal PY 2010 VL 7 AR 22 DI 10.4103/1742-6413.71740 PG 2 WC Pathology SC Pathology GA V23LY UT WOS:000208345500022 PM 21085619 ER PT J AU Dhillon, I Pitman, MB DeMay, RM Archuletta, P Shidham, VB AF Dhillon, Inderpreet Pitman, Martha B. DeMay, Richard M. Archuletta, Pamela Shidham, Vinod B. TI Compensation crisis related to the onsite adequacy evaluation during FNA procedures-Urgent proactive input from cytopathology community is critical to establish appropriate reimbursement for CPT code 88172 (or its new counterpart if introduced in the future) SO CYTOJOURNAL LA English DT Editorial Material DE CPT; FNA; Biospy; on site adequacy evaluation; 88172; Cytology; cytopathology AB The confusion centered around appropriate use of the CPT billing code 88172 is addressed in the commentary from the Economic and Government Affairs Committee of the American Society of Cytopathology (ASC) who have written a timely commentary in this issue of Cytojournal, "Adequate Reimbursement is Crucial to Support Cost-Effective Rapid Onsite Cytopathology Evaluations". Currently, lack of standardized use within and between pathology departments is stirring unhealthy practices of denying reimbursements for this critical and legitimate cytopathology service. This editorial discusses the important concerns raised in this commentary and recommends immediate corrective action. (See also Al-Abbadi MA, et al. Adequate reimbursement is crucial to support cost-effective rapid on-site cytopathology evaluations. CytoJournal 2010;7:22) C1 [Dhillon, Inderpreet; Archuletta, Pamela; Shidham, Vinod B.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Pitman, Martha B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [DeMay, Richard M.] Univ Chicago, Chicago, IL 60637 USA. RP Shidham, VB (reprint author), Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. EM idhillon@dmc.org; mpitman@partners.org; rdemay@uchicago.edu; parchule@med.wayne.edu; vshidham@med.wayne.edu NR 11 TC 7 Z9 7 U1 0 U2 1 PU MEDKNOW PUBLICATIONS PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0974-5963 J9 CYTOJOURNAL JI CytoJournal PY 2010 VL 7 AR 23 DI 10.4103/1742-6413.71741 PG 5 WC Pathology SC Pathology GA V23LY UT WOS:000208345500023 PM 21082041 ER PT S AU Russell, M Misra, M AF Russell, Melissa Misra, Madhusmita BE Jurimae, J Hills, AP Jurimae, T TI Influence of Ghrelin and Adipocytokines on Bone Mineral Density in Adolescent Female Athletes with Amenorrhea and Eumenorrheic Athletes SO CYTOKINES, GROWTH MEDIATORS AND PHYSICAL ACTIVITY IN CHILDREN DURING PUBERTY SE Medicine and Sport Science LA English DT Article; Book Chapter ID MULTIPLE SKELETAL SITES; MAPK SIGNALING PATHWAY; ANOREXIA-NERVOSA; LUTEINIZING-HORMONE; GROWTH-HORMONE; HEALTHY ADOLESCENTS; HUMAN OSTEOBLASTS; PLASMA-LEVELS; LEPTIN; ADIPONECTIN AB Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes. Copyright (C) 2010 S. Karger AG, Basel C1 [Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, 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 Jurimae, Jaak/G-9692-2016; Hills, Andrew/M-3199-2014 OI Hills, Andrew/0000-0002-7787-7201 FU NICHD NIH HHS [R01 HD060827, R01HD060827] NR 61 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0254-5020 BN 978-3-8055-9558-2 J9 MED SPORT SCI JI Med.Sport Sci. PY 2010 VL 55 BP 103 EP 113 PG 11 WC Sport Sciences SC Sport Sciences GA BRT51 UT WOS:000283627300008 PM 20956863 ER PT J AU Chen, T Yu, WH Izard, J Baranova, OV Lakshmanan, A Dewhirst, FE AF Chen, Tsute Yu, Wen-Han Izard, Jacques Baranova, Oxana V. Lakshmanan, Abirami Dewhirst, Floyd E. TI The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article AB The human oral microbiome is the most studied human microflora, but 53% of the species have not yet been validly named and 35% remain uncultivated. The uncultivated taxa are known primarily from 16S rRNA sequence information. Sequence information tied solely to obscure isolate or clone numbers, and usually lacking accurate phylogenetic placement, is a major impediment to working with human oral microbiome data. The goal of creating the Human Oral Microbiome Database (HOMD) is to provide the scientific community with a body site-specific comprehensive database for the more than 600 prokaryote species that are present in the human oral cavity based on a curated 16S rRNA gene-based provisional naming scheme. Currently, two primary types of information are provided in HOMD-taxonomic and genomic. Named oral species and taxa identified from 16S rRNA gene sequence analysis of oral isolates and cloning studies were placed into defined 16S rRNA phylotypes and each given unique Human Oral Taxon (HOT) number. The HOT interlinks phenotypic, phylogenetic, genomic, clinical and bibliographic information for each taxon. A BLAST search tool is provided to match user 16S rRNA gene sequences to a curated, full length, 16S rRNA gene reference data set. For genomic analysis, HOMD provides comprehensive set of analysis tools and maintains frequently updated annotations for all the human oral microbial genomes that have been sequenced and publicly released. Oral bacterial genome sequences, determined as part of the Human Microbiome Project, are being added to the HOMD as they become available. We provide HOMD as a conceptual model for the presentation of microbiome data for other human body sites. Database URL: http://www.homd.org C1 [Chen, Tsute; Yu, Wen-Han; Izard, Jacques; Baranova, Oxana V.; Lakshmanan, Abirami; Dewhirst, Floyd E.] Forsyth Inst, Boston, MA 02115 USA. [Chen, Tsute; Izard, Jacques; Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Chen, T (reprint author), Forsyth Inst, Boston, MA 02115 USA. EM tchen@forsyth.org OI Izard, Jacques/0000-0002-5904-5436 FU National Institute of Dental and Craniofacial Research [U01 DE016937, DE017106]; American Recovery and Reinvestment Act [DE016937] FX National Institute of Dental and Craniofacial Research (contract U01 DE016937 and grant DE017106, partial); American Recovery and Reinvestment Act of 2009 (DE016937, supplement). Funding for open access charge: U01 DE016937. NR 51 TC 161 Z9 164 U1 2 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2010 AR baq013 DI 10.1093/database/baq013 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V21ER UT WOS:000208191400016 ER PT J AU Jacobsen, JC Zhang, BH Block, SD Maciejewski, PK Prigerson, HG AF Jacobsen, Juliet C. Zhang, Baohui Block, Susan D. Maciejewski, Paul K. Prigerson, Holly G. TI DISTINGUISHING SYMPTOMS OF GRIEF AND DEPRESSION IN A COHORT OF ADVANCED CANCER PATIENTS SO DEATH STUDIES LA English DT Article ID BEREAVEMENT-RELATED DEPRESSION; COMPLICATED GRIEF; TRAUMATIC GRIEF; PSYCHIATRIC-DISORDERS; MEDICALLY ILL; DEMORALIZATION; DISTINCT; HEALTH; PSYCHOTHERAPY; VALIDATION AB Several studies have shown that the symptoms of grief are different from symptoms of depression among bereaved family members. This study is an attempt to replicate this finding among advanced cancer patients and examine clinical correlates of patient grief and depression. Analyses were conducted on data from interviews with 123 advanced cancer patients. Grief was measured using symptoms from the patient version of the Inventory of Complicated GriefRevised (ICG-R) and symptoms of depression were assessed using the Structured Clinical Interview for DSM-IV (SCID). A factor analysis revealed that symptoms of patient grief formed a coherent factor that was distinct from a depression factor. Patient grief ocasenesso (defined as being in the top 10% of the distribution of grief scores), but not major depressive disorder, was uniquely associated with the wish to die (odds ratio [OR] 10.13 [0.1.08-95.06]). Both depression and grief were significantly associated with mental health service use (OR 16.07 [1.68, 153.77] vs. 4.82; CI=[1.09, 21.41]) and negative religious coping (OR 1.36 [1.06, 1.73] vs. 1.25 [1.05, 1.49]); neither was associated with terminal illness acknowledgement. C1 [Jacobsen, Juliet C.; Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Jacobsen, Juliet C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Zhang, Baohui; Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Jacobsen, JC (reprint author), 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM JJacobsen@partners.org FU NCI NIH HHS [R01 CA106370-04, R01 CA106370, CA106370]; NIMH NIH HHS [MH56529] NR 50 TC 24 Z9 24 U1 1 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2010 VL 34 IS 3 BP 257 EP 273 AR PII 919417037 DI 10.1080/07481180903559303 PG 17 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 561LI UT WOS:000274978300003 PM 20953316 ER PT J AU Kleespies, PM AF Kleespies, Phillip M. TI PSYCHOLOGICAL AND ETHICAL CONSIDERATIONS CONCERNING THE DEBREATHER AND ASSISTED SUICIDE: A COMMENTARY ON OGDEN SO DEATH STUDIES LA English DT Article ID ACCESS; CARE AB This article offers a commentary on the report by Russel Ogden (2010/this issue) on the use of the "debreather'' for suicide assistance by the NuTech (or New Technologies for Self-Deliverance) program. The emergence of NuTech is set within its historical and political context. Nu Tech is criticized for its anarchic and extreme advocacy of self-determination to the neglect of other psychological and ethical considerations (e. g., the individual's emotional state, the mutability of his or her quality of life, and his or her decision-making capacity). Some of the risks of covert, unregulated, assisted death are noted as is a potential shift in healthcare that might diminish interest in the undignified NuTech methods of dying. C1 [Kleespies, Phillip M.] Boston Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, 116B,150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM phillip.kleespies@aol.com NR 15 TC 2 Z9 2 U1 0 U2 0 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PY 2010 VL 34 IS 4 BP 318 EP 324 DI 10.1080/07481181003613859 PG 7 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 579ZQ UT WOS:000276416400002 PM 24479189 ER PT J AU Lin, F Wharton, W Dowling, NM Ries, ML Johnson, SC Carlsson, CM Asthana, S Gleason, CE AF Lin, Feng Wharton, Whitney Dowling, N. Maritza Ries, Michele L. Johnson, Sterling C. Carlsson, Cynthia M. Asthana, Sanjay Gleason, Carey E. TI Awareness of Memory Abilities in Community-Dwelling Older Adults with Suspected Dementia and Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Anosognosia; Dementia; Mild cognitive impairment; Memory; Neuropsychology; Community-dwelling ID ALZHEIMERS-DISEASE; SELF-APPRAISAL; ANOSOGNOSIA; DEFICITS; QUESTIONNAIRE; UNAWARENESS; CONSORTIUM; COMPLAINT; ESTABLISH; REGISTRY AB Aims: To examine awareness of memory abilities by groups (healthy control, suspected dementia/mild cognitive impairment, MCI, and diagnosed dementia/MCI), and to describe group differences in the relationship between awareness and cognitive performance in a community sample. Methods: In a cross-sectional design, 183 subjects were evaluated in a community setting and categorized into 3 groups based on their cognitive performance and reported medical history. Awareness of memory abilities was quantified using a published anosognosia ratio (AR) comparing the estimated to the objective memory performance by subjects. Each group was further categorized into 'overestimators', 'accurate estimators', and 'underestimators' based on their AR scores. Results: The suspected and diagnosed dementia/MCI groups had significantly higher AR scores than the controls. The suspected group also had a significantly larger proportion (96.2%) of overestimators than the diagnosed (73.3%) and control groups (26.1%). Impaired awareness in overestimators of the suspected and diagnosed groups was correlated with deficits in executive function, language or global cognition. Conclusion: Impaired awareness of memory abilities was prevalent in community-dwelling older adults with suspected and diagnosed dementia or MCI. Those with suspected dementia or MCI were more likely to overestimate their memory abilities than their diagnosed counterparts, suggesting that limited awareness of deficits may hinder utilization of dementia diagnostic services. Copyright (C) 2010 S. Karger AG, Basel C1 [Lin, Feng] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Wharton, Whitney; Ries, Michele L.; Johnson, Sterling C.; Carlsson, Cynthia M.; Asthana, Sanjay; Gleason, Carey E.] Univ Wisconsin, Dept Med, Sect Geriatr & Gerontol, Sch Med & Publ Hlth, Madison, WI USA. [Dowling, N. Maritza] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. [Wharton, Whitney; Dowling, N. Maritza; Ries, Michele L.; Johnson, Sterling C.; Carlsson, Cynthia M.; Asthana, Sanjay; Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Lin, Feng; Johnson, Sterling C.; Carlsson, Cynthia M.; Asthana, Sanjay; Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Gleason, CE (reprint author), Madison VA GRECC D4211 2500 Overlook Terrace, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU NIH-National Institute on Aging [K23 AG024302] FX This research was supported by NIH-National Institute on Aging grants K23 AG024302 (PI CEG) and P50 AG033514, and by the Extendicare Foundation Inc. The Biostatistics and Data Management Core of the Wisconsin ADRC provided statistical consultation and assistance with analyses. NR 41 TC 9 Z9 9 U1 2 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 30 IS 1 BP 83 EP 92 DI 10.1159/000318752 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 638YP UT WOS:000280936900014 PM 20714155 ER PT J AU Gold, M Alderton, C Zvartau-Hind, M Egginton, S Saunders, AM Irizarry, M Craft, S Landreth, G Linnamagi, U Sawchak, S AF Gold, Michael Alderton, Claire Zvartau-Hind, Marina Egginton, Sally Saunders, Ann M. Irizarry, Michael Craft, Suzanne Landreth, Gary Linnamaegi, Uella Sawchak, Sharon TI Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer's Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Rosiglitazone; extended release; Monotherapy; Alzheimer's disease; Peroxisome proliferator-activated receptor-gamma; Cognition; Apolipoprotein E allele epsilon 4; Health outcomes; Donepezil ID CLINICAL-TRIALS; INSULIN-RESISTANCE; VASCULAR DEMENTIA; COGNITIVE IMPAIRMENT; DIABETES-MELLITUS; APOLIPOPROTEIN-E; MEMORY; RIVASTIGMINE; EFFICACY; DECLINE AB Background/Aims: A phase II study of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E (APOE)-epsilon 4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR. Methods: This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (epsilon 4-positive, epsilon 4-negative), subjects were randomized (2: 2: 2: 1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+). Results: At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in A POE-epsilon 4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%). Conclusion: No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-epsilon 4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology. Copyright (C) 2010 S. Karger AG, Basel C1 [Gold, Michael; Irizarry, Michael; Sawchak, Sharon] GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Res Triangle Pk, NC 27709 USA. [Alderton, Claire; Zvartau-Hind, Marina] GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Stockley Pk, England. [Egginton, Sally] GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Harlow, Essex, England. [Saunders, Ann M.] Duke Univ, Med Ctr, Div Neurol, Deane Drug Discovery Inst, Durham, NC 27710 USA. [Craft, Suzanne] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Landreth, Gary] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. [Linnamaegi, Uella] Univ Tartu, Dept Neurol & Neurosurg, EE-50090 Tartu, Estonia. RP Gold, M (reprint author), GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Res Triangle Pk, NC 27709 USA. EM michael.2.gold@gsk.com FU GlaxoSmithKline [NCT00428090, NCT00550420] FX Funding for these studies was provided by GlaxoSmithKline (NCT00428090 and NCT00550420). The authors wish to acknowledge the following: the participating subjects and their caregivers and the REFLECT-1 and REFLECT-5 study investigators; David Hosford, Marc Risner, CarlChiang, Conn Harrington, Carly Donovan and Barbara Jeter of GlaxoSmithKline for their contributions during the study and the study analysis, and Mary Richardson of GlaxoSmithKline for critical review during the development of the manuscript. Editorial support in the form of editorial suggestions on draft versions of this paper, assembling tables and figures, collating author comments and copyediting was provided by Ann Garvey, PhD, at UBC Evidence Solutions and was funded by GlaxoSmithKline. NR 61 TC 131 Z9 135 U1 3 U2 18 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 30 IS 2 BP 131 EP 146 DI 10.1159/000318845 PG 16 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 651YR UT WOS:000281965700005 PM 20733306 ER PT J AU Teng, E Becker, BW Woo, E Cummings, JL Lu, PH AF Teng, Edmond Becker, Brian W. Woo, Ellen Cummings, Jeffrey L. Lu, Po H. TI Subtle Deficits in Instrumental Activities of Daily Living in Subtypes of Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Mild cognitive impairment; Functional impairment; Activities of daily living; Memory performance; Executive function ID VASCULAR RISK-FACTORS; DATA SET UDS; ALZHEIMERS-DISEASE; OLDER-ADULTS; CLINICAL SUBTYPES; EVERYDAY FUNCTION; DEMENTIA; MCI; MEMORY; INDIVIDUALS AB Background/Aims: Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices. Methods: We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ). Results: IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function. Conclusions: IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk. Copyright (C) 2010 S. Karger AG, Basel C1 [Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Neurobehav Unit, Los Angeles, CA 90095 USA. [Teng, Edmond; Becker, Brian W.] Univ Calif Los Angeles, David Geffen Sch Med, Geriatr Res Educ & Clin Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Teng, Edmond; Woo, Ellen; Cummings, Jeffrey L.; Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit 116AF, Bldg 500,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging [U01 AG016976, P50 AG16570]; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation FX This research was supported by grants from the National Institute on Aging (U01 AG016976 to the National Alzheimer's Coordinating Center and P50 AG16570 to the Mary S. Easton Center for Alzheimer's Disease Research at UCLA), the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation. We would like to thank Nathaniel Mercaldo for his assistance with data management. NR 55 TC 39 Z9 41 U1 2 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 30 IS 3 BP 189 EP 197 DI 10.1159/000313540 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 651YS UT WOS:000281965800001 PM 20798539 ER PT J AU Devier, DJ Villemarette-Pittman, N Brown, P Pelton, G Stern, Y Sano, M Devanand, DP AF Devier, Deidre J. Villemarette-Pittman, Nicole Brown, Patrick Pelton, Gregory Stern, Yaakov Sano, Mary Devanand, D. P. TI Predictive Utility of Type and Duration of Symptoms at Initial Presentation in Patients with Mild Cognitive Impairment SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Age at onset; Alzheimer's disease; Behavioral symptoms; Mild cognitive impairment; Neuropsychological assessment ID ALZHEIMERS-DISEASE; MEMORY COMPLAINTS; OBJECTIVE MEMORY; DEMENTIA; ONSET; CONVERSION; DIAGNOSIS; AGE; COMMUNITY; ANOSOGNOSIA AB Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer's disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e. g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than non-converters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD. Copyright (C) 2010 S. Karger AG, Basel C1 [Devier, Deidre J.; Villemarette-Pittman, Nicole] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, New Orleans, LA 70112 USA. [Brown, Patrick; Pelton, Gregory; Stern, Yaakov; Devanand, D. P.] Columbia Univ Coll Phys & Surg, Div Geriatr Psychiat, New York, NY 10032 USA. [Brown, Patrick; Pelton, Gregory; Stern, Yaakov; Devanand, D. P.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Brown, Patrick; Pelton, Gregory; Stern, Yaakov; Devanand, D. P.] Taub Inst Res Alzheimers Dis & Aging Brain, Sergievsky Ctr, Dept Neurol, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Sano, Mary] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA. [Sano, Mary] James J Peters VA Med Ctr, Dept Neurol, Bronx, NY USA. RP Devier, DJ (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, 1542 Tulane Ave,Floor 7, New Orleans, LA 70112 USA. EM ddevie@lsuhsc.edu FU National Institute on Aging [R01AG17761] FX This study was supported in part by grant No. R01AG17761 from the National Institute on Aging. NR 40 TC 9 Z9 11 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 EI 1421-9824 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 30 IS 3 BP 238 EP 244 DI 10.1159/000320137 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 651YS UT WOS:000281965800007 PM 20847554 ER PT J AU Chuang, YF Hayden, KM Norton, MC Tschanz, J Breitner, JCS Welsh-Bohmer, KA Zandi, PP AF Chuang, Yi-Fang Hayden, Kathleen M. Norton, Maria C. Tschanz, Joann Breitner, John C. S. Welsh-Bohmer, Kathleen A. Zandi, Peter P. CA Cache County Investigators TI Association between APOE epsilon 4 Allele and Vascular Dementia: The Cache County Study SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE APOE; Vascular dementia ID APOLIPOPROTEIN-E POLYMORPHISM; ALZHEIMERS-DISEASE; POPULATION; CHOLESTEROL; FREQUENCY; QUESTIONNAIRE; RELIABILITY; PREVALENCE; GENOTYPE; VALIDITY AB Background: The APOE epsilon 4 allele is an established risk factor for Alzheimer's disease, but reports of its association with vascular dementia (VaD) have been inconsistent. We examined the relationship between APOE epsilon 4 allele and the risk of incident VaD in a large, population-based cohort of elderly adults with up to 10 years of follow-up between 1995 and 2005. Methods: A total of 3,424 elderly men and women free of dementia were genotyped at the baseline assessment. Incident VaD was identified through standardized procedures administered at 3 follow-up assessments. Cox proportional hazards models were used to evaluate the risk of VaD associated with APOE epsilon 4. Results: The adjusted hazard ratio was 1.6 for the participants with 1 APOE epsilon 4 allele (95% CI: 0.9-2.7; p = 0.083) and 4.4 for those with 2 APOE epsilon 4 alleles ( 95% CI: 1.6-12.5; p = 0.005). The increased risk did not appear to be mediated by vascular risk factors. Conclusions: The APOE epsilon 4 allele is associated with an increased risk of VaD in a dose-dependent fashion and accounts for almost 20% of VaD in the population. Copyright (C) 2010 S. Karger AG, Basel C1 [Chuang, Yi-Fang; Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Durham, NC USA. [Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Seattle, WA 98195 USA. [Norton, Maria C.; Tschanz, Joann] Utah State Univ, Logan, UT 84322 USA. RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU National Institute of Aging [R01 AG11380] FX We would like to thank all of the study participants for their contributions to this work. We are grateful to the neurogenetics laboratory of the Bryan Alzheimer's Disease Research Center at Duke University for APOE genotyping. We would also like to thank study coordinators Nancy Sassano ( Utah State University) and Michelle McCart ( Duke University); and Cara Brewer, Tony Calvert, Tiffany Newman, Roxane Pfister, Sarah Schwartz, and Joslin Werstak, of Utah State University for their expert technical assistance in data collection and entry. The work on this study was support by a grant from the National Institute of Aging (R01 AG11380) NR 40 TC 27 Z9 28 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 29 IS 3 BP 248 EP 253 DI 10.1159/000285166 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 584WA UT WOS:000276783100008 PM 20375505 ER PT J AU Freeman, MP Davis, MF AF Freeman, Marlene P. Davis, Melinda F. TI SUPPORTIVE PSYCHOTHERAPY FOR PERINATAL DEPRESSION: PRELIMINARY DATA FOR ADHERENCE AND RESPONSE SO DEPRESSION AND ANXIETY LA English DT Article DE pregnancy; postpartum; supportive; psychotherapy; depression ID SEROTONIN-REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; PERSISTENT PULMONARY-HYPERTENSION; POSTPARTUM DEPRESSION; INTERPERSONAL PSYCHOTHERAPY; POSTNATAL DEPRESSION; MAJOR DEPRESSION; PREGNANT-WOMEN; ANTIDEPRESSANT TREATMENT; PRIMARY-CARE AB Background: We sought to determine patient factors associated with adherence and response to a manualized supportive psychotherapy designed for pregnant and postpartum women with major depressive disorder (MDD). Methods: Supportive psychotherapy was provided to all participants in parallel to a placebo-controlled trial of omega-3 fatty acids. The Supportive psychotherapy was a six-session, manualized intervention. Clinicians recorded participation and adherence. Symptom rating scales were completed at baseline and every 2 weeks and included the Hamilton Depression Rating Scale (HAM-D) as the primary outcome. N = 59 participants were enrolled. Subjects were referred by obstetrical and pediatric health-care providers. Descriptive statistics and general linear models were used to assess the study outcomes. Results: The mean number of completed sessions was 4.4 out of a full course of 6. There were no significant differences found between omega-3 fatty acid and placebo groups in the parallel assessments. We found significantly lower adherence to the psychotherapy sessions for women who were not married, were unemployed, and those with higher scores on the HAM-D at baseline. Completion of a greater number of psychotherapy sessions, lower baseline depression scores, and postpartum Status (compared with pregnant status) were associated with lower final HAM-D scores. Overall, the response rate was 52.9% (>= 50% decrease on HAM-D scores), and the remission rate (final score<8) was 31.4%. Conclusions: Study limitations included small sample size, and possible nonspecific and placebo effects. Adherence appears important in response to Supportive psychotherapy in women with perinatal MDD, and future efforts to improve adherence in perinatal women with MDD are warranted. Depression and Anxiety 2 7.39-45, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Freeman, Marlene P.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. [Davis, Melinda F.] Univ Arizona, Dept Psychol, Coll Social & Behav Sci, Tucson, AZ 85721 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, 185 Cambridge St,2nd Floor, Boston, MA 02114 USA. EM mfreeman@partners.org OI Davis, Melinda/0000-0003-4413-2112 FU NIMH NIH HHS [K23 MH66265] NR 53 TC 12 Z9 14 U1 3 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2010 VL 27 IS 1 BP 39 EP 45 DI 10.1002/da.20596 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 542CF UT WOS:000273468300007 PM 19691033 ER PT J AU Bendlin, BB Fitzgerald, ME Ries, ML Xu, GF Kastman, EK Thiel, BW Rowley, HA Lazar, M Alexander, AL Johnson, SC AF Bendlin, Barbara B. Fitzgerald, Michele E. Ries, Michele L. Xu, Guofan Kastman, Erik K. Thiel, Brent W. Rowley, Howard A. Lazar, Mariana Alexander, Andrew L. Johnson, Sterling C. TI White Matter in Aging and Cognition: A Cross-Sectional Study of Microstructure in Adults Aged Eighteen to Eighty-Three SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID ANTERIOR THALAMIC NUCLEI; HUMAN CEREBRAL-CORTEX; DIFFUSION-TENSOR MRI; OLDER-ADULTS; ALZHEIMERS-DISEASE; WORKING-MEMORY; TEMPORAL-LOBE; NEUROPSYCHOLOGICAL PERFORMANCE; FRACTIONAL ANISOTROPY; LONGITUDINAL CHANGES AB Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood. White matter microstructure can be measured with diffusion tensor imaging (DTI), but whether DTI can provide unique information on brain aging that is not explained by white matter volume is not known. In the current study, the relationship between white matter microstructure, age, and neuropsychological function was assessed using DTI in a statistical framework that employed white matter volume as a voxel-wise covariate in a sample of 120 healthy adults across a broad age range (18-83). Memory function and executive function were modestly correlated with the DTI measures while processing speed showed the greatest extent of correlation. The results suggest that age-related white matter alterations underlie age-related declines in cognitive function. Mean diffusivity and fractional anisotropy in several white matter brain regions exhibited a nonlinear relationship with age, while white matter volume showed a primarily linear relationship with age. The complex relationships between cognition, white matter microstructure, and white matter volume still require further investigation. C1 [Bendlin, Barbara B.; Fitzgerald, Michele E.; Ries, Michele L.; Xu, Guofan; Kastman, Erik K.; Thiel, Brent W.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Bendlin, Barbara B.; Fitzgerald, Michele E.; Ries, Michele L.; Xu, Guofan; Kastman, Erik K.; Thiel, Brent W.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Rowley, Howard A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI USA. [Lazar, Mariana] NYU, Sch Med, Dept Radiol, New York, NY USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Univ Wisconsin, Dept Psychiat, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Alexander, Andrew L.] Waisman Lab Brain Imaging & Behav, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem VA Hosp, GRECC, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu RI Kastman, Erik/N-6645-2016; OI Kastman, Erik/0000-0001-7221-9042; Lazar, Mariana/0000-0001-9285-8124; Bendlin, Barbara/0000-0002-0580-9875; Johnson, Sterling/0000-0002-8501-545X FU Department of Veterans Affairs [R01 MH 65723, ROI AG021155-01] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs, R01 MH 65723, ROI AG021155-01 (SCJ), and by the facilities and resources at the William S. Middleton Memorial Veterans Hospital; GRECC manuscript number 2009-15. NR 82 TC 58 Z9 62 U1 2 U2 9 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2010 VL 35 IS 3 BP 257 EP 277 AR PII 921878108 DI 10.1080/87565641003696775 PG 21 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 594EX UT WOS:000277518100003 PM 20446132 ER PT J AU Chen, YI Choi, JK Xu, HB Ren, JQ Andersen, SL Jenkins, BG AF Chen, Y. Iris Choi, Ji-Kyung Xu, Haibo Ren, Jiaqian Andersen, Susan L. Jenkins, Bruce G. TI Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Ontogeny; Dopamine; D1 receptor; D2 receptor; Functional MRI; Pharmacological MRI ID INDUCED LOCOMOTOR-ACTIVITY; HUMAN CEREBRAL-CORTEX; RAT-BRAIN; MESSENGER-RNA; POSTNATAL-DEVELOPMENT; PREFRONTAL CORTEX; D-2 RECEPTORS; FEMALE RATS; ADULT RATS; DEVELOPMENTAL DIFFERENCES AB Characterization of the ontogeny of the cerebral dopaminergic system is crucial for gaining a greater understanding of normal brain development and its alterations in response to drugs of abuse or conditions such as attention-deficit hyperactivity disorder. Pharmacological MRI (phMRI) was used to determine the response to dopamine transporter (DAT) blockers cocaine and methylphenidate (MPH), the dopamine releaser D-amphetamine (AMPH), the selective D1 agonist dihydrexidine, and the D2/D3 agonist quinpirole in young (<30 days old) and adult (>60 days old) rats. In adult rats, cocaine (0.5 mg/kg i.v.) or MPH (2 mg/kg) induced primarily positive cerebral blood volume (rCBV) changes in the dopaminergic circuitry, but negative rCBV changes in the young animals. Microdialysis measurements in the striatum showed that young rats have a smaller increase in extracellular dopamine in response to cocaine than adults. The young rats showed little rCBV response to the selective D1 agonist dihydrexidine in contrast to robust rCBV increases observed in the adults, whereas there was a similar negative rCBV response in the young and adult rats to the D2 agonist quinpirole. We also performed a meta-analysis of literature data on the development of D1 and D2 receptors and the DAT. These data suggest a predominance of D2-like over D1-like function between 20 and 30 days of age. These combined results suggested that the dopamine D1 receptor is functionally inhibited at young age. Copyright (C) 2010 S. Karger AG, Basel C1 [Chen, Y. Iris; Choi, Ji-Kyung; Ren, Jiaqian; Jenkins, Bruce G.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Andersen, Susan L.] McLean Hosp, Dev Psychopharmacol Lab, Belmont, MA 02178 USA. [Xu, Haibo] Union Hosp, Wuhan, Peoples R China. RP Chen, YI (reprint author), Martinos Ctr Biomed Imaging, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu; bgj@nmr.mgh.harvard.edu FU National Institute of Health (National Centre for Complementary and Alternative Medicine) [PO1 AT002048, 1R21AT004455-01A2]; National Institute on Drug Abuse [5R01 DA16187-05] FX Dr. Young Kim synthesized and provided the contrast agent MION. John Moore conducted the surgical preparation for MRI studies. This study was supported by the National Institute of Health (National Centre for Complementary and Alternative Medicine) PO1 AT002048, 1R21AT004455-01A2, and National Institute on Drug Abuse 5R01 DA16187-05 NR 87 TC 33 Z9 37 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2010 VL 32 IS 2 BP 125 EP 138 DI 10.1159/000286215 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 621OY UT WOS:000279591600004 PM 20523024 ER PT J AU Cheng, S Massaro, JM Fox, CS Larson, MG Keyes, MJ McCabe, EL Robins, SJ O'Donnell, CJ Hoffmann, U Jacques, PF Booth, SL Vasan, RS Wolf, M Wang, TJ AF Cheng, Susan Massaro, Joseph M. Fox, Caroline S. Larson, Martin G. Keyes, Michelle J. McCabe, Elizabeth L. Robins, Sander J. O'Donnell, Christopher J. Hoffmann, Udo Jacques, Paul F. Booth, Sarah L. Vasan, Ramachandran S. Wolf, Myles Wang, Thomas J. TI Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study SO DIABETES LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; METABOLIC SYNDROME; INSULIN SENSITIVITY; BODY-FAT; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; HYPOVITAMINOSIS-D; TISSUE VOLUMES AB OBJECTIVE-Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS-We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS-In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (-1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (-2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m(2)). The prevalence of Vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS-Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study. Diabetes 59:242-248, 2010 C1 [Cheng, Susan; Massaro, Joseph M.; Fox, Caroline S.; Larson, Martin G.; Keyes, Michelle J.; McCabe, Elizabeth L.; Robins, Sander J.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan; McCabe, Elizabeth L.; O'Donnell, Christopher J.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Cheng, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Sch Med, Boston, MA 02215 USA. [Massaro, Joseph M.; Larson, Martin G.; Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Dept Med,Med Sch, Boston, MA 02115 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jacques, Paul F.; Booth, Sarah L.] Tufts Univ, Human Nutr Res Ctr Aging, Nutrit Epidemiol Program, Jean Mayer USDA, Boston, MA 02111 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA 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 Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195, R01-DK-80739]; American Heart Association FX This work was supported in part by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) contract N01-HC-25195, R01-DK-80739, and a grant from the American Heart Association.; M.W. has received honoraria for educational presentations from Abbott Laboratories. T.J.W. has served on the scientific advisory board for DiaSorin. No other potential conflicts of interest relevant to this article were reported.; We thank Karol Pencina, MS, for assistance with statistical analyses. NR 51 TC 205 Z9 215 U1 3 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2010 VL 59 IS 1 BP 242 EP 248 DI 10.2337/db09-1011 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 542DS UT WOS:000273472500031 PM 19833894 ER PT J AU Kahn, SE Haffner, SM Viberti, G Herman, WH Lachin, JM Kravitz, BG Yu, DH Paul, G Holman, RR Zinman, B AF Kahn, Steven E. Haffner, Steven M. Viberti, Giancarlo Herman, William H. Lachin, John M. Kravitz, Barbara G. Yu, Dahong Paul, Gitanjali Holman, Rury R. Zinman, Bernard CA Diabet Outcome Progression Trial A TI Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain: Observations from A Diabetes Outcome Progression Trial (ADOPT) SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE ATHEROSCLEROSIS; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; GAMMA-AGONIST; PIOGLITAZONE; INFLAMMATION; RISK AB OBJECTIVE - C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown. RESEARCH DESIGN AND METHODS - In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years. RESULTS - Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. p reduction was greater in the rosiglitazone group by -47.6% relative to glyburide and by -30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 g with rosiglitazone, 1.8 kg with glyburide, and -2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin(r = 0.20) groups but not in the rosiglitazone(r = -0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any Of the three treatment groups. CONCLUSIONS - Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone. C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Viberti, Giancarlo] Kings Coll London, Sch Med, London WC2R 2LS, England. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Kravitz, Barbara G.; Yu, Dahong; Paul, Gitanjali] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Holman, Rury R.] Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Zinman, Bernard] Univ Toronto, Toronto, ON M5S 1A1, Canada. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU GlaxoSmithKline (GSK); GSK FX ADOPT was overseen by a steering committee comprised of Steven Kahn, Giancarlo Viberti (cochairs), Steven Haffner, William Herman, Rury Holman, Nigel Jones, John Lachin, Colleen O'Neill, and Bernard Zinman, The study was supported by funds from GlaxoSmithKline (GSK). S.E.K., S.M.H., G.V., W.H.H., J.M.L., R.R.H,, and B.Z. received honoraria, consulting fees, and/or grant/research support from GSK. B.G.K., DY, and G.P. are employees of GSK. No other potential conflicts of interest relevant to this article were reported. NR 36 TC 22 Z9 22 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2010 VL 33 IS 1 BP 177 EP 183 DI 10.2337/dc09-1661 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544AA UT WOS:000273622200036 PM 19808911 ER PT J AU Funnell, MM Brown, TL Childs, BP Haas, LB Hosey, GM Jensen, B Maryniuk, M Peyrot, M Piette, JD Reader, D Siminerio, LM Weinger, K Weiss, MA AF Funnell, Martha M. Brown, Tammy L. Childs, Belinda P. Haas, Linda B. Hosey, Gwen M. Jensen, Brian Maryniuk, Melinda Peyrot, Mark Piette, John D. Reader, Diane Siminerio, Linda M. Weinger, Katie Weiss, Michael A. TI National Standards for Diabetes Self-Management Education SO DIABETES CARE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; IMPROVE GLYCEMIC CONTROL; PRIMARY-CARE PATIENTS; HEALTH-CARE; COMPLICATIONS TRIAL; PATIENT EDUCATION; AFRICAN-AMERICAN; COMMUNITY-HEALTH; CHRONIC ILLNESS C1 [Funnell, Martha M.] Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Brown, Tammy L.] Indian Hlth Serv, Albuquerque, NM USA. [Haas, Linda B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Childs, Belinda P.] MidAmer Diabet Associates, Wichita, KS USA. [Hosey, Gwen M.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Jensen, Brian] Lakeshore Apothacare, Two Rivers, WI USA. [Maryniuk, Melinda; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Piette, John D.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Peyrot, Mark] Loyola Coll, Baltimore, MD 21210 USA. [Piette, John D.] Univ Michigan, Dept Internal Med, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. [Reader, Diane] Int Diabet Ctr, Minneapolis, MN USA. [Siminerio, Linda M.] Univ Pittsburgh, Med Ctr, Inst Diabet, Pittsburgh, PA USA. [Weiss, Michael A.] Patient Centered Solut, Pittsburgh, PA USA. RP Funnell, MM (reprint author), Univ Michigan, Dept Med Educ, Ctr Diabet Res & Training, Ann Arbor, MI 48109 USA. EM mfunnell@umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [N1H5P60 DK20572, 1 R18 OK062323] FX Work on this article was supported in part by grant nos. N1H5P60 DK20572 and 1 R18 OK062323 from the National Institute of Diabetes and Digestive and Kidney Diseases Of the National Institutes of Health NR 164 TC 61 Z9 64 U1 4 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2010 VL 33 SU 1 BP S89 EP S96 DI 10.2337/dc10-S089 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544AC UT WOS:000273622400007 PM 20042780 ER PT S AU Kahn, CR Suzuki, R AF Kahn, C. Ronald Suzuki, Ryo BE Craft, S Christen, Y TI Insulin Action in the Brain and the Pathogenesis of Alzheimer's Disease SO DIABETES, INSULIN AND ALZHEIMER'S DISEASE SE Research and Perspectives in Alzheimers Disease LA English DT Proceedings Paper CT 24th Symposium on Medicine and Research of Alzhemers Disease CY APR 06, 2009 CL Fondat IPSEN, Paris, FRANCE HO Fondat IPSEN ID FACTOR-I-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; AMYLOID BETA-PROTEIN; DEGRADING ENZYME; TYROSINE PHOSPHORYLATION; APOLIPOPROTEIN-E; SIGNALING PATHWAY; DIABETIC-RATS; A-BETA AB Over 24 million people in the U.S. have diabetes mellitus, and about 90% of these have the type 2 form of the disease. In addition, an estimated 40-60 million people have pre-type 2 diabetes, impaired glucose tolerance or the cluster of abnormalities referred to variably as the metabolic syndrome or syndrome X (Reaven 1988). In all of these disorders, a central component of the pathophysiology is insulin resistance. Insulin resistance is also closely linked to other common health problems, including obesity, polycystic ovarian disease, hyperlipidemia, hypertension and atherosclerosis (Biddinger and Kahn 2006). Recent data also indicate a link between insulin resistance, type 2 diabetes and Alzheimer's disease (Craft 2007). Cross-sectional studies have suggested an association between type 2 diabetes and cognitive decline, especially in aspects of verbal memory (Strachan et al. 1997). Longitudinal studies have revealed that patients with type 2 diabetes have a 1.5-fold greater change over time in measures of cognitive function than those without diabetes (Cukierman et al. 2005). While some of this change may certainly be due to the increased prevalence of atherosclerosis in diabetic patients, there is increasing evidence that insulin resistance itself may affect CNS function and risk of Alzheimer's disease. In this review we will explore this relationship, focusing on experiments we have performed in mice. C1 [Kahn, C. Ronald; Suzuki, Ryo] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu; c.ronald.kahn@joslin.harvard.edu NR 131 TC 6 Z9 6 U1 2 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 978-3-642-04299-7 J9 RES PER ALZ PY 2010 BP 1 EP 20 DI 10.1007/978-3-642-04300-0_1 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BQS18 UT WOS:000281692500001 ER PT J AU Cyganek, K Hebda-Szydlo, A Katra, B Skupien, J Klupa, T Janas, I Kaim, I Sieradzki, J Reron, A Malecki, MT AF Cyganek, Katarzyna Hebda-Szydlo, Alicja Katra, Barbara Skupien, Jan Klupa, Tomasz Janas, Izabela Kaim, Irena Sieradzki, Jacek Reron, Alfred Malecki, Maciej T. TI Glycemic Control and Selected Pregnancy Outcomes in Type 1 Diabetes Women on Continuous Subcutaneous Insulin Infusion and Multiple Daily Injections: The Significance of Pregnancy Planning SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID PUMP THERAPY; CONVENTIONAL INSULIN; MELLITUS; MALFORMATIONS; ADOLESCENTS; CARE; METAANALYSIS; NATIONWIDE; WEIGHT; ASPART AB Background: Two regimens are used to achieve excellent glycemic control during pregnancy in type 1 diabetes mellitus (T1DM): continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). We assessed their efficacy and safety and the effect of pregnancy planning. Methods: We examined 269 pregnant T1DM women: 157 treated with MDI (MDI group), 42 with CSII (CSII group), and 70 who switched from MDI to CSII in the first trimester (MDI/CSII group). There were 116 women who planned pregnancy: 58 in the MDI group, 38 in the CSII group, and 20 in the MDI/CSII group. The estimated differences in glycemic control and maternal and fetal outcomes were adjusted for baseline characteristics. Results: Mean glycated A1c (HbA1c) in the first trimester in the whole group was 6.9%, and the women differed depending on whether they planned pregnancy or not (P < 0.0001). A multiple regression model showed an average difference of about 0.9% in favor of pregnancy planning, with no interaction between the planning and treatments. In the second trimester, HbA1c decreased to a mean value of 5.8%, with improvement of HbA1c across all treatments: by 1.5% in not-planning and 0.9% in planning women. Despite greater improvement, not-planning women still had a higher HbA1c (by 0.3%, P = 0.05). In the third trimester, there was no further significant changes; nevertheless, women who planned pregnancy still had a lower HbA1c (by 0.5%, P = 0.02). There were 14 malformations, stillbirths, and perinatal infant deaths in the not-planning versus five in the planning group (P = 0.07). Patients in the CSII group had a 2 kg greater weight gain compared to the MDI group (15.0 kg vs. 13.0 kg; P = 0.005). Conclusions: In pregnancy with T1DM, both MDI and CSII can provide excellent glycemic control. Pregnancy planning has a beneficial effect on glycemic control, independent from the therapy model. CSII seems to predispose to a larger weight gain in mothers. C1 [Cyganek, Katarzyna; Hebda-Szydlo, Alicja; Katra, Barbara; Klupa, Tomasz; Janas, Izabela; Sieradzki, Jacek; Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, 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; Klupa, Tomasz; Kaim, Irena; Sieradzki, Jacek; 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, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31511 Krakow, Poland. EM malecki_malecki@yahoo.com FU Polish Ministry of Science [N N407 414436] FX This work was supported by the Polish Ministry of Science grant N N407 414436. The authors would like to express their gratefulness to The Great Orchestra of Christmas Charity, a non- governmental aid organization in Poland that provided insulin pumps to most women included in this study. NR 38 TC 21 Z9 23 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JAN PY 2010 VL 12 IS 1 BP 41 EP 47 DI 10.1089/dia.2009.0081 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544RG UT WOS:000273676100005 PM 20082584 ER PT J AU Jacobson, AM Paterson, AD Ryan, CM Cleary, PA Waberski, BH Weinger, K Musen, G Dahms, W Bayless, M Silvers, N Harth, J Boright, AP AF Jacobson, A. M. Paterson, A. D. Ryan, C. M. Cleary, P. A. Waberski, B. H. Weinger, K. Musen, G. Dahms, W. Bayless, M. Silvers, N. Harth, J. Boright, A. P. CA DCCT EDIC Res Grp TI The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort SO DIABETIC MEDICINE LA English DT Article DE angiotensin-converting enzyme; apolipoprotein E; cognition; genetics; Type 1 diabetes ID APOE GENE; PERFORMANCE; GENOTYPE; COMPLICATIONS; METAANALYSIS; INDIVIDUALS; NEPHROPATHY; PROGRESSION; IMPAIRMENT; VARIANTS AB Aims Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive dysfunction in the general population, yet little research has examined whether genetic factors influence risk of cognitive dysfunction in patients with Type 1 diabetes. The long-term follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) population provides an opportunity to examine if specific genetic variations in APOE and ACE alter risk for cognitive decline. Methods Neurocognitive function in Type 1 diabetic subjects from the DCCT/EDIC study was assessed at DCCT entry and re-assessed approximately 18 years later, using a comprehensive cognitive test battery. Glycated haemoglobin (HbA(1c)) and the frequency of severe hypoglycaemic events leading to coma or seizures were measured over the 18-year follow-up. We determined whether the APO epsilon 4 and ACE intron 16 indel genotypes were associated with baseline cognitive function and with change over time, and whether they conferred added risk in those subjects experiencing severe hypoglycaemic events or greater glycaemic exposure. Results None of the APOE or ACE polymorphisms were associated with either baseline cognitive performance or change in cognition over the 18-year follow-up. Moreover, none of the genotype variations altered the risk of cognitive dysfunction in those subjects with severe hypoglycaemic episodes or high HbA(1c). Conclusions In this sample of young and middle-aged adults with Type 1 diabetes, APO epsilon 4 and ACED alleles do not appear to increase risk of cognitive dysfunction. C1 [Jacobson, A. M.; Weinger, K.; Musen, G.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Paterson, A. D.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Paterson, A. D.; Boright, A. P.] Univ Toronto, Toronto, ON, Canada. [Ryan, C. M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Cleary, P. A.; Waberski, B. H.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Dahms, W.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Bayless, M.] Univ Iowa, Coll Med, Iowa City, IA USA. [Silvers, N.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harth, J.] Univ Western Ontario, Schulich Sch Med, London, ON, Canada. [Boright, A. P.] Univ Hlth Network, London, ON, Canada. RP Jacobson, AM (reprint author), Winthrop Univ Hosp, 222 Stn Plaza N Suite 300, Mineola, NY 11501 USA. EM amjacobson@winthrop.org RI Paterson, Andrew/A-4088-2011 OI Paterson, Andrew/0000-0002-9169-118X FU National Institutes of Health [R01 DK06221802, R01 DK077510, N01-6-2204]; National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute of Neurological Disorders and Stroke; The General Clinical Research Centers Program; National Center for Research Resources; The Herbert Graetz Psychosocial Research Fund FX Funding for this study was provided by Grant R01 DK06221802, R01 DK077510, the National Institutes of Health subcontract N01-6-2204, and contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases; National Eye Institute; National Institute of Neurological Disorders and Stroke; The General Clinical Research Centers Program; National Center for Research Resources; The Herbert Graetz Psychosocial Research Fund; and by Genetech through a cooperative research and development agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Contributions of free or discounted supplies and /or equipment included Lifescan, Roche, Aventis, Eli Lilly, Omnipod, Can-Am, B-D, Animas, Medtronic, Medtronic Minimed, Bayer (donation one time in 2008) and Omron. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute ofDiabetes and Digestive and KidneyDiseases or the National Institutes of Health. A complete list of the individuals and institutions participating in the DCCT/EDIC Research Group appears in: Jacobson AM, Ryan CM, Cleary P, Waberski B, Burwood A, Weinger K et al. Long-term effects of diabetes and its treatment on cognitive function. N Engl J Med 2007; 356: 1842 -1852. NR 32 TC 2 Z9 3 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JAN PY 2010 VL 27 IS 1 BP 15 EP 22 DI 10.1111/j.1464-5491.2009.02885.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541WM UT WOS:000273451900003 PM 20121884 ER PT J AU Reiling, E Jafar-Mohammadi, B van't Riet, E Weedon, MN van Vliet-Ostaptchouk, JV Hansen, T Saxena, R van Haeften, TW Arp, PA Das, S Nijpels, G Groenewoud, MJ van Hove, EC Uitterlinden, AG Smit, JWA Morris, AD Doney, ASF Palmer, CNA Guiducci, C Hattersley, AT Frayling, TM Pedersen, O Slagboom, PE Altshuler, DM Groop, L Romijn, JA Maassen, JA Hofker, MH Dekker, JM McCarthy, MI 't Hart, LM AF Reiling, E. Jafar-Mohammadi, B. van't Riet, E. Weedon, M. N. van Vliet-Ostaptchouk, J. V. Hansen, T. Saxena, R. van Haeften, T. W. Arp, P. A. Das, S. Nijpels, G. Groenewoud, M. J. van Hove, E. C. Uitterlinden, A. G. Smit, J. W. A. Morris, A. D. Doney, A. S. F. Palmer, C. N. A. Guiducci, C. Hattersley, A. T. Frayling, T. M. Pedersen, O. Slagboom, P. E. Altshuler, D. M. Groop, L. Romijn, J. A. Maassen, J. A. Hofker, M. H. Dekker, J. M. McCarthy, M. I. 't Hart, L. M. TI Genetic association analysis of LARS2 with type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Genetics; LARS2; Mitochondria; SNP; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; MELLITUS; GLUCOSE; REPLICATION; LOCI; DETERMINANTS; DYSFUNCTION; POPULATION; PREVALENCE; SELECTION AB LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk. We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we attempted replication of rs9825041 (a proxy for this group) and the previously identified H324Q variant in up to 35,715 participants of European descent. No association between the common SNPs in LARS2 and type 2 diabetes was found. Our replication studies for the two low-frequency variants, rs9825041 and H324Q, failed to confirm an association with type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95-1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715 respectively). In this study, the largest study examining the role of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility. C1 [Reiling, E.; Groenewoud, M. J.; van Hove, E. C.; Maassen, J. A.; 't Hart, L. M.] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands. [van't Riet, E.; Nijpels, G.; Dekker, J. M.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [van't Riet, E.; Dekker, J. M.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Diabet Genet Inst Biomed & Clin Sci, Exeter, Devon, England. [van Vliet-Ostaptchouk, J. V.; Hofker, M. H.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Sect, NL-9713 AV Groningen, Netherlands. [Hansen, T.; Pedersen, O.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Saxena, R.; Guiducci, C.; Altshuler, D. M.] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA. [Slagboom, P. E.] Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands. [van Haeften, T. W.] Univ Med Ctr Utrecht, Dept Internal Med, Utrecht, Netherlands. [Arp, P. A.; Uitterlinden, A. G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Nijpels, G.] Vrije Univ Amsterdam Med Ctr, Dept Gen Practice, Amsterdam, Netherlands. [Smit, J. W. A.; Romijn, J. A.] Leiden Univ, Med Ctr, Dept Endocrinol, NL-2300 RC Leiden, Netherlands. [Pedersen, O.] Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark. [Pedersen, O.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Altshuler, D. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, D. M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Groop, L.] Lund Univ, Clin Res Ctr, Dept Clin Sci, Malmo Univ Hosp, Malmo, Sweden. [Groop, L.] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland. [Maassen, J. A.] Vrije Univ Amsterdam Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. [Morris, A. D.; Doney, A. S. F.; Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Dundee DD1 9SY, Scotland. [Hansen, T.] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [McCarthy, M. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Altshuler, D. M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Saxena, R.; Guiducci, C.; Altshuler, D. M.] Harvard Univ, Cambridge, MA 02138 USA. [Hansen, T.; Pedersen, O.] Hagedorn Res Inst, Gentofte, Denmark. [van Vliet-Ostaptchouk, J. V.; Hofker, M. H.] Univ Groningen, Groningen, Netherlands. [Jafar-Mohammadi, B.; McCarthy, M. I.] Univ Oxford, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England. [Jafar-Mohammadi, B.; Das, S.; McCarthy, M. I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. RP 't Hart, LM (reprint author), Leiden Univ, Med Ctr, Dept Mol Cell Biol, POB 9600, NL-2300 RC Leiden, Netherlands. EM l.m.t_hart@lumc.nl RI Palmer, Colin/C-7053-2008; Altshuler, David/A-4476-2009; Smit, J.W.A./H-8091-2014; Study, GoDARTS/K-9448-2016; Slagboom, P. Eline/R-4790-2016 OI Palmer, Colin/0000-0002-6415-6560; Altshuler, David/0000-0002-7250-4107; Slagboom, P. Eline/0000-0002-2875-4723 FU Netherlands Organization for Scientific Research; ZonMW RIDE; Dutch Diabetes Research Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP); Danish Health Research Council; European Union (EUGENE2) [LSHM-CT-2004-512013]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113, GR072960]; Wellcome Trust (Biomedical Collections); Diabetes UK [RD04/0002809]; UK Medical Research Council [G0601261]; Oxford NIHR Biomedical Research Centre FX This study was supported by the Netherlands Organization for Scientific Research, the ZonMW RIDE programme and the Dutch Diabetes Research Foundation. The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP), the Danish Health Research Council and The European Union (EUGENE2, grant no. LSHM-CT-2004-512013). We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. We thank the staff and senior management of the UK Blood Services responsible for the UK Blood Services Collection. Diabetes UK funded the collection of the Warren 2 resource and the UK Type 2 Diabetes Genetics Consortium collection was supported by the Wellcome Trust (Biomedical Collections Grant GR072960). We also acknowledge funding from Diabetes UK (Grant RD04/0002809), Wellcome Trust (076113 and GR072960), UK Medical Research Council (G0601261) and the Oxford NIHR Biomedical Research Centre. The DIAGRAM consortium is acknowledged for sharing data. B. Jafar-Mohammadi is a Diabetes UK clinical training fellow. The authors would like to acknowledge the participants of all study cohorts for their cooperation. NR 26 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2010 VL 53 IS 1 BP 103 EP 110 DI 10.1007/s00125-009-1557-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 529PV UT WOS:000272530600015 PM 19847392 ER PT J AU Vetere, A Li, WC Paroni, F Juhl, K Guo, L Nishimura, W Dai, X Bonner-Weir, S Sharma, A AF Vetere, A. Li, W. -C. Paroni, F. Juhl, K. Guo, L. Nishimura, W. Dai, X. Bonner-Weir, S. Sharma, A. TI OVO homologue-like 1 (Ovol1) transcription factor: a novel target of neurogenin-3 in rodent pancreas SO DIABETOLOGIA LA English DT Article DE ChIP cloning; Neurogenin 3; Pancreatic progenitors; Proliferation/differentiation ID INSULIN GENE-TRANSCRIPTION; ENDOCRINE PANCREAS; PROGENITOR CELLS; BETA-CELLS; C-MYC; EXPRESSION; MICE; SPERMATOGENESIS; DIFFERENTIATION; PROLIFERATION AB The basic helix-loop-helix transcription factor neurogenin-3 (NGN3) commits the fates of pancreatic progenitors to endocrine cell types, but knowledge of the mechanisms regulating the choice between proliferation and differentiation of these progenitors is limited. Using a chromatin immunoprecipitation cloning approach, we searched for direct targets of NGN3 and identified a zinc-finger transcription factor, OVO homologue-like 1 (OVOL1). Transactivation experiments were carried out to elucidate the functional role of NGN3 in Ovol1 gene expression. Embryonic and adult rodents pancreases were immunostained for OVOL1, Ki67 and NGN3. We showed that NGN3 negatively regulates transcription of Ovol1 in an E-box-dependent fashion. The presence of either NGN3 or NEUROD1, but not MYOD, reduced endogenous Ovol1 mRNA. OVOL1 was detected in pancreatic tissue around embryonic day 15.5, after which OVOL1 levels dramatically increased. In embryonic pancreas, OVOL1 protein levels were low in NGN3(+) or Ki67(+) cells, but high in quiescent differentiated cells. OVOL1 presence was maintained in adult pancreas, where it was detected in islets, pancreatic ducts and some acinar cells. Additionally OVOL1 presence was lacking in proliferating ductules in regenerating pancreas and induced in cells as they began to acquire their differentiated phenotype. The timing of OVOL1 appearance in pancreas and its increased levels in differentiated cells suggest that OVOL1 promotes the transition of cells from a proliferating, less-differentiated state to a quiescent more-differentiated state. We conclude that OVOL1, a downstream target of NGN3, may play an important role in regulating the balance between proliferation and differentiation of pancreatic cells. C1 [Vetere, A.] Univ Trieste, Dept Life Sci, Trieste, Italy. [Dai, X.] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. [Dai, X.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA. [Vetere, A.; Li, W. -C.; Paroni, F.; Juhl, K.; Guo, L.; Nishimura, W.; Bonner-Weir, S.; Sharma, A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Vetere, A (reprint author), Univ Trieste, Dept Life Sci, Trieste, Italy. EM amedeo.vetere@joslin.harvard.edu OI Vetere, Amedeo/0000-0001-5608-0773; Nishimura, Wataru/0000-0002-8068-1277 FU NIH [P30 DK36836]; Endocrinology Research Center (DERC) Advanced Microscopy Core, JDRF Research Grant; Diabetes Research and Wellness Foundation; JDRF Post Doctoral Fellowship FX This study was supported by the NIH P30 DK36836 Joslin Diabetes and Endocrinology Research Center (DERC) Advanced Microscopy Core, JDRF Research Grant (to A. Sharma), the Diabetes Research and Wellness Foundation, and by a group of private donors. W.-C. Li was supported by a JDRF Post Doctoral Fellowship, W. Nishimura by the Mary K. Iacocca Fellowship and K. Juhl by a Lundbeckfonden fellowship. Mouse monoclonal anti-NGN3 antibody developed by O. D. Madsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by Department of Biological Sciences, University of Iowa, Iowa, IA, USA. NR 35 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2010 VL 53 IS 1 BP 115 EP 122 DI 10.1007/s00125-009-1567-5 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 529PV UT WOS:000272530600017 PM 19882138 ER PT J AU Katsuta, H Akashi, T Katsuta, R Nagaya, M Kim, D Arinobu, Y Hara, M Bonner-Weir, S Sharma, AJ Akashi, K Weir, GC AF Katsuta, H. Akashi, T. Katsuta, R. Nagaya, M. Kim, D. Arinobu, Y. Hara, M. Bonner-Weir, S. Sharma, A. J. Akashi, K. Weir, G. C. TI Single pancreatic beta cells co-express multiple islet hormone genes in mice SO DIABETOLOGIA LA English DT Article DE Heterogeneity; Pancreatic beta cell; Single-cell nested RT-PCR ID INDIVIDUAL B-CELLS; ENDOCRINE PANCREAS; INSULIN PROMOTER; PRECURSOR CELLS; GLUCOSE; EXPRESSION; MOUSE; HETEROGENEITY; DIFFERENTIATION; SECRETION AB It is widely accepted that production of insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells is specific to beta, alpha, delta and pancreatic polypeptide cells, respectively. We examined whether beta cells express other genes encoding islet hormones. Nested RT-PCR was performed on single beta cells of transgenic mice with green fluorescent protein (GFP) driven by mouse insulin I promoter (MIP-GFP). Only 55% of adult beta cells expressed the insulin gene alone, while others expressed two or more islet hormone genes; 4% expressed all four hormone genes. In embryonic and neonatal cells, 60% to 80% of GFP(+) cells co-expressed pancreatic polypeptide and insulin genes in contrast to 29% in adult. To clarify cell fate, we conducted lineage tracing using rat insulin II promoter-cre mice crossed with reporter mice Gt(ROSA)26Sor-loxP-flanked STOP-cassette-GFP. All GFP(+) cells expressed insulin I and II genes, and showed similar heterogeneity of co-expression to that seen in MIP-GFP mice. Although we report expression of other hormone genes in a significant proportion of beta cells, our lineage tracing results demonstrate that after inducing InsII (also known as Ins2) expression, beta cell progenitors do not redifferentiate to non-beta cells. This study shows co-expression of multiple hormone genes in beta cells of adult mice as well as in embryos and neonates. This finding could: (1) represent residual expression from beta cell precursors; (2) result from alternative developmental pathways for beta cells; or (3) denote the differentiation potential of these cells. It may be linked to functional heterogeneity. This heterogeneity in gene expression may provide a means to characterise the functional, cellular and developmental heterogeneity seen in beta cells. C1 [Katsuta, H.; Akashi, T.; Katsuta, R.; Nagaya, M.; Kim, D.; Bonner-Weir, S.; Sharma, A. J.; Weir, G. C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Arinobu, Y.; Akashi, K.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Hara, M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM Gordon.Weir@joslin.harvard.edu FU Juvenile Diabetes Research Foundation; National Institutes of Health [DK66056, P30 DK36836]; Diabetes Research and Wellness Foundation FX The authors thank S. Yatoh for helpful discussions, and J. Lock, J. LaVecchio and G. Buruzula for excellent technical assistance. This study was supported by: the Juvenile Diabetes Research Foundation; the National Institutes of Health (DK66056); the National Institutes of Health (P30 DK36836)-Flow Cytometry Core of Joslin Diabetes and Endocrinology Research Center (DERC); the Diabetes Research and Wellness Foundation. NR 48 TC 33 Z9 33 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2010 VL 53 IS 1 BP 128 EP 138 DI 10.1007/s00125-009-1570-x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 529PV UT WOS:000272530600019 PM 19851748 ER PT J AU Weinstock, DM AF Weinstock, David M. TI Epstein-Barr Virus, Lymphoma Risk and the Potential Role of HIV Infection in IBD Patients Undergoing Immunosuppression SO DIGESTIVE DISEASES LA English DT Article; Proceedings Paper CT Conference on Pathophysiology on Inflammatory Bowel Disease Treatment CY MAR, 2010 CL Miami, FL DE Epstein-Barr virus; Hepatosplenic T cell lymphoma; Inflammatory bowel disease; Lymphoma; Thiopurine ID INFLAMMATORY-BOWEL-DISEASE; THERAPY; AZATHIOPRINE; CANCER AB For decades, lymphoma has been considered a dreaded and untoward complication of autoimmune disorders, including inflammatory bowel disease (IBD). Yet until recently, the data linking inflammatory bowel disease with an increased risk for lymphoma has been equivocal. With the publication of the CESAME trial in 2009, a greater understanding of lymphoma risk has begun to emerge. In this Falk Symposium paper, I discuss the available data from studies that interrogated the relationship between lymphoma and IBD, thiopurines and TNF alpha-directed agents. While recent data has clarified some aspects of lymphoma epidemiology in patients with IBD, causality and the mechanisms that underlie it remain very poorly understood. Copyright (C) 2010 S. Karger AG, Basel C1 [Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Boston, MA USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 510B, Boston, MA 02115 USA. EM davidm_weinstock@dfci.harvard.edu NR 19 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 3 BP 519 EP 524 DI 10.1159/000320411 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660SE UT WOS:000282663400021 PM 20926881 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Vaccines and Inflammatory Bowel Disease SO DIGESTIVE DISEASES LA English DT Article; Proceedings Paper CT Conference on Pathophysiology on Inflammatory Bowel Disease Treatment CY MAR, 2010 CL Miami, FL DE Immunosuppression; Inflammatory bowel disease; Vaccine ID DISSEMINATED PRIMARY VARICELLA; CROHNS-DISEASE; HERPES-ZOSTER; ULCERATIVE-COLITIS; RISK-FACTORS; HEPATITIS-B; OPPORTUNISTIC INFECTIONS; RHEUMATOID-ARTHRITIS; INFLIXIMAB TREATMENT; INFLUENZA VACCINE AB Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are at increased risk for infection due to both their underlying disease and the immunosuppressive therapy used to treat the disease. Numerous groups and papers support the routine vaccination of IBD patients, yet many opportunities to vaccinate this vulnerable population are missed. While immunogenicity may be somewhat attenuated, some protection is likely to be provided, especially when vaccination is performed during periods of reduced immunosuppression. Live viral vaccines should be avoided during periods of more intense immunosuppression; further specific guidance on this as well as information on individual vaccines is provided. Copyright (C) 2010 S. Karger AG, Basel C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. [Kotton, Camille Nelson] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 61 TC 11 Z9 12 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 3 BP 525 EP 535 DI 10.1159/000320412 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660SE UT WOS:000282663400022 PM 20926882 ER PT J AU Pandol, SJ Gorelick, FS Gerloff, A Lugea, A AF Pandol, Stephen J. Gorelick, Fred S. Gerloff, Andreas Lugea, Aurelia TI Alcohol Abuse, Endoplasmic Reticulum Stress and Pancreatitis SO DIGESTIVE DISEASES LA English DT Article DE Pancreas; Pancreatitis; Unfolded protein response; Alcohol; Smoking ID INFLAMMATORY-BOWEL-DISEASE; C-ALPHA PHOSPHORYLATION; STELLATE CELLS; BASOLATERAL EXOCYTOSIS; CIGARETTE-SMOKING; ACINAR-CELLS; ZYMOGEN ACTIVATION; ETHANOL DIET; RISK-FACTOR; ER STRESS AB Alcohol abuse is a common cause of both acute and chronic pancreatitis. There is a wide spectrum of pancreatic manifestations in heavy drinkers from no apparent disease in most individuals to acute inflammatory and necrotizing pancreatitis in a minority of individuals with some progressing to chronic pancreatitis characterized by replacement of the gland by fibrosis and chronic inflammation. Both smoking and African-American ethnicity are associated with increased risk of alcoholic pancreatitis. In this review we describe how our recent studies demonstrate that ethanol feeding in rodents causes oxidative stress in the endoplasmic reticulum (ER) of the digestive enzyme synthesizing acinar cell of the exocrine pancreas. This ER stress is attenuated by a robust unfolded protein response (UPR) involving X-box binding protein-1 (XBP1) in the acinar cell. When the UPR activation is prevented by genetic reduction in XBP1, ethanol feeding causes significant pathological responses in the pancreas. These results suggest that the reason most individuals who drink alcohol heavily do not get significant pancreatic disease is because the pancreas mounts an adaptive UPR to attenuate the ER stress that ethanol causes. We hypothesize that disease in the pancreas results when the UPR is insufficiently robust to alleviate the ER stress caused by alcohol abuse. Copyright (C) 2011 S. Karger AG, Basel C1 [Pandol, Stephen J.] Univ Calif Los Angeles, Dept Vet Affairs, UCLA Ctr Excellence Pancreat Dis, So Calif Res Ctr Alcohol Liver Pancreat Dis & Cir, Los Angeles, CA 90073 USA. [Pandol, Stephen J.; Gerloff, Andreas; Lugea, Aurelia] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Gorelick, Fred S.] Yale Univ, Dept Med, West Haven, CT USA. [Gorelick, Fred S.] Yale Univ, Dept Cell Biol, West Haven, CT USA. [Gorelick, Fred S.] New England VA Hlth Care Syst, West Haven, CT USA. RP Pandol, SJ (reprint author), Univ Calif Los Angeles, Dept Vet Affairs, UCLA Ctr Excellence Pancreat Dis, So Calif Res Ctr Alcohol Liver Pancreat Dis & Cir, Bldg 258,Rm 340,11310 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Stephen.pandol@va.gov FU Department of Veterans Affairs; Greater Los Angeles Healthcare System; USC-UCLA Southern California Research Center for ALPD and Cirrhosis [P60 AA11999]; UCLA Center for Excellence in Pancreatic Diseases [P01AT003960]; National Institute of Health, NIDDK [1R21 AA016010-01] FX The authors acknowledge support from the Department of Veterans Affairs, Greater Los Angeles Healthcare System, USC-UCLA Southern California Research Center for ALPD and Cirrhosis (P60 AA11999), UCLA Center for Excellence in Pancreatic Diseases (P01AT003960), and National Institute of Health, NIDDK (1R21 AA016010-01). NR 72 TC 25 Z9 25 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 6 BP 776 EP 782 DI 10.1159/000327212 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 757ND UT WOS:000290093200011 PM 21525762 ER PT J AU Gerloff, A Feick, P Singer, MV AF Gerloff, Andreas Feick, Peter Singer, Manfred V. TI Pancreas - Non-Alcoholic Constituents and Their Effects SO DIGESTIVE DISEASES LA English DT Article DE Non-alcoholic constituents of alcoholic beverages; Alcoholic beverages and pancreatitis; Beer and pancreatic secretion ID ALCOHOLIC PANCREATITIS; ENZYME SECRETION; ACINAR-CELLS; IN-VITRO; EXOCRINE PANCREAS; DRINKING HABITS; RISK-FACTORS; BEER; BEVERAGES; ETHANOL AB Alcoholic beverages contain numerous non-alcoholic compounds that could have beneficial or pathological effects. For example, up to now in beer more than 2,000 and in wine more than 1,000 organic and inorganic constituents have been identified. Whereas the role of alcohol (ethanol) in the development of pancreatic diseases-in particular acute and chronic pancreatitis-has been intensively investigated, only little is known about the effects of non-alcoholic compounds in this context. Some of the non-alcoholic constituents have been shown to be biologically active, although discussions of the results in appropriate publications were often not performed with regard to their consumption as a mixture in alcoholic beverages. In this article we provide an overview about the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion and their possible role in alcoholic pancreatitis. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. However, there is accumulating evidence that non-alcoholic compounds of alcoholic beverages exert different effects on the pancreas. The effects and mechanisms of most single compounds and their combinations are still unknown and thus caution is required in attempting to draw firm conclusions on the effect of non-alcoholic compounds of alcoholic beverages on defining alcoholic etiology of pancreatitis. Copyright (C) 2011 S. Karger AG, Basel C1 [Gerloff, Andreas; Feick, Peter; Singer, Manfred V.] Univ Heidelberg Hosp, Dept Med 2, D-68135 Mannheim, Germany. [Gerloff, Andreas] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gerloff, Andreas] Univ Calif Los Angeles, Los Angeles, CA USA. RP Gerloff, A (reprint author), LA Healthcare Syst, UCLA Med VA Greater, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM andreas_gerloff@web.de NR 28 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 6 BP 812 EP 819 DI 10.1159/000324290 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 757ND UT WOS:000290093200016 PM 21525767 ER PT J AU Henderson, LM Patel, S Giordano, TP Green, L El-Serag, HB AF Henderson, Louise M. Patel, Shital Giordano, Thomas P. Green, Linda El-Serag, Hashem B. TI Statin Therapy and Serum Transaminases Among a Cohort of HCV-Infected Veterans SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis C virus; Statins; Transaminases; Veterans ID VIRUS-RNA REPLICATION; HEPATITIS-C VIRUS; LIVER-DISEASE; SAFETY; HEPATOTOXICITY; GERANYLGERANYLATION; REDUCTASE; TRIAL; CELLS AB Background We sought to determine the effect of statin therapy on serum AST and ALT levels in a cohort of HCV-infected veterans with well-characterized liver disease. Study We examined liver biopsy records of consecutive HCV-infected patients and identified 20 patients who were prescribed statins. We matched them on age, stage of fibrosis, and time between HCV diagnosis and statin start dates with up to four HCV-infected patients who did not use statins. ALT and AST values from up to four time points within 1 year of follow-up were abstracted from the medical record. We compared median ALT and AST levels using Wilcoxon-Mann-Whitney tests and assessed changes in ALT and AST over time between the statin and non-statin groups using a non-parametric repeated measures ANOVA model, adjusting for the matching factors, receipt of HCV treatment, BMI, and diabetes. Results Patients prescribed statins had higher median BMIs, were more likely to have diabetes, and had higher total cholesterol levels. Median baseline ALT levels were higher among those prescribed statins (P = 0.04) while median baseline AST levels were lower among statin users (P = 0.03). From baseline to follow-up, the median decreases in both ALT (-13.5 vs. -4.0) and AST (-4.5 vs. -0.5) were significantly larger among statin users compared to non-statin users ( P = 0.03 and P = 0.0007, respectively) even after adjustment. Conclusions Among HCV-infected patients AST and ALT levels for those prescribed statins decreased over a 6 to 12-month follow-up period compared to patients not taking statins. C1 [Henderson, Louise M.; Giordano, Thomas P.; El-Serag, Hashem B.] Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. [Henderson, Louise M.; Patel, Shital; Giordano, Thomas P.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Green, Linda] Michael E DeBakey VA Med Ctr, Dept Pathol, Houston, TX USA. RP El-Serag, HB (reprint author), Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston Vet Affairs Med Ctr 152,2002 Holcombe Blv, Houston, TX 77030 USA. EM hasheme@bcm.edu FU NIH [K24DK078154-03, DK56338]; Texas Medical Center Digestive Disease Center FX The work was partly supported by NIH K24DK078154-03 for Dr. El-Serag, and Public Health Service Grant DK56338, which funds the Texas Medical Center Digestive Disease Center. NR 25 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2010 VL 55 IS 1 BP 190 EP 195 DI 10.1007/s10620-009-0959-1 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 542TZ UT WOS:000273520500031 PM 19731022 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Discrete Calculus: History and Future SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter ID TOTAL VARIATION MINIMIZATION; POLYNOMIAL-TIME ALGORITHM; SURFACE-BASED ANALYSIS; ACTIVE CONTOUR MODELS; MARKOV RANDOM-FIELDS; MINIMUM CYCLE BASIS; IMAGE SEGMENTATION; ENERGY MINIMIZATION; COMPLEX NETWORKS; CORTICAL SURFACE AB The goal of this book is to bring together three active areas of current research into a single framework and show how each area benefits from more exposure to the other two. The areas are: discrete calculus, complex networks, and algorithmic content extraction. Although there have been a few intersections in the literature between these areas, they have largely developed independently of one another. However, we believe that researchers working in any one of these three areas can strongly benefit from the tools and techniques being developed in the others. We begin this book by outlining each of these three areas, their history and their relationship to one another. Subsequently, we outline the structure of this work and help the reader navigate its contents. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 1 EP + DI 10.1007/978-1-84996-290-2_1 D2 10.1007/978-1-84996-290-2 PG 27 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500001 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Introduction to Discrete Calculus SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Editorial Material; Book Chapter AB In this chapter we review conventional vector calculus from the standpoint of a generalized exposition in terms of exterior calculus and the theory of forms. This generalization allows us to distill the important elements necessary to operate the basic machinery of conventional vector calculus. This basic machinery is then redefined in a discrete setting to produce appropriate definitions of the domain, boundary,, functions, integrals, metric and derivative. These definitions are then employed to demonstrate how the structure of the discrete calculus behaves analogously to the conventional vector calculus in many different ways. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 13 EP 89 DI 10.1007/978-1-84996-290-2_2 D2 10.1007/978-1-84996-290-2 PG 77 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500002 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Circuit Theory and Other Discrete Physical Models SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB In this chapter we present linear electric circuit theory as the central physical model for performing calculus on networks. We adopt circuit theory as the central physical model for applying and understanding the concepts of discrete calculus on graphs for three reasons: because much of the progress in graph theory over the last century was created in the context of circuit theory; because of the early connection made between circuit theory and algebraic topology (Branin Jr. in Proc. of Conf. on Neural Networks, pp. 453-491, 1966; Roth in Proceedings of the National Academy of Sciences of the United States of America 41(7):518-521, 1955); and because circuits are physical, realizable systems which need not be seen as discretizations of an underlying continuous domain but rather as a domain unto themselves. Our focus in this chapter will be to cover the main concepts in linear circuit theory from an algebraic standpoint with a focus on operators. This will prepare the reader with notation and concepts that tie naturally to the previous chapter in which the discrete analogues of differential operators were introduced. We begin with definitions of the physical quantities and corresponding quantities in circuit theory, then proceed to define the laws that relate the quantities to each other, treat methods of solving for the unknowns, and end by connecting circuit theory to other discrete processes. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 91 EP 122 DI 10.1007/978-1-84996-290-2_3 D2 10.1007/978-1-84996-290-2 PG 32 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500003 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Building a Weighted Complex from Data SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB In some applications, both the neighborhood structure of the data and the weights of the cells are naturally and directly defined by the problem at hand (e.g., road networks, social networks, communication networks, chemical graph theory or surface simplification). However, in many other applications the appropriate representation of the data to be analyzed is not provided (e.g., machine learning). Therefore, to use the tools of discrete calculus, a practitioner must determine the topology and weights of the graph or complex from the data that is most appropriate for solving the problem. In this chapter, we will discuss different techniques for generating a meaningful weighted complex from an embedding or from the data itself. Our focus will be primarily on generating weighted edges and faces from node and/or edge data, but we additionally demonstrate how these techniques may be applied to weighting higher-order structures. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 125 EP 154 DI 10.1007/978-1-84996-290-2_4 D2 10.1007/978-1-84996-290-2 PG 30 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500004 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Filtering on Graphs SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB Measured data often includes noise. A data point measured in isolation offers little opportunity to tease signal apart from noise. However, this separation of noise from the signal becomes more possible when multiple data points are acquired which have a relationship with each other. A spatial relationship, such as the edge set of a graph, permits the use of the collective data acquisition to make better decisions about the true data underlying each measurement. This process whereby the spatial relationships of the data are used to provide better estimates of the noiseless data is called a filtering or a denoising process. In this chapter, we outline the assumptions used to justify spatial filtering, describe the equivalent of Fourier analysis on a general graph and discuss how different parameter settings of a small number of variational approaches to filtering lead to a large number of commonly used filters. Although our focus in this chapter is on the filtering of node data (0-cochains), we also discuss how these techniques may be applied to the filtering of edge data (i.e., flows, or 1-cochains) and to the filtering of data associated with higher-dimensional cells. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 155 EP 197 DI 10.1007/978-1-84996-290-2_5 D2 10.1007/978-1-84996-290-2 PG 43 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500005 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Clustering and Segmentation SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB Clustering algorithms are used to find communities of nodes that all belong to the same group. This grouping process is also known as image segmentation in image processing. The clustering problem is also deeply connected to machine learning because a solution to the clustering problem may be used to propagate labels from observed data to unobserved data. In general network analysis, the identification of a grouping allows for the analysis of the nodes within each group as separate entities. In this chapter, we use the tools of discrete calculus to examine both the targeted clustering problem (i.e., finding a specific group) and the untargeted clustering problem (i.e., discovering all groups). We additionally show how to apply these clustering models to the clustering of higher-order cells, e.g., to cluster edges. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 199 EP 242 DI 10.1007/978-1-84996-290-2_6 D2 10.1007/978-1-84996-290-2 PG 44 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500006 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Manifold Learning and Ranking SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB A prominent theme of this book is the spatial analysis of networks and data independent of an embedding in an ambient space. The topology and metric of the network/complex have been sufficient to define the domain upon which we may perform data analysis. However, an intrinsic metric defined on a network may be interpreted as the metric that would have been obtained if the network had been embedded into an ambient space equipped with its own metric. Consequently, it is possible to calculate an embedding map for which the induced metric approximates the intrinsic metric defined on the network. The calculation of such embeddings by manifold learning techniques is one way in which the structure of the network may be examined and visualized. A different method of examining the structure of a network is to calculate an importance ranking for each node. In contrast to the majority of this book, the ranking algorithms are generally used to examine the structure of directed graphs. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 243 EP 266 DI 10.1007/978-1-84996-290-2_7 D2 10.1007/978-1-84996-290-2 PG 24 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500007 ER PT B AU Grady, LJ Polimeni, JR AF Grady, Leo J. Polimeni, Jonathan R. BA Grady, LJ Polimeni, JR BF Grady, LJ Polimeni, JR TI Measuring Networks SO DISCRETE CALCULUS: APPLIED ANALYSIS ON GRAPHS FOR COMPUTATIONAL SCIENCE LA English DT Article; Book Chapter AB We have adopted the view of graphs and, more generally, cell complexes as a domain upon which we may apply the tools of calculus to formulate differential equations and to analyze data. An important aspect of the discrete differential operators is that the operators are defined by the topology of the domain itself Therefore, in an effort to provide a complete treatment of these differential operators, we examine in this chapter the properties of the network which may be extracted from the structure of these operators. In addition to the network properties extracted directly from the differential operators, we also review other methods for measuring the structural properties of a network. Specifically, the properties of the network that we consider are based on distances, partitioning, geometry, and topology. Our particular focus will be on the measurement of these properties from the graph structure. Applications will illustrate the use of these measures to predict the importance of nodes and to relate these measures to other properties of the subject being modeled by the network. C1 [Grady, Leo J.] Siemens Corp Res, Princeton, NJ 08540 USA. [Polimeni, Jonathan R.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Grady, LJ (reprint author), Siemens Corp Res, 755 Coll Rd E, Princeton, NJ 08540 USA. EM leo.grady@siemens.com; jonp@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-289-6 PY 2010 BP 267 EP 289 DI 10.1007/978-1-84996-290-2_8 D2 10.1007/978-1-84996-290-2 PG 23 WC Mathematics, Applied; Imaging Science & Photographic Technology SC Mathematics; Imaging Science & Photographic Technology GA BQH32 UT WOS:000281005500008 ER PT J AU Pai, SY Kim, C Williams, DA AF Pai, Sung-Yun Kim, Chaekyun Williams, David A. TI Rac GTPases in human diseases SO DISEASE MARKERS LA English DT Article DE Rho GTPases; Rac; neutrophils; leukocyte adhesion deficiency; RhoH; lymphocytes ID GUANOSINE TRIPHOSPHATASES REPRESENT; PRIMARY GRANULE EXOCYTOSIS; GTP-BINDING-PROTEIN; BREAST-CANCER CELLS; RHO-GTPASES; STEM-CELLS; IN-VIVO; SUPEROXIDE-PRODUCTION; NEUTROPHIL FUNCTIONS; ACTIN CYTOSKELETON AB Rho GTPases are members of the Ras superfamily of GTPases that regulate a wide variety of cellular functions. While Rho GTPase pathways have been implicated in various pathological conditions in humans, to date coding mutations in only the hematopoietic specific GTPase, RAC2, have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by life-threatening infections in infancy. Interestingly, the phenotype was predicted by a mouse knock-out of Rac2 and resembles leukocyte adhesion deficiency (LAD). Here we review Rho GTPases with a specific focus on Rac GTPases. In particular, we discuss a new understanding of the unique and overlapping roles of Rac2 in blood cells that has developed since the generation of mice deficient in Rac1, Rac2 and Rac3 proteins. We propose that Rac2 mutations leading to disease be termed LAD type IV. C1 [Pai, Sung-Yun; Williams, David A.] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Pai, Sung-Yun; Williams, David A.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kim, Chaekyun] Inha Univ, Sch Med, Inchon, South Korea. RP Williams, DA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Dana Farber Canc Inst, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM DAWilliams@childrens.harvard.edu FU National Institutes of Health [DK062757, CA113969, AI083907]; Children's Hospital Boston Translational Investigator Service; Korea Healthcare technology RD Project [A080244] FX We thank Dr. James Verbsky and Dr. John Routes for sharing unpublished data with us regarding the case of Rac2 deficiency detected by universal newborn screening. We thank Megan Smith for administrative assistance. The authors are supported by National Institutes of Health (DK062757, CA113969, DAW; AI083907, SYP); Children's Hospital Boston Translational Investigator Service (SYP); Korea Healthcare technology R&D Project (A080244, CK). NR 92 TC 33 Z9 34 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2010 VL 29 IS 3-4 BP 177 EP 187 DI 10.3233/DMA-2010-0738 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 696RF UT WOS:000285458400007 PM 21178276 ER PT J AU Liu, G Cescon, DW Zhai, R Zhou, W Kulke, MH Ma, C Xu, W Su, L Asomaning, K Heist, RS Wain, JC Lynch, TJ Christiani, DC AF Liu, G. Cescon, D. W. Zhai, R. Zhou, W. Kulke, M. H. Ma, C. Xu, W. Su, L. Asomaning, K. Heist, R. S. Wain, J. C. Lynch, T. J. Christiani, D. C. TI p53 Arg72Pro, MDM2 T309G and CCND1 G870A polymorphisms are not associated with susceptibility to esophageal adenocarcinoma SO DISEASES OF THE ESOPHAGUS LA English DT Article DE esophageal adenocarcinoma; molecular epidemiology; p53; risk factors; single nucleotide polymorphism (SNP) ID SINGLE NUCLEOTIDE POLYMORPHISM; MDM2 PROMOTER POLYMORPHISM; CANCER-RISK; GENETIC POLYMORPHISMS; CYCLIN D1; PATHWAY; CARCINOMA; SNP309; XPD AB p53 Arg72Pro, MDM2 T309G, and CCND1 G870A are functional single-nucleotide polymorphisms ( SNPs) in key genes that regulate apoptosis and cell cycle. Variant genotypes of these SNPs have been associated with increased risk and earlier age of onset in some cancers. We investigated the association of these SNPs with susceptibility to esophageal adenocarcinoma in a large, North American case-control study. Three hundred and twelve cases and 454 cancer-free controls recruited in Boston, USA were genotyped for each of the three SNPs, and demographic and clinical data were collected. Genotype frequencies for each of the three SNPs did not deviate from the Hardy-Weinberg equilibrium, and did not differ between cases and controls. Odds ratios ( OR), adjusted for clinical risk factors, for the homozygous variant genotypes were 0.99 (95% confidence interval [CI] 0.57-1.72) for p53 Pro/Pro, 0.81 ( 95% CI 0.52-1.28) for MDM2 G/G, and 0.97 ( 95% CI 0.64-1.49) for CCND1 A/A. The analysis was adequately powered (80%) to detect ORs of 1.37, 1.35, and 1.34 for each SNP, respectively. In contrast to the results of smaller published studies, no association between p53 Arg72Pro, MDM2 T309G, and CCND1 G870A SNPs and susceptibility C1 [Liu, G.; Cescon, D. W.] Univ Toronto, Dept Med, Div Hematol & Med Oncol, Princess Margaret Hosp, Toronto, ON M5S 1A1, Canada. [Liu, G.; Cescon, D. W.] Univ Toronto, Dept Med Biophys, Div Appl Mol Oncol, Princess Margaret Hosp, Toronto, ON M5S 1A1, Canada. [Ma, C.; Xu, W.] Univ Toronto, Princess Margaret Hosp, Biostat Unit, Toronto, ON M5S 1A1, Canada. [Liu, G.; Zhai, R.; Zhou, W.; Su, L.; Asomaning, K.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Div Environm & Occupat Med & Epidemiol, Boston, MA 02115 USA. [Heist, R. S.; Lynch, T. J.; Christiani, D. C.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Kulke, M. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wain, J. C.] Harvard Univ, Sch Med, Dept Surg, Div Thorac Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm Unit, Boston, MA USA. RP Liu, G (reprint author), 610 Univ Ave,Suite 7-124, Toronto, ON M5G 2M9, Canada. EM Geoffrey.Liu@uhn.on.ca RI Liu, Geoffrey/N-4421-2016 FU NIH [R01 CA074386]; Posluns Family Foundation; Alan Brown Chair in Molecular Genomics; FAMRI; CIHR; Doris Duke Charitable Foundation FX This work was supported by NIH R01 CA074386, Posluns Family Foundation, Alan Brown Chair in Molecular Genomics, FAMRI, CIHR and Doris Duke Charitable Foundation. NR 21 TC 25 Z9 27 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2010 VL 23 IS 1 BP 36 EP 39 DI 10.1111/j.1442-2050.2009.00960.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546PA UT WOS:000273821500007 PM 19302219 ER PT J AU Becker, L Huang, Q Mashimo, H AF Becker, L. Huang, Q. Mashimo, H. TI Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett's esophagus and esophageal adenocarcinoma SO DISEASES OF THE ESOPHAGUS LA English DT Article DE Barrett's esophagus; cancer stem cell; dysplasia; esophageal adenocarcinoma; Lgr5 ID PROTEIN-COUPLED RECEPTOR; ACUTE MYELOID-LEUKEMIA; PROSPECTIVE IDENTIFICATION; PANCREATIC-CANCER; TUMOR-GROWTH; DYSPLASIA; P53; PROGRESSION; MUTATIONS; COLON AB P>Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), a recently discovered intestinal stem cell marker, is expressed in premalignant lesions including Barrett's esophagus (BE) and cancers including colon cancer, ovarian cancer, and hepatocellular carcinoma. It was also recently found to be expressed in tumor spheres prepared from colon cancer, suggesting that it will likely serve as a cancer stem cell marker. We sought to examine Lgr5 as a biomarker in BE-associated neoplasia. Using standard immunohistochemistry, we performed immunostaining on 81 esophageal specimens (53 biopsy specimens and 28 surgical resections) representing BE, BE-associated dysplasia, and esophageal adenocarcinoma (EAC). Each immunostain was scored based on intensity of immunostaining and percentage of positive cells. For 24 EAC cases, survival analysis was performed with expression scores and other clinicopathological variables. We found that Lgr5 expression was detected in 70% of BE cases and between 90 and 100% of advanced dysplastic lesions and EAC. The intensity of expression was significantly higher in high-grade dysplasia and EAC than BE. In EAC, high Lgr5 expression scores (>= 5) were associated with worse survival, independent of stage, age, and neoadjuvant/adjuvant therapy (P = 0.03). Our findings suggest that Lgr5 has potential utility as a biomarker for BE-associated dysplasia and EAC. C1 [Becker, L.; Huang, Q.; Mashimo, H.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Becker, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Becker, L.; Huang, Q.; Mashimo, H.] Harvard Univ, Sch Med, Boston, MA USA. RP Mashimo, H (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy,Res 151,Bldg 3,Room 2B104, Boston, MA 02132 USA. EM hmashimo@hms.harvard.edu FU VA Merit Research Award; Beth Israel Deaconess Medical Center [T32 DK 07760] FX Sources of support include VA Merit Research Award and T32 DK 07760 institutional grant through Beth Israel Deaconess Medical Center (Program director: J. Thomas Lamont, MD). NR 57 TC 36 Z9 41 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2010 VL 23 IS 2 BP 168 EP 174 DI 10.1111/j.1442-2050.2009.00979.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 556VT UT WOS:000274622100013 PM 19549212 ER PT J AU Mak, RH Mamon, HJ Ryan, DP Miyamoto, DT Ancukiewicz, M Kobayashi, WK Willett, CG Choi, NC Blaszkowsky, LS Hong, TS AF Mak, R. H. Mamon, H. J. Ryan, D. P. Miyamoto, D. T. Ancukiewicz, M. Kobayashi, W. K. Willett, C. G. Choi, N. C. Blaszkowsky, L. S. Hong, T. S. TI Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older SO DISEASES OF THE ESOPHAGUS LA English DT Article DE chemotherapy; elderly; esophageal cancer; radiation; toxicity ID ELDERLY-PATIENTS; SURGERY; CHEMORADIOTHERAPY; RADIOTHERAPY; THERAPY; COMORBIDITY; CARCINOMA; TRIAL AB P>Randomized trials of chemoradiation for esophageal cancer have included very few patients age >= 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age >= 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity >= grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed. C1 [Ancukiewicz, M.; Kobayashi, W. K.; Choi, N. C.; Hong, T. S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mak, R. H.; Miyamoto, D. T.] Dana Farber Brigham & Womens Canc Ctr, Harvard Radiat Oncol Program, Boston, MA USA. [Mamon, H. J.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Ryan, D. P.; Blaszkowsky, L. S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Willett, C. G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM tshong1@partners.org NR 19 TC 16 Z9 18 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2010 VL 23 IS 4 BP 316 EP 323 DI 10.1111/j.1442-2050.2009.01014.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 602AA UT WOS:000278109300007 PM 19788436 ER PT S AU Giaccia, AJ Schipani, E AF Giaccia, Amato J. Schipani, Ernestina BE Simon, MC TI Role of Carcinoma-Associated Fibroblasts and Hypoxia in Tumor Progression SO DIVERSE EFFECTS OF HYPOXIA ON TUMOR PROGRESSION SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID MESENCHYMAL STEM-CELLS; UNFOLDED PROTEIN RESPONSE; INDUCIBLE FACTOR-I; BONE-MARROW; STROMAL CELLS; CIRCULATING FIBROCYTES; GENE-EXPRESSION; PROLYL HYDROXYLATION; CANCER-THERAPY; LYSYL OXIDASE AB In recent years, a variety of experimental evidence has convincingly shown that progression of malignant tumors does not depend exclusively on cell-autonomous properties of the cancer cells, but can also be influenced by the tumor stroma. The concept that cancer cells are subjected to microenvironmental control has thus emerged as an important chapter in cancer biology. Recent findings have suggested an important role, in particular, for macrophages, endothelial cells, and cancer-associated fibroblasts (CAFs) in tumor growth and progression. Numerous lines of evidence indicate that the bone marrow is the source, at least in part, of these cells. This chapter summarizes our current knowledge of how bone marrow contributes to the tumor stroma, with particular emphasis on CAFs. The potential role of hypoxia in modulating the differentiation and activity of CAFs, and the therapeutical implications of targeting CAFs for anticancer therapy are discussed. C1 [Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Div Canc & Radiat Biol, Sch Med, Stanford, CA 94305 USA. [Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02114 USA. RP Giaccia, AJ (reprint author), Stanford Univ, Dept Radiat Oncol, Div Canc & Radiat Biol, Sch Med, Stanford, CA 94305 USA. EM giaccia@stanford.edu NR 113 TC 14 Z9 15 U1 3 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-13328-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 345 BP 31 EP 45 DI 10.1007/82_2010_73 D2 10.1007/978-3-642-13329-9 PG 15 WC Immunology; Microbiology SC Immunology; Microbiology GA BQY47 UT WOS:000282105100003 PM 20517716 ER PT B AU Shen, HC Taplin, ME Balk, SP AF Shen, Howard C. Taplin, Mary-Ellen Balk, Steven P. BE Figg, WD Chau, CH Small, EJ TI Androgen Receptor Antagonists SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Prostate cancer; Androgen receptor; Steroid; Steroid receptor; Testosterone; Dihydrotestosterone; Antagonist; Bicalutamide; Flutamide; Nilutamide ID ADVANCED PROSTATE-CANCER; LIGAND-BINDING DOMAIN; ANTIANDROGEN WITHDRAWAL SYNDROME; BONE-MINERAL DENSITY; NUCLEAR RECEPTOR; N-COR; STRUCTURAL BASIS; BICALUTAMIDE MONOTHERAPY; FLUTAMIDE WITHDRAWAL; NONSTEROIDAL LIGANDS AB Androgen receptor (AR) antagonists used clinically include steroidal (cyproterone acetate) and nonsteroidal antagonists (bicalutamide, flutamide, and nilutamide), with the latter nonsteroidal compounds being the only ones in general use in the United States. AR antagonists are used as single agents or in conjunction with surgical or medical castration (combined androgen blockade) for the initial systemic treatment of prostate cancer (CaP). AR antagonists are somewhat less effective than castration but may be preferred in some patients due to potentially fewer side effects. Combined androgen blockade is more effective than castration alone based on rapid declines in serum prostate-specific antigen (PSA) levels and the lower nadir PSA levels, but this translates into only a very small survival advantage. Patients treated with single or combined therapies invariably relapse with CaP that has been termed castration-resistant prostate cancer (CRPC). Significantly, the AR is expressed at high levels and is transcriptionally active in most cases of CRPC, and a subset of these CRPC patients respond to AR antagonist treatment. However, these responses are generally partial and transient. Molecular mechanisms that contribute to AR reactivation in CRPC and impair the activity of AR antagonists are described in this chapter. Understanding these mechanisms is critical for the development of strategies to overcome resistance and for the generation of more effective AR antagonists. C1 [Balk, Steven P.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shen, Howard C.] Harvard Univ, Sch Med, Dept Med, Bth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Taplin, Mary-Ellen] Harvard Univ, Sch Med, Lank Ctr Genitourinary, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Balk, SP (reprint author), Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM sbalk@bidmc.harvard.edu NR 94 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 71 EP 81 DI 10.1007/978-1-60327-829-4_6 D2 10.1007/978-1-60327-829-4 PG 11 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600006 ER PT B AU Rosenberg, J AF Rosenberg, Jonathan BE Figg, WD Chau, CH Small, EJ TI Beyond Docetaxel: Emerging Agents in the Treatment of Advanced Prostate Cancer SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE mTOR inhibition; Novel therapeutics; Histone deacetylation; Insulin-like growth factor 1; HSP90 ID GROWTH-FACTOR-I; PHASE-II; RECEPTOR EXPRESSION; SOMATOSTATIN ANALOG; DEPSIPEPTIDE FK228; AKT; CELLS; PROGRESSION; HORMONE; TRIAL AB Increased understanding of the biology of advanced prostate cancer has yielded multiple targets that are worthy of evaluation. Multiple signaling pathways appear to play a role in the maintenance and progression of the malignant phenotype. These pathways, such as PI3 kinase/Akt pathway, the mTOR pathway, the Hsp90 pathway, and the insulin-like growth factor 1 pathway, are currently being investigated in clinical trials. Other fundamental processes such as histone deacetylation are also involved in prostate cancer progression. Testing agents targeting these pathways will provide crucial information regarding whether inhibition will yield clinical benefit for prostate cancer patients. C1 Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Rosenberg, J (reprint author), Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Boston, MA USA. EM jonathan_rosenberg@dfci.harvard.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 147 EP 151 DI 10.1007/978-1-60327-829-4_13 D2 10.1007/978-1-60327-829-4 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600013 ER PT B AU Brick, A Niu, JY Huang, JT Oh, WK AF Brick, Ashley Niu, Junyang Huang, Jiaoti Oh, William K. BE Figg, WD Chau, CH Small, EJ TI Platinum Agents in Prostate Cancer SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Carboplatin; Neuroendocrine; Castration-resistant; Chemotherapy ID PHASE-II TRIAL; ANDROGEN-INDEPENDENT GROWTH; CIRCULATING CHROMOGRANIN-A; SMALL-CELL CARCINOMA; NEUROENDOCRINE DIFFERENTIATION; ESTRAMUSTINE PHOSPHATE; ONCOLOGY-GROUP; RECEPTOR EXPRESSION; PLUS PREDNISONE; CARBOPLATIN AB The standard first-line treatment for metastatic castration-resistant prostate cancer (CRPC) is docetaxel chemotherapy. Platinum drugs, including cisplatin and carboplatin, when used as single agents and in combinations, have shown a moderate response in metastatic CRPC patients, as both first- and second-line treatment. Furthermore, the relationship between neuroendocrine differentiation and castration-resistant disease progression suggests that there may be a possible role for platinum agents. Newer platinum analogs, including picoplatin, oxaliplatin, and satraplatin have been recently studied in CRPC. Though a Phase III trial demonstrated a progression-free survival benefit favoring satraplatin plus prednisone versus prednisone alone, no overall survival benefit was demonstrated in the second-line setting. Further trials will be needed to demonstrate a clear role for platinum agents in CRPC. C1 [Oh, William K.] Dana Farber Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. [Brick, Ashley] Dana Farber Canc Inst, Boston, MA 02115 USA. [Niu, Junyang] Anhui Prov Hosp, Dept Pathol, Hefei, Anhui, Peoples R China. [Huang, Jiaoti] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA. EM william.oh@mssm.edu NR 74 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 153 EP 161 DI 10.1007/978-1-60327-829-4_14 D2 10.1007/978-1-60327-829-4 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600014 ER PT B AU Elfiky, AA Kelly, WK AF Elfiky, Aymen A. Kelly, William Kevin BE Figg, WD Chau, CH Small, EJ TI Bevacizumab in Advanced Prostate Cancer SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Angiogenesis; Prostate cancer; Drugs; Bevacizumab ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; TUMOR ANGIOGENESIS; PHASE-II; ANTIANGIOGENIC THERAPY; BREAST-CARCINOMA; SOLID TUMORS; IN-VIVO; METASTASIS; DOCETAXEL AB Prostate cancer is the leading non-cutaneous malignancy in American men. Only the combination of docetaxel and prednisone has been shown to improve survival in patients with metastatic castration-resistant prostate cancer. Typically responses to docetaxel in patients with castrate-resistant disease are modest and additional therapies are needed. Angiogenesis has been shown to be a prerequisite event for tumor growth and metastasis in prostate cancer. Several strategies have been used to target angiogenesis in prostate cancer, which include blocking of pro-angiogenic factors via monoclonal antibodies or small-molecule inhibitors that target downstream signaling pathways for angiogenesis, direct inhibition of endothelial cells, or targeting other receptors involved in cell adhesion, proliferation, and survival. The following sections will discuss further the rationale for targeting the angiogenesis pathway in prostate cancer and the emergence of bevacizumab as a promising agent for the treatment of prostate cancer. C1 [Kelly, William Kevin] Thomas Jefferson Univ, Dept Med Oncol, Philadelphia, PA 19107 USA. [Kelly, William Kevin] Thomas Jefferson Univ, Jefferson Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Elfiky, Aymen A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA. RP Kelly, WK (reprint author), Thomas Jefferson Univ, Dept Med Oncol, Suite 314, Philadelphia, PA 19107 USA. EM wm.kevin.kelly@jefferson.edu NR 45 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 207 EP 214 DI 10.1007/978-1-60327-829-4_18 D2 10.1007/978-1-60327-829-4 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600018 ER PT B AU Saylor, PJ Smith, MR AF Saylor, Philip J. Smith, Matthew R. BE Figg, WD Chau, CH Small, EJ TI Bisphosphonates for Prevention and Treatment of Bone Metastases SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Prostate cancer; Bone metastases; Osteoclast; Bisphosphonate; Skeletal-related events; Denosumab; Odanacatib ID ANDROGEN-DEPRIVATION THERAPY; NONMETASTATIC PROSTATE-CANCER; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ORAL SODIUM CLODRONATE; ZOLEDRONIC ACID; DOUBLE-BLIND; MULTIPLE-MYELOMA; MINERAL DENSITY; SKELETAL METASTASES AB Most men with advanced prostate cancer develop bone metastases. The most common sites of bone metastases from prostate cancer are the spine, pelvis, and ribs. Though they typically have a sclerotic or osteoblastic appearance when imaged, these metastases feature excess activity by both osteoblasts and osteoclasts. Pathologic osteoclast activation is associated with skeletal complications, disease progression, and death. The clinical burden of bone metastases is high as they commonly present with pain but can also present with spinal cord compression, fractures, and myelophthisis. Zoledronic acid is a potent intravenous bisphosphonate. In men with castration-resistant prostate cancer and bone metastases, zoledronic acid decreases the risk of disease-related skeletal complications. There is limited information about the optimal frequency and duration of therapy for men with castration-resistant disease and bone metastases. The role of zoledronic acid and other bisphosphonates in androgen-sensitive disease or for prevention of bone metastases is unknown. Further clinical trials are needed to establish its optimal frequency, dose, and duration of therapy. Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor-kappa-B ligand (RANKL). Denosumab is currently under investigation in three major prostate cancer trials that are designed to evaluate its ability to prevent fractures, bone metastases, and disease-related skeletal events. C1 [Smith, Matthew R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol,Dept Med,Canc Ctr, Boston, MA 02115 USA. RP Saylor, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol,Dept Med,Canc Ctr, Boston, MA 02115 USA. EM psaylor@partners.org NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 267 EP 275 DI 10.1007/978-1-60327-829-4_24 D2 10.1007/978-1-60327-829-4 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600024 ER PT J AU Fintelmann, RE Naseri, A AF Fintelmann, Robert E. Naseri, Ayman TI Prophylaxis of Postoperative Endophthalmitis Following Cataract Surgery Current Status and Future Directions SO DRUGS LA English DT Review ID VIGAMOX(R) MOXIFLOXACIN 0.5-PERCENT; ACUTE-ONSET ENDOPHTHALMITIS; NATIONAL PROSPECTIVE SURVEY; OCULAR SURFACE FLUID; HUMAN AQUEOUS-HUMOR; PREVENTING ENDOPHTHALMITIS; RISK-FACTORS; INTRACAMERAL MOXIFLOXACIN; POVIDONE-IODINE; VISUAL OUTCOMES AB Endophthalmitis is an uncommon but potentially devastating intraocular infection that can occur after routine cataract surgery. Although a broad spectrum of organisms have been shown to cause acute postoperative endophthalmitis, most cases are caused by Gram-positive bacteria, which may be introduced at the time of surgery from colonization of adjacent conjunctiva or eyelid skin. Risk factors for the development of endophthalmitis following cataract surgery include patient age, intraoperative surgical complications and poor wound construction. There are several antibacterial strategies employed to prevent postoperative endophthalmitis, with topical, intracameral and subconjunctival delivery being the most common. Worldwide, there seems to be significant regional variance in the type and method of prophylactic antibacterial regimens; for example, topical fluoroquinolones are commonly used in the US, while intracameral cephalosporins are employed widely in Europe. The optimal antibacterial strategy for the prevention of endophthalmitis should be safe, inexpensive and broad in microbiological activity spectrum, while not requiring patient compliance for its effectiveness. C1 [Naseri, Ayman] San Francisco Vet Adm Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. [Fintelmann, Robert E.; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Fintelmann, Robert E.; Naseri, Ayman] Univ Calif San Francisco, Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA 94143 USA. RP Naseri, A (reprint author), San Francisco Vet Adm Med Ctr, Dept Ophthalmol, 4150 Clement St, San Francisco, CA 94121 USA. EM ayman.naseri@va.gov NR 78 TC 14 Z9 18 U1 0 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2010 VL 70 IS 11 BP 1395 EP 1409 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 640RC UT WOS:000281068600005 PM 20614947 ER PT J AU Albert, SM Colombi, A Hanlon, J AF Albert, Steven M. Colombi, Alberto Hanlon, Joseph TI Potentially Inappropriate Medications and Risk of Hospitalization in Retirees Analysis of a US Retiree Health Claims Database SO DRUGS & AGING LA English DT Article ID OLDER-PEOPLE; EXPLICIT CRITERIA; CONSENSUS PANEL; BEERS CRITERIA; ELDERLY-PEOPLE; QUALITY; DRUGS AB Background and Objective: One important health outcome of inappropriate medication use in the elderly is risk of hospitalization. We examined this relationship over 3 years in a retiree health claims database to determine the strength of this association using alternative definitions of potentially inappropriate medications. Methods: Prescription and hospitalization claims for US retirees from a single large corporation were examined over the 3-year period, 2003-5. Purging the database of non-employees (dependents, spouses), employees aged <65 years (who were not Medicare-eligible) and retirees not covered for the full 3-year period left a sample of 7459 retirees. Respondents' medications were categorized according to two lists of 'drugs to avoid': Beers (2003 update) and the National Committee for Quality Assurance (NCQA). Logistic regression models were developed to examine risk of hospitalization in 2005 relative to use of potentially inappropriate medications across different periods of follow-up. Results: Retirees taking one or more of the potentially inappropriate medications on the Beers or NCQA lists were 1.8-1.9 times more likely to have a hospital admission in models that adjusted for age, gender, number of prescriptions overall and aggregate disease severity. Risk of hospitalization increased in a dose-response relationship according to number of potentially inappropriate medications. Conclusion: Consistency in the strength of the association between 'drugs to avoid' and hospital admission across different definitions of inappropriate medication use suggests the finding is robust. Findings from the retiree cohort provide further evidence for the inappropriateness of these medications among the elderly. C1 [Albert, Steven M.] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Colombi, Alberto] PPG Ind Inc, Pittsburgh, PA USA. [Hanlon, Joseph] Univ Pittsburgh, Dept Geriatr Med, Sch Med, Pittsburgh, PA 15261 USA. [Hanlon, Joseph] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15261 USA. [Hanlon, Joseph] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Geriatr Res Educ, Pittsburgh, PA USA. [Hanlon, Joseph] Vet Affairs Pittsburgh Healthcare Syst, Ctr Clin, Pittsburgh, PA USA. RP Albert, SM (reprint author), Univ Pittsburgh, Dept Behav & Community Hlth Sci, Grad Sch Publ Hlth, A211 Crabtree Hall,120 DeSoto Ave, Pittsburgh, PA 15261 USA. EM smalbert@pitt.edu OI Albert, Steven/0000-0001-6786-9956 FU National Institute of Aging [R01 AG027017, P30 AG024827]; VA Health Services Research [IIR-06-062] FX Chongji Wei assisted with data pre-processing. PPG Industries, Inc., provided retiree data through Healthcare Business of Thomson Reuters.; This study was supported in part by National Institute of Aging grants R01 AG027017 and P30 AG024827 and VA Health Services Research grant IIR-06-062.; The authors have no conflicts of interest that are directly relevant to the content of this study. NR 23 TC 41 Z9 41 U1 0 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PY 2010 VL 27 IS 5 BP 407 EP 415 PG 9 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 605NX UT WOS:000278355400005 PM 20450238 ER PT J AU Richardson, DM Bain, KT Diamond, JJ Novielli, KD Lee, SP Goldfarb, NI AF Richardson, Diane M. Bain, Kevin T. Diamond, James J. Novielli, Karen D. Lee, Seina P. Goldfarb, Neil I. TI Effectiveness of Guideline-Recommended Cardiac Drugs for Reducing Mortality in the Elderly Medicare Heart Failure Population A Retrospective, Survey-Weighted, Cohort Analysis SO DRUGS & AGING LA English DT Article ID VENTRICULAR EJECTION FRACTIONS; OBSTRUCTIVE PULMONARY-DISEASE; CONVERTING ENZYME-INHIBITORS; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; ACE-INHIBITORS; OLDER PATIENTS; CO-MORBIDITY; SURVIVAL; ENALAPRIL AB Background: Heart failure (HF) management guidelines recommend that most patients with HF receive an ACE inhibitor or an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) and a beta-blocker (beta-adrenoceptor antagonist), collectively referred to as 'cardiac drugs', based on results from randomized controlled trials showing that these drugs reduce mortality. However, the results of randomized controlled trials may not be generalizable to the population most likely (i.e. the elderly) to receive these drugs in clinical practice. Objective: To determine the effectiveness of cardiac drugs for reducing mortality in the elderly Medicare HF population. Study Design: Retrospective, survey-weighted, cohort analysis of the 2002 Medicare Current Beneficiary Survey Cost and Use files. Participants: 12 697 beneficiaries, of whom 1062 had a diagnosis of HF and 577 were eligible to receive cardiac drugs. Measurements: Association between mortality and cardiac drugs, adjusted for sociodemographics, co-morbidity and propensity to receive cardiac drugs. Results: The mortality rate among the 577 eligible beneficiaries with HF was 9.7%. The mortality rate for those receiving an ACE inhibitor or ARB alone, a beta-blocker alone, or both an ACE inhibitor or ARB and a beta-blocker, was 6.1%, 5.9% and 5.3%, respectively; in the absence of any of the three cardiac drugs, the mortality rate was 20.0% (p < 0.0001). In multivariable analyses, ARB mortality rates remained significantly lower for beneficiaries receiving an ACE inhibitor or ARB alone (odds ratio [OR] 0.24; 95% CI 0.11, 0.50), a beta-blocker alone (OR 0.17; 95% CI 0.07, 0.41), or both an ACE inhibitor or ARB and a beta-blocker (OR 0.24; 95% CI 0.10, 0.55) compared with patients who did not receive any of the three cardiac drugs. Conclusions: Use of guideline-recommended cardiac drugs is associated with reduced mortality in the elderly Medicare HF population. Providing evidence of the benefit of cardiac drugs among the elderly with HF will become increasingly important as the size of the Medicare population grows. C1 [Goldfarb, Neil I.] Thomas Jefferson Univ, Sch Populat Hlth, Philadelphia, PA 19107 USA. [Richardson, Diane M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bain, Kevin T.] excelleRx Inc, Philadelphia, PA USA. [Diamond, James J.; Novielli, Karen D.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Family & Community Med, Philadelphia, PA 19107 USA. [Lee, Seina P.] Johnson & Johnson Pharmaceut Serv, Horsham, PA USA. RP Goldfarb, NI (reprint author), Thomas Jefferson Univ, Sch Populat Hlth, 1015 Walnut St,Suite 115, Philadelphia, PA 19107 USA. EM neil.goldfarb@jefferson.edu FU excelleRx Inc. FX This research was supported by a grant from excelleRx Inc., an Omnicare company. Kevin T. Bain is an employee of excelleRx Inc. and has received honoraria from Eisai for consultancy services. Seina P. Lee is an employee of Johnson & Johnson Pharmaceutical Services. Some of these findings were presented at the International Society for Pharmacoeconomics and Outcomes Research 13th Annual International Meeting, Toronto, Ontario, Canada, 3-7 May 2008. NR 41 TC 6 Z9 6 U1 0 U2 1 PU S INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2010 VL 27 IS 10 BP 845 EP 854 PG 10 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 672VA UT WOS:000283613800007 PM 20883064 ER PT J AU Stedman, J Roccara, A Leleu, X Ghobrial, IM AF Stedman, J. Roccara, A. Leleu, X. Ghobrial, I. M. TI NEW THERAPEUTIC APPROACHES FOR WALDENSTROM'S MACROGLOBULINEMIA SO DRUGS OF THE FUTURE LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; EXTENDED RITUXIMAB THERAPY; COOPERATIVE-ONCOLOGY-GROUP; WAIDENSTROMS MACROGLOBULINEMIA; PROGNOSTIC-FACTORS; PLUS RITUXIMAB; FLUDARABINE THERAPY; MULTIPLE-MYELOMA; DEXAMETHASONE AB Waldenstrom's macro globulinemia (WM) is a B-cell disorder characterized by the infiltration of the bone marrow with lymphoplasmacytic cells, as well as detection of an immuno globulin M (IgM) monoclonal gammopathy in the serum. WM is an incurable disease, with an overall median survival of only 5-6 years. First-line therapy of WM has been based on single-agent or combination therapy with alkylating agents (e.g., chlorambucil or cyclophosphamide), nucleoside analogues (cladribine or fludarabine phosphate) and the monoclonal antibody rituximab. Novel therapeutic agents that have demonstrated efficacy in WM include thalidomide, lenalidomide, bortezomib, everolimus, atacicept and perifosine. The range of the overall response rate to these agents is 25-80%. Ongoing and planned clinical trials include those using protein kinase C (PKC) inhibitors such as enzastaurin hydrochloride, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as panobinostat, humanized CD20 antibodies such as ofatumumab and additional alkylating agents such as bendamustine hydrochloride. In comparison with traditional chemotherapeutic agents, these agents may in the future lead to greater responses, longer remissions and better quality of life for patients with WM. C1 [Stedman, J.; Roccara, A.; Ghobrial, I. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, X.] Ctr Hosp Reg & Univ Lille, Hop Huriez, Serv Malad Sang, F-59037 Lille, France. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu OI Stedman, Jennifer/0000-0002-9850-0091 FU NCI NIH HHS [R21 CA126119, R21 CA126119-02] NR 53 TC 1 Z9 1 U1 1 U2 1 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JAN PY 2010 VL 35 IS 1 BP 53 EP 58 DI 10.1358/dof.2010.35.1.1410182 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 578UL UT WOS:000276321400007 PM 21869855 ER PT B AU Bonmassar, G Mullinger, KJ AF Bonmassar, Giorgio Mullinger, Karen J. BE Mulert, C Lemieux, L TI Specific Issues Related to EEG-fMRI at B-0 > 3 T SO EEG-FMRI: PHYSIOLOGICAL BASIS, TECHNIQUE AND APPLICATIONS LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; ABSORPTION RATE; HIGH-FIELD; DIELECTRIC-PROPERTIES; BIOLOGICAL TISSUES; FUNCTIONAL MRI; 7 TESLA; SAFETY; ELECTRODES; SYSTEMS C1 [Bonmassar, Giorgio] Massachusetts Gen Hosp, AbiLab, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mullinger, Karen J.] Univ Nottingham, Sch Phys & Astron, Sir Peter Mansfield Magnet Resonance Ctr, Nottingham NG7 2RD, England. RP Bonmassar, G (reprint author), Massachusetts Gen Hosp, AbiLab, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM giorgio@nmr.mgh.harvard.edu NR 76 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-87918-3 PY 2010 BP 201 EP 220 DI 10.1007/978-3-540-87919-0_11 D2 10.1007/978-3-540-87919-0 PG 20 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BML87 UT WOS:000272754600011 ER PT S AU Connell, NT Abramson, JS AF Connell, Nathan T. Abramson, Jeremy S. BE Scheld, WM Grayson, ML Hughes, JM TI Human Immunodeficiency Virus-Associated Malignancies SO EMERGING INFECTIONS 9 SE Emerging Infections Series LA English DT Article; Book Chapter ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; NON-HODGKINS-LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; SQUAMOUS INTRAEPITHELIAL LESIONS; PAPILLOMAVIRUS-ASSOCIATED CANCERS; PEGYLATED-LIPOSOMAL DOXORUBICIN; PROTEIN-COUPLED RECEPTOR; HIV-INFECTED INDIVIDUALS C1 [Connell, Nathan T.] Brown Univ, Alpert Med Sch, Dept Med, Providence, RI 02903 USA. [Abramson, Jeremy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Connell, NT (reprint author), Brown Univ, Alpert Med Sch, Dept Med, Providence, RI 02903 USA. NR 103 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA SN 1542-4502 BN 978-1-55581-525-7 J9 EMERG INFECT JI Emerg. Infect. PY 2010 VL 9 BP 169 EP 183 PG 15 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BTW84 UT WOS:000288320400010 ER PT B AU Verfaellie, M AF Verfaellie, M. BE Koob, GF LeMoal, M Thompson, RF TI Amnesia SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 1: A-G LA English DT Article; Book Chapter ID MEMORY C1 [Verfaellie, M.] VA Boston Healthcare Syst, Boston, MA USA. [Verfaellie, M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Boston, MA USA. RI koob, george/P-8791-2016 NR 14 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 BP 41 EP 46 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WW UT WOS:000335045400008 ER PT B AU Handforth, A AF Handforth, Adrian BE Kompoliti, K Metman, LV TI Harmaline Tremor Model SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID INFERIOR OLIVARY NEURONS; SYSTEM; RATS C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Handforth, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 9 EP 12 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600005 ER PT B AU Hu, SC Kim, HM Samii, A AF Hu, S. C. Kim, H. M. Samii, A. BE Kompoliti, K Metman, LV TI Manganese SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID INDUCED PARKINSONISM; NEUROTOXICITY; SCIENCE C1 [Hu, S. C.; Kim, H. M.; Samii, A.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Kim, H. M.; Samii, A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Hu, SC (reprint author), Univ Washington, Sch Med, Seattle, WA 98195 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 155 EP 159 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600050 ER PT B AU Walker, RH AF Walker, R. H. BE Kompoliti, K Metman, LV TI McLeod Syndrome SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID NEUROACANTHOCYTOSIS C1 [Walker, R. H.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Walker, R. H.] Mt Sinai Sch Med, New York, NY USA. RP Walker, RH (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 162 EP 164 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600052 ER PT B AU Walker, RH AF Walker, R. H. BE Kompoliti, K Metman, LV TI Neuroacanthocytosis Syndromes SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter C1 [Walker, R. H.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Walker, R. H.] Mt Sinai Sch Med, Nyc, NY USA. RP Walker, RH (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 259 EP 261 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600083 ER PT B AU Chasson, GS Wilhelm, S AF Chasson, G. S. Wilhelm, S. BE Kompoliti, K Metman, LV TI Obsessive-Compulsive Disorder SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter C1 [Chasson, G. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chasson, GS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 319 EP 323 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600099 ER PT B AU Walker, RH AF Walker, R. H. BE Kompoliti, K Metman, LV TI Torsin A SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 3: Q-Z LA English DT Article; Book Chapter ID DYSTONIA C1 [Walker, R. H.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Walker, R. H.] Mt Sinai Sch Med, New York, NY USA. RP Walker, RH (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 243 EP 247 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XF UT WOS:000335076900077 ER PT J AU Ribeiro, MO Bianco, SDC Kaneshige, M Schultz, JJ Cheng, SY Bianco, AC Brent, GA AF Ribeiro, Miriam O. Bianco, Suzy D. C. Kaneshige, Masahiro Schultz, James J. Cheng, Sheue-yann Bianco, Antonio C. Brent, Gregory A. TI Expression of Uncoupling Protein 1 in Mouse Brown Adipose Tissue Is Thyroid Hormone Receptor-beta Isoform Specific and Required for Adaptive Thermogenesis SO ENDOCRINOLOGY LA English DT Article ID DIET-INDUCED THERMOGENESIS; IODOTHYRONINE DEIODINASES; BODY-TEMPERATURE; RESPONSE ELEMENT; GENE-EXPRESSION; MICE; TRIIODOTHYRONINE; MUTANT; CHOLESTEROL; ACTIVATION AB Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T-3, and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor-beta (TR beta) isoform-selective agonist demonstrated that after TR-beta stimulation alone, adaptive thermogenesis was markedly impaired, although UCP-1 expression in BAT was normal. We used mice with a dominant-negative TR beta PV mutation (frameshift mutation in resistance to thyroid hormone patient PV) to determine the role of TR beta in adaptive thermogenesis and UCP1 expression. Wild-type and PV mutant mice were made hypothyroid and replaced with T3 (7ng/g.d) for 10 d to produce similar serum thyroid hormone concentration in the wild-type and mutant mice. The thermogenic response of interscapular BAT, as determined by heat production during iv infusions of norepinephrine, was reduced in PV beta heterozygous and homozygous mutant mice. The level of UCP1, the key thermogenic protein in BAT, was progressively reduced in PV beta(-/-) and PV beta(-/-) mutant mice. Brown adipocytes isolated from PV mutant mice had some reduction in cAMP and glycerol production in response to adrenergic stimulation. Defective adaptive thermogenesis in TR beta PV mutant mice is due to reduced UCP1 expression and reduced adrenergic responsiveness. TR beta mediates T-3 regulation of UCP1 in BAT and is required for adaptive thermogenesis. (Endocrinology 151: 432-440, 2010) C1 [Brent, Gregory A.] Univ Calif Los Angeles, Mol Endocrinol Lab, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Ribeiro, Miriam O.] Univ Presbiteriana Mackenzie, Curso Ciencias Biol, Curso Ciencias Biol & Saude, BR-01301903 Sao Paulo, Brazil. [Bianco, Antonio C.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA. [Bianco, Suzy D. C.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Kaneshige, Masahiro; Cheng, Sheue-yann] NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, Mol Endocrinol Lab, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu RI Bianco, Suzy/E-8892-2010; Bianco, Antonio/A-4965-2008; Ribeiro, Miriam/A-9367-2013; Ribeiro, Miriam/B-6085-2015; Ribeiro, Miriam/C-6364-2016 OI Bianco, Suzy/0000-0003-3794-9853; Bianco, Antonio/0000-0001-7737-6813; Ribeiro, Miriam/0000-0002-7870-9701; FU NIH [RO1 DK43714, RO1 DK65055]; Coordenacao de Aperfeioamento de Pessoal de Nivel Superior (CAPES) in Brazil; Veterans Affairs Medical Research Funds FX This work was supported by NIH RO1 DK43714 (G.A.B.), a fellowship from the Coordenacao de Aperfeioamento de Pessoal de Nivel Superior (CAPES) in Brazil (M.O.R.), Veterans Affairs Medical Research Funds (G.A.B.), and NIH RO1 DK65055 (A.C.B.). NR 51 TC 48 Z9 51 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2010 VL 151 IS 1 BP 432 EP 440 DI 10.1210/en.2009-0667 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 535NT UT WOS:000272977700047 PM 19906816 ER PT B AU DiMaio, CJ Brugge, W AF DiMaio, Christopher J. Brugge, William BE Shami, VM Kahaleh, M TI Fine Needle Injection Therapy SO ENDOSCOPIC ULTRASOUND-BOOK SE Clinical Gastroenterology LA English DT Article; Book Chapter DE EUS-guided fine needle injection; Therapeutic EUS; EUS-guided pancreatic cyst ablation; EUS-guided fiducial placement ID INTENSITY FOCUSED ULTRASOUND; PERCUTANEOUS ETHANOL INJECTION; MIXED LYMPHOCYTE CULTURE; UNRESECTABLE PANCREATIC-CARCINOMA; GUIDED FIDUCIAL PLACEMENT; TERM-FOLLOW-UP; PHASE-I TRIAL; REPLICATION-SELECTIVE ADENOVIRUS; BIODEGRADABLE BLOCK-COPOLYMERS; PAPILLARY MUCINOUS NEOPLASMS AB Endoscopic ultrasound (EUS) has revolutionized many of the current diagnostic and treatment algorithms for patients with neoplastic lesions. The power of EUS is that it is a minimally invasive modality with the ability to provide real-time, high resolution imaging, in close proximity to organs, thus allowing for image-guided intervention. EUS allows us to utilize novel therapies by a minimally invasive approach to lesions that have traditionally required more invasive (i.e., surgical) or high risk (i.e., percutanous) routes. This paper discusses the invaluable role of EUS-guided fine-needle injection (EUS-FNI) therapy. C1 [DiMaio, Christopher J.; Brugge, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP DiMaio, CJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 133 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-479-1 J9 CLIN GASTROENT-SER PY 2010 BP 443 EP 474 DI 10.1007/978-1-60327-480-7_19 D2 10.1007/978-1-60327-480-7 PG 32 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA BRG26 UT WOS:000282668200019 ER PT S AU Moskowitz, SM Ernst, RK AF Moskowitz, Samuel M. Ernst, Robert K. BE Wang, X Quinn, PJ TI The Role of Pseudomonas Lipopolysaccharide in Cystic Fibrosis Airway Infection SO ENDOTOXINS: STRUCTURE, FUNCTION AND RECOGNITION SE Subcellular Biochemistry LA English DT Article; Book Chapter DE Pseudomonas aeruginosa; Cystic fibrosis; Lipopolysaccharide; Lipid A; Chronic infection; Antibiotic resistance; Innate immunity; inflammation ID CATIONIC ANTIMICROBIAL PEPTIDES; 2-COMPONENT REGULATORY SYSTEM; TOLL-LIKE RECEPTOR-4; LIPID-A; SALMONELLA-TYPHIMURIUM; AERUGINOSA INFECTION; BACTERIAL BIOFILMS; LUNG-DISEASE; POLYMYXIN-B; PHOP-PHOQ AB Pseudomonas aeruginosa (PA) is a ubiquitous environmental Gram-negative bacterium found in soil and water. This opportunistic pathogen can cause infections in individuals with impaired phagocytic function, such as those with burns, exposure to chemotherapy, or cystic fibrosis (CF). PA infects the lungs of most individuals with CF, and is associated with severe progressive pulmonary disease that is the major cause of premature death in this disorder. The specific adaptations of PA to the CF airway responsible for bacterial persistence and antibiotic tolerance are not completely understood but may include increased alginate production (i.e., mucoid phenotype), biofilm formation, and specific lipid A modifications. During adaptation to the CF airway, PA synthesizes a variety of lipid A structures that alter host innate immune responses and promote bacterial persistence and chronic infection. The synthesis of specific lipid A structures is attributable to bacterial enzymes that: (1) remove the 3OH-C10:0 acyl chain from the 3-position (PagL); (2) add a C 16:0 acyl chain to the 3OH-C10:0 chain at the 3'-position (PagP); (3) add C12:0 and 2OH-C12:0 acyl chains to the 3OH-C12:0 chains at the 2- and 2'-positions (HtrB and LpxO); and (4) add aminoarabinose to phosphate groups at the 1- and 4'-positions (PmrH, PmrF, Pmrl, Pmr.1, PmrK, and PmrE). These lipid A modifications represent an essential aspect of PA adaptation to the CF airway. C1 [Ernst, Robert K.] Univ Maryland, Dept Microbial Pathogenesis, Sch Dent, Baltimore, MD 21201 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Simches Res Ctr, Boston, MA 02114 USA. RP Ernst, RK (reprint author), Univ Maryland, Dept Microbial Pathogenesis, Sch Dent, 650 W Baltimore St,8 South, Baltimore, MD 21201 USA. EM rkernst@umaryland.edu FU NHLBI NIH HHS [K08 HL067903-05, K08 HL067903, K08 HL067903-01, K08 HL067903-02, K08 HL067903-03, K08 HL067903-04]; NIAID NIH HHS [R01 AI047938-10, R01 AI067653, R01 AI067653-03, R01 AI067653-02, R01AI047938, R01AI067653, R01 AI067653-01A2, R01 AI047938-09, R01 AI047938-07, R01 AI047938-06A1, R01 AI047938-08, R01 AI067653-04, R01 AI047938] NR 42 TC 25 Z9 25 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0306-0225 BN 978-90-481-9077-5 J9 SUBCELL BIOCHEM JI Subcell. Biochem. PY 2010 VL 53 BP 241 EP 253 DI 10.1007/978-90-481-9078-2_11 D2 10.1007/978-90-481-9078-2 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BPV78 UT WOS:000280111400011 PM 20593270 ER PT S AU Thibodeau-Beganny, S Maeder, ML Joung, JK AF Thibodeau-Beganny, Stacey Maeder, Morgan L. Joung, J. Keith BE Mackay, JP Segal, DJ TI Engineering Single Cys2His2 Zinc Finger Domains Using a Bacterial Cell-Based Two-Hybrid Selection System SO ENGINEERED ZINC FINGER PROTEINS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bacterial two-hybrid; zinc finger selection ID DNA-BINDING PROTEINS; DRUG DISCOVERY; NUCLEASES AB Individual synthetic Cys2His2 zinc finger domains with novel DNA-binding specificities can be identified from large randomized libraries using selection methodologies such as phage display. We have previously demonstrated that a bacterial cell-based two-hybrid system is at least as effective as phage display for selecting zinc fingers with desired specificities from such libraries. In this chapter we provide updated, detailed protocols for performing zinc finger selections using the bacterial two-hybrid system. C1 [Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. [Thibodeau-Beganny, Stacey; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. RP Thibodeau-Beganny, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA. FU NIDDK NIH HHS [K08 DK002883]; NIGMS NIH HHS [R01 GM069906]; NIH HHS [DP1 OD006862] NR 13 TC 3 Z9 3 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-752-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 649 BP 31 EP 50 DI 10.1007/978-1-60761-753-2_2 D2 10.1007/978-1-60761-753-2 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQJ71 UT WOS:000281187700002 PM 20680826 ER PT S AU Perlin, JB Baggett, KA AF Perlin, Jonathan B. Baggett, Kelvin A. BE Rouse, WB Cortese, DA TI Government, health and system transformation SO ENGINEERING THE SYSTEM OF HEALTHCARE DELIVERY SE Studies in Health Technology and Informatics LA English DT Article; Book Chapter ID UNITED-STATES; PART-D; CARE; QUALITY; OUTCOMES; DEMAND; ADULTS AB All levels of government have an economic and social interest in health. In the United States, Federal, state and local government are involved in the development of health policy, funding health care, and maintaining or improving public health. Federal, State and most municipalities also engage in delivery of health services. As with the private sector, government is grappling with accelerating health care costs, increasing service demands generated by an aging and more chronically ill society, and accumulating evidence that American health outcomes are not commensurate with the resources invested. Unlike the private sector, attempts to improve value in health care - whether through legislation in Congress or regulation or program design in the Executive branch - are subject to the full intensity of the partisan political process. In order to engage effectively with government in health system transformation, an understanding of both the civic processes and the political dynamics is necessary. This chapter provides an overview of the major governmental roles in health care as formally structured and identifies points of influence in the political process. C1 [Perlin, Jonathan B.] HCA, Clin Serv, Nashville, TN 37203 USA. [Perlin, Jonathan B.] HCA, Nashville, TN USA. [Perlin, Jonathan B.] US Dept Vet Affairs, Hlth, Washington, DC USA. [Perlin, Jonathan B.] Vet Hlth Adm, Washington, DC USA. [Perlin, Jonathan B.] Natl Qual Forum, Washington, DC USA. [Perlin, Jonathan B.] Meharry Med Coll, Joint Commiss, Nashville, TN USA. [Perlin, Jonathan B.] Natl eHlth Collaborat, Washington, DC USA. [Perlin, Jonathan B.] HHS Hlth IT Stand Comm, Washington, DC USA. [Perlin, Jonathan B.] Amer Coll Physicians, College Pk, MD USA. [Perlin, Jonathan B.] Amer Coll Med Informat, College Pk, MD USA. [Baggett, Kelvin A.] HCA, Clin Serv Grp, Nashville, TN USA. [Baggett, Kelvin A.] Duke Univ, Sch Med, Durham, NC 27706 USA. RP Perlin, JB (reprint author), HCA, Clin Serv, Nashville, TN 37203 USA. EM jonathan.perlin@hcahealthcare.com NR 41 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-533-4; 978-1-60750-532-7 J9 STUD HEALTH TECHNOL PY 2010 VL 153 BP 415 EP 434 DI 10.3233/978-1-60750-533-4-415 PG 20 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BC2MQ UT WOS:000351085000023 PM 20543256 ER PT S AU Avruch, J Long, XM Lin, YS Ortiz-Vega, S Rapley, J Oshiro, N AF Avruch, Joseph Long, Xiaomeng Lin, Yenshou Ortiz-Vega, Sara Rapley, Joseph Oshiro, Noriko BE Hall, MN Tamanoi, F TI Regulation of TOR Complex 1 by Amino Acids Through Small GTPases SO ENZYMES, VOL 27: STRUCTURE, FUNCTION AND REGULATION OF TOR COMPLEXES FROM YEASTS TO MAMMALS, PT A SE Enzymes LA English DT Article; Book Chapter ID ACTIVATED PROTEIN-KINASE; P70 S6 KINASE; RICH AKT SUBSTRATE; MAMMALIAN TARGET; RAPAMYCIN COMPLEX-1; TUBEROUS SCLEROSIS; MTORC1 ACTIVITY; FISSION YEAST; CELL-GROWTH; RAG GTPASES AB TOR complex 1 (TORC1), composed of the TOR (target of rapamycin) protein kinase, the substrate binding subunit raptor, and the 36 kDa WD propellor protein Lst8/G beta L, controls cell growth in all eukaryotes in response to nutrient availability, and in metazoans, to insulin and growth factors, energy status, and stress conditions. This chapter will focus on the mechanisms underlying mammalian TORC1 regulation by amino acids, in the context of overall TORC1 regulation in metazoan cells. C1 [Avruch, Joseph; Ortiz-Vega, Sara; Rapley, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Diabet Unit,Med Serv, Boston, MA 02114 USA. [Long, Xiaomeng] SuperArray Biosci Corp, Frederick, MD USA. [Lin, Yenshou] Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan. [Oshiro, Noriko] Kobe Univ, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 657, Japan. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Diabet Unit,Med Serv, Simches Res Bldg, Boston, MA 02114 USA. NR 69 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1874-6047 BN 978-0-12-381540-8 J9 ENZYMES JI Enzymes PY 2010 VL 27 BP 57 EP 73 DI 10.1016/S1874-6047(10)27004-X PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCV58 UT WOS:000311574900005 ER PT S AU Strachan, LR Ghadially, R AF Strachan, Lauren R. Ghadially, Ruby BE Turksen, K TI Limiting Dilution Analysis of Murine Epidermal Stem Cells Using an In Vivo Regeneration Assay SO EPIDERMAL CELLS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Stem cell; Transit amplifying cell; Epidermis; Limiting dilution; Skin; Regeneration ID TERM REPOPULATING CELLS; SIDE POPULATION; 5-FLUOROURACIL; KERATINOCYTES; EXPRESSION; PROGENITORS; VITRO AB Epidermal stem cells are of major importance for tissue homeostasis, wound repair, tumor initiation, and gene therapy. Here we describe an in vivo regeneration assay to test for the ability of keratinocyte progenitors to maintain an epidermis over the long-term in vivo. Limiting dilution analysis of epidermal repopulating units in this in vivo regeneration assay at sequential time points allows the frequency of short-term (transit amplifying cell) and long-term (stem cell) repopulating cells to be quantified. C1 [Strachan, Lauren R.; Ghadially, Ruby] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Strachan, LR (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. FU NIAMS NIH HHS [R01 AR053765, R01 AR053765-04] NR 24 TC 2 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-379-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 585 BP 421 EP 432 DI 10.1007/978-1-60761-380-0_29 D2 10.1007/978-1-60761-380-0 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMP85 UT WOS:000273301700029 PM 19908020 ER PT J AU Lopez-Meraz, ML Niquet, J Wasterlain, CG AF Lopez-Meraz, Maria-Leonor Niquet, Jerome Wasterlain, Claude G. TI Distinct caspase pathways mediate necrosis and apoptosis in subpopulations of hippocampal neurons after status epilepticus SO EPILEPSIA LA English DT Article DE Pilocarpine; Hippocampus; Development; Injury ID PILOCARPINE STATUS EPILEPTICUS; RAT-BRAIN; DIFFERENTIAL EXPRESSION; IMMATURE; DEATH; ACTIVATION; INJURY AB P>Status epilepticus in the immature brain induces neuronal injury in the hippocampal formation, but the mode and mechanism of death are poorly understood. Our laboratory has recently investigated the role of caspase-3, -8, and -9 in neuronal injury, using a lithium-pilocarpine model of status epilepticus in 2-week-old rat pups. Our results showed that dying neurons in the dentate gyrus and CA1-subiculum area do not share the same mechanism of death. In CA1-subiculum, caspase-8 upregulation preceded caspase-3 activation in morphologically necrotic neurons. The pan-caspase inhibitor Q-VD-OPH reduced CA1 damage, showing that caspases contribute to status epilepticus-induced necrosis. In the dentate gyrus, dying neurons were caspase-9 and -3 immunoreactive and morphologically apoptotic. It is not clear why the same seizures cause different types of cell death in neurons that are connected in series along the same hippocampal circuit, but the apoptotic dentate neurons express doublecortin, and do not express calbindin-D28k, suggesting that their immaturity may be a factor in producing an apoptotic mode of death. C1 [Lopez-Meraz, Maria-Leonor; Niquet, Jerome; Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Lopez-Meraz, Maria-Leonor] Univ Veracruzana, Programa Neurobiol, Cordoba, Veracruz, Mexico. [Niquet, Jerome; Wasterlain, Claude G.] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd,Bldg 114,Room 139, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU Epilepsy Foundation of America; VHA Research Service, NINDS [RO1 NS13515]; UC MEXUS-CONACyT FX Supported by research grants from the Epilepsy Foundation of America (JN), VHA Research Service, NINDS (grant RO1 NS13515), and by a UC MEXUS-CONACyT postdoctoral fellowship to MLLM. NR 14 TC 14 Z9 19 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 PY 2010 VL 51 SU 3 BP 56 EP 60 DI 10.1111/j.1528-1167.2010.02611.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 619PP UT WOS:000279442400011 PM 20618402 ER PT J AU Karr, L Pan, YZ Rutecki, PA AF Karr, Linda Pan, Yu-Zhen Rutecki, Paul A. TI CB1 receptor antagonism impairs the induction of epileptiform activity by group I metabotropic glutamate receptor activation SO EPILEPSIA LA English DT Article DE Long-term depression (LTD); Dihydroxy phenylglycine (DHPG); Endocannabinoid; CA3; SR 141716; AM 251 ID HIPPOCAMPAL-NEURONS; PROTEIN-SYNTHESIS; PLASTICITY; HYPEREXCITABILITY AB P>Exposure to the group I metabotropic glutamate receptor (mGluR) agonist dihydroxy phenylglycine (DHPG) induces epileptiform activity in the CA3 region of the hippocampus that persists following washout of DHPG. DHPG also can cause long-term depression of synaptic transmission, and at some synapses this may be mediated by endocannabinoids. We evaluated whether the selective cannabinoid type 1 (CB1) receptor antagonists SR 141716 or AM 251 could modify induction of epileptiform activity produced by DHPG exposure. The induction of epileptiform activity by DHPG exposure was significantly reduced by CB1 receptor antagonists, SR 141716 or AM 251. Minimal effects on epileptiform activity were noted once the activity had been induced. In control slices, exposure to DHPG for 30 min produced long-term depression (LTD) of synaptic transmission, on average about a 70% reduction in slope of the field excitatory postsynaptic potential (EPSP). When slices were exposed to both DHPG and SR 141716 (3 mu m), LTD did not occur and the population EPSP remained at control values or greater. These results suggest that CB1 receptors mediate some of DHPG effects that result in persistent epileptiform activity, and antagonism of CB1 receptors has antiepileptogenic properties. Paradoxically DHPG also caused LTD of excitatory synaptic transmission in the CA3 region and CB1 receptor antagonism prevents the depression. We hypothesize that the ictal activity induced by DHPG requires depression of synaptic strength and CB1 receptor antagonism prevents this depression and the induction of ictal activity. C1 Univ Wisconsin, Neurol Serv, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53705 USA. RP Rutecki, PA (reprint author), Univ Wisconsin, Dept Neurol, William Middleton VA Hosp, Madison, WI 53705 USA. EM rutecki@neurology.wisc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service FX This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Service (grant to PAR). The contents do not represent the views of the Dept. of Veterans Affairs or the United States Government. NR 15 TC 5 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2010 VL 51 SU 3 BP 121 EP 125 DI 10.1111/j.1528-1167.2010.02625.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 619PP UT WOS:000279442400025 PM 20618416 ER PT J AU Dudek, FE Pouliot, WA Rossi, CA Staley, KJ AF Dudek, F. Edward Pouliot, Wendy A. Rossi, Christina A. Staley, Kevin J. TI The effect of the cannabinoid-receptor antagonist, SR141716, on the early stage of kainate-induced epileptogenesis in the adult rat SO EPILEPSIA LA English DT Article DE Epilepsy; Febrile seizures; Status epilepticus; Seizure threshold ID PROLONGED FEBRILE SEIZURES; LONG-TERM; HYPEREXCITABILITY; EPILEPSY; MODEL; EXCITABILITY; PLASTICITY AB P>Pretreatment with the endocannabinoid-receptor antagonist, SR141716, has been reported to suppress the long-lasting hyperexcitability and increased seizure susceptibility present after 30 min of hyperthermia-induced convulsions in immature rats, an animal model of complex febrile seizures in children, which may be a cause of temporal lobe epilepsy. The present experiments tested the hypothesis that SR141716 suppresses epileptogenesis in the adult kainate model, an animal model of temporal lobe epilepsy. Adult male rats (n = 35), implanted for electroencephalography (EEG) recordings, were treated with kainate. Immediately after the first acute electrographic seizure during kainate-induced status epilepticus, either vehicle or SR141716 (10 mg/kg) was injected intraperitoneally. Chronic video-EEG data were collected for the first 2-week period after kainate-induced status epilepticus. More than one-half of both the vehicle- and drug-treated animals showed spontaneous recurrent seizures. Similarly, mean seizure frequency did not differ significantly for the drug- and vehicle-treated animals during the first 2 weeks (n = 9 and 8, respectively). Therefore, no significant differences were found between SR141716-treated and control animals during the first 2 weeks of epileptogenesis. These results suggest that the endocannabinoid-receptor antagonist, SR141716, had no detectable effect on the early stages of epileptogenesis in the adult kainate model. We discuss several potential explanations for the differences in the effects of SR141716 in the adult-rat, kainate versus immature-rat, hyperthermia models. C1 [Dudek, F. Edward; Pouliot, Wendy A.; Rossi, Christina A.] Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. RP Dudek, FE (reprint author), Univ Utah, Sch Med, Dept Physiol, 420 Chipeta Way,Suite 1700, Salt Lake City, UT 84108 USA. EM ed.dudek@hsc.utah.edu FU National Institute of Neurological Disorders and Stroke [NS045144, N01-NS-4-2359] FX Supported by the National Institute of Neurological Disorders and Stroke (NS045144 and N01-NS-4-2359). NR 14 TC 16 Z9 16 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2010 VL 51 SU 3 BP 126 EP 130 DI 10.1111/j.1528-1167.2010.02626.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 619PP UT WOS:000279442400026 PM 20618417 ER PT B AU Van Cott, AC Brenner, RP AF Van Cott, Anne C. Brenner, Richard P. BE Fisch, BJ TI ENCEPHALOPATHY AND PROGNOSIS IN COMA SO EPILEPSY AND INTENSIVE CARE MONITORING: PRINCIPLES AND PRACTICE LA English DT Article; Book Chapter ID NONCONVULSIVE STATUS EPILEPTICUS; INDUCED HYPERAMMONEMIC ENCEPHALOPATHY; EPILEPSIA PARTIALIS CONTINUA; CRITICALLY-ILL PATIENTS; LOCKED-IN-SYNDROME; STEROID-RESPONSIVE ENCEPHALOPATHY; REFRACTORY STATUS EPILEPTICUS; MYOCLONIC STATUS EPILEPTICUS; SENSORY EVOKED-POTENTIALS; EPISODIC LOW-AMPLITUDE C1 [Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Brenner, Richard P.] Univ Pittsburgh, Dept Neurol, Med Ctr, Pittsburgh, PA 15260 USA. RP Van Cott, AC (reprint author), Univ Pittsburgh, Dept Neurol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. NR 140 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-13-6 PY 2010 BP 309 EP 329 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BLW95 UT WOS:000271242500021 ER PT J AU Ettinger, AB Copeland, LA Zeber, JE Van Cott, AC Pugh, MJV AF Ettinger, Alan B. Copeland, Laurel A. Zeber, John E. Van Cott, Anne C. Pugh, Mary Jo V. TI Are psychiatric disorders independent risk factors for new-onset epilepsy in older individuals? SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Comorbidity; Elderly; Mental disorders; Veterans ID TEMPORAL-LOBE EPILEPSY; ADMINISTRATIVE DATA; MAJOR DEPRESSION; UNPROVOKED SEIZURES; SYMPTOMS; COMORBIDITY; PREVALENCE; DISEASE; VETERANS; SURGERY AB This retrospective study examined whether psychiatric conditions are directly related to epilepsy or, rather, are associated with underlying central nervous system (CNS) disorders linked to subsequent epilepsy. We examined data from a sample of older veterans (>65 years) receiving care from the Veterans Health Administration during fiscal year 2000. We compared individuals with new-onset epilepsy and individuals without epilepsy to examine the extent to which psychiatric disorders were associated with new-onset epilepsy; this analysis controlled for demographic and premorbid neurological risk factors previously associated with new-onset epilepsy. Premorbid psychiatric conditions occurred at higher rates in the epilepsy versus nonepilepsy groups, foremost including depression (17% vs 12%), anxiety (12% vs 8%), psychosis (12% vs 5%), and substance abuse (8% vs 4%). However, in the final model, only psychosis (OR = 1.4, CI 1.2-1.6) was significantly associated with epilepsy when controlling for neurological disorders and psychiatric conditions (e.g., stroke, dementia, brain tumor, head injury). Published by Elsevier Inc. C1 [Ettinger, Alan B.] Neurol Surg PC, Lake Success, NY 11042 USA. [Copeland, Laurel A.; Zeber, John E.; Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst VERDICT, San Antonio, TX USA. [Copeland, Laurel A.; Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Van Cott, Anne C.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Van Cott, Anne C.] Univ Pittsburgh, Pittsburgh, PA USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Ettinger, AB (reprint author), Neurol Surg PC, 1991 Marcus Ave,Suite 108, Lake Success, NY 11042 USA. EM aettinge@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 02-274]; VERDICT Research Program at the South Texas Veterans Health Care System, San Antonio, TX; University of Texas Health Science Center at San Antonio; VA Health Services Research and Development program [IIR-06-062] FX The authors thank Dale Hesdorffer, Ph.D., for her helpful suggestions in the preparation of this article and Jeffrey Tabares for his invaluable assistance in preparation of this article.; This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (IIR 02-274, PI: Pugh). This work was completed with the additional support of the VERDICT Research Program at the South Texas Veterans Health Care System, San Antonio, TX, and the University of Texas Health Science Center at San Antonio. M.J. Pugh, J.E. Zeber, and L.A. Copeland were partially supported by VA HRSD IIR-06-062 from the VA Health Services Research and Development program. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 35 TC 20 Z9 20 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JAN PY 2010 VL 17 IS 1 BP 70 EP 74 DI 10.1016/j.yebeh.2009.10.010 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 546UF UT WOS:000273837700010 PM 19913462 ER PT B AU Yee, AJ Ramaswamy, S AF Yee, Andrew J. Ramaswamy, Sridhar BE Ginsburg, GS Willard, HF TI DNA Microarrays in Biological Discovery and Patient Care SO ESSENTIALS OF GENOMIC AND PERSONALIZED MEDICINE LA English DT Article; Book Chapter ID PARAFFIN-EMBEDDED TISSUES; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION PATTERNS; B-CELL LYMPHOMA; BREAST-CANCER PROGRESSION; ACUTE MYELOID-LEUKEMIA; MESSENGER-RNA; OLIGONUCLEOTIDE ARRAYS; CLINICAL-ONCOLOGY; CDNA MICROARRAYS C1 [Ramaswamy, Sridhar] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 127 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095811-8; 978-0-12-374934-5 PY 2010 BP 73 EP 88 DI 10.1016/B978-0-12-374934-5.00007-6 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BID62 UT WOS:000327733200008 ER PT B AU Wiggs, JL AF Wiggs, Janey L. BE Ginsburg, GS Willard, HF TI Genomic Considerations in Ophthalmology SO ESSENTIALS OF GENOMIC AND PERSONALIZED MEDICINE LA English DT Article; Book Chapter ID OPEN-ANGLE GLAUCOMA; COMPLEMENT FACTOR-H; GRANULAR CORNEAL-DYSTROPHY; DOMINANT RETINITIS-PIGMENTOSA; NUCLEAR PULVERULENT CATARACT; COMMON SEQUENCE VARIANTS; B-CRYSTALLIN MUTATION; GROENOUW TYPE-I; MACULAR DEGENERATION; PSEUDOEXFOLIATION SYNDROME C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 97 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095811-8; 978-0-12-374934-5 PY 2010 BP 712 EP 721 DI 10.1016/B978-0-12-374934-5.00055-6 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BID62 UT WOS:000327733200056 ER EF